Protection by the flavonoids quercetin and luteolin against peroxide- or menadione-induced oxidative stress in MC3T3-E1 osteoblast cells.

PubMed

Fatokun, Amos A; Tome, Mercedes; Smith, Robert A; Darlington, L Gail; Stone, Trevor W

2015-01-01

Potential protective effects of the flavonoids quercetin and luteolin have been examined against the oxidative stress of MC3T3-E1 osteoblast-like cells. Although hydrogen peroxide and menadione reduced cell viability, the toxicity was prevented by desferrioxamine or catalase but not superoxide dismutase, suggesting the involvement of hydrogen peroxide in both cases. Quercetin and luteolin reduced the oxidative damage, especially that caused by hydrogen peroxide. When cultures were pre-incubated with quercetin or luteolin, protection was reduced or lost. Protection was also reduced when a 24 h pre-incubation with the flavonoids was followed by exposure to menadione alone. Pretreating cultures with luteolin impaired protection by quercetin, whereas quercetin pretreatment did not affect protection by luteolin. It is concluded that quercetin and luteolin suppress oxidative damage to MC3T3-E1 cells, especially caused by peroxide. The reduction in protection by pretreatment implies a down-regulation of part of the toxic transduction pathway.

[Chemical constituents of the roots of Vaccinium bracteatum].

PubMed

Lv, Xiao-Lan; Mai, Xi; Guo, Hui; Lai, Xiao-Ping

2012-06-01

To study the chemical constituents of the roots of Vaccinium bracteatum. The constituents were separated and purified with chromatographic methods (including silica gel, Sephadex LH-20 and RP-18 column chromatography), and their structures were determined by spectroscopic methods (including MS, 1H-NMR and 13C-NMR). 10 compounds were isolated from the roots of Vaccinium bracteatu and were elucidated as chlorogenic acid (1), pinoresinol (2), ferulic acid (3), kaempferol (4), trans-caffeic acid (5), beta-sitosterol (6), quercetin (7), oleanolic acid (8), apigenin (9) and luteolin (10). Compounds 1 -3 are obtained from this plant for the first time.

Identification and quantification of flavonoids of Mexican oregano (Lippia graveolens) by LC-DAD-ESI/MS analysis

PubMed Central

Lin, Long-Ze; Mukhopadhyay, Sudarsan; Robbins, Rebecca J.; Harnly, James M.

2013-01-01

LC-DAD-ESI/MS was used to identify 23 flavonoids in the extract of Mexican oregano (Lippia graveolens H.B.K.), a spice and herb, used in the USA and Mexico. The identification of luteolin-7-O-glucoside, apigenin 7-O-glucoside, phloridzin, taxifolin, eriodictyol, scutellarein, luteolin, quercetin, naringenin, pinocembrin and galangin was confirmed by direct comparison with standards. Identification of 6-hydroxyluteolin, two 6-hydroxyluteolin 7-O-glycosides, three pentahydroxyflavanone hexosides, scutellarein 7-O-hexoside, 3-hydroxyphloretin hexoside, and three other flavones, was made by detailed analysis of their UV and mass spectral data. The identification of the flavonoid glycosides was further confirmed through detection of their aglycones following hydrolysis of the samples. The concentration of the identified flavonoids in three samples was also estimated. This is the first report of detection of over 20 flavonoids, including chalcones, in this plant material. PMID:24812440

Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential.

PubMed

Caltagirone, S; Rossi, C; Poggi, A; Ranelletti, F O; Natali, P G; Brunetti, M; Aiello, F B; Piantelli, M

2000-08-15

Flavonoids are a class of polyphenolic compounds widely distributed in the plant kingdom, which display a variety of biological activities, including chemoprevention and tumor growth inhibition. Our aim was to investigate the effects of several polyphenols on the growth and metastatic potential of B16-BL6 melanoma cells in vivo. Intraperitoneal administration of quercetin, apigenin, (-)-epigallocathechin-3-gallate (EGCG), resveratrol, and the anti-estrogen tamoxifen, at the time of i.m. injection of B16-BL6 cells into syngeneic mice, resulted in a significant, dose-dependent delay of tumor growth, without toxicity. The relative descending order of potency was EGCG > apigenin = quercetin = tamoxifen > resveratrol > control. Furthermore, polyphenols significantly potentiated the inhibitory effect of a non-toxic dose of cisplatin. When tested for the ability to inhibit lung colonization, quercetin, apigenin, and tamoxifen (but not EGCG or resveratrol) significantly decreased the number of B16-BL6 colonies in the lungs in a dose-dependent manner, with quercetin and apigenin being more effective than tamoxifen. Interestingly, quercetin, apigenin, and tamoxifen (but not EGCG or resveratrol) significantly decreased the invasion of B16-BL6 cells in vitro, with quercetin and apigenin being more effective than tamoxifen. This suggests that anti-invasive activity is one of the mechanisms underlying inhibition of lung colonization by quercetin and apigenin. In conclusion, quercetin and apigenin inhibit melanoma growth and invasive and metastatic potential; therefore, they may constitute a valuable tool in the combination therapy of metastatic melanoma. Copyright 2000 Wiley-Liss, Inc.

Dietary Flavonoids and Acarbose Synergistically Inhibit α-Glucosidase and Lower Postprandial Blood Glucose.

PubMed

Zhang, Bo-Wei; Li, Xia; Sun, Wen-Long; Xing, Yan; Xiu, Zhi-Long; Zhuang, Chun-Lin; Dong, Yue-Sheng

2017-09-27

The inhibition of porcine pancreatic α-amylase and mammalian α-glucosidase by 16 individual flavonoids was determined. The IC 50 values for baicalein, (+)-catechin, quercetin, and luteolin were 74.1 ± 5.6, 175.1 ± 9.1, 281.2 ± 19.2, and 339.4 ± 16.3 μM, respectively, against α-glucosidase. The IC 50 values for apigenin and baicalein were 146.8 ± 7.1 and 446.4 ± 23.9 μM, respectively, against α-amylase. The combination of baicalein, quercetin, or luteolin with acarbose showed synergistic inhibition, and the combination of (+)-catechin with acarbose showed antagonistic inhibition of α-glucosidase. The combination of baicalein or apigenin with acarbose showed additive inhibition of α-amylase at lower concentrations and antagonistic inhibition at a higher concentration. Kinetic studies of α-glucosidase activity revealed that baicalein alone, acarbose alone, and the combination showed noncompetitive, competitive, and mixed-type inhibition, respectively. Molecular modeling revealed that baicalein had higher affinity to the noncompetitive binding site of maltase, glucoamylase, and isomaltase subunits of α-glucosidase, with glide scores of -7.64, -6.98, and -6.88, respectively. (+)-Catechin had higher affinity to the active sites of maltase and glucoamylase and to the noncompetitive site of isomaltase. After sucrose loading, baicalein dose-dependently reduced the postprandial blood glucose (PBG) level in mice. The combination of 80 mg/kg baicalein and 1 mg/kg acarbose synergistically lowered the level of PBG, and the hypoglycemic effect was comparable to 8 mg/kg acarbose. The results indicated that baicalein could be used as a supplemental drug or dietary supplement in dietary therapy for diabetes mellitus.

The Flavones Apigenin and Luteolin Induce FOXO1 Translocation but Inhibit Gluconeogenic and Lipogenic Gene Expression in Human Cells

PubMed Central

Bumke-Vogt, Christiane; Osterhoff, Martin A.; Borchert, Andrea; Guzman-Perez, Valentina; Sarem, Zeinab; Birkenfeld, Andreas L.; Bähr, Volker; Pfeiffer, Andreas F. H.

2014-01-01

The flavones apigenin (4′,5,7,-trihydroxyflavone) and luteolin (3′,4′,5,7,-tetrahydroxyflavone) are plant secondary metabolites with antioxidant, antiinflammatory, and anticancer activities. We evaluated their impact on cell signaling pathways related to insulin-resistance and type 2 diabetes. Apigenin and luteolin were identified in our U-2 OS (human osteosarcoma) cell screening assay for micronutrients triggering rapid intracellular translocation of the forkhead box transcription factor O1 (FOXO1), an important mediator of insulin signal transduction. Insulin reversed the translocation of FOXO1 as shown by live cell imaging. The impact on the expression of target genes was evaluated in HepG2 (human hepatoma) cells. The mRNA-expression of the gluconeogenic enzymes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pc), the lipogenic enzymes fatty-acid synthase (FASN) and acetyl-CoA-carboxylase (ACC) were down-regulated by both flavones with smaller effective dosages of apigenin than for luteolin. PKB/AKT-, PRAS40-, p70S6K-, and S6-phosphorylation was reduced by apigenin and luteolin but not that of the insulin-like growth factor receptor IGF-1R by apigenin indicating a direct inhibition of the PKB/AKT-signaling pathway distal to the IGF-1 receptor. N-acetyl-L-cysteine did not prevent FOXO1 nuclear translocation induced by apigenin and luteolin, suggesting that these flavones do not act via oxidative stress. The roles of FOXO1, FOXO3a, AKT, sirtuin1 (SIRT1), and nuclear factor (erythroid-derived2)-like2 (NRF2), investigated by siRNA knockdown, showed differential patterns of signal pathways involved and a role of NRF2 in the inhibition of gluconeogenic enzyme expression. We conclude that these flavones show an antidiabetic potential due to reduction of gluconeogenic and lipogenic capacity despite inhibition of the PKB/AKT pathway which justifies detailed investigation in vivo. PMID:25136826

Absorption and Emission of the Apigenin and Luteolin Flavonoids: A TDDFT Investigation

NASA Astrophysics Data System (ADS)

Amat, Anna; Clementi, Catia; de Angelis, Filippo; Sgamellotti, Antonio; Fantacci, Simona

2009-09-01

The absorption and emission properties of the two components of the yellow color extracted from weld (Reseda luteola L.), apigenin and luteolin, have been extensively investigated by means of DFT and TDDFT calculations. Our calculations reproduce the absorption spectra of both flavonoids in good agreement with the experimental data and allow us to assign the transitions giving rise to the main spectral features. For apigenin, we have also computed the electronic spectrum of the monodeprotonated species, providing a rationale for the red-shift of the experimental spectrum with increasing pH. The fluorescence emission of both apigenin and luteolin has then been investigated. Excited-state TDDFT geometry optimizations have highlighted an excited-state intramolecular proton transfer (ESIPT) from the 5-hydroxyl to the 4-carbonyl oxygen of the substituted benzopyrone moiety. By computing the potential energy curves at the ground and excited states as a function of an approximate proton transfer coordinate for apigenin, we have been able to trace an ESIPT pathway and thus explain the double emission observed experimentally.

HPLC-UV-ESI-MS analysis of phenolic compounds and antioxidant properties of Hypericum undulatum shoot cultures and wild-growing plants.

PubMed

Rainha, Nuno; Koci, Kamila; Coelho, Ana Varela; Lima, Elisabete; Baptista, José; Fernandes-Ferreira, Manuel

2013-02-01

LC-UV and LC-MS analysis were used to study the phenolic composition of water extracts of Hypericum undulatum (HU) shoot cultures and wild-growing (WG) plants. Total phenolic content (TPC), determined using the Folin-Ciocalteu assay, and the antioxidant activity measured by two complementary methods were also performed for each sample. Mass spectrometry revealed several phenolics acids with quinic acid moieties, flavonols, mostly quercetin, luteolin and apigenin glycosides, flavan-3-ols (catechin and epicatechin) and the xanthonoid mangiferin. Differences in phenolic composition profile and TPC were found between the samples. The major phenolic in HU culture-growing (CG) samples is chlorogenic acid, followed by epicatechin, quercitrin and isoquercitrin. The WG plants presents hyperoside as the main phenolic, followed by isoquercitrin, chlorogenic acid and quercetin. The TPC and antioxidant activity were higher in samples from WG plants. Copyright © 2012 Elsevier Ltd. All rights reserved.

Comparison of phenolic acids and flavonoids contents in various cultivars and parts of common lavender (Lavandula angustifolia) derived from Poland.

PubMed

Adaszyńska-Skwirzyńska, M; Dzięcioł, M

2017-11-01

The aim of study was to compare the content of phenolic acids and flavonoids in two cultivars of Lavandula angustifolia: 'Blue River' and 'Ellagance Purple', including flowers and leafy stalks. Total phenolics and total flavonoids contents were determined by UV-Vis spectroscopy. The contents of total phenolics in leafy stalks (3.71-4.06 mg g -1 d.m.) were higher than in flowers (1.13-1.14 mg g -1 d.m.). Similarly, higher total contents of flavonoids were determined in leafy stalks (3.41-3.51 mg g -1 d.m.), as compared with flowers (0.86-0.91 mg g -1 d.m.). Phenolic acids and flavonoids were identified and quantified using HPLC and UPLC methods. Three phenolic acids were determined: rosmarinic, ferulic and caffeic acid. Lavender extracts contained also flavonoids from group of apigenin, luteolin and quercetin. Higher amounts of luteolin diglucuronide and luteolin glucuronide were found in leafy stalks in comparison to flowers. Obtained results indicate that leafy stalks of lavender can be also valuable source of antioxidant compounds.

Distinct mechanisms of relaxation to bioactive components from chamomile species in porcine isolated blood vessels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roberts, R.E., E-mail: Richard.roberts@nottingham.ac.uk; Allen, S.; Chang, A.P.Y.

2013-11-01

German chamomile (Matricaria recutita L.), a widely-used herbal medicine, has been reported to have a wide range of biological effects, including smooth muscle relaxation. The aim of this study was to compare the effects of representative compounds from chamomile (apigenin, luteolin, (−)-α-bisabolol, farnesene, umbelliferone; 3–30 μM) on vascular tone using porcine coronary and splenic arteries mounted for isometric tension recording in isolated tissue baths and precontracted with the thromboxane-mimetic U46619. Apigenin, luteolin, and (−)-α-bisabolol produced slow, concentration-dependent relaxations in both the coronary and splenic arteries that were not blocked by inhibition of nitric oxide synthase or potassium channels. Removal ofmore » extracellular calcium inhibited the relaxations to all three compounds, and these compounds also inhibited calcium re-addition-evoked contractions, indicating that the relaxation response may be mediated through inhibition of calcium influx. Apigenin and luteolin, but not (−)-α-bisabolol, enhanced the relaxation to the nitric oxide donor sodium nitroprusside, indicating that apigenin and luteolin may act to regulate cyclic GMP levels. Umbelliferone produced a rapid, transient relaxation in the splenic artery, but not the coronary artery, that was inhibited by L-NAME and removal of the endothelium, suggesting an influence on nitric oxide production. Farnesene, at concentrations up to 30 μM, was without effect in either blood vessel. In conclusion, hydroxylated compounds (apigenin, luteolin and (−)-α-bisabolol) found in chamomile all caused a slow relaxation of isolated blood vessels through an effect on calcium influx. Umbelliferone, on the other hand, produced a rapid, transient relaxation dependent upon release of nitric oxide from the endothelium. - Highlights: • Apigenin, luteolin, and (-)-α-bisabolol are present in chamomile. • They produced slow, concentration-dependent relaxations in arteries. • These relaxations were associated with an inhibition of calcium entry. • Farnesene, at concentrations up to 30 μM, was without effect in either blood vessel. • Umbelliferone produced a rapid, transient nitric oxide-dependent relaxation.« less

Distinct mechanisms of relaxation to bioactive components from chamomile species in porcine isolated blood vessels.

PubMed

Roberts, R E; Allen, S; Chang, A P Y; Henderson, H; Hobson, G C; Karania, B; Morgan, K N; Pek, A S Y; Raghvani, K; Shee, C Y; Shikotra, J; Street, E; Abbas, Z; Ellis, K; Heer, J K; Alexander, S P H

2013-11-01

German chamomile (Matricaria recutita L.), a widely-used herbal medicine, has been reported to have a wide range of biological effects, including smooth muscle relaxation. The aim of this study was to compare the effects of representative compounds from chamomile (apigenin, luteolin, (-)-α-bisabolol, farnesene, umbelliferone; 3-30 μM) on vascular tone using porcine coronary and splenic arteries mounted for isometric tension recording in isolated tissue baths and precontracted with the thromboxane-mimetic U46619. Apigenin, luteolin, and (-)-α-bisabolol produced slow, concentration-dependent relaxations in both the coronary and splenic arteries that were not blocked by inhibition of nitric oxide synthase or potassium channels. Removal of extracellular calcium inhibited the relaxations to all three compounds, and these compounds also inhibited calcium re-addition-evoked contractions, indicating that the relaxation response may be mediated through inhibition of calcium influx. Apigenin and luteolin, but not (-)-α-bisabolol, enhanced the relaxation to the nitric oxide donor sodium nitroprusside, indicating that apigenin and luteolin may act to regulate cyclic GMP levels. Umbelliferone produced a rapid, transient relaxation in the splenic artery, but not the coronary artery, that was inhibited by L-NAME and removal of the endothelium, suggesting an influence on nitric oxide production. Farnesene, at concentrations up to 30 μM, was without effect in either blood vessel. In conclusion, hydroxylated compounds (apigenin, luteolin and (-)-α-bisabolol) found in chamomile all caused a slow relaxation of isolated blood vessels through an effect on calcium influx. Umbelliferone, on the other hand, produced a rapid, transient relaxation dependent upon release of nitric oxide from the endothelium. © 2013.

Isolation and in silico evaluation of antidiabetic molecules of Cynodon dactylon (L.).

PubMed

Annapurna, Hasthi V; Apoorva, Babu; Ravichandran, Natesan; Arun, Kallur Purushothaman; Brindha, Pemaiah; Swaminathan, Sethuraman; Vijayalakshmi, Mahadevan; Nagarajan, Arumugam

2013-02-01

Cynodon dactylon is a potential source of metabolites such as flavanoids, alkaloids, glycosides and β-sitosterol and has been traditionally employed to treat urinary tract and other microbial infections and dysentery. The present work attempts to evaluate the activity of C. dactylon extracts for glycemic control. Aqueous extracts of C. dactylon analyzed by HPLC-ESI MS have identified the presence of apigenin, luteolin, 6-C-pentosyl-8-C-hexosyl apigenin and 6-C-hexosyl-8-C-pentosyl luteolin. Evaluation of hypoglycemic activity through an extensive in silico docking approach with PPARγ (Peroxisome Proliferator-Activated Receptor), GLUT-4 (glucose transporter-4) and SGLT2 (sodium glucose co-transporter-2) revealed that luteolin, apigenin, 6-C-pentosyl-8-C-hexosyl apigenin, 6-C-hexosyl-8-C-pentosyl luteolin interact with SGLT2. Interactions of these molecules with Gln 295 and Asp 294 residues of SGLT2 have been shown to compare well with that of the phase III drug, dapagliflozin. These residues have been proven to be responsible for sugar sensing and transport. This work establishes C. dactylon extract as a potential SGLT2 inhibitor for diabetic neuropathy thus enabling a possibility of this plant extract as a new alternative to existing diabetic approaches. Copyright © 2012 Elsevier Inc. All rights reserved.

An efficient preparative procedure for main flavonoids from the peel of Trichosanthes kirilowii Maxim. using polyamide resin followed by semi-preparative high performance liquid chromatography.

PubMed

Li, Aifeng; Sun, Ailing; Liu, Renmin; Zhang, Yongqing; Cui, Jichun

2014-08-15

In this study, a simple and efficient preparative procedure was developed for preparation of seven flavonoids from the peel of Trichosanthes kirilowii Maxim. using polyamide resin followed by semi-preparative high performance liquid chromatography (SPHPLC). First, the ethyl acetate fraction from the peel of T. kirilowii Maxim. obtained "prefractionation" using polyamide resin, which yielded two subfractions. And then the two subfractions were isolated by SPHPLC with an isocratic elution of methanol-water. Finally, seven known flavonoids were purified from 35 g of ethyl acetate extract including quercetin-3-O-[α-l-rhamnose (1→2)-β-d-glucopyranosyl]-5-O-β-d-glucopyranoside (19 mg), quercetin-3-O-rutinoside (24 mg), apigenin-7-O-β-d-glucopyranoside (10mg), diosmetin-7-O-β-d-glucopyranoside (45 mg), luteolin (21 mg), apigenin (15 mg), and diosmetin (56 mg). The purities of the compounds were determined by HPLC and the chemical structures were confirmed by UV and NMR analysis. In the present study, a simple, effective, and rapid procedure was established for preparative separation of multiple components from the peel of T. kirilowii Maxim. Furthermore, it was scalable and economical, so it was a promising basis for large-scale preparation of flavonoids from other plant extracts. Copyright © 2014. Published by Elsevier B.V.

Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies.

PubMed

Cao, Lei; Kwara, Awewura; Greenblatt, David J

2017-12-01

Excessive exposure to acetaminophen (APAP, paracetamol) can cause liver injury through formation of a reactive metabolite that depletes hepatic glutathione and causes hepatocellular oxidative stress and damage. Generation of this metabolite is mediated by Cytochrome-P450 (CYP) isoforms, mainly CYP2E1. A number of naturally occurring flavonoids can mitigate APAP-induced hepatotoxicity in experimental animal models. Our objective was to determine the mechanism of these protective effects and to evaluate possible human applicability. Two flavonoids, luteolin and quercetin, were evaluated as potential inhibitors of eight human CYP isoforms, of six UDP-glucuronosyltransferase (UGT) isoforms and of APAP glucuronidation and sulfation. The experimental model was based on in-vitro metabolism by human liver microsomes, using isoform-specific substrates. Luteolin and quercetin inhibited human CYP isoforms to varying degrees, with greatest potency towards CYP1A2 and CYP2C8. However, 50% inhibitory concentrations (IC 50 values) were generally in the micromolar range. UGT isoforms were minimally inhibited. Both luteolin and quercetin inhibited APAP sulfation but not glucuronidation. Inhibition of human CYP activity by luteolin and quercetin occurred with IC 50 values exceeding customary in-vivo human exposure with tolerable supplemental doses of these compounds. The findings indicate that luteolin and quercetin are not likely to be of clinical value for preventing or treating APAP-induced hepatotoxicity. © 2017 Royal Pharmaceutical Society.

Anticholinesterase, antioxidant activity and phytochemical investigation into aqueous extracts from five species of Agrimonia genus.

PubMed

Kubínová, Renata; Švajdlenka, Emil; Jankovská, Dagmar

2016-01-01

Aqueous extracts of aerial flowering parts of five Agrimonia species (Rosaceae): Agrimonia coreana Nakai, Agrimonia japonica (Miq.) Koidz, Agrimonia procera Wallr., Agrimonia eupatoria L. and Agrimonia leucantha Kunze were investigated on their antioxidant activity, measured using five different methods; the best was the extract from A. procera with IC50 values from 6 to 29 μg/mL. All the extracts displayed inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) at the tested concentration of 100 μg/mL. We found the highest inhibition of cholinesterase in the extract of A. japonica with inhibition 70.4% for AChE and 79.8% for BuChE. These findings are statistically significant in comparison with those of other extracts (p < 0.001). The phytochemical analyses showed that the antioxidant activity of Agrimonia extracts can be affected especially by hexahydroxydiphenoyl (HHDP)-glucose and quercetin glycosides, and inhibition of cholinesterases by apigenin, luteolin and quercetin glycosides.

Extraction and identification of flavonoids from parsley extracts by HPLC analysis

NASA Astrophysics Data System (ADS)

Stan, M.; Soran, M. L.; Varodi, C.; Lung, I.

2012-02-01

Flavonoids are phenolic compounds isolated from a wide variety of plants, and are valuable for their multiple properties, including antioxidant and antimicrobial activities. In the present work, parsley (Petroselinum crispum L.) extracts were obtained by three different extraction techniques: maceration, ultrasonic-assisted and microwave-assisted solvent extractions. The extractions were performed with ethanol-water mixtures in various ratios. From these extracts, flavonoids like the flavones apigenin and luteolin, and the flavonols quercetin and kaempferol were identified using an HPLC Shimadzu apparatus equipped with PDA and MS detectors. The separation method involved a gradient step. The mobile phase consisted of two solvents: acetonitrile and distilled water with 0.1% formic acid. The separation was performed on a RP-C18 column.

Influence of the target molecule on the oxygen radical absorbance capacity index: a comparison between alizarin red- and fluorescein-based methodologies.

PubMed

Martin, I; Aspée, A; Torres, P; Lissi, E; López-Alarcón, C

2009-12-01

A comparison of alizarin red (AR) and fluorescein (FL) as target molecules in oxygen radical absorbance capacity (ORAC)-like methods is reported. Galangin, apigenin, ferulic acid, and coumaric acid decreased AR initial consumption rate, whereas quercetin, kaempferol, luteolin, caffeic acid, and sinapic acid inhibited its consumption through an induction time, associated with a repair mechanism. On the other hand, all compounds protected FL with a clear induction time. AR was more selective and provides ORAC-AR values considerably smaller for compounds of low reactivity. The ORAC-AR value for luteolin was nearly 200 times that of coumaric acid. However, the ratio of ORAC-FL values for luteolin and coumaric acid was only 1.2. This different selectivity implies that AR provides ORAC values more related to reactivity than FL. ORAC-AR values of infusions were considerably smaller than the corresponding ORAC-FL values. These differences are interpreted in terms of the capacity of FL to generate induction times, irrespective of the reactivity of the additive. It is proposed that comparison of ORAC-AR and ORAC-FL values could afford a rough estimation of the average reactivity of the antioxidants titrated by the ORAC-FL methodology.

Microspore development of three coniferous species: affinity of nuclei for flavonoids.

PubMed

Feucht, Walter; Treutter, Dieter; Dithmar, Heike; Polster, Jürgen

2008-12-01

The nuclear localization of blue-staining flavanols was investigated histochemically throughout microsporogenesis in yellow cypress (Callitropsis nootkatensis (D. Don) Oerst., formerly Cupressus nootkatensis), juniper (Juniperus communis L.) and yew (Taxus baccata L.). During meiotic development, both the cytoplasm and nuclei of microspores of all species contained varying amounts of flavanols; however, the flavanols were largely confined to the nuclei in microspores just released from tetrads. Quantification by HPLC analysis indicated that, in all species, catechin and epicatechin were the dominant nuclear flavanols. At the early free microspore stage, the nuclear flavanols were barely detectable in all species, but they increased fivefold on incubation in the presence of 0.1 mM benzylaminopurine (BA) or zeatin. Histochemical studies revealed that, in addition to non-fluorescing flavanols, microspores contained yellow-fluorescing flavonoids, which yielded a distinct HPLC flavonoid profile for each species. In yellow cypress, the hydrolyzed flavonoids were identified as quercetin, apigenin, kaempferol and luteolin, whereas only quercetin and myricetin were found in microspores of juniper and in anthers of yew. Application of a UV-VIS titration technique revealed that the aglycone quercetin seems to interact more strongly with histone H3 than either glycoside rutin or kaempferol.

Antimicrobial Activities of Three Medicinal Plants and Investigation of Flavonoids of Tripleurospermum disciforme.

PubMed

Tofighi, Zahra; Molazem, Maryam; Doostdar, Behnaz; Taban, Parisa; Shahverdi, Ahmad Reza; Samadi, Nasrin; Yassa, Narguess

2015-01-01

Rosa damascena, Tripleurospermum disciforme and Securigera securidaca were used as disinfectant agents and for treatment of some disease in folk medicine of Iran. The antimicrobial effects of different fractions of seeds extract of S. securidaca, petals extract of R. damascena and aerial parts extract of T. disciforme were examined against some gram positive, gram negative and fungi by cup plate diffusion method. The petroleum ether and chloroform fractions of S. securidaca showed antibacterial activities against Staphylococcus aureus and Pseudomonas aeruginosa, while its methanol fraction had no antibacterial effects. R. damascena petals extract demonstrated antibacterial activities against Bacillus cereus, Staphylococcus epidermidis, S. aureus and Pseudomonas aeruginosa. T. disciforme aerial parts extract exhibited antimicrobial effects only against S. aureus and S. epidermidis. None of the fractions had any antifungal activities. Therefore, present study confirmed utility of these plants as disinfectant agents. Six flavonoids were isolated from T. disciforme: Luteolin, Quercetin-7-O-glucoside, Kaempferol, Kaempferol-7-O-glucoside, Apigenin and Apigenin-7-O-glucoside. The flavonoids and the antimicrobial activity of T. disciforme are reported for the first time.

Antimicrobial Activities of Three Medicinal Plants and Investigation of Flavonoids of Tripleurospermum disciforme

PubMed Central

Tofighi, Zahra; Molazem, Maryam; Doostdar, Behnaz; Taban, Parisa; Shahverdi, Ahmad Reza; Samadi, Nasrin; Yassa, Narguess

2015-01-01

Rosa damascena, Tripleurospermum disciforme and Securigera securidaca were used as disinfectant agents and for treatment of some disease in folk medicine of Iran. The antimicrobial effects of different fractions of seeds extract of S. securidaca, petals extract of R. damascena and aerial parts extract of T. disciforme were examined against some gram positive, gram negative and fungi by cup plate diffusion method. The petroleum ether and chloroform fractions of S. securidaca showed antibacterial activities against Staphylococcus aureus and Pseudomonas aeruginosa, while its methanol fraction had no antibacterial effects. R. damascena petals extract demonstrated antibacterial activities against Bacillus cereus, Staphylococcus epidermidis, S. aureus and Pseudomonas aeruginosa. T. disciforme aerial parts extract exhibited antimicrobial effects only against S. aureus and S. epidermidis. None of the fractions had any antifungal activities. Therefore, present study confirmed utility of these plants as disinfectant agents. Six flavonoids were isolated from T. disciforme: Luteolin, Quercetin-7-O-glucoside, Kaempferol, Kaempferol-7-O-glucoside, Apigenin and Apigenin-7-O-glucoside. The flavonoids and the antimicrobial activity of T. disciforme are reported for the first time. PMID:25561928

Luteolin, a flavonoid, inhibits AP-1 activation by basophils.

PubMed

Hirano, Toru; Higa, Shinji; Arimitsu, Junsuke; Naka, Tetsuji; Ogata, Atsushi; Shima, Yoshihito; Fujimoto, Minoru; Yamadori, Tomoki; Ohkawara, Tomoharu; Kuwabara, Yusuke; Kawai, Mari; Matsuda, Hisashi; Yoshikawa, Masayuki; Maezaki, Naoyoshi; Tanaka, Tetsuaki; Kawase, Ichiro; Tanaka, Toshio

2006-02-03

Flavonoids including luteolin, apigenin, and fisetin are inhibitors of IL-4 synthesis and CD40 ligand expression by basophils. This study was done to search for compounds with greater inhibitory activity of IL-4 expression and to clarify the molecular mechanisms through which flavonoids inhibit their expression. Of the 37 flavonoids and related compounds examined, ayanin, luteolin, and apigenin were the strongest inhibitors of IL-4 production by purified basophils in response to anti-IgE antibody plus IL-3. Luteolin did not suppress Syk or Lyn phosphorylation in basophils, nor did suppress p54/46 SAPK/JNK, p38 MAPK, and p44/42 MAPK activation by a basophilic cell line, KU812 cells, stimulated with A23187 and PMA. However, luteolin did inhibit phosphorylation of c-Jun and DNA binding activity of AP-1 in nuclear lysates from stimulated KU812 cells. These results provide a fundamental structure of flavonoids for IL-4 inhibition and demonstrate a novel action of flavonoids that suppresses the activation of AP-1.

Pea, Pisum sativum, and Its Anticancer Activity

PubMed Central

Rungruangmaitree, Runchana; Jiraungkoorskul, Wannee

2017-01-01

Pisum sativum (Family: Fabaceae), as known as green pea or garden pea, has long been important in diet due to its content of fiber, protein, starch, trace elements, and many phytochemical substances. It has been shown to possess antibacterial, antidiabetic, antifungal, anti-inflammatory, antihypercholesterolemia, and antioxidant activities and also shown anticancer property. Its nonnutritive biologically active components include alkaloids, flavonoids, glycosides, isoflavones, phenols, phytosterols, phytic acid, protease inhibitors, saponins, and tannins. This plant is rich in apigenin, hydroxybenzoic, hydroxycinnamic, luteolin, and quercetin, all of which have been reported to contribute to its remedial properties including anticarcinogenesis property. Based on established literature on the anticancer property of P. sativum and possible mode of action, this review article has focused to demonstrate that P. sativum could be further explored for the development of anticancer treatment. PMID:28503053

Luteolin, a flavonoid, inhibits AP-1 activation by basophils

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hirano, Toru; Higa, Shinji; Arimitsu, Junsuke

Flavonoids including luteolin, apigenin, and fisetin are inhibitors of IL-4 synthesis and CD40 ligand expression by basophils. This study was done to search for compounds with greater inhibitory activity of IL-4 expression and to clarify the molecular mechanisms through which flavonoids inhibit their expression. Of the 37 flavonoids and related compounds examined, ayanin, luteolin, and apigenin were the strongest inhibitors of IL-4 production by purified basophils in response to anti-IgE antibody plus IL-3. Luteolin did not suppress Syk or Lyn phosphorylation in basophils, nor did suppress p54/46 SAPK/JNK, p38 MAPK, and p44/42 MAPK activation by a basophilic cell line, KU812more » cells, stimulated with A23187 and PMA. However, luteolin did inhibit phosphorylation of c-Jun and DNA binding activity of AP-1 in nuclear lysates from stimulated KU812 cells. These results provide a fundamental structure of flavonoids for IL-4 inhibition and demonstrate a novel action of flavonoids that suppresses the activation of AP-1.« less

Anti-chikungunya activity of luteolin and apigenin rich fraction from Cynodon dactylon.

PubMed

Murali, Krishnan Saravana; Sivasubramanian, Srinivasan; Vincent, Savariar; Murugan, Shanmugaraj Bala; Giridaran, Bupesh; Dinesh, Sundaram; Gunasekaran, Palani; Krishnasamy, Kaveri; Sathishkumar, Ramalingam

2015-05-01

To obtain luteolin and apigenin rich fraction from the ethanolic extract of Cynodon dactylon (L.) (C. dactylon) Pers and evaluate the fraction's cytotoxicity and anti-Chikungunya potential using Vero cells. The ethanolic extract of C. dactylon was subjected to silica gel column chromatography to obtain anti-chikungunya virus (CHIKV) fraction. Reverse phase-HPLC and GC-MS studies were carried out to identify the major phytochemicals in the fraction using phytochemical standards. Cytotoxicity and the potential of the fraction against CHIKV were evaluated in vitro using Vero cells. Reduction in viral replication was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) after treating the viral infected Vero cells with the fraction. Reverse Phase-HPLC and GC-MS studies confirmed the presence of flavonoids, luteolin and apigenin as major phytochemicals in the anti-CHIKV ethanolic fraction of C. dactylon. The fraction was found to exhibit potent viral inhibitory activity (about 98%) at the concentration of 50 µg/mL as observed by reduction in cytopathic effect, and the cytotoxic concentration of the fraction was found to be 250 µg/mL. RT-PCR analyses indicated that the reduction in viral mRNA synthesis in fraction treated infected cells was much higher than the viral infected control cells. Luteolin and apigenin rich ethanolic fraction from C. dactylon can be utilized as a potential therapeutic agent against CHIKV infection as the fraction does not show cytotoxicity while inhibiting the virus. Copyright © 2015 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

Simultaneous determination of eight flavonoids in the flowers of Matricaria chamomilla by high performance liquid chromatography.

PubMed

Xie, Xiao-Yu; Chen, Fang-Fang; Shi, Yan-Ping

2014-01-01

An HPLC method was developed for simultaneous determination of five flavones (apigenin, three apigenin 7-O-glucoside acylated derivatives, and luteolin) and three methoxylated flavonols in Matricaria chamomilla. Full validation of the assay was carried out including linearity, LODs, LOQs, precision, repeatability, stability, and accuracy. The results demonstrated that the method developed was simple, accurate, and reliable. Five batches of M. chamomilla samples were determined using the developed method, and total contents of the eight flavonoids ranged from 1.843 to 2.134 mg/g. Among them, the content of apigenin was the highest with values of 0.538 to 0.618 mg/g. In addition, the extract solution from M. chamomilla exhibited a significant dose-dependent inhibition of 2,2-diphenyl-1-picrylhydrazyl (DPPH) activity, with a 50% inhibition (SC50) at a concentration of 3.06 +/- 0.09 mg/mL, and the flavonoids apigenin-7-O-(6"-acetyl)-glucoside, luteolin, apigenin, eupatolitin, and chrysosplenol D played an important role in the antioxidant activities of the extract solution from M. chamomilla.

Potentiation of luteolin cytotoxicity by flavonols fisetin and quercetin in human chronic lymphocytic leukemia cell lines.

PubMed

Sak, Katrin; Kasemaa, Kristi; Everaus, Hele

2016-09-14

Despite numerous studies chronic lymphocytic leukemia (CLL) still remains an incurable disease. Therefore, all new compounds and novel strategies which are able to eradicate CLL cells should be considered as valuable clues for a potential future remedy against this malignancy. In the present study, the cytotoxic profiles of natural flavonoids were described in two human CLL cell lines, HG-3 and EHEB, indicating the flavone luteolin as the most potent flavonoid with half-maximal inhibitory constants (IC50) of 37 μM and 26 μM, respectively. Luteolin significantly increased the apoptotic cell population in both cell lines by increasing the activities of caspases-3 and -9 and triggering the intrinsic apoptotic pathway. Two flavonols, fisetin and quercetin, were somewhat less efficient in suppressing cellular viability, whereas baicalein, chrysin, (+)-catechin and hesperetin exerted only a small or no response at doses as high as 100 μM. Both fisetin and quercetin were able to augment the cytotoxic activity of luteolin in both cell lines by reducing the IC50 values up to four fold. As a result of this, luteolin displayed cytotoxicity activity already at low micromolar concentrations that could potentially be physiologically achievable through oral ingestion. No other tested flavonoids were capable of sensitizing CLL cells to luteolin pointing to a specific binding of fisetin and quercetin to the cellular targets which interfere with the signaling pathways induced by luteolin. Although further molecular studies to unravel this potentiating mechanism are certainly needed, this phenomenon could contribute to future remedies for prevention and treatment of chronic lymphocytic leukemia.

Evaluation of the Antibacterial Effects of Flavonoid Combination from the Leaves of Dracontomelon dao by Microcalorimetry and the Quadratic Rotary Combination Design

PubMed Central

Li, Yang; Xia, Houlin; Wu, Mingquan; Wang, Jiabo; Lu, Xiaohua; Wei, Shizhang; Li, Kun; Wang, Lifu; Wang, Ruilin; Zhao, Pan; Zhao, Yanling; Xiao, Xiaohe

2017-01-01

Skin infectious disease is a common public health problem due to the emergence of drug-resistant bacteria caused by the antibiotic misuse. Dracontomelon dao (Blanco) Merr. et Rolfe, a traditional Chinese medicine, has been used for the treatment of various skin infectious diseases over 1000 of years. Previous reports have demonstrated that the leaves of D. dao present favorable antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtitles. The flavonoids are the main components of the ethyl acetate extract of D. dao leaf. However, the correlation between flavonoids and antibacterial activities is yet to be determined. In this study, the combined antibacterial activities of these flavonoids were investigated. Three samples with the different concentrations of flavonoids (S1–S3) were obtained. By microcalorimetric measurements, the results showed that the IC50 value of S2 was lower than those of S1 and S3. The contents of main flavonoids (including Luteolin, L-Epicatechin, Cianidanol, and Quercetin) in S1–S3 were various, confirmed by the method of the Ultra High Performance Liquid Chromatography (UPLC). Based on the method of quadratic general rotary unitized design, the antibacterial effect of single flavonoid, and the potential synergistic effects between Luteolin and Quercetin, Luteolin and Cianidanol were calculated, which were also proved by microcalorimetric analysis. The antibacterial activities of main flavonoids were Luteolin > Cianidanol > Quercetin > L-Epicatechin. Meanwhile, the synergistic effects of Luteolin and Cianidanol (PL+C = 1.425), Quercetin and Luteolin (PL+Q = 1.129) on anti-microbial activity were validated. Finally, we found that the contents of Luteolin, L-Epicatechin, Cianidanol, Quercetin were 1061.00–1061.00, 189.14–262.86, 15,990.33–16,973.62, 6799.67–7662.64 ng·ml−1 respectively, with the antibacterial rate over 60.00%. In conclusion, this study could provide reference for quality evaluation and pharmacodynamics research of D. dao. PMID:28261101

[Chemical constituents from Neo-Taraxacum siphonathum].

PubMed

Shi, Shuyun; Zhou, Honghao; Zhang, Yuping; Huang, Kelong; Liu, Suqin

2009-04-01

To study the chemical constituents from the antioxidant fraction of Neo-Taraxacum siphonathum. Various chromatographic techniques were used to isolate and purify the constituents. The structures were elucidated on the basis of chemical evidence and spectral analysis. Ten compounds were isolated and identified from Neo-T. siphonathum, caffeic acid (1), chlorogenic acid (2), quercetin (3), luteolin (4), quercetin-3-O-beta-D-glucopyranoside (5), quercetin-3-O-alpha-D-arabinofuranoside (6), quercetin-3-O-alpha-D-arabinopyranoside (7), luteolin-7-O-beta-D-glucopyranoside (8), beta-sitosterol (9) and daucosterol (10). Compounds 1-10 were isolated from this plant for the first time.

Metal-organic framework MIL-101 as sorbent based on double-pumps controlled on-line solid-phase extraction coupled with high-performance liquid chromatography for the determination of flavonoids in environmental water samples.

PubMed

Liu, Yue; Hu, Jia; Li, Yan; Li, Xiao-Shuang; Wang, Zhong-Liang

2016-10-01

A novel method with high sensitivity for the rapid determination of chrysin, apigenin and luteolin in environment water samples was developed by double-pumps controlled on-line solid-phase extraction (SPE) coupled with high-performance liquid chromatography (HPLC). In the developed technique, metal organic framework MIL-101 was synthesized and applied as a sorbent for SPE. The as-synthesized MIL-101 was characterized by scanning electron microscope, X-ray diffraction spectrometry, thermal gravimetric analysis and micropore physisorption analysis. The MIL-101 behaved as a fast kinetics in the adsorption of chrysin, apigenin and luteolin. On-line SPE of chrysin, apigenin and luteolin was processed by loading a sample solution at a flow rate of 1.0 mL/min for 10 min. The extracted analytes were subsequently eluted into a ZORBAX Bonus-RP analytical column (25 cm long × 4.6 mm i.d.) for HPLC separation under isocratic condition with a mobile phase (MeOH: ACN: 0.02 M H 3 PO 4 = 35:35:30) at a flow rate of 1.0 mL/min. Experimental conditions, including ionic strength, sample pH, sample loading rates, sample loading time and desorption analytes time, were further optimized to obtain efficient preconcentration and high-precision determination of the analytes mentioned above. The method achieved the merits of simplicity, rapidity, sensitivity, wide linear range and high sample throughput. The possible mechanism for the adsorption of flavonoids on MIL-101 was proposed. The developed method has been applied to determine trace chrysin, apigenin and luteolin in a variety of environmental water samples. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Wild Roman chamomile extracts and phenolic compounds: enzymatic assays and molecular modelling studies with VEGFR-2 tyrosine kinase.

PubMed

Guimarães, Rafaela; Calhelha, Ricardo C; Froufe, Hugo J C; Abreu, Rui M V; Carvalho, Ana Maria; Queiroz, Maria João R P; Ferreira, Isabel C F R

2016-01-01

Angiogenesis is a process by which new blood vessels are formed from the pre-existing vasculature, and it is a key process that leads to tumour development. Some studies have recognized phenolic compounds as chemopreventive agents; flavonoids, in particular, seem to suppress the growth of tumor cells modifying the cell cycle. Herein, the antiangiogenic activity of Roman chamomile (Chamaemelum nobile L.) extracts (methanolic extract and infusion) and the main phenolic compounds present (apigenin, apigenin-7-O-glucoside, caffeic acid, chlorogenic acid, luteolin, and luteolin-7-O-glucoside) was evaluated through enzymatic assays using the tyrosine kinase intracellular domain of the Vascular Endothelium Growth Factor Receptor-2 (VEGFR-2), which is a transmembrane receptor expressed fundamentally in endothelial cells involved in angiogenesis, and molecular modelling studies. The methanolic extract showed a lower IC50 value (concentration that provided 50% of VEGFR-2 inhibition) than the infusion, 269 and 301 μg mL(-1), respectively. Regarding phenolic compounds, luteolin and apigenin showed the highest capacity to inhibit the phosphorylation of VEGFR-2, leading us to believe that these compounds are involved in the activity revealed by the methanolic extract.

Compositional characterization of native Peruvian chili peppers (Capsicum spp.).

PubMed

Meckelmann, Sven W; Riegel, Dieter W; van Zonneveld, Maarten J; Ríos, Llermé; Peña, Karla; Ugas, Roberto; Quinonez, Lourdes; Mueller-Seitz, Erika; Petz, Michael

2013-03-13

The national Capsicum germplasm bank of Peru at INIA holds a unique collection of more than 700 Capsicum accessions, including many landraces. These conserved accessions have never been thoroughly characterized or evaluated. Another smaller collection exists at UNALM, and CIDRA provided taxonomically characterized fruits from the Amazon region of Ucayali. Of these collections, 147 accessions have been selected to represent the biodiversity of Peruvian Capsicum annuum , Capsicum baccatum , Capsicum chinense , and Capsicum frutescens by morphological traits as well as by agronomic characteristics and regional origin. All fruits from the selected accessions have been oven-dried and ground in Peru and analyzed in Germany. Results are reported for each accession by total capsaicinoids and capsaicinoid pattern, total polyphenol content, antioxidant capacity, specific flavonoids (quercetin, kaempferol, luteolin, apigenin), fat content, vitamin C, surface color, and extractable color. A wide variability in phytochemical composition and concentration levels was found.

Metabolomic Characterization of Hot Pepper (Capsicum annuum "CM334") during Fruit Development.

PubMed

Jang, Yu Kyung; Jung, Eun Sung; Lee, Hyun-Ah; Choi, Doil; Lee, Choong Hwan

2015-11-04

Non-targeted metabolomic analysis of hot pepper (Capsicum annuum "CM334") was performed at six development stages [16, 25, 36, 38, 43, and 48 days post-anthesis (DPA)] to analyze biochemical changes. Distinct distribution patterns were observed in the changes of metabolites, gene expressions, and antioxidant activities by early (16-25 DPA), breaker (36-38 DPA), and later (43-48 DPA) stages. In the early stages, glycosides of luteolin, apigenin, and quercetin, shikimic acid, γ-aminobutyric acid (GABA), and putrescine were highly distributed but gradually decreased over the breaker stage. At later stages, leucine, isoleucine, proline, phenylalanine, capsaicin, dihydrocapsaicin, and kaempferol glycosides were significantly increased. Pathway analysis revealed metabolite-gene interactions in the biosynthesis of amino acids, capsaicinoids, fatty acid chains, and flavonoids. The changes in antioxidant activity were highly reflective of alterations in metabolites. The present study could provide useful information about nutrient content at each stage of pepper cultivation.

Comparative polyphenolic content and antioxidant activities of Genista tinctoria L. and Genistella sagittalis (L.) Gams (Fabaceae).

PubMed

Hanganu, Daniela; Olah, Neli Kinga; Benedec, Daniela; Mocan, Andrei; Crisan, Gianina; Vlase, Laurian; Popica, Iulia; Oniga, Ilioara

2016-01-01

The aim of this study was focused on the polyphenolic composition and antioxidant capacity of Genista tinctoria L. and Genistella sagittalis (L.) Gams. A qualitative and quantitative characterization of the main phenolic compounds from the extracts were carried out using a HPLC-MS method. The total polyphenolic and flavonoid content was spectrophotometrically determined. The antioxidant activity towards various radicals generated in different systems was evaluated usingDPPH bleaching method, Trolox equivalent antioxidant capacity assay (TEAC) and Oxygen radical absorbance capacity (ORAC), and all indicated that G. tinctoria extract was more antioxidant than G. sagittalis extract.That was in good agreement with the total polyphenolic and flavonoidic content.Chlorogenic acid, p-coumaric acid, isoquercitrin and apigenin were identified in bothspecies. Caffeic acid, ferulic acid, hyperoside, rutin, quercitrin and luteolin were found only in G. tinctoria, while quercetin was determined in G. sagittalis.

LC-QTOF characterization of non-anthocyanic flavonoids in four Tunisian fig varieties.

PubMed

Soltana, Hala; De Rosso, Mirko; Lazreg, Houda; Vedova, Antonio Dalla; Hammami, Mohamed; Flamini, Riccardo

2018-06-02

Flavonoids are compounds characterized by antioxidant activity and their intake in the human diet is considered useful for health and nutrition. Non-anthocyanic flavonoids in four different types of Tunisian figs belonging to the smyrna-type Ficus carica varieties known as Kholi, Tchich Asal, Himri and Bidhi were studied by liquid chromatography/high-resolution mass spectrometry UHPLC-QTOF. Twenty-two compounds belonging to the classes of flavanones (naringenin and eriodictyol), flavones (3 apigenin and 5 luteolin derivatives) and flavonols (2 kaempferol and 7 quercetin derivatives), were identified. Three O-methoxy flavonols (tamarixetin, syringetin and isorhamnetin-3-O-glucoside) were found in figs for the first time. Total content of non-anthocyanic flavonoids found in dark varieties (between 410-830 mg/Kg) show that these Ficus carica are fruits qualitatively and quantitatively rich of dietary polyphenols. This article is protected by copyright. All rights reserved.

Apigenin and quercetin promote. Delta. pH-dependent accumulation of IAA in membrane vesicles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woolard, D.D.; Clark, K.A.

1990-05-01

Flavonoids may act as regulators of polar auxin transport. In the presence of a pH gradient (pH 8{sub in}/6{sub out}) the flavonoids quercetin and apigenin, as well as the synthetic herbicide napthylphthalamic acid (NPA), promote the accumulation of IAA in membrane vesicles from dark-grown zucchini hypocotyls. Simultaneous accumulation of {sup 3}H-IAA (10 nM) and {sup 14}C-butyric acid (5 {mu}M; included as a pH probe) was determined by a filtration assay after incubating the vesicles with 3 nM to 100 {mu}M quercetin, apigenin, NPA or unlabeled IAA. Maximal stimulation (% of Control) was observed with 3 {mu}M NPA (130%), 1 {mu}Mmore » quercetin (120%), or 3 {mu}M apigenin (115%); {Delta}pH was not affected by these concentrations. As reported by others, IAA uptake was saturable: 1 {mu}M unlabeled IAA eliminated {Delta}pH-dependent uptake of {sup 3}H-IAA without altering {Delta}pH. However, at 30 to 100 {mu}M, every compound tested collapsed the imposed pH gradient and therefore abolished specific {sup 3}H-IAA uptake.« less

Phenolic composition and antiparasitic activity of plants from the Brazilian Northeast "Cerrado".

PubMed

Calixto Júnior, João Tavares; de Morais, Selene Maia; Gomez, Celeste Vega; Molas, Cathia Coronel; Rolon, Miriam; Boligon, Aline Augusti; Athayde, Margareth Linde; de Morais Oliveira, Cícera Datiane; Tintino, Saulo Relison; Henrique Douglas, Melo Coutinho

2016-05-01

This work describes the antiparasitic and cytotoxic activities of three plant species from the Cerrado biome, Northeastern Brazil. Significant antiparasitic inhibition was observed against Trypanosoma cruzi (63.86%), Leishmania brasiliensis (92.20%) and Leishmania infantum (95.23%) when using ethanol extract from leaves of Guazuma ulmifolia Lam. (Malvaceae), at a concentration of 500 μg/mL. However, low levels of inhibition were observed when assessing leishmanicidal and trypanocidal (Clone CL-B5) activities of crude ethanol extracts from leaves and bast tissue of Luehea paniculata (Malvaceae) and leaves and bark of Prockia crucis (Salicaceae) at a concentration of 500 μg/mL. The extracts revealed the presence of phenolic acids such as gallic acid, chlorogenic acid, caffeic acid and rosmarinic acid, as well as flavonoids such as rutin, luteolin, apigenin and quercetin - the latter detected only in G. ulmifolia. G. ulmifolia extract displayed higher leishmanicidal activity probably due to the presence of quercetin, a potent known leishmanicidal compound. A cytotoxicity test indicated values over 50% at the highest concentration (1000 μg/mL) for all natural products, which were considered cytotoxic. This points out the need for further tests to enable future in vivo trials, including antineoplastic activity on human tumor cells.

Phenolic composition and antiparasitic activity of plants from the Brazilian Northeast “Cerrado”

PubMed Central

Calixto Júnior, João Tavares; de Morais, Selene Maia; Gomez, Celeste Vega; Molas, Cathia Coronel; Rolon, Miriam; Boligon, Aline Augusti; Athayde, Margareth Linde; de Morais Oliveira, Cícera Datiane; Tintino, Saulo Relison; Henrique Douglas, Melo Coutinho

2015-01-01

This work describes the antiparasitic and cytotoxic activities of three plant species from the Cerrado biome, Northeastern Brazil. Significant antiparasitic inhibition was observed against Trypanosoma cruzi (63.86%), Leishmania brasiliensis (92.20%) and Leishmania infantum (95.23%) when using ethanol extract from leaves of Guazuma ulmifolia Lam. (Malvaceae), at a concentration of 500 μg/mL. However, low levels of inhibition were observed when assessing leishmanicidal and trypanocidal (Clone CL-B5) activities of crude ethanol extracts from leaves and bast tissue of Luehea paniculata (Malvaceae) and leaves and bark of Prockia crucis (Salicaceae) at a concentration of 500 μg/mL. The extracts revealed the presence of phenolic acids such as gallic acid, chlorogenic acid, caffeic acid and rosmarinic acid, as well as flavonoids such as rutin, luteolin, apigenin and quercetin – the latter detected only in G. ulmifolia. G. ulmifolia extract displayed higher leishmanicidal activity probably due to the presence of quercetin, a potent known leishmanicidal compound. A cytotoxicity test indicated values over 50% at the highest concentration (1000 μg/mL) for all natural products, which were considered cytotoxic. This points out the need for further tests to enable future in vivo trials, including antineoplastic activity on human tumor cells. PMID:27081371

Catalase inhibition an anti cancer property of flavonoids: A kinetic and structural evaluation.

PubMed

Majumder, Debashis; Das, Asmita; Saha, Chabita

2017-11-01

Flavonoids are dietary polyphenols that present abundantly in fruits and vegetables. Flavonoids have inhibitory effects on enzymes and catalase is one among them. Catalase is a common enzyme ubiquitously found in all living organisms exposed to oxygen. It catalyzes the decomposition of hydrogen peroxide to water and oxygen (2H 2 O 2 →2H 2 O+O 2 ) . Inhibition of pure and cellular catalase from K562 cells by flavonoids was similar and exhibited the following efficacy; Myrecetin>Quercetin>Kaempferol and Quercetin>Luteolin>Apigenin demonstrating structure activity relationship. Circular Dichroism (CD) spectra have shown distinct loss in α-helical structure of the catalase on interaction with the flavonoids. All flavonoids inhibited the catalase activity by uncompetitive mechanism. The K m and V max values of pure catalase were observed to be 294mM -1 and 0.222mM -1 s -1 respectively and on inhibition with myrecetin the values decreased to a minimum of 23mM -1 and 0.014mM -1 s -1 respectively. Inhibition of catalase will directly results in increased production of Reactive Oxygen Species (ROS) and pro-oxidant property of flavonoids. This inhibition was reversed in presence of Cu 2+ ions because of the chelating affect of flavonoids. Copyright © 2017 Elsevier B.V. All rights reserved.

Health effects and bioavailability of dietary flavonols.

PubMed

Hollman, P C; Katan, M B

1999-12-01

Flavonoids are polyphenolic compounds that are ubiquitously present in foods of plant origin. Flavonoids are categorised into flavonols, flavones, catechins, flavanones, anthocyanidins, and isoflavonoids. They may have beneficial health effects because of their antioxidant properties and their inhibitory role in various stages of tumour development in animal studies. It is estimated that the human intake of all flavonoids is a few hundreds of milligram per day. Flavonoids present in foods used to be considered non-absorbable because they are bound to sugars as beta-glycosides. However, we found that human absorption of the quercetin glycosides from onions (52%) is far better than that of the pure aglycone (24%). The sugar moiety is an important determinant of their absorption and bioavailability. Flavonol glycosides might contribute to the antioxidant defences of blood. The average intake of the flavonols quercetin, myricetin and kaempferol and the flavones luteolin and apigenin in the Netherlands was 23 mg/day. The intake of these flavonols and flavones was inversely associated with subsequent coronary heart disease in some but not all prospective epidemiological studies. A protective effect of flavonols on cancer was found in one prospective study; two others showed no association. Thus the epidemiological evidence does not yet allow a decision on the involvement of flavonols in the etiology of either cardiovascular diseases or cancer.

Intake of potentially anticarcinogenic flavonoids and their determinants in adults in The Netherlands.

PubMed

Hertog, M G; Hollman, P C; Katan, M B; Kromhout, D

1993-01-01

Flavonoids are strong antioxidants that occur naturally in foods and can inhibit carcinogenesis in rodents. Accurate data on population-wide intakes of flavonoids are not available. Here, using data of the Dutch National Food Consumption Survey 1987-1988, we report the intake of the potentially anticarcinogenic flavonoids quercetin, kaempferol, myricetin, apigenin, and luteolin among 4,112 adults. The flavonoid content of vegetables, fruits, and beverages was determined by high-performance liquid chromatography. In all subjects, average intake of all flavonoids combined was 23 mg/day. The most important flavonoid was the flavonol quercetin (mean intake 16 mg/day). The most important sources of flavonoids were tea (48% of total intake), onions (29%), and apples (7%). Flavonoid intake did not vary between seasons; it was not correlated with total energy intake (r = 0.001), and it was only weakly correlated with the intake of vitamin A (retinol equivalents, r = 0.14), dietary fiber (r = 0.21), and vitamin C (r = 0.26). Our use of new analytic technology suggests that in the past flavonoid intake has been overestimated fivefold. However, on a milligram-per-day basis, the intake of the antioxidant flavonoids still exceeded that of the antioxidants beta-carotene and vitamin E. Thus flavonoids represent an important source of antioxidants in the human diet.

A comparison of flavonoid glycosides by electrospray tandem mass spectrometry

NASA Astrophysics Data System (ADS)

March, Raymond E.; Lewars, Errol G.; Stadey, Christopher J.; Miao, Xiu-Sheng; Zhao, Xiaoming; Metcalfe, Chris D.

2006-01-01

A comparison is presented of product ion mass spectra of protonated and deprotonated molecules of kaempferol-3-O-glucoside, quercitin-3-O-glucoside (isoquercitrin), quercitin-3-O-galactoside (hyperoin), apigenin-7-O-glucoside, luteolin-7-O-glucoside, genistein-7-O-glucoside, naringenin-7-O-glucoside (prunin), luteolin-4'-O-glucoside, luteolin-6-C-glucoside (homoorientin, known also as isoorientin), apigenin-8-C-glucoside (vitexin), and luteolin-8-C-glucoside (orientin) together with the product ion mass spectrum of deprotonated kaempferol-7-O-glucoside. All isomeric ions were distinguishable on the basis of their product ion mass spectra. For protonated 3-O-, 7-O-, and 4'-O-glycosides at a collision energy of 46-47 eV, homolytic cleavage of the O-glycosidic bond yielded aglycon Y+ ions, whereas in deprotonated 3-O-, 7-O-, and 4'-O-glycosides, heterolytic and homolytic cleavage of the O-glycosidic bond yielded radical aglycon (Y-H)- and aglycon (Y-) ions. In each case, fragmentation of either the glycan or the aglycon or both was observed. For 6-C- and 8-C-glycosides at a collision energy of 46-47 eV, fragmentation was restricted almost exclusively to the glycan. For luteolin-6-C-glucoside, the integrity of the aglycon structure is preserved at the expense of the glycan for which some 30 fragmentations were observed. Breakdown curves were determined as a function of collision energy for protonated and deprotonated luteolin-6-C-glucoside. An attempt has been made to rationalize the product ion mass spectra derived from C-O- and C-C-luteolin glucosides in terms of computed structures that indicate significant intramolecular hydrogen bonding and rotation of the B-ring to form a coplanar luteolin structure. It is proposed that protonated and deprotonated luteolin-6-C-glucoside may afford examples of cooperative interactive bonding that plays a major role in directing fragmentation.

Quantitative determination of phenolic compounds by UHPLC-UV-MS and use of principal component analysis to differentiate chemo-types of chamomile/chrysanthemum flowerheads

USDA-ARS?s Scientific Manuscript database

A new rapid UHPLC-UV-QTOF/MS method has been developed for the simultaneous analysis of nine phenolic compounds [cis-GMCA, chlorogenic acid, trans-GMCA, quercetagetin-7-O-ß-D-glucopyranoside, luteolin-7-O-ß-D-glucoside, apigenin-7-O- ß-Dglucoside, chamaemeloside, apigenin 7-O-(6"-O-acetyl-ß-D-glucop...

LC-MS/MS method for the simultaneous quantification of luteolin, wedelolactone and apigenin in mice plasma using hansen solubility parameters for liquid-liquid extraction: Application to pharmacokinetics of Eclipta alba chloroform fraction.

PubMed

Cheruvu, Hanumanth Srikanth; Yadav, Navneet K; Valicherla, Guru R; Arya, Rakesh K; Hussain, Zakir; Sharma, Chetan; Arya, Kamal R; Singh, Rama K; Datta, Dipak; Gayen, Jiaur R

2018-04-01

Eclipta alba (Bhringraj) in ayurveda has been widely used as a traditional medicine for its multi-therapeutic properties for ages. Luteolin (LTL), wedelolactone (WDL) and apigenin (APG) are the three main bioactive phytochemicals present in Eclipta alba extract. However there was a lack of sensitive bioanalytical method for the pharmacokinetics of these free compounds in plasma which majorly contributes for their activities after oral administration of Eclipta alba. The present study aims to develop a sensitive, rapid and reliable liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the simultaneous estimation of mice plasma concentrations of LTL, WDL and APG using quercetin as an internal standard for the pharmacokinetic analysis. Analytes were separated on Phenomenex Luna C18 (150 × 4.6 mm, 3.0 μm) column with mobile phase containing methanol: acetonitrile (90: 10, v/v) and 0.1% formic acid in 10 mM ammonium formate buffer in the ratio of 70: 30 (v/v) in isocratic mode. Liquid-liquid extraction was optimized using Hansen solubility parameters and diethyl ether finalized as an extraction solvent for the recovery ranging from 61 to 76% for all analytes in mice plasma. The validated method has an accuracy and precision over the linearity range of 0.1-200 ng/mL with a correlation coefficient (r 2 ) of ≥0.997. The intra and inter-day assay accuracy was between 98.17 and 107% and 95.83-107.89% respectively and the intra and inter day assay precision ranged from 0.37-6.05% and 1.85-10.76%, respectively for all the analytes. This validated method can be used for future clinical investigation studies of Eclipta alba extracts. Copyright © 2018 Elsevier B.V. All rights reserved.

Greater apparent absorption of flavonoids is associated with lesser human fecal flavonoid disappearance rates.

PubMed

Simons, Andrean L; Renouf, Mathieu; Murphy, Patricia A; Hendrich, Suzanne

2010-01-13

It was hypothesized that 5,7,4'-OH-flavonoids disappeared more rapidly from human fecal incubations and were less absorbable by humans than flavonoids without 5-OH moieties. Anaerobic fecal disappearance rates over 24 h were determined for 15 flavonoids in samples from 20 men and 13 women. In these anaerobic fecal mixtures, flavonoids with 5,7,4'-OH groups, genistein, apigenin, naringenin, luteolin, kaempferol, and quercetin (disappearance rate, k=0.46+/-0.10 h(-1)), and methoxylated flavonoids, hesperetin and glycitein (k=0.24+/-0.21 h(-1)), disappeared rapidly compared with flavonoids lacking 5-OH (e.g., daidzein, k=0.07+/-0.03 h(-1)). Apparent absorption of flavonoids that disappeared rapidly from in vitro fecal incubations, genistein, naringenin, quercetin, and hesperetin, was compared with that of daidzein, a slowly disappearing flavonoid, in 5 men and 5 women. Subjects ingested 104 micromol of genistein and 62 micromol of daidzein (soy milk), 1549 micromol of naringenin and 26 micromol of hesperetin (grapefruit juice), and 381 micromol of quercetin (onions) in three test meals, each separated by 1 week. Blood and urine samples were collected over 24 h after each test meal. Plasma flavonoid concentrations ranged from 0.01 to 1 microM. The apparent absorption, expressed as percentage of ingested dose excreted in urine, was significantly less for naringenin (3.2+/-1.7%), genistein (7.2+/-4.6%), hesperetin (7.3+/-3.2%), and quercetin (5.6+/-3.7%) compared with daidzein (43.4+/-15.5%, p=0.02). These data affirmed the hypothesis that the 5,7,4'-OH of flavonoids limited apparent absorption of these compounds in humans.

Effect of citrus flavonoids on HL-60 cell differentiation.

PubMed

Kawaii, S; Tomono, Y; Katase, E; Ogawa, K; Yano, M

1999-01-01

Twenty-seven Citrus flavonoids were examined for their activity of induction of terminal differentiation of human promyelocytic leukemia cells (HL-60) by nitro blue tetrazolium (NBT) reducing, nonspecific esterase, specific esterase, and phagocytic activities. 10 flavonoids were judged to be active (percentage of NBT reducing cells was more than 40% at a concentration of 40 microM), and the rank order of potency was natsudaidain, luteolin, tangeretin, quercetin, apigenin, 3, 3, '4, '5, 6, 7, 8-heptamethoxyflavone, nobiletin, acacetin, eriodictyol, and taxifolin. These flavonoids exerted their activity in a dose-dependent manner. HL-60 cells treated with these flavonoids differentiated into mature monocyte/macrophage. The structure-activity relationship established from comparison between flavones and flavanones revealed that ortho-catechol moiety in ring B and C2-C3 double bond had an important role for induction of differentiation of HL-60. In polymethoxylated flavones, hydroxyl group at C3 and methoxyl group at C8 enhanced the differentiation-inducing activity.

SERS study of riboflavin on green-synthesized silver nanoparticles prepared by reduction using different flavonoids: What is the role of flavonoid used?

NASA Astrophysics Data System (ADS)

Švecová, Marie; Ulbrich, Pavel; Dendisová, Marcela; Matějka, Pavel

2018-04-01

Spectroscopy of surface-enhanced Raman scattering (SERS) is nowadays widely used in the field of bio-science and medicine. These applications require new enhancing substrates with special properties. They should be non-toxic, environmentally friendly and (bio-) compatible with examined samples. Flavonoids are natural antioxidants with many positive effects on human health. Simultaneously, they can be used as reducing agent in preparation procedure of plasmonic enhancing substrate for SERS spectroscopy. The best amplifiers of Raman vibrational spectroscopic signal are generally silver nanoparticles (AgNPs). In this study, several flavonoids (forming a logical set) were used as reducing agent in AgNPs preparation procedures. Reactivity of 10 structurally arranged flavonoids (namely flavone, chrysin, apigenin, luteolin, tricetin, 3-hydroxyflavone, galangin, kaempferol, quercetin and myricetin) was compared and SERS-activity of prepared AgNPs was tested using model analyte riboflavin. Riboflavin was detected down to concentration 10-9 mol/l.

Biogenesis of C-Glycosyl Flavones and Profiling of Flavonoid Glycosides in Lotus (Nelumbo nucifera)

PubMed Central

Li, Shan-Shan; Wu, Jie; Chen, Li-Guang; Du, Hui; Xu, Yan-Jun; Wang, Li-Jing; Zhang, Hui-Jin; Zheng, Xu-Chen; Wang, Liang-Sheng

2014-01-01

Flavonoids in nine tissues of Nelumbo nucifera Gaertner were identified and quantified by high-performance liquid chromatography with diode array detector (HPLC-DAD) and HPLC-electrospray ionization-mass spectrometry (HPLC-ESI-MSn). Thirty-eight flavonoids were identified; eleven C-glycosides and five O-glycosides were discovered for the first time in N. nucifera. Most importantly, the C-glycosyl apigenin or luteolin detected in lotus plumules proved valuable for deep elucidation of flavonoid composition in lotus tissues and for further utilization as functional tea and medicine materials. Lotus leaves possessed the significantly highest amount of flavonoids (2.06E3±0.08 mg 100 g−1 FW) and separating and purifying the bioactive compound, quercetin 3-O-glucuronide, from leaves showed great potential. In contrast, flavonoids in flower stalks, seed coats and kernels were extremely low. Simultaneously, the optimal picking time was confirmed by comparing the compound contents in five developmental phases. Finally, we proposed the putative flavonoid biosynthesis pathway in N. nucifera. PMID:25279809

Evaluation of the inhibitory effects of quercetin-related flavonoids and tea catechins on the monoamine oxidase-A reaction in mouse brain mitochondria.

PubMed

Bandaruk, Yauhen; Mukai, Rie; Kawamura, Tomoyuki; Nemoto, Hisao; Terao, Junji

2012-10-17

Quercetin, a typical dietary flavonoid, is thought to exert antidepressant effects by inhibiting the monoamine oxidase-A (MAO-A) reaction, which is responsible for regulation of the metabolism of the neurotransmitter 5-hydroxytryptamine (5-HT) in the brain. This study compared the MAO-A inhibitory activity of quercetin with those of O-methylated quercetin (isorhamnetin, tamarixetin), luteolin, and green tea catechins ((-)-epicatechin, (-)-epicatechin gallate, (-)-epigallocatechin, and (-)-epigallocatechin gallate) by measuring the formation of the oxidative deamination product of 5-HT, 5-hydroxyindole aldehyde (5-HIAL), in mouse brain mitochondria. Quercetin was inferior to luteolin in the inhibition of MAO-A activity, whereas isorhamnetin, tamarixetin, and tea catechins scarcely exerted inhibitory activity. Quercetin did not affect MAO-A activity in mouse intestinal mitochondria, indicating that it does not evoke side effects on the metabolism of dietary monoamines in the gut. These data suggest that quercetin is a weak (but safe) MAO-A inhibitor in the modulation of 5-HT levels in the brain.

Phytochemical constituents and chemosystematic significance of Chrozophora tinctoria (L.) Raf.

PubMed

Marzouk, Mona M; Hussein, Sameh R; Kassem, Mona E S; Kawashty, Salwa A; El Negoumy, Sabry I M

2016-07-01

Twelve compounds were isolated from Chrozophora tinctoria (L.) Raf. They were identified as kaempferol, kaempferol 3-O-β-glucopyranoside, kaempferol 3-O-(6″-α-rhamnopyranosyl)-β-glucopyranoside, quercetin, quercetin 3-O-β-glucopyranoside, quercetin 3-O-(6″-α-rhamnopyranosyl)-β-glucopyranoside, apigenin, apigenin 7-O-β-glucopyranoside, acacetin, gallic acid, methyl gallate and β-sitosterol-3-O-β-glucopyranoside. Their structures were elucidated by chemical and spectral methods. Furthermore, chemosystematics of the isolated compounds is briefly discussed. It was indicated that C. tinctoria is the only species of Chrozophora that has the capability to synthesis kaempferol aglycone and their glycosides, and the finding is supported by its distinct morphological and anatomical aspects.

Chemical and Biological insights of Ouratea hexasperma (A. St.-Hil.) Baill.: a source of bioactive compounds with multifunctional properties.

PubMed

Fidelis, Queli Cristina; Faraone, Immacolata; Russo, Daniela; Aragão Catunda, Francisco Eduardo; Vignola, Lisiana; de Carvalho, Mario Geraldo; de Tommasi, Nunziatina; Milella, Luigi

2018-01-16

The study aimed to evaluate in vitro antioxidant, anticholinesterase and antidiabetic properties of Ouratea hexasperma (A. St.-Hil.) Baill. The inflorescence methanol extract and the ethyl acetate fraction of leaves and stems reported the highest Relative Antioxidant Capacity Index (RACI), whereas the dichloromethane fraction of leaves was the best inhibitor of α-amylase and α-glucosidase. Trans-3-O-methyl-resveratrol-2-C-β-glucoside, lithospermoside, 2,5-dimethoxy-p-benzoquinone, lup-20(30)-ene-3β,28-diol, 7-O-methylgenistein, apigenin and luteolin and amentoflavone were isolated from O. hexasperma. Resveratrol derivative was isolated for the first time in Ochnaceae family. Luteolin, followed by apigenin, reported the highest Relative Antioxidant Capacity Index and they were also the best inhibitors of α-glucosidase enzyme.

Comparison of extraction methods for the analysis of natural dyes in historical textiles by high-performance liquid chromatography.

PubMed

Valianou, Lemonia; Karapanagiotis, Ioannis; Chryssoulakis, Yannis

2009-12-01

Different methods for the extraction of Dactylopius coccus Costa, Rubia tinctorum L., Isatis tinctoria L., Reseda luteola L., Curcuma longa L. and Cotinus coggygria Scop. from wool fibres are investigated using high-performance liquid chromatography with diode array detector (HPLC-DAD). The efficiencies of five extraction methods which include the use of HCl (widely used extraction method), citric acid, oxalic acid, TFA and a combination of HCOOH and EDTA are compared on the basis of the (a) number, (b) relative quantities, measured as HPLC peak areas and (c) signal-to-noise ratios (S/N) of the compounds extracted from the wool substrates. Flavonoid glycosides and curcuminoids contained in R. luteola L. and C. longa L., respectively, according to liquid chromatography with mass spectrometry (LC-MS) identifications, are not detected after treating the fibres with HCl. All the other milder methods are successful in extracting these compounds. Experiments are performed using HPLC-DAD to compare the HPLC peak areas and the S/N of the following extracted compounds: indigotin, indirubin, curcumin, demethoxycurcumin, bisdemethoxycurcumin, fisetin, sulfuretin, luteolin, luteolin-7-O-glucoside, apigenin, carminic acid, alizarin, puruprin and rubiadin. It is shown that the TFA method provides overall the best results as it gives elevated extraction yields except for fisetin, luteolin, apigenin and luteolin-7-O-glucoside and highest S/N except for fisetin and luteolin-7-O-glucoside. It is noteworthy that treatment of the fibres with the typical HCl extraction method results overall in very low S/N. The TFA method is selected for further studies, as follows. First, it is applied on silk dyed samples and compared with the HCl method. The same relative differences of the TFA and HCl methods observed for the wool dyed samples are reported for the silk dyed samples too, except for rubiadin, luteolin and apigenin. Thus, in most cases, the nature of the substrate (wool or silk) appears to have negligible effects on the relative difference of the two extraction methods. Second, the selected TFA method is applied to treat wool and silk historical samples extracted from textiles of the Mamluk period, resulting in the identification of several colouring compounds. In all extraction methods mentioned above, DMSO is used to dissolve the dyes, after acid treatment.

Phenolic metabolites in leaves of the invasive shrub, Lonicera maackii, and their potential phytotoxic and anti-herbivore effects.

PubMed

Cipollini, Don; Stevenson, Randall; Enright, Stephanie; Eyles, Alieta; Bonello, Pierluigi

2008-02-01

Lonicera maackii is an invasive shrub in North America for which allelopathic effects toward other plants or herbivores have been suspected. We characterized the major phenolic metabolites present in methanol extracts of L. maackii leaves. In addition, we examined the effects of methanol-water extracts of L. maackii leaves on seed germination of a target plant species and on feeding preference and growth rate of a generalist insect herbivore. A total of 13 individual major and minor compounds were detected in crude leaf extracts by high-performance liquid chromatography coupled to electronspray ionization-tandem mass spectrometry (ESI-MS/MS). Extracts were dominated by two major flavones, apigenin and luteolin, and their glucoside derivatives, apigenin-7-glucoside and luteolin-7-glucoside. Quantities of these compounds, along with chlorogenic acid, varied between two sampling points. Leaf extracts that contained these compounds were inhibitory to seed germination of Arabidopsis thaliana. In addition, treatment of artificial diet with leaf extracts deterred feeding of the generalist herbivore, Spodoptera exigua, in choice experiments but had no effect on growth rate in short-term no-choice bioassays. Purified apigenin tended to deter feeding by S. exigua and inhibited seed germination of A. thaliana. We conclude that leaves of L. maackii contain phenolic compounds, including apigenin and chlorogenic acid, capable of having biological effects on other plants and insects.

Chemical compositions and antibacterial activity of extracts obtained from the inflorescences of Cirsium canum (L.) all.

PubMed

Kozyra, Małgorzata; Biernasiuk, Anna; Malm, Anna; Chowaniec, Marcin

2015-01-01

The aim of this study was to investigate phenolic acids and flavonoids in methanolic, dichloromethane, acetone and ethyl acetate extracts and fractions from inflorescences of Cirsium canum (L.). RP-HPLC analysis enabled identification of the following: chlorogenic acid, caffeic acid, p-coumaric acid, protocatechuic acid, p-hydroxybenzoic acid, vanillic acid, syringic acid, trans-cinnamic acid, luteolin-7-glucoside, apigenin-7-glucoside, kaempferol-3-glucoside, linarin, apigenin, rutoside, luteolin and kaempferol. The antimicrobial activity of tested extracts was determined in vitro against reference microorganisms, including bacteria or fungi, belonging to yeasts. Our data showed that the tested extracts had no influence on the growth of the reference strains of Gram-negative bacteria and yeasts belonging to Candida spp. Among them, the fractions possessed the highest activity against Gram-positive bacteria, especially Streptococcus aureus and Streptococcus pneumoniae belonging to pathogens and Streptococcus epidermidis, Bacilluscereus and Bacillus subtilis belonging to opportunistic microorganisms.

Flavonoid C- and O-glycosides from the Mongolian medicinal plant Dianthus versicolor Fisch.

PubMed

Obmann, Astrid; Werner, Ingrid; Presser, Armin; Zehl, Martin; Swoboda, Zita; Purevsuren, Sodnomtseren; Narantuya, Samdan; Kletter, Christa; Glasl, Sabine

2011-09-27

Eighteen flavonoids were identified from an aqueous extract of the aerial parts of Dianthus versicolor, a plant used in traditional Mongolian medicine against liver diseases. The flavonoid C- and O-glycosides isoorientin-7-O-rutinoside, isoorientin-7-O-rhamnosyl-galactoside, isovitexin-7-O-rutinoside, isovitexin-7-O-rhamnosyl-galactoside, isoscoparin-7-O-rutinoside, isoscoparin-7-O-rhamnosyl-galactoside, isoscoparin-7-O-galactoside, and isoorientin-7-O-galactoside were isolated and structurally elucidated. Their structures were established on the basis of extensive spectroscopic techniques including LC-UV-DAD, LC-MS(n), LC-HRMS, 1D and 2D NMR spectroscopy, and by GC-MS analysis after hydrolysis. Flavonoids with such a high glycosylation pattern are rare within the genus Dianthus. Furthermore, isovitexin-7-O-glucoside (saponarin), isovitexin-2″-O-rhamnoside, apigenin-6-glucoside (isovitexin), luteolin-7-O-glucoside, apigenin-7-O-glucoside, as well as the aglycons luteolin, apigenin, chrysoeriol, diosmetin, and acacetin were identified by TLC and LC-DAD-MS(n) in comparison to reference substances or literature data. The NMR data of seven structures have not been reported in the literature to date. Copyright © 2011 Elsevier Ltd. All rights reserved.

Apigenin Inhibits Cancer Stem Cell-Like Phenotypes in Human Glioblastoma Cells via Suppression of c-Met Signaling.

PubMed

Kim, Boram; Jung, Narae; Lee, Sanghun; Sohng, Jae Kyung; Jung, Hye Jin

2016-11-01

Glioblastoma (GBM) is a highly malignant human brain tumor with limited treatment choices. The extremely aggressive characteristics of GBM result from GBM stem cells (GSCs), a subpopulation in tumor having self-renewal potential and resistance to chemotherapy and radiotherapy. Therefore, eliminating GSCs is an effective strategy to treat this fatal disease. In this study, we investigated the therapeutic effects of dietary flavonoids, including apigenin, quercetin, and naringenin, against cancer stem cell-like phenotypes of human GBM cell lines U87MG and U373MG. Among flavonoids studied, apigenin and quercetin significantly suppressed not only the self-renewal capacity such as cell growth and clonogenicity, but also the invasiveness of GBM stem-like cells. Notably, apigenin blocked the phosphorylation of c-Met and its downstream effectors, transducer and activator of transcription 3, AKT (Protein kinase B), and mitogen-activated protein kinase in the GSCs, thereby reducing the expression levels of GSC markers such as CD133, Nanog, and Sox2. These results suggest that the GSC inhibition effect of apigenin may be caused by downregulation of c-Met signaling pathway. Copyright © 2016 John Wiley & Sons, Ltd.

Determination of anthocyanins and non-anthocyanin polyphenols by ultra performance liquid chromatography/electrospray ionization mass spectrometry (UPLC/ESI-MS) in jussara (Euterpe edulis) extracts.

PubMed

Vieira, Gláucia S; Marques, Anna S F; Machado, Mariana T C; Silva, Vanessa M; Hubinger, Miriam D

2017-06-01

This work aimed to propose two analytical methods for the quantitative and qualitative analysis of major anthocyanins and non-anthocyanin phenolic compounds in jussara ( Euterpe edulis ) extracts, using ultra performance liquid chromatography-mass spectrometry. These methods were evaluated for selectivity, precision, linearity, detection and quantification limits. The complete separation of 5 anthocyanins and 22 non-anthocyanins polyphenols was achieved in 4.5 and 7 min, respectively. Limits of detection ranged from 0.55 to 9.24 µg/L, with relative standard deviation for concentration up to 7.0%. In jussara extract, 13 of the 27 analytes were characterized. The dominant compound was cyanidin-3-O-rutinoside, representing about 73% of the total phenolic compounds content (approximately 23 mg/g of extract in dry weight). Other phenolic compounds found in the extract were: cyanidin-3-O-glucoside, pelargonidin-3-O-glucoside, quercetin, rutin, myricetin, kaempferol, kaempferol-3-O-rutinoside, luteolin, apigenin, catechin, ellagic acid and 4,5-dicaffeoylquinic acid.

Effects of Luteolin and Quercetin in Combination with Some Conventional Antibiotics against Methicillin-Resistant Staphylococcus aureus

PubMed Central

Usman Amin, Muhammad; Khurram, Muhammad; Khan, Taj Ali; Faidah, Hani S.; Ullah Shah, Zia; Ur Rahman, Shafiq; Haseeb, Abdul; Ilyas, Muhammad; Ullah, Naseem; Umar Khayam, Sahibzada Muhammad; Iriti, Marcello

2016-01-01

The present study was designed to evaluate the effects of flavonoids luteolin (L) and quercetin + luteolin (Q + L) in combination with commonly used antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates and S. aureus (ATCC 43300). Minimum inhibitory concentrations (MICs) of L and Q + L, as well as the MICs of flavonoids in combination with antibiotics were determined and results showed an increased activity of flavonoids with antibiotics. The synergistic, additive, or antagonistic relationships between flavonoids (L and Q + L) and antibiotics were also evaluated, and additive and synergistic effects were observed for some antibiotic + flavonoid combinations. In addition, some combinations were also found to damage the bacterial cytoplasmic membrane, as assessed through potassium leakage assay. The effects of flavonoids and flavonoids + antibiotics on mecA gene mutations were also tested, and no functional variation was detected in the coding region. PMID:27879665

Berry and Citrus Phenolic Compounds Inhibit Dipeptidyl Peptidase IV: Implications in Diabetes Management

PubMed Central

Fan, Junfeng; Lila, Mary Ann; Yousef, Gad

2013-01-01

Beneficial health effects of fruits and vegetables in the diet have been attributed to their high flavonoid content. Dipeptidyl peptidase IV (DPP-IV) is a serine aminopeptidase that is a novel target for type 2 diabetes therapy due to its incretin hormone regulatory effects. In this study, well-characterized anthocyanins (ANC) isolated from berry wine blends and twenty-seven other phenolic compounds commonly present in citrus, berry, grape, and soybean, were individually investigated for their inhibitory effects on DPP-IV by using a luminescence assay and computational modeling. ANC from blueberry-blackberry wine blends strongly inhibited DPP-IV activity (IC50, 0.07 ± 0.02 to >300 μM). Of the twenty-seven phenolics tested, the most potent DPP-IV inhibitors were resveratrol (IC50, 0.6 ± 0.4 nM), luteolin (0.12 ± 0.01 μM), apigenin (0.14 ± 0.02 μM), and flavone (0.17 ± 0.01 μM), with IC50 values lower than diprotin A (4.21 ± 2.01 μM), a reference standard inhibitory compound. Analyses of computational modeling showed that resveratrol and flavone were competitive inhibitors which could dock directly into all three active sites of DPP-IV, while luteolin and apigenin docked in a noncompetitive manner. Hydrogen bonding was the main binding mode of all tested phenolic compounds with DPP-IV. These results indicate that flavonoids, particularly luteolin, apigenin, and flavone, and the stilbenoid resveratrol can act as naturally occurring DPP-IV inhibitors. PMID:24069048

Identification and partial characterization of C-glycosylflavone markers in Asian plant dyes using liquid chromatography-tandem mass spectrometry.

PubMed

Mouri, Chika; Laursen, Richard

2011-10-14

Flavonoids in the grasses (Poaceae family), Arthraxon hispidus (Thunb.) Makino and Miscanthus tinctorius (Steudel) Hackel have long histories of use for producing yellow dyes in Japan and China, but up to now there have been no analytical procedures for characterizing the dye components in textiles dyed with these materials. LC-MS analysis of plant material and of silk dyed with extracts of these plants shows the presence, primarily, of flavonoid C-glycosides, three of which have been tentatively identified as luteolin 8-C-rhamnoside, apigenin 8-C-rhamnoside and luteolin 8-C-(4-ketorhamnoside). Two of these compounds, luteolin 8-C-rhamnoside (M=432), apigenin 8-C-rhamnoside (M=416), along with the previously known tricin (M=330) and several other flavonoids that appear in varying amounts, serve as unique markers for identifying A. hispidus and M. tinctorius as the source of yellow dyes in textiles. Using this information, we have been able to identify grass-derived dyes in Japanese textiles dated to the Nara and Heian periods. However, due to the high variability in the amounts of various flavonoid components, our goal of distinguishing between the two plant sources remains elusive. Copyright © 2011 Elsevier B.V. All rights reserved.

Comparative study of the flavonoids of some Verbena species cultivated in Egypt by using high-performance liquid chromatography coupled with ultraviolet spectroscopy and atmospheric pressure chemical ionization mass spectrometry.

PubMed

El-Hela, Atef A; Al-Amier, Hussein A; Ibrahim, Taghreed A

2010-10-08

Verbena rigida L., Verbena tenera Spreng. and Verbena venosa L. were investigated for their flavonoid content. Analysis was carried out by high-performance liquid chromatography coupled to diode array UV detection (LC-UV), using different techniques, also using post-column addition of shift reagents, afforded precise structural information about the position of the free hydroxyl groups in the flavonoid nucleus. LC-MS using atmospheric pressure chemical ionization (APCI) in the positive mode provided the molecular weight, the number of hydroxyl groups, the number of sugars and an idea about the substitution pattern of the flavonoid. On-line UV and MS data demonstrated the presence of orientin, vitexin, isovitexin, luteolin, luteolin 7-O-glucoside, apigenin 7-O-glucoside in addition to luteolin, chryseriol and apigenin aglycones in the three Verbena species with different concentrations. Quantitative determination of flavonoid content revealed the presence of 69.84 mg/g dry sample, 88.26 mg/g dry sample and 85.82 mg/g dry sample total flavonoid compounds in V. rigida L., V. tenera Spreng. and V. venosa L., respectively. The method developed for identification is useful for further chromatographic fingerprinting of plant flavonoids. Copyright © 2010 Elsevier B.V. All rights reserved.

[Influence of cutting seedling on growth, quality and yield of both aerial and underground part by cutting seedling in Scutellaria baicalensis].

PubMed

Liu, Rong-Xiu; Li, Yong-Jie; Li, Lin; Miao, Xiao-Su; Wang, Xue-Sen; Zhang, Dan; Wei, Sheng-Li

2016-06-01

By measuring the growth data of Scutellaria baicalensis in different cutting-seedling and determined active ingredient contents by HPLC and ultraviolet spectrophotometric determination. such as flavonoids. baicalin. wogonoside. baicalein. wogonin. oroxylin A. scutellarin. luteolin. and apigenin in the whole plant. Under circumstances of guaranteeing the quality and yield of medicinal materials. the yield of medicinal materials. and stems and leaves reached 193.60,63.21 kg/mu after twice cutting seedling. Not only yield but also active ingredient contents have been improved to some extent. the contents of flavonoids. baicalin. wogonoside. baicalein. wogonin. oroxylin A reached 18.52%. 15.13%. 4.03%. 1.04%. 1.04%. 0.12%. respectively in roots. Luteolin was not detected in young stems and leaves of S. baicalensis,the contents of other active ingredients such as scutellarin. luteolin and apigenin reached 7.00%. 0.96%. 0.04% respectively under twice cutting seedling. Therefore. regular cutting seedling could be regard as a new cultivation technique for wider range of promotion. And gaining high quality and yield of medicinal materials and tea with the purpose of rational utilization of natural resources and promoting the development of integration of herbal combination. Copyright© by the Chinese Pharmaceutical Association.

Evaluation on bioactivities of total flavonoids from Lavandula angustifolia.

PubMed

Zhao, Jun; Xu, Fang; Huang, Hua; Ji, Tengfei; Li, Chenyang; Tan, Wei; Chen, Yan; Ma, Long

2015-07-01

Lavandula angustifolia was used to treat flus and fevers, joint swelling and pain in Uighur medicine. This study aimed to investigate antioxidant, antit anti-inflammatory and antalgic noids content (530.1mg/g rutin/g dry extract) with stronger DPPH scavenging abilities and reduciactivities of total flavonoids from Lavandula angustifolia (LTF). Results indicated that LTF possesses the highest total flavong power. Some flavonoids separated from LTF, and their DPPH scavenging abilities as follows: rosmarinic acid (2, near to Vit C) >luteolin (3) >apigenin (4) >luteolin 7-O-β-D-glucoside (5) >apigenin 7-O-β-D-glucoside (6) >luteolin 7-O-β-D-glucuronide (7). LTF significantly decreased malondialdehyde (MDA) level in D-galactose induced aging model compared to the control group (P<0.05), as well as significantly increased plasma superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities (P<0.05). Moreover, 17.4, 34.8 and 69.6 mg/kg doses of LTF were exhibited significant analgesic and anti-inflammatory activities in a dose dependent manner (P<0.05). Cytotoxicity of LTF on Bel-7402 and Hela cell lines were showed by MTT assay also. These results verified traditional usage of this plant and suggested also that LTF is worth developing and studying further.

Simultaneous determination of phenolic acids and flavonoids in rice using solid-phase extraction and RP-HPLC with photodiode array detection.

PubMed

Irakli, Maria N; Samanidou, Victoria F; Biliaderis, Costas G; Papadoyannis, Ioannis N

2012-07-01

An analytical method based on an optimized solid-phase extraction procedure and followed by high-performance liquid chromatography (HPLC) separation with diode array detection was developed and validated for the simultaneous determination of phenolic acids (gallic, protocatechuic, 4-hydroxy-benzoic, vanillic, caffeic, syringic, p-coumaric, ferulic, sinapic, and cinnamic acids), flavanols (catechin and epicatechin), flavonols (myricetin, quercetin, kaempferol, quercetin-3-O-glucoside, hyperoside, and rutin), flavones (luteolin and apigenin) and flavanones (naringenin and hesperidin) in rice flour (Oryza sativa L.). Chromatographic separation was carried out on a PerfectSil Target ODS-3 (250 mm × 4.6 mm, 3 μm) column at temperature 25°C using a mobile phase, consisting of 0.5% (v/v) acetic acid in water, methanol, and acetonitrile at a flow rate 1 mL min(-1) , under gradient elution conditions. Application of optimum extraction conditions, elaborated on both Lichrolut C(18) and Oasis HLB cartridges, have led to extraction of phenolic acids and flavonoids from rice flour with mean recoveries 84.3-113.0%. The developed method was validated in terms of linearity, accuracy, precision, stability, and sensitivity. Repeatability (n = 5) and inter-day precision (n = 4) revealed relative standard deviation (RSD) <13%. The optimized method was successfully applied to the analysis of phenolic acids and flavonoids in pigmented (red and black rice) and non-pigmented rice (brown rice) samples. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Flavonol and flavone intakes in US health professionals.

PubMed

Sampson, Laura; Rimm, Eric; Hollman, Peter C H; de Vries, Jeanne H M; Katan, Martijn B

2002-10-01

To determine flavonoid content of US foods, mean individual intakes, major food sources, and associations with other nutrients. US men (n = 37,886) and women (n = 78,886) who completed a semiquantitative food frequency questionnaire in 1990. Men and women completed a questionnaire that listed 132 items, including onions as a garnish and as a vegetable, rings, or soup. Foods known to be important sources of flavonols (quercetin, myricetin, and kaempferol) and flavones (luteolin and apigenin) were analyzed biochemically. The database contained values from the analyzed foods, previously published values from Dutch foods, and imputed values. Means and standard deviations, contributions of foods to summed intake of each flavonoid, and Pearson correlation coefficients were calculated. Of the flavonols and flavones studied, quercetin contributed 73% in women and 76% in men. The mean flavonol and flavone intake was approximately 20 to 22 mg per day. Onions, tea, and apples contained the highest amounts of flavonols and flavones. Correlations between the intakes of flavonols and flavones and intakes of beta carotene, vitamin E, vitamin C, folic acid, and dietary fiber did not exceed 0.35. Although flavonols and flavones are subgroups of flavonoids hypothesized to be associated with reduced risk of coronary heart disease, data on flavonoid intake has been limited due to the lack of food composition data. Nutrition professionals can use these and other published data to estimate intake of flavonoids in their populations. This work should facilitate the investigation of this class of dietary antioxidants as a contributor to disease prevention.

Inhibition of Angiotensin-Converting Enzyme Activity by Flavonoids: Structure-Activity Relationship Studies

PubMed Central

Guerrero, Ligia; Castillo, Julián; Quiñones, Mar; Garcia-Vallvé, Santiago; Arola, Lluis; Pujadas, Gerard; Muguerza, Begoña

2012-01-01

Previous studies have demonstrated that certain flavonoids can have an inhibitory effect on angiotensin-converting enzyme (ACE) activity, which plays a key role in the regulation of arterial blood pressure. In the present study, 17 flavonoids belonging to five structural subtypes were evaluated in vitro for their ability to inhibit ACE in order to establish the structural basis of their bioactivity. The ACE inhibitory (ACEI) activity of these 17 flavonoids was determined by fluorimetric method at two concentrations (500 µM and 100 µM). Their inhibitory potencies ranged from 17 to 95% at 500 µM and from 0 to 57% at 100 µM. In both cases, the highest ACEI activity was obtained for luteolin. Following the determination of ACEI activity, the flavonoids with higher ACEI activity (i.e., ACEI >60% at 500 µM) were selected for further IC50 determination. The IC50 values for luteolin, quercetin, rutin, kaempferol, rhoifolin and apigenin K were 23, 43, 64, 178, 183 and 196 µM, respectively. Our results suggest that flavonoids are an excellent source of functional antihypertensive products. Furthermore, our structure-activity relationship studies show that the combination of sub-structures on the flavonoid skeleton that increase ACEI activity is made up of the following elements: (a) the catechol group in the B-ring, (b) the double bond between C2 and C3 at the C-ring, and (c) the cetone group in C4 at the C-ring. Protein-ligand docking studies are used to understand the molecular basis for these results. PMID:23185345

Effects of food formulation and thermal processing on flavones in celery and chamomile.

PubMed

Hostetler, Gregory L; Riedl, Ken M; Schwartz, Steven J

2013-11-15

Flavones isolated from celery varied in their stability and susceptibility to deglycosylation during thermal processing at pH 3, 5, or 7. Apigenin 7-O-apiosylglucoside was converted to apigenin 7-O-glucoside when heated at pH 3 and 100°C. Apigenin 7-O-glucoside showed little conversion or degradation at any pH after 5h at 100°C. Apigenin, luteolin, and chrysoeriol were most stable at pH 3 but progressively degraded at pH 5 or 7. Chamomile and celery were used to test the effects of glycosidase-rich foods and thermal processing on the stability of flavone glycosides. Apigenin 7-O-glucoside in chamomile extract was readily converted to apigenin aglycone after combination with almond, flax seed, or chickpea flour. Apigenin 7-O-apiosylglucoside in celery leaves was resistant to conversion by β-glucosidase-rich ingredients, but was converted to apigenin 7-O-glucoside at pH 2.7 when processed at 100°C for 90min and could then be further deglycosylated when mixed with almond or flax seed. Thus, combinations of acid hydrolysis and glycosidase enzymes in almond and flax seed were most effective for developing a flavone-rich, high aglycone food ingredient from celery. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effects of food formulation and thermal processing on flavones in celery and chamomile

PubMed Central

Hostetler, Gregory L.; Riedl, Ken M.; Schwartz, Steven J.

2013-01-01

Flavones isolated from celery varied in their stability and susceptibility to deglycosylation during thermal processing at pH 3, 5, or 7. Apigenin 7-O-apiosylglucoside was converted to apigenin 7-O-glucoside when heated at pH 3 and 100 °C. Apigenin 7-O-glucoside showed little conversion or degradation at any pH after 5 h at 100 °C. Apigenin, luteolin, and chrysoeriol were most stable at pH 3 but progressively degraded at pH 5 or 7. Chamomile and celery were used to test the effects of glycosidase-rich foods and thermal processing on the stability of flavone glycosides. Apigenin 7-O-glucoside in chamomile extract was readily converted to apigenin aglycone after combination with almond, flax seed, or chickpea flour. Apigenin 7-O-apiosylglucoside in celery leaves was resistant to conversion by β-glucosidase-rich ingredients, but was converted to apigenin 7-O-glucoside at pH 2.7 when processed at 100 °C for 90 min and could then be further deglycosylated when mixed with almond or flax seed. Thus, combinations of acid hydrolysis and glycosidase enzymes in almond and flax seed were most effective for developing a flavone-rich, high aglycone food ingredient from celery. PMID:23790931

Qualitative and quantitative analyses of flavonoids in Spirodela polyrrhiza by high-performance liquid chromatography coupled with mass spectrometry.

PubMed

Qiao, Xue; He, Wen-ni; Xiang, Cheng; Han, Jian; Wu, Li-jun; Guo, De-an; Ye, Min

2011-01-01

Spirodela polyrrhiza (L.) Schleid. is a traditional Chinese herbal medicine for the treatment of influenza. Despite its wide use in Chinese medicine, no report on quality control of this herb is available so far. To establish qualitative and quantitative analytical methods by high-performance liquid chromatography (HPLC) coupled with mass spectrometry (MS) for the quality control of S. polyrrhiza. The methanol extract of S. polyrrhiza was analysed by HPLC/ESI-MS(n). Flavonoids were identified by comparing with reference standards or according to their MS(n) (n = 2-4) fragmentation behaviours. Based on LC/MS data, a standardised HPLC fingerprint was established by analysing 15 batches of commercial herbal samples. Furthermore, quantitative analysis was conducted by determining five major flavonoids, namely luteolin 8-C-glucoside, apigenin 8-C-glucoside, luteolin 7-O-glucoside, apigenin 7-O-glucoside and luteolin. A total of 18 flavonoids were identified by LC/MS, and 14 of them were reported from this herb for the first time. The HPLC fingerprints contained 10 common peaks, and could differentiate good quality batches from counterfeits. The total contents of five major flavonoids in S. polyrrhiza varied significantly from 4.28 to 19.87 mg/g. Qualitative LC/MS and quantitative HPLC analytical methods were established for the comprehensive quality control of S. polyrrhiza. Copyright © 2011 John Wiley & Sons, Ltd.

Inhibition of human cytochromes P450 2A6 and 2A13 by flavonoids, acetylenic thiophenes and sesquiterpene lactones from Pluchea indica and Vernonia cinerea.

PubMed

Boonruang, Supattra; Prakobsri, Khanistha; Pouyfung, Phisit; Srisook, Ekaruth; Prasopthum, Aruna; Rongnoparut, Pornpimol; Sarapusit, Songklod

2017-12-01

The human liver cytochrome P450 (CYP) 2A6 and the respiratory CYP2A13 enzymes play role in nicotine metabolism and activation of tobacco-specific nitrosamine carcinogens. Inhibition of both enzymes could offer a strategy for smoking abstinence and decreased risks of respiratory diseases and lung cancer. In this study, activity-guided isolation identified four flavonoids 1-4 (apigenin, luteolin, chrysoeriol, quercetin) from Vernonia cinerea and Pluchea indica, four hirsutinolide-type sesquiterpene lactones 5-8 from V. cinerea, and acetylenic thiophenes 9-11 from P. indica that inhibited CYP2A6- and CYP2A13-mediated coumarin 7-hydroxylation. Flavonoids were most effective in inhibition against CYP2A6 and CYP2A13, followed by thiophenes, and hirsutinolides. Hirsutinolides and thiophenes exhibited mechanism-based inhibition and in irreversible mode against both enzymes. The inactivation kinetic K I values of hirsutinolides against CYP2A6 and CYP2A13 were 5.32-15.4 and 0.92-8.67 µM, respectively, while those of thiophenes were 0.11-1.01 and 0.67-0.97 µM, respectively.

Molecular mechanisms of flavonoids in melanin synthesis and the potential for the prevention and treatment of melanoma

PubMed Central

Liu-Smith, Feng; Meyskens, Frank

2016-01-01

Flavonoids are becoming popular nutraceuticals. Different flavonoids show similar or distinct biological effects on different tissues or cell types, which may limit or define their usefulness in cancer prevention and/or treatment application. This review focuses on a few selected flavonoids and discusses their functions in normal and transformed pigment cells, including cyanidin, apigenin, genistein, fisetin, EGCG, luteolin, baicalein, quercetin and kaempferol. Flavonoids exhibit melanogenic or anti-melanogenic effects mainly via transcriptional factor MiTF and/or the melanogenesis enzymes tyrosinase, DCT2 or TYRP-1. To identify a direct target has been a challenge as most studies were not able to discriminate whether the effect(s) of the flavonoid were from direct targeting or represented indirect effects. Flavonoids exhibit an anti-melanoma effect via inhibiting cell proliferation and invasion and inducing apoptosis. The mechanisms are also multi-fold, via ROS-scavenging, immune-modulation, cell cycle regulation and epigenetic modification including DNA methylation and histone deacetylation. In summary, although many flavonoid compounds are extremely promising nutraceuticals, their detailed molecular mechanism and their multi-target (simultaneously targeting multiple molecules) nature warrant further investigation before advancement to translation studies or clinical trials. PMID:26865001

[Advance in chemical constituents of genus Clematis].

PubMed

Sun, Feng; Yang, Depo

2009-10-01

Progresses in the studies on chemical constituents of Clematis L. (belonging to the family Ranunculaceae) were systematiically reviewed in this article. The plants in this genus have a wide spectrum of constituents as follows: triterpenes, flavonoids, lignans, coumarins, alkaloids, volatile oils, steroids, organic acids, macrocyclic compounds and phenols, etc., among which triterpenoid saponins, flavonoids and lignans are the main components. The triterpenoid saponins are mainly oleanolic type and hederagenin type, most of which are bidesmosidic saponins, substituted with oligosaccharide chains at both C-3 and C-28, and some are substituted with acetyl, caffeoyl, isoferuloyl, p-methoxy cinnamyl and 3,4-dimethoxy cinnamyl groups in the oligosaccharide chains. The flavonoids from Clematis species are mainly flavones, flavonols, flavanones, isoflavones, xanthones and their glucosides (sugar moieties are connected to the aglycone through either the oxygen or the carbon atoms), the aglycones of which are mainly apigenin, kaempferol, luteolin and quercetin. The lignans from Clematis are mainly eupomatene lignans, cyclolignans, monoepoxylignans, bisepoxylignans and lignanolides. Clematis spp. are rich in resources, however, studies on their chemical constituents have only been carried out on twenty or so spp. As a result, it is necessary to expand our study on other spp. from this genus for better utilization of medicinal resources.

Carbonic anhydrase inhibitors: in vitro inhibition of α isoforms (hCA I, hCA II, bCA III, hCA IV) by flavonoids.

PubMed

Ekinci, Derya; Karagoz, Lutfi; Ekinci, Deniz; Senturk, Murat; Supuran, Claudiu T

2013-04-01

A series of flavonoids, such as quercetin, catechin, apigenin, luteolin, morin, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase (CA). The compounds were tested against four α-CA isozymes purified from human and bovine (hCA I, hCA II, bCA III, hCA IV) tissues. The four isozymes showed quite diverse inhibition profiles with these compounds. The flavonoids inhibited hCA I with K(I)-s in the range of 2.2-12.8 μM, hCA II with K(I)-s in the range of 0.74-6.2 μM, bCA III with K(I)-s in the range of 2.2-21.3 μM, and hCA IV with inhibition constants in the range of 4.4-15.7, with an esterase assay using 4-nitrophenyl acetate as substrate. Some simple phenols/sulfonamides were also investigated as standard inhibitors. The flavonoids incorporate phenol moieties which inhibit these CAs through a diverse, not yet determined inhibition mechanism, compared to classic inhibitors such as the sulfonamide/sulfamate ones.

Synergistic inhibition of Haemonchus contortus exsheathment by flavonoid monomers and condensed tannins

PubMed Central

Klongsiriwet, Chaweewan; Quijada, Jessica; Williams, Andrew R.; Mueller-Harvey, Irene; Williamson, Elizabeth M.; Hoste, Hervé

2015-01-01

This study investigated the separate and combined anthelmintic (AH) effects of different phenolic compounds, including condensed tannins and flavonoids, all of which are known to occur in willow leaves, a potentially valuable dry season feed. A range of contrasting model tannins, which span the whole range of willow tannins, were isolated from tilia flowers, goat willow leaves, black currant leaves and red currant leaves. All together, the tested compounds represented the major tannin types (procyanidins and prodelphinidins) and flavonoid types (flavonols, flavones and flavanones). The larval exsheathment inhibition assay (LEIA) was used to assess their in vitro effects on Haemonchus contortus third stage larvae. Arbutin, vanillic acid, and taxifolin proved to be ineffective whereas naringenin, quercetin and luteolin were highly effective at 250 μM concentrations. Procyanidin (PC) tannins tended to be less active than prodelphinidin tannins (PD). Experiments with combinations of tannins and quercetin or luteolin revealed for the first time the existence of synergistic AH effects between tannins and flavonoid monomers. They also provided evidence that synergistic effects appear to occur at slightly lower concentrations of PC than PD. This suggests that the AH activity of condensed tannins can be significantly enhanced by the addition of quercetin or luteolin. This information may prove useful for plant breeding or selection and for designing optimal feed mixtures. PMID:26199861

Identification and screening of active components from Ziziphora clinopodioides Lam. in regulating autophagy.

PubMed

Zhang, Xuan-Ming; An, Dong-Qing; Guo, Long-Long; Yang, Ning-Hui; Zhang, Hua

2018-04-03

This study investigated the flavonoid constituents of a traditional Chinese medical plant Ziziphora clinopodioides Lam. by using ultra-performance liquid chromatography coupled with quadruple time-of-flight mass spectrometry and screened the active components in regulating autophagy.Normal rat kidney (NRK) cells transfected with green fluorescent protein- microtubule-associated protein 1 light Chain 3(GFP-LC3) were treated with Z. clinopodioides flavonoids and its chemical compositions. After 4 h of treatment, the auto-phagy spot aggregation in NRK cells was photographed and observed by laser scanning confocal microscopy. The following 10 flavonoid components of Z. clinopodioides were identified: baicalein(1), quercetin(2), hyperoside(3), quercetin3-O-β-d-glucopyranoside(4), apigenin(5), kaempferol(6), chrysin(7), diosimin(8), linarin(9) and rutin(10). Among these flavonoids, chrysin, apigenin and quercetin were identified as the active principles in activating autophagy. This research may provide a reference for further developing and utilizing Z. clinopodioides.

Interactions of flavonoids with iron and copper ions: a mechanism for their antioxidant activity.

PubMed

Mira, Lurdes; Fernandez, M Tereza; Santos, Marta; Rocha, Rui; Florêncio, M Helena; Jennings, Keith R

2002-11-01

The metal chelating properties of flavonoids suggest that they may play a role in metal-overload diseases and in all oxidative stress conditions involving a transition metal ion. A detailed study has been made of the ability of flavonoids to chelate iron (including Fe3+) and copper ions and its dependence of structure and pH. The acid medium may be important in some pathological conditions. In addition, the ability of flavonoids to reduce iron and copper ions and their activity-structure relationships were also investigated. To fulfill these objectives, flavones (apigenin, luteolin, kaempferol, quercetin, myricetin and rutin), isoflavones (daidzein and genistein), flavanones (taxifolin, naringenin and naringin) and a flavanol (catechin) were investigated. All flavonoids studied show higher reducing capacity for copper ions than for iron ions. The flavonoids with better Fe3+ reducing activity are those with a 2,3-double bond and possessing both the catechol group in the B-ring and the 3-hydroxyl group. The copper reducing activity seems to depend largely on the number of hydroxyl groups. The chelation studies were carried out by means of ultraviolet spectroscopy and electrospray ionisation mass spectrometry. Only flavones and the flavanol catechin interact with metal ions. At pH 7.4 and pH 5.5 all flavones studied appear to chelate Cu2+ at the same site, probably between the 5-hydroxyl and the 4-oxo groups. Myricetin and quercetin, however, at pH 7.4, appear to chelate Cu2+ additionally at the ortho-catechol group, the chelating site for catechin with Cu2+ at pH 7.4. Chelation studies of Fe3+ to flavonoids were investigated only at pH 5.5. Only myricetin and quercetin interact strongly with Fe3+, complexation probably occurring again between the 5-hydroxyl and the 4-oxo groups. Their behaviour can be explained by their ability to reduce Fe3+ at pH 5.5, suggesting that flavonoids reduce Fe3+ to Fe2+ before association.

Assessment of anti-inflammatory, antinociceptive, immunomodulatory, and antioxidant activities of Cajanus cajan L. seeds cultivated in Egypt and its phytochemical composition.

PubMed

Hassan, Emad M; Matloub, Azza A; Aboutabl, Mona E; Ibrahim, Nabaweya A; Mohamed, Samy M

2016-08-01

Cajanus cajan L. (Fabaceae), a food crop, is widely used in traditional medicine. The phytochemical composition of C. cajan seeds and evaluation of the anti-inflammatory, immunomodulatory, antinociceptive, and antioxidant activities were studied. Unsaponifiable matter and fatty acids were analyzed by GC and GC/MS. The n-butanol fraction was chromatographed on polyamide column. The anti-inflammatory activity of hexane extract (200 and 400 mg/kg, p.o.) was evaluated using the carrageenan-induced rat paw edema at 1, 2, and 3 h. The serum tumor necrosis factor-α, interleukin-6, and immunoglobulin G levels were detected by ELISA. The hexane extract antinociceptive activity was determined by adopting the writhing test in mice. DPPH radical scavenging, total reduction capability, and inhibition of lipid peroxidation of butanol fraction were evaluated. Twenty-one unsaponifiable compounds (mainly phytol, 2,6-di-(t-butyl)-4-hydroxy-4-methyl-2,5-cyclohexadiene-1-one, β-sitosterol, stigmasterol, and campesterol), as well as 12 fatty acids (primarily 9,12-octadecadienoic and palmitic acids) were identified in hexane extract of C. cajan seeds. n-BuOH fraction contains quercetin-3-O-β-d-glucopyranoside, orientin, vitexin, quercetin, luteolin, apigenin, and isorhamnetin. For the first time, quercetin-3-O-β-d-glucopyranoside is isolated from C. cajan plant. The hexane extract (200 and 400 mg/kg) inhibited carrageenan-induced inflammation by 85 and 95%, respectively, 3 h post-carrageenan challenge. This was accompanied by an 11 and 20%, 8 and 13%, respectively, decrease of TNF-α and IL-6, as well as significant decrease in IgG serum levels. Moreover, hexane extract (200 and 400 mg/kg) decreased the number of writhings by 61 and 83%, respectively. The butanol fraction showed DPPH radical scavenging (inhibitory concentration (IC50) value: 9.07 μg/ml).

Inhibition of proinflammatory biomarkers in THP1 macrophages by polyphenols derived from chamomile, meadowsweet and willow bark.

PubMed

Drummond, Elaine M; Harbourne, Niamh; Marete, Eunice; Martyn, Danika; Jacquier, Jc; O'Riordan, Dolores; Gibney, Eileen R

2013-04-01

Antiinflammatory compounds in the diet can alleviate excessive inflammation, a factor in the pathogenesis of common diseases such as rheumatoid arthritis, atherosclerosis and diabetes. This study examined three European herbs, chamomile (Matricaria chamomilla), meadowsweet (Filipendula ulmaria L.) and willow bark (Salix alba L.), which have been traditionally used to treat inflammation and their potential for use as antiinflammatory agents. Aqueous herbal extracts and isolated polyphenolic compounds (apigenin, quercetin and salicylic acid, 0-100 μM) were incubated with THP1 macrophages, and interleukin (IL)-1β, IL-6 and tumour necrosis factor-alpha (TNF-α) were measured. At concentrations of 10 μM, both apigenin and quercetin reduced IL-6 significantly ( p < 0.05). Apigenin at 10 μM and quercetin at 25 μM reduced TNF-α significantly ( p < 0.05). Amongst the herbal extracts, willow bark had the greatest antiinflammatory activity at reducing IL-6 and TNF-α production. This was followed by meadowsweet and then chamomile. The lowest effective antiinflammatory concentrations were noncytotoxic (MTT mitochondrial activity assay). The Comet assay, which was used to study the protective effect of the isolated phenols against oxidative damage, showed positive results for all three polyphenols. These are the first findings that demonstrate the antiinflammatory capacity of these herbal extracts. Copyright © 2012 John Wiley & Sons, Ltd.

Antioxidant activities and quali-quantitative analysis of different Smallanthus sonchifolius [(Poepp. and Endl.) H. Robinson] landrace extracts.

PubMed

Russo, D; Malafronte, N; Frescura, D; Imbrenda, G; Faraone, I; Milella, L; Fernandez, E; De Tommasi, N

2015-01-01

Five landraces of Smallanthus sonchifolius [(Poepp. and Endl.) H. Robinson], known as yacon, were investigated in total phenolic content, antioxidant activity and chemical composition of ethanol extracts (EEs) and decoction extracts (DEs). The results demonstrated that DEs are rich in phenolic acids as caffeic acid, while the EEs show an higher amount of flavonoids, as luteolin 3',7-O-diglucoside and luteolin 7-O-glucoside. These flavonoid glycosides were identified for the first time in yacon extracts, together with apigenin and luteolin. The phytochemical profile explains the different antioxidant activities shown in our study. The landraces PER6-DE and PER4-DE showed the highest radical-scavenging activity and reducing power related to their polyphenolic contents. Results also show that yacon can be considered an important source of bioactive compounds with significant differences among the analysed landraces.

Quantitative determination of phenolic compounds by UHPLC-UV-MS and use of partial least-square discriminant analysis to differentiate chemo-types of Chamomile/Chrysanthemum flower heads.

PubMed

Avula, Bharathi; Wang, Yan-Hong; Wang, Mei; Avonto, Cristina; Zhao, Jianping; Smillie, Troy J; Rua, Diego; Khan, Ikhlas A

2014-01-01

A new rapid UHPLC-UV-QTOF/MS method has been developed for the simultaneous analysis of nine phenolic compounds [(Z)-2-β-d-glucopyranosyloxy-4-methoxycinnamic acid (cis-GMCA), chlorogenic acid, (E)-2-β-d-glucopyranosyloxy-4-methoxycinnamic acid (trans-GMCA), quercetagetin-7-O-β-d-glucopyranoside, luteolin-7-O-β-d-glucoside, apigenin-7-O-β-d-glucoside, chamaemeloside, apigenin 7-O-(6″-O-acetyl-β-d-glucopyranoside), apigenin] and one polyacetylene (tonghaosu) from the flower heads of Chamomile/Chrysanthemum samples. The chromatographic separation was achieved using a reversed phase C18 column with a mobile phase of water and acetonitrile, both containing 0.05% formic acid. The ten compounds were completely separated within 15min at a flow rate of 0.25mL/min with a 2μL injection volume. The different chemo-types of Chamomiles/Chrysanthemum displayed variations in the presence of chemical constituents. German Chamomile samples confirmed the presence of cis-GMCA, trans-GMCA, apigenin-7-O-β-d-glucoside and tonghaosu as major constituents whereas Roman chamomile samples confirmed the presence of chamamaeloside and apigenin as major compounds. The Chrysanthemum morifolium samples showed the presence of luteolin-7-O-β-d-glucose as the major compound. The method was applied for the analysis of various commercial products including capsules, tea bags, body and hair care products. LC-mass spectrometry with electrospray ionization (ESI) interface method is described for the evaluation of ten compounds in plant samples and commercial products. This method involved the detection of [M+Na](+) and [M+H](+) ions in the positive mode. Partial least squares discriminant analysis (PLS-DA) was used to visualize commercial samples quality and may be of value for discriminating between chamomile types and Chrysanthemum with regards to the relative content of individual constituents. The results indicated that the method is suitable as a quality control test for various Chamomile/Chrysanthemum samples and market products. Copyright © 2013 Elsevier B.V. All rights reserved.

Inhibitory effect of luteolin on estrogen biosynthesis in human ovarian granulosa cells by suppression of aromatase (CYP19).

PubMed

Lu, Dan-feng; Yang, Li-juan; Wang, Fei; Zhang, Guo-lin

2012-08-29

Inhibition of aromatase, the key enzyme in estrogen biosynthesis, is an important strategy in the treatment of breast cancer. Several dietary flavonoids show aromatase inhibitory activity, but their tissue specificity and mechanism remain unclear. This study found that the dietary flavonoid luteolin potently inhibited estrogen biosynthesis in a dose- and time-dependent manner in KGN cells derived from human ovarian granulosa cells, the major source of estrogens in premenopausal women. Luteolin decreased aromatase mRNA and protein expression in KGN cells. Luteolin also promoted aromatase protein degradation and inhibited estrogen biosynthesis in aromatase-expressing HEK293A cells, but had no effect on recombinant expressed aromatase. Estrogen biosynthesis in KGN cells was inhibited with differing potencies by extracts of onion and bird chili and by four other dietary flavonoids: kaempferol, quercetin, myricetin, and isorhamnetin. The present study suggests that luteolin inhibits estrogen biosynthesis by decreasing aromatase expression and destabilizing aromatase protein, and it warrants further investigation as a potential treatment for estrogen-dependent cancers.

Measurement of xanthine oxidase inhibition activity of phenolics and flavonoids with a modified cupric reducing antioxidant capacity (CUPRAC) method.

PubMed

Ozyürek, Mustafa; Bektaşoğlu, Burcu; Güçlü, Kubilay; Apak, Reşat

2009-03-16

Various dietary polyphenolics have been found to show an inhibitory effect on xanthine oxidase (XO) which mediates oxidative stress-originated diseases because of its ability to generate reactive oxygen species (ROS), including superoxide anion radical (O(2)(-)) and hydrogen peroxide. XO activity has usually been determined by following the rate of uric acid formation from xanthine-xanthine oxidase (X-XO) system using the classical XO activity assay (UV-method) at 295nm. Since some polyphenolics have strong absorption from the UV to visible region, XO-inhibitory activity of polyphenolics was alternatively determined without interference by directly measuring the formation of uric acid and hydrogen peroxide using the modified CUPRAC (cupric reducing antioxidant capacity) spectrophotometric method at 450nm. The CUPRAC absorbance of the incubation solution due to the reduction of Cu(II)-neocuproine reagent by the products of the X-XO system decreased in the presence of polyphenolics, the difference being proportional to the XO inhibition ability of the tested compound. The structure-activity relationship revealed that the flavones and flavonols with a 7-hydroxyl group such as apigenin, luteolin, kaempferol, quercetin, and myricetin inhibited XO-inhibitory activity at low concentrations (IC(50) values from 1.46 to 1.90microM), while the flavan-3-ols and naringin were less inhibitory. The findings of the developed method for quercetin and catechin in the presence of catalase were statistically alike with those of HPLC. In addition to polyphenolics, five kinds of herbs were evaluated for their XO-inhibitory activity using the developed method. The proposed spectrophotometric method was practical, low-cost, rapid, and could reliably assay uric acid and hydrogen peroxide in the presence of polyphenols (flavonoids, simple phenolic acids and hydroxycinnamic acids), and less open to interferences by UV-absorbing substances.

Differential inhibition of oxidized LDL-induced apoptosis in human endothelial cells treated with different flavonoids.

PubMed

Jeong, Yu-Jin; Choi, Yean-Jung; Kwon, Hyang-Mi; Kang, Sang-Wook; Park, Hyoung-Sook; Lee, Myungsook; Kang, Young-Hee

2005-05-01

High plasma level of cholesterol is a well-known risk factor for atherosclerotic diseases. Oxidized LDL induces cellular and nuclear damage that leads to apoptotic cell death. We tested the hypothesis that flavonoids may function as antioxidants with regard to LDL incubated with 5 microm-Cu(2+) alone or in combination with human umbilical vein endothelial cells (HUVEC). Cytotoxicity and formation of thiobarbituric acid-reactive substances induced by Cu(2+)-oxidized LDL were examined in the presence of various subtypes of flavonoid. Flavanols, flavonols and flavanones at a non-toxic dose of 50 microm markedly inhibited LDL oxidation by inhibiting the formation of peroxidative products. In contrast, the flavones luteolin and apigenin had no such effect, with >30 % of cells killed after exposure to 0.1 mg LDL/ml. Protective flavonoids, especially (-)-epigallocatechin gallate, quercetin, rutin and hesperetin, inhibited HUVEC nuclear condensation and fragmentation induced by Cu(2+)-oxidized LDL. In addition, immunochemical staining and Western blot analysis revealed that anti-apoptotic Bcl-2 expression was enhanced following treatment with these protective flavonoids. However, Bax expression and caspase-3 cleavage stimulated by 18 h incubation with oxidized LDL were reduced following treatment with these protective flavonoids. The down-regulation of Bcl-2 and up-regulation of caspase-3 activation were reversed by the cytoprotective flavonoids, (-)-epigallocatechin gallate, quercetin and hesperetin, at >/=10 microm. These results suggest that flavonoids may differentially prevent Cu(2+)-oxidized LDL-induced apoptosis and promote cell survival as potent antioxidants. Survival potentials of certain flavonoids against cytotoxic oxidized LDL appeared to stem from their disparate chemical structure. Furthermore, dietary flavonoids may have therapeutic potential for protecting the endothelium from oxidative stress and oxidized LDL-triggered atherogenesis.

Dietary flavonoids and cancer risk in the Zutphen Elderly Study.

PubMed

Hertog, M G; Feskens, E J; Hollman, P C; Katan, M B; Kromhout, D

1994-01-01

Flavonoids are polyphenolic antioxidants naturally present in vegetable foods. Some flavonoids, such as quercetin, inhibit carcinogenesis in rodents, but their effect in humans is unknown. We measured the flavonoids quercetin, kaempferol, myricetin, apigenin, and luteolin in foods and assessed flavonoid intake in 1985 by dietary history in 738 men aged 65-84 years without a history of cancer, who were then followed for five years. Mean flavonoid intake was 25.9 mg/day. The major sources of flavonoid intake were tea at 61% and vegetables and fruits (mainly onions, kale, endive, and apples) at 38%. Between 1985 and 1990, 75 men developed cancer (all sites) and 34 men died from cancer. Flavonoid intake in 1985 was not associated with incidence of all-cause cancer (p for trend = 0.54) or with mortality from all-cause cancer (p for trend = 0.51). Flavonoid intake was also not associated with risk of cancers of the alimentary and respiratory tract (p for trend = 0.92). Adjustment for age, body mass index, smoking, physical activity, and vitamin C, vitamin E, beta-carotene, and dietary fiber intake did not change the relative risks. A high intake of flavonoids from vegetables and fruits only was inversely associated with risk of cancer of the alimentary and respiratory tract (relative risk of highest vs. lowest tertile = 0.51, 95% confidence interval 0.25-1.05); these results suggest the presence of other nonvitamin components with anticarcinogenic potential in these foods. We conclude that intake of flavonoids, mainly from tea, apples, and onions, does not predict a reduced risk of all-cause cancer or of cancer of the alimentary and respiratory tract in elderly men. The effect of flavonoids on risk of cancer at specific sites needs further investigation in prospective cohort studies.

Flavonoids from Argentine Tagetes (Asteraceae) with antimicrobial activity.

PubMed

Tereschuk, María L; Baigorí, Mario D; De Figueroa, Lucia I C; Abdala, Lidia R

2004-01-01

The flavonoids, constituting one of the most numerous and widespread groups of natural plant constituents, are important to humans not only because they contribute to plant colors but also because many members are physiologically active. These low-molecular-weight substances, found in all vascular plants, are phenylbenzopyrones. Over 4000 structures have been identified in plant sources, and they are categorized into several groups. Primarily recognized as pigments responsible for the autumnal burst of hues and the many shades of yellow, orange, and red in flowers and food, the flavonoids are found in fruits, vegetables, nuts, seeds, stems, flowers, and leaves as well as tea and wine and are important constituents of the human diet. They are prominent components of citrus fruits and other food sources. Flavonols (quercetin, myricetin, and kaempferol) and flavones (apigenin and luteolin) are the most common phenolics in plant-based foods. Quercetin is also a predominant component of onions, apples, and berries. Such flavanones as naringin are typically present in citrus fruit, and flavanols, particularly catechin, are present as catechin gallate in such beverages as green or black tea and wine. Some major sources of flavonoids are outlined in Table 1. The daily intake of flavonoids in humans has been estimated to be approx 25 mg/d, a quantity that could provide pharmacologically significant concentrations in body fluids and tissues, assuming good absorption from the gastrointestinal tract. Biological activity of flavonoids was first suggested by Szent-Gÿorgyi 1938, who reported that citrus peel flavonoids were effective in preventing the capillary bleeding and fragility associated with scurvy. The broad spectrum of biological activity within the group and the multiplicity of actions displayed by a certain individual members make the flavonoids one of the most promising classes of biologically active compounds.

Metabolic profile of the bioactive compounds of burdock (Arctium lappa) seeds, roots and leaves.

PubMed

Ferracane, Rosalia; Graziani, Giulia; Gallo, Monica; Fogliano, Vincenzo; Ritieni, Alberto

2010-01-20

In this work the bioactive metabolic profile, the antioxidant activity and total phenolic content of burdock (Arctium lappa) seeds, leaves and roots were obtained. TEAC values and total phenolic content for hydro-alcoholic extracts of burdock ranged from 67.39 to 1.63 micromol Trolox equivalent/100g dry weight (DW), and from 2.87 to 45 g of gallic acid equivalent/100g DW, respectively. Phytochemical compounds were analyzed by liquid chromatography coupled to electrospray tandem mass spectrometry (LC/MS/MS) in negative mode. The main compounds of burdock extracts were caffeoylquinic acid derivatives, lignans (mainly arctiin) and various flavonoids. The occurrence of some phenolic acids (caffeic acid, chlorogenic acid and cynarin) in burdock seeds; arctiin, luteolin and quercetin rhamnoside in burdock roots; phenolic acids, quercetin, quercitrin and luteolin in burdock leaves was reported for the first time.

HPLC-DAD-ESI/MS(n) profiling of phenolic compounds from Lathyrus cicera L. seeds.

PubMed

Ferreres, F; Magalhães, S C Q; Gil-Izquierdo, A; Valentão, P; Cabrita, A R J; Fonseca, A J M; Andrade, P B

2017-01-01

Lathyrus cicera L. seeds are of interest for food and feed purposes. Despite the recognized antioxidant activity of the seeds, arising from the phenolic fraction, their phenolic compounds have not been studied in depth yet. Therefore, to determine the phenolics profile of these seeds, a target analysis was performed using high-performance liquid chromatography coupled to photodiode-array detection and electrospray ionization/ion trap mass spectrometry (HPLC-DAD-ESI/MS(n)). Thirty-seven glycosylated flavonoids were identified for the first time in the seeds of this species and, according to their MS fragmentation, clustered in flavonol-3-O-di-/tri-glycosides-7-O-rhamnosides and other flavonol-glycosides, and flavonol-3-O-(cinnamoyl)glycoside-7-O-rhamnosides, flavonol-3-O-(dihydrophaseoyl, cinnamoyl)glycoside-7-O-rhamnosides and flavonol-3-O-(malonyl)glycoside-7-O-rhamnosides. Glycosides of kaempferol were the main flavonoids found (10 non-acylated and 21 acylated), followed by those of quercetin (3) and those of isorhamnetin, apigenin and luteolin (1). The most abundant flavonols were identified as kaempferol-3-O-(2-hexosyl)hexoside-7-O-rhamnosides. The methodology used allowed to increase the knowledge on a relevant phytochemical class of seeds from L. cicera. Copyright © 2016 Elsevier Ltd. All rights reserved.

Plant flavonoids in cancer chemoprevention: role in genome stability.

PubMed

George, Vazhappilly Cijo; Dellaire, Graham; Rupasinghe, H P Vasantha

2017-07-01

Carcinogenesis is a multistage process that involves a series of events comprising of genetic and epigenetic changes leading to the initiation, promotion and progression of cancer. Chemoprevention is referred to as the use of nontoxic natural compounds, synthetic chemicals or their combinations to intervene in multistage carcinogenesis. Chemoprevention through diet modification, i.e., increased consumption of plant-based food, has emerged as a most promising and potentially cost-effective approach to reducing the risk of cancer. Flavonoids are naturally occurring polyphenols that are ubiquitous in plant-based food such as fruits, vegetables and teas as well as in most medicinal plants. Over 10,000 flavonoids have been characterized over the last few decades. Flavonoids comprise of several subclasses including flavonols, flavan-3-ols, anthocyanins, flavanones, flavones, isoflavones and proanthocyanidins. This review describes the most efficacious plant flavonoids, including luteolin, epigallocatechin gallate, quercetin, apigenin and chrysin; their hormetic effects; and the molecular basis of how these flavonoids contribute to the chemoprevention with a focus on protection against DNA damage caused by various carcinogenic factors. The present knowledge on the role of flavonoids in chemoprevention can be used in developing effective dietary strategies and natural health products targeted for cancer chemoprevention. Copyright © 2016 Elsevier Inc. All rights reserved.

Assessment of Olea europaea L. fruit extracts: Phytochemical characterization and anticancer pathway investigation.

PubMed

Maalej, Amina; Bouallagui, Zouhaier; Hadrich, Fatma; Isoda, Hiroko; Sayadi, Sami

2017-06-01

Olea europaea L. has been widely used as an advantageous rich source of bioactive compounds of high economic value leading to its use in pharmaceutical, cosmetic, and agriculture industries. Ethanolic extracts of olive fruits from three different cultivars (OFE) were studied for their phytochemical contents and were investigated for antioxidant activities and anticancer potential. Major polyphenols detected in these extracts were tyrosol, hydroxytyrosol, oleuropein, rutin, quercetin and glucoside forms of luteolin and apigenin. All these compounds have shown to significantly contribute to the antioxidant activity of OFE, which was evaluated by DPPH and ABTS assays. Proliferation of hepatic and colon cancer cells, HepG2 and Caco-2, were shown to be sensitive to OFE with IC 50 less than 1.6mg/ml for all tested extracts. Moreover, flow cytometry analysis showed that OFE induced cell cycle arrest in the S-phase within both HepG2 and Caco-2 cells. This has triggered a cell death mechanism as shown by DNA fragmentation, expression of p53 and phosphorylation level of Akt and Erk proteins. Interestingly, these extracts could be further used as a potential source of natural compounds with both antioxidant and anticancer effects. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

New Apigenin Glycoside, Polyphenolic Constituents, Anti-inflammatory and Hepatoprotective Activities of Gaillardia grandiflora and Gaillardia pulchella Aerial Parts.

PubMed

Moharram, Fatma A; El Dib, Rabab Abd El Moneim; Marzouk, Mohamed S; El-Shenawy, Siham M; Ibrahim, Haitham A

2017-07-01

Gaillardia grandiflora Hort. ex Van Houte and Gaillardia pulchella Foug are flowering plants widely cultivated in Egypt for their ornamental value. Previous reports demonstrated that sesquiterpene derivatives represent the major compounds in both species. Moreover, only few flavones were identified from genus Gaillardia and few studies on the cytotoxicity of G. pulchella were found. Investigation of the phenolic constituents of the aerial parts of both species and evaluation of their anti-inflammatory and hepatoprotective activities. The 80% aqueous methanol extracts (AME) were prepared for both plants and evaluated for their biological activities. Phytochemical investigation of both extracts resulted in isolation of twelve compounds, which have been identified on the basis of ultraviolet, 1D and 2D nuclear magnetic resonance spectroscopy and negative ESI-MS. The new 8-hydroxyapigenin 6- O -β-D-apiofuranosyl-(1'''→6'')- C -β-D- 4 C 1 -glucopyranoside was isolated from G. grandiflora for the first time in nature, along with schaftoside, luteolin 6-C-β-D- 4 C 1 -glucopyranoside 8-methyl ether, apigenin 6- C -β-D- 4 C 1 -glucopyranoside 8-methyl ether, isoorientin, isovitexin, 6-methoxyluteolin and hispidulin, as well as vicenin-2, vitexin, luteolin and apigenin, which were isolated from G. pulchella together with 6-methoxyluteolin. Furthermore, the AME of both species were found to be nontoxic to mice and exhibited significant anti-inflammatory and hepatoprotective activities in dose dependent manner. Current results shed light on the phenolic constituents of G. grandiflora and G. pulchella aerial parts and the safety of the AME of both species, in addition to their significant anti-inflammatory and hepatoprotective activities. Both plant species may be promising candidates for natural anti-inflammatory and hepatoprotective drugs. Phytochemical investigation of Gaillardia grandiflora and Gaillardia pulchella 80% aqueous methanol extracts of the aerial parts led to the isolation of twelve compoundsThe new compound 8-hydroxyapigenin 6- O -β-D-apiofuranosyl-(1''''→6'')- C -β-D-4C1-glucopyranoside was isolated from G. grandiflora for the first time in natureSchaftoside, luteolin 6- C -β-D-4C1-glucopyranoside 8-methyl ether, apigenin 6- C -β-D-4C1-glucopyranoside 8-methyl ether, isoorientin, isovitexin, 6-methoxyluteolin and hispidulin were isolated from G. grandiflora Vicenin-2, vitexin, luteolin, apigenin and 6-methoxyluteolin were isolated from G. pulchella The extracts of both species were nontoxic to mice up to 5 g/kg body weightBoth extracts exhibited significant anti-inflammatory and hepatoprotective activities in dose dependent manner Abbreviations used: ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AME: The 80% aqueous methanol extract of G. grandiflora or G. pulchella aerial parts; AST: Aspartate aminotransferase; br d: Broad doublet; Comp-PC: Comparative paper chromatography; d: Doublet; 2D-PC: Two-dimensional paper chromatography; DMSO-d6: Deuterated dimethyl sulfoxide; G.: Gaillardia ; GPx: Glutathione peroxidase; GRd: Glutathione reductase; GSH: glutathione; GST: Glutathione-S-transferase; J : Nuclear spin-spin coupling constant; m: Multiplet; [M-H]-: Molecular ion peak; MDA: Malondialdehyde; m / z : Mass/charge ratio; NO: Nitric oxide; p: Probability; PC: Paper chromatography; Rf: Retention flow; rpm: Rotation per minute; s: Singlet; SDE: The ethanol extract of Scoparia dulcis ; SE: Standard error; SOD: Superoxide dismutase; TMS: Tetramethylsilane; λmax: Maximum fluorescence emission wavelength.

New Apigenin Glycoside, Polyphenolic Constituents, Anti-inflammatory and Hepatoprotective Activities of Gaillardia grandiflora and Gaillardia pulchella Aerial Parts

PubMed Central

Moharram, Fatma A.; El Dib, Rabab Abd El Moneim; Marzouk, Mohamed S.; El-Shenawy, Siham M.; Ibrahim, Haitham A.

2017-01-01

Background: Gaillardia grandiflora Hort. ex Van Houte and Gaillardia pulchella Foug are flowering plants widely cultivated in Egypt for their ornamental value. Previous reports demonstrated that sesquiterpene derivatives represent the major compounds in both species. Moreover, only few flavones were identified from genus Gaillardia and few studies on the cytotoxicity of G. pulchella were found. Aim of the Study: Investigation of the phenolic constituents of the aerial parts of both species and evaluation of their anti-inflammatory and hepatoprotective activities. Materials and Methods: The 80% aqueous methanol extracts (AME) were prepared for both plants and evaluated for their biological activities. Phytochemical investigation of both extracts resulted in isolation of twelve compounds, which have been identified on the basis of ultraviolet, 1D and 2D nuclear magnetic resonance spectroscopy and negative ESI-MS. Results: The new 8-hydroxyapigenin 6-O-β-D-apiofuranosyl-(1’’’→6’’)-C-β-D-4C1-glucopyranoside was isolated from G. grandiflora for the first time in nature, along with schaftoside, luteolin 6-C-β-D-4C1-glucopyranoside 8-methyl ether, apigenin 6-C-β-D-4C1-glucopyranoside 8-methyl ether, isoorientin, isovitexin, 6-methoxyluteolin and hispidulin, as well as vicenin-2, vitexin, luteolin and apigenin, which were isolated from G. pulchella together with 6-methoxyluteolin. Furthermore, the AME of both species were found to be nontoxic to mice and exhibited significant anti-inflammatory and hepatoprotective activities in dose dependent manner. Conclusion: Current results shed light on the phenolic constituents of G. grandiflora and G. pulchella aerial parts and the safety of the AME of both species, in addition to their significant anti-inflammatory and hepatoprotective activities. Both plant species may be promising candidates for natural anti-inflammatory and hepatoprotective drugs. SUMMARY Phytochemical investigation of Gaillardia grandiflora and Gaillardia pulchella 80% aqueous methanol extracts of the aerial parts led to the isolation of twelve compoundsThe new compound 8-hydroxyapigenin 6-O-β-D-apiofuranosyl-(1’’’’→6’’)-C-β-D-4C1-glucopyranoside was isolated from G. grandiflora for the first time in natureSchaftoside, luteolin 6-C-β-D-4C1-glucopyranoside 8-methyl ether, apigenin 6-C-β-D-4C1-glucopyranoside 8-methyl ether, isoorientin, isovitexin, 6-methoxyluteolin and hispidulin were isolated from G. grandifloraVicenin-2, vitexin, luteolin, apigenin and 6-methoxyluteolin were isolated from G. pulchellaThe extracts of both species were nontoxic to mice up to 5 g/kg body weightBoth extracts exhibited significant anti-inflammatory and hepatoprotective activities in dose dependent manner Abbreviations used: ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AME: The 80% aqueous methanol extract of G. grandiflora or G. pulchella aerial parts; AST: Aspartate aminotransferase; br d: Broad doublet; Comp-PC: Comparative paper chromatography; d: Doublet; 2D-PC: Two-dimensional paper chromatography; DMSO-d6: Deuterated dimethyl sulfoxide; G.: Gaillardia; GPx: Glutathione peroxidase; GRd: Glutathione reductase; GSH: glutathione; GST: Glutathione-S-transferase; J: Nuclear spin-spin coupling constant; m: Multiplet; [M-H]−: Molecular ion peak; MDA: Malondialdehyde; m/z: Mass/charge ratio; NO: Nitric oxide; p: Probability; PC: Paper chromatography; Rf: Retention flow; rpm: Rotation per minute; s: Singlet; SDE: The ethanol extract of Scoparia dulcis; SE: Standard error; SOD: Superoxide dismutase; TMS: Tetramethylsilane; λmax: Maximum fluorescence emission wavelength. PMID:28808387

Elevated CO2 and salinity are responsible for phenolics-enrichment in two differently pigmented lettuces.

PubMed

Sgherri, Cristina; Pérez-López, Usue; Micaelli, Francesco; Miranda-Apodaca, Jon; Mena-Petite, Amaia; Muñoz-Rueda, Alberto; Quartacci, Mike Frank

2017-06-01

Both salt stress and high CO 2 level, besides influencing secondary metabolism, can affect oxidative status of plants mainly acting in an opposite way with salinity provoking oxidative stress and elevated CO 2 alleviating it. The aim of the present work was to study the changes in the composition of phenolic acids and flavonoids as well as in the antioxidant activity in two differently pigmented lettuce cvs (green or red leaf) when submitted to salinity (200 mM NaCl) or elevated CO 2 (700 ppm) or to their combination in order to evaluate how a future global change can affect lettuce quality. Following treatments, the red cv. always maintained higher levels of antioxidant secondary metabolites as well as antioxidant activity, proving to be more responsive to altered environmental conditions than the green one. Overall, these results suggest that the application of moderate salinity or elevated CO 2 , alone or in combination, can induce the production of some phenolics that increase the health benefits of lettuce. In particular, moderate salinity was able to induce the synthesis of the flavonoids quercetin, quercetin-3-O-glucoside, quercetin-3-O-glucuronide and quercitrin. Phenolics-enrichment as well as a higher antioxidant capacity were also observed under high CO 2 with the red lettuce accumulating cyanidin, free chlorogenic acid, conjugated caffeic and ferulic acid as well as quercetin, quercetin-3-O-glucoside, quercetin-3-O-glucuronide, luteolin-7-O-glucoside, rutin, quercitrin and kaempferol. When salinity was present in combination with elevated CO 2 , reduction in yield was prevented and a higher presence of phenolic compounds, in particular luteolin, was observed compared to salinity alone. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

[Studies on chemical constituents from herbs of Taraxacum mongolicum].

PubMed

Shi, Shu-Yun; Zhou, Chang-Xin; Xu, Yan; Tao, Qiao-Feng; Bai, Hua; Lu, Fu-Sheng; Lin, Wen-Yan; Chen, Hai-Yong; Zheng, Wei; Wang, Li-Wei; Wu, Yi-Hang; Zeng, Su; Huang, Ke-Xin; Zhao, Yu; Li, Xiao-Kun; Qu, Jia

2008-05-01

To investigate the chemical constituents of the herbs of Taraxacum mongolicum. The chemical constituents were isolated by various column chromatographic methods and their structures elucidated mainly by NMR and MS evidences. Forty-four components were obtained and identified were as artemetin (1), quercetin (2), quercetin-3', 4', 7-trime-thyl ether (3), luteolin (4), luteolin-7-O-beta-D-glucopyranoside (5), luteolin-7-O-beta-D-galactopyranoside (6), genkwanin (7), isoetin (8), hesperetin (9), genkwanin-4'-O-beta-D-lutinoside (10), hesperidin (11), quercetin-7-O-[beta-D-glucopyranosyl (1-->6) -beta-D-glucopyranoside (12), quercetin-3, 7-O-beta-D-diglucopyranoside (13), isoetin-7-O-beta-D-glucopyranosyl- 2'-O-alpha-L-arabinopyranoside (14), isoetin-7-O-beta-D-glucopyranosyl-2'-O-alpha-D-glucopyranoside (15), isoetin-7- O-beta-D-glucopyranosyl-2'-O-beta-D-xyloypyranoside (16), caffeic acid (17), furulic acid (18), 3-O-caffeoylquinic acid (19), 3, 5-di-O-caffeoylquinic acid (20), 3, 4-di-O-caffeoylquinic acid (21), 4, 5-di-O-caffeoylquinic acid (22), 1-hydroxymethyl-5-hydroxy-phenyl-2-O-beta-D-glucopyranoside (23), p-hydroxybenzoic acid (24), p-coumaric acid (25), 3, 5-dihydroxylbenzoic acid (26), gallic acid (27), gallicin (28), syringic acid (29), 3, 4-dihydroxybenzoic acid (30), caffeic acid ethyl ester (31), esculetin (32), rufescidride (33), mongolicumin A [6, 9, 10-trihydroxy-benzoxanthene-1, 2-dicarboxylic acid] (34), mongolicumin B [1 l-hydroxy-2-oxo-guaia-1 (10), 3, 5-trien-8, 12-lactone] (35), isodonsesquitin A (36), taraxacin (37), sesquiterpene ketolactone (38), taraxasteryl acetate (39), phi-taraxasteryl acetate (40) and lupenol acetate (41), palmitic acid (42), beta-sitosterol (43), and stigmasterol (44). Four compounds (14, 15, 34 and 35) were new compounds, compounds 1, 3, 6-13, 20-22, 30 and 31 were isolated from this genus for the first time, while compounds 18, 23-29, 32 and 37-42 were obtained from this species for the first time.

[Studies on chemical constituents from herbs of Botrychium lanuginosum].

PubMed

Wang, Dong; Liu, Xiao-qiu; Yao, Chun-suo; Fang, Wei-shuo

2008-11-01

To study the chemical constituents of Botrychium lanuginosum. Various chromatographic techniques were used to isolate and purify the constituents. The structures were elucidated by chemical evidence and spectroscopic methods. Ten compounds were isolated from the 95% ethanol extract of the herb of B. lanuginosum and their structures were elucidated as 30-nor-21beta-hopan-22-one (1), beta-sitosterol (2), luteolin (3), thunberginol A (4), apigenin (5), (6'-O-palmitoyl)-sitosterol-3-O-beta-D-glucoside (6), daucosterol (7), 1-O-beta-D-glucopyranosyl-(2S, 3R, 4E, 8Z)-2-[(2R-hydroxy hexadecanoyl) amino]-4, 8-octadecadiene-1, 3-diol (8), luteolin-7-O-glucoside (9), sucrose (10). Compounds 1-10 were isolated from this genus for the first time.

Synergistic activity and mechanism of action of ceftazidime and apigenin combination against ceftazidime-resistant Enterobacter cloacae.

PubMed

Eumkeb, Griangsak; Chukrathok, Somnuk

2013-02-15

The purpose of this investigation was to examine the antibacterial and synergistic effect of naturally occurring flavonoids, apigenin, quercetin, naringenin and ceftazidime when use singly and in combination against ceftazidime-resistant Enterobacter cloacae strains by minimum inhibitory concentration (MIC), checkerboard and viable count methods. The mode of actions were also studied by electronmicoscopy, enzyme assay, outer and inner membrane permeabilisation. The results showed that these strains were positive in the ESBL-ampC genes combination by multiplex PCR. These findings were confirmed by MICs that these strains were resistant to ceftazidime, cefepime and flomoxef at >1024, 16-24, >256 μg/ml respectively, while susceptible to imipenem at 1-2 μg/ml. The synergistic activity was observed at ceftazidime plus either apigenin or naringenin combinations with FIC indixes between <0.01 and <0.27 against these strains, whereas ceftazidime plus clavulanic acid or quercetin did not exhibit synergy. The modulation of ceftazidime-resistance by apigenin or narigenin significantly enhanced the activities of ceftazidime. The 5,7-OH group of A ring and one 4'-OH group of the B ring in apigenin and naringenin are important for synergistic activity. Viable counts showed that the killing of ceftazidime-resistant E. cloacae DMST 21394 (CREC) cells by 3 μg/ml ceftazidime was potentiated by 3 μg/ml apigenin to low levels (10(3) cfu/ml) over 6h. Electronmicroscopy clearly showed that ceftazidime 3 μg/ml in combination with 3 μg/ml of apigenin also caused marked morphological damage of cell wall, cell shape and plasma membrane of this strain. Enzymes assays indicated that apigenin showed marked inhibitory activity against penicillinase type IV from E. cloacae. The results for outer membrane (OM) permeabilization in both nitrocefin (NCF) assay and crystal violet uptake showed that the combination of ceftazidime plus apigenin significantly altered OM permeabilisation of CREC compared to control or single treatment of these agents. Both o-nitrophenyl-β-D-galactoside (ONPG) uptake and release of UV-absorbing material concentrations results exhibited that ceftazidime and apigenin combination damaged CREC cytoplasmic membrane (CM) and caused subsequent leakage of intracellular constituents. From the results, it can be concluded that apigenin and naringenin have the synergistic effect with ceftazidime to reverse bacterial resistance to this cephalosporin against CREC. This activity may be involved three mechanisms of action by apigenin. The first is on the peptidoglycan synthesis inhibition. The second mechanism is inhibition the activity of certain β-lactamase enzymes. The third mode of action is alteration of OM and CM permeabilization. Apigenin and naringenin have a sufficient margin of safety for therapeutic use. For this reason, apigenin and naringenin offer for the development of a valuable adjunct to ceftazidime against CREC, which currently almost cephalosporins resistance. Copyright © 2012 Elsevier GmbH. All rights reserved.

Apigenin inhibits the inducible expression of programmed death ligand 1 by human and mouse mammary carcinoma cells.

PubMed

Coombs, Melanie R Power; Harrison, Megan E; Hoskin, David W

2016-10-01

Programmed death ligand 1 (PD-L1) is expressed by many cancer cell types, as well as by activated T cells and antigen-presenting cells. Constitutive and inducible PD-L1 expression contributes to immune evasion by breast cancer (BC) cells. We show here that the dietary phytochemical apigenin inhibited interferon (IFN)-γ-induced PD-L1 upregulation by triple-negative MDA-MB-468 BC cells, HER2(+) SK-BR-3 BC cells, and 4T1 mouse mammary carcinoma cells, as well as human mammary epithelial cells, but did not affect constitutive PD-L1 expression by triple-negative MDA-MB-231 BC cells. IFN-β-induced expression of PD-L1 by MDA-MB-468 cells was also inhibited by apigenin. In addition, luteolin, the major metabolite of apigenin, inhibited IFN-γ-induced PD-L1 expression by MDA-MB-468 cells. Apigenin-mediated inhibition of IFN-γ-induced PD-L1 expression by MDA-MB-468 and 4T1 cells was associated with reduced phosphorylation of STAT1, which was early and transient at Tyr701 and sustained at Ser727. Apigenin-mediated inhibition of IFN-γ-induced PD-L1 expression by MDA-MB-468 cells also increased proliferation and interleukin-2 synthesis by PD-1-expressing Jurkat T cells that were co-cultured with MDA-MB-468 cells. Apigenin therefore has the potential to increase the vulnerability of BC cells to T cell-mediated anti-tumor immune responses. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Phenolic compounds from the leaf extract of artichoke (Cynara scolymus L.) and their antimicrobial activities.

PubMed

Zhu, Xianfeng; Zhang, Hongxun; Lo, Raymond

2004-12-01

A preliminary antimicrobial disk assay of chloroform, ethyl acetate, and n-butanol extracts of artichoke (Cynara scolymus L.) leaf extracts showed that the n-butanol fraction exhibited the most significant antimicrobial activities against seven bacteria species, four yeasts, and four molds. Eight phenolic compounds were isolated from the n-butanol soluble fraction of artichoke leaf extracts. On the basis of high-performance liquid chromatography/electrospray ionization mass spectrometry, tandem mass spectrometry, and nuclear magnetic resonance techniques, the structures of the isolated compounds were determined as the four caffeoylquinic acid derivatives, chlorogenic acid (1), cynarin (2), 3,5-di-O-caffeoylquinic acid (3), and 4,5-di-O-caffeoylquinic acid (4), and the four flavonoids, luteolin-7-rutinoside (5), cynaroside (6), apigenin-7-rutinoside (7), and apigenin-7-O-beta-D-glucopyranoside (8), respectively. The isolated compounds were examined for their antimicrobial activities on the above microorganisms, indicating that all eight phenolic compounds showed activity against most of the tested organisms. Among them, chlorogenic acid, cynarin, luteolin-7-rutinoside, and cynaroside exhibited a relatively higher activity than other compounds; in addition, they were more effective against fungi than bacteria. The minimum inhibitory concentrations of these compounds were between 50 and 200 microg/mL.

Antiproliferative activity of flavonoids: influence of the sequential methoxylation state of the flavonoid structure.

PubMed

Moghaddam, Ghazaal; Ebrahimi, Soltan Ahmad; Rahbar-Roshandel, Nahid; Foroumadi, Alireza

2012-07-01

Dracocephalum kotschyi Boiss. has been used as part of an ethnobotanical remedy against many forms of human cancer in Iran. It has been demonstrated that a flavonoid named xanthomicrol from D. kotschyi contributes to its preferential antiproliferative activity against malignant cells. In the present study, the antiproliferative activity of its flavonoid fraction was further characterized. Using liquid-liquid extraction and a semi-preparative reversed-phase HPLC method, eight flavonoid aglycones were isolated from the aerial parts of the plant and their identities were confirmed through MS and NMR analyses as luteolin, naringenin, apigenin, isokaempferide, cirsimaritin, penduletin, xanthomicrol and calycopterin. The in vitro antiproliferative activity of each compound was evaluated against a panel of established normal and malignant cell lines using the MTT assay and some structure-activity relationships were observed. The hydroxyflavones (luteolin, apigenin and isokaempferide) exerted comparable antiproliferative activities against malignant and normal cells, while the methoxylated hydroxyflavones (cirsimaritin, penduletin, xanthomicrol and calycopterin) showed preferential activities against tumor cells. This activity may be of value in treating tumors as it would exert few side effects in normal tissues. Xanthomicrol selectively inhibited the growth of human gastric adenocarcinoma, while calycopterin selectively prevented human acute promyelocytic leukemia and human colon carcinoma cells proliferation. Copyright © 2011 John Wiley & Sons, Ltd.

Cellular Targets of Dietary Polyphenol Resveratrol

DTIC Science & Technology

2006-09-01

their mechanism(s) have demonstrated that even ubiquitous, non-nutritional secondary plant metabolites, such as flavonoids and polyphenolics widely...P.G. Natali, M. Brunetti, F.B. Aiello, M. Piantelli, Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential, Int. J. Cancer

Characterization of regioselective flavonoid O-methyltransferase from the Streptomyces sp. KCTC 0041BP.

PubMed

Darsandhari, Sumangala; Dhakal, Dipesh; Shrestha, Biplav; Parajuli, Prakash; Seo, Joo-Hyun; Kim, Tae-Su; Sohng, Jae Kyung

2018-06-01

A flavonoid comprises polyphenol compounds with pronounced antiviral, antioxidant, anticarcinogenic, and anti-inflammatory effects. The flavonoid modification by methylation provides a greater stability and improved pharmacokinetic properties. The methyltransferase from plants or microorganisms is responsible for such substrate modifications in a regiospecific or a promiscuous manner. GerMIII, originally characterized as a putative methyltransferase in a dihydrochalcomycin biosynthetic gene cluster of the Streptomyces sp. KCTC 0041BP, was tested for the methylation of the substrates of diverse chemical structures. Among the various tested substrates, flavonoids emerged as the favored substrates for methylation. Further, among the flavonoids, quercetin is the most favorable substrate, followed by luteolin, myricetin, quercetin 3-O-β-D-glucoside, and fisetin, while only a single product was formed in each case. The products were confirmed by HPLC and mass-spectrometry analyses. A detailed NMR spectrometric analysis of the methylated quercetin and luteolin derivatives confirmed the regiospecific methylation at the 4'-OH position. Modeling and molecular docking provided further insight regarding the most favorable mechanism and substrate architecture for the enzymatic catalysis. Accordingly, a double bond between the C 2 and the C 3 and a single-ring-appended conjugate-hydroxyl group are crucial for the favorable enzymatic conversions of the GerMIII catalysis. Thus, in this study, the enzymatic properties of GerMIII and a mechanistic overview of the regiospecific modification that was implemented for the acceptance of quercetin as the most favorable substrate are presented. Copyright © 2018 Elsevier Inc. All rights reserved.

[Chemical constituents from Exochorda racemosa].

PubMed

Zhang, Jiajia; Li, Xiangmei; Ren, Lihua; Fang, Chengwu; Wang, Fei

2011-05-01

To study the chemical constituents of Exochorda racemosa. Compounds were isolated and purified by silica gel, Sephadex LH-20, MCI gel and RP-18 column chromatography, and their structures were determined by spectroscopic analysis. Twenty compounds were isolated and identified as N-p-coumaroyl-N'-caffeoylputrescine (1), sutherlandin trans-p-coumarate (2), apigenin 7-O-methylglucuronide (3), astragalin (4), nicotiflorin (5), kaempferol 3-neohesperidoside (6), rutin (7), apigenin (8), luteolin (9), linalool-1-oic acid (10), betulalbuside A (11), ursolic acid (12) , corosolic acid (13), gynuramide II (14), beta-sitosterol (15), daucosterol (16), uridine (17), adenosine (18), syringin (19), and trans4-hydroxycinnamic acid (20), respectively. All compounds were obtained from this plant for the first time, moreover, 1 was reported as a new natural product, and 2 is a naturally rare cyanogenic glycoside.

Phytoconstituents from Vitex agnus-castus fruits

PubMed Central

Chen, Shao-Nong; Friesen, J. Brent; Webster, Donna; Nikolic, Dejan; van Breemen, Richard B.; Wang, Z. Jim; Fong, Harry H.S.; Farnsworth, Norman R.; Pauli, Guido F.

2011-01-01

A new labdane-diterpene, viteagnusin I (1), together with 23 known phytoconstituents were isolated from the fruits of Vitex agnus-castus L, and their structures characterized by spectroscopic method (NMR and MS). The known compounds include ten flavonoids, five terpenoids, three neolignans, and four phenolic compounds, as well as one glyceride. Biological evaluation identified apigenin, 3-methylkaempferol, luteolin, and casticin as weak ligands of delta and mu opioid receptors, exhibiting dose-dependent receptor binding. PMID:21163339

Mangifera indica L. Leaf Extract in Combination With Luteolin or Quercetin Enhances VO2peak and Peak Power Output, and Preserves Skeletal Muscle Function During Ischemia-Reperfusion in Humans.

PubMed

Gelabert-Rebato, Miriam; Wiebe, Julia C; Martin-Rincon, Marcos; Gericke, Nigel; Perez-Valera, Mario; Curtelin, David; Galvan-Alvarez, Victor; Lopez-Rios, Laura; Morales-Alamo, David; Calbet, Jose A L

2018-01-01

It remains unknown whether polyphenols such as luteolin (Lut), mangiferin and quercetin (Q) have ergogenic effects during repeated all-out prolonged sprints. Here we tested the effect of Mangifera indica L. leaf extract (MLE) rich in mangiferin (Zynamite®) administered with either quercetin (Q) and tiger nut extract (TNE), or with luteolin (Lut) on sprint performance and recovery from ischemia-reperfusion. Thirty young volunteers were randomly assigned to three treatments 48 h before exercise. Treatment A: placebo (500 mg of maltodextrin/day); B: 140 mg of MLE (60% mangiferin) and 50 mg of Lut/day; and C: 140 mg of MLE, 600 mg of Q and 350 mg of TNE/day. After warm-up, subjects performed two 30 s Wingate tests and a 60 s all-out sprint interspaced by 4 min recovery periods. At the end of the 60 s sprint the circulation of both legs was instantaneously occluded for 20 s. Then, the circulation was re-opened and a 15 s sprint performed, followed by 10 s recovery with open circulation, and another 15 s final sprint. MLE supplements enhanced peak (Wpeak) and mean (Wmean) power output by 5.0-7.0% ( P < 0.01). After ischemia, MLE+Q+TNE increased Wpeak by 19.4 and 10.2% compared with the placebo ( P < 0.001) and MLE+Lut ( P < 0.05), respectively. MLE+Q+TNE increased Wmean post-ischemia by 11.2 and 6.7% compared with the placebo ( P < 0.001) and MLE+Lut ( P = 0.012). Mean VO 2 during the sprints was unchanged, suggesting increased efficiency or recruitment of the anaerobic capacity after MLE ingestion. In women, peak VO 2 during the repeated sprints was 5.8% greater after the administration of MLE, coinciding with better brain oxygenation. MLE attenuated the metaboreflex hyperpneic response post-ischemia, may have improved O 2 extraction by the Vastus Lateralis (MLE+Q+TNE vs. placebo, P = 0.056), and reduced pain during ischemia ( P = 0.068). Blood lactate, acid-base balance, and plasma electrolytes responses were not altered by the supplements. In conclusion, a MLE extract rich in mangiferin combined with either quercetin and tiger nut extract or luteolin exerts a remarkable ergogenic effect, increasing muscle power in fatigued subjects and enhancing peak VO 2 and brain oxygenation in women during prolonged sprinting. Importantly, the combination of MLE+Q+TNE improves skeletal muscle contractile function during ischemia/reperfusion.

GRID and docking analyses reveal a molecular basis for flavonoid inhibition of Src family kinase activity.

PubMed

Wright, Bernice; Watson, Kimberly A; McGuffin, Liam J; Lovegrove, Julie A; Gibbins, Jonathan M

2015-11-01

Flavonoids reduce cardiovascular disease risk through anti-inflammatory, anti-coagulant and anti-platelet actions. One key flavonoid inhibitory mechanism is blocking kinase activity that drives these processes. Flavonoids attenuate activities of kinases including phosphoinositide-3-kinase, Fyn, Lyn, Src, Syk, PKC, PIM1/2, ERK, JNK and PKA. X-ray crystallographic analyses of kinase-flavonoid complexes show that flavonoid ring systems and their hydroxyl substitutions are important structural features for their binding to kinases. A clearer understanding of structural interactions of flavonoids with kinases is necessary to allow construction of more potent and selective counterparts. We examined flavonoid (quercetin, apigenin and catechin) interactions with Src family kinases (Lyn, Fyn and Hck) applying the Sybyl docking algorithm and GRID. A homology model (Lyn) was used in our analyses to demonstrate that high-quality predicted kinase structures are suitable for flavonoid computational studies. Our docking results revealed potential hydrogen bond contacts between flavonoid hydroxyls and kinase catalytic site residues. Identification of plausible contacts indicated that quercetin formed the most energetically stable interactions, apigenin lacked hydroxyl groups necessary for important contacts and the non-planar structure of catechin could not support predicted hydrogen bonding patterns. GRID analysis using a hydroxyl functional group supported docking results. Based on these findings, we predicted that quercetin would inhibit activities of Src family kinases with greater potency than apigenin and catechin. We validated this prediction using in vitro kinase assays. We conclude that our study can be used as a basis to construct virtual flavonoid interaction libraries to guide drug discovery using these compounds as molecular templates. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Antioxidant properties of aqueous extracts of unripe Musa paradisiaca on sodium nitroprusside induced lipid peroxidation in rat pancreas in vitro.

PubMed

Shodehinde, Sidiqat Adamson; Oboh, Ganiyu

2013-06-01

To evaluate and compare antioxidant activities of the aqueous extracts of unripe plantain (Musa paradisiaca), assess their inhibitory action on sodium nitroprusside induced lipid peroxidation in rat pancreas in vitro and to characterize the main phenolic constituents of the plantain products using gas chromatography analysis. Aqueous extracts of plantain products (raw, elastic pastry, roasted and boiled) flour of 0.1 g/mL (each) were used to determine their total phenol, total flavonoid, 1,1 diphenyl-2 picrylhydrazyl (DPPH) and hydroxyl (OH) radical scavenging ability. The inhibitory effect of the extracts on sodium nitroprusside induced lipid peroxidation was also determined. The results revealed that all the aqueous extracts showed antioxidant activity. The boiled flour had highest DPPH and OH radical scavenging ability while raw flour had the highest Fe(2+) chelating ability, sodium nitroprusside inhibitory effect and vitamin C content. The antioxidant results showed that elastic pastry had the highest total phenol and total flavonoid content. Characterization of the unripe plantain products for polyphenol contents using gas chromatography showed varied quantity of apigenin, myricetin, luteolin, capsaicin, isorhaemnetin, caffeic acid, kampferol, quercetin, p-hydroxybenzoic acid, shogaol, glycitein and gingerol per product on the spectra. Considering the antioxidant activities and ability to inhibit lipid peroxidation of unripe plantain, this could justify their traditional use in the management/prevention of diseases related to stress.

Chemical analysis of bioactive substances in seven siberian Saussurea species

NASA Astrophysics Data System (ADS)

Avdeeva, Elena; Reshetov, Yaroslav; Shurupova, Margarita; Zibareva, Larisa; Borisova, Evgeniia; Belousov, Mikhail

2017-11-01

Main groups of biologically active substances of seven siberian Saussurea species (S. controversa DC., S. latifolia Ledeb., S. parviflora (Poir.) DC., S. frolowii Ledeb, S. amara (L.) DC., S. salicifolia (L.) DC. and S. daurica Adams) have been studied using paper, thin-layer, performance liquid chromatography, IR spectroscopy, spectrophotometry and mass spectrometry with inductively coupled plasma. Siberian Saussurea species have a rich elemental composition and contain a variety of phenolic compounds, amino acids, polysaccharides. The majority of polysaccharides are accumulated by S. controversa, S. salicifolia and S. frolowii. These plants contain a significant amount of calcium that may be a species characteristic. All plants contain quercetin and its glycosides, in some species luteolin, kaempferol, glycosides of apigenin and myricetin were revealed. Phenolic acids with predominant content of caffeic, chlorogenic and cinnamic acids were found in all the species. The maximum amount of phenolic acids and flavonoids was determined in the grass of S. latifolia, S. controversa and S. daurica. Characteristic absorption bands of lactone carbonyl of sesquiterpenoids in IR spectrum found in S. latifolia, S. controversa, S. daurica, S. amara and S. salicifolia. HPLC / UV analysis showed that peaks with absorption maxima of 242-246 nm due to the presence of α,β-unsaturated ketone group in the structure of ecdysteroids were found in S. salicifolia, S. controversa, S. daurica and S. latifolia.

Antioxidant, Cytotoxic, and Toxic Activities of Propolis from Two Native Bees in Brazil: Scaptotrigona depilis and Melipona quadrifasciata anthidioides

PubMed Central

Bonamigo, Thaliny; Campos, Jaqueline Ferreira; Alfredo, Tamaeh Monteiro; Balestieri, José Benedito Perrella; Cardoso, Claudia Andrea Lima; Paredes-Gamero, Edgar Julian; de Picoli Souza, Kely

2017-01-01

Propolis is a natural mixture of compounds produced by various bee species, including stingless bees. This compound has been shown to exhibit antioxidant, antiproliferative, and antitumor activities. The present study aimed to determine the chemical constituents as well as the antioxidant, cytotoxic, and toxic activities of ethanol extracts of propolis obtained from the stingless bees Scaptotrigona depilis and Melipona quadrifasciata anthidioides, which are found in Brazil. Phytosterols, terpenes, phenolic compounds, and tocopherol were identified in the ethanol extracts of propolis (EEPs) in different concentrations. The compounds stigmasterol, taraxasterol, vanilic acid, caffeic acid, quercetin, luteolin, and apigenin were found only in EEP-M. The EEPs were able to scavenge the free radicals 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and protected human erythrocytes against lipid peroxidation, with the latter effect being demonstrated by their antihemolytic activity and inhibition of malondialdehyde formation. The EEPs showed cytotoxic activity against erythroleukemic cells and necrosis was the main mechanism of death observed. In addition, the concentrations at which the EEPs were cytotoxic were not toxic against Caenorhabditis elegans. In this context, it is concluded that EEP-S and EEP-M show antioxidant and cytotoxic activities and are promising bioactive mixtures for the control of diseases associated with oxidative stress and tumor cell proliferation. PMID:28377794

Antioxidant, Cytotoxic, and Toxic Activities of Propolis from Two Native Bees in Brazil: Scaptotrigona depilis and Melipona quadrifasciata anthidioides.

PubMed

Bonamigo, Thaliny; Campos, Jaqueline Ferreira; Alfredo, Tamaeh Monteiro; Balestieri, José Benedito Perrella; Cardoso, Claudia Andrea Lima; Paredes-Gamero, Edgar Julian; de Picoli Souza, Kely; Dos Santos, Edson Lucas

2017-01-01

Propolis is a natural mixture of compounds produced by various bee species, including stingless bees. This compound has been shown to exhibit antioxidant, antiproliferative, and antitumor activities. The present study aimed to determine the chemical constituents as well as the antioxidant, cytotoxic, and toxic activities of ethanol extracts of propolis obtained from the stingless bees Scaptotrigona depilis and Melipona quadrifasciata anthidioides , which are found in Brazil. Phytosterols, terpenes, phenolic compounds, and tocopherol were identified in the ethanol extracts of propolis (EEPs) in different concentrations. The compounds stigmasterol, taraxasterol, vanilic acid, caffeic acid, quercetin, luteolin, and apigenin were found only in EEP-M. The EEPs were able to scavenge the free radicals 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and protected human erythrocytes against lipid peroxidation, with the latter effect being demonstrated by their antihemolytic activity and inhibition of malondialdehyde formation. The EEPs showed cytotoxic activity against erythroleukemic cells and necrosis was the main mechanism of death observed. In addition, the concentrations at which the EEPs were cytotoxic were not toxic against Caenorhabditis elegans . In this context, it is concluded that EEP-S and EEP-M show antioxidant and cytotoxic activities and are promising bioactive mixtures for the control of diseases associated with oxidative stress and tumor cell proliferation.

Infrared spectroscopy of flavones and flavonols. Reexamination of the hydroxyl and carbonyl vibrations in relation to the interactions of flavonoids with membrane lipids

NASA Astrophysics Data System (ADS)

Baranović, Goran; Šegota, Suzana

2018-03-01

Detailed vibrational assignments for twelve flavonoids (seven flavones (flavone, 3- and 5-hydroxyflavone, chrysin, apigenin, fisetin and luteolin) and five flavonols (galangin, kaempferol, quercetin, morin and myricetin)) have been made based on own and reported experimental data and calculations at the B3LYP/6-31 + G(d,p) level of theory. All the molecules are treated in a uniform way by using the same set of redundancy-free set of internal coordinates. A generalized harmonic mode mixing is used to corroborate the vibrational characteristics of this important class of molecules. Each flavonoid molecule can be treated from the vibrational point of view as made of relatively weakly coupled chromone and phenyl part. It has been shown that the strongest band around 1600 cm- 1 need not be attributable to the Cdbnd O stretching. The way the vibrations of any of the hydroxyl groups are mixed with ring vibrations and vibrations of other neighboring hydroxyl groups is rather involved. This imposes severe limitations on any attempt to describe normal modes of a flavonol in terms of hydroxyl or carbonyl group vibrations. The role of water molecules in the appearance of flavonoid IR spectra is emphasized. Knowing for the great affinity of phosphate groups in lipids towards water, the immediate consequence is a reasonable assumption that flavonoid lipid interactions is mediated by water.

A novel molybdenum disulfide nanosheet self-assembled flower-like monolithic sorbent for solid-phase extraction with high efficiency and long service life.

PubMed

Ran, Fanpeng; Liu, Hongmei; Wang, Xiaoqi; Guo, Yong

2017-07-21

A novel material consisting of molybdenum disulfide (MoS 2 ) nanosheet that self-assemble into flower-like microspheres which aggregate to form a monolithic matrix with a micro or nano-scaled mesopore structure was successfully synthesized and used as an efficient sorbent for solid-phase extraction (SPE) due to its large specific adsorption area and good stability. The extraction properties of the as-prepared sorbent were evaluated by high-performance liquid chromatography with variable wavelength detection (HPLC-VWD) by analyzing four flavonoids (apigenin, quercetin, luteolin, and kaempferol). Under optimal conditions, the LODs and LOQs were found to be in the ranges of 0.1-0.25 and 0.4-0.5μgL -1 , respectively, and wide linear ranges were obtained with correlation coefficients (R) ranging from 0.9991 to 0.9996. Compared with commercial C18 and Alumina-N sorbents, the as-prepared sorbent showed high extraction efficiency at different concentrations of flavonoids. After 100 uses, the extraction ability of the self-assembled MoS 2 nanosheet monolithic sorbent had no evident decline, denoting a long service life. Finally, the SPE-HPLC-VWD method using the as-prepared sorbent was applied to flavonoid analysis in beverage samples with satisfactory results. Copyright © 2017 Elsevier B.V. All rights reserved.

Antioxidant properties of aqueous extracts of unripe Musa paradisiaca on sodium nitroprusside induced lipid peroxidation in rat pancreas in vitro

PubMed Central

Shodehinde, Sidiqat Adamson; Oboh, Ganiyu

2013-01-01

Objective To evaluate and compare antioxidant activities of the aqueous extracts of unripe plantain (Musa paradisiaca), assess their inhibitory action on sodium nitroprusside induced lipid peroxidation in rat pancreas in vitro and to characterize the main phenolic constituents of the plantain products using gas chromatography analysis. Methods Aqueous extracts of plantain products (raw, elastic pastry, roasted and boiled) flour of 0.1 g/mL (each) were used to determine their total phenol, total flavonoid, 1,1 diphenyl-2 picrylhydrazyl (DPPH) and hydroxyl (OH) radical scavenging ability. The inhibitory effect of the extracts on sodium nitroprusside induced lipid peroxidation was also determined. Results The results revealed that all the aqueous extracts showed antioxidant activity. The boiled flour had highest DPPH and OH radical scavenging ability while raw flour had the highest Fe2+ chelating ability, sodium nitroprusside inhibitory effect and vitamin C content. The antioxidant results showed that elastic pastry had the highest total phenol and total flavonoid content. Characterization of the unripe plantain products for polyphenol contents using gas chromatography showed varied quantity of apigenin, myricetin, luteolin, capsaicin, isorhaemnetin, caffeic acid, kampferol, quercetin, p-hydroxybenzoic acid, shogaol, glycitein and gingerol per product on the spectra. Conclusions Considering the antioxidant activities and ability to inhibit lipid peroxidation of unripe plantain, this could justify their traditional use in the management/prevention of diseases related to stress. PMID:23730557

A Multidirectional Perspective for Novel Functional Products: In vitro Pharmacological Activities and In silico Studies on Ononis natrix subsp. hispanica

PubMed Central

Yerlikaya, Serife; Zengin, Gokhan; Mollica, Adriano; Baloglu, Mehmet C.; Celik Altunoglu, Yasemin; Aktumsek, Abdurrahman

2017-01-01

The genus Ononis has important value as traditional drugs and foods. In the present work, we aimed to assess the chemical profiles and biological effects of Ononis natrix subsp. hispanica extracts (ethyl acetate, methanol, and water). For chemical profile, total and individual phenolic components were detected. For biological effects, antioxidant (DPPH, ABTS, CUPRAC, FRAP, phosphomolybdenum, and metal chelating assays), enzyme inhibitory (against cholinesterase, tyrosinase, α-amylase and α-glucosidase), antimicrobial, DNA protection and cytotoxic abilities were tested. The predominant phenolics were apigenin, luteolin, and quercetin in the tested extracts. Generally, the ethyl acetate and methanol extracts were noted as the most active in the antioxidant and enzyme inhibitory assays. Water extract with different concentrations indicated high level of DNA protection activity. Methanol and ethyl acetate extracts showed antibacterial effect against to Staphylococcus aureus and Staphylococcus epidermidis strains. The cytotoxic effects of O. natrix subsp. hispanica extracts on the survival of HeLa and PC3 cells were determined by MTT cell viability assay. Water and methanol extracts caused initiation of apoptosis for PC3 cell line. Furthermore, molecular docking was performed to better understand interactions between dominant phenolic compounds and selected enzymes. Our results clearly indicate that O. natrix subsp. hispanica could be considered a potential candidate for designing novel pharmaceuticals, cosmeceuticals and nutraceuticals. PMID:28919860

Exploring the Therapeutic Mechanism of Desmodium styracifolium on Oxalate Crystal-Induced Kidney Injuries Using Comprehensive Approaches Based on Proteomics and Network Pharmacology.

PubMed

Hou, Jiebin; Chen, Wei; Lu, Hongtao; Zhao, Hongxia; Gao, Songyan; Liu, Wenrui; Dong, Xin; Guo, Zhiyong

2018-01-01

Purpose: As a Chinese medicinal herb, Desmodium styracifolium (Osb.) Merr (DS) has been applied clinically to alleviate crystal-induced kidney injuries, but its effective components and their specific mechanisms still need further exploration. This research first combined the methods of network pharmacology and proteomics to explore the therapeutic protein targets of DS on oxalate crystal-induced kidney injuries to provide a reference for relevant clinical use. Methods: Oxalate-induced kidney injury mouse, rat, and HK-2 cell models were established. Proteins differentially expressed between the oxalate and control groups were respectively screened using iTRAQ combined with MALDI-TOF-MS. The common differential proteins of the three models were further analyzed by molecular docking with DS compounds to acquire differential targets. The inverse docking targets of DS were predicted through the platform of PharmMapper. The protein-protein interaction (PPI) relationship between the inverse docking targets and the differential proteins was established by STRING. Potential targets were further validated by western blot based on a mouse model with DS treatment. The effects of constituent compounds, including luteolin, apigenin, and genistein, were investigated based on an oxalate-stimulated HK-2 cell model. Results: Thirty-six common differentially expressed proteins were identified by proteomic analysis. According to previous research, the 3D structures of 15 major constituents of DS were acquired. Nineteen differential targets, including cathepsin D (CTSD), were found using molecular docking, and the component-differential target network was established. Inverse-docking targets including p38 MAPK and CDK-2 were found, and the network of component-reverse docking target was established. Through PPI analysis, 17 inverse-docking targets were linked to differential proteins. The combined network of component-inverse docking target-differential proteins was then constructed. The expressions of CTSD, p-p38 MAPK, and p-CDK-2 were shown to be increased in the oxalate group and decreased in kidney tissue by the DS treatment. Luteolin, apigenin, and genistein could protect oxalate-stimulated tubular cells as active components of DS. Conclusion: The potential targets including the CTSD, p38 MAPK, and CDK2 of DS in oxalate-induced kidney injuries and the active components (luteolin, apigenin, and genistein) of DS were successfully identified in this study by combining proteomics analysis, network pharmacology prediction, and experimental validation.

[Chemical Constituents of Ethyl Acetate Fraction of Suaeda glauca].

PubMed

Qiu, Ping; Wang, Qi-zhi; Yin, Min; Wang, Ming; Zhao, You-yi; Shan, Yu; Feng, Xu

2015-04-01

To study the chemical constituents of Suaeda glauca. The chemical constituents were isolated and purified with several separation and purification techniques. Their structures were identified by physicochemical properties and various spectroscopic methods. Ten compounds were isolated from the ethyl acetate fraction as lignoceric acid (1), β-amyrin-n-nonyl ether(2), β-sitosterol(3), β-daucosterol(4), quercetin(5), luteolin(6), luteolin-7-O-β-D-glucoside(7), isorhamnetin(8), scopoletin (9) and stigmasterol(10). Compounds 1, 2, 6, 7, 8, 9 and 10 are isolated from Suaeda genus for the first time and compounds 3 - 5 are isolated from this plant for the first time.

Transcriptome and Biochemical Analysis of a Flower Color Polymorphism in Silene littorea (Caryophyllaceae)

PubMed Central

Casimiro-Soriguer, Inés; Narbona, Eduardo; Buide, M. L.; del Valle, José C.; Whittall, Justen B.

2016-01-01

Flower color polymorphisms are widely used as model traits from genetics to ecology, yet determining the biochemical and molecular basis can be challenging. Anthocyanin-based flower color variations can be caused by at least 12 structural and three regulatory genes in the anthocyanin biosynthetic pathway (ABP). We use mRNA-Seq to simultaneously sequence and estimate expression of these candidate genes in nine samples of Silene littorea representing three color morphs (dark pink, light pink and white) across three developmental stages in hopes of identifying the cause of flower color variation. We identified 29 putative paralogs for the 15 candidate genes in the ABP. We assembled complete coding sequences for 16 structural loci and nine of ten regulatory loci. Among these 29 putative paralogs, we identified 622 SNPs, yet only nine synonymous SNPs in Ans had allele frequencies that differentiated pigmented petals (dark pink and light pink) from white petals. These Ans allele frequency differences were further investigated with an expanded sequencing survey of 38 individuals, yet no SNPs consistently differentiated the color morphs. We also found one locus, F3h1, with strong differential expression between pigmented and white samples (>42x). This may be caused by decreased expression of Myb1a in white petal buds. Myb1a in S. littorea is a regulatory locus closely related to Subgroup 7 Mybs known to regulate F3h and other loci in the first half of the ABP in model species. We then compare the mRNA-Seq results with petal biochemistry which revealed cyanidin as the primary anthocyanin and five flavonoid intermediates. Concentrations of three of the flavonoid intermediates were significantly lower in white petals than in pigmented petals (rutin, quercetin and isovitexin). The biochemistry results for rutin, quercetin, luteolin and apigenin are consistent with the transcriptome results suggesting a blockage at F3h, possibly caused by downregulation of Myb1a. PMID:26973662

Hollow fibre-based liquid phase microextraction combined with high-performance liquid chromatography for the analysis of flavonoids in Echinophora platyloba DC. and Mentha piperita.

PubMed

Hadjmohammadi, Mohammadreza; Karimiyan, Hanieh; Sharifi, Vahid

2013-11-15

A simple, inexpensive and efficient three phase hollow fibre liquid phase microextraction (HF-LPME) technique combined with HPLC was used for the simultaneous determination of flavonoids in Echinophora platyloba DC. and Mentha piperita. Different factors affecting the HF-LPME procedure were investigated and optimised. The optimised extraction conditions were as follows: 1-octanol as an organic solvent, pHdonor=2, pHacceptor=9.75, stirring rate of 1000rpm, extraction time of 80min, without addition of salt. Under these conditions, the enrichment factors ranged between 146 and 311. The values of intra and inter-day relative standard deviations (RSD) were in the range of 3.18-6.00% and 7.25-11.00%, respectively. The limits of detection (LODs) ranged between 0.5 and 7.0ngmL(-1). Among the investigated flavonoids quercetin was found in E. platyloba DC. and luteolin was found in M. piperita. Concentration of quercetin and luteolin was 0.015 and 0.025mgg(-1) respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

Flavonoids in vegetable foods commonly consumed in Brazil and estimated ingestion by the Brazilian population.

PubMed

Arabbi, Paola R; Genovese, Maria Inés; Lajolo, Franco M

2004-03-10

The objective of this work was to quantify the flavonoids present in foods most commonly consumed by the Brazilian population. The predominant flavonoids found in largest abundance in all of the analyzed vegetables were glycosides of quercetin. In lettuce, a small amount of luteolin was also detected. In sweet pepper, quercetin and luteolin were both present. White onion [48-56 mg/100 g of fresh weight (FW), expressed as aglycon], red onion (40-100 mg/100 g of FW), red lettuce (67-67.2 mg/100 g of FW), arugula (41-118 mg/100 g of FW), and chicory (18-38 mg/100 g of FW) were highest in total flavonoids. In fruits, the highest concentrations of flavonoids were found in the peel (125-170 mg/100 g of FW) and pulp (35-44 mg/100 g of FW) of oranges and in some apple varieties (14-36 mg/100 g of FW). Variability in flavonoid content due to time of harvesting was high for leafy vegetables and red onions. The estimated ingestion by Brazilian population ranged from 60 to 106 mg/day.

[Chemical constituents from leaves of Paulownia fortunei].

PubMed

Li, Xiao-Qiang; Wu, Jing-Lian; Cao, Fei-Hua; Li, Chong

2008-06-01

To study the chemical constituents of leaves of Paulownia fortunei (Seem.) Hemsl. The constituents were isolated by column chromatography and their structures were elucidated through spectroscopic analysis. The compounds were identified as mimulone (I), apigenin (II), luteolin (III), 2alpha, 3beta, 19beta-trihydroxyurs-28-O-beta-D-galactonopyranos ylester (anserinoside, IV), 3alpha-hydroxyl-ursolicacid (V), ursolicacid (VI), daucosterol (VII), beta-sitosterol (VIII). The compounds I - V are obtained from leaves of Paulownia fortunei (Seem.) Hemsl for the first time.

Chemotaxonomic features associated with flavonoids of cannabinoid-free cannabis (Cannabis sativa subsp. sativa L.) in relation to hops (Humulus lupulus L.).

PubMed

Vanhoenacker, Gerd; Van Rompaey, Philippe; De Keukeleire, Denis; Sandra, Pat

2002-02-01

The major flavonoids present in the leaves and flowers of the cannabinoid-free cannabis (Cannabis sativa subsp. sativa L.) cultivars Felina and Futura are orientin (1), vitexin (2), luteolin-7-O-beta-D-glucuronide (3), and apigenin-7-O-beta-D-glucuronide (4), while prenylated flavonoids, to which the potent estrogenicity of hops (Humilus lupulus L.) is associated, are absent. The different composition of flavonoids has chemotaxonomic value.

Phytoconstituents from Vitex agnus-castus fruits.

PubMed

Chen, Shao-Nong; Friesen, J Brent; Webster, Donna; Nikolic, Dejan; van Breemen, Richard B; Wang, Z Jim; Fong, Harry H S; Farnsworth, Norman R; Pauli, Guido F

2011-06-01

A new labdane-diterpene, viteagnusin I (1), together with 23 known phytoconstituents were isolated from the fruits of Vitex agnus-castus L, and their structures characterized by spectroscopic methods (NMR and MS). The known compounds include ten flavonoids, five terpenoids, three neolignans, and four phenolic compounds, as well as one glyceride. Biological evaluation identified apigenin, 3-methylkaempferol, luteolin, and casticin as weak ligands of delta and mu opioid receptors, exhibiting dose-dependent receptor binding. Copyright © 2011 Elsevier B.V. All rights reserved.

Mixed hemimicelles solid-phase extraction based on ionic liquid-coated Fe3O4/SiO2 nanoparticles for the determination of flavonoids in bio-matrix samples coupled with high performance liquid chromatography.

PubMed

He, Huan; Yuan, Danhua; Gao, Zhanqi; Xiao, Deli; He, Hua; Dai, Hao; Peng, Jun; Li, Nan

2014-01-10

A novel magnetic solid-phase extraction (MSPE) method based on mixed hemimicelles of room temperature ionic liquids (RTILs) coated Fe3O4/SiO2 nanoparticles (NPs) was developed for simultaneous extraction of trace amounts of flavonoids in bio-matrix samples. A comparative study on the use of RTILs (C16mimBr) and CTAB-coated Fe3O4/SiO2 NPs as sorbents was presented. Owing to bigger adsorption amounts for analytes, RTILs-coated Fe3O4/SiO2 NPs was selected as MSPE materials and three analytes luteolin, quercetin and kaempferol can be quantitatively extracted and simultaneously determined coupled with high performance liquid chromatography (HPLC) in urine samples. No interferences were caused by proteins or endogenous compounds. Good linearity (R(2)>0.9993) for all calibration curves was obtained, and the limits of detection (LOD) for luteolin, quercetin and kaempferol were 0.10 ng/mL, 0.50 ng/mL and 0.20 ng/mL in urine samples, respectively. Satisfactory recoveries (93.5-97.6%, 90.1-95.4% and 93.3-96.6% for luteolin, quercetin and kaempferol) in biological matrices were achieved. It was notable that while using a small amount of Fe3O4/SiO2 NPs (4.0 mg) and C16mimBr (1.0 mg), satisfactory preconcentration factors and extraction recoveries for the three flavonoids were obtained. To the best of our knowledge, this is the first time a mixed hemimicelles MSPE method based on RTILs and Fe3O4/SiO2 NPs magnetic separation has ever been used for pretreatment of complex biological samples. Copyright © 2013 Elsevier B.V. All rights reserved.

Two new constituents from Erigeron breviscapus.

PubMed

Li, Jing; Yu, De-Quan

2013-09-01

Two novel constituents, named erigeronones A (1) and B (2), together with apigenin-7-O-β-galacturonide (3), quercetin-7-O-β-glucuronide (4), quercetin-3-O-β-galacturonide (5), and eriodictyol-7-O-β-glucuronide (6), were isolated from the whole grass of Erigeron breviscapus (Vant) Hand.-Mazz (Compositae). Their structures were established on the basis of spectral analyses and comparison with the literature data. Both new compounds 1 and 2 possess a γ-pyrone moiety that is rare in nature. Compound 1 showed significant protective effect on H2O2-injured human umbilical vein endothelial cells.

[Chemical Constituents of Paris polyphylla var. chinensis Aerial Parts].

PubMed

Yin, Wei; Song, Zu-rong; Liu, Jin-qi; Zhang, Guo-sheng

2015-09-01

To study the chemical constituents of aerial parts of Paris polyphylla var. chinensis . Aerial parts of Paris polyphylla var. chinensis was extracted with 95% EtOH, and separated and purified by silica gel, RP 18 and Sephadex LH-20 col- umn chromatography. The structures were identified by spectroscopic analysis. A total of ten compounds were isolated and iden- tified as β-sitosterol (1) ergosta-7, 22-dien-3-one (2), β-ecdysone (3), kaempferol (4), daucosterol (5) luteolin (6) calonysterone (7), luteolin-7-O-glucoside (8), quercetin (9), and 3β, 5α, 9α-trihydroxyergosta-7, 22-dien-6-one (10). Compounds 2,6 and 10 are isolated from Paris polyphylla var. chinensis for the first time.

Characterisation of phenolics in Flor-Essence--a compound herbal product and its contributing herbs.

PubMed

Saleem, Ammar; Walshe-Roussel, Brendan; Harris, Cory; Asim, Muhammad; Tamayo, Carmen; Sit, Summer; Arnason, John Thor

2009-01-01

Commercially available herbal mixture FE, a proprietary natural health product manufactured by Flora Manufacturing and Distributing Ltd (Flora), is a unique North American traditional herbal product. FE is a chemically complex mixture of eight herbs and has not been subjected to phytochemical analysis. To develop analytical methods to undertake detailed phytochemical analyses of FE, and its eight contributing herbs, including burdock (Arctium lappa L.), sheep sorrel (Rumex acetosella L.), Turkish rhubarb (Rheum palmatum L.), slippery elm Muhl. (Ulmus rubra), watercress (Nasturtium officinale R. Br.), red clover (Trifolium pratense L.), blessed thistle (Cnicus benedictus L.) and kelp (Laminaria digitata Lmx.). The identification was undertaken by a combination of reversed phase high performance liquid chromatography-diode array detection-atmospheric pressure chemical ionisation-mass selective detection (RP-HPLC-DAD-APCI-MSD) analysis and phenolics metabolomic library matching. New separation methods facilitated the identification of 43 markers in the individual herbs which constitute FE. Sixteen markers could be identified in FE originating from four contributing herbs including four caffeoyl quinic acids, three dicaffeoyl quinic acids and two caffeic acid derivatives from A. lappa, luteolin-7-O-glucoside, luteolin, five apigenin glycosides and apigenin from R. acetocella and N. officinale and sissostrin from T. pretense. A validated method for quantitative determination of three markers is reported with good intraday, interday and interoperator repeatability using a reliable alcohol based extraction technique. FE and its contributing herbs predominantly contain phenolics. This methodology can be applied to further develop full-scale validation of this product.

Homoisoflavonoids Are Potent Glucose Transporter 2 (GLUT2) Inhibitors: A Potential Mechanism for the Glucose-Lowering Properties of Polygonatum odoratum.

PubMed

Wang, Huijun; Fowler, Mark I; Messenger, David J; Terry, Leon A; Gu, Xuelan; Zhou, Luxian; Liu, Ruimin; Su, Juan; Shi, Songshan; Ordaz-Ortiz, Jose Juan; Lian, Guoping; Berry, Mark J; Wang, Shunchun

2018-03-28

Foods of high carbohydrate content such as sucrose or starch increase postprandial blood glucose concentrations. The glucose absorption system in the intestine comprises two components: sodium-dependent glucose transporter-1 (SGLT1) and glucose transporter 2 (GLUT2). Here five sappanin-type (SAP) homoisoflavonoids were identified as novel potent GLUT2 inhibitors, with three of them isolated from the fibrous roots of Polygonatum odoratum (Mill.) Druce. SAP homoisolflavonoids had a stronger inhibitory effect on 25 mM glucose transport (41.6 ± 2.5, 50.5 ± 7.6, 47.5 ± 1.9, 42.6 ± 2.4, and 45.7 ± 4.1% for EA-1, EA-2, EA-3, MOA, and MOB) than flavonoids (19.3 ± 2.2, 11.5 ± 3.7, 16.4 ± 2.4, 5.3 ± 1.0, 3.7 ± 2.2, and 18.1 ± 2.4% for apigenin, luteolin, quercetin, naringenin, hesperetin, and genistein) and phloretin (28.1 ± 1.6%) at 15 μM. SAP homoisoflavonoids and SGLT1 inhibitors were found to synergistically inhibit the uptake of glucose using an in vitro model comprising Caco-2 cells. This observed new mechanism of the glucose-lowering action of P. odoratum suggests that SAP homoisoflavonoids and their combination with flavonoid monoglucosides show promise as naturally functional ingredients for inclusion in foods and drinks designed to control postprandial glucose levels.

Total phenolic compounds, flavonoids, and radical scavenging activity of 21 selected tropical plants.

PubMed

Mustafa, R A; Abdul Hamid, A; Mohamed, S; Bakar, F Abu

2010-01-01

Free radical scavenging activity of 21 tropical plant extracts was evaluated using 1,1-diphenyl-2-picrylhydrazyl assay (DPPH). Total phenolic compounds and flavonoids were determined using Folin-Ciocalteu and HPLC, respectively. Results of the study revealed that all the plants tested exhibited excellent antioxidant activity with IC(50) in the range of 21.3 to 89.6 microg/mL. The most potent activity was demonstrated by Cosmos caudatus (21.3 microg/mL) and Piper betle (23.0 microg/mL) that are not significantly different than that of -tocopherol or BHA. L. inermis extract was found to consist of the highest concentration of phenolics, catechin, epicatechin, and naringenin. High content of quercetin, myricetin, and kaempferol were identified in Vitex negundo, Centella asiatica, and Sesbania grandiflora extracts, respectively. Luteolin and apigenin, on the other hand, were found in Premna cordifolia and Kaempferia galanga extracts. Strong correlation (R = 0.8613) between total phenolic compounds and total flavonoids (R = 0.8430) and that of antioxidant activity of the extracts were observed. The study revealed that phenolic, in particular flavonoids, may be the main contributors to the antioxidant activity exhibited by the plants. Potent antioxidant from natural sources is of great interest to replace the use of synthetic antioxidants. In addition, some of the plants have great potential to be used in the development of functional ingredients/foods that are currently in demand for the health benefits associated with their use.

Sensory-guided decomposition of roasted cocoa nibs (Theobroma cacao) and structure determination of taste-active polyphenols.

PubMed

Stark, Timo; Bareuther, Sabine; Hofmann, Thomas

2005-06-29

Sequential application of solvent extraction, gel permeation chromatography, and RP-HPLC in combination with taste dilution analyses, followed by LC-MS and 1D/2D-NMR experiments and thiolytic degradation, revealed that, besides theobromine and caffeine, the flavan-3-ols epicatechin, catechin, procyanidin B-2, procyanidin B-5, procyanidin C-1, [epicatechin-(4beta-->8)](3)-epicatechin, and [epicatechin-(4beta-->8)](4)-epicatechin were among the key compounds contributing to the bitter taste as well as the astringent mouthfeel imparted upon consumption of roasted cocoa. In addition, a series of quercetin, naringenin, luteolin, and apigenin glycopyranosides as well as a family of not previously identified amino acid amides, namely, (+)-N-[4'-hydroxy-(E)-cinnamoyl]-L-aspartic acid, (+)-N-[3',4'-dihydroxy-(E)-cinnamoyl]-L-aspartic acid, (-)-N-[3',4'-dihydroxy-(E)-cinnamoyl]-L-glutamic acid, (-)-N-[4'-hydroxy-(E)-cinnamoyl]-L-glutamic acid, (-)-N-[4'-hydroxy-(E)-cinnamoyl]-3-hydroxy-L-tyrosine, (+)-N-[4'-hydroxy-3'-methoxy-(E)-cinnamoyl]-L-aspartic acid, and (+)-N-(E)-cinnamoyl-L-aspartic acid, have been identified as key astringent compounds of roasted cocoa. Furthermore, (-)-N-[3',4'-dihydroxy-(E)-cinnamoyl]-3-hydroxy-l-tyrosine (clovamide), (-)-N-[4'-hydroxy-(E)-cinnamoyl]-L-tyrosine (deoxyclovamide), and (-)-N-[3',4'-dihydroxy-(E)-cinnamoyl]-L-tyrosine, reported previously as antioxidants, have been found as contributors of cocoa's astringent taste. By means of the half-tongue test, the taste thresholds of flavan-3-ols and glycosides have been determined.

Anti-oxidative assays as markers for anti-inflammatory activity of flavonoids.

PubMed

Chanput, Wasaporn; Krueyos, Narumol; Ritthiruangdej, Pitiporn

2016-11-01

The complexity of in vitro anti-inflammatory assays, the cost and time consumed, and the necessary skills can be a hurdle to apply to promising compounds in a high throughput setting. In this study, several antioxidative assays i.e. DPPH, ABTS, ORAC and xanthine oxidase (XO) were used to examine the antioxidative activity of three sub groups of flavonoids: (i) flavonol: quercetin, myricetin, (ii) flavanone: eriodictyol, naringenin (iii) flavone: luteolin, apigenin. A range of flavonoid concentrations was tested for their antioxidative activities and were found to be dose-dependent. However, the flavonoid concentrations over 50ppm were found to be toxic to the THP-1 monocytes. Therefore, 10, 20 and 50ppm of flavonoid concentrations were tested for their anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated THP-1 monocytes. Expression of inflammatory genes, IL-1β, IL-6, IL-8, IL-10 and TNF-α was found to be sequentially decreased when flavonoid concentration increased. Principle component analysis (PCA) was used to investigate the relationship between the data sets of antioxidative assays and the expression of inflammatory genes. The results showed that DPPH, ABTS and ORAC assays have an opposite correlation with the reduction of inflammatory genes. Pearson correlation exhibited a relationship between the ABTS assay and the expression of three out of five analyzed genes; IL-1β, IL-6 and IL-8. Our findings indicate that ABTS assay can potentially be an assay marker for anti-inflammatory activity of flavonoids. Copyright © 2016 Elsevier B.V. All rights reserved.

Switching on fluorescence for selective visual recognition of naringenin and morin with a metal-organic coordination polymer of Zn(bix) [bix = 1,4-bis(imidazol-1-ylmethyl)benzene

NASA Astrophysics Data System (ADS)

Zhao, Xi Juan; Wang, Hui Juan; Liang, Li Jiao; Li, Yuan Fang

2013-02-01

Flavonoids such as naringenin and morin are ubiquitous in a wide range of foods isolated from plants, and have diverse effects on plants even on human health. Here, we establish a selective visual method for recognition of aringenin and morin based on the "switched on" fluorescence induced by a metal-organic coordination polymer of Zn(bix) [bix = 1,4-bis(imidazol-1-ylmethyl)benzene]. Owing to the coordination interaction of aringenin and morin with Zn(II) from the polymeric structure of Zn(bix), the conformational free rotation of naringenin and morin is restricted leading to relatively rigid structures. And as a consequence, the fluorescence is switched on. While luteolin and quercetin, holding a very similar structure with naringenin and morin, have no such fluorescence enhancement most likely owing to the 3'-hydroxy substitution in the B ring. Under 365 nm UV lamp light, we can visually recognize and discriminate naringenin and morin from them each other and luteolin as well as quercetin based on the colors of their emission. With this recognition system, the detection of naringenin and morin in human urine was made with satisfactory results.

Intake of selected bioactive compounds from plant food supplements containing fennel (Foeniculum vulgare) among Finnish consumers.

PubMed

Uusitalo, Liisa; Salmenhaara, Maija; Isoniemi, Merja; Garcia-Alvarez, Alicia; Serra-Majem, Lluís; Ribas-Barba, Lourdes; Finglas, Paul; Plumb, Jenny; Tuominen, Pirkko; Savela, Kirsti

2016-03-01

The purpose of this study was to estimate the intake of selected bioactive compounds from fennel-containing plant food supplements (PFS) among Finnish consumers. The estimated average intake of estragole was 0.20mg/d, of trans-anethole 1.15mg/d, of rosmarinic acid 0.09mg/d, of p-coumaric acid 0.0068mg/d, of kaempferol 0.0034mg/d, of luteolin 0.0525μg/d, of quercetin 0.0246mg/d, of matairesinol 0.0066μg/d and of lignans 0.0412μg/d. The intakes of kaempferol, quercetin, luteolin, matairesinol and lignans from PFS were low in comparison with their dietary supply. The intake of estragole was usually moderate, but a heavy consumption of PFS may lead to a high intake of estragole. The intake of trans-anethole did not exceed the acceptable daily intake, but PFS should be taken into account when assessing the total exposure. To our knowledge, this study provided the first intake estimates of trans-anethole, p-coumaric acid and rosmarinic acid in human populations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Structural dependence of flavonoid interactions with Cu2+ ions: implications for their antioxidant properties.

PubMed Central

Brown, J E; Khodr, H; Hider, R C; Rice-Evans, C A

1998-01-01

The flavonoids constitute a large group of polyphenolic phytochemicals with antioxidant properties in vitro. The interactions of four structurally related flavonoids (quercetin, kaempferol, rutin and luteolin) with Cu2+ ions were investigated in terms of the extent to which they undergo complex formation through chelation or modification through oxidation, as well as in their structural dependence. The ortho 3',4'-dihydroxy substitution in the B ring is shown to be important for Cu2+-chelate formation, thereby influencing the antioxidant activity. The presence of a 3-hydroxy group in the flavonoid structure enhances the oxidation of quercetin and kaempferol, whereas luteolin and rutin, each lacking the 3-hydroxy group, do not oxidize as readily in the presence of Cu2+ ions. The results also demonstrate that the reactivities of the flavonoids in protecting low-density lipoprotein (LDL) against Cu2+ ion-induced oxidation are dependent on their structural properties in terms of the response of the particular flavonoid to Cu2+ ions, whether chelation or oxidation, their partitioning abilities between the aqueous compartment and the lipophilic environment within the LDL particle, and their hydrogen-donating antioxidant properties. PMID:9494082

[Study on the chemical constituents in Pouzolzia zeylanica].

PubMed

Fu, Ming; Niu, You-Ya; Yu, Juan; Kong, Qing-Tong

2012-11-01

To study the chemical constituents of Pouzolzia zeylanica. Many chromatography means were used in separation and purification, and the structures of all compounds were identified by the means of spectroscopic analysis and physicochemical properties. 14 compounds were elucidated as: beta-sitosterol (1), daucosterol (2), oleanolic acid (3), epicatechin (4), alpha-amyrin (5), eugenyl-beta-rutinoside (6), 2alpha, 3alpha, 19alpha-trihydroxyurs-12-en-28-oic (7), scopolin (8), scutellarein-7-O-alpha-L-rhamnoside (9), scopoletin (10), quercetin (11), quercetin-3-O-beta-D-glucoside (12), apigenin (13), 2alpha-hydroxyursolic acid (14). All compounds are obtained from this plant for the first time.

Flavonoid Apigenin Is an Inhibitor of the NAD+ase CD38

PubMed Central

Escande, Carlos; Nin, Veronica; Price, Nathan L.; Capellini, Verena; Gomes, Ana P.; Barbosa, Maria Thereza; O’Neil, Luke; White, Thomas A.; Sinclair, David A.; Chini, Eduardo N.

2013-01-01

Metabolic syndrome is a growing health problem worldwide. It is therefore imperative to develop new strategies to treat this pathology. In the past years, the manipulation of NAD+ metabolism has emerged as a plausible strategy to ameliorate metabolic syndrome. In particular, an increase in cellular NAD+ levels has beneficial effects, likely because of the activation of sirtuins. Previously, we reported that CD38 is the primary NAD+ase in mammals. Moreover, CD38 knockout mice have higher NAD+ levels and are protected against obesity and metabolic syndrome. Here, we show that CD38 regulates global protein acetylation through changes in NAD+ levels and sirtuin activity. In addition, we characterize two CD38 inhibitors: quercetin and apigenin. We show that pharmacological inhibition of CD38 results in higher intracellular NAD+ levels and that treatment of cell cultures with apigenin decreases global acetylation as well as the acetylation of p53 and RelA-p65. Finally, apigenin administration to obese mice increases NAD+ levels, decreases global protein acetylation, and improves several aspects of glucose and lipid homeostasis. Our results show that CD38 is a novel pharmacological target to treat metabolic diseases via NAD+-dependent pathways. PMID:23172919

Synthetic analogues of flavonoids with improved activity against platelet activation and aggregation as novel prototypes of food supplements.

PubMed

Del Turco, Serena; Sartini, Stefania; Cigni, Giulia; Sentieri, Cassandra; Sbrana, Silverio; Battaglia, Debora; Papa, Angela; Da Settimo, Federico; La Motta, Concettina; Basta, Giuseppina

2015-05-15

We investigated the ability of quercetin and apigenin to modulate platelet activation and aggregation, and compared the observed efficacy with that displayed by their synthetic analogues 2-phenyl-4H-pyrido[1,2-a]pyrimidin-4-ones, 1-4, and 2,3-diphenyl-4H-pyrido[1,2-a]pyrimidin-4-ones, 5-7. Platelet aggregation was explored through a spectrophotometric assay on platelet-rich plasma (PRP) treated with the thromboxane A2 mimetic U46619, collagen and thrombin in presence/absence of various bioisosteres of flavonoids (12.5-25-50-100 μM). The platelet density, (mean platelet component, MPC), was measured by the Advia 120 Hematology System as a marker surrogate of platelet activation. The induced P-selectin expression, which reflects platelet degranulation/activation, was quantified by flow cytometry on PRP. Our synthetic compounds modulated significantly both platelet activation and aggregation, thus turning out to be more effective than the analogues quercetin and apigenin when tested at a concentration fully consistent with their use in vivo. Accordingly, they might be used as food supplements to increase the efficacy of natural flavonoids. Copyright © 2014 Elsevier Ltd. All rights reserved.

Absorption and metabolism of bioactive molecules after oral consumption of cooked edible heads of Cynara scolymus L. (cultivar Violetto di Provenza) in human subjects: a pilot study.

PubMed

Azzini, E; Bugianesi, R; Romano, F; Di Venere, D; Miccadei, S; Durazzo, A; Foddai, M S; Catasta, G; Linsalata, V; Maiani, G

2007-05-01

The current growing interest for natural antioxidants has led to a renewed scientific attention for artichoke, due not only to its nutritional value, but, overall, to its polyphenolic content, showing strong antioxidant properties. The major constituents of artichoke extracts are hydroxycinnamic acids such as chlorogenic acid, dicaffeoylquinic acids caffeic acid and ferulic acid, and flavonoids such as luteolin and apigenin glycosides. In vitro studies, using cultured rat hepatocytes, have shown its hepatoprotective functions and in vivo studies have shown the inhibition of cholesterol biosynthesis in human subjects. Several studies have shown the effect on animal models of artichoke extracts, while information on human bioavailability and metabolism of hydroxycinnamates derivatives is still lacking. Results showed a plasma maximum concentration of 6.4 (SD 1.8) ng/ml for chlorogenic acid after 1 h and its disappearance within 2 h (P< 0.05). Peak plasma concentrations of 19.5 (SD 6.9) ng/ml for total caffeic acid were reached within 1 h, while ferulic acid plasma concentrations showed a biphasic profile with 6.4 (SD1.5) ng/ml and 8.4 (SD4.6) ng/ml within 1 h and after 8 h respectively. We observed a significant increase of dihydrocaffeic acid and dihydroferulic acid total levels after 8 h (P<0.05). No circulating plasma levels of luteolin and apigenin were present. Our study confirms the bioavailability of metabolites of hydroxycinnamic acids after ingestion of cooked edible Cynara scolymus L. (cultivar Violetto di Provenza).

Statistical optimization of an RP-HPLC method for the determination of selected flavonoids in berry juices and evaluation of their antioxidant activities.

PubMed

Ciric, Andrija; Jelikic-Stankov, Milena; Cvijovic, Milica; Djurdjevic, Predrag

2018-04-01

An isocratic RP-HPLC method for the separation and identification of selected flavonoids (quercetin, rutin, luteolin-7-O-glucoside, kaempferol and kaempferol-3-O-glucoside) in commercial berry juices (blackcurrant, blueberry, red raspberry and cherry) was developed with the aid of central composite design and response surface methodology. The optimal separation conditions were a mobile phase of 85:15 (% v/v) water-acetonitrile, pH 2.8 (adjusted with formic acid), flow rate 0.5 mL min -1 and column temperature 35°C. The obtained levels of bioflavonoids (mg per 100 mL of juice) were as follows: for quercetin, ca. 0.21-5.12; for kaempferol, ca. 0.05-1.2; for rutin, ca. 0.4-6.5; for luteolin-7-O-glucoside, ca. 5.6-10.2; and for kaempferol-3-O-glucoside, ca. 0.02-0.12. These are considerably lower than the values in fresh fruits. Total phenolic, flavonoid and anthocyanin contents were determined spectrophotometrically. Total flavonoid content varied as follows: blackcurrant > blueberry > red raspberry > cherry. The antioxidant activity of juice extracts (DPPH and ABTS methods) expressed as IC 50 values varied from 8.56 to 14.05 mg L -1 . These values are ~2.5-3 times lower than quercetin, ascorbic acid and Trolox®, but compared with rutin and butylhydroxytoluene, berries show similar or better antioxidant activity by both the DPPH and ABTS methods. Copyright © 2017 John Wiley & Sons, Ltd.

Quercetin, Morin, Luteolin, and Phloretin Are Dietary Flavonoid Inhibitors of Monocarboxylate Transporter 6.

PubMed

Jones, Robert S; Parker, Mark D; Morris, Marilyn E

2017-09-05

Monocarboxylate transporter 6 (MCT6; SLC16A5) has been recognized for its role as a xenobiotic transporter, with characterized substrates probenecid, bumetanide, and nateglinide. To date, the impact of commonly ingested dietary compounds on MCT6 function has not been investigated, and therefore, the objective of this study was to evaluate a variety of flavonoids for their potential MCT6-specific interactions. Flavonoids are a large group of polyphenolic phytochemicals found in commonly consumed plant-based products that have been recognized for their dietary health benefits. The uptake of bumetanide in human MCT6 gene-transfected Xenopus laevis oocytes was significantly decreased in the presence of a variety of flavonoids (e.g., quercetin, luteolin, phloretin, and morin), but was not significantly affected by flavonoid glycosides (e.g., naringin, rutin, phlorizin). The IC 50 values of quercetin, phloretin, and morin were determined to be 25.3 ± 3.36, 17.3 ± 2.37, and 33.1 ± 3.29 μM, respectively. The mechanism of inhibition of phloretin was reversible and competitive, with a K i value of 22.8 μM. Furthermore, typical MCT substrates were also investigated for their potential interactions with MCT6. Substrates of MCTs 1, 2, 4, 8, and 10 did not cause any significant decrease in MCT6-mediated bumetanide uptake, suggesting that MCT6 has distinct compound selectivity. In summary, these results suggest that dietary aglycon flavonoids may significantly alter the pharmacokinetics and pharmacodynamics of bumetanide and other MCT6-specific substrates, and may represent potential substrates for MCT6.

Flavonoids Are Inhibitors of Human Organic Anion Transporter 1 (OAT1)–Mediated Transport

PubMed Central

An, Guohua; Wang, Xiaodong

2014-01-01

Organic anion transporter 1 (OAT1) has been reported to be involved in the nephrotoxicity of many anionic xenobiotics. As current clinically used OAT1 inhibitors are often associated with safety issues, identifying potent OAT1 inhibitors with little toxicity is of great value in reducing OAT1-mediated drug nephrotoxicity. Flavonoids are a class of polyphenolic compounds with exceptional safety records. Our objective was to evaluate the effects of 18 naturally occurring flavonoids, and some of their glycosides, on the uptake of para-aminohippuric acid (PAH) in both OAT1-expressing and OAT1-negative LLC-PK1 cells. Most flavonoid aglycones produced substantial decreases in PAH uptake in OAT1-expressing cells. Among the flavonoids screened, fisetin, luteolin, morin, and quercetin exhibited the strongest effect and produced complete inhibition of OAT1-mediated PAH uptake at a concentration of 50 μM. Further concentration-dependent studies revealed that both morin and luteolin are potent OAT1 inhibitors, with IC50 values of <0.3 and 0.47 μM, respectively. In contrast to the tested flavonoid aglycones, all flavonoid glycosides had negligible or small effects on OAT1. In addition, the role of OAT1 in the uptake of fisetin, luteolin, morin, and quercetin was investigated and fisetin was found to be a substrate of OAT1. Taken together, our results indicate that flavonoids are a novel class of OAT1 modulators. Considering the high consumption of flavonoids in the diet and in herbal products, OAT1-mediated flavonoid-drug interactions may be clinically relevant. Further investigation is warranted to evaluate the nephroprotective role of flavonoids in relation to drug-induced nephrotoxicity mediated by the OAT1 pathway. PMID:25002746

Effects of flavonoids from Martynia annua and Tephrosia purpurea on cutaneous wound healing

PubMed Central

Lodhi, Santram; Jain, Avijeet; Jain, Alok Pal; Pawar, Rajesh Singh; Singhai, Abhay Kumar

2016-01-01

Objective: Martynia annua L. (M. annua), (Martyniaccae) has been traditionally used in the treatment of epilepsy, sore throat and inflammatory disorders. The leaf paste is used topically on Tuberculosis of the lymphatic glands and wounds of domestic animals. Tephrosia purpurea (T. purpurea), (Fabaceae) has been used traditionally as a remedy for asthma, gonorrhea, rheumatism and ulcers. This study aimed to evaluate the potential wound healing effects of different fractions ofethanol extract of M. annua leaves and aerial parts of T. purpurea. Materials and Methods: Methanol fraction of M. annua (MAF-C) and ethyl acetate fraction of T. purpurea (TPF-A) were evaluated for healing potential in dead-space and burn wound models. An ointment (5% w/w) of MAF-C and TPF-A, pongamol (0.2 and 0.5% w/w) and luteolin (0.2 and 0.5% w/w) was applied topically twice a day. The effects were compared with Povidone Iodine ointment with respect to protein, collagen content, enzymatic assay and histopathological finding of granuloma tissues. Results: Ethanol extracts of M. annua and T. purpureawere exhibited total flavonoid contents of 126.2 ± 4.69 and 171.6 ± 6.38 mg (quercetin equivalent), respectively. HPLC fingerprinting confirmed the presence of luteolin in M. annua and quercetin in T. purpurea. TPF-A and MAF-C ointments (5% w/w) significantly increases the hydroxyproline and protein contents. Luteolin and pongamol ointments were also found to be effective in both wound models. Conclusion: Our findings suggested that 5% w/w ointment of TPF-A and MAF-C fractions were more effective than isolated flavonoids in wound healing which may be due to synergistic interactions between the flavonoids and other constituents. PMID:27761428

[Studies on the flavonoids from Dendranthema lavandulifolium].

PubMed

Shen, Y X; Quan, L H; Guan, L; Chen, J M

1997-06-01

From the whole plant of Dendranthema lavandulifolium, two flavonoides (I, II) and two flavone glycosides (III, IV) were isolated. They were identified as luteolin (I), apigenin (II), 5-hydroxy-4'-methoxy-flavone-7-O-alpha-L-rhamnopyranosyl(1-->6)-beta- D-glucopyranosyl (acaciin III) and 5-hydroxy-4'-methoxy-flavone-7-O-alpha-L-rhamnopyranosyl (1-->6) [2-O-acetyl-beta-D-glucopyranosyl(1-->2)]-beta-D-glucopyranoside (IV) by means of IR, UV, 1H-NMR, 13C-NMR, EI-MS, HRFAB, etc. Among these four compounds, I, II were isolated for the first time from this plant, IV is a new compound.

Phytochemical analysis of Hibiscus caesius using high performance liquid chromatography coupled with mass spectrometry.

PubMed

Ain, Quratul; Naveed, Muhammad Na; Mumtaz, Abdul Samad; Farman, Muhammad; Ahmed, Iftikhar; Khalid, Nauman

2015-09-01

Various species in genus Hibiscus are traditionally known for their therapeutic attributes. The present study focused on the phytochemical analysis of a rather unexplored species Hibiscus caesius (H. caesius), using high-pressure liquid chromatography coupled with mass spectrometry (HPLC-MS). The analysis revealed five major compounds in the aqueous extract, viz. vanillic acid, protocatechoic acid, quercetin, quercetin glucoside and apigenin, being reported for the first time in H. caesius. Literature suggests that these compounds have important pharmacological traits such as anti-cancer, anti-inflammatory, anti-bacterial and hepatoprotective etc. however, this requires further pharmacological investigations at in vitro and in vivo scale. The above study concluded the medicinal potential of H. caesius.

Biochemical changes in phenols, flavonoids, tannins, vitamin E, β-carotene and antioxidant activity during soaking of three white sorghum varieties

PubMed Central

Afify, Abd El-Moneim MR; El-Beltagi, Hossam S; El-Salam, Samiha M Abd; Omran, Azza A

2012-01-01

Objective To investigate the changes in total phenols, flavonoids, tannins, vitamin E, β-carotene and antioxidant activity during soaking of three white sorghum varieties. Methods The changes in total phenols, total flavonoids, tannins, phenolic acids compounds, flavonoid components, vitamin E, β-carotene and antioxidant activity during soaking of sorghum grains were determined. Results Total phenols, total flavonoids, tannins, vitamin E, β-carotene and antioxidant activity in raw sorghum were ranged from 109.21 to 116.70, 45.91 to 54.69, 1.39 to 21.79 mg/100 g, 1.74 to 5.25, 0.54 to 1.19 mg/kg and 21.72% to 27.69% and 25.29% to 31.97%, respectively. The above measured compounds were significantly decreased after soaking. p-Hydroxybenzoic acid, vanillic acid, syringic acid and cinnamic acid represent the major phenolic acids in Dorado variety. While ferulic acid, p-coumaric acid, gallic acid and caffeic acid represent the major phenolic acids in Shandaweel-6. On the other hand, protocatechuic acid represents the major phenolic acids in Giza-15. Regarding flavonoids components, Dorado was the highest variety in kampferol and naringenin while Shandaweel-6 was the highest variety in luteolin, apigenin, hypersoid, quercetin and christen. Finally, Giza-15 was the highest variety in catechin. Phenolic acids, flavonoid compounds and antioxidant activities were decreased after soaking. Conclusions Sorghum varieties have moderate quantities from total phenols, total flavonoids, tannins, phenolic acids compounds, flavonoid components, vitamin E, β-carotene and antioxidant activity which decreased after soaking. PMID:23569898

Biochemical changes in phenols, flavonoids, tannins, vitamin E, β-carotene and antioxidant activity during soaking of three white sorghum varieties.

PubMed

Afify, Abd El-Moneim M R; El-Beltagi, Hossam S; El-Salam, Samiha M Abd; Omran, Azza A

2012-03-01

To investigate the changes in total phenols, flavonoids, tannins, vitamin E, β-carotene and antioxidant activity during soaking of three white sorghum varieties. The changes in total phenols, total flavonoids, tannins, phenolic acids compounds, flavonoid components, vitamin E, β-carotene and antioxidant activity during soaking of sorghum grains were determined. Total phenols, total flavonoids, tannins, vitamin E, β-carotene and antioxidant activity in raw sorghum were ranged from 109.21 to 116.70, 45.91 to 54.69, 1.39 to 21.79 mg/100 g, 1.74 to 5.25, 0.54 to 1.19 mg/kg and 21.72% to 27.69% and 25.29% to 31.97%, respectively. The above measured compounds were significantly decreased after soaking. p-Hydroxybenzoic acid, vanillic acid, syringic acid and cinnamic acid represent the major phenolic acids in Dorado variety. While ferulic acid, p-coumaric acid, gallic acid and caffeic acid represent the major phenolic acids in Shandaweel-6. On the other hand, protocatechuic acid represents the major phenolic acids in Giza-15. Regarding flavonoids components, Dorado was the highest variety in kampferol and naringenin while Shandaweel-6 was the highest variety in luteolin, apigenin, hypersoid, quercetin and christen. Finally, Giza-15 was the highest variety in catechin. Phenolic acids, flavonoid compounds and antioxidant activities were decreased after soaking. Sorghum varieties have moderate quantities from total phenols, total flavonoids, tannins, phenolic acids compounds, flavonoid components, vitamin E, β-carotene and antioxidant activity which decreased after soaking.

New validated high-performance liquid chromatographic method for simultaneous analysis of ten flavonoid aglycones in plant extracts using a C18 fused-core column and acetonitrile-tetrahydrofuran gradient.

PubMed

Olszewska, Monika A

2012-09-01

An HPLC method of high resolution has been developed and validated for the simultaneous determination of ten prominent flavonoid aglycones in plant materials using a fused-core C18-silica column (Ascentis® Express, 4.6 mm × 150 mm, 2.7 μm). The separation was accomplished with an acetonitrile-tetrahydrofuran gradient elution at a flow rate of 1 mL/min and temperature of 30°C. UV spectrophotometric detection was employed at 370 nm for flavonols (quercetin [QU], myricetin [MY], isorhamnetin [IS], kaempferol [KA], sexangularetin [SX], and limocitrin [LM]) and 340 nm for flavones (apigenin [AP], acacetin [AC], chrysoeriol [CH], and luteolin [LU]). The high resolution of critical pairs QU/LU (10.50), QU/CH (3.40), AP/CH (2.51), SX/LM (2.30), and IS/KA (2.70) was achieved within 30.3 min. The observed column back pressure was less than 4300 psi, thus acceptable for conventional HPLC equipment. The method was sensitive enough having LODs of 0.115-0.525 ng and good linearity (r > 0.9999) over the test range. The precision values, expressed as RSD values, were <7.5%, and the accuracy was in the range of 95.3-100.2% for all analytes except MY (73.8%). The method was successfully employed for the determination of flavonoids in several medicinal plants, such as Ginkgo biloba, Betula pendula, and a variety of Sorbus species. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Differential patterns of inhibition of the sugar transporters GLUT2, GLUT5 and GLUT7 by flavonoids.

PubMed

Gauer, Julia S; Tumova, Sarka; Lippiat, Jonathan D; Kerimi, Asimina; Williamson, Gary

2018-06-01

Only limited data are available on the inhibition of the sugar transporter GLUT5 by flavonoids or other classes of bioactives. Intestinal GLUT7 is poorly characterised and no information exists concerning its inhibition. We aimed to study the expression of GLUT7 in Caco-2/TC7 intestinal cells, and evaluate inhibition of glucose transport by GLUT2 and GLUT7, and of fructose transport by GLUT2, GLUT5 and GLUT7, by flavonoids. Differentiated Caco-2/TC7 cell monolayers were used to investigate GLUT7 expression, as well as biotinylation and immunofluorescence to assess GLUT7 location. For mechanistic sugar transport studies, X. laevis oocytes were injected with individual mRNA, and GLUT protein expression on oocyte membranes was confirmed. Oocytes were incubated with D-[ 14 C(U)]-glucose or D-[ 14 C(U)]-fructose in the presence of flavonoids, and uptake was estimated by liquid scintilation counting. In differentiated Caco-2/TC7 cell monolayers, GLUT7 was mostly expressed apically. When applied apically, or to both compartments, sorbitol, galactose, L-glucose or sucrose did not affect GLUT7 mRNA expression. Fructose applied to both sides increased GLUT7 mRNA (13%, p ≤ 0.001) and total GLUT7 protein (2.7-fold, p ≤ 0.05), while the ratio between apical, basolateral and total GLUT7 protein was unchanged. In the X. laevis oocyte model, GLUT2-mediated glucose and fructose transport were inhibited by quercetin, (-)-epigallocatechin gallate (EGCG) and apigenin, GLUT5-mediated fructose transport was inhibited by apigenin and EGCG, but not by quercetin, and GLUT7-mediated uptake of both glucose and fructose was inhibited by apigenin, but not by quercetin nor EGCG. Expression of GLUT7 was increased by fructose, but only when applied to Caco-2/TC7 cells both apically and basolaterally. Since GLUT2, GLUT5 and GLUT7 show different patterns of inhibition by the tested flavonoids, we suggest that they have the potential to be used as investigational tools to distinguish sugar transporter activity in different biological settings. Copyright © 2018 Elsevier Inc. All rights reserved.

Sonochemical Effects on 14 Flavonoids Common in Citrus: Relation to Stability

PubMed Central

Qiao, Liping; Sun, Yujing; Chen, Rongrong; Fu, Yu; Zhang, Wenjuan; Li, Xin; Chen, Jianchu; Shen, Yan; Ye, Xingqian

2014-01-01

The sonochemical effects of ultrasound (US) treatment on 14 flavonoids representing the main flavonoids in citrus fruit were investigated in a standard mixture by stability evaluation of a model system. Degradation products were further tentatively identified by Fourier transform infrared spectroscopy and high-performance liquid chromatography–ultraviolet detection–electrospray ionization tandem mass spectrometry. Thirteen flavonoids (i.e., eriocitrin, narirutin, neohesperidin, quercitrin, eridictyol, didymin, naringenin, luteolin, sinensetin, nobiletin, tangeretin, naringin, and hesperidin) were fairly stable whereas quercetin was degraded significantly by US treatment. The types of solvent and temperature used were important factors that determined the resulting degradation reactions. The degradation rate of quercetin was highest in 80% ethanol aqueous solution and decreased with increasing temperature. Longer US durations caused increases in the extent of quercetin degradation. Liquid height, ultrasonic intensity, pulse length, and duty cycle of US affected degradation rates but did not change the nature of degradation of the flavonoids. Four types of reactions occurred simultaneously for quercetin under US treatment: oxidation, addition, polymerization, and decomposition. Eight degradation products were tentatively identified as dimer, alcohol addition, oxidation, and decomposition products. PMID:24516562

Sonochemical effects on 14 flavonoids common in citrus: relation to stability.

PubMed

Qiao, Liping; Sun, Yujing; Chen, Rongrong; Fu, Yu; Zhang, Wenjuan; Li, Xin; Chen, Jianchu; Shen, Yan; Ye, Xingqian

2014-01-01

The sonochemical effects of ultrasound (US) treatment on 14 flavonoids representing the main flavonoids in citrus fruit were investigated in a standard mixture by stability evaluation of a model system. Degradation products were further tentatively identified by Fourier transform infrared spectroscopy and high-performance liquid chromatography-ultraviolet detection-electrospray ionization tandem mass spectrometry. Thirteen flavonoids (i.e., eriocitrin, narirutin, neohesperidin, quercitrin, eridictyol, didymin, naringenin, luteolin, sinensetin, nobiletin, tangeretin, naringin, and hesperidin) were fairly stable whereas quercetin was degraded significantly by US treatment. The types of solvent and temperature used were important factors that determined the resulting degradation reactions. The degradation rate of quercetin was highest in 80% ethanol aqueous solution and decreased with increasing temperature. Longer US durations caused increases in the extent of quercetin degradation. Liquid height, ultrasonic intensity, pulse length, and duty cycle of US affected degradation rates but did not change the nature of degradation of the flavonoids. Four types of reactions occurred simultaneously for quercetin under US treatment: oxidation, addition, polymerization, and decomposition. Eight degradation products were tentatively identified as dimer, alcohol addition, oxidation, and decomposition products.

Simultaneous determination of thirteen flavonoids from Xiaobuxin-Tang extract using high-performance liquid chromatography coupled with electrospray ionization mass spectrometry.

PubMed

Cen, Meifeng; Ruan, Jinxiu; Huang, Lihua; Zhang, Zhenqing; Yu, Nengjiang; Zhang, Youzhi; Cheng, Xuange; Xiong, Xiaohong; Wang, Guixiang; Zang, Linquan; Wang, Sujun

2015-11-10

A simple and reliable high performance liquid chromatography coupled with electrospray ionization mass spectrometry (HPLC-ESI-MS) analysis method was established to simultaneously determine thirteen flavonoids of Xiaobuxing-Tang in intestine perfusate, namely onpordin, 3'-O-methylorobol, glycitein, patuletin, genistein, luteolin, quercetin, nepitrin, quercimeritrin, daidzin, patulitrin, quercetagitrin and 3-glucosylisorhamnetin. Detection was performed on a quadrupole mass spectrometer equipped with an electrospray ionization (ESI) source operating in negative ionization mode. Negative ion ESI was used to form deprotonated molecules at m/z 315 for onpordin, m/z 299 for 3'-O-methylorobol, m/z 283 for glycitein, m/z 331 for patuletin, m/z 269 for genistein, m/z 285 for luteolin, m/z 301 for quercetin, m/z 477 for nepitrin, m/z 463 for quercimeritrin, m/z 461 for daidzin, m/z 493 for patulitrin, m/z 479 for quercetagitrin, m/z 477 for 3-glucosylisorhamnetin and m/z 609.2 for rutin. The linearity, sensitivity, selectivity, repeatability, accuracy, precision, recovery and matrix effect of the assay were evaluated. The proposed method was successfully applied to simultaneous determination of these thirteen flavonoids, and using this method, the intestinal absorption profiles of thirteen flavonoids were preliminarily predicted. Copyright © 2015 Elsevier B.V. All rights reserved.

SERS-Based Flavonoid Detection Using Ethylenediamine-β-Cyclodextrin as a Capturing Ligand

PubMed Central

Choi, Jae Min; Hahm, Eunil; Park, Kyeonghui; Jeong, Daham; Rho, Won-Yeop; Kim, Jaehi; Jeong, Dae Hong; Lee, Yoon-Sik; Jhang, Sung Ho; Chung, Hyun Jong; Cho, Eunae; Yu, Jae-Hyuk; Jun, Bong-Hyun; Jung, Seunho

2017-01-01

Ethylenediamine-modified β-cyclodextrin (Et-β-CD) was immobilized on aggregated silver nanoparticle (NP)-embedded silica NPs (SiO2@Ag@Et-β-CD NPs) for the effective detection of flavonoids. Silica NPs were used as the template for embedding silver NPs to create hot spots and enhance surface-enhanced Raman scattering (SERS) signals. Et-β-CD was immobilized on Ag NPs to capture flavonoids via host-guest inclusion complex formation, as indicated by enhanced ultraviolet absorption spectra. The resulting SiO2@Ag@Et-β-CD NPs were used as the SERS substrate for detecting flavonoids, such as hesperetin, naringenin, quercetin, and luteolin. In particular, luteolin was detected more strongly in the linear range 10−7 to 10−3 M than various organic molecules, namely ethylene glycol, β-estradiol, isopropyl alcohol, naphthalene, and toluene. In addition, the SERS signal for luteolin captured by the SiO2@Ag@Et-β-CD NPs remained even after repeated washing. These results indicated that the SiO2@Ag@Et-β-CD NPs can be used as a rapid, sensitive, and selective sensor for flavonoids. PMID:28336842

Food Antioxidants and Their Anti-Inflammatory Properties: A Potential Role in Cardiovascular Diseases and Cancer Prevention

PubMed Central

Griffiths, Keith; Aggarwal, Bharat B.; Singh, Ram B.; Buttar, Harpal S.; Wilson, Douglas; De Meester, Fabien

2016-01-01

Mediterranean-style diets caused a significant decline in cardiovascular diseases (CVDs) in early landmark studies. The effect of a traditional Mediterranean diet on lipoprotein oxidation showed that there was a significant reduction in oxidative stress in the intervention group (Mediterranean diet + Virgin Olive Oil) compared to the low-fat diet group. Conversely, the increase in oxidative stress causing inflammation is a unifying hypothesis for predisposing people to atherosclerosis, carcinogenesis, and osteoporosis. The impact of antioxidants and anti-inflammatory agents on cancer and cardiovascular disease, and the interventive mechanisms for the inhibition of proliferation, inflammation, invasion, metastasis, and activation of apoptosis were explored. Following the Great Oxygen Event some 2.3 billion years ago, organisms have needed antioxidants to survive. Natural products in food preservatives are preferable to synthetic compounds due to their lower volatility and stability and generally higher antioxidant potential. Free radicals, reactive oxygen species, antioxidants, pro-oxidants and inflammation are described with examples of free radical damage based on the hydroxyl, nitric oxide and superoxide radicals. Flavonoid antioxidants with 2- or 3-phenylchroman structures such as quercetin, kaempferol, myricetin, apigenin, and luteolin, constituents of fruits, vegetables, tea, and wine, which may reduce coronary disease and cancer, are described. The protective effect of flavonoids on the DNA damage caused by hydroxyl radicals through chelation is an important mechanism, though the converse may be possible, e.g., quercetin. The antioxidant properties of carotenoids, which are dietary natural pigments, have been studied in relation to breast cancer risk and an inverse association was found with plasma concentrations: higher levels mean lower risk. The manipulation of primary and secondary human metabolomes derived especially from existing or transformed gut microbiota was explored as a possible alternative to single-agent dietary interventions for cancer and cardiovascular disease. Sustained oxidative stress leading to inflammation and thence to possibly to cancer and cardiovascular disease is described for spices and herbs, using curcumin as an example of an intervention, based on activation of transcription factors which suggest that oxidative stress, chronic inflammation, and cancer are closely linked. PMID:28933408

Interactions of pharmacokinetic profile of different parts from Ginkgo biloba extract in rats.

PubMed

Guan, HanLiang; Qian, Dawei; Ren, Hao; Zhang, Wei; Nie, Hui; Shang, Erxing; Duan, Jinao

2014-08-08

Extracts from Ginkgo biloba L. leaves confer their therapeutic effects through the synergistic actions of flavonoid and terpenoid components, but some non-flavonoid and non-terpenoid components also exist in this extract. In the study of this paper, an investigation was carried out to compare the pharmacokinetic parameters of fourteen compounds to clarify the influences of non-flavonoid and non-terpenoid fraction (WEF) on the pharmacokinetics profile of the flavonoid fraction (FF) and the terpene lactone fraction (TLF) from Ginkgo biloba extracts. A selective and sensitive UPLC-MS/MS method was established to determine the plasma concentrations of the fourteen compounds to compare the pharmacokinetic parameters after orally administration of FF, TLF, FF-WEF, FF-TLF, TLF-WEF and FF-TLF-WEF with approximately the same dose. At different time points, the concentration of rutin (1), isoquercitrin (2), quercetin 3-O-[4-O-(-β-D-glucosyl)-α-L-rhamnoside] (3), ginkgolide C (4), bilobalide (5), quercitrin (6), ginkgolide B (7), ginkgolide A (8), luteolin (9), quercetin (10), apigenin (11), kaempferol (12), isorhamnetin (13), genkwanin (14) in rat plasma were determined and main pharmacokinetic parameters including T1/2, Tmax, Cmax and AUC were calculated using the DAS 3.2 software package. The statistical analysis was performed using the Student׳s t-test with P<0.05 as the level of significance. FF and WEF had no effect on the pharmacokinetic behaviors and parameters of the four terpene lactones, but the pharmacokinetic profiles and parameters of flavonoids changed while co-administered with non-flavonoid components. It was found that Cmax and AUC of six flavonoid aglycones in group FF-WEF, FF-TLF and FF-TLF-WEF had varying degrees of reduction in comparison with group FF, especially in group FF-TLF-WEF. On the contrary, the values of Cmax, Tmax and AUC of four flavonoid glycosides in group FF-TLF-WEF were significantly increased compared with those in group FF. These results indicate that non-flavonoid components in Ginkgo biloba extracts could increase the absorption and improve the bioavailability of flavonoid glycosides but decrease the absorption and reduce the bioavailability of flavonoid aglycones. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Design and Synthesis of a Novel Class of Flavonoid Derivatives via Sequential Phosphorylation and its Application for Greener Nanoparticle Synthesis

NASA Astrophysics Data System (ADS)

Osonga, Francis Juma

Flavonoids exhibit arrays of biological effects that are beneficial to humans, including anti-viral, anti-oxidative, anti-inflammatory and anti-carcinogenic effects. However, these applications have been hindered by their poor stability and solubility in common solvents. Consequently, there is significant interest in the modification of flavonoids to improve their solubility. This poor solubility is also believed to be responsible for its permeability and bioavailability. Hence the central goal of this work is to design synthetic strategies for the sequential protection of the -OH groups in order to produce phosphorylated quercetin and apigenin derivatives. This work is divided into two parts: the first part presents the design, synthesis, and characterization of novel flavonoid derivatives via global and sequential phosphorylation. The second part focuses on the application of the synthesized derivatives for greener nanoparticle synthesis. This work shows for the first time that sequential phosphorylation of Quercetin is feasible through the design of 4 new derivatives namely: 5,4'-O-Quercetin Diphosphate (QDPI), 4'-O-phosphate Quercetin (4'-QPI), 5,4'-Quercetin Diphosphate (5,4'-QDP) and monophosphate 4-QP. The synthesis of 4'-QP and 5, 4'-QDP was successful with 85% and 60.5% yields respectively. In addition, the progress towards the total synthesis of apigenin phosphate derivatives (7, 4'-ADP and 7-AP) is presented. The synthesized derivatives were characterized using 1H, 13C, and 31P NMR. The phosphorylated derivatives were subsequently explored as reducing agents for sustainable synthesis of gold, silver and copper nanoparticles. We have successfully demonstrated the photochemical synthesis of gold nanoplates of sizes ranging from 10 - 200 nm using water soluble QDP in the presence of sunlight. This work contributes immensely in promoting the ideals of green nanosynthesis by (i) eliminating the use of organic solvents in the nanosynthesis, (ii) exploiting the naturally-derived flavonoids as reducing and stabilizing reagents without any other extraneous reagents, and (iii) achieving anisotropic nanosynthesis using sunlight and at room temperature.

Analysis of phenolic compounds in Matricaria chamomilla and its extracts by UPLC-UV

PubMed Central

Haghi, G.; Hatami, A.; Safaei, A.; Mehran, M.

2014-01-01

Chamomile (Matricaria chamomilla L.) is a widely used medicinal plant possessing several pharmacological effects due to presence of active compounds. This study describes a method of using ultra performance liquid chromatography (UPLC) coupled with photodiode array (PDA) detector for the separation of phenolic compounds in M. chamomilla and its crude extracts. Separation was conducted on C18 column (150 mm × 2 mm, 1.8 μm) using a gradient elution with a mobile phase consisting of acetonitrile and 4% aqueous acetic acid at 25°C. The method proposed was validated for determination of free and total apigenin and apigenin 7-glucoside contents as bioactive compounds in the extracts by testing sensitivity, linearity, precision and recovery. In general, UPLC produced significant improvements in method sensitivity, speed and resolution. Extraction was performed with methanol, 70% aqueous ethanol and water solvents. Total phenolic and total flavonoid contents ranged from 1.77 to 50.75 gram (g) of gallic acid equivalent (GAE)/100 g and 0.82 to 36.75 g quercetin equivalent (QE)/100 g in dry material, respectively. There was a considerable difference from 40 to 740 mg/100 g for apigenin and 210 to 1110 mg/100 g for apigenin 7-glucoside in dry material. PMID:25598797

Flavonoid apigenin is an inhibitor of the NAD+ ase CD38: implications for cellular NAD+ metabolism, protein acetylation, and treatment of metabolic syndrome.

PubMed

Escande, Carlos; Nin, Veronica; Price, Nathan L; Capellini, Verena; Gomes, Ana P; Barbosa, Maria Thereza; O'Neil, Luke; White, Thomas A; Sinclair, David A; Chini, Eduardo N

2013-04-01

Metabolic syndrome is a growing health problem worldwide. It is therefore imperative to develop new strategies to treat this pathology. In the past years, the manipulation of NAD(+) metabolism has emerged as a plausible strategy to ameliorate metabolic syndrome. In particular, an increase in cellular NAD(+) levels has beneficial effects, likely because of the activation of sirtuins. Previously, we reported that CD38 is the primary NAD(+)ase in mammals. Moreover, CD38 knockout mice have higher NAD(+) levels and are protected against obesity and metabolic syndrome. Here, we show that CD38 regulates global protein acetylation through changes in NAD(+) levels and sirtuin activity. In addition, we characterize two CD38 inhibitors: quercetin and apigenin. We show that pharmacological inhibition of CD38 results in higher intracellular NAD(+) levels and that treatment of cell cultures with apigenin decreases global acetylation as well as the acetylation of p53 and RelA-p65. Finally, apigenin administration to obese mice increases NAD(+) levels, decreases global protein acetylation, and improves several aspects of glucose and lipid homeostasis. Our results show that CD38 is a novel pharmacological target to treat metabolic diseases via NAD(+)-dependent pathways.

Flavonoids such as luteolin, fisetin and apigenin are inhibitors of interleukin-4 and interleukin-13 production by activated human basophils.

PubMed

Hirano, Toru; Higa, Shinji; Arimitsu, Junsuke; Naka, Tetsuji; Shima, Yoshihito; Ohshima, Shiro; Fujimoto, Minoru; Yamadori, Tomoki; Kawase, Ichiro; Tanaka, Toshio

2004-06-01

We have previously shown that fisetin, a flavonol, inhibits IL-4 and IL-13 synthesis by allergen- or anti-IgE-antibody-stimulated basophils. This time, we investigated the inhibition of IL-4 and IL-13 production by basophils by other flavonoids and attempted to determine the fundamental structure of flavonoids related to inhibition. We additionally investigated whether flavonoids suppress leukotriene C4 synthesis by basophils and IL-4 synthesis by T cells in response to anti-CD3 antibody. Highly purified peripheral basophils were stimulated for 12 h with anti-IgE antibody alone or anti-IgE antibody plus IL-3 in the presence of various concentrations of 18 different kinds of flavones and flavonols. IL-4 and IL-13 concentrations in the supernatants were then measured. Leukotriene C4 synthesis was also measured after basophils were stimulated for 1 h in the presence of flavonoids. Regarding the inhibitory activity of flavonoids on IL-4 synthesis by T cells, peripheral blood mononuclear cells were cultured with flavonoids in anti-CD3-antibody-bound plates for 2 days. Luteolin, fisetin and apigenin were found to be the strongest inhibitors of both IL-4 and IL-13 production by basophils but did not affect leukotriene C4 synthesis. At higher concentrations, these flavonoids suppressed IL-4 production by T cells. Based on a hierarchy of inhibitory activity, the basic structure for IL-4 inhibition by basophils was determined. Due to the inhibitory activity of flavonoids on IL-4 and IL-13 synthesis, it can be expected that the intake of flavonoids, depending on the quantity and quality, may ameliorate allergic symptoms or prevent the onset of allergic diseases. Copyright 2004 S. Karger AG, Basel

In vitro selection and characterization of single stranded DNA aptamers for luteolin: A possible recognition tool.

PubMed

Tuma Sabah, Jinan; Zulkifli, Razauden Mohamed; Shahir, Shafinaz; Ahmed, Farediah; Abdul Kadir, Mohammed Rafiq; Zakaria, Zarita

2018-05-15

Distinctive bioactivities possessed by luteolin (3', 4', 5, 7-tetrahydroxy-flavone) are advantageous for sundry practical applications. This paper reports the in vitro selection and characterization of single stranded-DNA (ssDNA) aptamers, specific for luteolin (LUT). 76-mer library containing 1015 randomized ssDNA were screened via systematic evolution of ligands by exponential enrichment (SELEX). The recovered ssDNA pool from the 8th round was amplified with unlabeled primers and cloned into PSTBlue-1 vector prior to sequencing. 22 of LUT-binding aptamer variants were further classified into one of the seven groups based on their N40 random sequence regions, wherein one representative from each group was characterized. The dissociation constant of aptamers designated as LUT#28, LUT#20 and LUT#3 was discerned to be 107, 214 and 109 nM, respectively with high binding affinity towards LUT. Prediction analysis of the secondary structure suggested discrete features with typical loop and stem motifs. Furthermore, LUT#3 displayed higher specificity with insignificant binding toward kaempferol and quercetin despite its structural and functional similarity compared to LUT#28 and LUT#20. Further LUT#3 can detect free luteolin within 0.2-1 mM in solution. It was suggested that LUT#3 aptamer were the most suitable for LUT recognition tool at laboratory scale based on the condition tested. Copyright © 2018 Elsevier Inc. All rights reserved.

Differential metabolomic analysis of the potential antiproliferative mechanism of olive leaf extract on the JIMT-1 breast cancer cell line.

PubMed

Barrajón-Catalán, Enrique; Taamalli, Amani; Quirantes-Piné, Rosa; Roldan-Segura, Cristina; Arráez-Román, David; Segura-Carretero, Antonio; Micol, Vicente; Zarrouk, Mokhtar

2015-02-01

A new differential metabolomic approach has been developed to identify the phenolic cellular metabolites derived from breast cancer cells treated with a supercritical fluid extracted (SFE) olive leaf extract. The SFE extract was previously shown to have significant antiproliferative activity relative to several other olive leaf extracts examined in the same model. Upon SFE extract incubation of JIMT-1 human breast cancer cells, major metabolites were identified by using HPLC coupled to electrospray ionization quadrupole-time-of-flight mass spectrometry (ESI-Q-TOF-MS). After treatment, diosmetin was the most abundant intracellular metabolite, and it was accompanied by minor quantities of apigenin and luteolin. To identify the putative antiproliferative mechanism, the major metabolites and the complete extract were assayed for cell cycle, MAPK and PI3K proliferation pathways modulation. Incubation with only luteolin showed a significant effect in cell survival. Luteolin induced apoptosis, whereas the whole olive leaf extract incubation led to a significant cell cycle arrest at the G1 phase. The antiproliferative activity of both pure luteolin and olive leaf extract was mediated by the inactivation of the MAPK-proliferation pathway at the extracellular signal-related kinase (ERK1/2). However, the flavone concentration of the olive leaf extract did not fully explain the strong antiproliferative activity of the extract. Therefore, the effects of other compounds in the extract, probably at the membrane level, must be considered. The potential synergistic effects of the extract also deserve further attention. Our differential metabolomics approach identified the putative intracellular metabolites from a botanical extract that have antiproliferative effects, and this metabolomics approach can be expanded to other herbal extracts or pharmacological complex mixtures. Copyright © 2014 Elsevier B.V. All rights reserved.

Validated UPLC-MS/MS method for quantification of seven compounds in rat plasma and tissues: Application to pharmacokinetic and tissue distribution studies in rats after oral administration of extract of Eclipta prostrata L.

PubMed

Du, Guangyan; Fu, Lingling; Jia, Jun; Pang, Xu; Yu, Haiyang; Zhang, Youcai; Fan, Guanwei; Gao, Xiumei; Han, Lifeng

2018-06-01

A rapid, sensitive and specific ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) method was developed to investigate the pharmacokinetics and tissue distribution of Eclipta prostrata extract. Rats were orally administrated the 70% ethanol extract of E. prostrata, and their plasma as well as various organs were collected. The concentrations of seven main compounds, ecliptasaponin IV, ecliptasaponin A, apigenin, 3'-hydroxybiochanin A, luteolin, luteolin-7-O-glucoside and wedelolactone, were quantified by UPLC-MS/MS through multiple reactions monitoring method. The precisions (RSD) of the analytes were all <15.00%. The extraction recoveries ranged from 74.65 to 107.45% with RSD ≤ 15.36%. The matrix effects ranged from 78.00 to 118.06% with RSD ≤ 15.04%. To conclude, the present pharmacokinetic and tissue distribution studies provided useful information for the clinical usage of Eclipta prostrata L. Copyright © 2018 John Wiley & Sons, Ltd.

Phytochemical analysis of hydroethanolic extract of Turnera diffusa Willd and evaluation of its effects on astrocyte cell death

PubMed Central

Bezerra, Andréia Gomes; Negri, Giuseppina; Duarte-Almeida, Joaquim Maurício; Smaili, Soraya Soubhi; Carlini, Elisaldo Araújo

2016-01-01

ABSTRACT Objective To evaluate the phytochemical composition of hydroethanolic extracts from powdered aerial parts of Turnera diffusa Willd (Turneraceae; T. diffusa), as well as its toxicity in astrocytes. Methods Chemical analyses of hydroethanolic extract from powdered aerial parts of T. diffusa were carried out using HPLC-DAD-ESI-MS/MS. In vitro assays using astrocytes culture were performed to evaluate cell death. Results Flavone-C, O-diglycosides, such as, luteolin-8-C-[6-deoxy-2-O-rhamnosyl]-xylo-hexos-3-uloside, apigenin-8-C-[6-deoxy-2-O-rhamnosyl]-xylo-hexos-3-uloside and apigenin-7-O-6”-p-coumaroylglucoside were the main compounds found in this hydroethanolic extract. Concentration time-effect demonstrated the toxicity of this extract at a concentration of 1,000µg/mL in astrocyte culture, after 6 and 24 hours of incubation. Conclusion In phytochemical analyses, important antioxidants (mainly flavonoids) were observed. T. diffusa extracts presented cytotoxic effect in high concentrations, leading to increased cell death in astrocyte culture. PMID:27074236

Simulated Gastrointestinal Digestion, Bioaccessibility and Antioxidant Capacity of Polyphenols from Red Chiltepin (Capsicum annuum L. Var. glabriusculum) Grown in Northwest Mexico.

PubMed

Ovando-Martínez, Maribel; Gámez-Meza, Nohemí; Molina-Domínguez, Claudia Celeste; Hayano-Kanashiro, Corina; Medina-Juárez, Luis Angel

2018-06-01

Chiltepin, a wild chili mostly used in different traditional foods and traditional medicine in Northwest Mexico, represents a source of polyphenols. However, studies about the bioaccessibility of polyphenols as a parameter to measure the nutritional quality and bioefficacy of them in the fruit after consumption are scarce. Chiltepin showed phenolic acids and flavonoids contents between 387 and 65 μg/g, respectively. Nevertheless, these values decreased after the digestion process. Before digestion, gallic acid, 4-hydroxibenzoinc acid, chlorogenic acid, caffeic acid, p-coumaric acid, quercetin and luteolin were the main polyphenols found in chiltepin by HPLC-DAD and confirmed by FIA-ESI-IT-MS/MS. Gallic and chlorogenic acids were non-detected in the gastric phase, while only p-coumaric acid (5.35 ± 3.89 μg/g), quercetin (5.91 ± 0.92 μg/g) and luteolin (2.86 ± 0.62 μg/g) were found in the intestinal phase. The bioaccessibility of phenolic acids, flavonoids, and total polyphenols after the intestinal phase was around 24, 17 and 23%, respectively. Overall, results indicated that release of polyphenols from chiltepin fruit might be affected by the food matrix and gastrointestinal conditions due to the low bioaccessibility values observed.

Simultaneous determination of eight flavonoids in propolis using chemometrics-assisted high performance liquid chromatography-diode array detection.

PubMed

Sun, Yan-Mei; Wu, Hai-Long; Wang, Jian-Yao; Liu, Zhi; Zhai, Min; Yu, Ru-Qin

2014-07-01

A fast analytical strategy of second-order calibration method based on the alternating trilinear decomposition algorithm (ATLD)-assisted high performance liquid chromatography coupled with a diode array detector (HPLC-DAD) was established for the simultaneous determination of eight flavonoids (rutin, quercetin, luteolin, kaempferol, isorhamnetin, apigenin, galangin and chrysin) in propolis capsules samples. The chromatographic separation was implemented on a Wondasil™ C18 column (250mm×4.6mm, 5μm) within 13min with a binary mobile phase composed of water with 1% formic acid and methanol at a flow rate of 1.0mLmin(-1) after flavonoids were only extracted with methanol by ultrasound extraction for 15min. The baseline problem was overcome by considering background drift as additional compositions or factors as well as the target analytes, and ATLD was employed to handle the overlapping peaks from analytes of interest or from analytes and co-eluting matrix compounds. The linearity was good with the correlation coefficients no less than 0.9947; the limit of detections (LODs) within the range of 3.39-33.05ngmL(-1) were low enough; the accuracy was confirmed by the recoveries ranged from 91.9% to 110.2% and the root-mean-square-error of predictions (RMSEPs) less than 1.1μg/mL. The results indicated that the chromatographic method with the aid of ATLD is efficient, sensitive and cost-effective and can realize the resolution and accurate quantification of flavonoids even in the presence of interferences, thus providing an alternative method for accurate quantification of analytes especially when the complete separation is not easily accomplished. The method was successfully applied to propolis capsules samples and the satisfactory results were obtained. Copyright © 2014 Elsevier B.V. All rights reserved.

Development of an ultra-fast liquid chromatography-tandem mass spectrometry method for simultaneous determination of seven flavonoids in rat plasma: Application to a comparative pharmacokinetic investigation of Ginkgo biloba extract and single pure ginkgo flavonoids after oral administration.

PubMed

Wang, Tianyang; Xiao, Jie; Hou, Huiping; Li, Pei; Yuan, Ziyue; Xu, Huarong; Liu, Ran; Li, Qing; Bi, Kaishun

2017-08-15

For deeper pharmacokinetic investigation and further curative application of ginkgo flavonoids, a delicate, efficient and precise UFLC-MS/MS technique for synchronous quantitation of seven flavonoids, apigenin, luteolin, naringenin, quercetin, diosmetin, kaempferol and isorhamnetin in rat plasma has been established. After mixing with the internal standard (IS) linarin, bio-samples were pretreated via ethyl acetate for liquid-liquid extraction, then isolated at 0.2ml/min flow rate on a Venusil MP C 18 chromatographic column (100mm×2.1mm, 3μm) by means of gradient elution. 0.1% formic acid-water and methanol system was used as the mobile phase. Mass spectrometric inspection was conducted on a 4000Q UFLC-MS/MS system with turbo ion spray source in patterns of negative ion and multiple reaction-monitoring (MRM). All calibration curves proved favorable linearity (R 2 ≥0.9918) in linear ranges. Intra-day and inter-day precisions didn't exceed 14.0% for all the analytes, and the accuracy was within 6.9%. Extraction recoveries of analytes and IS were less than ±15.0% of nominal concentrations. This method has been under thorough and firm verification for a comparative pharmacokinetic research after gavage between Ginkgo biloba extract and single pure ginkgo flavonoids. The results demonstrated that there're evident pharmacokinetic discrepancies, and possible structural influences were innovatively proposed. Generally, substitution with 3-hydroxylation, a double bond in ring C, ring B methoxylation often confer longer onset period. The existence of ring B catechol group gives rise to faster clearance. Copyright © 2017. Published by Elsevier B.V.

Inhibition effects of Vernonia cinerea active compounds against cytochrome P450 2A6 and human monoamine oxidases, possible targets for reduction of tobacco dependence.

PubMed

Prasopthum, Aruna; Pouyfung, Phisit; Sarapusit, Songklod; Srisook, Ekaruth; Rongnoparut, Pornpimol

2015-04-01

The human cytochrome P450 2A6 (CYP2A6) and monoamine oxidases (MAO-A and MAO-B), catalyzing nicotine and dopamine metabolisms, respectively, are two therapeutic targets of nicotine dependence. Vernonia cinerea, a medicinal plant commonly used for treatment of diseases such as asthma and bronchitis, has been shown reducing tobacco dependence effect among tobacco users. In the present study, we found eight active compounds isolated from V. cinerea that comprise inhibitory activity toward CYP2A6 and MAO-A and MAO-B enzymes using activity-guided assays, with coumarin as substrate of CYP2A6 and kynuramine of MAOs. These compounds were three flavones (apigenin, chrysoeriol, luteolin), one flavonol (quercetin), and four hirsutinolide-type sesquiterpene lactones (8α-(2-methylacryloyloxy)-hirsutinolide-13-O-acetate, 8α-(4-hydroxymethacryloyloxy)-hirsutinolide-13-O-acetate, 8α-tigloyloxyhirsutinolide-13-O-acetate, and 8α-(4-hydroxytigloyloxy)-hirsutinolide-13-O-acetate). Modes and kinetics of inhibition against the three enzymes were determined. Flavonoids possessed strong inhibitory effect on CYP2A6 in reversible mode, while inhibition by hirsutinolides was mechanism-based (NADPH-, concentration-, and time-dependence) and irreversible. Inhibition by hirsutinolides could not be reversed by dialysis and by addition of trapping agents or potassium ferricyanide. Flavonoids inhibited MAOs with variable degrees and were more prominent in inhibition toward MAO-A than hirsutinolides, while two of hirsutinolides inhibited MAO-B approximately comparable to two flavonoids. These results could have implications in combination of drug therapy for smoking cessation. Copyright © 2014 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Metabolite biodiversity in pepper (Capsicum) fruits of thirty-two diverse accessions: variation in health-related compounds and implications for breeding.

PubMed

Wahyuni, Yuni; Ballester, Ana-Rosa; Sudarmonowati, Enny; Bino, Raoul J; Bovy, Arnaud G

2011-08-01

A comprehensive study on morphology and biochemical compounds of 32 Capsicum spp. accessions has been performed. Accessions represented four pepper species, Capsicum annuum, Capsicum frutescens, Capsicum chinense and Capsicum baccatum which were selected by their variation in morphological characters such as fruit color, pungency and origin. Major metabolites in fruits of pepper, carotenoids, capsaicinoids (pungency), flavonoid glycosides, and vitamins C and E were analyzed and quantified by high performance liquid chromatography. The results showed that composition and level of metabolites in fruits varied greatly between accessions and was independent of species and geographical location. Fruit color was determined by the accumulation of specific carotenoids leading to salmon, yellow, orange, red and brown colored fruits. Levels of both O- and C-glycosides of quercetin, luteolin and apigenin varied strongly between accessions. All non-pungent accessions were devoid of capsaicins, whereas capsaicinoid levels ranged from 0.07 up to 80 mg/100g fr. wt. in fruit pericarp. In general, pungent accessions accumulated the highest capsaicinoid levels in placenta plus seed tissue compared to pericarp. The non-pungent capsaicinoid analogs, capsiates, could be detected at low levels in some pungent accessions. All accessions accumulated high levels of vitamin C, up to 200 mg/100g fr. wt. The highest vitamin E concentration found was 16 mg/100g fr. wt. Based on these metabolic data, five accessions were selected for further metabolic and molecular analysis, in order to isolate key genes involved in the production of these compounds and to assist future breeding programs aimed at optimizing the levels of health-related compounds in pepper fruit. Copyright © 2011 Elsevier Ltd. All rights reserved.

Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study.

PubMed

Hertog, M G; Feskens, E J; Hollman, P C; Katan, M B; Kromhout, D

1993-10-23

Flavonoids are polyphenolic antioxidants naturally present in vegetables, fruits, and beverages such as tea and wine. In vitro, flavonoids inhibit oxidation of low-density lipoprotein and reduce thrombotic tendency, but their effects on atherosclerotic complications in human beings are unknown. We measured the content in various foods of the flavonoids quercetin, kaempferol, myricetin, apigenin, and luteolin. We then assessed the flavonoid intake of 805 men aged 65-84 years in 1985 by a cross-check dietary history; the men were then followed up for 5 years. Mean baseline flavonoid intake was 25.9 mg daily. The major sources of intake were tea (61%), onions (13%), and apples (10%). Between 1985 and 1990, 43 men died of coronary heart disease. Fatal or non-fatal myocardial infarction occurred in 38 of 693 men with no history of myocardial infarction at baseline. Flavonoid intake (analysed in tertiles) was significantly inversely associated with mortality from coronary heart disease (p for trend = 0.015) and showed an inverse relation with incidence of myocardial infarction, which was of borderline significance (p for trend = 0.08). The relative risk of coronary heart disease mortality in the highest versus the lowest tertile of flavonoid intake was 0.42 (95% CI 0.20-0.88). After adjustment for age, body-mass index, smoking, serum total and high-density-lipoprotein cholesterol, blood pressure, physical activity, coffee consumption, and intake of energy, vitamin C, vitamin E, beta-carotene, and dietary fibre, the risk was still significant (0.32 [0.15-0.71]). Intakes of tea, onions, and apples were also inversely related to coronary heart disease mortality, but these associations were weaker. Flavonoids in regularly consumed foods may reduce the risk of death from coronary heart disease in elderly men.

The impact of date palm fruits and their component polyphenols, on gut microbial ecology, bacterial metabolites and colon cancer cell proliferation.

PubMed

Eid, Noura; Enani, Sumia; Walton, Gemma; Corona, Giulia; Costabile, Adele; Gibson, Glenn; Rowland, Ian; Spencer, Jeremy P E

2014-01-01

The fruit of the date palm (Phoenix dactylifera L.) is a rich source of dietary fibre and polyphenols. We have investigated gut bacterial changes induced by the whole date fruit extract (digested date extract; DDE) and its polyphenol-rich extract (date polyphenol extract; DPE) using faecal, pH-controlled, mixed batch cultures mimicking the distal part of the human large intestine, and utilising an array of microbial group-specific 16S rRNA oligonucleotide probes. Fluorescence microscopic enumeration indicated that there was a significant increase in the growth of bifidobacteria in response to both treatments, whilst whole dates also increased bacteroides at 24 h and the total bacterial counts at later fermentation time points when compared with DPE alone. Bacterial metabolism of whole date fruit led to the production of SCFA, with acetate significantly increasing following bacterial incubation with DDE. In addition, the production of flavonoid aglycones (myricetin, luteolin, quercetin and apigenin) and the anthocyanidin petunidin in less than 1 h was also observed. Lastly, the potential of DDE, DPE and metabolites to inhibit Caco-2 cell growth was investigated, indicating that both were capable of potentially acting as antiproliferative agents in vitro, following a 48 h exposure. This potential to inhibit growth was reduced following fermentation. Together these data suggest that consumption of date fruits may enhance colon health by increasing beneficial bacterial growth and inhibiting the proliferation of colon cancer cells. This is an early suggestion that date intake by humans may aid in the maintenance of bowel health and even the reduction of colorectal cancer development.

Complementary cereals and legumes for health: Synergistic interaction of sorghum flavones and cowpea flavonols against LPS-induced inflammation in colonic myofibroblasts.

PubMed

Agah, Shima; Kim, Hyemee; Mertens-Talcott, Susanne U; Awika, Joseph M

2017-07-01

Cereals and legumes are traditionally consumed together in many cultures, and may provide complementary health benefits beyond what is known about improved indispensable amino acid intake. Here, we use an in vitro model of inflammatory pathways to investigate whether the different flavonoids in sorghum and cowpea could synergistically reduce inflammation. Interactive effect of combining apigenin and quercetin, as well as extracts (70% acetone, v/v) from a flavone-dominated white sorghum and flavonol-dominated white cowpea, against LPS-induced NF-κB and downstream cytokines (TNF-α, IL-6, IL-8) gene and protein expression was evaluated using the CCD18Co colon myofibroblasts. Combination of apigenin and quercetin, and sorghum and cowpea extracts synergistically downregulated LPS-induced NF-κB gene and protein expression in a dose-dependent manner, with additive effect producing IC 50 values that were 14.6 and 14.0 times, respectively, higher than 1:1 combined treatments. Similar strong synergistic interactions were observed for the downstream cytokines (IC 50 values for additive effect 8.3-21 times higher than combined treatments). Furthermore, the ratios of the different combined treatments significantly affected the magnitude of synergy. Combining the structurally related cereal flavones and legume flavonols elicit strong synergistic anti-inflammatory response in LPS-stimulated nonmalignant colonocytes, likely by targeting interdependent mechanisms. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Isolation of phenolic compounds from iceberg lettuce and impact on enzymatic browning.

PubMed

Mai, Franziska; Glomb, Marcus A

2013-03-20

Enzymatic browning is generally reported as the reaction between phenolic substances and enzymes. The quality of iceberg lettuce is directly linked to this discoloration. In particular, the color change of lettuce stems considerably reduces consumer acceptance and thus decreases sales revenue of iceberg lettuce. Ten phenolic compounds (caffeic acid, chlorogenic acid, phaseolic acid, chicoric acid, isochlorogenic acid, luteolin-7-O-glucuronide, quercetin-3-O-glucuronide, quercetin-3-O-galactoside, quercetin-3-O-glucoside, and quercetin-3-O-(6″-malonyl)-glucoside) were isolated from Lactuca sativa var. capitata by multilayer countercurrent chromatography (MLCCC) and preparative high-performance liquid chromatography (HPLC). In addition, syringin was identified for the first time in iceberg lettuce. This polyphenolic ingredient was previously not mentioned for the family of Cichorieae in general. The purity and identity of isolated compounds were confirmed by different NMR experiments, HPLC-DAD-MS, and HR-MS techniques. Furthermore, the relationship between discoloration of iceberg lettuce and enzymatic browning was thoroughly investigated. Unexpectedly, the total concentration of phenolic compounds and the activity of polyphenol oxidase were not directly related to the browning processes. Results of model incubation experiments of plant extract solutions led to the conclusion that in addition to the typical enzymatic browning induced by polyphenol oxidases, further mechanisms must be involved to explain total browning of lettuce.

Characterization of Flavonoid Glycosides from Fenugreek (Trigonella foenum-graecum) Crude Seeds by HPLC–DAD–ESI/MS Analysis

PubMed Central

Benayad, Zakia; Gómez-Cordovés, Carmen; Es-Safi, Nour Eddine

2014-01-01

Fenugreek (Trigonella foenum-graecum) is a medicinal plant which is widely used for its pharmacological properties. In this study the phenolic composition of fenugreek crude seeds originating from Morocco has been investigated. Extraction was performed from defatted seeds by a hydromethanolic solution using an Accelerated Solvent Extractor. HPLC technique coupled to negative ion electrospray ionization mass spectrometry and diode array detection was employed to identify the polyphenol in the obtained extract. The obtained results allowed the detection of 32 phenolic compounds among which various flavonoid glycosides and phenolic acids have been tentatively identified on the basis of their UV and MS spectra, and comparisons with standards when available, as well as with literature data. A systematic study of the obtained MS spectra and the observed fragmentation showed that most of the identified compounds were acylated and non-acylated flavonoids with apigenin, luteolin and kaempferol as aglycons. Hydroxycinnamic acids mostly dominated by caffeic acid derivatives were also detected. The quantitative analysis of the identified compounds showed that the phenolic composition of the studied crude fenugreek seeds was predominantly acylated and non-acylated flavone derivatives with apigenin as the main aglycon. PMID:25393509

Characterization of flavonoid glycosides from fenugreek (Trigonella foenum-graecum) crude seeds by HPLC-DAD-ESI/MS analysis.

PubMed

Benayad, Zakia; Gómez-Cordovés, Carmen; Es-Safi, Nour Eddine

2014-11-11

Fenugreek (Trigonella foenum-graecum) is a medicinal plant which is widely used for its pharmacological properties. In this study the phenolic composition of fenugreek crude seeds originating from Morocco has been investigated. Extraction was performed from defatted seeds by a hydromethanolic solution using an Accelerated Solvent Extractor. HPLC technique coupled to negative ion electrospray ionization mass spectrometry and diode array detection was employed to identify the polyphenol in the obtained extract. The obtained results allowed the detection of 32 phenolic compounds among which various flavonoid glycosides and phenolic acids have been tentatively identified on the basis of their UV and MS spectra, and comparisons with standards when available, as well as with literature data. A systematic study of the obtained MS spectra and the observed fragmentation showed that most of the identified compounds were acylated and non-acylated flavonoids with apigenin, luteolin and kaempferol as aglycons. Hydroxycinnamic acids mostly dominated by caffeic acid derivatives were also detected. The quantitative analysis of the identified compounds showed that the phenolic composition of the studied crude fenugreek seeds was predominantly acylated and non-acylated flavone derivatives with apigenin as the main aglycon.

Structure related effects of flavonoid aglycones on cell cycle progression of HepG2 cells: Metabolic activation of fisetin and quercetin by catechol-O-methyltransferase (COMT).

PubMed

Poór, Miklós; Zrínyi, Zita; Kőszegi, Tamás

2016-10-01

Dietary flavonoids are abundant in the Plant Kingdom and they are extensively studied because of their manifold pharmacological activities. Recent studies highlighted that cell cycle arrest plays a key role in their antiproliferative effect in different tumor cells. However, structure-activity relationship of flavonoids is poorly characterized. In our study the influence of 18 flavonoid aglycones (as well as two metabolites) on cell cycle distribution was investigated. Since flavonoids are extensively metabolized by liver cells, HepG2 tumor cell line was applied, considering the potential metabolic activation/inactivation of flavonoids. Our major observations are the followings: (1) Among the tested compounds diosmetin, fisetin, apigenin, lutelin, and quercetin provoked spectacular extent of G2/M phase cell cycle arrest. (2) Inhibition of catechol-O-methyltransferase enzyme by entacapone decreased the antiproliferative effects of fisetin and quercetin. (3) Geraldol and isorhamnetin (3'-O-methylated metabolites of fisetin and quercetin, respectively) demonstrated significantly higher antiproliferative effect on HepG2 cells compared to the parent compounds. Based on these results, O-methylated flavonoid metabolites or their chemically modified derivatives may be suitable candidates of tumor therapy in the future. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Chemosystematic significance of flavonoids isolated from Diplotaxis acris (Brassicaceae) and related taxa.

PubMed

Hussein, Sameh R; Marzouk, Mona M; Kassem, Mona E S; Abdel Latif, Rasha R; Mohammed, Reda S

2017-02-01

The chemosystematic relationship of four Diplotaxis species; Diplotaxis acris, Diplotaxis erucoides, Diplotaxis harra and Diplotaxis muralis were surveyed from the flavonoids point of view. These species were found to produce 33 flavonoids (7 flavones and 26 flavonols), including 11 compounds were isolated in the present study from D. acris. Among them, seven flavonoids were identified for the first time; luteolin (4), kaempferol (8), kaempferol 3-O-β-glucopyranoside-7-O-α-rhamnopyranoside (13), quercetin 3-O-β-glucopyranoside (16), quercetin 7-O-β-glucopyranoside (20), isorhamnetin (22) and isorhamnetin 3-O-β-glucopyranoside-7-O-α-rhamnopyranoside (32). Their structures were recognized on the basis of chemical and spectroscopic techniques (1D & 2D NMR, UV, EI & ESI/MS). The isolated flavonoids may provide useful taxonomic characters at the infraspecific levels of classification where the flavonoid profile of D. acris and D. harra is similar and different from the other species.

In vitro and in silico analyses of Vicia faba L. on Peroxisome proliferator-activated receptor gamma.

PubMed

Prabhu, D Sathya; Rajeswari, V Devi

2018-06-20

The agonists of peroxisome proliferator-activated receptor gamma (PPARγ) from natural victual products were used as antidiabetic agents. Faba bean (Vicia faba L.) is a consequential legume that was known to possess potential antidiabetic activity, whose mechanism of action was unknown. The current study was focused to ascertain gene expression of the nuclear receptor PPARγ by Faba bean pod extract in rat cell lines (RINm5F).The real-time polymerase chain reaction analysis demonstrated that Faba bean pod extract in concentrations of 160 µg/mL have shown 4.97-fold stimulation compared with control. The cells treated with 320 µg/mL has shown 5.89-fold upregulation, respectively. Furthermore, in silico docking analysis was carried out against PPARγ, using the bioactive compounds identified from Faba bean pod extracts, which were known reported compounds from the literature. The results suggest that gene expression of PPARγ was inhibited by the constituents in Faba bean. In silico analysis prognosticates, butein has a high binding energy (-8.6 kcal/mol) with an atomic contact energy of -214.10, followed by Apigenin and Quercetin against PPARγ. Similarly, the percentage of interaction was high for butein, followed by Apigenin and Quercetin than other compounds comparatively. Hence, the results conclude inhibition of PPARγ by the bioactive compounds from Faba bean, which may provide insights into developing future therapeutic molecules for diabetes mellitus. © 2018 Wiley Periodicals, Inc.

Bio-effectiveness of the main flavonoids of Achillea millefolium in the pathophysiology of neurodegenerative disorders- a review

PubMed Central

Ayoobi, Fatemeh; Shamsizadeh, Ali; Fatemi, Iman; Vakilian, Alireza; Allahtavakoli, Mohammad; Hassanshahi, Gholamhossein; Moghadam-Ahmadi, Amir

2017-01-01

The Achillea millefolium L. (Yarrow) is a common herb which is widely being used, worldwide. Achillea is being used for treatment of many disorders since centuries. It is considered safe for supplemental use and flavonoids such as kaempferol, luteolin and apigenin are of main constituents present in Achillea. Most of both antioxidant and anti-inflammatory properties of this herb have been attributed to its flavonoid content. Oxidative and inflammatory processes play important roles in pathogenesis of neurodegenerative diseases. Present review was aimed to review the latest literature evidences regarding application of Achillea and/or its three main flavonoid constituents on epilepsy, Alzheimer’s disease, multiple sclerosis, Parkinson’s disease and stroke. PMID:28868116

Protective effects of dietary chamomile tea on diabetic complications.

PubMed

Kato, Atsushi; Minoshima, Yuka; Yamamoto, Jo; Adachi, Isao; Watson, Alison A; Nash, Robert J

2008-09-10

Matricaria chamomilla L., known as "chamomile", has been used as an herbal tea or supplementary food all over the world. We investigated the effects of chamomile hot water extract and its major components on the prevention of hyperglycemia and the protection or improvement of diabetic complications in diabetes mellitus. Hot water extract, esculetin (3) and quercetin (7) have been found to show moderate inhibition of sucrase with IC50 values of 0.9 mg/mL and 72 and 71 microM, respectively. In a sucrose-loading test, the administration of esculetin (50 mg/kg body weight) fully suppressed hyperglycemia after 15 and 30 min, but the extract (500 mg/kg body weight) and quercetin (50 mg/kg body weight) were less effective. On the other hand, a long-term feed test (21 days) using a streptozotocin-induced rat diabetes model revealed that the same doses of extract and quercetin showed significant suppression of blood glucose levels. It was also found that these samples increased the liver glycogen levels. Moreover, chamomile extract showed potent inhibition against aldose reductase (ALR2), with an IC50 value of 16.9 microg/mL, and its components, umbelliferone (1), esculetin (3), luteolin (6), and quercetin (7), could significantly inhibit the accumulation of sorbitol in human erythrocytes. These results clearly suggested that daily consumption of chamomile tea with meals could contribute to the prevention of the progress of hyperglycemia and diabetic complications.

Chemical Composition and Seasonality of Aromatic Mediterranean Plant Species by NMR-Based Metabolomics

PubMed Central

Scognamiglio, Monica; D'Abrosca, Brigida; Esposito, Assunta; Fiorentino, Antonio

2015-01-01

An NMR-based metabolomic approach has been applied to analyse seven aromatic Mediterranean plant species used in traditional cuisine. Based on the ethnobotanical use of these plants, the approach has been employed in order to study the metabolic changes during different seasons. Primary and secondary metabolites have been detected and quantified. Flavonoids (apigenin, quercetin, and kaempferol derivatives) and phenylpropanoid derivatives (e.g., chlorogenic and rosmarinic acid) are the main identified polyphenols. The richness in these metabolites could explain the biological properties ascribed to these plant species. PMID:25785229

Cellular antioxidant activity (CAA) assay for assessing antioxidants, foods, and dietary supplements.

PubMed

Wolfe, Kelly L; Liu, Rui Hai

2007-10-31

A cellular antioxidant activity (CAA) assay for quantifying the antioxidant activity of phytochemicals, food extracts, and dietary supplements has been developed. Dichlorofluorescin is a probe that is trapped within cells and is easily oxidized to fluorescent dichlorofluorescein (DCF). The method measures the ability of compounds to prevent the formation of DCF by 2,2'-azobis(2-amidinopropane) dihydrochloride (ABAP)-generated peroxyl radicals in human hepatocarcinoma HepG2 cells. The decrease in cellular fluorescence when compared to the control cells indicates the antioxidant capacity of the compounds. The antioxidant activities of selected phytochemicals and fruit extracts were evaluated using the CAA assay, and the results were expressed in micromoles of quercetin equivalents per 100 micromol of phytochemical or micromoles of quercetin equivalents per 100 g of fresh fruit. Quercetin had the highest CAA value, followed by kaempferol, epigallocatechin gallate (EGCG), myricetin, and luteolin among the pure compounds tested. Among the selected fruits tested, blueberry had the highest CAA value, followed by cranberry > apple = red grape > green grape. The CAA assay is a more biologically relevant method than the popular chemistry antioxidant activity assays because it accounts for some aspects of uptake, metabolism, and location of antioxidant compounds within cells.

The antioxidant effect of the Malaysian Gelam honey on pancreatic hamster cells cultured under hyperglycemic conditions.

PubMed

Batumalaie, Kalaivani; Qvist, Rajes; Yusof, Kamaruddin Mohd; Ismail, Ikram Shah; Sekaran, Shamala Devi

2014-05-01

Type 2 diabetes consists of progressive hyperglycemia, insulin resistance, and pancreatic β-cell failure which could result from glucose toxicity, inflammatory cytokines, and oxidative stress. In the present study, we investigate the effect of pretreatment with Gelam honey (Melaleuca spp.) and the individual flavonoid components chrysin, luteolin, and quercetin, on the production of reactive oxygen species (ROS), cell viability, lipid peroxidation, and insulin content in hamster pancreatic cells (HIT-T15 cells), cultured under normal and hyperglycemic conditions. Phenolic extracts from a local Malaysian species of Gelam honey (Melaleuca spp.) were prepared using the standard extraction methods. HIT-T15 cells were cultured in 5 % CO2 and then preincubated with Gelam honey extracts (20, 40, 60, and 80 μg/ml) as well as some of its flavonoid components chrysin, luteolin, and quercetin (20, 40, 60, and 80 μM), prior to stimulation by 20 and 50 mM of glucose. The antioxidative effects were measured in these cultured cells at different concentrations and time point by DCFH-DA assay. Pretreatment of cells with Gelam honey extract or the flavonoid components prior to culturing in 20 or 50 mM glucose showed a significant decrease in the production of ROS, glucose-induced lipid peroxidation, and a significant increase in insulin content and the viability of cells cultured under hyperglycemic condition. Our results show the in vitro antioxidative property of the Gelam honey and the flavonoids on the β-cells from hamsters and its cytoprotective effect against hyperglycemia.

Structure-activity relationships of flavonoids as natural inhibitors against E. coli β-glucuronidase.

PubMed

Weng, Zi-Miao; Wang, Ping; Ge, Guang-Bo; Dai, Zi-Ru; Wu, Da-Chang; Zou, Li-Wei; Dou, Tong-Yi; Zhang, Tong-Yan; Yang, Ling; Hou, Jie

2017-11-01

Bacterial β-glucuronidases play key roles in the deconjugation of a variety of endogenous and drug glucuronides, thus have been recognized as important targets to modulate the enterohepatic circulation of various glucuronides. In this study, more than 30 natural flavonoids were collected and their inhibitory effects against E. coli β-glucuronidase (EcGUS) were assayed. The results demonstrated that some flavonoids including scutellarein, luteolin, baicalein, quercetin and scutellarin displayed strong to moderate inhibitory effects against EcGUS, with the IC 50 values ranging from 5.76 μM to 29.64 μM, while isoflavones and dihydroflavones displayed weak inhibitory effects against EcGUS. Further investigation on inhibition kinetics revealed that scutellarein and luteolin functioned as potent competitive inhibitors against EcGUS-mediated PNPG hydrolysis, with the K i values less than 3.0 μM. Molecular docking simulations demonstrated that scutellarein and luteolin could be well-docked into the catalytic site of EcGUS, while the binding areas of these two natural inhibitors on EcGUS were highly overlapped with that of PNPG on EcGUS. Additionally, the structure-inhibition relationships of natural flavonoids against EcGUS are also summarized, which will be very helpful for the medicinal chemists to design and develop more potent flavonoid-type inhibitors against EcGUS. Copyright © 2017 Elsevier Ltd. All rights reserved.

The flavonoid luteolin inhibits niacin-induced flush

PubMed Central

Papaliodis, D; Boucher, W; Kempuraj, D; Theoharides, T C

2008-01-01

Background and purpose: Sustained release niacin effectively lowers serum cholesterol, LDL and triglycerides, while raising HDL. However, 75% of patients experience cutaneous warmth and itching known as flush, leading to discontinuation. Acetylsalicylic acid (aspirin) reduces this flush only by about 30%, presumably through decreasing prostaglandin D2 (PGD2). We investigated whether niacin-induced flush in a rat model involves PGD2 and 5-HT, and the effect of certain flavonoids. Experimental approach: Three skin temperature measurements from each ear were recorded with an infrared pyrometer for each time point immediately before i.p. injection with either niacin or a flavonoid. The temperature was then measured every 10 min for 60 min. Key results: Niacin (7.5 mg per rat, equivalent to a human dose of 1750 mg per 80 kg) maximally increased ear temperature to 1.9±0.2 oC at 45 min. Quercetin and luteolin (4.3 mg per rat; 1000 mg per human), administered i.p. 45 min prior to niacin, inhibited the niacin effect by 96 and 88%, respectively. Aspirin (1.22 mg per rat; 325 mg per human) inhibited the niacin effect by only 30%. Niacin almost doubled plasma PGD2 and 5-HT, but aspirin reduced only PGD2 by 86%. In contrast, luteolin inhibited both plasma PGD2 and 5-HT levels by 100 and 67%, respectively. Conclusions and implications. Niacin-induced skin temperature increase is associated with PGD2 and 5-HT elevations in rats; luteolin may be a better inhibitor of niacin-induced flush because it blocks the rise in both mediators. PMID:18223672

Cell culture protection and in vivo neuroprotective capacity of flavonoids.

PubMed

Dajas, Federico; Rivera, Felicia; Blasina, Fernanda; Arredondo, Florencia; Echeverry, Carolina; Lafon, Laura; Morquio, Andrea; Heinzen, Horacio; Heizen, Horacio

2003-01-01

Flavonoids are an important group of recognized antioxidants ubiquitous in fruits, vegetables and herbs. There are epidemiological evidences for the stroke-protecting capacity of flavonoids and while the neuroprotective power of complex extracts rich in flavonoids like those of Ginkgo biloba, green tea or lyophilized red wine have been demonstrated in several studies, neuroprotection by individual flavonoids has been poorly studied in vivo. The neuroprotective capacity of individual flavonoids was studied in PC12 cells in culture and in a model of permanent focal ischemia (permanent Middle Cerebral Artery Occlusion - pMCAO). In the in vivo experiments, flavonoids were administered in lecithin preparations to facilitate the crossing of the blood brain barrier. The simultaneous incubation of PC12 cells with 200 micro M hydrogen peroxide (H2O2) and different flavonoids for 30 min resulted in a conspicuous profile: quercetin, fisetin, luteolin and myricetin significantly increased cell survival while catechin, kaempherol and taxifolin did not. Quercetin was detected in brain tissue 30 min and 1 h after intraperitoneal administration. When one of the protective flavonoids (quercetin) and one of those that failed to increase PC12 cell survival (catechin) were assessed for their protective capacity in the pMCAO model, administered i.p. 30 min after vessel occlusion, quercetin significantly decreased the brain ischemic lesion while catechin did not. It is concluded that when administered in liposomal preparations, flavonoids structurally related to quercetin could become leads for the development of a new generation of molecules to be clinically effective in human brain ischemia.

The SOS Chromotest applied for screening plant antigenotoxic agents against ultraviolet radiation.

PubMed

Fuentes, J L; García Forero, A; Quintero Ruiz, N; Prada Medina, C A; Rey Castellanos, N; Franco Niño, D A; Contreras García, D A; Córdoba Campo, Y; Stashenko, E E

2017-09-13

In this work, we investigated the usefulness of the SOS Chromotest for screening plant antigenotoxic agents against ultraviolet radiation (UV). Fifty Colombian plant extracts obtained by supercritical fluid (CO 2 ) extraction, twelve plant extract constituents (apigenin, carvacrol, β-caryophyllene, 1,8-cineole, citral, p-cymene, geraniol, naringenin, pinocembrin, quercetin, squalene, and thymol) and five standard antioxidant and/or photoprotective agents (curcumin, epigallocatechin gallate, resveratrol, α-tocopherol, and Trolox®) were evaluated for their genotoxicity and antigenotoxicity against UV using the SOS Chromotest. None of the plant extracts, constituents or agents were genotoxic in the SOS Chromotest at tested concentrations. Based on the minimal extract concentration that significantly inhibited UV-genotoxicity (CIG), five plant extracts were antigenotoxic against UV as follows: Baccharis nítida (16 μg mL -1 ) = Solanum crotonifolium (16 μg mL -1 ) > Hyptis suaveolens (31 μg mL -1 ) = Persea caerulea (31 μg mL -1 ) > Lippia origanoides (62 μg mL -1 ). Based on CIG values, the flavonoid compounds showed the highest antigenotoxic potential as follows: apigenin (7 μM) > pinocembrin (15 μM) > quercetin (26 μM) > naringenin (38 μM) > epigallocatechin gallate (108 μM) > resveratrol (642 μM). UV-genotoxicity inhibition with epigallocatechin gallate, naringenin and resveratrol was related to its capability for inhibiting protein synthesis. A correlation analysis between compound antigenotoxicity estimates and antioxidant activity evaluated by the oxygen radical absorbance capacity (ORAC) assay showed that these activities were not related. The usefulness of the SOS Chromotest for bioprospecting of plant antigenotoxic agents against UV was discussed.

Suppression of bacterial cell-cell signalling, biofilm formation and type III secretion system by citrus flavonoids.

PubMed

Vikram, A; Jayaprakasha, G K; Jesudhasan, P R; Pillai, S D; Patil, B S

2010-08-01

This study investigated the quorum sensing, biofilm and type three secretion system (TTSS) inhibitory properties of citrus flavonoids. Flavonoids were tested for their ability to inhibit quorum sensing using Vibrio harveyi reporter assay. Biofilm assays were carried out in 96-well plates. Inhibition of biofilm formation in Escherichia coli O157:H7 and V. harveyi by citrus flavonoids was measured. Furthermore, effect of naringenin on expression of V. harveyi TTSS was investigated by semi-quantitative PCR. Differential responses for different flavonoids were observed for different cell-cell signalling systems. Among the tested flavonoids, naringenin, kaempferol, quercetin and apigenin were effective antagonists of cell-cell signalling. Furthermore, these flavonoids suppressed the biofilm formation in V. harveyi and E. coli O157:H7. In addition, naringenin altered the expression of genes encoding TTSS in V. harveyi. The results of the study indicate a potential modulation of bacterial cell-cell communication, E. coli O157:H7 biofilm and V. harveyi virulence, by flavonoids especially naringenin, quercetin, sinensetin and apigenin. Among the tested flavonoids, naringenin emerged as potent and possibly a nonspecific inhibitor of autoinducer-mediated cell-cell signalling. Naringenin and other flavonoids are prominent secondary metabolites present in citrus species. Therefore, citrus, being a major source of some of these flavonoids and by virtue of widely consumed fruit, may modulate the intestinal microflora. Currently, a limited number of naturally occurring compounds have demonstrated their potential in inhibition of cell-cell communications; therefore, citrus flavonoids may be useful as lead compounds for the development of antipathogenic agents.

Antioxidant, anti-inflammatory, and enzyme inhibitory activity of natural plant flavonoids and their synthesized derivatives.

PubMed

Nile, Shivraj Hariram; Keum, Young Soo; Nile, Arti Shivraj; Jalde, Shivkumar S; Patel, Rahul V

2018-01-01

The synthesized flavonoid derivatives were examined for their antioxidant, anti-inflammatory, xanthine oxidase (XO), urease inhibitory activity, and cytotoxicity. Except few, all the flavonoids under this study showed significant antioxidant activity (45.6%-85.5%, 32.6%-70.6%, and 24.9%-65.5% inhibition by DPPH, ferric reducing/antioxidant power, and oxygen radical absorption capacity assays) with promising TNF-α inhibitory activity (42%-73% at 10 μM) and IL-6 inhibitory activity (54%-81% at 10 μM) compared with that of control dexamethasone. The flavonoids luteolin, apigenin, diosmetin, chrysin, O 3Ꞌ , O 7 -dihexyl diosmetin, O 4Ꞌ , O 7 -dihexyl apigenin, and O 7 -hexyl chrysin, showed an inhibition with IC 50 values (4.5-8.1 μg/mL), more than allopurinol (8.5 μg/mL) at 5 μM against XO and showing more than 50% inhibition at a final concentration (5 mM) with an IC 50 value of ranging from 4.8 to 7.2 (μg/mL) in comparison with the positive control thiourea (5.8 μg/mL) for urease inhibition. Thus, the flavonoid derivatives may be considered as potential antioxidant and antigout agents. © 2017 Wiley Periodicals, Inc.

Effect of the γ-radiation on phenol fractions obtained from the leaves of Echinodorus macrophyllus Mich.

NASA Astrophysics Data System (ADS)

Silva, T. M.; Dias, M. D.; Pereira, M. T.; Takahashi, J. A.; Ferraz, V. P.; Piló-Veloso, D.; Alcântara, A. F. C.

2012-01-01

Echinodorus macrophyllus Mich. (Chapéu-de-couro) is popularly used as diuretic, anti-arrhythmic, anti-inflammatory, and anti-rheumatic agents. Leaves of this species are largely commercialized and show high level of microbiological contamination (bacteria and fungi). This work describes the effect of the 60Co γ-radiation on the phenol fractions obtained from the leaves of E. macrophyllus. trans-Ferulic acid, ( E)-caffeoyltartronic acid, 6- C-(1 -hexitol)-apigenin, and 6- C-(1 -hexitol)-luteolin were isolated by preparative HPLC. HPLC chromatograms showed concentration changes of some phenolic constituents, suggesting the formation of radiolytic products. The phenol fractions were active against Bacillus subitilis and Staphylococcus aureus and showed high antioxidant activity. However, the antibacterial and antioxidant activities reduced when the absorbed dose was increased.

Phenolics of Selected Cranberry Genotypes (Vaccinium macrocarpon Ait.) and Their Antioxidant Efficacy.

PubMed

Abeywickrama, Gihan; Debnath, Samir C; Ambigaipalan, Priyatharini; Shahidi, Fereidoon

2016-12-14

Free, esterified, and bound phenolic fractions of berries from five different cranberry genotypes and two market samples were evaluated for their total phenolic, flavonoid, and monomeric anthocyanin contents as well as their antioxidant efficacy using TEAC, ORAC, DPPH radical, reducing power, and ferrous ion chelation capacity assays. HPLC-MS/MS analysis was performed for two of the rich sources (Pilgrim and wild clone NL2) of phenolics and high antioxidant activity. Among the genotypes, Pilgrim showed the highest phenolic and flavonoid contents and wild clones NL3 and NL2 showed the highest monomeric anthocyanin and proanthocyanidin content, respectively. Protocatechuic and syringic acids were detected only in Pilgrim, whereas luteolin 7-O-glucoside, quercetin 3-O-rhamnoside, quercetin 3-O-galactoside, proanthocyanidin B-type, and myricetin 3-O-galactoside were found in wild clone NL3 genotype. Moreover, proanthocyanin trimer A-type and dimer B-type predominated in the wild clone NL2, whereas proanthocyanidin dimer B and trimer A were predominant in Pilgrim.

Determination of phenolic acids and flavonoids in raw propolis by silica-supported ionic liquid-based matrix solid phase dispersion extraction high performance liquid chromatography-diode array detection.

PubMed

Wang, Zhibing; Sun, Rui; Wang, Yuanpeng; Li, Na; Lei, Lei; Yang, Xiao; Yu, Aimin; Qiu, Fangping; Zhang, Hanqi

2014-10-15

The silica-supported ionic liquid (S-SIL) was prepared by impregnation and used as the dispersion adsorbent of matrix solid phase dispersion (MSPD) for the simultaneous extraction of eight phenolic acids and flavonoids, including caffeic acid, ferulic acid, morin, luteolin, quercetin, apigenin, chrysin, and kaempferide in raw propolis. High performance liquid chromatography with a Zorbax SB-C18 column (150mm×4.6mm, 3.5μm) was used for separation of the analytes. The mobile phase consisted of 0.2% phosphoric acid aqueous solution and acetonitrile and the flow rate of the mobile phase was 0.5mL/min. The experimental conditions for silica-supported ionic liquid-based matrix solid phase dispersion (S-SIL-based MSPD) were optimized. S-SIL containing 10% [C6MIM]Cl was used as dispersant, 20mL of n-hexane as washing solvent and 15mL of methanol as elution solvent. The ratio of S-SIL to sample was selected to be 4:1. The standard curves showed good linear relationship (r>0.9995). The limits of detection and quantification were in the range of 5.8-22.2ngmL(-1) and 19.2-74.0ngmL(-1), respectively. The relative standard deviations (RSDs) of intra-day and inter-day determination were lower than 8.80% and 11.19%, respectively. The recoveries were between 65.51% and 92.32% with RSDs lower than 8.95%. Compared with ultrasound-assisted extraction (UAE) and soxhlet extraction, the present method consumed less sample, organic solvent, and extraction time, although the extraction yields obtained by S-SIL-based MSPD are slightly lower than those obtained by UAE. Copyright © 2014 Elsevier B.V. All rights reserved.

Post-column mobile phase adjustment: a strategy to eliminate the contradiction between liquid chromatography and mass spectrometry in the determination of flavonoids in rat plasma.

PubMed

Zheng, Shirui; Ma, Zhiyuan; Han, Haixia; Ye, Jianfeng; Wang, Ruwei; Cai, Sheng; Zhou, Hui; Yu, Lushan; Zeng, Su; Jiang, Huidi

2014-07-01

Flavonoids are a group of important naturally occurring polyphenolic compounds with a wide range of biological effects. In this study, a sensitive liquid chromatography tandem mass spectrometry method was developed to simultaneously determine multiple active flavonoids, including quercetin (Que), kaempferol (Kae), apigenin (Api), isorhamnetin (Iso), luteolin (Lut), and naringenin (Nar), in rat plasma. To achieve a satisfied peak shape and LC separation, formic acid with the concentration between 0.05 and 0.2%, or in some case 5%, was generally used to acidify the LC mobile phase in reported studies. Here we found that even 0.05% formic acid could lead to strong mass signal suppression, and the absence of formic acid could reverse the signal suppression but cause serious peak tailing. There is an irreconcilable contradiction between liquid chromatography (LC) and mass spectrometry (MS). In order to simultaneously satisfy LC and MS, LC mobile phase with 0.00075% formic acid and post column mobile phase adjustment with 0.0677% ammonium solution in isopropanol were applied. Compared with the conventional method with mobile phase containing 0.05% formic acid, the mass signal response of Que, Kae, Api, Iso, Lut, Nar, and Oka increased 26.2, 18.6, 13.6, 23.5, 17.5, 15.6 and 15.4 fold, respectively. In addition, the post column mobile phase addition exhibited the better peak shape for the reduction of analytes longitudinal diffusion. The method has been fully validated according to FDA guidelines within the linear range between 0.328 ng mL⁻¹ and 168 ng mL⁻¹, and successfully applied to a pilot pharmacokinetic study of rats after administering 5.43 g kg⁻¹ Pollen of Brassica campestris. Copyright © 2014 Elsevier B.V. All rights reserved.

Phenolic composition profiling of different edible parts and by-products of date palm (Phoenix dactylifera L.) by using HPLC-DAD-ESI/MSn.

PubMed

Abu-Reidah, Ibrahim M; Gil-Izquierdo, Ángel; Medina, Sonia; Ferreres, Federico

2017-10-01

Fruits and vegetables are an important source of dietary antioxidants and epidemiological studies show that their regular intake in the diet may decrease the risk of several chronic diseases. Phoenix dactylifera L. (date palm or dates) is an important crop, widely used in the Arabian region and in other parts of the world as a food and also in folk medicine, due to its health-promoting properties. Antioxidant phytochemicals present in plant foods are partly responsible for such health benefits. The antioxidants present in dates are mainly phenolics, like flavonoids and phenolic acids. The fruits of dates have been widely studied with regard to their phenolic composition. However, few studies are available in the bibliography regarding other, non-edible parts of the date palm tree. In this context, in the present work the phenolic components of different parts of P. dactylifera (cv. Medjool or Mejhool) - namely, fruit pulp and skin, fronds (leaves), clusters, and pollen - have been investigated using HPLC-DAD-ESI/MS n in the negative ionization mode. The overall analysis of the phenolic compounds revealed that there was a qualitative similarity among the different dates parts analyzed. The method used provided tentative identification of 52 compounds: mainly flavonoid glycosides of quercetin, luteolin, apigenin, chrysoeriol, kaempferol, isorhamnetin, 3-methyl-isorhamnetin, sulfates, and malonyl derivatives. In the present work, more than 30 phenolic derivatives are described for the first time in dates. To the best of our knowledge, kaempferol glycosides and malonyl derivatives have not been described previously in P. dactylifera. The results highlight the importance of P. dactylifera L. as a promising source of functional ingredients and boost its potential use in the food and nutraceutical industries. The MS data, MS n fragmentation pattern, and UV information obtained have been of great help in the interpretation of the compounds detected and in their structural identification. Copyright © 2016 Elsevier Ltd. All rights reserved.

Antimicrobial flavonoids from Tridax procumbens.

PubMed

Jindal, Alka; Kumar, Padma

2012-01-01

Callus culture of Tridax procumbens has been established on Murashige and Skoog's medium supplemented with NAA and BAP from nodal segments. Free and bound flavonoids were extracted from 2, 4, 6 and 8 weeks old calli by a well-established method. These free flavonoids were then screened against Staphylococcus aureus (bacteria) and Candida albicans (yeast) for their antimicrobial potential. Minimum inhibitory concentration, minimum bactericidal/fungicidal concentrations and total activity were also evaluated. Apigenin, quercetin and kaempferol were identified from free flavonoids of 4 weeks old callus (most active) through, thin layer chromatography, (TLC) preparative TLC, MP and IR spectral studies.

Stimulatory actions of bioflavenoids on tyrosine uptake into cultured bovine adrenal chromaffin cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morita, K.; Hamano, S.; Oka, M.

1990-09-28

The effects of flavenoids on L-({sup 14}C)tyrosine uptake into cultured adrenal chromaffin cells were examined. Flavone markedly stimulated tyrosine uptake into these cells in a manner dependent on its concentration. Apigenin also caused a moderate stimulatory action, but quercetin had no significant effect on the uptake. Flavone also stimulated the uptake of histidine, but did not affect the uptake of serine, lysine, or glutamic acid. These results are considered to propose the possibility that flavonoids may be able to stimulate the precursor uptake into the cells, resulting in an enhancement of the biogenic amine production.

Protective effects of flavonoids isolated from Korean milk thistle Cirsium japonicum var. maackii (Maxim.) Matsum on tert-butyl hydroperoxide-induced hepatotoxicity in HepG2 cells.

PubMed

Jung, Hyun Ah; Abdul, Qudeer Ahmed; Byun, Jeong Su; Joung, Eun-Ji; Gwon, Wi-Gyeong; Lee, Min-Sup; Kim, Hyeung-Rak; Choi, Jae Sue

2017-09-14

Milk thistle leaves and flowers have been traditionally used as herbal remedy to alleviate liver diseases for decades. Korean milk thistle, Cirsium japonicum var. maackii (Maxim.) Matsum has been employed in traditional folk medicine as diuretic, antiphlogistic, hemostatic, and detoxifying agents. The aim of current investigation was to evaluate hepatoprotective properties of the MeOH extract of the roots, stems, leaves and flowers of Korean milk thistle as well as four isolated flavonoids, luteolin, luteolin 5-O-glucoside, apigenin and apigenin 7-O-glucuronide during t-BHP-induced oxidative stress in HepG2 cells. Hepatoprotective potential of the MeOH extracts and flavonoids derived from Korean milk thistle against t-BHP-induced oxidative stress in HepG2 cells were evaluated following MTT method. Incubating HepG2 cells with t-BHP markedly decreased the cell viability and increased the intracellular ROS generation accompanied by depleted GSH levels. Protein expression of heme oxygenase (HO-1) and nuclear factor-E2-related factor 2 (Nrf-2) was determined by Western blot. Our findings revealed that pretreating HepG2 cells with MeOH extracts and bioactive flavonoids significantly attenuated the t-BHP-induced oxidative damage, followed by increased cell viability in a dose-dependent manner. The results illustrate that excess ROS generation was reduced and GSH levels increased dose-dependently when HepG2 cells were pretreated with four flavonoids. Moreover, Western blotting analysis demonstrated that protein expressions of Nrf-2 and HO-1 were also up-regulated by flavonoids treatment. These results clearly demonstrate that the MeOH extracts and flavonoids from Korean milk thistle protected HepG2 cells against oxidative damage triggered by t-BHP principally by modulating ROS generation and restoring depleted GSH levels in addition to the increased Nrf-2/HO-1 signaling cascade. These flavonoids are potential natural antioxidative biomarkers against oxidative stress-induced hepatotoxicity. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Antioxidant activity and phenolic profile of pistachio (Pistacia vera L., variety Bronte) seeds and skins.

PubMed

Tomaino, Antonio; Martorana, Maria; Arcoraci, Teresita; Monteleone, Domenico; Giovinazzo, Corrado; Saija, Antonella

2010-09-01

Pistachio (Pistacia vera L.; Anacardiaceae) is native of aride zones of Central and West Asia and distributed throughout the Mediterranean basin. In Italy, a pistachio cultivar of high quality is typical of Bronte (Sicily), an area around the Etna volcano, where the lava land and climate allow the production of a nut with intense green colour and aromatic taste, very appreciated in international markets. Pistachio nuts are a rich source of phenolic compounds, and have recently been ranked among the first 50 food products highest in antioxidant potential. Pistachio nuts are often used after removing the skin, which thus represents a significant by-product of pistachio industrial processing. The present study was carried out to better characterize the phenolic composition and the antioxidant activity of Bronte pistachios, with the particular aim to evaluate the differences between pistachio seeds and skins. The total content of phenolic compounds in pistachios was shown to be significantly higher in skins than in seeds. By HPLC analysis, gallic acid, catechin, eriodictyol-7-O-glucoside, naringenin-7-O-neohesperidoside, quercetin-3-O-rutinoside and eriodictyol were found both in pistachio seeds than in skins; furthermore, genistein-7-O-glucoside, genistein, daidzein and apigenin appeared to be present only in pistachio seeds, while epicatechin, quercetin, naringenin, luteolin, kaempferol, cyanidin-3-O-galactoside and cyanidin-3-O-glucoside are contained only in pistachio skins. The antioxidant activity of pistachio seeds and skins were determined by means of four different assays (DPPH assay, Folin-Ciocalteau colorimetric method and TEAC assay, SOD-mimetic assay). As expected on the basis of the chemical analyses, pistachio skins have shown to possess a better activity with respect to seeds in all tests. The excellent antioxidant activity of pistachio skins can be explained by its higher content of antioxidant phenolic compounds. By HPLC-TLC analysis, gallic acid, catechin, cyanidin-3-O-galactoside, eriodictyol-7-O-glucoside and epicatechin appeared to be responsible for the antioxidant activity of pistachio skin, together with other unidentified compounds. In conclusion, our work has contributed to clarify some particular characteristics of Bronte pistachios and the specific antioxidant power of pistachio skins. Introduction of pistachios in daily diet may be of undoubted utility to protect human health and well-being against cancer, inflammatory diseases, cardiovascular pathologies and, more generally, pathological conditions related to free radical overproduction. On the other hand, pistachio skins could be successfully employed in food, cosmetic and pharmaceutical industry. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

Simultaneous determination of active ingredients in Erigeron breviscapus (Vant.) Hand-Mazz. by capillary electrophoresis with electrochemical detection.

PubMed

Chu, Qingcui; Wu, Ting; Fu, Liang; Ye, Jiannong

2005-03-09

A high-performance capillary electrophoresis (CE) with electrochemical detection (ED) method was developed for the determination of the pharmacologically active ingredients in Erigeron breviscapus (Vant.) Hand-Mazz. and its extract phytopharmaceuticals in this work. Under the optimum conditions, nine analytes, baicalein, naringenin, scopoletin, kaempferol, apigenin, scutellarin, luteolin, caffeic acid and protocatechuic acid were separated within 24 min in a borax buffer (pH 8.7). Notably, excellent linearity was obtained over two orders of magnitude with detection limits (S/N=3) ranged from 1.0 x 10(-7) g/mL to 5.6 x 10(-7) g/mL for all nine analytes. This method was successfully used in the analysis of E. breviscapus (Vant.) Hand-Mazz. and its phytopharmaceuticals with a relatively simple extraction procedure, and the assay results were satisfactory.

(Anti)estrogenic effects of phytochemicals on human primary mammary fibroblasts, MCF-7 cells and their co-culture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meeuwen, J.A. van; Korthagen, N.; Jong, P.C. de

In the public opinion, phytochemicals (PCs) present in the human diet are often considered beneficial (e.g. by preventing breast cancer). Two possible mechanisms that could modulate tumor growth are via interaction with the estrogen receptor (ER) and inhibition of aromatase (CYP19). Multiple in vitro studies confirmed that these compounds act estrogenic, thus potentially induce tumor growth, as well as aromatase inhibitory, thus potentially reduce tumor growth. It is thought that in the in vivo situation breast epithelial (tumor) cells communicate with surrounding connective tissue by means of cytokines, prostaglandins and estradiol forming a complex feedback mechanism. Recently our laboratory developedmore » an in vitro co-culture model of healthy mammary fibroblasts and MCF-7 cells that (at least partly) simulated this feedback mechanism (M. Heneweer et al., TAAP vol. 202(1): 50-58, 2005). In the present study biochanin A, chrysin, naringenin, apigenin, genistein and quercetin were studied for their estrogenic properties (cell proliferation, pS2 mRNA) and aromatase inhibition in MCF-7 breast tumor cells, healthy mammary fibroblasts and their co-culture. The proliferative potency of these compounds in the MCF-7 cells derived from their EC{sub 50}s decreased in the following order: estadiol (4*10{sup -3} nM) > biochanin A (9 nM) > genistein (32 nM) > testosterone (46 nM) > naringenin (287 nM) > apigenin (440 nM) > chrysin (4 {mu}M). The potency to inhibit aromatase derived from their IC{sub 50}s decreased in the following order: chrysin (1.5 {mu}M) > naringenin (2.2 {mu}M) > genistein (3.6 {mu}M) > apigenin (4.1 {mu}M) > biochanin A (25 {mu}M) > quercetin (30 {mu}M). The results of these studies show that these PCs can induce cell proliferation or inhibit aromatase in the same concentration range (1-10 {mu}M). Results from co-cultures did not elucidate the dominant effect of these compounds. MCF-7 cell proliferation occurs at concentrations that are not uncommon in blood of individuals using food supplements. Results also indicate that estrogenicity of these PCs is quantitatively more sensitive than aromatase inhibition. It is suggested that perhaps a more cautionary approach should be taken for these PCs before taken as food supplements.« less

Edible Flowers: A Rich Source of Phytochemicals with Antioxidant and Hypoglycemic Properties.

PubMed

Loizzo, Monica Rosa; Pugliese, Alessandro; Bonesi, Marco; Tenuta, Maria Concetta; Menichini, Francesco; Xiao, Jianbo; Tundis, Rosa

2016-03-30

Edible flowers are receiving renewed interest as rich sources of bioactive compounds. Ethanol extracts of eight edible flowers were phytochemically characterized and investigated for their bioactivity. Rutin, quercetin, luteolin, kaempferol, and myricetin were selected as standards and quantified by HPLC. The fatty acid profile was analyzed by GC and GC-MS. Antioxidant properties were evaluated by using different in vitro tests. The hypoglycemic effects were investigated via the inhibition of α-amylase and α-glucosidase. Sambucus nigra exhibited the highest radical-scavenging activity (IC50 of 1.4 μg/mL), followed by Hedysarum coronarium (IC50 of 1.6 μg/mL). Both species contained high quercetin and rutin contents. S. nigra extract exerted the highest activity in preventing lipid oxidation. Malva sylvestris extract inhibited both α-amylase and α-glucosidase with IC50 values of 7.8 and 11.3 μg/mL, respectively. These findings support the consumption of edible flowers as functional foods and their use as sources of natural antioxidants by the food industry.

Quantitative determination of the major saponin mixture bacoside A in Bacopa monnieri by HPLC.

PubMed

Deepak, M; Sangli, G K; Arun, P C; Amit, A

2005-01-01

Bacoside A, the putative bioactive component of the Indian medicinal plant Bacopa monnieri, was found to be a mixture of saponins with bacoside A3 (1), bacopaside II (2), jujubogenin isomer of bacopasaponin C (3) and bacopasaponin C (4) as major constituents. An HPLC method together with an optimised extraction procedure was developed for the estimation of 1-4 in B. monnieri to enable standardisation of the latter. Concentration ranges of the analytes in samples of B. monnieri collected from different regions of India were 0.14-0.85% (w/w) (1), 0.12-0.69% (2), 0.05-0.72% (3) and 0.05-0.44% (4). The importance of using bacoside A, with known concentrations of 1-4, as a reference standard for the routine analysis of B. monnieri is highlighted. Two common flavonoids, luteolin and apigenin, were present in all samples of B. monnieri.

Pollination effects on antioxidant content of Perilla frutescens seeds analysed by NMR spectroscopy.

PubMed

Ferrazzi, Paola; Vercelli, Monica; Chakir, Amina; Romane, Abderrahmane; Mattana, Monica; Consonni, Roberto

2017-12-01

The effects of Perilla frutescens pollination on the content of seed antioxidants were analysed by agronomical and pollination trials, comparing seeds produced from bagged plants in 2013 (A) to prevent access to pollinating insects, and seeds from open-pollinated plants in 2013 (B) and 2015 (C). The seeds of open-pollinated plants were significantly more numerous and heavier than those of self-pollinated plants. 1 H NMR seed analysis showed a higher presence of phenolic compounds in open-pollinated seeds, mainly rosmarinic acid and flavonoids, apigenin and luteolin. Flavonoids were present in the glucosylated form in seeds (A) and (C), and in the aglycone form in seeds from (B) plants. Saturated and unsaturated fatty acids (palmitic, linoleic and linolenic) were more abundant in seeds from self-pollinated flowers. Pollination performed almost exclusively by the honeybee notably increased the antioxidant content in perilla seeds and gave rise to a reduction in the fatty acid content.

Antiproliferative activity of flavonoids on several cancer cell lines.

PubMed

Kawaii, S; Tomono, Y; Katase, E; Ogawa, K; Yano, M

1999-05-01

Twenty-seven Citrus flavonoids were examined for their antiproliferative activities against several tumor and normal human cell lines. As a result, 7 flavonoids were judged to be active against the tumor cell lines, while they had weak antiproliferative activity against the normal human cell lines. The rank order of potency was luteolin, natsudaidain, quercetin, tangeretin, eriodictyol, nobiletin, and 3,3',4',5,6,7,8-heptamethoxyflavone. The structure-activity relationship established from comparison among these flavones and flavanones showed that the ortho-catechol moiety in ring B and a C2-C3 double bond were important for the antiproliferative activity. As to polymethoxylated flavones, C-3 hydroxyl and C-8 methoxyl groups were essential for high activity.

Activity of plant flavonoids against antibiotic-resistant bacteria.

PubMed

Xu, H X; Lee, S F

2001-02-01

Thirty eight plant-derived flavonoids representing seven different structural groups were tested for activities against antibiotic-resistant bacteria using the disc-diffusion assay and broth dilution assay. Among the flavonoids examined, four flavonols (myricetin, datiscetin, kaempferol and quercetin) and two -flavones (flavone and luteolin) exhibited inhibitory activity against methicillin-resistant Staphylococcus aureus (MRSA). Myricetin was also found to inhibit the growth of multidrug-resistant Burkholderia -cepacia, vancomycin-resistant enterococci (VRE) and other medically important organisms such as -Klebsiella pneumoniae and Staphylococcus epidermidis. Myricetin was bactericidal to B. cepacia. The results of the radiolabel incorporation assay showed that myricetin inhibited protein synthesis by -B. cepacia. The structure-activity relationship of these flavonoids is discussed. Copyright 2001 John Wiley & Sons, Ltd.

[Chemical constituents from stems of Ilex pubescens].

PubMed

Xing, Xian-dong; Zhang, Qian; Feng, Feng; Liu, Wen-yuan

2012-09-01

To study the chemical constituents from the stems of Ilex pubescens Hook. et Am. The chemical constituents were isolated and purified by various column chromatographic methods with diatomite, silica gel, ODS and Sephadex LH-20. Their structures were identified on physical properties and spectroscopic methods. Nine compounds were isolated and determined as luteolin(1), quercetin(2), hyperoside(3), rutin(4), 1, 5-dihydroxy-3-methyl-anthraquinone(5),3,5-dimethoxy-4-hydroxy-benzoic acid-1-O-beta-D-glucoside(6), hexadecanoic acid(7), stearic acid(8), n-tetratriacontanol(9), respectively. All the compounds are isolated from this plant for the first time, and compounds 5 and 6 are isolated from this genus for the first time.

The Content of Dietary Fibre and Polyphenols in Morphological Parts of Buckwheat (Fagopyrum tataricum).

PubMed

Dziedzic, Krzysztof; Górecka, Danuta; Szwengiel, Artur; Sulewska, Hanna; Kreft, Ivan; Gujska, Elżbieta; Walkowiak, Jarosław

2018-03-01

In this report, we presented the profile of polyphenolic substances in flowers, leaves, stalk and roots of Fagopyrum tataricum estimated by using RP-UHPLC-ESI-MS equipment (reversed-phase ultra-high-performance liquid chromatography electrospray ionisation mass spectrometry). The neutral detergent fibre, acid detergent fibre, acid detergent lignin, cellulose and hemicellulose were also determined. Flowers, leaves, stalk and roots showed varying levels of dietary fibre and polyphenols. The highest content of neutral and acid detergent fibre were found in the roots (63.92 and 45.45% d.m., respectively) while the most rich in phenolic compounds were flowers (4.8 mg/1 g d.m.). Root and stalk contained the highest level of cellulose, 38.70 and 25.57% d.m., respectively. Among the investigated polyphenolic substances such as: 2,6-dihydroxybenzoic acid, 3,4-dihydroxybenzoic acid, 3,5-dihydroxybenzoic acid, 4-hydrobenzoic acid, caffeic acid, catechin, chlorogenic acid, fagopyrin, ferulic acid, myricetin, gallic acid, isovanilic acid, isovitexin, kaempferol, luteolin, p-coumaric acid, procyanidin B2, quercetin, quercetin 3-D galactoside, rutin, syringic acid and vitexin, we observed that the contents of rutin and chlorogenic acid were the highest. We found some correlation between dietary fibre fractions and individual phenolic substances. The levels of acid detergent fibre (ADF), cellulose and hemicellulose were negatively correlated with isovitexin, kaempferol, vitexin, fagopyrin, caffeic acid and procyanidin B2 content. In this investigation, two solvents (water and methanol) were estimated regarding their extraction efficiency of phenolic compounds. Taking these results into consideration, we recommend using methanol as the extractor to isolate chlorogenic acid, fagopyrin, kaempferol, procyanidin B2, quercetin, quercetin 3-D-galactoside, rutin, vitexin, and water for other investigated polyphenolic substances obtained from Fagopyrum tataricum.

Effect of glycine nitrogen on lettuce growth under soilless culture: a metabolomics approach to identify the main changes occurred in plant primary and secondary metabolism.

PubMed

Yang, Xiao; Feng, Lei; Zhao, Li; Liu, Xiaosong; Hassani, Danial; Huang, Danfeng

2018-01-01

Lettuce is a significant source of antioxidants and bioactive compounds. Nitrate is a cardinal fertilizer in horticulture and influences vegetable yield and quality; however, the negative effects of nitrate on the biosynthesis of flavonoids require further study. It is expected that using fertilizers containing organic nitrogen (N) could promote the synthesis of health-promoting compounds. Lettuces were hydroponically cultured in media containing 9 mmol L -1 nitrate or 9 mmol L -1 glycine for 4 weeks. Primary and secondary metabolites were analyzed using gas chromatography/mass spectrometry (GC/MS) and ultra-performance liquid chromatography/ion mobility spectrometry/quadrupole time-of-flight mass spectrometry (UPLC/IMS/QTOF-MS). Data analysis revealed that 29 metabolites were significantly altered between nitrate and glycine treatments. Metabolites were tentatively identified by comparison with online databases, literature and standards and using collision cross-section values. Significant differences in flavonoid biosynthesis, phenolic biosynthesis and the tricarboxylic acid (TCA) cycle response were observed between N sources. Compared with nitrate, glycine promoted accumulation of glycosylated flavonoids (quercetin 3-glucoside, quercetin 3-(6″-malonyl-glucoside), luteolin 7-glucuronide, luteolin 7-glucoside), ascorbic acid and amino acids (l-valine, l-leucine, l-glutamine, asparagine, l-serine, l-ornithine, 4-aminobutanoic acid, l-phenylalanine) but reduced phenolic acids (dihydroxybenzoic acid hexose isomers 1 and 2, chicoric acid, chicoric acid isomer 1) and TCA intermediates (fumaric, malic, citric and succinic acids). The novel methodology applied in this study can be used to characterize metabolites in lettuce. Accumulation of glycosylated flavonoids, amino acids and ascorbic acid in response to glycine supply provides strong evidence supporting the idea that using amino acids as an N source alters the nutritional value of vegetable crops. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

High-energy and low-energy collision-induced dissociation of protonated flavonoids generated by MALDI and by electrospray ionization

NASA Astrophysics Data System (ADS)

March, Raymond E.; Li, Hongxia; Belgacem, Omar; Papanastasiou, Dimitris

2007-04-01

Product ion mass spectra of a series of nine protonated flavonoids have been observed by electrospray ionization combined with quadrupole/time-of-flight (ESI QTOF), and matrix-assisted laser desorption ionization combined either with quadrupole ion trap (MALDI QIT) tandem mass spectrometry or time-of-flight tandem mass spectrometry (MALDI TOF ReTOF). The compounds examined are 3,6-, 3,2'-, and 3,3'-dihydoxyflavone, apigenin (5,7,4'-trihydroxyflavone), luteolin (5,7,3',4'-tetrahydroxyflavone), apigenin-7-O-glucoside, hesperidin (5,7,3'-trihydroxy-4'-methoxyflavanone), daidzen (7,4'-dihydroxyisoflavone), and rutin (quercitin-3-O-rutinoside) where quercitin is 3,5,7,3',4'-pentahydroxyflavone; sodiated rutin was examined also. The center-of-mass energies in ESI QTOF and MALDI QIT are similar (1-4 eV) and their product ion mass spectra are virtually identical. In the MALDI TOF ReTOF instrument, center-of-mass energies range from 126-309 eV for sodiated rutin to protonated dihydroxyflavones, respectively. Due to the high center-of-mass energies available with the MALDI TOF ReTOF instrument, some useful structural information may be obtained; however, with increasing precursor mass/charge ratio, product ion mass spectra become simplified so as to be of limited structural value. Electronic excitation of the protonated (and sodiated) species examined here offers an explanation for the very simple product ion mass spectra observed particularly for glycosylated flavonoids.

Assessment of the potential health benefits of certain total extracts from Vitis vinifera, Aesculus hyppocastanum and Curcuma longa

PubMed Central

MARGINĂ, DENISA; OLARU, OCTAVIAN TUDOREL; ILIE, MIHAELA; GRĂDINARU, DANIELA; GUȚU, CLAUDIA; VOICU, SORINA; DINISCHIOTU, ANCA; SPANDIDOS, DEMETRIOS A.; TSATSAKIS, ARISTIDIS M.

2015-01-01

A number of recent studies have illustrated the active role of food/natural components in the prevention of chronic diseases and in the improvement of the quality of life. In the present study, we aimed to obtain and characterize certain extracts from Vitis vinifera L., Aesculus hippocastanum L. and Curcuma longa L., focusing on their antioxidant effects in vitro. Three vegetal extracts were obtained for each plant: in water, 50% water-alcohol and in 96% ethanol. These extracts were then analyzed for their qualitative composition by high performance thin layer chromatography (HPTLC) and total phenolic content by ultraviolet-visible spectrophotometry (UV-VIS). The antioxidant activity of the extracts was assessed in vitro by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay; the effects of lipid peroxidation on the cell membrane were evaluated using Jurkat cells in two experimental models: normoglycemic and hyperglycemic medium, in order for the results to be able to be translated into clinical practice. In addition, the resistance of the extracts to acid and alkaline hydrolysis was investigated. The obtained extracts had 0.4–39 µg phenolics/mg total extract. The largest amount of phenolics was found in the Cucurma longa extracts, while the lowest was found in the Aesculus hippocastanum extacts. HPTLC analysis identified the main phenolic compounds in the extracts which were ferulic acid, gallic acid, caffeic acid and coumaric acid, as well as quercetin, kaempferol, apigenin, curcumin, luteolin and esculetin. The Aesculus hippocastanum extracts had a low antioxidant efficacy, while both the Curcuma longa and Vitis vinifera extracts had a high antioxidant activity; the products resulting from alkaline hydrolisis were significantly more efficient in scavenging DPPH radicals compared to the products resulting from acid hydrolisis. The antioxidant effects of the Curcuma longa extracts exerted on the membranes of Jurkat cells were the most prominent under both normal and hyperglycemic conditions. The results of the present study may be translated into clinical practice and demonstrate that Curcuma longa extracts may be effective in both the prevention of diabetes mellitus and in attenuating the development of complications associated with the disease. PMID:26640536

Insights into the molecular mechanisms of Polygonum multiflorum Thunb-induced liver injury: a computational systems toxicology approach.

PubMed

Wang, Yin-Yin; Li, Jie; Wu, Zeng-Rui; Zhang, Bo; Yang, Hong-Bin; Wang, Qin; Cai, Ying-Chun; Liu, Gui-Xia; Li, Wei-Hua; Tang, Yun

2017-05-01

An increasing number of cases of herb-induced liver injury (HILI) have been reported, presenting new clinical challenges. In this study, taking Polygonum multiflorum Thunb (PmT) as an example, we proposed a computational systems toxicology approach to explore the molecular mechanisms of HILI. First, the chemical components of PmT were extracted from 3 main TCM databases as well as the literature related to natural products. Then, the known targets were collected through data integration, and the potential compound-target interactions (CTIs) were predicted using our substructure-drug-target network-based inference (SDTNBI) method. After screening for hepatotoxicity-related genes by assessing the symptoms of HILI, a compound-target interaction network was constructed. A scoring function, namely, Ascore, was developed to estimate the toxicity of chemicals in the liver. We conducted network analysis to determine the possible mechanisms of the biphasic effects using the analysis tools, including BiNGO, pathway enrichment, organ distribution analysis and predictions of interactions with CYP450 enzymes. Among the chemical components of PmT, 54 components with good intestinal absorption were used for analysis, and 2939 CTIs were obtained. After analyzing the mRNA expression data in the BioGPS database, 1599 CTIs and 125 targets related to liver diseases were identified. In the top 15 compounds, seven with Ascore values >3000 (emodin, quercetin, apigenin, resveratrol, gallic acid, kaempferol and luteolin) were obviously associated with hepatotoxicity. The results from the pathway enrichment analysis suggest that multiple interactions between apoptosis and metabolism may underlie PmT-induced liver injury. Many of the pathways have been verified in specific compounds, such as glutathione metabolism, cytochrome P450 metabolism, and the p53 pathway, among others. Hepatitis symptoms, the perturbation of nine bile acids and yellow or tawny urine also had corresponding pathways, justifying our method. In conclusion, this computational systems toxicology method reveals possible toxic components and could be very helpful for understanding the mechanisms of HILI. In this way, the method might also facilitate the identification of novel hepatotoxic herbs.

Assessment of the potential health benefits of certain total extracts from Vitis vinifera, Aesculus hyppocastanum and Curcuma longa.

PubMed

Margină, Denisa; Olaru, Octavian Tudorel; Ilie, Mihaela; Grădinaru, Daniela; GuȚu, Claudia; Voicu, Sorina; Dinischiotu, Anca; Spandidos, Demetrios A; Tsatsakis, Aristidis M

2015-11-01

A number of recent studies have illustrated the active role of food/natural components in the prevention of chronic diseases and in the improvement of the quality of life. In the present study, we aimed to obtain and characterize certain extracts from Vitis vinifera L., Aesculus hippocastanum L. and Curcuma longa L., focusing on their antioxidant effects in vitro . Three vegetal extracts were obtained for each plant: in water, 50% water-alcohol and in 96% ethanol. These extracts were then analyzed for their qualitative composition by high performance thin layer chromatography (HPTLC) and total phenolic content by ultraviolet-visible spectrophotometry (UV-VIS). The antioxidant activity of the extracts was assessed in vitro by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay; the effects of lipid peroxidation on the cell membrane were evaluated using Jurkat cells in two experimental models: normoglycemic and hyperglycemic medium, in order for the results to be able to be translated into clinical practice. In addition, the resistance of the extracts to acid and alkaline hydrolysis was investigated. The obtained extracts had 0.4-39 µg phenolics/mg total extract. The largest amount of phenolics was found in the Cucurma longa extracts, while the lowest was found in the Aesculus hippocastanum extacts. HPTLC analysis identified the main phenolic compounds in the extracts which were ferulic acid, gallic acid, caffeic acid and coumaric acid, as well as quercetin, kaempferol, apigenin, curcumin, luteolin and esculetin. The Aesculus hippocastanum extracts had a low antioxidant efficacy, while both the Curcuma longa and Vitis vinifera extracts had a high antioxidant activity; the products resulting from alkaline hydrolisis were significantly more efficient in scavenging DPPH radicals compared to the products resulting from acid hydrolisis. The antioxidant effects of the Curcuma longa extracts exerted on the membranes of Jurkat cells were the most prominent under both normal and hyperglycemic conditions. The results of the present study may be translated into clinical practice and demonstrate that Curcuma longa extracts may be effective in both the prevention of diabetes mellitus and in attenuating the development of complications associated with the disease.

Oral administration of fisetin promotes the induction of hippocampal long-term potentiation in vivo.

PubMed

He, Wen-Bin; Abe, Kazuho; Akaishi, Tatsuhiro

2018-01-01

To explore memory enhancing effect of the flavonoid fisetin, we investigated the effect of oral administration of flavonoids on the induction of long-term potentiation (LTP) at hippocampal CA1 synapses of anesthetized rats. Among four flavonoids (fisetin, quercetin, luteolin and myricetin) tested, only fisetin significantly facilitated the induction of hippocampal LTP. The effect of oral fisetin was abolished by intracerebroventricular injection of U0126, an agent that was previously found to inhibit its effect in hippocampal slices in vitro. These results suggest that orally administered fisetin crosses the blood-brain barrier and promotes synaptic functions in the hippocampus. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

The polyphenolics and carbohydrates as indicators of botanical and geographical origin of Serbian autochthonous clones of red spice paprika.

PubMed

Mudrić, Sanja Ž; Gašić, Uroš M; Dramićanin, Aleksandra M; Ćirić, Ivanka Ž; Milojković-Opsenica, Dušanka M; Popović-Đorđević, Jelena B; Momirović, Nebojša M; Tešić, Živoslav Lj

2017-02-15

Spice peppers (Capsicum annuum L.) var. Lemeška and Lakošnička paprika were investigated to evaluate their polyphenolic and carbohydrate profiles and antioxidant activity. A total of forty-nine polyphenolics were identified using ultrahigh-performance liquid chromatography (UHPLC) coupled to LTQ OrbiTrap mass analyzer. Twenty-five of them were quantified using available standards, while the other compounds were confirmed by exact mass search of their deprotonated molecule [M-H](-) and its MS(4) fragmentation. Thirteen carbohydrates were quantified using high-performance anion exchange chromatography (HPAEC) with pulsed amperometric detection (PAD). Radical scavenging activity (RSA) ranged from 17.32 to 48.34mmol TE (Trolox equivalent)/kg DW (dry weight) and total phenolics content (TPC) was ranged between 7.03 and 14.92g GAE (gallic acid equivalents)/kg DW. To our best knowledge, five polyphenolic compounds were for the first time tentatively identified in paprika: 5-O-p-coumaroylquinic acid, luteolin 7-O-(2″-O-pentosyl-4″-O-hexosyl)hexoside, quercetin 3-O-(2″-O-hexosyl)rhamnoside, isorhamnetin 3-O-[6″-O-(5-hydroxyferuloyl)hexoside]-7-O-rhamnoside, and luteolin 7-O-[2″-O-(5'″-O-sinapoyl)pentosyl-6″-O-malonyl]hexoside. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mass spectrometric imaging of flavonoid glycosides and biflavonoids in Ginkgo biloba L.

PubMed

Beck, Sebastian; Stengel, Julia

2016-10-01

Ginkgo biloba L. is known to be rich in flavonoids and flavonoid glycosides. However, the distribution within specific plant organs (e.g. within leaves) is not known. By using HPLC-MS and MS/MS we have identified a number of previously known G. biloba flavonoid glycosides and biflavonoids from leaves. Namely, kaempferol, quercetin, isorhamnetin, myricetin, laricitrin/mearnsetin and apigenin glycosides were identified. Furthermore, biflavonoids like ginkgetin/isoginkgetin were also detected. The application of MALDI mass spectrometric imaging, enabled the compilation of concentration profiles of flavonoid glycosides and biflavonoids in G. biloba L. leaves. Both, flavonoid glycosides and biflavonoids show a distinct distribution in leaf thin sections of G. biloba L. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preharvest treatments with malic, oxalic, and acetylsalicylic acids affect the phenolic composition and antioxidant capacity of coriander, dill and parsley.

PubMed

El-Zaeddi, Hussein; Calín-Sánchez, Ángel; Nowicka, Paulina; Martínez-Tomé, Juan; Noguera-Artiaga, Luis; Burló, Francisco; Wojdyło, Aneta; Carbonell-Barrachina, Ángel A

2017-07-01

The effects of a preharvest treatment with malic (MA), oxalic (OA), or acetylsalicylic (ASA) acid at three concentrations (1, 2 and 3mM) on the bioactivity and antioxidant capacity of coriander, dill, and parsley were investigated. The antioxidant capacity of the herbs extracts was assayed by spectrophotometric methods by using three different analytical methods: ORAC, FRAP, and ABTS; the effects of treatments were very positive in coriander, produced intermediate results in dill, and no effects were found in parsley plants. Polyphenol compounds were identified by LC-MS-QTof and quantified by UPLC-PDA-FL. Thirty phenolic compounds were identified in these three herbs. The major compounds were (i) coriander: dimethoxycinnamoyl hexoside and quercetin-3-O-rutinoside, (ii) dill: neochlorogenic acid and quercetin glucuronide, and (iii) parsley: apigenin-7-apiosylglucoside (apiin) and isorhamnetin-3-O-hexoside. The application of these three organic acids favored the accumulation of phenolic compounds in coriander plants, but had no significant positive effects on dill and parsley. The treatments leading to the best results in all three plants were the application of MA or OA at 1mM. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antiradical and cytotoxic activity of different Helichrysum plicatum flower extracts.

PubMed

Bigović, Dubravka; Savikin, Katarina; Janković, Teodora; Menković, Nebojsa; Zdunić, Gordana; Stanojković, Tatjana; Djurić, Zorica

2011-06-01

Flowers of Helichrysum plicatum were extracted under different experimental conditions, and their antioxidant activity was determined by DPPH radical scavenging assay. Extracts obtained with higher concentration of ethyl acetate (90% or 100%) were found to contain the greatest amount of total phenolics (> 250 mg gallic acid equivalents/g of dried extract), and high correlation between total phenolic content and antiradical activity was observed (r = -0.79). Based on the total phenolic content and antiradical activity, some extracts were selected for investigation of cytotoxic activity toward PC3, HeLa and K562 human cancer cell lines in vitro. All tested extracts exhibited moderate activity against HeLa cells (41.9-42.1 microg/mL), whereas the extract obtained with 100% ethyl acetate was the most active against K562 and PC3 cell lines (25.9 and 39.2 microg/mL, respectively). Statistical analysis revealed significant correlation between total phenolic content and cytotoxic activity against PC3 and K562 cells. HPLC identification of phenolic compounds from the extracts indicated the presence of apigenin, naringenin and kaempferol as free aglycones, and glycosides of apigenin, naringenin, quercetin and kaempferol. Among aglycones, kaempferol displayed moderate cytostatic activity against all cell lines (24.8-64.7 microM).

Characterization of Virgin Olive Oils with Two Kinds of 'Frostbitten Olives' Sensory Defect.

PubMed

Romero, Inmaculada; Aparicio-Ruiz, Ramón; Oliver-Pozo, Celia; Aparicio, Ramón; García-González, Diego L

2016-07-13

The frost of olives on the tree due to drops of temperature can produce sensory defects in virgin olive oil (VOO). Temperature changes can be abrupt with freeze-thaw cycles or gradual, and they produce sensory and chemical variations in the oil. This study has analyzed the quality parameters (free fatty acids, peroxide value, UV absorption, and fatty acid ethyl esters) and phenols of VOOs described with the 'frostbitten olives' sensory defect. The phenol profiles allowed grouping these VOOs into two types. One of them, characterized with "soapy" and "strawberry-like" aroma descriptors, had higher values of 1-acetoxypinoresinol, pinoresinol, and aldehydic form of the ligstroside aglycon. The other one, characterized with "wood" and "humidity" descriptors, had higher concentrations of luteolin and apigenin. Most VOOs (75%) from the first group, associated with abrupt drops of temperature, have concentration of phenols higher than the value established by the health claim on olive oil polyphenols approved by the European Commission.

Effect of Nitrogen Fertilization and Harvest Time on Steviol Glycosides, Flavonoid Composition, and Antioxidant Properties in Stevia rebaudiana Bertoni.

PubMed

Tavarini, Silvia; Sgherri, Cristina; Ranieri, Anna Maria; Angelini, Luciana G

2015-08-12

This work investigated the effect of nitrogen fertilization and harvest time on the flavonoid composition and antioxidant properties of Stevia rebaudiana leaves. At the same time, changes in stevioside (Stev) and rebaudioside A (RebA) contents were recorded. A pot trial under open air conditions was set up, testing five N rates and three harvest times. The results showed that, by using an adequate N rate and choosing an appropriate harvest time, it was possible to significantly increase and optimize the bioactive compound levels. In particular, higher RebA, RebA/Stev ratio, total phenols and flavonoids, luteolin-7-O-glucoside, and apigenin-7-O-glucoside levels and antioxidant capacity were recorded by supplying 150 kg N ha(-1). Reduced or increased N availability in comparison with N150 had no consistent effect on Stevia phytochemicals content. Significant correlations were also found between stevioside and some of the flavonoids, indicating a possible role of flavonoids in the stevioside metabolic pathway, which deserves more investigations.

Flavonoids as matrices for MALDI-TOF mass spectrometric analysis of transition metal complexes

NASA Astrophysics Data System (ADS)

Petkovic, Marijana; Petrovic, Biljana; Savic, Jasmina; Bugarcic, Zivadin D.; Dimitric-Markovic, Jasmina; Momic, Tatjana; Vasic, Vesna

2010-02-01

Matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a suitable method for the analysis of inorganic and organic compounds and biomolecules. This makes MALDI-TOF MS convenient for monitoring the interaction of metallo-drugs with biomolecules. Results presented in this manuscript demonstrate that flavonoids such as apigenin, kaempferol and luteolin are suitable for MALDI-TOF MS analysis of Pt(II), Pd(II), Pt(IV) and Ru(III) complexes, giving different signal-to-noise ratios of the analyte peak. The MALDI-TOF mass spectra of inorganic complexes acquired with these flavonoid matrices are easy to interpret and have some advantages over the application of other commonly used matrices: a low number of matrix peaks are detectable and the coordinative metal-ligand bond is, in most cases, preserved. On the other hand, flavonoids do not act as typical matrices, as their excess is not required for the acquisition of MALDI-TOF mass spectra of inorganic complexes.

Infusions of artichoke and milk thistle represent a good source of phenolic acids and flavonoids.

PubMed

Pereira, Carla; Barros, Lillian; Carvalho, Ana Maria; Santos-Buelga, Celestino; Ferreira, Isabel C F R

2015-01-01

Cynara scolymus L. (artichoke) and Silybum marianum (L.) Gaertn (milk thistle) are two herbs well-known for their efficiency in the prevention/treatment of liver injuries, among other chronic diseases. Therefore, the aim of this work was to characterize specific bioactive components, phenolic compounds, in hydromethanolic extracts but also in infusions (the most commonly used preparations) obtained from the whole plant of milk thistle and artichoke. The phenolic profiles were accessed using HPLC-DAD-MS/ESI. Infusions of both species presented higher phenolic contents than the hydromethanolic extracts. Milk thistle presented a similar phenolic composition between the two preparations, revealing only differences in the quantities obtained. Nevertheless, artichoke revealed a slightly different profile considering infusion and hydromethanolic extracts. Apigenin-7-O-glucuronide was the major flavonoid found in milk thistle, while luteolin-7-O-glucuronide was the most abundant in artichoke. Therefore, infusions of both artichoke and milk thistle represent a good source of bioactive compounds, especially phenolic acids and flavonoids.

Study of flavonoids of Sechium edule (Jacq) Swartz (Cucurbitaceae) different edible organs by liquid chromatography photodiode array mass spectrometry.

PubMed

Siciliano, Tiziana; De Tommasi, Nunziatina; Morelli, Ivano; Braca, Alessandra

2004-10-20

A liquid chromatography-mass spectrometry (LC-MS)-based method was developed for the characterization of flavonoids from Sechium edule (Jacq) Swartz (Cucurbitaceae) edible organs, a plant cultivated since pre-Colombian times in Mexico where the fruit is called chayote. Chayote is used for human consumption in many countries; in addition to the fruits, stems, leaves and the tuberous part of the roots are also eaten. Eight flavonoids, including three C-glycosyl and five O-glycosyl flavones, were detected, characterized by nuclear magnetic resonance spectroscopic data, and quantified in roots, leaves, stems, and fruits of the plant by LC-photodiode array-MS. The aglycone moieties are represented by apigenin and luteolin, while the sugar units are glucose, apiose, and rhamnose. The results indicated that the highest total amount of flavonoids was in the leaves (35.0 mg/10 g of dried part), followed by roots (30.5 mg/10 g), and finally by stems (19.3 mg/10 g). Copyright 2004 American Chemical Society

By-product of Lavandula latifolia essential oil distillation as source of antioxidants.

PubMed

Méndez-Tovar, Inés; Herrero, Baudilio; Pérez-Magariño, Silvia; Pereira, José Alberto; Asensio-S-Manzanera, M Carmen

2015-06-01

The objective of this work was to evaluate the antioxidant properties of Lavandula latifolia waste obtained after essential oil distillation. Samples of 12 wild populations of the Lavandula genus collected between 2009 and 2010 were hydrodistilled and their by-products were analyzed using the Folin-Ciocalteu, free radical scavenging activity (2,2-diphenyl-1-picrylhydrazyl), and the ferric reducing antioxidant power (FRAP) methods. Rosmarinic acid, apigenin, and luteolin contents were analyzed by high-performance liquid chromatography-diode array detection. The mean of total phenolic content ranged from 1.89 ± 0.09 mg gallic acid equivalents/g dry weight to 3.54 ± 0.22 mg gallic acid equivalents/g dry weight. The average value of the half maximal effective concentration (EC 50 ) for scavenging activity ranged from 5.09 ± 0.17 mg/mL to 14.30 ± 1.90 mg/mL and the variability of the EC 50 in FRAP ranged from 3.72 ± 0.12 mg/mL to 18.55 ± 0.77 mg/mL. Annual variation was found among this samples and the environmental conditions of 2009 were found to be more favorable. The plants collected from Sedano showed the highest antioxidant power. Our results show that rosmarinic acid and apigenin in L. latifolia contributed to the antioxidant properties of the waste. In conclusion, the by-product of the distillation industry could be valorizing as a source of natural antioxidants. Copyright © 2014. Published by Elsevier B.V.

Olive leaf extracts protect cardiomyocytes against 4-hydroxynonenal-induced toxicity in vitro: comparison with oleuropein, hydroxytyrosol, and quercetin.

PubMed

Bali, Elif Burcu; Ergin, Volkan; Rackova, Lucia; Bayraktar, Oğuz; Küçükboyaci, Nurgün; Karasu, Çimen

2014-08-01

Olive (Olea europaea) leaf, an important traditional herbal medicine, displays cardioprotection that may be related to the cellular redox modulating effects of its polyphenolic constituents. This study was undertaken to investigate the protective effect of the ethanolic and methanolic extracts of olive leaves compared to the effects of oleuropein, hydroxytyrosol, and quercetin as a positive standard in a carbonyl compound (4-hydroxynonenal)-induced model of oxidative damage to rat cardiomyocytes (H9c2). Cell viability was detected by the MTT assay; reactive oxygen species production was assessed by the 2',7'-dichlorodihydrofluorescein diacetate method, and the mitochondrial membrane potential was determined using a JC-1 dye kit. Phospho-Hsp27 (Ser82), phospho-MAPKAPK-2 (Thr334), phospho-c-Jun (Ser73), cleaved-caspase-3 (cl-CASP3) (Asp175), and phospho-SAPK/JNK (Thr183/Tyr185) were measured by Western blotting. The ethanolic and methanolic extracts of olive leaves inhibited 4-hydroxynonenal-induced apoptosis, characterized by increased reactive oxygen species production, impaired viability (LD50: 25 µM), mitochondrial dysfunction, and activation of pro-apoptotic cl-CASP3. The ethanolic and methanolic extracts of olive leaves also inhibited 4-hydroxynonenal-induced phosphorylation of stress-activated transcription factors, and the effects of extracts on p-SAPK/JNK, p-Hsp27, and p-MAPKAPK-2 were found to be concentration-dependent and comparable with oleuropein, hydroxytyrosol, and quercetin. While the methanolic extract downregulated 4-hydroxynonenal-induced p-MAPKAPK-2 and p-c-Jun more than the ethanolic extract, it exerted a less inhibitory effect than the ethanolic extract on 4-hydroxynonenal-induced p-SAPK/JNK and p-Hsp27. cl-CASP3 and p-Hsp27 were attenuated, especially by quercetin. Experiments showed a predominant reactive oxygen species inhibitory and mitochondrial protecting ability at a concentration of 1-10 µg/mL of each extract, oleuropein, hydroxytyrosol, and quercetin. The ethanolic extract of olive leaves, which contains larger amounts of oleuropein, hydroxytyrosol, verbascoside, luteolin, and quercetin (by HPLC) than the methanolic one, has more protecting ability on cardiomyocyte viability than the methanolic extract or each phenolic compound against 4-hydroxynonenal-induced carbonyl stress and toxicity. Georg Thieme Verlag KG Stuttgart · New York.

Antioxidant Capacity of the Leaf Extract Obtained from Arrabidaea chica Cultivated in Southern Brazil

PubMed Central

Siraichi, Jackeline Tiemy Guinoza; Felipe, Daniele Fernanda; Brambilla, Lara Zampar Serra; Gatto, Melissa Junqueira; Terra, Vânia Aparecida; Cecchini, Alessandra Lourenco; Cortez, Lucia Elaine Ranieri; Rodrigues-Filho, Edson; Cortez, Diógenes Aparício Garcia

2013-01-01

Arrabidaea chica leaf extract has been used by people as an anti-inflammatory and astringent agent as well as a remedy for intestinal colic, diarrhea, leucorrhea, anemia, and leukemia. A. chica is known to be a good producer of phenolics. Therefore, in the present study, we investigated its antioxidant activity. The phenolic composition of A. chica leaves was studied by liquid chromatography coupled to diode array detection (LC–DAD) and liquid chromatography coupled to electrospray ionization-tandem mass spectrometry (LC–ESI-MS/MS), and isoscutellarein, 6-hydroxyluteolin, hispidulin, scutellarein, luteolin, and apigenin were identified. The extract from leaves of A. chica was tested for antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, β-carotene bleaching test, and total reactive antioxidant potential (TRAP) method. The crude extract quenched DPPH free radicals in a dose-dependent manner, and the IC50 of the extract was 13.51 µg/mL. The β-carotene bleaching test showed that the addition of the A. chica extract in different concentrations (200 and 500 µg/mL) prevented the bleaching of β-carotene at different degrees (51.2% ±3.38% and 94% ±4.61%, respectively). The TRAP test showed dose-dependent correlation between the increasing concentrations of A. chica extract (0.1, 0.5, and 1.0 µg/mL) and the TRAP values obtained by trolox (hydro-soluble vitamin E) 0.4738±0.0466, 1.981±0.1603, and 6.877±1.445 µM, respectively. The 2 main flavonoids, scutellarein and apigenin, were separated, and their antioxidant activity was found to be the same as that of the plant extract. These 2 flavonoids were quantified in the plant extract by using a validated HPLC-UV method. The results of these tests showed that the extract of A. chica had a significant antioxidant activity, which could be attributed to the presence of the mixture of flavonoids in the plant extract, with the main contribution of scutellarein and apigenin. PMID:24009700

Antioxidant activities of different colored sweet bell peppers (Capsicum annuum L.).

PubMed

Sun, T; Xu, Z; Wu, C-T; Janes, M; Prinyawiwatkul, W; No, H K

2007-03-01

Antioxidant compounds and their antioxidant activity in 4 different colored (green, yellow, orange, and red) sweet bell peppers (Capsicum annuum L.) were investigated. The total phenolics content of green, yellow, orange, and red peppers determined by the Folin-Ciocalteau method were 2.4, 3.3, 3.4, and 4.2 micromol catechin equivalent/g fresh weight, respectively. The red pepper had significantly higher total phenolics content than the green pepper. Among the 4 different colored peppers, red pepper contained a higher level of beta-carotene (5.4 microg/g), capsanthin (8.0 microg/g), quercetin (34.0 microg/g), and luteolin (11.0 microg/g). The yellow pepper had the lowest beta-carotene content (0.2 microg/g), while the green one had undetectable capsanthin and the lowest content of luteolin (2.0 microg/g). The free radical scavenging abilities of peppers determined by the 2,2'-diphenyl-1-picrylhydrazyl (DPPH) method were lowest for the green pepper (2.1 micromol Trolox equivalent/g) but not significantly different from the other 3 peppers. All 4 colored peppers exhibited significant abilities in preventing the oxidation of cholesterol or docosahexaenoic acid (DHA) (C22:6) during heating. However, these 4 peppers did not show significant differences in their abilities in preventing cholesterol oxidation. The green pepper showed slightly higher capability in preventing the oxidation of DHA compared to the other 3 peppers.

Anticancer Activity of Key Lime, Citrus aurantifolia

PubMed Central

Narang, Nithithep; Jiraungkoorskul, Wannee

2016-01-01

Citrus aurantifolia (family: Rutaceae) is mainly used in daily consumption, in many cultural cuisines, and in juice production. It is widely used because of its antibacterial, anticancer, antidiabetic, antifungal, anti-hypertensive, anti-inflammation, anti-lipidemia, and antioxidant properties; moreover, it can protect heart, liver, bone, and prevent urinary diseases. Its secondary metabolites are alkaloids, carotenoids, coumarins, essential oils, flavonoids, phenolic acids, and triterpenoids. The other important constituents are apigenin, hesperetin, kaempferol, limonoids, quercetin, naringenin, nobiletin, and rutin, all of these contribute to its remedial properties. The scientific searching platforms were used for publications from 1990 to present. The abstracts and titles were screened, and the full-text articles were selected. The present review is up-to-date of the phytochemical property of C. aurantifolia to provide a reference for further study. PMID:28082795

Versatile Redox Chemistry Complicates Antioxidant Capacity Assessment: Flavonoids as Milieu-Dependent Antiand Pro-Oxidants

PubMed Central

Chobot, Vladimir; Kubicova, Lenka; Bachmann, Gert; Hadacek, Franz

2013-01-01

Some antioxidants have been shown to possess additional pro-oxidant effects. Diverse methodologies exist for studying redox properties of synthetic and natural chemicals. The latter are substantial components of our diet. Exploration of their contribution to life-extending or -compromising effects is mandatory. Among reactive oxygen species (ROS), hydroxyl radical (•OH) is the most damaging species. Due to its short half-life, the assay has to contain a specific generation system. Plants synthesize flavonoids, phenolic compounds recognized as counter-agents to coronary heart disease. Their antioxidant activities are affected by their hydroxylation patterns. Moreover, in the plant, they mainly occur as glycosides. We chose three derivatives, quercetin, luteolin, and rutin, in attempts to explore their redox chemistry in contrasting hydrogen peroxide environments. Initial addition of hydrogen peroxide in high concentration or gradual development constituted a main factor affecting their redox chemical properties, especially in case of quercetin. Our study exemplifies that a combination of a chemical assay (deoxyribose degradation) with an electrochemical method (square-wave voltammetry) provides insightful data. The ambiguity of the tested flavonoids to act either as anti- or pro-oxidant may complicate categorization, but probably contributed to their evolution as components of a successful metabolic system that benefits both producer and consumer. PMID:23736691

Effect of In Vitro Digestion on the Total Antioxidant Capacity and Phenolic Content of 3 Species of Oregano (Hedeoma patens, Lippia graveolens, Lippia palmeri).

PubMed

Gutiérrez-Grijalva, Erick Paul; Angulo-Escalante, Miguel Angel; León-Félix, Josefina; Heredia, J Basilio

2017-12-01

Oregano phenolic compounds have been studied for their anti-inflammatory properties. Nonetheless, after ingestion, the gastrointestinal environment can affect their antioxidant stability and thus their bioactive properties. To evaluate the effect of in vitro gastrointestinal (GI) digestion on the phenolic compounds of 3 species of oregano (Hedeoma patens, Lippia graveolens, and Lippia palmeri), the total reducing capacity, total flavonoid content, and antioxidant capacity were evaluated before and after in vitro GI digestion. In addition, the phenolic compounds of the 3 oregano species were identified and quantified by UPLC-PDA before and after in vitro GI digestion. It was shown that the reducing capacity, flavonoid content and antioxidant capacity were affected by the GI digestion process. Moreover, the phenolic compounds identified were apigenin-7-glucoside, scutellarein, luteolin, luteolin-7-glucoside, phloridzin and chlorogenic acid, and their levels were affected by the in vitro GI process. Our results showed that the phenolic compounds from these 3 species of oregano are affected by the in vitro digestion process, and this effect is largely attributable to pH changes. These changes can modify the bioavailability and further anti-inflammatory activity of oregano phenolics, and thus, further research is needed. Oregano is a rich source of polyphenols that have shown bioactive properties like anti-inflammatory potential. However, little is known of the gastrointestinal fate of oregano polyphenols which is imperative to fully understand its bioaccessibility. Our results are important to develop new administration strategies which could help protect the antioxidant and anti-inflammatory potential and bioaccessibility of such compounds. © 2017 Institute of Food Technologists®.

Molecular Structure-Affinity Relationship of Flavonoids in Lotus Leaf (Nelumbo nucifera Gaertn.) on Binding to Human Serum Albumin and Bovine Serum Albumin by Spectroscopic Method.

PubMed

Tang, Xiaosheng; Tang, Ping; Liu, Liangliang

2017-06-23

Lotus leaf has gained growing popularity as an ingredient in herbal formulations due to its various activities. As main functional components of lotus leaf, the difference in structure of flavonoids affected their binding properties and activities. In this paper, the existence of 11 flavonoids in lotus leaf extract was confirmed by High Performance Liquid Chromatography (HPLC) analysis and 11 flavonoids showed various contents in lotus leaf. The interactions between lotus leaf extract and two kinds of serum albumins (human serum albumin (HSA) and bovine serum albumin (BSA)) were investigated by spectroscopic methods. Based on the fluorescence quenching, the interactions between these flavonoids and serum albumins were further checked in detail. The relationship between the molecular properties of flavonoids and their affinities for serum albumins were analyzed and compared. The hydroxylation on 3 and 3' position increased the affinities for serum albumins. Moreover, both of the methylation on 3' position of quercetin and the C₂=C₃ double bond of apigenin and quercetin decreased the affinities for HSA and BSA. The glycosylation lowered the affinities for HSA and BSA depending on the type of sugar moiety. It revealed that the hydrogen bond force played an important role in binding flavonoids to HSA and BSA.

Isolation of Flavonoids From Wild Aquilaria sinensis Leaves by an Improved Preparative High-Speed Counter-Current Chromatography Apparatus.

PubMed

Yang, Mao-Xun; Liang, Yao-Guang; Chen, He-Ru; Huang, Yong-Fang; Gong, Hai-Guang; Zhang, Tian-You; Ito, Yoichiro

2018-01-01

Four flavonoids including apigenin-7,4'-dimethylether, genkwanin, quercetin, and kaempferol were isolated in a preparative or semi-preparative scale from the leaves of wild Aquilaria sinensis using an improved preparative high-speed counter-current chromatography apparatus. The separations were performed with a two-phase solvent system composed of hexane-ethyl acetate, methanol-water at suitable volume ratios. The obtained fractions were analyzed by HPLC, and the identification of each target compound was carried out by ESI-MS and NMR. The yields of the above four target flavonoids were 4.7, 10.0, 11.0 and 4.4%, respectively. All these four flavonoids exhibited nitrite scavenging activities with the clearance rate of 12.40 ± 0.20%, 5.84 ± 0.03%, 28.10 ± 0.17% and 5.19 ± 0.11%, respectively. Quercetin was originally isolated from the Thymelaeaceae family, while kaempferol was isolated from the Aquilaria genus for the first time. In cytotoxicity test these two flavonoids exhibited moderate inhibitory activities against HepG2 cells with the IC50 values of 12.54 ± 1.37 and 38.63 ± 4.05 μM, respectively. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Nitric Oxide Synthase-Mediated Phytoalexin Accumulation in Soybean Cotyledons in Response to the Diaporthe phaseolorum f. sp. meridionalis Elicitor1

PubMed Central

Modolo, Luzia Valentina; Cunha, Fernando Queiroz; Braga, Márcia Regina; Salgado, Ione

2002-01-01

Phytoalexin biosynthesis is part of the defense mechanism of soybean (Glycine max) plants against attack by the fungus Diaporthe phaseolorum f. sp. meridionalis (Dpm), the causal agent of stem canker disease. The treatment of soybean cotyledons with Dpm elicitor or with sodium nitroprusside (SNP), a nitric oxide (NO) donor, resulted in a high accumulation of phytoalexins. This response did not occur when SNP was replaced by ferricyanide, a structural analog of SNP devoid of the NO moiety. Phytoalexin accumulation induced by the fungal elicitor, but not by SNP, was prevented when cotyledons were pretreated with NO synthase (NOS) inhibitors. The Dpm elicitor also induced NOS activity in soybean tissues proximal to the site of inoculation. The induced NOS activity was Ca2+- and NADPH-dependent and was sensitive to the NOS inhibitors NG-nitro-l-arginine methyl ester, aminoguanidine, and l-N6-(iminoethyl) lysine. NOS activity was not observed in SNP-elicited tissues. An antibody to brain NOS labeled a 166-kD protein in elicited and nonelicited cotyledons. Isoflavones (daidzein and genistein), pterocarpans (glyceollins), and flavones (apigenin and luteolin) were identified after exposure to the elicitor or SNP, although the accumulation of glyceollins and apigenin was limited in SNP-elicited compared with fungal-elicited cotyledons. NOS activity preceded the accumulation of these flavonoids in tissues treated with the Dpm elicitor. The accumulation of these metabolites was faster in SNP-elicited than in fungal-elicited cotyledons. We conclude that the response of soybean cotyledons to Dpm elicitor involves NO formation via a constitutive NOS-like enzyme that triggers the biosynthesis of antimicrobial flavonoids. PMID:12427995

Phytochemical components and biological activities of Silene arenarioides Desf.

PubMed

Golea, Lynda; Benkhaled, Mohammed; Lavaud, Catherine; Long, Christophe; Haba, Hamada

2017-12-01

In this study, six known compounds 1-6 were isolated from the aerial parts of Silene arenarioides Desf. using different chromatographic methods. The structures of these compounds were identified as maltol glycoside (1), soyacerebroside I (2), chrysin (3), apigenin (4), quercetin (5) and stigmasterol glucoside (6). The compounds (1) and (2) are reported for the first time from this genus. The isolated compounds were determined using NMR techniques ( 1 H NMR, 13 C NMR, COSY, HSQC and HMBC) and mass spectroscopy (ESI-MS). The antibacterial and antioxidant activities of extracts and of compound (1) have been evaluated. The antioxidant activity was performed by DPPH radical scavenging method, which showed that methanol extract possesses a good antioxidant activity with value of IC 50  = 8.064 ± 0.005 μg/mL.

Supercritical Carbon Dioxide Extraction of Bioactive Compounds from Ampelopsis grossedentata Stems: Process Optimization and Antioxidant Activity

PubMed Central

Wang, Yuefei; Ying, Le; Sun, Da; Zhang, Shikang; Zhu, Yuejin; Xu, Ping

2011-01-01

Supercritical carbon dioxide (SC-CO2) extraction of bioactive compounds including flavonoids and phenolics from Ampelopsis grossedentata stems was carried out. Extraction parameters such as pressure, temperature, dynamic time and modifier, were optimized using an orthogonal array design of L9 (34), and antioxidant activities of the extracts were evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay and ferrous ion chelating (FIC) assay. The best conditions obtained for SC-CO2 extraction of flavonoids was 250 bar, 40 °C, 50 min, and with a modifier of methanol/ethanol (1:3, v/v), and that for phenolics extraction was 250 bar, 40 °C, 50 min, and with a modifier of methanol/ethanol (1:1, v/v). Meantime, flavonoids and phenolics were found to be mainly responsible for the DPPH scavenging activity of the extracts, but not for the chelating activity on ferrous ion according to Pearson correlation analysis. Furthermore, several unreported flavonoids such as apigenin, vitexin, luteolin, etc., have been detected in the extracts from A. grossedentata stems. PMID:22072923

Anti-gout Potential of Malaysian Medicinal Plants.

PubMed

Abu Bakar, Fazleen I; Abu Bakar, Mohd F; Rahmat, Asmah; Abdullah, Norazlin; Sabran, Siti F; Endrini, Susi

2018-01-01

Gout is a type of arthritis that causes painful inflammation in one or more joints. In gout, elevation of uric acid in the blood triggers the formation of crystals, causing joint pain. Malaysia is a mega-biodiversity country that is rich in medicinal plants species. Therefore, its flora might offer promising therapies for gout. This article aims to systematically review the anti-gout potential of Malaysian medicinal plants. Articles on gout published from 2000 to 2017 were identified using PubMed, Scopus, ScienceDirect, and Google Scholar with the following keyword search terms: "gout," "medicinal plants," "Malaysia," "epidemiology," " in vitro," and " in vivo ." In this study, 85 plants were identified as possessing anti-gout activity. These plants had higher percentages of xanthine oxidase inhibitory activity (>85%); specifically, the Momordica charantia, Chrysanthemum indicum, Cinnamomum cassia, Kaempferia galanga, Artemisia vulgaris , and Morinda elliptica had the highest values, due to their diverse natural bioactive compounds, which include flavonoids, phenolics, tannin, coumarins, luteolin, and apigenin. This review summarizes the anti-gout potential of Malaysian medicinal plants but the mechanisms, active compounds, pharmacokinetics, bioavailability, and safety of the plants still remain to be elucidated.

Urtica spp.: Phenolic composition, safety, antioxidant and anti-inflammatory activities.

PubMed

Carvalho, Ana Rita; Costa, Gustavo; Figueirinha, Artur; Liberal, Joana; Prior, João A V; Lopes, Maria Celeste; Cruz, Maria Teresa; Batista, Maria Teresa

2017-09-01

Urtica dioica and other less studied Urtica species (Urticaceae) are often used as a food ingredient. Fifteen hydroxycinnamic acid derivatives and sixteen flavonoids, flavone and flavonol-type glycosides were identified in hydroalcoholic extracts from aerial parts of Urtica dioica L., Urtica urens L. and Urtica membranacea using HPLC-PDA-ESI/MS n . Among them, the 4-caffeoyl-5-p-coumaroylquinic acid and three statin-like 3-hydroxy-3-methylglutaroyl flavone derivatives were identified for the first time in Urtica urens and U. membranacea respectively. Urtica membranacea showed the higher content of flavonoids, mainly luteolin and apigenin C-glycosides, which are almost absent in the other species studied. In vitro, Urtica dioica exhibited greater antioxidant activity but Urtica urens exhibited stronger anti-inflammatory potential. Interestingly, statin-like compounds detected in Urtica membranacea have been associated with hypocholesterolemic activity making this plant interesting for future investigations. None of the extracts were cytotoxic to macrophages and hepatocytes in bioactive concentrations (200 and 350μg/mL), suggesting their safety use in food applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Recovering Bioactive Compounds from Olive Oil Filter Cake by Advanced Extraction Techniques

PubMed Central

Lozano-Sánchez, Jesús; Castro-Puyana, María; Mendiola, Jose A.; Segura-Carretero, Antonio; Cifuentes, Alejandro; Ibáñez, Elena

2014-01-01

The potential of by-products generated during extra-virgin olive oil (EVOO) filtration as a natural source of phenolic compounds (with demonstrated bioactivity) has been evaluated using pressurized liquid extraction (PLE) and considering mixtures of two GRAS (generally recognized as safe) solvents (ethanol and water) at temperatures ranging from 40 to 175 °C. The extracts were characterized by high-performance liquid chromatography (HPLC) coupled to diode array detection (DAD) and electrospray time-of-flight mass spectrometry (HPLC-DAD-ESI-TOF/MS) to determine the phenolic-composition of the filter cake. The best isolation procedure to extract the phenolic fraction from the filter cake was accomplished using ethanol and water (50:50, v/v) at 120 °C. The main phenolic compounds identified in the samples were characterized as phenolic alcohols or derivatives (hydroxytyrosol and its oxidation product), secoiridoids (decarboxymethylated and hydroxylated forms of oleuropein and ligstroside aglycones), flavones (luteolin and apigenin) and elenolic acid derivatives. The PLE extraction process can be applied to produce enriched extracts with applications as bioactive food ingredients, as well as nutraceuticals. PMID:25226536

HMG-CoA reductase inhibitory activity and phytocomponent investigation of Basella alba leaf extract as a treatment for hypercholesterolemia.

PubMed

Baskaran, Gunasekaran; Salvamani, Shamala; Ahmad, Siti Aqlima; Shaharuddin, Noor Azmi; Pattiram, Parveen Devi; Shukor, Mohd Yunus

2015-01-01

The enzyme 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase is the key enzyme of the mevalonate pathway that produces cholesterol. Inhibition of HMG-CoA reductase reduces cholesterol biosynthesis in the liver. Synthetic drugs, statins, are commonly used for the treatment of hypercholesterolemia. Due to the side effects of statins, natural HMG-CoA reductase inhibitors of plant origin are needed. In this study, 25 medicinal plant methanol extracts were screened for anti-HMG-CoA reductase activity. Basella alba leaf extract showed the highest inhibitory effect at about 74%. Thus, B. alba was examined in order to investigate its phytochemical components. Gas chromatography with tandem mass spectrometry and reversed phase high-performance liquid chromatography analysis revealed the presence of phenol 2,6-bis(1,1-dimethylethyl), 1-heptatriacotanol, oleic acid, eicosyl ester, naringin, apigenin, luteolin, ascorbic acid, and α-tocopherol, which have been reported to possess antihypercholesterolemic effects. Further investigation of in vivo models should be performed in order to confirm its potential as an alternative treatment for hypercholesterolemia and related cardiovascular diseases.

HMG-CoA reductase inhibitory activity and phytocomponent investigation of Basella alba leaf extract as a treatment for hypercholesterolemia

PubMed Central

Baskaran, Gunasekaran; Salvamani, Shamala; Ahmad, Siti Aqlima; Shaharuddin, Noor Azmi; Pattiram, Parveen Devi; Shukor, Mohd Yunus

2015-01-01

The enzyme 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase is the key enzyme of the mevalonate pathway that produces cholesterol. Inhibition of HMG-CoA reductase reduces cholesterol biosynthesis in the liver. Synthetic drugs, statins, are commonly used for the treatment of hypercholesterolemia. Due to the side effects of statins, natural HMG-CoA reductase inhibitors of plant origin are needed. In this study, 25 medicinal plant methanol extracts were screened for anti-HMG-CoA reductase activity. Basella alba leaf extract showed the highest inhibitory effect at about 74%. Thus, B. alba was examined in order to investigate its phytochemical components. Gas chromatography with tandem mass spectrometry and reversed phase high-performance liquid chromatography analysis revealed the presence of phenol 2,6-bis(1,1-dimethylethyl), 1-heptatriacotanol, oleic acid, eicosyl ester, naringin, apigenin, luteolin, ascorbic acid, and α-tocopherol, which have been reported to possess antihypercholesterolemic effects. Further investigation of in vivo models should be performed in order to confirm its potential as an alternative treatment for hypercholesterolemia and related cardiovascular diseases. PMID:25609924

Antioxidant Properties and Flavonoid Profile in Leaves of Calabrian Lavandula multifida L., an Autochthon Plant of Mediterranean Southern Regions.

PubMed

Panuccio, Maria Rosaria; Fazio, Angela; Papalia, Teresa; Barreca, Davide

2016-04-01

Lavandula multifida is a rare short-lived plant characteristic of Mediterranean basin able to survive in hot and arid climatic conditions on poorly evolved limestone soils. In this work, we characterize the enzymatic antioxidant system and phenolic composition, as well as the antioxidant properties of L. multifida fresh leaves. Enzymatic patterns show high level of peroxidases, ascorbate peroxidase, and dehydroascorbate reductase activities, when compared with L. angustifolia. The same trend is evident in total carotenoids, ascorbic acid, and reduced glutathione, and in the total antioxidant capacity assay. Moreover, RP-DAD-HPLC analyses of EtOH extract, obtained from fresh leaves, reveal main components, carvacrol, vitexin, and 7- or 8-glucoside derivatives of hypolaetin, scutellarein, luteolin, isoscutellarein, apigenin, and chrysoeriol. The analysis of this autochthon plant depicted a series of strategies adopted by L. multifida to survive in its stressful natural habitat and richness in health-promoting compounds that can be a resource for the preservation of this variety in dangerous of extinction. © 2016 Verlag Helvetica Chimica Acta AG, Zürich.

Metabolic profile and biological activities of Lavandula pedunculata subsp. lusitanica (Chaytor) Franco: studies on the essential oil and polar extracts.

PubMed

Costa, Patrícia; Gonçalves, Sandra; Valentão, Patrícia; Andrade, Paula B; Almeida, Carlos; Nogueira, José M F; Romano, Anabela

2013-12-01

We investigated the metabolic profile and biological activities of the essential oil and polar extracts of Lavandula pedunculata subsp. lusitanica (Chaytor) Franco collected in south Portugal. Gas chromatography-mass spectrometry (GC-MS) analysis revealed that oxygen-containing monoterpenes was the principal group of compounds identified in the essential oil. Camphor (40.6%) and fenchone (38.0%) were found as the major constituents. High-performance liquid chromatography with diode array detection (HPLC-DAD) analysis allowed the identification of hydroxycinnamic acids (3-O-caffeoylquinic, 4-O-caffeoylquinic, 5-O-caffeoylquinic and rosmarinic acids) and flavones (luteolin and apigenin) in the polar extracts, with rosmarinic acid being the main compound in most of them. The bioactive compounds from L. pedunculata polar extracts were the most efficient free-radical scavengers, Fe(2+) chelators and inhibitors of malondialdehyde production, while the essential oil was the most active against acetylcholinesterase. Our results reveal that the subspecies of L. pedunculata studied is a potential source of active metabolites with a positive effect on human health. Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical composition and biological activity of the essential oil from leaves of Moringa oleifera Lam. cultivated in Mozambique.

PubMed

Marrufo, Tatiana; Nazzaro, Filomena; Mancini, Emilia; Fratianni, Florinda; Coppola, Raffaele; De Martino, Laura; Agostinho, Adelaide Bela; De Feo, Vincenzo

2013-09-09

The antioxidant capacity and antimicrobial activity of the essential oil of Moringa oleifera (Moringaceae) grown in Mozambique was investigated. The chemical composition was studied by means of GC and GC-MS analysis. Hexacosane (13.9%), pentacosane (13.3%) and heptacosane (11.4%) were the main components. Ultra High Performance Chromatography-DAD analysis detected the flavonoids quercetin (126 μg/g) and luteolin (6.2 μg/g). The essential oil exhibited a relatively low free radical scavenging capacity. The antimicrobial activity of the essential oil was assayed against two Gram-positive strains (Bacillus cereus, Staphylococcus aureus), two Gram-negative strains (Escherichia coli, Pseudomonas aeruginosa), and five fungal strains of agro-food interest (Penicillium aurantiogriseum, Penicillium expansum, Penicillium citrinum, Penicillium digitatum, and Aspergillus niger spp.). B. cereus and P. aeruginosa, as well as the fungal strains were sensitive to the essential oil.

In Vitro Phytotoxicity and Antioxidant Activity of Selected Flavonoids

PubMed Central

De Martino, Laura; Mencherini, Teresa; Mancini, Emilia; Aquino, Rita Patrizia; De Almeida, Luiz Fernando Rolim; De Feo, Vincenzo

2012-01-01

The knowledge of flavonoids involved in plant-plant interactions and their mechanisms of action are poor and, moreover, the structural characteristics required for these biological activities are scarcely known. The objective of this work was to study the possible in vitro phytotoxic effects of 27 flavonoids on the germination and early radical growth of Raphanus sativus L. and Lepidium sativum L., with the aim to evaluate the possible structure/activity relationship. Moreover, the antioxidant activity of the same compounds was also evaluated. Generally, in response to various tested flavonoids, germination was only slightly affected, whereas significant differences were observed in the activity of the various tested flavonoids against radical elongation. DPPH test confirms the antioxidant activity of luteolin, quercetin, catechol, morin, and catechin. The biological activity recorded is discussed in relation to the structure of compounds and their capability to interact with cell structures and physiology. No correlation was found between phytotoxic and antioxidant activities. PMID:22754304

Scientific basis for the therapeutic use of Cymbopogon citratus, stapf (Lemon grass)

PubMed Central

Shah, Gagan; Shri, Richa; Panchal, Vivek; Sharma, Narender; Singh, Bharpur; Mann, A. S.

2011-01-01

Cymbopogon citratus, Stapf (Lemon grass) is a widely used herb in tropical countries, especially in Southeast Asia. The essential oil of the plant is used in aromatherapy. The compounds identified in Cymbopogon citratus are mainly terpenes, alcohols, ketones, aldehyde and esters. Some of the reported phytoconstituents are essential oils that contain Citral α, Citral β, Nerol Geraniol, Citronellal, Terpinolene, Geranyl acetate, Myrecene and Terpinol Methylheptenone. The plant also contains reported phytoconstituents such as flavonoids and phenolic compounds, which consist of luteolin, isoorientin 2’-O-rhamnoside, quercetin, kaempferol and apiginin. Studies indicate that Cymbopogon citratus possesses various pharmacological activities such as anti-amoebic, antibacterial, antidiarrheal, antifilarial, antifungal and anti-inflammatory properties. Various other effects like antimalarial, antimutagenicity, antimycobacterial, antioxidants, hypoglycemic and neurobehaviorial have also been studied. These results are very encouraging and indicate that this herb should be studied more extensively to confirm these results and reveal other potential therapeutic effects. PMID:22171285

Anticancer activity of flavonoids isolated from Achyrocline satureioides in gliomas cell lines.

PubMed

Souza, Priscila Oliveira de; Bianchi, Sara Elis; Figueiró, Fabrício; Heimfarth, Luana; Moresco, Karla Suzana; Gonçalves, Rosângela Mayer; Hoppe, Juliana Bender; Klein, Caroline Peres; Salbego, Christianne Gazzana; Gelain, Daniel Pens; Bassani, Valquíria Linck; Zanotto Filho, Alfeu; Moreira, José Claudio Fonseca

2018-05-04

Achyrocline satureioides, popularly known as "marcela", is a medicinal plant found in South America. This plant is rich in flavonoids, which have been reported to exert numerous biological activities. The aim of this study was to purify, identify and evaluate the mechanisms underlining anticancer activity of A. satureioides flavonoids in glioma cell lines (U87, U251 and C6) as well as their comparative toxicity in normal brain cells (primary astrocytes, neurons and organotypic hippocampal cultures). The main flavonoids present in A. satureioides are luteolin, quercetin, 3-O-methyl-quercetin and achyrobichalcone, the later a very unique metabolite present in this plant. Isolated flavonoids as well as A. satureioides extracts reduced proliferation and clonogenic survival, and induced apoptosis of glioma cell lines. In addition, A. satureioides flavonoids potentiated the cytotoxic effect and apoptosis induction by the glioma chemotherapeutic temozolomide (TMZ). Importantly, A. satureioides flavonoids were less cytotoxic to astrocytes, neuron:astrocytes co-cultures and hippocampal cultures if compared to gliomas. Investigation of 10 cancer-related pathways showed a reduced activation of MYC and the Map kinases ERK and JNK by A. satureioides flavonoid-enriched extract, an effect not observed when individual flavonoids were evaluated. Altogether, the herein presented results show that A. satureioides extract possesses a combination of flavonoids, some unique for this plant, which have synergistic anticancer activity and potential for further studies in vivo. Copyright © 2018 Elsevier Ltd. All rights reserved.

Chemical profile and antiacetylcholinesterase, antityrosinase, antioxidant and α-glucosidase inhibitory activity of Cynometra cauliflora L. leaves.

PubMed

Ado, Muhammad Abubakar; Abas, Faridah; Ismail, Intan Safinar; Ghazali, Hasanah M; Shaari, Khozirah

2015-02-01

The aim of the current study was (i) to evaluate the bioactive potential of the leaf methanolic extract of Cynometra cauliflora L., along with its respective hexane, dichloromethane, ethyl acetate (EtOAc), n-butanol (n-BuOH) and aqueous fractions, in inhibiting the enzymes α-glucosidase, acetylcholinesterase (AChE) and tyrosinase as well as evaluating their antioxidant activities. (ii) In addition, in view of the limited published information regarding the metabolite profile of C. cauliflora, we further characterized the profiles of the EtOAc and n-BuOH fractions using liquid chromatography-diode array detection-electrospray ionization-tandem mass spectrometry. The leaf methanolic extract of C. cauliflora exhibited potent inhibition of all three enzymes and high antioxidant activity. The bioactivity was found to be concentrated in the EtOAc and n-BuOH fractions. A total of 18 compounds were identified in these bioactive fractions, comprising a procyanidin trimer, procyanidin tetramer, procyanidin hexamer, taxifolin pentoside, catechin, vitexin, isovitexin, kaempferol hexoside, quercetin pentoside, quercetin hexoside, apigenin-6-C-glucoside-8-C-glucoside, kaempferol-coumaroyl hexoside and isorhamnetin hexoside. The results indicated that C. cauliflora, the leaves in particular, is a rich source of bioactive compounds and could be beneficial for further development of high-value phytomedicinal preparations and functional food products. © 2014 Society of Chemical Industry.

Activity based evaluation of a traditional Ayurvedic medicinal plant: Saraca asoca (Roxb.) de Wilde flowers as estrogenic agents using ovariectomized rat model.

PubMed

Swar, Gauri; Shailajan, Sunita; Menon, Sasikumar

2017-01-04

Saraca asoca (Roxb.) de Wilde, Ashok, is a popular traditional plant used for gynecological disorders. In India, the juice of Ashok flowers is traditionally consumed as a tonic by women in case of uterine disorders. But despite the use, its estrogenic potency is not yet evaluated and thus lacks the scientific recognition and acclaim. This study is designed to investigate the estrogenic potential of standardized ethanolic extract of Saraca asoca flowers (SAF) using ovariectomized (OVX) female albino Wistar rat model. Saraca asoca flowers were extracted in ethanol using hot maceration technique and the extract was standardized in terms of content of four phytoestrogens like quercetin, kaempferol, β-sitosterol and luteolin using HPTLC technique. Safety of the extract was evaluated at a dose of 2000mg/kg body weight in female albino Wistar rats as per the OECD guidelines. Bilateral ovariectomy surgery was performed for the excision of both the ovaries. The OVX animals were treated with the ethanolic extract of SAF at three dose levels- 100mg/kg, 200mg/kg and 400mg/kg body weight in distilled water as a vehicle, orally once a day for two weeks. Estradiol valerate was employed as a modern drug for comparative evaluation of the results. Estrogenic potency was studied by assaying the activities of serum and plasma marker enzymes and hormones viz. G6PDH, LDH, 17β-estradiol, progesterone along with cholesterol, triglycerides and HDL, and vaginal cornification. The uterotrophic effect was evaluated by studying the histoarchitecture of the uterus, effect on uterine weight and changes in the levels of uterine glycogen content. HPTLC revealed the presence of markers like quercetin, kaempferol, β-sitosterol and luteolin from the ethanolic extract of SAF. The content of the four markers was found to be 1.543mg/g, 0.924mg/g, 4.481mg/g and 2.349mg/g, respectively. SAF extract was found to be safe at an oral dose of 2000mg/kg body weight in rats. Among the three doses administered to ovariectomized rats, treatment with high dose was found to be more efficacious when compared with ovariectomized rats. The findings of this study firmly support the estrogenic potency of ethanolic extract of SAF which may be by the reason of phytoestrogens. Copyright © 2016. Published by Elsevier Ireland Ltd.

Potential New Pharmacological Agents Derived From Medicinal Plants for the Treatment of Pancreatic Cancer.

PubMed

Azimi, Haniye; Khakshur, Ali Asghar; Abdollahi, Mohammad; Rahimi, Roja

2015-01-01

In the present article, we reviewed plants and phytochemical compounds demonstrating beneficial effects in pancreatic cancer to find new sources of pharmaceutical agents. For this purpose, Scopus, PubMed, Web of Science, and Google scholar were searched for plants or herbal components with beneficial effects in the treatment of pancreatic cancer. Data were collected up to January 2013. The search terms were "plant," "herb," "herbal therapy," or "phytotherapy" and "pancreatic cancer" or "pancreas." All of the human in vivo and in vitro studies were included. According to studies, among diverse plants and phytochemicals, 12 compounds including apigenin, genistein, quercetin, resveratrol, epigallocatechin gallate, benzyl isothiocyanate, sulforaphane, curcumin, thymoquinone, dihydroartemisinin, cucurbitacin B, and perillyl alcohol have beneficial action against pancreatic cancer cells through 4 or more mechanisms. Applying their plausible synergistic effects can be an imperative approach for finding new efficient pharmacological agents in the treatment of pancreatic cancer.

Antioxidant capacity and total phenolic contents of oregano (Origanum vulgare), lavender (Lavandula angustifolia) and lemon balm (Melissa officinalis) from Romania.

PubMed

Spiridon, Iuliana; Colceru, Svetlana; Anghel, Narcis; Teaca, Carmen Alice; Bodirlau, Ruxanda; Armatu, Alice

2011-10-01

The study reported here presents a comparative screening of three medicinal plants including oregano (Origanum vulgare L.), lavender (Lavandula angustifolia) and lemon balm (Melissa officinalis) having the same geographical origin, the Southeast region of Romania, and growing in the same natural conditions. The contents of total phenolics and total flavonoids for the extracts of these were determined. Furthermore, the total antioxidant capacity was also evaluated. It was found that Origanum vulgare and Melissa officinalis extracts present the most effective antioxidant capacity in scavenging DPPH radicals, while Lavandula angustifolia is less active. High performance liquid chromatography-mass spectrometry analysis was used to identify the components of extracts. Major phenolic acids identified in the analysed species were ferulic, rosmarinic, p-coumaric and caffeic, while predominant flavonoids were quercetin, apigenin kaempherol, which were present as glucosides.

Preparation, characterization and antitumor activity evaluation of apigenin nanoparticles by the liquid antisolvent precipitation technique.

PubMed

Wu, Weiwei; Zu, Yuangang; Wang, Li; Wang, Lingling; Wang, Huimei; Li, Yuanyuan; Wu, Mingfang; Zhao, Xiuhua; Fu, Yujie

2017-11-01

The present work aimed to apply the liquid antisolvent precipitation (LAP) method for preparing the apigenin nanoparticles and thereby improving the solubility and bioavailability of apigenin. The different experimental parameters on particle size were optimized through central composite design (CCD) using the Design-Expert ® software. Under the optimum conditions, the particle size of the apigenin nanosuspension was about 159.2 nm. In order to get apigenin nanoparticles, the freeze-drying method was selected and the mannitol was used as a cryoprotectant. Then the solid state properties of the apigenin nanoparticles were investigated using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermo gravimetric (TG), and X-ray diffraction (XRD). The results obtained displayed that the apigenin nanoparticles exhibited near-spherical shape and could be transformed into an amorphous form. In addition, the dissolving test, the bioavailability in rats, and the antitumor activity were also studied. The experimental results showed that the solubility of the apigenin nanoparticles were about 29.61 times and 64.81 times of raw apigenin in artificial gastric juice and in artificial intestinal juice, respectively, and the apigenin nanoparticles showed higher dissolution rates compared to raw apigenin, and was about 6.08 times and 6.14 times than that of raw apigenin in artificial gastric juice and in artificial intestinal juice. The oral bioavailability of apigenin nanoparticles was about 4.96 times higher than that of the raw apigenin, but the apigenin nanoparticles had no toxic effect on the organs of rats. In addition, the apigenin nanoparticles had a higher inhibition to HepG2 cells by lower IC50 than that of raw apigenin.

Metabolic Disposition of Luteolin Is Mediated by the Interplay of UDP-Glucuronosyltransferases and Catechol-O-Methyltransferases in Rats.

PubMed

Wang, Liping; Chen, Qingwei; Zhu, Lijun; Li, Qiang; Zeng, Xuejun; Lu, Linlin; Hu, Ming; Wang, Xinchun; Liu, Zhongqiu

2017-03-01

Luteolin partially exerts its biologic effects via its metabolites catalyzed by UDP-glucuronosyltransferases (UGTs) and catechol-O-methyltransferases (COMTs). However, the interplay of UGTs and COMTs in mediating luteolin disposition has not been well clarified. In this study, we investigated the glucuronidation and methylation pathways of luteolin mediated by the interplay of UGTs and COMTs in vivo and in vitro. A total of nine luteolin metabolites was detected in rat plasma and bile by liquid chromatography-tandem mass spectrometry, namely, three glucuronides, two methylated metabolites, and four methylated glucuronides. Luteolin-3'-glucuronide (Lut-3'-G) exhibited the highest systemic exposure among these metabolites. Kinetics studies in rat liver S9 fractions suggested two pathways, as follows: 1) Luteolin was glucuronidated to luteolin-7-glucuronide, luteolin-4'-glucuronide, and Lut-3'-G by UGTs, and then Lut-7-G was methylated to chrysoeriol-7-glucuronide and diosmetin-7-glucuronide by COMTs. 2) Alternatively, luteolin was methylated to chrysoeriol and diosmetin by COMTs, and then chrysoeriol and diosmetin were glucuronidated by UGTs to their respective glucuronides. The methylation rate of luteolin was significantly increased by the absence of glucuronidation, whereas the glucuronidation rate was increased by the absence of methylation, but to a lesser extent. In conclusion, two pathways mediated by the interplay of UGTs and COMTs are probably involved in the metabolic disposition of luteolin. The glucuronidation and methylation of luteolin compensate for each other, although glucuronidation is the predominant pathway. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Resveratrol as a Bioenhancer to Improve Anti-Inflammatory Activities of Apigenin.

PubMed

Lee, Jin-Ah; Ha, Sang Keun; Cho, EunJung; Choi, Inwook

2015-11-19

The aim of this study was to improve the anti-inflammatory activities of apigenin through co-treatment with resveratrol as a bioenhancer of apigenin. RAW 264.7 cells pretreated with hepatic metabolites formed by the co-metabolism of apigenin and resveratrol (ARMs) in HepG2 cells were stimulated with lipopolysaccharide (LPS). ARMs prominently inhibited (p < 0.05) the production of nitric oxide (NO), prostaglandin E₂ (PGE₂), interleukin (IL)-1β, IL-6 and TNF-α. Otherwise no such activity was observed by hepatic metabolites of apigenin alone (AMs). ARMs also effectively suppressed protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Co-administration of apigenin (50 mg/kg) and resveratrol (25 mg/kg) also showed a significant reduction of carrageenan-induced paw edema in mice (61.20% to 23.81%). Co-administration of apigenin and resveratrol led to a 2.39 fold increase in plasma apigenin levels compared to administration of apigenin alone, suggesting that co-administration of resveratrol could increase bioavailability of apigenin. When the action of resveratrol on the main apigenin metabolizing enzymes, UDP-glucuronosyltransferases (UGTs), was investigated, resveratrol mainly inhibited the formation of apigenin glucuronides by UGT1A9 in a non-competitive manner with a Ki value of 7.782 μM. These results suggested that resveratrol helps apigenin to bypass hepatic metabolism and maintain apigenin's anti-inflammatory activities in the body.

Low-density-lipoprotein (LDL)-bound flavonoids increase the resistance of LDL to oxidation and glycation under pathophysiological concentrations of glucose in vitro.

PubMed

Wu, Chi-Hao; Lin, Jer-An; Hsieh, Wen-Ching; Yen, Gow-Chin

2009-06-10

The higher susceptibility of low-density lipoprotein (LDL) to oxidation and glycation in diabetes has been shown to be related to poor glycemic control. The aim of this study was to determine whether LDL-bound flavonoids attenuate high-glucose (HG)-mediated LDL oxidation and glycation. For this purpose, human plasma was preincubated with individual flavonoids for 3 h, followed by sequential ultracentrifugation and extensive dialysis to remove unbound flavonoid samples. Enriched LDL was subsequently isolated and challenged for its resistance to oxidation and glycation. Results showed that glucose (5-30 mM) dose-dependently accelerates copper (Cu(2+))-mediated LDL oxidative modification. The enrichment of flavonoids such as luteolin, naringenin, and kaempferol significantly increased the resistance of LDL to oxidation and prevented endogenous alpha-tocopherol consumption caused by HG/Cu(2+) (p < 0.05). The long-term glycation of LDL, which was measured by advanced glycation endproducts (AGEs)-related fluorescence and boronate affinity chromatography, was found to be inhibited by LDL-bound flavonoids in the following order: rutin > luteolin > quercetin > kaempferol > naringenin > catechin approximately EC > naringin. Moreover, a solid-phase extraction system with HPLC-diode array detection provided evidence that flavonoids were bound to LDL particles to a certain extent concurrently facilitating the lipoprotein antioxidant and antiglycation activities. In conclusion, this study supports the hypothesis that HG promoted oxidative and glycative modifications of LDL. This is the first study to show that the introduction of flavonoids into LDL particles protects the lipoprotein against glycotoxin-mediated adverse effects.

Luteolin Inhibits Human Prostate Tumor Growth by Suppressing Vascular Endothelial Growth Factor Receptor 2-Mediated Angiogenesis

PubMed Central

Pratheeshkumar, Poyil; Son, Young-Ok; Budhraja, Amit; Wang, Xin; Ding, Songze; Wang, Lei; Hitron, Andrew; Lee, Jeong-Chae; Kim, Donghern; Divya, Sasidharan Padmaja; Chen, Gang; Zhang, Zhuo; Luo, Jia; Shi, Xianglin

2012-01-01

Angiogenesis, the formation of new blood vessels from pre-existing vascular beds, is essential for tumor growth, invasion, and metastasis. Luteolin is a common dietary flavonoid found in fruits and vegetables. We studied the antiangiogenic activity of luteolin using in vitro, ex vivo, and in vivo models. In vitro studies using rat aortic ring assay showed that luteolin at non-toxic concentrations significantly inhibited microvessel sprouting and proliferation, migration, invasion and tube formation of endothelial cells, which are key events in the process of angiogenesis. Luteolin also inhibited ex vivo angiogenesis as revealed by chicken egg chorioallantoic membrane assay (CAM) and matrigel plug assay. Gelatin zymographic analysis demonstrated the inhibitory effect of luteolin on the activation of matrix metalloproteinases MMP-2 and MMP-9. Western blot analysis showed that luteolin suppressed VEGF induced phosphorylation of VEGF receptor 2 and their downstream protein kinases AKT, ERK, mTOR, P70S6K, MMP-2, and MMP-9 in HUVECs. Proinflammatory cytokines such as IL-1β, IL-6, IL-8, and TNF-α level were significantly reduced by the treatment of luteolin in PC-3 cells. Luteolin (10 mg/kg/d) significantly reduced the volume and the weight of solid tumors in prostate xenograft mouse model, indicating that luteolin inhibited tumorigenesis by targeting angiogenesis. CD31 and CD34 immunohistochemical staining further revealed that the microvessel density could be remarkably suppressed by luteolin. Moreover, luteolin reduced cell viability and induced apoptosis in prostate cancer cells, which were correlated with the downregulation of AKT, ERK, mTOR, P70S6K, MMP-2, and MMP-9 expressions. Taken together, our findings demonstrate that luteolin inhibits human prostate tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis. PMID:23300633

Anticancer effect of luteolin is mediated by downregulation of TAM receptor tyrosine kinases, but not interleukin-8, in non-small cell lung cancer cells.

PubMed

Lee, Youn Ju; Lim, Taeho; Han, Min Su; Lee, Sun-Hwa; Baek, Suk-Hwan; Nan, Hong-Yan; Lee, Chuhee

2017-02-01

TAM receptor tyrosine kinases (RTKs), Tyro3, Axl and MerTK, transduce diverse signals responsible for cell survival, growth, proliferation and anti-apoptosis. In the present study, we demonstrated the effect of luteolin, a flavonoid with antioxidant, anti-inflammatory and anticancer activities, on the expression and activation of TAM RTKs and the association with its cytotoxicity in non-small cell lung cancer (NSCLC) cells. We observed the cytotoxic effect of luteolin in parental A549 and H460 cells as well as in cisplatin-resistant A549/CisR and H460/CisR cells. Exposure of these cells to luteolin also resulted in a dose‑dependent decrease in clonogenic ability. Next, luteolin was found to decrease the protein levels of all three TAM RTKs in the A549 and A549/CisR cells in a dose‑dependent manner. In a similar manner, in H460 and H460/CisR cells, the protein levels of Axl and Tyro3 were decreased following luteolin treatment. In addition, Axl promoter activity was decreased by luteolin, indicating that luteolin suppresses Axl expression at the transcriptional level. We next found that luteolin abrogated Axl phosphorylation in response to growth arrest-specific 6 (Gas6), its ligand, implying the inhibitory effect of luteolin on Gas6-induced Axl activation. Ectopic expression of Axl was observed to attenuate the antiproliferative effect of luteolin, while knockdown of the Axl protein level using a gold nanoparticle-assisted gene delivery system increased its cytotoxicity. In contrast to the inhibitory effect of luteolin on the expression of TAM RTKs, interleukin-8 (IL-8) production was not decreased by luteolin in H460 and H460/CisR cells, while IL-8 production/cell was increased. Collectively, our data suggest that TAM RTKs, but not IL-8, are promising therapeutic targets of luteolin to abrogate cell proliferation and to overcome chemoresistance in NSCLC cells.

Luteolin suppresses angiogenesis and vasculogenic mimicry formation through inhibiting Notch1-VEGF signaling in gastric cancer.

PubMed

Zang, Mingde; Hu, Lei; Zhang, Baogui; Zhu, Zhenglun; Li, Jianfang; Zhu, Zhenggang; Yan, Min; Liu, Bingya

2017-08-26

Gastric cancer is a great threat to the health of the people worldwide and lacks effective therapeutic regimens. Luteolin is one of Chinese herbs and presents in many fruits and green plants. In our previous study, we observed that luteolin inhibited cell migration and promoted cell apoptosis in gastric cancer. In the present study, luteolin significantly inhibited tube formation of human umbilical vein endothelial cells (HUVECs) through decreasing cell migration and proliferation of HUVECs in a dose-dependent manner. Vasculogenic mimicry (VM) tubes formed by gastric cancer cells were also inhibited with luteolin treatment. To explore how luteolin inhibited tubes formation, ELISA assay for VEGF was performed. Both of the VEGF secretion from Hs-746T cells and HUVECs were significantly decreased subsequent to luteolin treatment. In addition, cell migration was increased with the interaction between gastric cancer cells and HUVECs in co-culture assays. However, the promoting effects were abolished subsequent to luteolin treatment. Furthermore, luteolin inhibited VEGF secretion through suppressing Notch1 expression in gastric cancer. Overexpression of Notch1 in gastric cancer cells partially rescued the effects on cell migration, proliferation, HUVECs tube formation, and VM formation induced by luteolin treatment. In conclusion, luteolin inhibits angiogenesis and VM formation in gastric cancer through suppressing VEGF secretion dependent on Notch1 expression. Copyright © 2017 Elsevier Inc. All rights reserved.

Apigenin inhibits renal cell carcinoma cell proliferation.

PubMed

Meng, Shuai; Zhu, Yi; Li, Jiang-Feng; Wang, Xiao; Liang, Zhen; Li, Shi-Qi; Xu, Xin; Chen, Hong; Liu, Ben; Zheng, Xiang-Yi; Xie, Li-Ping

2017-03-21

Apigenin, a natural flavonoid found in vegetables and fruits, has antitumor activity in several cancer types. The present study evaluated the effects and mechanism of action of apigenin in renal cell carcinoma (RCC) cells. We found that apigenin suppressed ACHN, 786-0, and Caki-1 RCC cell proliferation in a dose- and time-dependent manner. A comet assay suggested that apigenin caused DNA damage in ACHN cells, especially at higher doses, and induced G2/M phase cell cycle arrest through ATM signal modulation. Small interfering RNA (siRNA)-mediated p53 knockdown showed that apigenin-induced apoptosis was likely p53 dependent. Apigenin anti-proliferative effects were confirmed in an ACHN cell xenograft mouse model. Apigenin treatment reduced tumor growth and volume in vivo, and immunohistochemical staining revealed lower Ki-67 indices in tumors derived from apigenin-treated mice. These findings suggest that apigenin exposure induces DNA damage, G2/M phase cell cycle arrest, p53 accumulation and apoptosis, which collectively suppress ACHN RCC cell proliferation in vitro and in vivo. Given its antitumor effects and low in vivo toxicity, apigenin is a highly promising agent for treatment of RCC.

Pharmacokinetic properties and drug interactions of apigenin, a natural flavone.

PubMed

Tang, Ding; Chen, Keli; Huang, Luqi; Li, Juan

2017-03-01

Apigenin, a natural flavone, is widely distributed in plants such as celery, parsley and chamomile. It is present principally as glycosylated in nature. Higher intake of apigenin could reduce the risk of chronic diseases. It has gained particular interest in recent years as a beneficial, health-promoting agent with low intrinsic toxicity. Areas covered: This review summarizes and the absorption, distribution, metabolism and excretion (ADME) properties of apigenin, and drug-drug interaction of apigenin. Expert opinion: Since apigenin is a bioactive plant flavone and is widely distributed in common food, its consumption through the diet is recommended. Apigenin-enriched drugs are better for some chronic diseases, but may affect animal and human health if present in the daily diet. Dietary or therapeutic apigenin has value as a good cellular regulator in cancer, especially cancers of the gastrointestinal tract. Due to apigenin's limitations on absorption and bioavailability, novel carriers would need to be developed to enhance the oral bioavailability of apigenin. Further research about its ADME properties and drug-drug interactions are needed before apigenin can be brought to clinical trials.

Oxidative stress suppression by luteolin-induced heme oxygenase-1 expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Gui-bo; Sun, Xiao; Wang, Min

Luteolin, a flavonoid that exhibits antioxidative properties, exerts myocardial protection effects. However, the underlying molecular mechanisms are not yet fully understood. To investigate the effects of luteolin on myocardial injury protection and its possible mechanisms, a myocardial injury model was established with intragastric administration of 4 mg/kg isoproterenol (ISO) to male Sprague–Dawley rats (200–220 g) daily for 2 days. We found that pretreatment of luteolin (160, 80 and 40 mg/kg, i.g., respectively) daily for 15 days can prevent ISO-induced myocardial damage, including decrease of serum cardiac enzymes, improvement electrocardiography and heart vacuolation. Luteolin also improved the free radical scavenging andmore » antioxidant potential, suggesting one possible mechanism of luteolin-induced cardio-protection is mediated by blocking the oxidative stress. To clarify the mechanisms, we performed the in vitro study by hydrogen peroxide (H{sub 2}O{sub 2})-induced cytotoxicty model in H9c2 cells. We found that luteolin pretreatment prevented apoptosis, increased the expression of heme oxygenase-1 (HO-1), and enhanced the binding of Nrf2 to the antioxidant response element, providing an adaptive survival response against H{sub 2}O{sub 2}-derived oxidative cytotoxicity. The addition of Znpp, a selective HO-1 competitive inhibitor, reduced the cytoprotective ability of luteolin, indicating the vital role of HO-1 on these effects. Luteolin also activated Akt and ERK, whereas the addition of LY294002 and U0126, the pharmacologic inhibitors of PI3K and ERK, attenuated luteolin-induced HO-1 expression and cytoprotective effect. Taken together, the above findings suggest that luteolin protects against myocardial injury and enhances cellular antioxidant defense capacity through the activation of Akt and ERK signal pathways that leads to Nrf2 activation, and subsequently HO-1 induction. -- Highlights: ► Luteolin prevents isoproterenol-induced myocardial damage. ► Luteolin enhances cellular antioxidant defense capacity. ► Luteolin increases the expression of heme oxygenase-1 protein levels. ► Luteolin activates Akt and ERK signal pathways.« less

Flavonoids and urate antioxidant interplay in plasma oxidative stress.

PubMed

Filipe, P; Lança, V; Silva, J N; Morlière, P; Santus, R; Fernandes, A

2001-05-01

Flavonoids are naturally occurring plant compounds with antioxidant properties. Their consumption has been associated with the protective effects of certain diets against some of the complications of atherosclerosis. Low-density lipoprotein (LDL) oxidative modification is currently thought to be a significant event in the atherogenic process. Most of the experiments concerning the inhibition of LDL oxidation used isolated LDL. We used diluted human whole plasma to study the influence of flavonoids on lipid peroxidation (LPO) promoted by copper, and their interaction with uric acid, one of the most important plasma antioxidants. Lipid peroxidation was evaluated by the formation of thiobarbituric acid reactive substances (TBARS) and of free malondialdehyde (MDA). The comparative capability of the assayed flavonoids on copper (II) reduction was tested using the neocuproine colorimetric test. In our assay system, urate disappears and free MDA and TBARS formation increase during the incubation of plasma with copper. Most of the tested flavonoids inhibited copper-induced LPO. The inhibition of LPO by flavonoids correlated positively with their capability to reduce copper (II). The urate consumption during the incubation of plasma with copper was inhibited by myricetin, quercetin and kaempferol. The inhibition of urate degradation by flavonoids correlated positively with the inhibition of LPO. Urate inhibited the copper-induced LPO in a concentration-dependent mode. Luteolin, rutin, catechin and quercetin had an antioxidant synergy with urate. Our results show that some flavonoids could protect endogenous urate from oxidative degradation, and demonstrate an antioxidant synergy between urate and some of the flavonoids.

Purification and characterization of a novel phloretin-2'-O-glycosyltransferase favoring phloridzin biosynthesis.

PubMed

Zhang, Tingjing; Liang, Jianqiang; Wang, Panxue; Xu, Ying; Wang, Yutang; Wei, Xinyuan; Fan, Mingtao

2016-10-12

Phloretin-2'-O-glycosyltransferase (P2'GT) catalyzes the last glycosylation step in the biosynthesis of phloridzin that contributes to the flavor, color and health benefits of apples and processed apple products. In this work, a novel P2'GT of Malus x domestica (MdP2'GT) with a specific activity of 46.82 μkat/Kg protein toward phloretin and uridine diphosphate glucose (UDPG) at an optimal temperature of 30 °C and pH 8.0 was purified from the engineered Pichia pastoris broth to homogeneity by anion exchange chromatography, His-Trap affinity chromatography and gel filtration. The purified MdP2'GT was low N-glycosylated and secreted as a stable dimer with a molecular mass of 70.7 kDa in its native form. Importantly, MdP2'GT also exhibited activity towards quercetin and adenosine diphosphate glucose (ADPG), kaempferol and UDPG, quercetin and UDP-galactose, isoliquiritigenin and UDPG, and luteolin and UDPG, producing only one isoquercitrin, astragalin, hyperoside, isoliquiritin, or cynaroside, respectively. This broad spectrum of activities make MdP2'GT a promising biocatalyst for the industrial preparation of the corresponding polyphenol glycosides, preferably for their subsequent isolation and purification. Besides, MdP2'GT displayed the lowest K m and the highest k cat /K m for phloretin and UDPG compared to all previously reported P2'GTs, making MdP2'GT favor phloridzin synthesis the most.

Purification and characterization of a novel phloretin-2′-O-glycosyltransferase favoring phloridzin biosynthesis

PubMed Central

Zhang, Tingjing; Liang, Jianqiang; Wang, Panxue; Xu, Ying; Wang, Yutang; Wei, Xinyuan; Fan, Mingtao

2016-01-01

Phloretin-2′-O-glycosyltransferase (P2′GT) catalyzes the last glycosylation step in the biosynthesis of phloridzin that contributes to the flavor, color and health benefits of apples and processed apple products. In this work, a novel P2′GT of Malus x domestica (MdP2′GT) with a specific activity of 46.82 μkat/Kg protein toward phloretin and uridine diphosphate glucose (UDPG) at an optimal temperature of 30 °C and pH 8.0 was purified from the engineered Pichia pastoris broth to homogeneity by anion exchange chromatography, His-Trap affinity chromatography and gel filtration. The purified MdP2′GT was low N-glycosylated and secreted as a stable dimer with a molecular mass of 70.7 kDa in its native form. Importantly, MdP2′GT also exhibited activity towards quercetin and adenosine diphosphate glucose (ADPG), kaempferol and UDPG, quercetin and UDP-galactose, isoliquiritigenin and UDPG, and luteolin and UDPG, producing only one isoquercitrin, astragalin, hyperoside, isoliquiritin, or cynaroside, respectively. This broad spectrum of activities make MdP2′GT a promising biocatalyst for the industrial preparation of the corresponding polyphenol glycosides, preferably for their subsequent isolation and purification. Besides, MdP2′GT displayed the lowest Km and the highest kcat/Km for phloretin and UDPG compared to all previously reported P2′GTs, making MdP2′GT favor phloridzin synthesis the most. PMID:27731384

Variation in polyphenolic profiles, antioxidant and antimicrobial activity of different Achillea species as natural sources of antiglycative compounds.

PubMed

Afshari, Mahvash; Rahimmalek, Mehdi; Miroliaei, Mehran

2018-05-19

A comparative study was carried out on the methanolic extracts from six Achillea species and the examined polyphenols from these plants on the formation of advanced glycation end-products (AGE) in vitro. A. pachycephala which was richer in flavonoids (15 mg quercetin/g W) and phenolics (111.10 mg tannic acid/g DW) with substantial antioxidant activity (IC 50 = 365.5 μg/ml) presented strong anti-AGE properties. Chlorogenic acid, luteolin, quercetin and caffeic acid were identified as the major polyphenols in the extracts by HPLC. In general, polyphenolic content follows the order A. pachycephalla > A. nobilis > A. filipendulina > A. santolina > A. aucheri > A. millefolium. Most extracts exhibited marked anti-AGE ability in the bovine serum albumin (BSA)/methylglyoxal (MG) system, though A. pachycephala showed the highest potential. The formation of AGEs was assessed by monitoring the production of fluorescent products and Circular dichroism (CD) spectroscopy. Diminution in free radical production (assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays) is discussed as potential mechanism for delay or reduced AGE. The results demonstrate the antiglycative, antioxidant and antimicrobial potential of Achillea species which can be attribute to polyphenols content and the effectiveness on generation of AGEs, thus Achillea species can be considered as natural sources for slowing down glycation related diseases. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Antioxidant effects of Genkwa flos flavonoids on Freund׳s adjuvant-induced rheumatoid arthritis in rats.

PubMed

Zhang, Chun-Feng; Zhang, Su-Li; He, Xin; Yang, Xiao-Lin; Wu, Hai-Tao; Lin, Bao-Qin; Jiang, Cui-Ping; Wang, Jun; Yu, Chun-Hao; Yang, Zhong-Lin; Wang, Chong-Zhi; Li, Ping; Yuan, Chun-Su

2014-05-14

Genkwa flos (Daphne genkwa Sieb. et Zucc.), a Chinese herbal medicine, has been traditionally used for over two thousand years in China for inflammation related symptoms, including joint pain. To evaluate the antioxidative effects of flavonoid aglycones (FA) isolated from Genkwa flos on adjuvant arthritis in rats and to identify the relationship between antioxidant potential and whole blood viscosity (WBV). FA compounds were identified using LC-MS and the content was assayed by HPLC. Arthritis was induced by an intradermal injection of Freund׳s complete adjuvant in the footpad. The effects of FA on paw volumes, secondary arthritis scores, histopathology of joints, and body and organ weights were measured. The antioxidant effects of FA and WBV were determined. LC-MS analysis showed that the FA contained four major compounds: luteolin, apigenin, hydroxygenkwanin and genkwanin. FA significantly decreased paw edema, arthritis scores, and weight loss. These observations were consistent with the reduction of oxidative stress and the improvement of the WBV. FA significantly decreased arthritis in a rat model through antioxidant and hemorheological modulatory mechanisms. The Genkwa flos flavonoids may have clinical potential for the treatment of rheumatoid arthritis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Bioactive diterpenoids and flavonoids from the aerial parts of Scoparia dulcis.

PubMed

Liu, Qing; Yang, Qi-Ming; Hu, Hai-Jun; Yang, Li; Yang, Ying-Bo; Chou, Gui-Xin; Wang, Zheng-Tao

2014-07-25

Six new diterpenoids, 4-epi-7α-O-acetylscoparic acid A (1), 7α-hydroxyscopadiol (2), 7α-O-acetyl-8,17β-epoxyscoparic acid A (3), neo-dulcinol (4), dulcinodal-13-one (5), and 4-epi-7α-hydroxydulcinodal-13-one (6), and a new flavonoid, dillenetin 3-O-(6″-O-p-coumaroyl)-β-D-glucopyranoside (10), along with 12 known compounds, were isolated from the aerial parts of Scoparia dulcis. The 7S absolute configuration of the new diterpenoids 1-4 and 6 was deduced by comparing their NOESY spectra with that of a known compound, (7S)-4-epi-7-hydroxyscoparic acid A (7), which was determined by the modified Mosher's method. The flavonoids scutellarein (11), hispidulin (12), apigenin (15), and luteolin (16) and the terpenoids 4-epi-scopadulcic acid B (9) and betulinic acid (19) showed more potent α-glucosidase inhibitory effects (with IC50 values in the range 13.7-132.5 μM) than the positive control, acarbose. In addition, compounds 1, 11, 12, 15, 16, and acerosin (17) exhibited peroxisome proliferator-activated receptor gamma (PPAR-γ) agonistic activity, with EC50 values ranging from 0.9 to 24.9 μM.

High-performance liquid chromatography with diode array detection coupled to electrospray time-of-flight and ion-trap tandem mass spectrometry to identify phenolic compounds from a lemon verbena extract.

PubMed

Quirantes-Piné, R; Funes, L; Micol, V; Segura-Carretero, A; Fernández-Gutiérrez, A

2009-07-10

High-performance liquid chromatography with diode array and electrospray ionization mass spectrometric detection was used to carry out the comprehensive characterization of a lemon verbena extract with demonstrated antioxidant and antiinflammatory activity. Two different MS techniques have been coupled to HPLC: on one hand, time-of-flight mass spectrometry, and on the other hand, tandem mass spectrometry on an ion-trap. The use of a small particle size C18 column (1.8 microm) provided a great resolution and made possible the separation of several isomers. The UV-visible spectrophotometry was used to delimit the class of phenolic compound and the accurate mass measurements on time-of-flight spectrometer enabled to identify the compounds present in the extract. Finally, the fragmentation pattern obtained in MS-MS experiments confirmed the proposed structures. This procedure was able to determine many well-known phenolic compounds present in lemon verbena such as verbascoside and its derivatives, diglucuronide derivatives of apigenin and luteolin, and eukovoside. Also gardoside, verbasoside, cistanoside F, theveside, campneoside I, chrysoeriol-7-diglucuronide, forsythoside A and acacetin-7-diglucuronide were found for the first time in lemon verbena.

A new bioactive monoterpene-flavonoid from Satureja khuzistanica.

PubMed

Malmir, Maryam; Gohari, Ahmad Reza; Saeidnia, Soodabeh; Silva, Olga

2015-09-01

A new monoterpene-flavonoid, saturejin (3'-(2,5-dihydroxy-p-cymene) 5,7,4'-trihydroxy flavone) (4), together with twelve known flavonoids consist of two flavanonols (aromadendrin (8) and taxifolin (12)), two flavanones (naringenin (3) and 5,7,3',5'-tetrahydroxy flavanone (9)) and eight flavones (xanthomicrol (1), acacetin (2), cirsimaritin (5), 7-methoxy luteolin (6), apigenin (7), cirsilineol (10), diosmetin (11) and 6-hydroxyluteolin 7,3'-dimethyl ether (13)), were isolated from an ethyl acetate extract and identified for the first time in the dried aerial parts of Satureja khuzistanica Jamzad, an endemic medicinal plant traditionally used as dental anesthetic, oral antiseptic and anti-inflammatory among the nomadic inhabitants of southwestern Iran. The structures of these compounds were determined using the usual spectroscopic methods including 2D-NMR and MS analyses. Saturejin showed a significant β-glucosidase inhibitory activity at concentration of 10 μg as well as positive antioxidant activity at the amount of 1 μg. These results could be correlated with the in vitro and in vivo anti-inflammatory, anti-oxidant and anti-diabetic properties reported from this medicinal plant. Similar activities were also described for some of the other isolated compounds. Copyright © 2015 Elsevier B.V. All rights reserved.

Phytochemicals for the Management of Melanoma

PubMed Central

Pal, Harish Chandra; Hunt, Katherine Marchiony; Diamond, Ariana; Elmets, Craig A.; Afaq, Farrukh

2016-01-01

Melanoma claims approximately 80% of skin cancer-related deaths. Its life-threatening nature is primarily due to a propensity to metastasize. The prognosis for melanoma patients with distal metastasis is bleak, with median survival of six months even with the latest available treatments. The most commonly mutated oncogenes in melanoma are BRAF and NRAS accounting approximately 60% and 20% of cases, respectively. In malignant melanoma, accumulating evidence suggests that multiple signaling pathways are constitutively activated and play an important role in cell proliferation, cell survival, epithelial to mesenchymal transition, metastasis and resistance to therapeutic regimens. Phytochemicals are gaining considerable attention because of their low toxicity, low cost, and public acceptance as dietary supplements. Cell culture and animals studies have elucidated several cellular and molecular mechanisms by which phytochemicals act in the prevention and treatment of metastatic melanoma. Several promising phytochemicals, such as, fisetin, epigallocatechin-3-gallate, resveratrol, curcumin, proanthocyanidins, silymarin, apigenin, capsaicin, genistein, indole-3-carbinol, and luteolin are gaining considerable attention and found in a variety of fresh fruits, vegetables, roots, and herbs. In this review, we will discuss the preventive potential, therapeutic effects, bioavailability and structure activity relationship of these selected phytochemicals for the management of melanoma. PMID:26864554

Application of recombinant Pediococcus acidilactici BD16 (fcs⁺/ech⁺) in malolactic fermentation.

PubMed

Kaur, Baljinder; Kumar, Balvir; Kaur, Gaganjot; Chakraborty, Debkumar; Kaur, Kiranjeet

2015-04-01

This study was conducted to enhance flavor characteristics of wine by malolactic fermentation using recombinant Pediococcus acidilactici BD16 (fcs (+)/ech (+)) encoding synthetic genes of feruloyl-CoA synthetase and enoyl-CoA hydratase. After malolactic fermentation, wine phenolics were characterized using LCMS-ESI technique and a significant improvement in the antioxidant activity and flavor characteristics of wine was observed due to increased concentration of cinnamic acid derivatives. This proof of concept study highlights the role of recombinant P. acidilactici BD16 (fcs (+)/ech (+)) in improving flavor as well as aroma of wine due to production of several phenolic derivatives during secondary fermentation. A novel metabolic pathway was predicted from mass spectral analysis data that indicates biotransformation of cinnamic acid and derivatives into apigenin, catechin, coniferyl aldehyde, cyanidin, hydroxybenzoic acids, laricitrin, luteolin, malvidin 3-glucoside, myricetin, naringenin, pelargonin, piceatannol, querecitin, and vanillin that not only increased the overall consumer appreciation but also improved nutritional and probably the therapeutic properties of wines. This is a first evidence-based study where role of recombinant P. acidilactici BD16 (fcs (+)/ech (+)) in the wine secondary fermentation has been elucidated.

Phenolic acid composition and antioxidant properties of Malaysian honeys.

PubMed

Khalil, M I; Alam, N; Moniruzzaman, M; Sulaiman, S A; Gan, S H

2011-08-01

The phenolic acid and flavonoid contents of Malaysian Tualang, Gelam, and Borneo tropical honeys were compared to those of Manuka honey. Ferric reducing/antioxidant power assay (FRAP) and the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical-scavenging activities were also quantified. All honey extracts exhibited high phenolic contents (15.21 ± 0.51- 42.23 ± 0.64 mg/kg), flavonoid contents (11.52 ± 0.27- 25.31 ± 0.37 mg/kg), FRAP values (892.15 ± 4.97- 363.38 ± 10.57 μM Fe[II]/kg), and high IC₅₀ of DPPH radical-scavenging activities (5.24 ± 0.40- 17.51 ± 0.51 mg/mL). Total of 6 phenolic acids (gallic, syringic, benzoic, trans-cinnamic, p-coumaric, and caffeic acids) and 5 flavonoids (catechin, kaempferol, naringenin, luteolin, and apigenin) were identified. Among the Malaysian honey samples, Tualang honey had the highest contents of phenolics, and flavonoids, and DPPH radical-scavenging activities. We conclude that among Malaysian honey samples, Tualang honey is the richest in phenolic acids, and flavonoid compounds, which have strong free radical-scavenging activities. © 2011 Institute of Food Technologists®

Anti-gout Potential of Malaysian Medicinal Plants

PubMed Central

Abu Bakar, Fazleen I.; Abu Bakar, Mohd F.; Rahmat, Asmah; Abdullah, Norazlin; Sabran, Siti F.; Endrini, Susi

2018-01-01

Gout is a type of arthritis that causes painful inflammation in one or more joints. In gout, elevation of uric acid in the blood triggers the formation of crystals, causing joint pain. Malaysia is a mega-biodiversity country that is rich in medicinal plants species. Therefore, its flora might offer promising therapies for gout. This article aims to systematically review the anti-gout potential of Malaysian medicinal plants. Articles on gout published from 2000 to 2017 were identified using PubMed, Scopus, ScienceDirect, and Google Scholar with the following keyword search terms: “gout,” “medicinal plants,” “Malaysia,” “epidemiology,” “in vitro,” and “in vivo.” In this study, 85 plants were identified as possessing anti-gout activity. These plants had higher percentages of xanthine oxidase inhibitory activity (>85%); specifically, the Momordica charantia, Chrysanthemum indicum, Cinnamomum cassia, Kaempferia galanga, Artemisia vulgaris, and Morinda elliptica had the highest values, due to their diverse natural bioactive compounds, which include flavonoids, phenolics, tannin, coumarins, luteolin, and apigenin. This review summarizes the anti-gout potential of Malaysian medicinal plants but the mechanisms, active compounds, pharmacokinetics, bioavailability, and safety of the plants still remain to be elucidated. PMID:29628890

Antidiabetic Properties, Bioactive Constituents, and Other Therapeutic Effects of Scoparia dulcis.

PubMed

Pamunuwa, Geethi; Karunaratne, D Nedra; Waisundara, Viduranga Y

2016-01-01

This review discusses the antidiabetic activities of Scoparia dulcis as well as its antioxidant and anti-inflammatory properties in relation to the diabetes and its complications. Ethnomedical applications of the herb have been identified as treatment for jaundice, stomach problems, skin disease, fever, and kidney stones, reproductory issues, and piles. Evidence has been demonstrated through scientific studies as to the antidiabetic effects of crude extracts of S. dulcis as well as its bioactive constituents. The primary mechanisms of action of antidiabetic activity of the plant and its bioactive constituents are through α-glucosidase inhibition, curbing of PPAR-γ and increased secretion of insulin. Scoparic acid A, scoparic acid D, scutellarein, apigenin, luteolin, coixol, and glutinol are some of the compounds which have been identified as responsible for these mechanisms of action. S. dulcis has also been shown to exhibit analgesic, antimalarial, hepatoprotective, sedative, hypnotic, antiulcer, antisickling, and antimicrobial activities. Given this evidence, it may be concluded that S. dulcis could be promoted among the masses as an alternative and complementary therapy for diabetes, provided further scientific studies on the toxicological and pharmacological aspects are carried out through either in vivo or clinical means.

Antidiabetic Properties, Bioactive Constituents, and Other Therapeutic Effects of Scoparia dulcis

PubMed Central

Karunaratne, D. Nedra

2016-01-01

This review discusses the antidiabetic activities of Scoparia dulcis as well as its antioxidant and anti-inflammatory properties in relation to the diabetes and its complications. Ethnomedical applications of the herb have been identified as treatment for jaundice, stomach problems, skin disease, fever, and kidney stones, reproductory issues, and piles. Evidence has been demonstrated through scientific studies as to the antidiabetic effects of crude extracts of S. dulcis as well as its bioactive constituents. The primary mechanisms of action of antidiabetic activity of the plant and its bioactive constituents are through α-glucosidase inhibition, curbing of PPAR-γ and increased secretion of insulin. Scoparic acid A, scoparic acid D, scutellarein, apigenin, luteolin, coixol, and glutinol are some of the compounds which have been identified as responsible for these mechanisms of action. S. dulcis has also been shown to exhibit analgesic, antimalarial, hepatoprotective, sedative, hypnotic, antiulcer, antisickling, and antimicrobial activities. Given this evidence, it may be concluded that S. dulcis could be promoted among the masses as an alternative and complementary therapy for diabetes, provided further scientific studies on the toxicological and pharmacological aspects are carried out through either in vivo or clinical means. PMID:27594892

Phenolic Compounds in Extra Virgin Olive Oil Stimulate Human Osteoblastic Cell Proliferation.

PubMed

García-Martínez, Olga; De Luna-Bertos, Elvira; Ramos-Torrecillas, Javier; Ruiz, Concepción; Milia, Egle; Lorenzo, María Luisa; Jimenez, Brigida; Sánchez-Ortiz, Araceli; Rivas, Ana

2016-01-01

In this study, we aimed to clarify the effects of phenolic compounds and extracts from different extra virgin olive oil (EVOO) varieties obtained from fruits of different ripening stages on osteoblast cells (MG-63) proliferation. Cell proliferation was increased by hydroxytyrosol, luteolin, apigenin, p-coumaric, caffeic, and ferulic acids by approximately 11-16%, as compared with controls that were treated with one vehicle alone, while (+)-pinoresinol, oleuropein, sinapic, vanillic acid and derivative (vanillin) did not affect cell proliferation. All phenolic extracts stimulated MG-63 cell growth, and they induced higher cell proliferation rates than individual compounds. The most effective EVOO phenolic extracts were those obtained from the Picual variety, as they significantly increased cell proliferation by 18-22%. Conversely, Arbequina phenolic extracts increased cell proliferation by 9-13%. A decline in osteoblast proliferation was observed in oils obtained from olive fruits collected at the end of the harvest period, as their total phenolic content decreases at this late stage. Further research on the signaling pathways of olive oil phenolic compounds involved in the processes and their metabolism should be carried out to develop new interventions and adjuvant therapies using EVOO for bone health (i.e.osteoporosis) in adulthood and the elderly.

Phytochemicals for the Management of Melanoma.

PubMed

Pal, Harish Chandra; Hunt, Katherine Marchiony; Diamond, Ariana; Elmets, Craig A; Afaq, Farrukh

2016-01-01

Melanoma claims approximately 80% of skin cancer-related deaths. Its life-threatening nature is primarily due to a propensity to metastasize. The prognosis for melanoma patients with distal metastasis is bleak, with median survival of six months even with the latest available treatments. The most commonly mutated oncogenes in melanoma are BRAF and NRAS accounting approximately 60% and 20% of cases, respectively. In malignant melanoma, accumulating evidence suggests that multiple signaling pathways are constitutively activated and play an important role in cell proliferation, cell survival, epithelial to mesenchymal transition, metastasis and resistance to therapeutic regimens. Phytochemicals are gaining considerable attention because of their low toxicity, low cost, and public acceptance as dietary supplements. Cell culture and animals studies have elucidated several cellular and molecular mechanisms by which phytochemicals act in the prevention and treatment of metastatic melanoma. Several promising phytochemicals, such as, fisetin, epigallocatechin-3-gallate, resveratrol, curcumin, proanthocyanidins, silymarin, apigenin, capsaicin, genistein, indole-3-carbinol, and luteolin are gaining considerable attention and found in a variety of fresh fruits, vegetables, roots, and herbs. In this review, we will discuss the preventive potential, therapeutic effects, bioavailability and structure activity relationship of these selected phytochemicals for the management of melanoma.

Apigenin promotes TRAIL-mediated apoptosis regardless of ROS generation.

PubMed

Kang, Chang-Hee; Molagoda, Ilandarage Menu Neelaka; Choi, Yung Hyun; Park, Cheol; Moon, Dong-Oh; Kim, Gi-Young

2018-01-01

Apigenin is a bioactive flavone in several herbs including parsley, thyme, and peppermint. Apigenin possesses anti-cancer and anti-inflammatory properties; however, whether apigenin enhances TRAIL-mediated apoptosis in cancer cells is unknown. In the current study, we found that apigenin enhanced TRAIL-induced apoptosis by promoting caspase activation and death receptor 5 (DR5) expression and a chimeric antibody against DR5 completely blocked the apoptosis. Apigenin also upregulated reactive oxygen species (ROS) generation; however, intriguingly, ROS inhibitors, glutathione (GSH) or N-acetyl-l-cysteine (NAC), moderately increased apigenin/TRAIL-induced apoptosis. Additional results showed that an autophagy inducer, rapamycin, enhanced apigenin/TRAIL-mediated apoptosis by a slight increase of ROS generation. Accordingly, NAC and GSH rather decreased apigenin-induced autophagy formation, suggesting that apigenin-induced ROS generation increased autophagy formation. However, autophagy inhibitors, bafilomycin (BAF) and 3-methyladenine (3-MA), showed different result in apigenin/TRAIL-mediated apoptosis without ROS generation. 3-MA upregulated the apoptosis but remained ROS levels; however, no changes on apoptosis and ROS generation were observed by BAF treatment. Taken together, these findings reveal that apigenin enhances TRAIL-induced apoptosis by activating apoptotic caspases by upregulating DR5 expression regardless of ROS generation, which may be a promising strategy for an adjuvant of TRAIL. Copyright © 2017 Elsevier Ltd. All rights reserved.

Competitive binding experiments can reduce the false positive results of affinity-based ultrafiltration-HPLC: A case study for identification of potent xanthine oxidase inhibitors from Perilla frutescens extract.

PubMed

Wang, Zhiqiang; Kwon, Shin Hwa; Hwang, Seung Hwan; Kang, Young-Hee; Lee, Jae-Yong; Lim, Soon Sung

2017-03-24

The purpose of this study was to assess the possibility of using competitive binding experiments with ultrafiltration-HPLC analysis to identify potent xanthine oxidase (XO) inhibitors from the Perilla frutescens extract as an attempt to reduce the number of false positive results. To isolate the enzyme-ligand complex from unbound compounds, the P. frutescens extract was either incubated in the absence of XO, in the presence of XO, or with the active site blocked XO before the ultrafiltration was performed. Allopurinaol was used as the XO active site blocker. The unbound compounds were subjected to HPLC analysis. The degree of total binding (TBD) and degree of specific binding (SBD) of each compound were calculated using the peak areas. TBD represents the binding affinities of compounds from the P. frutescens extract for the XO binding site. SBD represents the XO competitive binding between allopurinol and ligands from the extract samples. Two criteria were applied to select putative targets that could help avoid false positives. These include TBD>30% and SBD>10%. Using that approach, kaempferol-3-O-rutinoside, rosmarinic acid, methyl-rosmarinic acid, apigenin, and 4',5,7-trimethoxyflavone were identified, from total 11 compounds, as potent XO inhibitors. Finally, apigenin, 4',5,7-trimethoxyflavone, and luteolin were XO inhibitors verified through an XO inhibition assay and structural simulation of the complex. These results showed that the newly developed strategy has the advantage that the number of targets identified via ultrafiltration-HPLC can be narrowed from many false positives. However, not all false positives can be eliminated with this approach. Some potent inhibitors might also be excluded with the use of this method. The limitations of this method are also discussed herein. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterization of phenolic compounds in green and red oak-leaf lettuce cultivars by UHPLC-DAD-ESI-QToF/MS using MSE scan mode.

PubMed

Viacava, Gabriela E; Roura, Sara I; Berrueta, Luis A; Iriondo, Carmen; Gallo, Blanca; Alonso-Salces, Rosa M

2017-12-01

Lettuce (Lactuca sativa) is one of the most popular leafy vegetables in the world and constitutes a major dietary source of phenolic compounds with health-promoting properties. In particular, the demand for green and red oak-leaf lettuces has considerably increased in the last years but few data on their polyphenol composition are available. Moreover, the usage of analytical edge technology can provide new structural information and allow the identification of unknown polyphenols. In the present study, the phenolic profiles of green and red oak-leaf lettuce cultivars were exhaustively characterized by ultrahigh-performance liquid chromatography (UHPLC) coupled online to diode array detection (DAD), electrospray ionization (ESI), and quadrupole time-of-flight mass spectrometry (QToF/MS), using the MS E instrument acquisition mode for recording simultaneously exact masses of precursor and fragment ions. One hundred fifteen phenolic compounds were identified in the acidified hydromethanolic extract of freeze-dried lettuce leaves. Forty-eight of these compounds were tentatively identified for the first time in lettuce, and only 20 of them have been previously reported in oak-leaf lettuce cultivars in literature. Both oak-leaf lettuce cultivars presented similar phenolic composition, except for apigenin-glucuronide and dihydroxybenzoic acid, only detected in the green cultivar; and for luteolin-hydroxymalonylhexoside, an apigenin conjugate with molecular formula C 40 H 54 O 19 (monoisotopic MW = 838.3259 u), cyanidin-3-O-glucoside, cyanidin-3-O-(3″-O-malonyl)glucoside, cyanidin-3-O-(6″-O-malonyl)glucoside, and cyanidin-3-O-(6″-O-acetyl)glucoside, only found in the red cultivar. The UHPLC-DAD-ESI-QToF/MS E approach demonstrated to be a useful tool for the characterization of phenolic compounds in complex plant matrices. Copyright © 2017 John Wiley & Sons, Ltd.

Anti-Inflammatory Activity of Butein and Luteolin Through Suppression of NFκB Activation and Induction of Heme Oxygenase-1.

PubMed

Sung, Jeehye; Lee, Junsoo

2015-05-01

Butein and luteolin are members of the flavonoid family, which displays a variety of biological activities. In this study, we demonstrated that butein and luteolin exert anti-inflammatory activities in RAW264.7 macrophages by inducing heme oxygenase-1 (HO-1) expression. Butein and luteolin dose-dependently attenuated inducible nitric oxide synthase (iNOS) expression, leading to the suppression of iNOS-derived nitric oxide (NO) production. The inhibitory effect of butein on NO production was greater than that of luteolin. Consistent with this finding, butein also showed higher inhibitory effects on lipopolysaccharide (LPS)-induced translocation of nuclear factor κB (NFκB) and NFκB reporter gene activity in macrophages than luteolin. Furthermore, the expression of HO-1 was dose-dependently induced by butein and luteolin treatments in macrophages. Additionally, the anti-inflammatory activities of butein and luteolin involved the induction of HO-1 expression, as confirmed by the zinc protoporphyrin (ZnPP) treatment (HO-1 selective inhibitor) and HO-1 small interfering (si)RNA system. ZnPP-mediated downregulation and siRNA-mediated knockdown of HO-1 significantly abolished the inhibitory effects of butein and luteolin on the production of NO in LPS-induced macrophages. Consequently, butein and luteolin were shown to be effective HO-1 inducers capable of inhibiting macrophage-derived proinflammatory mechanisms. These findings indicate that butein and luteolin are potential therapeutic agents for the treatment of inflammatory diseases.

Apigenin inhibits renal cell carcinoma cell proliferation

PubMed Central

Meng, Shuai; Zhu, Yi; Li, Jiang-Feng; Wang, Xiao; Liang, Zhen; Li, Shi-Qi; Xu, Xin; Chen, Hong; Liu, Ben; Zheng, Xiang-Yi; Xie, Li-Ping

2017-01-01

Apigenin, a natural flavonoid found in vegetables and fruits, has antitumor activity in several cancer types. The present study evaluated the effects and mechanism of action of apigenin in renal cell carcinoma (RCC) cells. We found that apigenin suppressed ACHN, 786-0, and Caki-1 RCC cell proliferation in a dose- and time-dependent manner. A comet assay suggested that apigenin caused DNA damage in ACHN cells, especially at higher doses, and induced G2/M phase cell cycle arrest through ATM signal modulation. Small interfering RNA (siRNA)-mediated p53 knockdown showed that apigenin-induced apoptosis was likely p53 dependent. Apigenin anti-proliferative effects were confirmed in an ACHN cell xenograft mouse model. Apigenin treatment reduced tumor growth and volume in vivo, and immunohistochemical staining revealed lower Ki-67 indices in tumors derived from apigenin-treated mice. These findings suggest that apigenin exposure induces DNA damage, G2/M phase cell cycle arrest, p53 accumulation and apoptosis, which collectively suppress ACHN RCC cell proliferation in vitro and in vivo. Given its antitumor effects and low in vivo toxicity, apigenin is a highly promising agent for treatment of RCC. PMID:28423637

Resveratrol as a Bioenhancer to Improve Anti-Inflammatory Activities of Apigenin

PubMed Central

Lee, Jin-Ah; Ha, Sang Keun; Cho, EunJung; Choi, Inwook

2015-01-01

The aim of this study was to improve the anti-inflammatory activities of apigenin through co-treatment with resveratrol as a bioenhancer of apigenin. RAW 264.7 cells pretreated with hepatic metabolites formed by the co-metabolism of apigenin and resveratrol (ARMs) in HepG2 cells were stimulated with lipopolysaccharide (LPS). ARMs prominently inhibited (p < 0.05) the production of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin (IL)-1β, IL-6 and TNF-α. Otherwise no such activity was observed by hepatic metabolites of apigenin alone (AMs). ARMs also effectively suppressed protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Co-administration of apigenin (50 mg/kg) and resveratrol (25 mg/kg) also showed a significant reduction of carrageenan-induced paw edema in mice (61.20% to 23.81%). Co-administration of apigenin and resveratrol led to a 2.39 fold increase in plasma apigenin levels compared to administration of apigenin alone, suggesting that co-administration of resveratrol could increase bioavailability of apigenin. When the action of resveratrol on the main apigenin metabolizing enzymes, UDP-glucuronosyltransferases (UGTs), was investigated, resveratrol mainly inhibited the formation of apigenin glucuronides by UGT1A9 in a non-competitive manner with a Ki value of 7.782 μM. These results suggested that resveratrol helps apigenin to bypass hepatic metabolism and maintain apigenin’s anti-inflammatory activities in the body. PMID:26610561

Stimulation of Fas/FasL-mediated apoptosis by luteolin through enhancement of histone H3 acetylation and c-Jun activation in HL-60 leukemia cells.

PubMed

Wang, Shih-Wei; Chen, Yun-Ru; Chow, Jyh-Ming; Chien, Ming-Hsien; Yang, Shun-Fa; Wen, Yu-Ching; Lee, Wei-Jiunn; Tseng, Tsui-Hwa

2018-07-01

Luteolin (3',4',5,7-tetrahydroxyflavone), which exists in fruits, vegetables, and medicinal herbs, is used in Chinese traditional medicine for treating various diseases, such as hypertension, inflammatory disorders, and cancer. However, the gene-regulatory role of luteolin in cancer prevention and therapy has not been clarified. Herein, we demonstrated that treatment with luteolin resulted in a significant decrease in the viability of human leukemia cells. In the present study, by evaluating fragmentation of DNA and poly (ADP-ribose) polymerase (PARP), we found that luteolin was able to induce PARP cleavage and nuclear fragmentation as well as an increase in the sub-G 0 /G 1 fraction. In addition, luteolin also induced Fas and Fas ligand (FasL) expressions and subsequent activation of caspases-8 and -3, which can trigger the extrinsic apoptosis pathway, while knocking down Fas-associated protein with death domain (FADD) prevented luteolin-induced PARP cleavage. Immunoblot and chromatin immunoprecipitation (ChIP) analyses revealed that luteolin increased acetylation of histone H3, which is involved in the upregulation of Fas and FasL. Moreover, both the extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) pathways are involved in luteolin-induced histone H3 acetylation. Finally, luteolin also activated the c-Jun signaling pathway, which contributes to FasL, but not Fas, gene expression and downregulation of c-Jun expression by small interfering RNA transfection which resulted in a significant decrease in luteolin-induced PARP cleavage. Thus, our results demonstrate that luteolin induced apoptosis of HL-60 cells, and this was associated with c-Jun activation and histone H3 acetylation-mediated Fas/FasL expressions. © 2018 Wiley Periodicals, Inc.

Quantification of major compounds from Ixeris dentata, Ixeris dentata Var. albiflora, and Ixeris sonchifolia and their comparative anti-inflammatory activity in lipopolysaccharide-stimulated RAW 264.7 cells.

PubMed

Karki, Subash; Park, Hee-Juhn; Nugroho, Agung; Kim, Eon Ji; Jung, Hyun Ah; Choi, Jae Sue

2015-01-01

The aim of the present study was to evaluate the comparative anti-inflammatory activities of Ixeris dentata (ID), Ixeris dentata var. albiflora (IDA), and Ixeris sonchifolia (IS) and to identify the main compounds present in extracts. The anti-inflammatory activity was evaluated through lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 murine macrophages. Five main compounds consisting of chlorogenic acid, caffeic acid, luteolin 7-O-glucoside, luteolin 7-O-glucuronide, and luteolin were used for simultaneous high-performance liquid chromatography quantification. The total phenolic content present in ID (30 mg/g GAE), IDA (35.33 mg/g GAE), and IS (43.79 mg/g GAE) was correlated to the corresponding LPS-induced NO production inhibitory effect in RAW 264.7 cells as expressed with IC(50) values 26.19, 21.43, and 7.59 μg/mL, respectively. Luteolin 7-O-glucoside was found as the major compound in ID (8.76 mg/g dry weight) and IDA (10.35 mg/g dry weight) and luteolin 7-O-glucuronide was the major compound in IS (34.66 mg/g dry weight). Luteolin 7-O-glucoside and luteolin 7-O-glucuronide inhibited LPS-induced NO production with IC(50) values of 30 and 4.5 μM, respectively. Furthermore, luteolin, luteolin 7-O-glucoside, and luteolin 7-O-glucuronide suppressed the expression of iNOS and COX-2, and t-BHP-induced ROS generation in LPS-stimulated RAW 264.7 cells. These results clearly showed that the anti-inflammatory potential of ID, IDA, and IS extract are primarily due to their contents of luteolin 7-O-glucoside and luteolin 7-O-glucuronide, respectively.

Luteolin and its inhibitory effect on tumor growth in systemic malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kapoor, Shailendra, E-mail: shailendrakapoor@yahoo.com

2013-04-01

Lamy et al have provided interesting data in their recent article in your esteemed journal. Luteolin augments apoptosis in a number of systemic malignancies. Luteolin reduces tumor growth in breast carcinomas. Luteolin mediates this effect by up-regulating the expression of Bax and down-regulating the expression of Bcl-xL. EGFR-induced MAPK activation is also attenuated. As a result there is increased G2/ M phase arrest. These effects have been seen both in vivo as well as in vitro. It also reduces ERα expression and causes inhibition of IGF-1 mediated PI3K–Akt pathway. Luteolin also activates p38 resulting in nuclear translocation of the apoptosis-inducingmore » factor. Simultaneously it also activates ERK. As a result there is increased intra-tumoral apoptosis which is caspase dependent as well as caspase independent. - Highlights: ► Luteolin and tumor growth in breast carcinomas. ► Luteolin and pulmonary cancer. ► Luteolin and colon cancer.« less

Luteolin inhibits Cr(VI)-induced malignant cell transformation of human lung epithelial cells by targeting ROS mediated multiple cell signaling pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pratheeshkumar, Poyil; Son, Young-Ok; Divya, Sasidharan Padmaja

Hexavalent chromium [Cr(VI)] is a well-known human carcinogen associated with the incidence of lung cancer. Inhibition of metal induced carcinogenesis by a dietary antioxidant is a novel approach. Luteolin, a natural dietary flavonoid found in fruits and vegetables, possesses potent antioxidant and anti-inflammatory activity. We found that short term exposure of human bronchial epithelial cells (BEAS-2B) to Cr(VI) (5 μM) showed a drastic increase in ROS generation, NADPH oxidase (NOX) activation, lipid peroxidation, and glutathione depletion, which were significantly inhibited by the treatment with luteolin in a dose dependent manner. Treatment with luteolin decreased AP-1, HIF-1α, COX-2, and iNOS promotermore » activity induced by Cr(VI) in BEAS-2B cells. In addition, luteolin protected BEAS-2B cells from malignant transformation induced by chronic Cr(VI) exposure. Moreover, luteolin also inhibited the production of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α) and VEGF in chronic Cr(VI) exposed BEAS-2B cells. Western blot analysis showed that luteolin inhibited multiple gene products linked to survival (Akt, Fak, Bcl-2, Bcl-xL), inflammation (MAPK, NF-κB, COX-2, STAT-3, iNOS, TNF-α) and angiogenesis (HIF-1α, VEGF, MMP-9) in chronic Cr(VI) exposed BEAS-2B cells. Nude mice injected with BEAS-2B cells chronically exposed to Cr(VI) in the presence of luteolin showed reduced tumor incidence compared to Cr(VI) alone treated group. Overexpression of catalase (CAT) or SOD2, eliminated Cr(VI)-induced malignant transformation. Overall, our results indicate that luteolin protects BEAS-2B cells from Cr(VI)-induced carcinogenesis by scavenging ROS and modulating multiple cell signaling mechanisms that are linked to ROS. Luteolin, therefore, serves as a potential chemopreventive agent against Cr(VI)-induced carcinogenesis. - Highlights: • Luteolin inhibited Cr(VI)-induced oxidative stress. • Luteolin inhibited chronic Cr(VI)-induced malignant transformation. • Luteolin inhibited chronic Cr(VI)-induced inflammation. • Luteolin inhibited chronic Cr(VI)-induced angiogenesis.« less

Apigenin induces apoptosis in human leukemia cells and exhibits anti-leukemic activity in vivo via inactivation of Akt and activation of JNK

PubMed Central

Budhraja, Amit; Gao, Ning; Zhang, Zhuo; Son, Young-Ok; Cheng, Senping; Wang, Xin; Ding, Songze; Hitron, Andrew; Chen, Gang; Luo, Jia; Shi, Xianglin

2015-01-01

In this study, we investigated the functional role of Akt and JNK signaling cascades in apigenin-induced apoptosis in U937 human leukemia cells and anti-leukemic activity of apigenin in vivo. Apigenin-induced apoptosis by inactivation of Akt with a concomitant activation of JNK, Mcl-1 and Bcl-2 down-regulation, cytochrome c release from mitochondria and activation of caspases. Constitutively active myristolated Akt prevented apigenin-induced JNK, caspases activation, and apoptosis. Conversely, LY294002 and a dominant negative construct of Akt potentiated apigenin-induced apoptosis in leukemia cells. Interruption of JNK pathway showed marked reduction in apigenin-induced caspases activation and apoptosis in leukemia cells. Furthermore, in vivo administration of apigenin resulted in attenuation of tumor growth in U937 xenografts accompanied inactivation of Akt and activation of JNK. Attenuation of tumor growth in U937 xenografts by apigenin raises the possibility that apigenin may have clinical implications and can be further tested for incorporating in leukemia treatment regimens. PMID:22084167

Anthocyanins and flavonols are responsible for purple color of Lablab purpureus (L.) sweet pods.

PubMed

Cui, Baolu; Hu, Zongli; Zhang, Yanjie; Hu, Jingtao; Yin, Wencheng; Feng, Ye; Xie, Qiaoli; Chen, Guoping

2016-06-01

Lablab pods, as dietary vegetable, have high nutritional values similar to most of edible legumes. Moreover, our studies confirmed that purple lablab pods contain the natural pigments of anthocyanins and flavonols. Compared to green pods, five kinds of anthocyanins (malvidin, delphinidin and petunidin derivatives) were found in purple pods by HPLC-ESI-MS/MS and the major contents were delphinidin derivatives. Besides, nine kinds of polyphenol derivatives (quercetin, myricetin, kaempferol and apigenin derivatives) were detected by UPLC-ESI-MS/MS and the major components were quercetin and myricetin derivatives. In order to discover their molecular mechanism, expression patterns of biosynthesis and regulatory gens of anthocyanins and flavonols were investigated. Experimental results showed that LpPAL, LpF3H, LpF3'H, LpDFR, LpANS and LpPAP1 expressions were significantly induced in purple pods compared to green ones. Meanwhile, transcripts of LpFLS were more abundant in purple pods than green or yellow ones, suggestind that co-pigments of anthocyanins and flavonols are accumulated in purple pods. Under continuously dark condition, no anthocyanin accumulation was detected in purple pods and transcripts of LpCHS, LpANS, LpFLS and LpPAP1 were remarkably repressed, indicating that anthocyanins and flavonols biosynthesis in purple pods was regulated in light-dependent manner. These results indicate that co-pigments of anthocyanins and flavonols contribute to purple pigmentations of pods. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Flavonoid content in leaf extracts of the fig (Ficus carica L.), carob (Ceratonia siliqua L.) and pistachio (Pistacia lentiscus L.).

PubMed

Vaya, Jacob; Mahmood, Saeed

2006-01-01

The total flavonoid content of leaf extracts (70% ethanol) from fig (Ficus carica L.), carob (Ceratonia siliqua L.) and pistachio (Pistacia lentiscus L.) plants were determined by using reverse phase high-performance liquid chromatography (HPLC)-and analyzed by UV/VIS array and electrospray ionization (ESI)-mass spectrometry (MS) detectors. As a base for comparison, flavonoid type and level were also determined in extracts from soybeans and grape seeds. It was found that the major flavonoids in Ficus are quercetin and luteolin, with a total of 631 and 681 mg/kg extract, respectively. In Ceratonia leaves, nine different flavonoids were detected. The major one was myricetin (1486 mg/kg extract), with a similar level in Pistacia (1331 mg/kg extract, myricetin). The present study is the first to report the presence of the isoflavone genistein in the Pistacia leaf, which was discovered to consist of about a third of the genistein level detected in soybean.

Investigation of flavonoids bearing different substituents on ring C and their cu2+ complex binding with bovine serum albumin: structure-affinity relationship aspects.

PubMed

Shi, Shuyun; Zhang, Yuping; Chen, Xiaoqin; Peng, Mijun

2011-10-12

The effects of 1:1 flavonoid-Cu(2+) complexes of four flavonoids with different C-ring substituents, quercetin (QU), luteolin (LU), taxifolin (TA), and (+)-catechin (CA), on bovine serum albumin (BSA) were investigated and compared with corresponding free flavonoids by spectroscopic analysis in an attempt to characterize the chemical association taking place. The results indicated that all of the quenching mechanisms were based on static quenching combined with nonradiative energy transfer. Cu(2+) chelation changed the binding constants for BSA depending on the structures of flavonoids and the detected concentrations. The reduced hydroxyl groups, increased steric hindrance, and hydrophilicity of Cu(2+) chelation may be the main reasons for the reduced binding constants, whereas the formation of stable flavonoid-Cu(2+) complexes and synergistic action could increase the binding constants. The changed trends of critical energy transfer distance (R(0)) for Cu(2+) chelation were contrary to those of binding constants.

Ultrasound assisted extraction of polyphenols and their distribution in whole mung bean, hull and cotyledon.

PubMed

Singh, Barinderjit; Singh, Narpinder; Thakur, Sheetal; Kaur, Amritpal

2017-03-01

In this study, extraction of polyphenols using different solvents (acetone, ethanol, methanol and water) with ultrasound and conventional method from whole mung bean (WMB), hull and cotyledon was conducted. Total phenolic content (TPC), total flavonoids content (TFC), total antioxidant activities (TAA), ferric reducing power (FRP) and DPPH radical scavenging activity were determined. Ultrasound treated extracts exhibited higher TPC, TFC, TAA, FRP and DPPH in different mung bean fractions than CSE. Among the solvents, acetone showed better TPC, TFC, TAA, FRP and DPPH. Hull had significantly higher TPC, TFC, TAA, FRP and DPPH than WMB and cotyledon. Sinapic acid (SA) was the major polyphenol in different fractions. Acetone extract of hull showed high polyphenol content. SA, ferulic acid, catechin, p-coumaric acid, resveratrol, quercetin and luteolin were the major contributors to antioxidant activity of acetone extract. Mung bean hull contained the maximum polyphenols and acetone was observed to be the best extraction medium for polyphenols in combination with ultrasound.

Carrier-mediated uptake of nobiletin, a citrus polymethoxyflavonoid, in human intestinal Caco-2 cells.

PubMed

Kimura, Osamu; Ohta, Chiho; Koga, Nobuyuki; Haraguchi, Koichi; Kato, Yoshihisa; Endo, Tetsuya

2014-07-01

The mechanism of intestinal absorption of nobiletin (NBL) was investigated using Caco-2 cells. The uptake of NBL from the apical membranes of Caco-2 cells was rapid and temperature-dependent and the presence of metabolic inhibitors, NaN3 and carbonylcyanide p-trifluoromethoxyphenylhydrazone, did not cause a decrease in NBL uptake. The relationship between the initial uptake of NBL and its concentration was saturable, suggesting the involvement of a carrier-mediated process. The Km and uptake clearance (Vmax/Km) values for NBL were 50.6 and 168.1μl/mg protein/min, respectively. This clearance value was about 9-fold greater than that of the non-saturable uptake clearance (Kd: 18.5μl/mg protein/min). The presence of structurally similar compounds, such as quercetin and luteolin, competitively inhibited NBL uptake. These results suggest that uptake of NBL from the apical membranes of Caco-2 cells is mainly mediated by an energy-independent facilitated diffusion process. Copyright © 2013 Elsevier Ltd. All rights reserved.

Identification of nonvolatile compounds in clove (Syzygium aromaticum) from Manado

NASA Astrophysics Data System (ADS)

Fathoni, A.; Saepudin, E.; Cahyana, A. H.; Rahayu, D. U. C.; Haib, J.

2017-07-01

Syzygium aromaticum (clove) are native to Indonesia and have been widely used in food industry due to their flavor. Nonvolatile compounds contribute to flavor, mainly in their taste. Currently, there is very little information available about nonvolatile compounds in clove. Identification of nonvolatile compounds is important to improve clove's value. Compound extraction was conducted by maceration in ethanol. Fractionations of the extract were performed by using gravity column chromatography on silica gel and Sephadex LH-20 as stationary phase. Nonvolatile compounds were identified by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). LC-MS/MS was operated in negative mode with 0.1 % formic acid in water and acetonitrile as mobile phase. Nonvolatile compounds were identified by fragment analysis and compared to references. Several compounds had been identified and characterized asquinic acid, monogalloylglucose, gallic acid, digalloylglucose, isobiflorin, biflorin, ellagic acid, hydroxygallic acid, luteolin, quercetin, naringenin, kaempferol, isorhamnetin, dimethoxyluteolin, and rhamnetin. These compounds had two main flavor perceptions, i.e. astringent, and bitter.

Cellular Antioxidant Effect of Four Bromophenols from the Red Algae, Vertebrata lanosa

PubMed Central

Olsen, Elisabeth K.; Hansen, Espen; Isaksson, Johan; Andersen, Jeanette H.

2013-01-01

Three known bromophenols, 2,3-dibromo-4,5-dihydroxybenzylaldehyde (1), 2,2′,3-tribromo-3′,4,4′,5-tetrahydroxy-6′-hydroxymethyldiphenylmethane (2) and bis(2,3-dibromo-4,5-dihydroxylbenzyl) ether (3), and one new one, 5,5″-oxybis(methylene)bis(3-bromo-4-(2′,3′-dibromo-4′,5′-dihydroxylbenzyl)benzene-1,2-diol) (4), were isolated from an extract of the red alga, Vertebrata lanosa. The antioxidant activity of these four bromophenols was examined using one biochemical and two cellular assays: Oxygen Radical Absorbance Capacity (ORAC), Cellular Antioxidant Activity (CAA) and Cellular Lipid Peroxidation Antioxidant Activity (CLPAA) assays. Compound 2 distinguished itself by showing potent activity, having a better antioxidant effect than luteolin in both the CAA and CLPAA assays and of quercetin in the CLPAA assay. Although several bromophenols are known to be potent antioxidants in biochemical assays, this is the first time their cellular antioxidant activity has been demonstrated. PMID:23921722

Apigenin Impacts the Growth of the Gut Microbiota and Alters the Gene Expression of Enterococcus.

PubMed

Wang, Minqian; Firrman, Jenni; Zhang, Liqing; Arango-Argoty, Gustavo; Tomasula, Peggy; Liu, LinShu; Xiao, Weidong; Yam, Kit

2017-08-03

Apigenin is a major dietary flavonoid with many bioactivities, widely distributed in plants. Apigenin reaches the colon region intact and interacts there with the human gut microbiota, however there is little research on how apigenin affects the gut bacteria. This study investigated the effect of pure apigenin on human gut bacteria, at both the single strain and community levels. The effect of apigenin on the single gut bacteria strains Bacteroides galacturonicus , Bifidobacterium catenulatum , Lactobacillus rhamnosus GG, and Enterococcus caccae , was examined by measuring their anaerobic growth profiles. The effect of apigenin on a gut microbiota community was studied by culturing a fecal inoculum under in vitro conditions simulating the human ascending colon. 16S rRNA gene sequencing and GC-MS analysis quantified changes in the community structure. Single molecule RNA sequencing was used to reveal the response of Enterococcus caccae to apigenin. Enterococcus caccae was effectively inhibited by apigenin when cultured alone, however, the genus Enterococcus was enhanced when tested in a community setting. Single molecule RNA sequencing found that Enterococcus caccae responded to apigenin by up-regulating genes involved in DNA repair, stress response, cell wall synthesis, and protein folding. Taken together, these results demonstrate that apigenin affects both the growth and gene expression of Enterococcus caccae .

SDF7, a group of Scoparia dulcis Linn. derived flavonoid compounds, stimulates glucose uptake and regulates adipocytokines in 3T3-F442a adipocytes.

PubMed

Beh, Joo Ee; Khoo, Li Teng; Latip, Jalifah; Abdullah, Mohd Paud; Alitheen, Noorjahan Baru Mohamed; Adam, Zainah; Ismail, Amin; Hamid, Muhajir

2013-10-28

Adipocytes are major tissues involved in glucose uptake second to skeletal muscle and act as the main adipocytokines mediator that regulates glucose uptake mechanism and cellular differentiation. The objective of this study were to examine the effect of the SDF7, which is a fraction consists of four flavonoid compounds (quercetin: p-coumaric acid: luteolin: apigenin=8: 26: 1: 3) from Scoparia dulcis Linn., on stimulating the downstream components of insulin signalling and the adipocytokines expression on different cellular fractions of 3T3-F442a adipocytes. Morphology and lipid accumulation of differentiated 3T3-F442a adipocytes by 100 nM insulin treated with different concentrations of SDF7 and rosiglitazone were examined followed by the evaluation of glucose uptake activity expressions of insulin signalling downstream components (IRS-1, PI3-kinase, PKB, PKC, TC10 and GLUT4) from four cellular fractions (plasma membrane, cytosol, high density microsome and low density microsome). Next, the expression level of adipocytokines (TNF-α, adiponectin and leptin) and immunoblotting of treated 3T3-F442 adipocytes was determined at 30 min and 480 min. Glucose transporter 4 (GLUT4) translocation of 3T3-F442a adipocytes membrane was also determined. Lastly, mRNA expression of adiponectin and PPAR-γ of 3T3-F442a adipocytes were induced and compared with basal concentration. It was found that SDF7 was able to induce adipocytes differentiation with great extends of morphological changes, lipid synthesis and lipid stimulation in vitro. SDF7 stimulation of glucose transport on 3T3-F442a adipocytes are found to be dose independent, time-dependent and plasma membrane GLUT4 expression-dependent. Moreover, SDF7 are observed to be able to suppress TNF-α and leptin expressions that were mediated by 3T3-F442a adipocytes, while stimulated adiponectin secretion on the cells. There was a significant expression (p<0.01) of protein kinase C and small G protein TC10 on 3T3-F442a adipocytes upon treatment with SDF7 as compared to the control. SDF7 was also found to be effective in stimulating adiponectin and PPAR-γ mRNA upregulation at 50 µg/ml. SDF7 exhibited good lipogenesis, adiponectinesis and glucose uptake stimulatory properties on 3T3-F442a adipocytes. © 2013 Elsevier Ireland Ltd. All rights reserved.

Protective Effects of Apigenin Against Paraquat-Induced Acute Lung Injury in Mice.

PubMed

Luan, Rui-Ling; Meng, Xiang-Xi; Jiang, Wei

2016-04-01

This study aimed to investigate the protective effects of apigenin against paraquat (PQ)-induced acute lung injury (ALI) in mice. Male Kunming mice were randomly divided into five groups: group 1 (control), group 2 (PQ), group 3 (PQ + apigenin 25 mg/kg), group 4 (PQ + apigenin 50 mg/kg), and group 5 (PQ + apigenin 100 mg/kg). The PQ + apigenin group received apigenin by gavage daily for consecutive 7 days, respectively, while the mice in control and PQ groups were given an equivalent volume of saline. We detected the lung wet/dry weight ratios and the histopathology of the lung. The levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were determined using enzyme-linked immunosorbent assay (ELISA) kits. The activity of nuclear factor (NF)-κB was also determined. The results indicated that apigenin administration decreased biochemical parameters of inflammation and oxidative stress, and improved oxygenation and lung edema in a dose-dependent manner. These protective effects of apigenin were associated with inhibition of NF-κB. In conclusion, apigenin reduces PQ-induced ALI by inhibition of inflammation and oxidative stress.

Luteolin inhibits the Nrf2 signaling pathway and tumor growth in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chian, Song; Thapa, Ruby; Chi, Zhexu

Highlights: • Luteolin inhibits the Nrf2 pathway in mouse liver and in xenografted tumors. • Luteolin markedly inhibits the growth of xenograft tumors. • Luteolin enhances the anti-cancer effect of cisplatin in mice in vivo. • Luteolin could serve as an adjuvant in the chemotherapy of NSCLC. - Abstract: Nuclear factor erythroid 2-related factor 2 (Nrf2) is over-expressed in many types of tumor, promotes tumor growth, and confers resistance to anticancer therapy. Hence, Nrf2 is regarded as a novel therapeutic target in cancer. Previously, we reported that luteolin is a strong inhibitor of Nrf2 in vitro. Here, we showed thatmore » luteolin reduced the constitutive expression of NAD(P)H quinone oxidoreductase 1 in mouse liver in a time- and dose-dependent manner. Further, luteolin inhibited the expression of antioxidant enzymes and glutathione transferases, decreasing the reduced glutathione in the liver of wild-type mice under both constitutive and butylated hydroxyanisole-induced conditions. In contrast, such distinct responses were not detected in Nrf2{sup −/−} mice. In addition, oral administration of luteolin, either alone or combined with intraperitoneal injection of the cytotoxic drug cisplatin, greatly inhibited the growth of xenograft tumors from non-small-cell lung cancer (NSCLC) cell line A549 cells grown subcutaneously in athymic nude mice. Cell proliferation, the expression of Nrf2, and antioxidant enzymes were all reduced in tumor xenograft tissues. Furthermore, luteolin enhanced the anti-cancer effect of cisplatin. Together, our findings demonstrated that luteolin inhibits the Nrf2 pathway in vivo and can serve as an adjuvant in the chemotherapy of NSCLC.« less

Novel stilbenoids, including cannabispiradienone glycosides, from Tragopogon tommasinii (Asteraceae, Cichorieae) and their potential anti-inflammatory activity.

PubMed

Granica, Sebastian; Piwowarski, Jakub P; Randazzo, Antonio; Schneider, Peter; Żyżyńska-Granica, Barbara; Zidorn, Christian

2015-09-01

A phytochemical investigation of Tragopogon tommasinii Sch.Bip. (Asteraceae, Cichorieae) yielded a total of 21 natural products, two simple phenolic acids (4-hydroxybenzoic acid and p-coumaric acid), four caffeic acid derivatives (chlorogenic acid, 3-O-caffeoylquinic acid, 3,5-O-dicaffeoylquinic acid, and 4,5-O-dicaffeoylquinic acid), six flavonoids (luteolin, luteolin 7-O-glucoside, vitexin, orientin, quercetin 3-O-glucoside, and isorhamnetin 3-O-glucoside), three simple bibenzyls [2-carboxyl-5-hydroxy-3-methoxy-4'-β-glucopyranosyl-oxybibenzyl, 3-caffeoyl-(9→5)-β-apiosyl-(1→6)-β-glucopyranosyloxy-5,4'-dihydroxy-3'-methoxybibenzyl, 3-caffeoyl-(9→5)-β-apiosyl-(1→6)-β-glucopyranosyloxy-4'-dihydroxy-5,3'-dimethoxybibenzyl], three phtalides [3-(4-β-glucopyranosyloxybenzyl)-7-hydroxy-5-methoxyphtalide, 7-β-glucopyranosyloxy-(S)-3-(4-hydroxybenzyl)-5-methoxyphtalide, and 7-(1→6)-α-rhamnosyl-β-glucopyranosyloxy-(S)-3-(4-hydroxybenzyl)-5-methoxyphtalide], two cannabispiradienone derivatives [3-O-β-glucopyranosyldemethoxycannabispiradienone and 3-caffeoyl-(9→5)-β-apiosyl-(1→6)-β-glucopyranosyloxydemethoxycannabispiradienone], and tetra-N-coumaroyl spermine. The three bibenzyls, the latter two benzylphthalides, and both cannabispiradienone derivatives represent new natural compounds and all compounds, except the caffeic acid derivatives and the flavonoids were new for T. tommasinii. The structures were established by HR mass spectrometry, extensive 1D and 2D NMR spectroscopy, and CD spectroscopy. Moreover, the potential anti-inflammatory activities of the new compounds were assayed using human neutrophils and their production of IL-1b, IL-8, TNF-α and MMP-9 as well as the expression of TLR-4, respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

Apigenin sensitizes BEL-7402/ADM cells to doxorubicin through inhibiting miR-101/Nrf2 pathway

PubMed Central

Gao, Ai-Mei; Zhang, Xiao-Yu; Ke, Zun-Ping

2017-01-01

Chemo-resistance is one of the main obstacle in hepatocellular carcinoma therapy. Apigenin as a natural bioflavonoid has been exhibited anti-cancer properties in various malignant cancers. The aim of this study is to evaluate the potential chemo-sensitization effect of apigenin in doxorubicin-resistant hepatocellular carcinoma cell line BEL-7402/ADM and to investigate its possible mechanism. We found that apigenin significantly reversed doxorubicin sensitivity and induced caspase-dependent apoptosis in BEL-7402/ADM cells. Furthermore, apigenin induced miR-101 expression, and overexpression of miR-101 mimicked the doxorubicin-sensitizing effect of apigenin. Importantly, we showed that miR-101 was able to target the 3′-UTR of Nrf2. The results suggested that apigenin sensitizes BEL-7402/ADM cells to doxorubicin through miR-101/Nrf2 pathway, which furtherly supports apigenin as a potential chemo-sensitizer for hepatocellular carcinoma. PMID:29137246

Apigenin reverses depression-like behavior induced by chronic corticosterone treatment in mice.

PubMed

Weng, Lianjin; Guo, Xiaohua; Li, Yang; Yang, Xin; Han, Yuanyuan

2016-03-05

Previous researches found that apigenin exerted antidepressant-like effects in rodents. However, it is unclear whether the neurotrophic system is involved in the antidepressant-like effects of apigenin. Our present study aimed to explore the neurotrophic related mechanism of apigenin in depressive-like mice induced by chronic corticosterone treatment. Mice were repeatedly injected with corticosterone (40 mg/kg) subcutaneously (s.c) once daily for consecutive 21 days. Apigenin (20 and 40 mg/kg) and fluoxetine (20 mg/kg) were administered 30 min prior to the corticosterone injection. The behavioral tests indicated that apigenin reversed the reduction of sucrose preference and the elevation of immobility time in mice induced by chronic corticosterone treatment. In addition, the increase in serum corticosterone levels and the decrease in hippocampal brain-derived neurotrophic factor (BDNF) levels in corticosterone-treated mice were also ameliorated by apigenin administration. Taken together, our findings intensively confirmed the antidepressant-like effects of apigenin and indicated that the antidepressant-like mechanism of apigenin was mediated, at least partly by up-regulation of BDNF levels in the hippocampus. Copyright © 2016 Elsevier B.V. All rights reserved.

Inhibition of Epstein-Barr virus reactivation by the flavonoid apigenin.

PubMed

Wu, Chung-Chun; Fang, Chih-Yeu; Cheng, Yu-Jhen; Hsu, Hui-Yu; Chou, Sheng-Ping; Huang, Sheng-Yen; Tsai, Ching-Hwa; Chen, Jen-Yang

2017-01-05

Lytic reactivation of EBV has been reported to play an important role in human diseases, including NPC carcinogenesis. Inhibition of EBV reactivation is considered to be of great benefit in the treatment of virus-associated diseases. For this purpose, we screened for inhibitory compounds and found that apigenin, a flavonoid, seemed to have the ability to inhibit EBV reactivation. We performed western blotting, immunofluorescence and luciferase analyses to determine whether apigenin has anti-EBV activity. Apigenin inhibited expression of the EBV lytic proteins, Zta, Rta, EAD and DNase in epithelial and B cells. It also reduced the number of EBV-reactivating cells detectable by immunofluorescence analysis. In addition, apigenin has been found to reduce dramatically the production of EBV virions. Luciferase reporter analysis was performed to determine the mechanism by which apigenin inhibits EBV reactivation: apigenin suppressed the activity of the immediate-early (IE) gene Zta and Rta promoters, suggesting it can block initiation of the EBV lytic cycle. Taken together, apigenin inhibits EBV reactivation by suppressing the promoter activities of two viral IE genes, suggesting apigenin is a potential dietary compound for prevention of EBV reactivation.

Dietary apigenin attenuates the development of atopic dermatitis-like skin lesions in NC/Nga mice.

PubMed

Yano, Satomi; Umeda, Daisuke; Yamashita, Shuya; Yamada, Koji; Tachibana, Hirofumi

2009-11-01

One of the flavones, apigenin has various physiological functions including anti-inflammatory activities. Atopic dermatitis (AD) is a chronically relapsing inflammatory disorder that is characterized by pruritic and eczematous skin lesions. To evaluate the anti-allergic effect of apigenin in vivo, we examined the effect of dietary apigenin on picrylchloride (PiCl)-induced AD-like pathology in NC/Nga mice. NC/Nga mice were fed experimental diets containing apigenin from Day 18 after sensitized with PiCl for 4 weeks. Dietary apigenin significantly alleviated the development of skin lesions, accompanied by lower serum immunoglobulin (Ig) G1 and IgE levels in NC/Nga mice. Interferon (IFN)-gamma mRNA expression level in spleen cells from NC/Nga mice was reduced by apigenin feeding. Moreover, interleukin 4-induced signal transducers and activators of transcription 6 phosphorylation in primary spleen cells from BALB/c mice was inhibited by treatment with apigenin. These results suggest that apigenin attenuates exacerbation of AD-like symptoms in part through the reduction of serum IgE level and IFN-gamma expression in NC/Nga mice.

Combined in Vitro Cell-Based/in Silico Screening of Naturally Occurring Flavonoids and Phenolic Compounds as Potential Anti-Alzheimer Drugs.

PubMed

Espargaró, Alba; Ginex, Tiziana; Vadell, Maria Del Mar; Busquets, Maria A; Estelrich, Joan; Muñoz-Torrero, Diego; Luque, F Javier; Sabate, Raimon

2017-02-24

Alzheimer's disease (AD) is the main cause of dementia in people over 65 years. One of the major culprits in AD is the self-aggregation of amyloid-β peptide (Aβ), which has stimulated the search for small molecules able to inhibit Aβ aggregation. In this context, we recently reported a simple, but effective in vitro cell-based assay to evaluate the potential antiaggregation activity of putative Aβ aggregation inhibitors. In this work this assay was used together with docking and molecular dynamics simulations to analyze the anti-Aβ aggregation activity of several naturally occurring flavonoids and phenolic compounds. The results showed that rosmarinic acid, melatonin, and o-vanillin displayed zero or low inhibitory capacity, curcumin was found to have an intermediate inhibitory potency, and apigenin and quercetin showed potent antiaggregation activity. Finally, the suitability of the combined in vitro cell-based/in silico approach to distinguish between active and inactive compounds was further assessed for an additional set of flavonols and dihydroflavonols.

Phytochemical screening, anticancer and antioxidant activities of Origanum vulgare L. ssp. viride (Boiss.) Hayek, a plant of traditional usage.

PubMed

Koldaş, Serkan; Demirtas, Ibrahim; Ozen, Tevfik; Demirci, Mehmet Ali; Behçet, Lütfi

2015-03-15

A detailed phytochemical analysis of Origanum vulgare L. ssp. viride (Boiss.) Hayek was carried out and the antioxidant activities of five different crude extracts were determined. The antiproliferative activities of the extracts were determined using the xCELLigence system (Real Time Cell Analyzer). Differences between the essential oil and volatile organic compound profiles of the plant were shown. The main component of the essential oil was caryophyllene oxide, while the main volatile organic compounds were sabinene and eucalyptol as determined by HS-GC/MS. Phenolic contents of the extracts were determined qualitatively and quantitatively by HPLC/TOF-MS. Ten phenolic compounds were found in the extracts from O. vulgare and Origanum acutidens: rosmarinic acid (in highest abundance), chicoric acid, caffeic acid, p-coumaric acid, gallic acid, quercetin, apigenin-7-glucoside, kaempferol, naringenin and 4-hydroxybenzaldehyde. This study provides first results on the antiproliferative and antioxidant properties and detailed phytochemical screening of O. vulgare ssp. viride (Boiss.) Hayek. © 2014 Society of Chemical Industry.

The investigation of some bioactive compounds and antioxidant properties of hawthorn (Crataegus monogyna subsp. monogyna Jacq)

PubMed Central

Keser, Serhat; Celik, Sait; Turkoglu, Semra; Yilmaz, Ökkes; Turkoglu, Ismail

2014-01-01

Aim: The antioxidant and pharmacological effects of hawthorn have mainly been attributed to the polyphenolic contents. The aim of this research is to determine some bioactive compounds and antioxidant properties of hawthorn aqueous and ethanol extracts of leaves, flowers, and ripened fruits. Materials and Methods: For this purpose, antioxidant activities of extracts were assessed on DPPH•, ABTS•+, superoxide scavenging, reducing power and ferrous metal chelating activity assays and phenolic content of extracts was determined by Folin—Cioacalteu’s reagent. Results: The flavonoids including rutin, apigenin, myricetin, quercetin, naringenin and kaempferol, were identified by high-performance liquid chromatography in the hawthorn extract. Conclusion: It was observed the aqueous and ethanol extracts of Crataegus monogyna subsp. monogyna fruits showed the highest activity in reducing power and metal chelating activity assays. In addition, it was determined that the aqueous flower extract showed higher flavonoid content than aqueous leaves extract. The antioxidant and pharmacological effects of hawthorn have mainly been attributed to the polyphenolic contents. PMID:26401347

Flavonoids Affect the Light Reaction of Photosynthesis in Vitro and in Vivo as Well as the Growth of Plants.

PubMed

Morales-Flores, Félix; Olivares-Palomares, Karen Susana; Aguilar-Laurents, María Isabel; Rivero-Cruz, José Fausto; Lotina-Hennsen, Blas; King-Díaz, Beatriz

2015-09-23

Flavonoids retusin (5-hydroxy-3,7,3',4'-tetramethoxyflavone) (1) and pachypodol (5,4'-dihydroxy-3,7,3'-trimethoxyflavone) (2) were isolated from Croton ciliatoglanduliferus Ort. Pachypodol acts as a Hill reaction inhibitor with its target on the water splitting enzyme located in PSII. In the search for new herbicides from natural compounds, flavonoids 1 and 2 and flavonoid analogues quercetin (3), apigenin (4), genistein (5), and eupatorin (6) were assessed for their effect in vitro on the photosynthetic electron transport chain and in vivo on the germination and growth of the plants Physalis ixocarpa, Trifolium alexandrinum and Lolium perenne. Flavonoid 3 was the most active inhibitor of the photosynthetic uncoupled electron flow (I50 = 114 μM) with a lower log P value (1.37). Results in vivo suggest that 1, 2, 3, and 5 behave as pre- and postemergent herbicides, with 3 and 5 being more active.

The investigation of some bioactive compounds and antioxidant properties of hawthorn (Crataegus monogyna subsp. monogyna Jacq).

PubMed

Keser, Serhat; Celik, Sait; Turkoglu, Semra; Yilmaz, Ökkes; Turkoglu, Ismail

2014-01-01

The antioxidant and pharmacological effects of hawthorn have mainly been attributed to the polyphenolic contents. The aim of this research is to determine some bioactive compounds and antioxidant properties of hawthorn aqueous and ethanol extracts of leaves, flowers, and ripened fruits. For this purpose, antioxidant activities of extracts were assessed on DPPH•, ABTS•+, superoxide scavenging, reducing power and ferrous metal chelating activity assays and phenolic content of extracts was determined by Folin-Cioacalteu's reagent. The flavonoids including rutin, apigenin, myricetin, quercetin, naringenin and kaempferol, were identified by high-performance liquid chromatography in the hawthorn extract. It was observed the aqueous and ethanol extracts of Crataegus monogyna subsp. monogyna fruits showed the highest activity in reducing power and metal chelating activity assays. In addition, it was determined that the aqueous flower extract showed higher flavonoid content than aqueous leaves extract. The antioxidant and pharmacological effects of hawthorn have mainly been attributed to the polyphenolic contents.

Dietary flavonoid luteolin attenuates uropathogenic Escherichia. Coli invasion of the urinary bladder.

PubMed

Shen, Xiao-Fei; Teng, Yan; Sha, Kai-Hui; Wang, Xin-Yuan; Yang, Xiao-Long; Guo, Xiao-Juan; Ren, Lai-Bin; Wang, Xiao-Ying; Li, Jingyu; Huang, Ning

2016-11-12

Uropathogenic Escherichia coli (UPEC), the primary uropathogen, adhere to and invade bladder epithelial cells (BECs) to establish a successful urinary tract infection (UTI). Emerging antibiotic resistance requires novel nonantibiotic strategies. Our previous study indicated that luteolin attenuated adhesive and invasive abilities as well as cytotoxicity of UPEC on T24 BECs through down-regulating UPEC virulence factors. The aims of this study were to investigate the possible function of the flavonoid luteolin and the mechanisms by which luteolin functions in UPEC-induced bladder infection. Firstly, obvious reduction of UPEC invasion but not adhesion were observed in luteolin-pretreated 5637 and T24 BECs sa well as mice bladder via colony counting. The luteolin-mediated suppression of UPEC invasion was linked to elevated levels of intracellular cAMP induced by inhibiting the activity of cAMP-phosphodiesterases (cAMP-PDEs), which resulting activation of protein kinase A, thereby negatively regulating Rac1-GTPase-mediated actin polymerization. Furthermore, p38 MAPK was primarily and ERK1/2 was partially involved in luteolin-mediated suppression of UPEC invasion and actin polymerization, as confirmed with chemical activators of p38 MAPK and ERK1/2. These data suggest that luteolin can protect bladder epithelial cells against UPEC invasion. Therefore, luteolin or luteolin-rich products as dietary supplement may be beneficial to control the UPEC-related bladder infections, and cAMP-PDEs may be a therapy target for UTIs treatment. © 2016 BioFactors, 42(6):674-685, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

Induction apoptosis of luteolin in human hepatoma HepG2 cells involving mitochondria translocation of Bax/Bak and activation of JNK

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, H.-J.; Wang, C.-J.; Kuo, H.-C.

2005-03-01

Since hepatocellular carcinoma remains a major challenging clinical problem in many parts of the world including Eastern Asia and Southern Africa, it is imperative to develop more effective chemopreventive and chemotherapy agents. Herein, we present an investigation regarding the anticancer potential of luteolin, a natural flavonoid, and the mechanism of its action in human hepatoma HepG2 cells. Using DNA fragmentation assay and nuclear staining assay, it showed that luteolin induced apoptosis of HepG2 cells. Luteolin induced the cytosolic release of cytochrome c and activated CPP32. We found that Bax and Bak translocated to mitochondria apparently, whereas Fas ligand (FasL) wasmore » unchanged after a treatment with luteolin for 3 h. In addition, it showed that c-Jun NH{sub 2}-terminal kinase (JNK) was activated after the treatment of luteolin for 3-12 h. Further investigation showed that a specific JNK inhibitor, SP600125, reduced the activation of CPP 32, the mitochondrial translocation of Bax, as well as the cytosolic release of cytochrome c that induced by luteolin. Finally, the apoptosis induced by luteolin was suppressed by a pretreatment with SP600125 via evaluating annexin V-FITC binding assay. These data suggest that luteolin induced apoptosis via mechanisms involving mitochondria translocation of Bax/Bak and activation of JNK.« less

Apigenin sensitizes colon cancer cells to anti-tumor activity of ABT-263

PubMed Central

Shao, Huanjie; Jing, Kai; Mahmoud, Esraa; Huang, Haihong; Fang, Xianjun; Yu, Chunrong

2013-01-01

Apigenin is an edible plant-derived flavonoid that shows modest anti-tumor activities in vitro and in vivo. Apigenin treatment resulted in cell growth arrest and apoptosis in various types of tumors by modulating several signaling pathways. In the present study, we evaluated interactions between apigenin and ABT-263 in colon cancer cells. We observed a synergistic effect between apigenin and ABT-263 on apoptosis of colon cancer cells. ABT-263 alone induced limited cell death while upregulating expression of Mcl-1, a potential mechanism for the acquired resistance to ABT-263. The presence of apigenin antagonized ABT-263-induced Mcl-1 upregulation and dramatically enhanced ABT-263-induced cell death. Meanwhile, apigenin suppressed AKT and ERK activation. Inactivation of either AKT or ERK by lentivirus-transduced shRNA or treatment with specific small molecule inhibitors of these pathways enhanced ABT-263-induced cell death, mirroring the effect of apigenin. Moreover, the combination response was associated with upregulation of Bim and activation of Bax. Downregulation of Bax eliminated the synergistic effect of apigenin and ABT-263 on cell death. Xenograft studies in SCID mice showed that the combined treatment with apigenin and ABT-263 inhibited tumor growth by up to 70% without obvious adverse effects, while either agent only inhibited around 30%. Our results demonstrate a novel strategy to enhance ABT-263 induced anti-tumor activity in human colon cancer cells by apigenin via inhibition of the Mcl-1, AKT and ERK pro-survival regulators. PMID:24126433

Flavonoid Apigenin Inhibits Lipopolysaccharide-Induced Inflammatory Response through Multiple Mechanisms in Macrophages

PubMed Central

Zhang, Xiaoxuan; Wang, Guangji; Gurley, Emily C.; Zhou, Huiping

2014-01-01

Background Apigenin is a non-toxic natural flavonoid that is abundantly present in common fruits and vegetables. It has been reported that apigenin has various beneficial health effects such as anti-inflammation and chemoprevention. Multiple studies have shown that inflammation is an important risk factor for atherosclerosis, diabetes, sepsis, various liver diseases, and other metabolic diseases. Although it has been long realized that apigenin has anti-inflammatory activities, the underlying functional mechanisms are still not fully understood. Methodology and Principal Findings In the present study, we examined the effect of apigenin on LPS-induced inflammatory response and further elucidated the potential underlying mechanisms in human THP-1-induced macrophages and mouse J774A.1 macrophages. By using the PrimePCR array, we were able to identify the major target genes regulated by apigenin in LPS-mediated immune response. The results indicated that apigenin significantly inhibited LPS-induced production of pro-inflammatory cytokines, such as IL-6, IL-1β, and TNF-α through modulating multiple intracellular signaling pathways in macrophages. Apigenin inhibited LPS-induced IL-1β production by inhibiting caspase-1 activation through the disruption of the NLRP3 inflammasome assembly. Apigenin also prevented LPS-induced IL-6 and IL-1β production by reducing the mRNA stability via inhibiting ERK1/2 activation. In addition, apigenin significantly inhibited TNF-α and IL-1β-induced activation of NF-κB. Conclusion and Significance Apigenin Inhibits LPS-induced Inflammatory Response through multiple mechanisms in macrophages. These results provided important scientific evidences for the potential application of apigenin as a therapeutic agent for inflammatory diseases. PMID:25192391

Apigenin in the regulation of cholesterol metabolism and protection of blood vessels

PubMed Central

Zhang, Kun; Song, Wei; Li, Dalin; Jin, Xing

2017-01-01

Hyperlipidemia is a major independent risk factor for atherosclerosis. Seeking natural compounds in medicinal plants capable of reducing blood fat and studying their mechanisms of action has been the focus of research in recent years. The aim of the present study was to analyze the mechanisms of apigenin in regulating cholesterol metabolism and protecting blood vessels, and to provide a theoretical basis for the clinical application of apigenin. The mouse model of hyperlipidemia was established to verify the efficacy of apigenin in improving hyperlipidemia and to observe the mechanism of action of apigenin in reducing cholesterol content. In vitro cell experiments were conducted to evaluate the role of apigenin in mediating reverse cholesterol transport. Additionally, H2O2-injured human umbilical venous endothelial cells (EA.hy926 cells) were used for further study on the roles of apigenin in resisting oxidization and protecting vascular endothelial cells. Apigenin significantly regulated blood fat, reduced animal weight, and reduced total cholesterol (P=0.024), triglyceride (P=0.031) and low-density lipoprotein cholesterol (P=0.014) in the serum of the high-fat diet mice. Apigenin improved the blood lipid metabolism of the hyper-lipidemia model mice. Body weight and serum cholesterol content increased abnormally (P=0.003) as a consequence of high-fat diet. Apigenin increased the activity of superoxide dismutase in EA.hy926 cells (P=0.043) and increased the amount of nitric oxide secreted by the cells (P=0.038). Apigenin also inhibited the proliferation of vascular smooth muscle cells in a dose-dependent manner (P=0.036). In conclusion, apigenin can regulate cholesterol metabolism in vivo and plays a role in reducing the level of blood fat by promoting cholesterol absorption and conversion, and accelerating reverse cholesterol transport. Apigenin also has a role in resisting oxidization and protecting blood vessels. PMID:28565758

Apigenin in the regulation of cholesterol metabolism and protection of blood vessels.

PubMed

Zhang, Kun; Song, Wei; Li, Dalin; Jin, Xing

2017-05-01

Hyperlipidemia is a major independent risk factor for atherosclerosis. Seeking natural compounds in medicinal plants capable of reducing blood fat and studying their mechanisms of action has been the focus of research in recent years. The aim of the present study was to analyze the mechanisms of apigenin in regulating cholesterol metabolism and protecting blood vessels, and to provide a theoretical basis for the clinical application of apigenin. The mouse model of hyperlipidemia was established to verify the efficacy of apigenin in improving hyperlipidemia and to observe the mechanism of action of apigenin in reducing cholesterol content. In vitro cell experiments were conducted to evaluate the role of apigenin in mediating reverse cholesterol transport. Additionally, H 2 O 2 -injured human umbilical venous endothelial cells (EA.hy926 cells) were used for further study on the roles of apigenin in resisting oxidization and protecting vascular endothelial cells. Apigenin significantly regulated blood fat, reduced animal weight, and reduced total cholesterol (P=0.024), triglyceride (P=0.031) and low-density lipoprotein cholesterol (P=0.014) in the serum of the high-fat diet mice. Apigenin improved the blood lipid metabolism of the hyper-lipidemia model mice. Body weight and serum cholesterol content increased abnormally (P=0.003) as a consequence of high-fat diet. Apigenin increased the activity of superoxide dismutase in EA.hy926 cells (P=0.043) and increased the amount of nitric oxide secreted by the cells (P=0.038). Apigenin also inhibited the proliferation of vascular smooth muscle cells in a dose-dependent manner (P=0.036). In conclusion, apigenin can regulate cholesterol metabolism in vivo and plays a role in reducing the level of blood fat by promoting cholesterol absorption and conversion, and accelerating reverse cholesterol transport. Apigenin also has a role in resisting oxidization and protecting blood vessels.

Synergistic Effects of Apigenin and Paclitaxel on Apoptosis of Cancer Cells

PubMed Central

Diao, Ying; Lu, Changyan; Fu, Jin; Luo, Lan; Yin, Zhimin

2011-01-01

Background It was well known that the clinical use of chemotherapeutic drugs is restricted by severe adverse reactions and drug resistances. Thus it is necessary to figure out a strategy to increase the specific anti-tumor efficiency of chemotherapeutic drugs. Apigenin, a kind of flavonoids, has been reported to possess anticancer activities with very low cytotoxicity to normal tissue. Methodology/Principal Findings Our results from cell viability assay, western-blots and TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay demonstrated the synergistic pro-apoptotic effects of a low dose of apigenin and paclitaxel in human cancer cell lines. To analyze the underlying mechanism, we examined reactive oxygen species (ROS) staining after cells were treated with a combination of apigenin and paclitaxel, or each of them alone. Data from flow-cytometry showed that superoxides but not reduction of peroxides accumulated in HeLa cells treated with apigenin or a combination of apigenin and paclitaxel. Apigenin and paclitaxel-induced HeLa cell apoptosis was related to the level of ROS in cells. We further evaluated activity and protein level of superoxide dismutase (SOD). Apigenin significantly inhibited SOD activity but did not alter the SOD protein level suggesting that apigenin promoted ROS accumulation through suppressing enzyme activity of SOD. Addition of Zn2+, Cu2+ and Mn2+ to cell lysates inhibited apigenin's effects on SOD activity. At the same time, data from caspase-2 over-expression and knocked-down experiments demonstrated that caspase-2 participated in apigenin and paclitaxel-induced HeLa cell apoptosis. Conclusions/Significance Taken together, our study demonstrated that apigenin can sensitize cancer cells to paclitaxel induced apoptosis through suppressing SOD activity, which then led to accumulation of ROS and cleavage of caspase-2, suggesting that the combined use of apigenin and paclitaxel was an effective way to decrease the dose of paclitaxel taken. PMID:22216199

Comparison of Antioxidant Constituents of Agriophyllum squarrosum Seed with Conventional Crop Seeds.

PubMed

Xu, Hai-Yan; Zheng, Hua-Chuan; Zhang, Hui-Wen; Zhang, Jin-Yu; Ma, Chao-Mei

2018-06-05

Twelve chemical constituents were identified from the Agriophyllum squarrosum seed (ASS). ASS contained large amounts of flavonoids, which were more concentrated in the seed coat. ASS-coat (1 g) contained 335.7 μg flavonoids of rutin equivalent, which was similar to the flavonoid content in soybean (351.2 μg/g), and greater than that in millet, wheat, rice, peanut, and corn. By LC-MS analysis, the major constituents in ASS were 3-O-[α-L-rhamnopyranosyl-(1→6)-β-D- glucopyranosyl]-7- O-(β-D-glucopyranosyl)-quercetin (1), rutin (4), quercetin-3-O-β-D- apiosyl(1→2)-[α-L-rhamnosyl(l→6)]-β-D-glucoside (2), isorhamnetin-3-O-rutinoside (5), and allantoin (3), compared with isoflavonoids-genistin (16), daidzin (14), and glycitin (18) in soybean. Among constituents in ASS, compounds 1, 2, 4, protocatechuic acid (8), isoquercitrin (11), and luteolin-6-C-glucoside (12) potently scavenged DPPH radicals and intracellular ROS; strongly protected against peroxyl radical-induced DNA scission; and upregulated Nrf2, phosphorylated p38, phosphorylated JNK, and Bcl-2 in HepG2 cells. These results indicate that ASS is rich in antioxidant constituents that can enrich the varieties of food flavonoids, with significant beneficial implications for those who suffer from oxidative stress-related conditions. This study found that A. squarrosum seed contains large amounts of antioxidative flavonoids and compared its chemical constituents with those of conventional foods. These results should increase the interest in planting the sand-fixing A. squarrosum on a large scale, thus preventing desertification and providing valuable foods. © 2018 Institute of Food Technologists®.

Apigenin Attenuates Melanoma Cell Migration by Inducing Anoikis through Integrin and Focal Adhesion Kinase Inhibition.

PubMed

Hasnat, Md Abul; Pervin, Mehnaz; Lim, Ji Hong; Lim, Beong Ou

2015-11-27

Apigenin, a nonmutagenic flavonoid, has been found to have antitumor properties and is therefore particularly relevant for the development of chemotherapeutic agents for cancers. In this study, time- and dose-dependent cell viability and cytotoxicity were assessed to determine the effects of apigenin on A2058 and A375 melanoma cells. Melanoma cells were pretreated with different concentrations of apigenin and analyzed for morphological changes, anoikis induction, cell migration, and levels of proteins associated with apoptosis. Apigenin reduced integrin protein levels and inhibited the phosphorylation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK1/2), which induce anoikis in human cutaneous melanoma cells. Apigenin exhibited dose-dependent inhibition of melanoma cell migration, unlike untreated controls. Furthermore, apigenin treatment increased apoptotic factors such as caspase-3 and cleaved poly(ADP-ribose) polymerase in a dose-dependent manner, demonstrating the metastasis of melanoma cells. Our results provide a new insight into the mechanisms by which apigenin prevents melanoma metastasis by sensitizing anoikis induced by the loss of integrin proteins in the FAK/ERK1/2 signaling pathway. These findings elucidate the related mechanisms and suggest the potential of apigenin in developing clinical treatment strategies against malignant melanoma.

Apigenin exhibits protective effects in a mouse model of d-galactose-induced aging via activating the Nrf2 pathway.

PubMed

Sang, Ying; Zhang, Fan; Wang, Heng; Yao, Jianqiao; Chen, Ruichuan; Zhou, Zhengdao; Yang, Kun; Xie, Yan; Wan, Tianfeng; Ding, Hong

2017-06-21

The aim of the present research was to study the protective effects and underlying mechanisms of apigenin on d-galactose-induced aging mice. Firstly, apigenin exhibited a potent antioxidant activity in vitro. Secondly, d-galactose was administered by subcutaneous injection once daily for 8 weeks to establish an aging mouse model to investigate the protective effect of apigenin. We found that apigenin supplementation significantly ameliorated aging-related changes such as behavioral impairment, decreased organic index, histopathological injury, increased senescence-associated β-galactosidase (SAβ-gal) activity and advanced glycation end product (AGE) level. Further data showed that apigenin facilitated Nrf2 nuclear translocation both in aging mice and normal young mice, and the Nrf2 expression of normal young mice was higher than that of natural senile mice. In addition, the expressions of Nrf2 downstream gene targets, including HO-1 and NQO1, were also promoted by apigenin administration. Moreover, apigenin also decreased the MDA level and elevated SOD and CAT activities. In conclusion, focusing on the Nrf2 pathway is a suitable strategy to delay the aging process, and apigenin may exert an anti-senescent effect process via activating the Nrf2 pathway.

Topical Apigenin Improves Epidermal Permeability Barrier Homeostasis in Normal Murine Skin by Divergent Mechanisms

PubMed Central

Hou, Maihua; Sun, Richard; Hupe, Melanie; Kim, Peggy L.; Park, Kyungho; Crumrine, Debra; Lin, Tzu-kai; Santiago, Juan Luis; Mauro, Theodora M.; Elias, Peter M.; Man, Mao-Qiang

2013-01-01

The beneficial effects of certain herbal medicines on cutaneous function have been appreciated for centuries. Among these agents, Chrysanthemum extract, apigenin, has been used for skin care, particularly in China, for millennia. However, the underlying mechanisms by which apigenin benefits the skin are not known. In the present study, we first determined whether topical apigenin positively influences permeability barrier homeostasis, and then the basis thereof. Hairless mice were treated topically with either 0.1% apigenin or vehicle alone twice-daily for 9 days. At the end of treatments, permeability barrier function was assessed with either an electrolytic water analyzer or a Tewameter. Our results show that topical apigenin significantly enhanced permeability barrier homeostasis after tape stripping, though basal permeability barrier function remained unchanged. Improved barrier function correlated with enhanced filaggrin expression and lamellar body production, which was paralleled by elevated mRNA levels for the epidermal ABCA12. The mRNA levels for key lipid synthetic enzymes also were up-regulated by apigenin. Finally, both CAMP and mBD3 immunostaining were increased by apigenin. We conclude that topical apigenin improves epidermal permeability barrier function by stimulating epidermal differentiation, lipid synthesis and secretion, as well as cutaneous antimicrobial peptide production. Apigenin could be useful for the prevention and treatment of skin disorders characterized by permeability barrier dysfunction, associated with reduced filaggrin levels, and impaired antimicrobial defenses, such as atopic dermatitis. PMID:23489424

Chemopreventive apigenin controls UVB-induced cutaneous proliferation and angiogenesis through HuR and thrombospondin-1

PubMed Central

Veliceasa, Dorina; Bridgeman, Bryan B.; Fitchev, Philip; Cornwell, Mona L.; Crawford, Susan E.; Pelling, Jill C.; Volpert, Olga V.

2014-01-01

Plant flavonoid apigenin prevents and inhibits UVB-induced carcinogenesis in the skin and has strong anti-proliferative and anti-angiogenic properties. Here we identify mechanisms, by which apigenin controls these oncogenic events. We show that apigenin acts, at least in part, via endogenous angiogenesis inhibitor, thrombospondin-1 (TSP1). TSP1 expression by the epidermal keratinocytes is potently inhibited by UVB. It inhibits cutaneous angiogenesis and UVB-induced carcinogenesis. We show that apigenin restores TSP1 in epidermal keratinocytes subjected to UVB and normalizes proliferation and angiogenesis in UVB-exposed skin. Importantly, reconstituting TSP1 anti-angiogenic function in UVB-irradiated skin with a short bioactive peptide mimetic representing exclusively its anti-angiogenic domain reproduced the anti-proliferative and anti-angiogenic effects of apigenin. Cox-2 and HIF-1α are important mediators of angiogenesis. Both apigenin and TSP1 peptide mimetic attenuated their induction by UVB. Finally we identified the molecular mechanism, whereby apigenin did not affect TSP1 mRNA, but increased de novo protein synthesis. Knockdown studies implicated the RNA-binding protein HuR, which controls mRNA stability and translation. Apigenin increased HuR cytoplasmic localization and physical association with TSP1 mRNA causing de novo TSP1 synthesis. HuR cytoplasmic localization was, in turn, dependent on CHK2 kinase. Together, our data provide a new mechanism, by which apigenin controls UVB-induced carcinogenesis. PMID:25526033

Comparative study of anti-angiogenic activities of luteolin, lectin and lupeol biomolecules.

PubMed

Ambasta, Rashmi K; Jha, Saurabh Kumar; Kumar, Dhiraj; Sharma, Renu; Jha, Niraj Kumar; Kumar, Pravir

2015-09-18

Angiogenesis is a hallmark feature in the initiation, progression and growth of tumour. There are various factors for promotion of angiogenesis on one hand and on the other hand, biomolecules have been reported to inhibit cancer through anti-angiogenesis mechanism. Biomolecules, for instance, luteolin, lectin and lupeol are known to suppress cancer. This study aims to compare and evaluate the biomolecule(s) like luteolin, lupeol and lectin on CAM assay and HT-29 cell culture to understand the efficacy of these drugs. The biomolecules have been administered on CAM assay, HT-29 cell culture, cell migration assay. Furthermore, bioinformatics analysis of the identified targets of these biomolecules have been performed. Luteolin has been found to be better in inhibiting angiogenesis on CAM assay in comparison to lupeol and lectin. In line with this study when biomolecules was administered on cell migration assay via scratch assay method. We provided evidence that Luteolin was again found to be better in inhibiting HT-29 cell migration. In order to identify the target sites of luteolin for inhibition, we used software analysis for identifying the best molecular targets of luteolin. Using software analysis best target protein molecule of these biomolecules have been identified. VEGF was found to be one of the target of luteolin. Studies have found several critical point mutation in VEGF A, B and C. Hence docking analysis of all biomolecules with VEGFR have been performed. Multiple allignment result have shown that the receptors are conserved at the docking site. Therefore, it can be concluded that luteolin is not only comparatively better in inhibiting blood vessel in CAM assay, HT-29 cell proliferation and cell migration assay rather the domain of VEGFR is conserved to be targeted by luteolin, lupeol and lectin.

Apigenin impacts growth of the gut microbiota and alters gene expression of Enterococcus

USDA-ARS?s Scientific Manuscript database

Apigenin is a major dietary flavonoid widely distributed in plants with many bioactivities. Apigenin reaches the colon region intact and interacts with the human gut microbiota; however, there is little research on how apigenin affects gut bacteria. This study investigated the effect of pure apigeni...

Luteolin Suppresses Inflammatory Mediator Expression by Blocking the Akt/NFκB Pathway in Acute Lung Injury Induced by Lipopolysaccharide in Mice.

PubMed

Li, Yi-Ching; Yeh, Chung-Hsin; Yang, Ming-Ling; Kuan, Yu-Hsiang

2012-01-01

Acute lung injury (ALI), instilled by lipopolysaccharide (LPS), is a severe illness with excessive mortality and has no specific treatment strategy. Luteolin is an anti-inflammatory flavonoid and widely distributed in the plants. Pretreatment with luteolin inhibited LPS-induced histological changes of ALI and lung tissue edema. In addition, LPS-induced inflammatory responses, including increased vascular permeability, tumor necrosis factor (TNF)-α and interleukin (IL)-6 production, and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), were also reduced by luteolin in a concentration-dependent manner. Furthermore, luteolin suppressed activation of NFκB and its upstream molecular factor, Akt. These results suggest that the protection mechanism of luteolin is by inhibition of NFκB activation possibly via Akt.

Co-ultramicronized Palmitoylethanolamide/Luteolin Promotes the Maturation of Oligodendrocyte Precursor Cells.

PubMed

Barbierato, Massimo; Facci, Laura; Marinelli, Carla; Zusso, Morena; Argentini, Carla; Skaper, Stephen D; Giusti, Pietro

2015-11-18

Oligodendrocytes have limited ability to repair the damage to themselves or to other nerve cells, as seen in demyelinating diseases like multiple sclerosis. An important strategy may be to replace the lost oligodendrocytes and/or promote the maturation of undifferentiated oligodendrocyte precursor cells (OPCs). Recent studies show that a composite of co-ultramicronized N-palmitoylethanolamine (PEA) and luteolin (co-ultramicronized PEA/luteolin, 10:1 by mass) is efficacious in improving outcome in experimental models of spinal cord and traumatic brain injuries. Here, we examined the ability of co-ultramicronized PEA/luteolin to promote progression of OPCs into a more differentiated phenotype. OPCs derived from newborn rat cortex were placed in culture and treated the following day with 10 μM co-ultramicronized PEA/luteolin. Cells were collected 1, 4 and 8 days later and analyzed for expression of myelin basic protein (MBP). qPCR and Western blot analyses revealed a time-dependent increase in expression of both mRNA for MBP and MBP content, along with an increased expression of genes involved in lipid biogenesis. Ultramicronized PEA or luteolin, either singly or in simple combination, were ineffective. Further, co-ultramicronized PEA/luteolin promoted morphological development of OPCs and total protein content without affecting proliferation. Co-ultramicronized PEA/luteolin may represent a novel pharmacological strategy to promote OPC maturation.

Luteolin attenuates TGF-β1-induced epithelial-mesenchymal transition of lung cancer cells by interfering in the PI3K/Akt-NF-κB-Snail pathway.

PubMed

Chen, Kun-Chieh; Chen, Chiu-Yuan; Lin, Chih-Ru; Lin, Chih-Ju; Yang, Tsung-Ying; Chen, Tzu-Hsiu; Wu, Li-Chen; Wu, Chun-Chi

2013-12-05

Luteolin is a natural flavonoid that possesses a variety of pharmacological activities, such as anti-inflammatory and anti-cancer abilities. Whether luteolin regulates the transformation ability of lung cancer cells remains unclear. The current study aims to uncover the effects and underlying mechanisms of luteolin in regulation of and epithelial-mesenchymal transition of lung cancer cells. The lung adenocarcinoma A549 cells were used in this experiment; the cells were pretreated with luteolin followed by administration with TGF-β1. The expression levels of various cadherin and related upstream regulatory modules were examined. Pretreatment of luteolin prevented the morphological change and downregulation of E-cadherin of A549 cells induced by TGF-β1. In addition, the activation of PI3K-Akt-IκBa-NF-κB-Snail pathway which leads to the decline of E-cadherin induced by TGF-β1 was also attenuated under the pretreatment of luteolin. We provide the mechanisms about how luteolin attenuated the epithelial-mesenchymal transition of A549 lung cancer cells induced by TGF-β1. This finding will strengthen the anti-cancer effects of flavonoid compounds via the regulation of migration/invasion and EMT ability of various cancer cells. © 2013.

Acid base chemistry of luteolin and its methyl-ether derivatives: A DFT and ab initio investigation

NASA Astrophysics Data System (ADS)

Amat, Anna; De Angelis, Filippo; Sgamellotti, Antonio; Fantacci, Simona

2008-09-01

The acid-base chemistry of luteolin, a flavonoid with important pharmacological and dyeing properties, and of the related methyl ether derivatives have been investigated by DFT and MP2 methods, testing different computational setups. We calculate the pK's of all the possible deprotonation sites, for which no experimental assignment could be achieved. The calculated pK's deliver a different acidity order for the two most acidic deprotonation sites between luteolin and its methyl ether derivatives, due to intramolecular hydrogen bonding in luteolin. A lowest p Ka of 6.19 is computed for luteolin, in good agreement with available experimental data.

Protective role of apigenin in cisplatin-induced renal injury.

PubMed

He, Xuexiu; Li, Chunmei; Wei, Zhengkai; Wang, Jingjing; Kou, Jinhua; Liu, Weijian; Shi, Mingyu; Yang, Zhengtao; Fu, Yunhe

2016-10-15

This study aimed to investigate the effects and molecular mechanisms of the effects of apigenin on cisplatin (CP)-induced kidney injury in mice. Apigenin was intraperitoneally administered for 3 consecutive days before CP treatment. We found that apigenin pretreatment significantly attenuated the damage to the kidneys and decreased the levels of serum creatinine, blood urea nitrogen (BUN), glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD), which were increased by CP. Apigenin significantly decreased the levels of TNF-α, IL-1β and TGFβ in the kidneys. Additionally, apigenin inhibited the activations of CYP2E1, phospho-NF-κB p65 and phospho-P38 MAPK in CP-induced renal injury. These results suggest that the renoprotective effects of apigenin may be related to the suppressions of oxidative stress and inflammation in CP-induced renal injury in mice. Copyright © 2016 Elsevier B.V. All rights reserved.

Apigenin inhibits TGF-β1-induced proliferation and migration of airway smooth muscle cells.

PubMed

Li, Li-Hua; Lu, Bin; Wu, Hong-Ke; Zhang, Hao; Yao, Fei-Fei

2015-01-01

It is well known that the proliferation and migration of ASM cells (ASMCs) plays an important role in the pathogenesis of airway remodeling in asthma. Previous studies reported that apigenin can inhibit airway remodeling in a mouse asthma model. However, its effects on the proliferation and migration of ASMCs in asthma remain unknown. Therefore, the aim of our present study was to investigate the effects of apigenin on ASMC proliferation and migration, and explore the possible molecular mechanism. We found that apigenin inhibited transforming growth factor-β1 (TGF-β1)-induced ASMC proliferation. The cell cycle was blocked at G1/S-interphase by apigenin. It also suppressed TGF-β1-induced ASMCs migration. Furthermore, apigenin inhibited TGF-β1-induced Smad 2 and Smad 3 phosphorylation in ASMCs. Taken together, these results suggested that apigenin inhibited the proliferation and migration of TGF-β1-stimulated ASMCs by inhibiting Smad signaling pathway. These data might provide useful information for treating asthma and show that apigenin has potential for attenuating airway remodeling.

Inhibition of the STAT3 signaling pathway contributes to apigenin-mediated anti-metastatic effect in melanoma

PubMed Central

Cao, Hui-Hui; Chu, Jian-Hong; Kwan, Hiu-Yee; Su, Tao; Yu, Hua; Cheng, Chi-Yan; Fu, Xiu-Qiong; Guo, Hui; Li, Ting; Tse, Anfernee Kai-Wing; Chou, Gui-Xin; Mo, Huan-Biao; Yu, Zhi-Ling

2016-01-01

Signal transducer and activator of transcription 3 (STAT3) signaling is constantly activated in human melanoma, and promotes melanoma metastasis. The dietary flavonoid apigenin is a bioactive compound that possesses low toxicity and exerts anti-metastatic activity in melanoma. However, the anti-metastasis mechanism of apigenin has not been fully elucidated. In the present study, we showed that apigenin suppressed murine melanoma B16F10 cell lung metastasis in mice, and inhibited cell migration and invasion in human and murine melanoma cells. Further study indicated that apigenin effectively suppressed STAT3 phosphorylation, decreased STAT3 nuclear localization and inhibited STAT3 transcriptional activity. Apigenin also down-regulated STAT3 target genes MMP-2, MMP-9, VEGF and Twist1, which are involved in cell migration and invasion. More importantly, overexpression of STAT3 or Twist1 partially reversed apigenin-impaired cell migration and invasion. Our data not only reveal a novel anti-metastasis mechanism of apigenin but also support the notion that STAT3 is an attractive and promising target for melanoma treatment. PMID:26911838

Apigenin suppresses the senescence-associated secretory phenotype and paracrine effects on breast cancer cells.

PubMed

Perrott, Kevin M; Wiley, Christopher D; Desprez, Pierre-Yves; Campisi, Judith

2017-04-01

Apigenin (4',5,7,-trihydroxyflavone) is a flavonoid found in certain herbs, fruits, and vegetables. Apigenin can attenuate inflammation, which is associated with many chronic diseases of aging. Senescent cells-stressed cells that accumulate with age in mammals-display a pro-inflammatory senescence-associated secretory phenotype (SASP) that can drive or exacerbate several age-related pathologies, including cancer. Flavonoids, including apigenin, were recently shown to reduce the SASP of a human fibroblast strain induced to senesce by bleomycin. Here, we confirm that apigenin suppresses the SASP in three human fibroblast strains induced to senesce by ionizing radiation, constitutive MAPK (mitogen-activated protein kinase) signaling, oncogenic RAS, or replicative exhaustion. Apigenin suppressed the SASP in part by suppressing IL-1α signaling through IRAK1 and IRAK4, p38-MAPK, and NF-κB. Apigenin was particularly potent at suppressing the expression and secretion of CXCL10 (IP10), a newly identified SASP factor. Further, apigenin-mediated suppression of the SASP substantially reduced the aggressive phenotype of human breast cancer cells, as determined by cell proliferation, extracellular matrix invasion, and epithelial-mesenchymal transition. Our results support the idea that apigenin is a promising natural product for reducing the impact of senescent cells on age-related diseases such as cancer.

Apigenin induced apoptosis in esophageal carcinoma cells by destruction membrane structures.

PubMed

Zhu, Haiyan; Jin, Hua; Pi, Jiang; Bai, Haihua; Yang, Fen; Wu, Chaomin; Jiang, Jinhuan; Cai, Jiye

2016-07-01

Apigenin has shown to have killing effects on some kinds of solid tumor cells. However, the changes in cell membrane induced by apigenin on subcellular- or nanometer-level were still unclear. In this work, human esophageal cancer cells (EC9706 and KYSE150 cells) were employed as cell model to detect the cytotoxicity of apigenin, including cell growth inhibition, apoptosis induction, membrane toxicity, etc. MTT assay showed that apigenin could remarkably inhibit the growth and proliferation in both types of cells. Annexin V/PI-based flow cytometry analysis showed that the cytotoxic effects of apigenin in KYSE150 cells were mainly through early apoptosis induction, while in EC9706 cells, necrosis, and apoptosis were both involved in cell death. The morphological and ultrastructural properties induced by apigenin were investigated at single cellular- or nanometer-level using atomic force microscopy (AFM). Additionally, lactate dehydrogenase (LDH) leakage was measured to assess the changes in membrane permeability. The results indicated that apigenin increased the membrane permeability and caused leakage of LDH, which was consistent with damages on membrane ultrastructure detected by AFM. Therefore, membrane toxicity, including membrane ultrastructure damages and enhanced membrane permeability, played vital roles in apigenin induced human esophageal cancer cell apoptosis. SCANNING 38:322-328, 2016. © 2015 Wiley Periodicals, Inc. © Wiley Periodicals, Inc.

Phytochemical Composition and Antibacterial Activity of Hydroalcoholic Extracts of Pterospartum tridentatum and Mentha pulegium against Staphylococcus aureus Isolates

PubMed Central

Aires, Alfredo; Marrinhas, Eduardo; Carvalho, Rosa; Dias, Carla; Saavedra, Maria José

2016-01-01

Pterospartum tridentatum and Mentha pulegium are largely used in Portuguese folk medicine to treat several human disorders and inflammatory processes but without any consistent evidence for those beneficial pointed properties. Thus, the aim of the current work is to evaluate its benefits and phytochemicals related to those beneficial properties. A distinct polyphenol profile between P. tridentatum and M. pulegium was found. Taxifolin, myricetin, ginestin, ginestein, and ginestein derivatives, biochanin A-glucoside, and biochanin A were identified in P. tridentatum, whilst in M. pulegium the luteolin-7-rutinoside, diosmin, and apigenin and respective derivatives were most representative polyphenols. These variations had implications in the antiradical and antibacterial activity and the P. tridentatum exhibited the highest antibacterial activity against methicillin-resistant and methicillin-sensitive Staphylococcus aureus MSSA, which was mainly dose-dependent. This antibacterial activity seems to be related to high content of flavonols, flavones, and isoflavones, which can act synergistically with each other against this type of bacteria. Our results showed consistent evidence that Pterospartum tridentatum and Mentha pulegium are an important reservoir of phytochemicals with antiradical activity and antibacterial capacity and thus they might be used in a preventive way or in a combined pharmaceutical and antibiotic therapy against pathogenic bacteria. PMID:27190990

Production of methoxylated flavonoids in yeast using ring A hydroxylases and flavonoid O-methyltransferases from sweet basil.

PubMed

Berim, Anna; Gang, David R

2018-07-01

Numerous methoxylated flavonoids exhibit pronounced bioactivities. Their biotechnological production and diversification are therefore of interest to pharmaceutical and nutraceutical industries. We used a set of enzymes from sweet basil (Ocimum basilicum) to construct five strains of Saccharomyces cerevisiae producing 8- and/or 6-substituted, methoxylated flavones from their natural precursor apigenin. After identifying several growth parameters affecting the overall yields and flux, we applied optimized conditions and explored the ability of the generated strains to utilize alternative substrates. The yeast cells produced substantial amounts of 6-hydroxylated, methylated derivatives of naringenin and luteolin while the corresponding derivatives of flavonol kaempferol were only detected in trace amounts. Analysis of the intermediates and by-products of the different bioconversions suggested that the substrate specificity of both the hydroxylases and the flavonoid O-methyltransferases is imposing barriers on yields obtained with alternative substrates and highlighted steps that appear to represent bottlenecks en route to increasing the strains' efficiencies. Additionally, analysis of flavonoid localization during fermentation revealed unequal distribution with strong intracellular accumulation of a number of methylated flavonoids and extracellular enrichment of several pathway intermediates. This work establishes a platform for the production of complex methoxylated flavonoids and discusses strategies for its improvement.

Phenolic Compounds in Extra Virgin Olive Oil Stimulate Human Osteoblastic Cell Proliferation

PubMed Central

García-Martínez, Olga; De Luna-Bertos, Elvira; Ramos-Torrecillas, Javier; Ruiz, Concepción; Milia, Egle; Lorenzo, María Luisa; Jimenez, Brigida; Sánchez-Ortiz, Araceli; Rivas, Ana

2016-01-01

In this study, we aimed to clarify the effects of phenolic compounds and extracts from different extra virgin olive oil (EVOO) varieties obtained from fruits of different ripening stages on osteoblast cells (MG-63) proliferation. Cell proliferation was increased by hydroxytyrosol, luteolin, apigenin, p-coumaric, caffeic, and ferulic acids by approximately 11–16%, as compared with controls that were treated with one vehicle alone, while (+)-pinoresinol, oleuropein, sinapic, vanillic acid and derivative (vanillin) did not affect cell proliferation. All phenolic extracts stimulated MG-63 cell growth, and they induced higher cell proliferation rates than individual compounds. The most effective EVOO phenolic extracts were those obtained from the Picual variety, as they significantly increased cell proliferation by 18–22%. Conversely, Arbequina phenolic extracts increased cell proliferation by 9–13%. A decline in osteoblast proliferation was observed in oils obtained from olive fruits collected at the end of the harvest period, as their total phenolic content decreases at this late stage. Further research on the signaling pathways of olive oil phenolic compounds involved in the processes and their metabolism should be carried out to develop new interventions and adjuvant therapies using EVOO for bone health (i.e.osteoporosis) in adulthood and the elderly. PMID:26930190

Apigenin Reduces Survival of Choriocarcinoma Cells by Inducing Apoptosis via the PI3K/AKT and ERK1/2 MAPK Pathways.

PubMed

Lim, Whasun; Park, Sunwoo; Bazer, Fuller W; Song, Gwonhwa

2016-12-01

Apigenin is a flavonoid found in parsley, onions, oranges, tea, chamomile, wheat, and sprouts. It has a variety of biological properties including anti-oxidant, anti-mutagenic, anti-carcinogenic, anti-inflammatory, anti-proliferative, and anti-spasmodic effects. Based on epidemiological and case-control studies, apigenin is regarded as a novel chemotherapeutic agent against various cancer types. However, little is known about the effects of apigenin on choriocarcinoma cells. Therefore, we investigated the anti-cancer effects of apigenin on choriocarcinoma cells (JAR and JEG3) in the present study. Apigenin reduced viability and migratory properties, increased apoptosis, and suppressed mitochondrial membrane potential in both the JAR and JEG3 cells. In addition, apigenin predominantly decreased phosphorylation of AKT, P70RSK, and S6 whereas the phosphorylation of ERK1/2 and P90RSK was increased by apigenin treatment of JAR and JEG3 cells in a dose-dependent manner. Moreover, treatment of JAR and JEG3 cells with both apigenin and pharmacological inhibitors of PI3K/AKT (LY294002) and ERK1/2 (U0126) revealed synergistic anti-proliferative effects. Collectively, these results indicated that the apigenin is an invaluable chemopreventive agent that inhibits progression and metastasis of choriocarcinoma cells through regulation of PI3K/AKT and ERK1/2 MAPK signal transduction mechanism. J. Cell. Physiol. 231: 2690-2699, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Apigenin, a dietary flavonoid, induces apoptosis, DNA damage, and oxidative stress in human breast cancer MCF-7 and MDA MB-231 cells.

PubMed

Vrhovac Madunić, Ivana; Madunić, Josip; Antunović, Maja; Paradžik, Mladen; Garaj-Vrhovac, Vera; Breljak, Davorka; Marijanović, Inga; Gajski, Goran

2018-05-01

Apigenin is found in several dietary plant foods such as vegetables and fruits. To investigate potential anticancer properties of apigenin on human breast cancer, ER-positive MCF-7 and triple-negative MDA MB-231 cells were used. Moreover, toxicological safety of apigenin towards normal cells was evaluated in human lymphocytes. Cytotoxicity of apigenin towards cancer cells was evaluated by MTT assay whereas further genotoxic and oxidative stress parameters were measured by comet and lipid peroxidation assays, respectively. In order to examine the type of cell death induced by apigenin, several biomarkers were used. Toxicological safety towards normal cells was evaluated by cell viability and comet assays. After the treatment with apigenin, we observed changes in cell morphology in a dose- (10 to 100 μM) and time-dependent manner. Moreover, apigenin caused cell death in both cell lines leading to significant toxicity and dominantly to apoptosis. Furthermore, apigenin proved to be genotoxic towards the selected cancer cells with a potential to induce oxidative damage to lipids. Of great importance is that no significant cytogenotoxic effects were detected in normal cells. The observed cytogenotoxic and pro-cell death activities of apigenin coupled with its low toxicity towards normal cells indicate that this natural product could be used as a future anticancer modality. Therefore, further analysis to determine the exact mechanism of action and in vivo studies on animal models are warranted.

Apigenin inhibits UVA-induced cytotoxicity in vitro and prevents signs of skin aging in vivo.

PubMed

Choi, Sungjin; Youn, Jeungyeun; Kim, Karam; Joo, Da Hye; Shin, Shanghun; Lee, Jeongju; Lee, Hyun Kyung; An, In-Sook; Kwon, Seungbin; Youn, Hae Jeong; Ahn, Kyu Joong; An, Sungkwan; Cha, Hwa Jun

2016-08-01

Apigenin (4',5,7-trihydroxyflavone) is a flavone that has been reported to have anti-inflammatory, antioxidant and anti-carcinogenic properties. In this study, we investigated the protective effects of apigenin on skin and found that, in experiments using cells, apigenin restored the viability of normal human dermal fibroblasts (nHDFs), which had been decreased by exposure to ultraviolet (UV) radiation in the UVA range. Using a senescence-associated (SA)-β-gal assay, we also demonstrate that apigenin protects against the UVA-induced senescence of nHDFs. Furthermore, we found that apigenin decreased the expression of the collagenase, matrix metalloproteinase (MMP)-1, in UVA-irradiated nHDFs. UVA, which has been previously identified as a photoaging-inducing factor, has been shown to induce MMP-1 expression. The elevated expression of MMP-1 impairs the collagen matrix, leading to the loss of elasticity and skin dryness. Therefore, we examined the clinical efficacy of apigenin on aged skin, using an apigenin‑containing cream for clinical application. Specifically, we measured dermal density, skin elasticity and the length of fine wrinkles in subjects treated with apigenin cream or the control cream without apigenin. Additionally, we investigated the effects of the apigenin-containing cream on skin texture, moisture and transepidermal water loss (TEWL). From these experiments, we found that the apigenin‑containing cream increased dermal density and elasticity, and reduced fine wrinkle length. It also improved skin evenness, moisture content and TEWL. These results clearly demonstrate the biological effects of apigenin, demonstrating both its cellular and clinical efficacy, and suggest that this compound holds promise as an anti-aging cosmetic ingredient.

Co-ultramicronized Palmitoylethanolamide/Luteolin Promotes the Maturation of Oligodendrocyte Precursor Cells

PubMed Central

Barbierato, Massimo; Facci, Laura; Marinelli, Carla; Zusso, Morena; Argentini, Carla; Skaper, Stephen D.; Giusti, Pietro

2015-01-01

Oligodendrocytes have limited ability to repair the damage to themselves or to other nerve cells, as seen in demyelinating diseases like multiple sclerosis. An important strategy may be to replace the lost oligodendrocytes and/or promote the maturation of undifferentiated oligodendrocyte precursor cells (OPCs). Recent studies show that a composite of co-ultramicronized N-palmitoylethanolamine (PEA) and luteolin (co-ultramicronized PEA/luteolin, 10:1 by mass) is efficacious in improving outcome in experimental models of spinal cord and traumatic brain injuries. Here, we examined the ability of co-ultramicronized PEA/luteolin to promote progression of OPCs into a more differentiated phenotype. OPCs derived from newborn rat cortex were placed in culture and treated the following day with 10 μM co-ultramicronized PEA/luteolin. Cells were collected 1, 4 and 8 days later and analyzed for expression of myelin basic protein (MBP). qPCR and Western blot analyses revealed a time-dependent increase in expression of both mRNA for MBP and MBP content, along with an increased expression of genes involved in lipid biogenesis. Ultramicronized PEA or luteolin, either singly or in simple combination, were ineffective. Further, co-ultramicronized PEA/luteolin promoted morphological development of OPCs and total protein content without affecting proliferation. Co-ultramicronized PEA/luteolin may represent a novel pharmacological strategy to promote OPC maturation. PMID:26578323

ATP-Binding Pocket-Targeted Suppression of Src and Syk by Luteolin Contributes to Its Anti-Inflammatory Action

PubMed Central

Lee, Jeong-Oog; Kim, Mi-Yeon

2015-01-01

Luteolin is a flavonoid identified as a major anti-inflammatory component of Artemisia asiatica. Numerous reports have demonstrated the ability of luteolin to suppress inflammation in a variety of inflammatory conditions. However, its exact anti-inflammatory mechanism has not been fully elucidated. In the present study, the anti-inflammatory mode of action in activated macrophages of luteolin from Artemisia asiatica was examined by employing immunoblotting analysis, a luciferase reporter gene assay, enzyme assays, and an overexpression strategy. Luteolin dose-dependently inhibited the secretion of nitric oxide (NO) and prostaglandin E2 (PGE2) and diminished the levels of mRNA transcripts of inducible NO synthase (iNOS), tumor necrosis factor- (TNF-) α, and cyclooxygenase-2 (COX-2) in lipopolysaccharide- (LPS-) and pam3CSK-treated macrophage-like RAW264.7 cells without displaying cytotoxicity. Luteolin displayed potent NO-inhibitory activity and also suppressed the nuclear translocation of NF-κB (p65 and p50) via blockade of Src and Syk, but not other mitogen-activated kinases. Overexpression of wild type Src and point mutants thereof, and molecular modelling studies, suggest that the ATP-binding pocket may be the luteolin-binding site in Src. These results strongly suggest that luteolin may exert its anti-inflammatory action by suppressing the NF-κB signaling cascade via blockade of ATP binding in Src and Syk. PMID:26236111

Luteolin restricts dengue virus replication through inhibition of the proprotein convertase furin.

PubMed

Peng, Minhua; Watanabe, Satoru; Chan, Kitti Wing Ki; He, Qiuyan; Zhao, Ya; Zhang, Zhongde; Lai, Xiaoping; Luo, Dahai; Vasudevan, Subhash G; Li, Geng

2017-07-01

In many countries afflicted with dengue fever, traditional medicines are widely used as panaceas for illness, and here we describe the systematic evaluation of a widely known natural product, luteolin, originating from the "heat clearing" class of herbs. We show that luteolin inhibits the replication of all four serotypes of dengue virus, but the selectivity of the inhibition was weak. In addition, ADE-mediated dengue virus infection of human cell lines and primary PBMCs was inhibited. In a time-of-drug-addition study, luteolin was found to reduce infectious virus particle formation, but not viral RNA synthesis, in Huh-7 cells. During the virus life cycle, the host protease furin cleaves the pr moiety from prM protein of immature virus particles in the trans-Golgi network to produce mature virions. Analysis of virus particles from luteolin-treated cells revealed that prM was not cleaved efficiently. Biochemical interrogation of human furin showed that luteolin inhibited the enzyme activity in an uncompetitive manner, with Ki value of 58.6 μM, suggesting that treatment may restrict the virion maturation process. Luteolin also exhibited in vivo antiviral activity in mice infected with DENV, causing reduced viremia. Given the mode of action of luteolin and its widespread source, it is possible that it can be tested in combination with other dengue virus inhibitors. Copyright © 2017 Elsevier B.V. All rights reserved.

Plant Flavone Apigenin Binds to Nucleic Acid Bases and Reduces Oxidative DNA Damage in Prostate Epithelial Cells

PubMed Central

Bhaskaran, Natarajan; Gupta, Sanjay

2014-01-01

Oxidative stress has been linked to prostate carcinogenesis as human prostate tissue is vulnerable to oxidative DNA damage. Apigenin, a dietary plant flavone, possesses anti-proliferative and anticancer effects; however, its antioxidant properties have not been fully elucidated. We investigated sub-cellular distribution of apigenin, it’s binding to DNA and protective effects against H2O2-induced DNA damage using transformed human prostate epithelial RWPE-1 cells and prostate cancer LNCaP, PC-3 and DU145 cells. Exposure of cells to apigenin exhibited higher accumulation in RWPE-1 and LNCaP cells, compared to PC-3 and DU145 cells. The kinetics of apigenin uptake in LNCaP cells was estimated with a Km value of 5 µmole/L and Vmax of 190 pmoles/million cells/h. Sub-cellular fractionation demonstrated that nuclear matrix retains the highest concentration of apigenin (45.3%), followed by cytosol (23.9%), nuclear membranes (17.9%) and microsomes (12.9%), respectively. Spectroscopic analysis of apigenin with calf-thymus DNA exhibited intercalation as the dominant binding mode to DNA duplex. Apigenin exposure resulted in significant genoprotective effects in H2O2-stressed RWPE-1 cells by reduction in reactive oxygen species levels. In addition, apigenin exposure suppressed the formation of 8-hydroxy-2′ deoxyguanosine and protected exposed cells from apoptosis. Our studies demonstrate that apigenin is readily taken up by normal prostatic epithelial cells and prostate cancer cells, and is incorporated into their nuclei, where its intercalation with nucleic acid bases may account for its antioxidant and chemopreventive activities. PMID:24614817

Plant flavone apigenin binds to nucleic acid bases and reduces oxidative DNA damage in prostate epithelial cells.

PubMed

Sharma, Haripaul; Kanwal, Rajnee; Bhaskaran, Natarajan; Gupta, Sanjay

2014-01-01

Oxidative stress has been linked to prostate carcinogenesis as human prostate tissue is vulnerable to oxidative DNA damage. Apigenin, a dietary plant flavone, possesses anti-proliferative and anticancer effects; however, its antioxidant properties have not been fully elucidated. We investigated sub-cellular distribution of apigenin, it's binding to DNA and protective effects against H2O2-induced DNA damage using transformed human prostate epithelial RWPE-1 cells and prostate cancer LNCaP, PC-3 and DU145 cells. Exposure of cells to apigenin exhibited higher accumulation in RWPE-1 and LNCaP cells, compared to PC-3 and DU145 cells. The kinetics of apigenin uptake in LNCaP cells was estimated with a Km value of 5 µmole/L and Vmax of 190 pmoles/million cells/h. Sub-cellular fractionation demonstrated that nuclear matrix retains the highest concentration of apigenin (45.3%), followed by cytosol (23.9%), nuclear membranes (17.9%) and microsomes (12.9%), respectively. Spectroscopic analysis of apigenin with calf-thymus DNA exhibited intercalation as the dominant binding mode to DNA duplex. Apigenin exposure resulted in significant genoprotective effects in H2O2-stressed RWPE-1 cells by reduction in reactive oxygen species levels. In addition, apigenin exposure suppressed the formation of 8-hydroxy-2' deoxyguanosine and protected exposed cells from apoptosis. Our studies demonstrate that apigenin is readily taken up by normal prostatic epithelial cells and prostate cancer cells, and is incorporated into their nuclei, where its intercalation with nucleic acid bases may account for its antioxidant and chemopreventive activities.

Apigenin Ameliorates Dyslipidemia, Hepatic Steatosis and Insulin Resistance by Modulating Metabolic and Transcriptional Profiles in the Liver of High-Fat Diet-Induced Obese Mice.

PubMed

Jung, Un Ju; Cho, Yun-Young; Choi, Myung-Sook

2016-05-19

Several in vitro and in vivo studies have reported the anti-inflammatory, anti-diabetic and anti-obesity effects of the flavonoid apigenin. However, the long-term supplementary effects of low-dose apigenin on obesity are unclear. Therefore, we investigated the protective effects of apigenin against obesity and related metabolic disturbances by exploring the metabolic and transcriptional responses in high-fat diet (HFD)-induced obese mice. C57BL/6J mice were fed an HFD or apigenin (0.005%, w/w)-supplemented HFD for 16 weeks. In HFD-fed mice, apigenin lowered plasma levels of free fatty acid, total cholesterol, apolipoprotein B and hepatic dysfunction markers and ameliorated hepatic steatosis and hepatomegaly, without altering food intake and adiposity. These effects were partly attributed to upregulated expression of genes regulating fatty acid oxidation, tricarboxylic acid cycle, oxidative phosphorylation, electron transport chain and cholesterol homeostasis, downregulated expression of lipolytic and lipogenic genes and decreased activities of enzymes responsible for triglyceride and cholesterol ester synthesis in the liver. Moreover, apigenin lowered plasma levels of pro-inflammatory mediators and fasting blood glucose. The anti-hyperglycemic effect of apigenin appeared to be related to decreased insulin resistance, hyperinsulinemia and hepatic gluconeogenic enzymes activities. Thus, apigenin can ameliorate HFD-induced comorbidities via metabolic and transcriptional modulations in the liver.

Apigenin and naringenin ameliorate PKCβII-associated endothelial dysfunction via regulating ROS/caspase-3 and NO pathway in endothelial cells exposed to high glucose.

PubMed

Qin, Weiwei; Ren, Bei; Wang, Shanshan; Liang, Shujun; He, Baiqiu; Shi, Xiaoji; Wang, Liying; Liang, Jingyu; Wu, Feihua

2016-10-01

Endothelial dysfunction is a key event in the progression of atherosclerosis with diabetes. Increasing cell apoptosis may lead to endothelial dysfunction. Apigenin and naringenin are two kinds of widely used flavones. In the present study, we investigated whether and how apigenin and naringenin reduced endothelial dysfunction induced by high glucose in endothelial cells. We showed that apigenin and naringenin protected against endothelial dysfunction via inhibiting phosphorylation of protein kinase C βII (PKCβII) expression and downstream reactive oxygen species (ROS) production in endothelial cells exposed to high glucose. Furthermore, we demonstrated that apigenin and naringenin reduced high glucose-increased apoptosis, Bax expression, caspase-3 activity and phosphorylation of NF-κB in endothelial cells. Moreover, apigenin and naringenin effectively restored high glucose-reduced Bcl-2 expression and Akt phosphorylation. Importantly, apigenin and naringenin significantly increased NO production in endothelial cells subjected to high glucose challenge. Consistently, high glucose stimulation impaired acetylcholine (ACh)-mediated vasodilation in the rat aorta, apigenin and naringenin treatment restored the impaired endothelium-dependent vasodilation via dramatically increasing eNOS activity and nitric oxide (NO) level. Taken together, our results manifest that apigenin and naringenin can ameliorate endothelial dysfunction via regulating ROS/caspase-3 and NO pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

Studies on the interaction of apigenin with calf thymus DNA by spectroscopic methods

NASA Astrophysics Data System (ADS)

Zhang, Shufang; Sun, Xuejun; Kong, Rongmei; Xu, Mingming

2015-02-01

The interaction between apigenin and calf thymus deoxyribonucleic acid (ctDNA) in a pH 7.4 Tris-HCl buffer solution was investigated by UV-Vis spectroscopy, fluorescence spectroscopy, DNA melting techniques, and viscosity measurements. It was found that apigenin molecules could intercalate into the base pairs of DNA, forming a apigenin-DNA complex with a binding constant of K310K = 6.4 × 104 L mol-1. The thermodynamic parameters enthalpy change (ΔH), entropy change (ΔS) and Gibbs free energy (ΔG) were calculated to be 7.36 × 104 J mol-1, 329 J K-1 mol-1 and -2.84 × 104 J mol-1 at 310 K, respectively. Hydrophobic interaction was the predominant intermolecular force in stabilizing the apigenin-DNA complex. Thermal denaturation study suggested that the stabilization of the ctDNA helix was increased when the apigenin binding to ctDNA as indicated by the increase in thermal denaturation temperature of ctDNA at around 5.0 °C in the presence of apigenin. Spectroscopic techniques together with melting techniques and viscosity determination provided evidences of intercalation mode of binding for the interaction between apigenin and ctDNA.

Apigenin inhibits COX-2, PGE2, and EP1 and also initiates terminal differentiation in the epidermis of tumor bearing mice.

PubMed

Kiraly, Alex J; Soliman, Eman; Jenkins, Audrey; Van Dross, Rukiyah T

2016-01-01

Non-melanoma skin cancer (NMSC) is the most prevalent cancer in the United States. NMSC overexpresses cyclooxygenase-2 (COX-2). COX-2 synthesizes prostaglandins such as PGE2 which promote proliferation and tumorigenesis by engaging G-protein-coupled prostaglandin E receptors (EP). Apigenin is a bioflavonoid that blocks mouse skin tumorigenesis induced by the chemical carcinogens, 7,12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA). However, the effect of apigenin on the COX-2 pathway has not been examined in the DMBA/TPA skin tumor model. In the present study, apigenin decreased tumor multiplicity and incidence in DMBA/TPA-treated SKH-1 mice. Analysis of the non-tumor epidermis revealed that apigenin reduced COX-2, PGE2, EP1, and EP2 synthesis and also increased terminal differentiation. In contrast, apigenin did not inhibit the COX-2 pathway or promote terminal differentiation in the tumors. Since fewer tumors developed in apigenin-treated animals which contained reduced epidermal COX-2 levels, our data suggest that apigenin may avert skin tumor development by blocking COX-2. Copyright © 2015 Elsevier Ltd. All rights reserved.

Apigenin inhibits rat neurosteroidogenic 5α-reductase 1 and 3α-hydroxysteroid dehydrogenase.

PubMed

Wu, Ying; Li, Lili; Zhou, Songyi; Shen, Qiuxia; Lin, Han; Zhu, Qiqi; Sun, Jianliang; Ge, Ren-Shan

2017-11-01

Apigenin, a common flavonoid, has extensive pharmacological activities. Apigenin inhibits some steroid biosynthetic enzymes, suggesting that it may block neurosteroid synthesis. Neurosteroids play many important roles in neurological functions. The objective of the present study is to investigate effects of apigenin on neurosteroidogenic enzymes, 5α-reductase 1 (SRD5A1), 3α-hydroxysteroid dehydrogenase (AKR1C9), and retinol dehydrogenase 2 (RoDH2), in rats. SRD5A1, AKR1C9, and RoDH2 were expressed in COS-1 cells and the effects of apigenin on these enzymes and modes of action were explored using radiolabeled substrates and thin-layer chromatographic separation coupled with radiometry. Apigenin inhibited SRD5A1, AKR1C9, and RoDH2 activities with IC 50 values of 100, 0.891 ± 0.065, and >100 μM, respectively. Apigenin competitively inhibited rat AKR1C9 when its substrate 5α-dihydrotestosterone was used and uncompetitively inhibited the enzyme when cofactor NADPH was used. In conclusion, apigenin is a potent inhibitor of rat AKR1C9, thereby controlling the rate of neurosteroid biosynthesis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Apigenin inhibits African swine fever virus infection in vitro.

PubMed

Hakobyan, Astghik; Arabyan, Erik; Avetisyan, Aida; Abroyan, Liana; Hakobyan, Lina; Zakaryan, Hovakim

2016-12-01

African swine fever virus (ASFV) is one of the most devastating diseases of domestic pigs for which no effective vaccines are available. Flavonoids, natural products isolated from plants, have been reported to have significant in vitro and in vivo antiviral activity against different viruses. Here, we tested the antiviral effect of five flavonoids on the replication of ASFV in Vero cells. Our results showed a potent, dose-dependent anti-ASFV effect of apigenin in vitro. Time-of-addition experiments revealed that apigenin was highly effective at the early stages of infection. Apigenin reduced the ASFV yield by more than 99.99 % when it was added at 1 hpi. The antiviral activity of apigenin was further investigated by evaluation of ASFV protein synthesis and viral factories. This flavonoid inhibited ASFV-specific protein synthesis and viral factory formation. ASFV-infected cells continuously treated with apigenin did not display a cytopathic effect. Further studies addressing the use of apigenin in vivo are needed.

Enhanced chemotherapeutic efficacy of apigenin liposomes in colorectal cancer based on flavone-membrane interactions.

PubMed

Banerjee, Kacoli; Banerjee, Shubhadeep; Mandal, Mahitosh

2017-04-01

Recent endeavors in exploiting vast array of natural phytochemicals to ameliorate colorectal cancer led us to investigate apigenin, a naturally occurring dietary flavone as a potential chemo-therapeutic agent. The present study focuses on establishing apigenin as a potential chemotherapeutic agent for alleviating colorectal cancer and reports the development of a stable liposomal nanocarrier with high encapsulation of the hydrophobic flavone apigenin for enhanced chemotherapeutic effects. The enhanced pharmacological activity of apigenin has been assigned to its ability to interact and subsequently influence membrane properties which also resulted in optimal yield of a stable, rigidified, non-leaky nano-carrier with ideal release kinetics. Extensive testing of drug and its liposomal counterpart for potential clinical chemotherapeutic applications yielded hemocompatibility and cytocompatibility with normal fibroblast cells while enhanced antineoplastic activity was observed in tumor xenograft model. The increased chemotherapeutic potential of liposomal apigenin highlights the clinical potential of apigenin-based vesicles. Copyright © 2016 Elsevier Inc. All rights reserved.

Mushroom (Agaricus bisporus) polyphenoloxidase inhibited by apigenin: Multi-spectroscopic analyses and computational docking simulation.

PubMed

Xiong, Zhiqiang; Liu, Wei; Zhou, Lei; Zou, Liqiang; Chen, Jun

2016-07-15

It has been revealed that some polyphenols can prevent enzymatic browning caused by polyphenoloxidase (PPO). Apigenin, widely distributed in many fruits and vegetables, is an important bioactive flavonoid compound. In this study, apigenin exhibited a strong inhibitory activity against PPO, and some reagents had synergistic effect with apigenin on inhibiting PPO. Apigenin inhibited PPO activity reversibly in a mixed-type manner. The fact that inactivation rate constant (k) of PPO increased while activation energy (Ea) and thermodynamic parameters (ΔG, ΔH and ΔS) decreased indicated that the thermosensitivity and stability of PPO decreased. The conformational changes of PPO were revealed by fluorescence emission spectra and circular dichroism. Atomic force microscopy observation suggested that the dimension of PPO molecules was larger after interacting with apigenin. Moreover, computational docking simulation indicated that apigenin bound to PPO and inserted into the hydrophobic cavity of PPO to interact with some amino acid residues. Copyright © 2016 Elsevier Ltd. All rights reserved.

Apigenin Restricts FMDV Infection and Inhibits Viral IRES Driven Translational Activity

PubMed Central

Qian, Suhong; Fan, Wenchun; Qian, Ping; Zhang, Dong; Wei, Yurong; Chen, Huanchun; Li, Xiangmin

2015-01-01

Foot-and-mouth disease (FMD) is a highly contagious disease of domestic and wild ruminants that is caused by FMD virus (FMDV). FMD outbreaks have occurred in livestock-containing regions worldwide. Apigenin, which is a flavonoid naturally existing in plant, possesses various pharmacological effects, including anti-inflammatory, anticancer, antioxidant and antiviral activities. Results show that apigenin can inhibit FMDV-mediated cytopathogenic effect and FMDV replication in vitro. Further studies demonstrate the following: (i) apigenin inhibits FMDV infection at the viral post-entry stage; (ii) apigenin does not exhibit direct extracellular virucidal activity; and (iii) apigenin interferes with the translational activity of FMDV driven by internal ribosome entry site. Studies on applying apigein in vivo are required for drug development and further identification of potential drug targets against FDMV infection. PMID:25835532

Apigenin inhibits NF-κB and snail signaling, EMT and metastasis in human hepatocellular carcinoma.

PubMed

Qin, Yuan; Zhao, Dong; Zhou, Hong-Gang; Wang, Xing-Hui; Zhong, Wei-Long; Chen, Shuang; Gu, Wen-Guang; Wang, Wei; Zhang, Chun-Hong; Liu, Yan-Rong; Liu, Hui-Juan; Zhang, Qiang; Guo, Yuan-Qiang; Sun, Tao; Yang, Cheng

2016-07-05

Apigenin is a naturally occurring compound with anti-inflammatory, antioxidant, and anticancer properties. In this study, we investigated the effects of apigenin on migration and metastasis in experimental human hepatocellular carcinoma (HCC) cell lines in vitro and in vivo. Apigenin dose-dependently inhibited proliferation, migration, and invasion by PLC and Bel-7402 human HCC cells. It also suppressed tumor growth in PLC cell xenografts without altering body weight, thereby prolonging survival. Apigenin reduced Snai1 and NF-κB expression, reversed increases in epithelial-mesenchymal transition (EMT) marker levels, increased cellular adhesion, regulated actin polymerization and cell migration, and inhibited invasion and migration by HCC cells. Apigenin may therefore inhibit EMT by inhibiting the NF-κB/Snail pathway in human HCC.

Apigenin inhibits NF-κB and Snail signaling, EMT and metastasis in human hepatocellular carcinoma

PubMed Central

Zhong, Wei-long; Chen, Shuang; Gu, Wen-guang; Wang, Wei; Zhang, Chun-hong; Liu, Yan-rong; Liu, Hui-juan; Zhang, Qiang; Guo, Yuan-qiang; Sun, Tao; Yang, Cheng

2016-01-01

Apigenin is a naturally occurring compound with anti-inflammatory, antioxidant, and anticancer properties. In this study, we investigated the effects of apigenin on migration and metastasis in experimental human hepatocellular carcinoma (HCC) cell lines in vitro and in vivo. Apigenin dose-dependently inhibited proliferation, migration, and invasion by PLC and Bel-7402 human HCC cells. It also suppressed tumor growth in PLC cell xenografts without altering body weight, thereby prolonging survival. Apigenin reduced Snai1 and NF-κB expression, reversed increases in epithelial-mesenchymal transition (EMT) marker levels, increased cellular adhesion, regulated actin polymerization and cell migration, and inhibited invasion and migration by HCC cells. Apigenin may therefore inhibit EMT by inhibiting the NF-κB/Snail pathway in human HCC. PMID:27203387

Apigenin restricts FMDV infection and inhibits viral IRES driven translational activity.

PubMed

Qian, Suhong; Fan, Wenchun; Qian, Ping; Zhang, Dong; Wei, Yurong; Chen, Huanchun; Li, Xiangmin

2015-03-31

Foot-and-mouth disease (FMD) is a highly contagious disease of domestic and wild ruminants that is caused by FMD virus (FMDV). FMD outbreaks have occurred in livestock-containing regions worldwide. Apigenin, which is a flavonoid naturally existing in plant, possesses various pharmacological effects, including anti-inflammatory, anticancer, antioxidant and antiviral activities. Results show that apigenin can inhibit FMDV-mediated cytopathogenic effect and FMDV replication in vitro. Further studies demonstrate the following: (i) apigenin inhibits FMDV infection at the viral post-entry stage; (ii) apigenin does not exhibit direct extracellular virucidal activity; and (iii) apigenin interferes with the translational activity of FMDV driven by internal ribosome entry site. Studies on applying apigein in vivo are required for drug development and further identification of potential drug targets against FDMV infection.

Luteolin and fisetin suppress oxidative stress by modulating sirtuins and forkhead box O3a expression under in vitro diabetic conditions.

PubMed

Kim, Arang; Lee, Wooje; Yun, Jung-Mi

2017-10-01

Chronic hyperglycemia induces oxidative stress via accumulation of reactive oxygen species (ROS) and contributes to diabetic complications. Hyperglycemia induces mitochondrial superoxide anion production through the increased activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. This study aimed to determine whether fisetin and luteolin treatments suppress the oxidative stress by modulating the expression of sirtuins (SIRTs) and forkhead box O3a (FOXO3a) under hyperglycemic conditions in human monocytes. Human monocytic cells (THP-1) were cultured under osmotic control (14.5 mmol/L mannitol), normoglycemic (NG, 5.5 mmol/L glucose), or hyperglycemic (HG, 20 mmol/L glucose) conditions, in the absence or presence of fisetin and luteolin for 48 h. To determine the effect of fisetin and luteolin treatments on high glucose-induced oxidative stress, western blotting and intracellular staining were performed. Hyperglycemic conditions increased the ROS production, as compared to normoglycemic condition. However, fisetin and luteolin treatments inhibited ROS production under hyperglycemia. To obtain further insight into ROS production in hyperglycemic conditions, evaluation of p47phox expression revealed that fisetin and luteolin treatments inhibited p47phox expression under hyperglycemic conditions. Conversely, the expression levels of SIRT1, SIRT3, SIRT6, and FOXO3a were decreased under high glucose conditions compared to normal glucose conditions, but exposure to fisetin and luteolin induced the expression of SIRT1, SIRT3, SIRT6, and FOXO3a. The above findings suggest that fisetin and luteolin inhibited high glucose-induced ROS production in monocytes through the activation of SIRTs and FOXO3a. The results of our study supports current researches that state fisetin and luteolin as potential agents for the development of novel strategies for diabetes.

Luteolin and fisetin suppress oxidative stress by modulating sirtuins and forkhead box O3a expression under in vitro diabetic conditions

PubMed Central

Kim, Arang; Lee, Wooje

2017-01-01

BACKGROUND/OBJECTIVE Chronic hyperglycemia induces oxidative stress via accumulation of reactive oxygen species (ROS) and contributes to diabetic complications. Hyperglycemia induces mitochondrial superoxide anion production through the increased activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. This study aimed to determine whether fisetin and luteolin treatments suppress the oxidative stress by modulating the expression of sirtuins (SIRTs) and forkhead box O3a (FOXO3a) under hyperglycemic conditions in human monocytes. MATERIALS/METHODS Human monocytic cells (THP-1) were cultured under osmotic control (14.5 mmol/L mannitol), normoglycemic (NG, 5.5 mmol/L glucose), or hyperglycemic (HG, 20 mmol/L glucose) conditions, in the absence or presence of fisetin and luteolin for 48 h. To determine the effect of fisetin and luteolin treatments on high glucose-induced oxidative stress, western blotting and intracellular staining were performed. RESULTS Hyperglycemic conditions increased the ROS production, as compared to normoglycemic condition. However, fisetin and luteolin treatments inhibited ROS production under hyperglycemia. To obtain further insight into ROS production in hyperglycemic conditions, evaluation of p47phox expression revealed that fisetin and luteolin treatments inhibited p47phox expression under hyperglycemic conditions. Conversely, the expression levels of SIRT1, SIRT3, SIRT6, and FOXO3a were decreased under high glucose conditions compared to normal glucose conditions, but exposure to fisetin and luteolin induced the expression of SIRT1, SIRT3, SIRT6, and FOXO3a. The above findings suggest that fisetin and luteolin inhibited high glucose-induced ROS production in monocytes through the activation of SIRTs and FOXO3a. CONCLUSIONS The results of our study supports current researches that state fisetin and luteolin as potential agents for the development of novel strategies for diabetes. PMID:28989580

Apigenin inhibits HGF-promoted invasive growth and metastasis involving blocking PI3K/Akt pathway and {beta}4 integrin function in MDA-MB-231 breast cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, W.-J.; Chen, W.-K.; Wang, C.-J.

2008-01-15

Hepatocyte growth factor (HGF) and its receptor, Met, known to control invasive growth program have recently been shown to play crucial roles in the survival of breast cancer patients. The diet-derived flavonoids have been reported to possess anti-invasion properties; however, knowledge on the pharmacological and molecular mechanisms in suppressing HGF/Met-mediated tumor invasion and metastasis is poorly understood. In our preliminary study, we use HGF as an invasive inducer to investigate the effect of flavonoids including apigenin, naringenin, genistein and kaempferol on HGF-dependent invasive growth of MDA-MB-231 human breast cancer cells. Results show that apigenin presents the most potent anti-migration andmore » anti-invasion properties by Boyden chamber assay. Furthermore, apigenin represses the HGF-induced cell motility and scattering and inhibits the HGF-promoted cell migration and invasion in a dose-dependent manner. The effect of apigenin on HGF-induced signaling activation involving invasive growth was evaluated by immunoblotting analysis, it shows that apigenin blocks the HGF-induced Akt phosphorylation but not Met, ERK, and JNK phosphorylation. In addition to MDA-MB-231 cells, apigenin exhibits inhibitory effect on HGF-induced Akt phosphorylation in hepatoma SK-Hep1 cells and lung carcinoma A549 cells. By indirect immunofluorescence microscopy assay, apigenin inhibits the HGF-induced clustering of {beta}4 integrin at actin-rich adhesive site and lamellipodia through PI3K-dependent manner. Treatment of apigenin inhibited HGF-stimulated integrin {beta}4 function including cell-matrix adhesion and cell-endothelial cells adhesion in MDA-MB-231 cells. By Akt-siRNA transfection analysis, it confirmed that apigenin inhibited HGF-promoted invasive growth involving blocking PI3K/Akt pathway. Finally, we evaluated the effect of apigenin on HGF-promoted metastasis by lung colonization of tumor cells in nude mice and organ metastasis of tumor cells in chick embryo. By histological and gross examination of mouse lung and real-time PCR analysis of human alu in host tissues, it showed that apigenin, wortmannin, as well as anti-{beta}4 antibody all inhibit HGF-promoted metastasis. These data support the inhibitory effect of apigenin on HGF-promoted invasive growth and metastasis involving blocking PI3K/Akt pathway and integrin {beta}4 function.« less

Transport of 3-bromopyruvate across the human erythrocyte membrane.

PubMed

Sadowska-Bartosz, Izabela; Soszyński, Mirosław; Ułaszewski, Stanisław; Ko, Young; Bartosz, Grzegorz

2014-06-01

3-Bromopyruvic acid (3-BP) is a promising anticancer compound because it is a strong inhibitor of glycolytic enzymes, especially glyceraldehyde 3-phosphate dehydrogenase. The Warburg effect means that malignant cells are much more dependent on glycolysis than normal cells. Potential complications of anticancer therapy with 3-BP are side effects due to its interaction with normal cells, especially erythrocytes. Transport into cells is critical for 3-BP to have intracellular effects. The aim of our study was the kinetic characterization of 3-BP transport into human erythrocytes. 3-BP uptake by erythrocytes was linear within the first 3 min and pH-dependent. The transport rate decreased with increasing pH in the range of 6.0-8.0. The Km and Vm values for 3-BP transport were 0.89 mM and 0.94 mmol/(l cells x min), respectively. The transport was inhibited competitively by pyruvate and significantly inhibited by DIDS, SITS, and 1-cyano-4-hydroxycinnamic acid. Flavonoids also inhibited 3-BP transport: the most potent inhibition was found for luteolin and quercetin.

Fermented Apulian table olives: Effect of selected microbial starters on polyphenols composition, antioxidant activities and bioaccessibility.

PubMed

D'Antuono, Isabella; Bruno, Angelica; Linsalata, Vito; Minervini, Fiorenza; Garbetta, Antonella; Tufariello, Maria; Mita, Giovanni; Logrieco, Antonio F; Bleve, Gianluca; Cardinali, Angela

2018-05-15

The effects of fermentation by autochthonous microbial starters on phenolics composition of Apulian table olives, Bella di Cerignola (BDC), Termite di Bitetto (TDB) and Cellina di Nardò (CEL) were studied, highlighting also the cultivars influence. In BDC with starter, polyphenols amount doubled compared with commercial sample, while in TDB and CEL, phenolics remain almost unchanged. The main phenolics were hydroxytyrosol, tyrosol, verbascoside and luteolin, followed by hydroxytyrosol-acetate detected in BDC and cyanidine-3-glucoside and quercetin in CEL. Scavenger capacity in both DPPH and CAA assays, assessed the highest antioxidant effect for CEL with starters (21.7 mg Trolox eq/g FW; 8.5 μmol hydroxytyrosol eq/100 g FW). The polyphenols were highly in vitro bioaccessible (>60%), although modifications in their profile, probably for combined effect of environment and microorganisms, were noted. Finally, fermented table olives are excellent source of health promoting compounds, since hydroxytyrosol and tyrosol are almost 8 times more than in olive oil. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inhibition of benzodiazepine binding in vitro by amentoflavone, a constituent of various species of Hypericum.

PubMed

Baureithel, K H; Büter, K B; Engesser, A; Burkard, W; Schaffner, W

1997-06-01

Flower extracts of Hypericum perforatum, Hypericum hirsutum, Hypericum patulum and Hypericum olympicum efficiently inhibited binding of [3H]flumazenil to rat brain benzodiazepine binding sites of the GABAA-receptor in vitro with IC50 values of 6.83, 6.97, 13.2 and 6.14 micrograms/ml, respectively. Single constituents of the extracts like hypericin, the flavones quercetin and luteolin, the glycosylated flavonoides rutin, hyperoside and quercitrin and the biflavone 13, II8-biapigenin did not inhibit binding up to concentrations of 1 microM. In contrast, amentoflavone revealed an IC50 = 14.9 +/- 1.9 nM on benzodiazepine binding in vitro. Comparative HPLC analyses of hypericin and amentoflavone in extracts of different Hypericum species revealed a possible correlation between the amentoflavone concentration and the inhibition of flumazenil binding. For hypericin no such correlation was observed. Our experimental data demonstrate that amentoflavone, in contrast to hypericin, presents a very active compound with regard to the inhibition of [3H]-flumazenil binding in vitro and thus might be involved in the antidepressant effects of Hypericum perforatum extracts.

A study on the GC-MS analysis of bioactive components and pancreato-protective effect of methanolic extract of Brassica oleracea L. var. botrytis.

PubMed

Rajapriya, Sadanandan; Geetha, Arumugam; Ganesan Kripa, Kavasseri

2017-09-01

The ever-increasing problem of pancreatitis due to alcohol abuse demands evaluation of novel drugs of plant origin. This study explores the therapeutic effects of the methanolic extract of Brassica oleraceae (MEBO) on ethanol and cerulein induced pancreatitis in rats. The MEBO was subjected to GC-MS and HPLC analysis. Male albino Wistar rats were divided into various groups, fed with alcohol (36% of total calories for 5 weeks) and cerulein (20 μg/kg b.wt i.p, weekly thrice for last three weeks) with or without MEBO (40 mg/kg b.wt). Serum lipase, amylase, IL-1β, IL-18, caspase-1, lipid peroxides, oxidative stress index and antioxidant status were assessed in pancreas. Six compounds were identified in GC-MS analysis. Co-administration of MEBO reduced the pancreatic marker enzymes in serum, IL-1β, IL-18 and caspase-1 and increased the antioxidant status of pancreas. The pancreato-protective effect of Brassica oleraceae may be attributed to well-known anti-inflammatory flavonoids, luteolin, quercetin and myricetin.

Inhibition of metallopeptidases by flavonoids and related compounds.

PubMed

Bormann, H; Melzig, M F

2000-02-01

To elucidate possible mechanisms of activity in medicinal plants containing flavonoids, the inhibitory potency of twenty flavones, flavonols, flavanones, phenylacrylic acids and various hydroxylated phenylacetic acids on the activity of neutral endopeptidase (NEP; EC 3.4.24.11), angiotensin-converting enzyme (ACE; EC 3.4.15.1) and aminopeptidase N (APN; EC 3.4.11.2) was investigated in vitro. The screening generally resulted that inhibition of these enzymes requires free hydroxyl groups at the flavone molecule. Flavone and methoxylated compounds (sinensetin) were without effects. Flavonoids with free hydroxyl functions in position 3',4' and 5,7 inhibited the activity of NEP (quercetin, luteolin, fisetin), with myricetin (IC50 = 42 microM) as strongest inhibitor. Inhibition of ACE and APN did not depend on this class of compounds and substitution pattern. E.g. 3,4-dihydroxyphenylacetic acid and 4-methylcatechol (urinary metabolites of flavonoids) also inhibited both APN and ACE activity, but not NEP activity. The results demonstrate that some of the pharmacological activities of flavonoids might be related to the inhibition of metallopeptidases responsible for the splitting of regulatory neuropeptides.

Inhibition of MDA-MB-231 breast cancer cell proliferation and tumor growth by apigenin through induction of G2/M arrest and histone H3 acetylation-mediated p21WAF1/CIP1 expression.

PubMed

Tseng, Tsui-Hwa; Chien, Ming-Hsien; Lin, Wea-Lung; Wen, Yu-Ching; Chow, Jyh-Ming; Chen, Chi-Kuan; Kuo, Tsang-Chih; Lee, Wei-Jiunn

2017-02-01

Apigenin (4',5,7-trihydroxyflavone), a flavonoid commonly found in fruits and vegetables, has anticancer properties in various malignant cancer cells. However, the molecular basis of the anticancer effect remains to be elucidated. In this study, we investigated the cellular mechanisms underlying the induction of cell cycle arrest by apigenin. Our results showed that apigenin at the nonapoptotic induction concentration inhibited cell proliferation and induced cell cycle arrest at the G2/M phase in the MDA-MB-231 breast cancer cell line. Immunoblot analysis indicated that apigenin suppressed the expression of cyclin A, cyclin B, and cyclin-dependent kinase-1 (CDK1), which control the G2-to-M phase transition in the cell cycle. In addition, apigenin upregulated p21 WAF1/CIP1 and increased the interaction of p21 WAF1/CIP1 with proliferating cell nuclear antigen (PCNA), which inhibits cell cycle progression. Furthermore, apigenin significantly inhibited histone deacetylase (HDAC) activity and induced histone H3 acetylation. The subsequent chromatin immunoprecipitation (ChIP) assay indicated that apigenin increased acetylation of histone H3 in the p21 WAF1/CIP1 promoter region, resulting in the increase of p21 WAF1/CIP1 transcription. In a tumor xenograft model, apigenin effectively delayed tumor growth. In these apigenin-treated tumors, we also observed reductions in the levels of cyclin A and cyclin B and increases in the levels of p21 WAF1/CIP1 and acetylated histone H3. These findings demonstrate for the first time that apigenin can be used in breast cancer prevention and treatment through epigenetic regulation. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 434-444, 2017. © 2016 Wiley Periodicals, Inc.

Oral Efficacy of Apigenin against Cutaneous Leishmaniasis: Involvement of Reactive Oxygen Species and Autophagy as a Mechanism of Action

PubMed Central

Fonseca-Silva, Fernanda; Inacio, Job D. F.; Canto-Cavalheiro, Marilene M.; Menna-Barreto, Rubem F. S.; Almeida-Amaral, Elmo E.

2016-01-01

Background The treatment for leishmaniasis is currently based on pentavalent antimonials and amphotericin B; however, these drugs result in numerous adverse side effects. The lack of affordable therapy has necessitated the urgent development of new drugs that are efficacious, safe, and more accessible to patients. Natural products are a major source for the discovery of new and selective molecules for neglected diseases. In this paper, we evaluated the effect of apigenin on Leishmania amazonensis in vitro and in vivo and described the mechanism of action against intracellular amastigotes of L. amazonensis. Methodology/Principal Finding Apigenin reduced the infection index in a dose-dependent manner, with IC50 values of 4.3 μM and a selectivity index of 18.2. Apigenin induced ROS production in the L. amazonensis-infected macrophage, and the effects were reversed by NAC and GSH. Additionally, apigenin induced an increase in the number of macrophages autophagosomes after the infection, surrounding the parasitophorous vacuole, suggestive of the involvement of host autophagy probably due to ROS generation induced by apigenin. Furthermore, apigenin treatment was also effective in vivo, demonstrating oral bioavailability and reduced parasitic loads without altering serological toxicity markers. Conclusions/Significance In conclusion, our study suggests that apigenin exhibits leishmanicidal effects against L. amazonensis-infected macrophages. ROS production, as part of the mechanism of action, could occur through the increase in host autophagy and thereby promoting parasite death. Furthermore, our data suggest that apigenin is effective in the treatment of L. amazonensis-infected BALB/c mice by oral administration, without altering serological toxicity markers. The selective in vitro activity of apigenin, together with excellent theoretical predictions of oral availability, clear decreases in parasite load and lesion size, and no observed compromises to the overall health of the infected mice encourage us to supports further studies of apigenin as a candidate for the chemotherapeutic treatment of leishmaniasis. PMID:26862901

Protective effect of apigenin on radiation-induced chromosomal damage in human lymphocytes

NASA Technical Reports Server (NTRS)

Rithidech, Kanokporn Noy; Tungjai, Montree; Whorton, Elbert B.

2005-01-01

The potential use of flavonoids as a radioprotector is of increasing interest because of their high antioxidant activity and abundance in the diet. The aim of this study is to examine genotoxic and radioprotective effects of one of the most common flavonoids, apigenin, on radiation-induced chromosome aberrations in human lymphocytes. The cytokinesis-block micronucleus (CBMN) assay was used to evaluate such effects of apigenin. Blood samples were collected from two non-smoking healthy male volunteers who had no history of previous exposure to other clastogenic agents. Isolated lymphocytes were cultured. There were two tubes per concentration for all treatments. To evaluate the genotoxicity of apigenin, cells were first treated with different concentrations of apigenin (0, 2.5, 5, 10 and 25 microg/mL) at 24 h after culture initiation, followed by cytochalasin-B (Cyt-B) treatment (3 microg/mL) and cell harvest at 44 and 72 h, respectively. Secondly, to investigate the radioprotective effect, cell cultures were exposed to different concentrations of apigenin as described above for 30 min before being irradiated to 2 Gy of 137Cs gamma rays (at a dose rate of 0.75 Gy/min). In all instances, the frequency of MN was scored in binucleated (BN) cells. The nuclear proliferation index also was calculated. We did not detect an increase in the frequency of MN in non-irradiated human lymphocyte cultures treated with 2.5, 5.0 or 10 microg/mL apigenin; although, we did observe an increase in cultures treated with 25 microg/mL apigenin (the highest concentration of apigenin used in our study). We also observed a significant increase in the frequency of MN in irradiated cells overall; however, the frequency was decreased as the concentration of apigenin increased, suggesting a radioprotective effect. These findings provide a basis for additional studies to help clarify the potential use and benefit of apigenin as a radioprotector.

Relaxation of isolated guinea-pig trachea by apigenin, a constituent of celery, via inhibition of phosphodiesterase.

PubMed

Chen, Junn-Lain; Ko, Wun-Chang

2017-09-15

Apigenin, was reported to have vasodilatory effects by inhibiting Ca 2+ influx through both voltage- and receptor-operated calcium channels, but not by inhibiting cAMP- or cGMP-phosphodiesterases (PDEs) in rat thoracic aorta. However, apigenin was reported to inhibit PDE1, 2 and 3 in guinea-pig lung and heart. The aim of this study was to clarify that guinea-pig tracheal relaxation by apigenin whether via PDE inhibition. We isometrically recorded the tension of isolated guinea-pig tracheal segments on a polygraph. Antagonistic effects of apigenin against cumulative contractile agents or Ca 2+ induced contractions of the trachealis in normal or isotonic high-K + , Ca 2+ -free Krebs solution, respectively. Effects of apigenin (15 and 30μM) on the cumulative forskolin- and nitroprusside-induced relaxations to histamine (30μM)-induced precontraction were performed. The inhibitory effects of 30-300μM apigenin and 3-isobutyl-1-methylxanthine (IBMX, positive control) on the cAMP- and cGMP-PDEs were determined. Apigenin concentration-dependently but non-competitively inhibited cumulative histamine-, carbachol- or Ca 2+ -induced contractions in normal or in the depolarized (K + , 60mM) trachealis, suggesting that Ca 2+ influx through voltage-dependent calcium channels is inhibited. However, apigenin (15-30μM) parallel leftward shifted the concentration-response curves of forskolin and nitroprusside, and significantly increased the pD 2 values of these two cyclase activators. Both apigenin and IBMX, a reference drug, concentration (10-300μM)-dependently and significantly, but non-selectively inhibited the activities of cAMP- and cGMP-PDEs in the trachealis. In conclusion, the relaxant effect of apigenin may be due to inhibition of both enzyme activities and reduction of intracellular Ca 2+ by inhibiting Ca 2+ influx in the trachealis. Copyright © 2017 Elsevier B.V. All rights reserved.

Apigenin manipulates the ubiquitin-proteasome system to rescue estrogen receptor-β from degradation and induce apoptosis in prostate cancer cells.

PubMed

Singh, Vishal; Sharma, Vikas; Verma, Vikas; Pandey, Deepti; Yadav, Santosh K; Maikhuri, Jagdamba P; Gupta, Gopal

2015-12-01

To investigate apigenin (5,7,4-trihydroxyflavone), a dietary flavonoid with proteasome-inhibitory activity (desired for the management of multiple types of cancers), against FDA-approved anticancer proteasome inhibitor bortezomib in context to its effects on the tumor suppressor estrogen receptor-beta (ER-β) in prostate cancer cells. Prostate cancer (PC-3) cells were treated with either apigenin or bortezomib, and proliferation inhibition was correlated with proteasomal biochemistry, ER-degradation and cell apoptosis. Apigenin specifically inhibited only chymotrypsin-like activity of proteasome without affecting trypsin and caspase-like activities, which was in contrast to the non-specific inhibition of all the three activities by bortezomib. Apigenin selectively increased the protein levels of ER-β at 1.8 and 10.0 µM (without affecting mRNA levels) and preferentially accumulated ubiquitinated ER-β over ER-α in PC-3. Apigenin-treated cells exhibited increased ER-β interactions with ubiquitin-protein ligase E6AP, downregulated PSMA5 (α-5 subunit for assembly of 20S proteasome) without affecting PSMB1 (β-1 subunit), PSMB2 (β-2 subunit) and PSMB5 (β-5 subunit, whose overexpression by bortezomib causes drug resistance) of proteasome at mRNA levels. Caspase-3 activation in PC-3 by apigenin was dependent on caspase-8 activity but independent of mitochondrial membrane depolarization. The deubiquitinase USP14 activity, which antagonizes degradation of proteins via proteasome, was significantly increased by apigenin treatment. Apigenin selectively inhibits proteasomal degradation of tumor suppressor ER-β by specifically inhibiting chymotrypsin-like activity of proteasome, preventing its assembly via PSMA5 and inhibiting USP14 enzyme activity in prostate cancer cells, resulting in cancer cell apoptosis. Unlike bortezomib, apigenin's actions are subtle, precise, mechanistically distinct and capable of abstaining drug resistance.

Apigenin overcomes drug resistance by blocking the signal transducer and activator of transcription 3 signaling in breast cancer cells

PubMed Central

Seo, Hye-Sook; Ku, Jin Mo; Choi, Hyeong Sim; Woo, Jong-Kyu; Lee, Byung Hoon; Kim, Doh Sun; Song, Hyun Jong; Jang, Bo-Hyoung; Shin, Yong Cheol; Ko, Seong-Gyu

2017-01-01

Drug resistance in chemotherapy is a serious obstacle for the successful treatment of cancer. Drug resistance is caused by various factors, including the overexpression of P-glycoprotein (P-gp, MDR1). The development of new, useful compounds that overcome drug resistance is urgent. Apigenin, a dietary flavonoid, has been reported as an anticancer drug in vivo and in vitro. In the present study, we investigated whether apigenin is able to reverse drug resistance using adriamycin-resistant breast cancer cells (MCF-7/ADR). In our experiments, apigenin significantly decreased cell growth and colony formation in MCF-7/ADR cells and parental MCF-7 cells. This growth inhibition was related to the accumulation of cells in the sub-G0/G1 apoptotic population and an increase in the number of apoptotic cells. Apigenin reduced the mRNA expression of multidrug resistance 1 (MDR1) and multidrug resistance-associated proteins (MRPs) in MCF-7/ADR cells. Apigenin also downregulated the expression of P-gp. Apigenin reversed drug efflux from MCF-7/ADR cells, resulting in rhodamine 123 (Rho123) accumulation. Inhibition of drug resistance by apigenin is related to the suppression of the signal transducer and activator of transcription 3 (STAT3) signaling pathway. Apigenin decreased STAT3 activation (p-STAT3) and its nuclear translocation and inhibited the secretion of VEGF and MMP-9, which are STAT3 target genes. A STAT3 inhibitor, JAK inhibitor I and an HIF-1α inhibitor decreased cell growth in MCF-7 and MCF-7/ADR cells. Taken together, these results demonstrate that apigenin can overcome drug resistance. PMID:28656316

The flavonoid apigenin reduces prostate cancer CD44(+) stem cell survival and migration through PI3K/Akt/NF-κB signaling.

PubMed

Erdogan, Suat; Doganlar, Oguzhan; Doganlar, Zeynep B; Serttas, Riza; Turkekul, Kader; Dibirdik, Ilker; Bilir, Ayhan

2016-10-01

Cancer stem cells (CSCs) are involved in drug resistance, metastasis and recurrence of cancers. The efficacy of apigenin on cell survival, apoptosis, migration and stemness properties were analyzed in CSCs. Prostate CSCs (CD44(+)) were isolated from human prostate cancer (PCa) PC3 cells using a magnetic-activated cell sorting system. PC3 and CSCs were treated with various concentrations of apigenin, docetaxel and their combinations for 48h. Apigenin dose dependently inhibited CSCs and PC3 cell survival, and this was accompanied with a significant increase of p21 and p27. Apigenin induced apoptosis via an extrinsic caspase-dependent pathway by upregulating the mRNA expressions of caspases-8, -3 and TNF-α, but failed to regulate the intrinsic pathway as determined by the Bax, cytochrome c (Cyt-c) and APAF-1 in CSCs. In contrary to CSCs, apigenin induced intrinsic apoptosis pathway as evidenced by the induction of Bax, Cyt-c and caspase-3 while caspase-8, TNF-α and Bcl-2 levels remained unchanged in PC3 cells. The flavonoid strongly suppressed the migration rate of CSCs compared to untreated cells. Significant downregulation of matrix metallopeptidases-2, -9, Snail and Slug exhibits the ability of apigenin treatment to suppress invasion. The expressions of NF-κB p105/p50, PI3K, Akt and the phosphorylation of pAkt were decreased after apigenin treatment. Moreover, apigenin treatment significantly reduced pluripotency marker Oct3/4 protein expression which might be associated with the down-regulation of PI3K/Akt/NF-κB signaling. Our data indicated that, apigenin could be a useful compound to prevent proliferation and migration of cancer cells as well as CSCs. Copyright © 2016 Elsevier Inc. All rights reserved.

Apigenin overcomes drug resistance by blocking the signal transducer and activator of transcription 3 signaling in breast cancer cells.

PubMed

Seo, Hye-Sook; Ku, Jin Mo; Choi, Hyeong Sim; Woo, Jong-Kyu; Lee, Byung Hoon; Kim, Doh Sun; Song, Hyun Jong; Jang, Bo-Hyoung; Shin, Yong Cheol; Ko, Seong-Gyu

2017-08-01

Drug resistance in chemotherapy is a serious obstacle for the successful treatment of cancer. Drug resistance is caused by various factors, including the overexpression of P‑glycoprotein (P‑gp, MDR1). The development of new, useful compounds that overcome drug resistance is urgent. Apigenin, a dietary flavonoid, has been reported as an anticancer drug in vivo and in vitro. In the present study, we investigated whether apigenin is able to reverse drug resistance using adriamycin‑resistant breast cancer cells (MCF‑7/ADR). In our experiments, apigenin significantly decreased cell growth and colony formation in MCF‑7/ADR cells and parental MCF‑7 cells. This growth inhibition was related to the accumulation of cells in the sub‑G0/G1 apoptotic population and an increase in the number of apoptotic cells. Apigenin reduced the mRNA expression of multidrug resistance 1 (MDR1) and multidrug resistance‑associated proteins (MRPs) in MCF‑7/ADR cells. Apigenin also downregulated the expression of P‑gp. Apigenin reversed drug efflux from MCF‑7/ADR cells, resulting in rhodamine 123 (Rho123) accumulation. Inhibition of drug resistance by apigenin is related to the suppression of the signal transducer and activator of transcription 3 (STAT3) signaling pathway. Apigenin decreased STAT3 activation (p‑STAT3) and its nuclear translocation and inhibited the secretion of VEGF and MMP‑9, which are STAT3 target genes. A STAT3 inhibitor, JAK inhibitor I and an HIF‑1α inhibitor decreased cell growth in MCF‑7 and MCF‑7/ADR cells. Taken together, these results demonstrate that apigenin can overcome drug resistance.

Apigenin induces apoptosis by targeting inhibitor of apoptosis proteins and Ku70–Bax interaction in prostate cancer

PubMed Central

Shukla, Sanjeev; Fu, Pingfu; Gupta, Sanjay

2014-01-01

Dysfunction of the apoptotic pathway in prostate cancer cells confers apoptosis resistance towards various therapies. A novel strategy to overcome resistance is to directly target the apoptotic pathway in cancer cells. Apigenin, an anticancer agent, selectively toxic to cancer cells induces cell cycle arrest and apoptosis through mechanisms which are not fully explored. In the present study we provide novel insight into the mechanisms of apoptosis induction by apigenin. Treatment of androgen-refractory human prostate cancer PC-3 and DU145 cells with apigenin resulted in dose-dependent suppression of XIAP, c-IAP1, c-IAP2 and survivin protein levels. Apigenin treatment resulted in significant decrease in cell viability and apoptosis induction with the increase of cytochrome C in time-dependent manner. These effects of apigenin were accompanied by decrease in Bcl-xL and Bcl-2 and increase in the active form of Bax protein. The apigenin-mediated increase in Bax was due to dissociation of Bax from Ku70 which is essential for apoptotic activity of Bax. Apigenin treatment resulted in the inhibition of class I histone deacetylases and HDAC1 protein expression, thereby increasing the acetylation of Ku70 and the dissociation of Bax resulting in apoptosis of cancer cells. Furthermore, apigenin significantly reduced HDAC1 occupancy at the XIAP promoter, suggesting that histone deacetylation might be critical for XIAP downregulation. These results suggest that apigenin targets inhibitor of apoptosis proteins and Ku70–Bax interaction in the induction of apoptosis in prostate cancer cells and in athymic nude mouse xenograft model endorsing its in vivo efficacy. PMID:24563225

Apigenin inhibited hypoxia induced stem cell marker expression in a head and neck squamous cell carcinoma cell line.

PubMed

Ketkaew, Yuwaporn; Osathanon, Thanaphum; Pavasant, Prasit; Sooampon, Sireerat

2017-02-01

Cancer stem cells contribute to tumor recurrence, and a hypoxic environment is critical for maintaining cancer stem cells. Apigenin is a natural product with anticancer activity. However, the effect of apigenin on cancer stem cells remains unclear. Our aim was to investigate the effect of apigenin on cancer stem cell marker expression in head and neck squamous cell carcinoma cells under hypoxia. We used three head and neck squamous cell carcinoma cell lines; HN-8, HN-30, and HSC-3. The mRNA expression of cancer stem cell markers was determined by semiquantitative RT-PCR and Real-time PCR. The cytotoxic effect of apigenin was determined by MTT colorimetric assay. Flow cytometry was used to reveal the number of cells expressing cancer stem cell surface markers. HN-30 cells, a cancer cell line from the pharynx, showed the greatest response to hypoxia by increasing their expression of CD44, CD105, NANOG, OCT-4, REX-1, and VEGF. Apigenin significantly decreased HN-30 cell viability in dose- and time-dependent manners. In addition, 40μM apigenin significantly down-regulated the mRNA expression of CD44, NANOG, and CD105. Consistent with these results, the hypoxia-induced increase in CD44 + cells, CD105 + cells, and STRO-1 + cells was significantly abolished by apigenin. Apigenin suppresses cancer stem cell marker expression and the number of cells expressing cell surface markers under hypoxia. Copyright © 2016 Elsevier Ltd. All rights reserved.

Apigenin ameliorates chronic mild stress-induced depressive behavior by inhibiting interleukin-1β production and NLRP3 inflammasome activation in the rat brain.

PubMed

Li, Ruipeng; Wang, Xiangxiang; Qin, Tingting; Qu, Rong; Ma, Shiping

2016-01-01

Increasing evidence suggests that inflammation and oxidative stress may contribute to the development of major depressive disorder (MDD). Apigenin, a type of bioflavonoid widely found in citrus fruits, has a number of biological actions including anti-inflammatory and antioxidant effects. Although apigenin has potential antidepressant activity, the mechanisms of this effect remain unclear. The present study aims to investigate the effects of apigenin on behavioral changes and inflammatory responses induced by chronic unpredictable mild stress (CUMS) in rats. GW9662, a selective peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor, was administered 30 min before apigenin. We found that treatment with apigenin (20mg/kg, intragastrically) for three weeks remarkably ameliorated CUMS-induced behavioral abnormalities, such as decreased locomotor activity and reduced sucrose consumption. In response to oxidative stress, the NLRP3 inflammasome was activated and IL-1β secretion increased in the prefrontal cortex (PFC) of CUMS rats. However, apigenin treatment upregulated PPARγ expression and downregulated the expression of NLRP3, which subsequently downregulated the production of IL-1β. In addition, GW9662 diminished the inhibitory effects of apigenin on the NLRP3 inflammasome. In conclusion, our results demonstrate that apigenin exhibits antidepressant-like effects in CUMS rats, possibly by inhibiting IL-1β production and NLRP3 inflammasome expression via the up-regulation of PPARγ expression. Copyright © 2015. Published by Elsevier B.V.

Apigenin prevents ultraviolet-B radiation induced cyclobutane pyrimidine dimers formation in human dermal fibroblasts.

PubMed

Britto, S Mary; Shanthakumari, D; Agilan, B; Radhiga, T; Kanimozhi, G; Prasad, N Rajendra

2017-09-01

Exposure to solar ultraviolet-B (UVB) radiation leads to the formation of cyclobutane pyrimidine dimers (CPDs). We investigated the protective effect of apigenin against UVB-induced CPDs formation in human dermal fibroblasts cells (HDFa). For this purpose, HDFa cells were treated with apigenin (15μM) prior to UVB irradiation (20mJ/cm 2 ); DNA damage and subsequent molecular end points were observed. Exposure to UVB radiation increased significant CPDs formation in HDFa cells and the frequencies of CPDs were reduced by treatment with apigenin (15μM). UVB-induced CPDs downregulates the expression of nucleotide excision repair (NER) genes such as xeroderma pigmentosum complementation group C, B, G and F (XPC, XPB, XPG and XPF), transcription factor II human (TFIIH) and excision repair cross-complementation group 1 (ERCC1) in HDFa cells. Conversely, apigenin treatment restored UVB-induced loss of NER proteins in HDFa cells, which indicates its preventive effect against CPDs formation. Besides, single low dose UVB-exposure induced nuclear fragmentation, apoptotic frequency and apoptotic proteins expression (Bax and Caspase-3) have been prevented by the apigenin pretreatment. Furthermore, apigenin exhibits strong UV absorbance property and showed 10.08 SPF value. Thus, apigenin can protect skin cells against UVB-induced CPDs formation probably through its sunscreen effect. Hence, apigenin can be considered as an effective protective agent against UV induced skin damages. Copyright © 2017 Elsevier B.V. All rights reserved.

Downregulation of NEDD9 by apigenin suppresses migration, invasion, and metastasis of colorectal cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dai, Jin; Van Wie, Peter G.; Fai, Leonard Yenwong

Apigenin is a natural flavonoid which possesses multiple anti-cancer properties such as anti-proliferation, anti-inflammation, and anti-metastasis in many types of cancers including colorectal cancer. Neural precursor cell expressed developmentally downregulated 9 (NEDD9) is a multi-domain scaffolding protein of the Cas family which has been shown to correlate with cancer metastasis and progression. The present study investigates the role of NEDD9 in apigenin-inhibited cell migration, invasion, and metastasis of colorectal adenocarcinoma DLD1 and SW480 cells. The results show that knockdown of NEDD9 inhibited cell migration, invasion, and metastasis and that overexpression of NEDD9 promoted cell migration and invasion of DLD1 cellsmore » and SW4890 cells. Apigenin treatment attenuated NEDD9 expression at protein level, resulting in reduced phosphorylations of FAK, Src, and Akt, leading to inhibition on cell migration, invasion, and metastasis of both DLD1 and SW480 cells. The present study has demonstrated that apigenin inhibits cell migration, invasion, and metastasis through NEDD9/Src/Akt cascade in colorectal cancer cells. NEDD9 may function as a biomarker for evaluation of cancer aggressiveness and for selection of therapeutic drugs against cancer progression. - Highlights: • Apigenin inhibits migration, invasion, and metastasis of colorectal cancer cells. • Apigenin downregulates NEDD9. • Apigenin decreases phosphorylations of FAK, Src, and Akt. • Apigenin inhibits cell migration, invasion, and metastasis through NEDD9/Src/Akt.« less

Activation of PPARγ by a Natural Flavonoid Modulator, Apigenin Ameliorates Obesity-Related Inflammation Via Regulation of Macrophage Polarization.

PubMed

Feng, Xiujing; Weng, Dan; Zhou, Feifei; Owen, Young D; Qin, Haohan; Zhao, Jingfa; WenYu; Huang, Yahong; Chen, Jiajia; Fu, Haijian; Yang, Nanfei; Chen, Dianhua; Li, Jianxin; Tan, Renxiang; Shen, Pingping

2016-07-01

PPARγ has emerged as a master regulator of macrophage polarization and is the molecular target of the thiazolidinedione drugs. Here we show that apigenin binds and activates PPARγ by acting as a modulator. Activation of PPARγ by apigenin blocks p65 translocation into nuclei through inhibition of p65/PPARγ complex translocation into nuclei, thereby decreasing NF-κB activation and favoringM2 macrophage polarization. In HFD and ob/ob mice, apigenin significantly reverses M1 macrophage into M2 and reduces the infiltration of inflammatory cells in liver and adipose tissues, as well as decreases the levels of pro-inflammatory cytokines, thereby alleviating inflammation. Strikingly, apigenin reduces liver and muscular steatosis, decreases the levels of ALT, AST, TC and TG, improving glucose resistance obviously. Unlike rosiglitazone, apigenin does not cause significant weight gain, osteoporosis et al. Our findings identify apigenin as a modulator of PPARγ and a potential lead compound for treatment of metabolic disorders. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Dietary Apigenin Exerts Immune-Regulatory Activity in Vivo by Reducing NF-κB Activity, Halting Leukocyte Infiltration and Restoring Normal Metabolic Function.

PubMed

Cardenas, Horacio; Arango, Daniel; Nicholas, Courtney; Duarte, Silvia; Nuovo, Gerard J; He, Wei; Voss, Oliver H; Gonzalez-Mejia, M Elba; Guttridge, Denis C; Grotewold, Erich; Doseff, Andrea I

2016-03-01

The increasing prevalence of inflammatory diseases and the adverse effects associated with the long-term use of current anti-inflammatory therapies prompt the identification of alternative approaches to reestablish immune balance. Apigenin, an abundant dietary flavonoid, is emerging as a potential regulator of inflammation. Here, we show that apigenin has immune-regulatory activity in vivo. Apigenin conferred survival to mice treated with a lethal dose of Lipopolysaccharide (LPS) restoring normal cardiac function and heart mitochondrial Complex I activity. Despite the adverse effects associated with high levels of splenocyte apoptosis in septic models, apigenin had no effect on reducing cell death. However, we found that apigenin decreased LPS-induced apoptosis in lungs, infiltration of inflammatory cells and chemotactic factors' accumulation, re-establishing normal lung architecture. Using NF-κB luciferase transgenic mice, we found that apigenin effectively modulated NF-κB activity in the lungs, suggesting the ability of dietary compounds to exert immune-regulatory activity in an organ-specific manner. Collectively, these findings provide novel insights into the underlying immune-regulatory mechanisms of dietary nutraceuticals in vivo.

Suppression of AKT Potentiates Synergistic Cytotoxicity of Apigenin with TRAIL in Anaplastic Thyroid Carcinoma Cells.

PubMed

Kim, Si Hyoung; Kang, Jun Goo; Kim, Chul Sik; Ihm, Sung-Hee; Choi, Moon Gi; Yoo, Hyung Joon; Lee, Seong Jin

2015-12-01

We studied the effect of apigenin in combination with tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) on cell survival and the influence of AKT inhibition on the combined effect of apigenin with TRAIL in anaplastic thyroid carcinoma (ATC) cells. The human 8505C and CAL62 ATC cell lines were used. Apigenin in combination with TRAIL, compared to apigenin alone, reduced cell viability and Bcl2 protein levels, elevated the percentage of dead cells, as well as the protein levels of cleaved PARP and phospho-ERK1/2. The protein levels of Bcl-xL, Bax, Bid, total ERK1/2, and total and phospho-AKT were unchanged. Administration of wortmannin further reduced cell viability, and elevated the percentage of dead cells, cytotoxic activity and cleaved PARP protein levels. Apigenin synergizes with TRAIL through regulation of Bcl2 family proteins in inducing cytotoxicity, and suppression of AKT potentiates synergistic cytotoxicity of apigenin with TRAIL in ATC cells. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Effects of luteolin on regulatory proteins and enzymes for myocyte calcium circulation in hypothermic preserved rat heart

PubMed Central

Yan, Qingfeng; Li, Yueping; Yan, Jia; Zhao, Ying; Liu, Yunzhong; Liu, Su

2018-01-01

Heart transplantation has been applied in the clinic as an optimal solution for patients with end stage cardiac failure for a number of years. However, hypothermic preservation of the heart remains limited to 4–6 h and calcium accumulation over time is an important factor resulting in cell death. To provide longer and safer storage for donor hearts, it was demonstrated in our previous study that luteolin, a traditional Chinese medicine used to treat cardiovascular diseases, inhibits cell death and L-type calcium currents during hypothermic preservation. In the current study, the protective role of luteolin in modulating cardiomyocyte calcium cycling was further investigated. Intracellular calcium overload has already been implicated in hypothermia-induced dysfunction of cardiomyocytes. University of Wisconsin (UW) solution supplemented with 7.5, 15 or 30 µmol/l luteolin was used to preserve fresh isolated cardiomyocytes at 4°C. The results demonstrated that all three doses of luteolin supplementation attenuated calcium overload over a 6 h preservation period. Luteolin also suppressed the accumulation of important regulatory proteins and enzymes for cardiomyocyte calcium circulation, mitochondria Ca2+ uniporter and calmodulin, which are normally induced by cold storage in UW solution. Protein Kinase A activity was also suppressed in cardiomyocytes preserved in luteolin supplemented UW solution, while Ca2+-Mg2+-ATPase activity was increased. The results demonstrated that luteolin confers a cardioprotective effect through inhibiting the changes of calcium regulators during cold storage and therefore ameliorates Ca2+ overload in rat cardiomyocytes. PMID:29399124

Hydrogen-bonding Interactions between Apigenin and Ethanol/Water: A Theoretical Study

NASA Astrophysics Data System (ADS)

Zheng, Yan-Zhen; Zhou, Yu; Liang, Qin; Chen, Da-Fu; Guo, Rui; Lai, Rong-Cai

2016-10-01

In this work, hydrogen-bonding interactions between apigenin and water/ethanol were investigated from a theoretical perspective using quantum chemical calculations. Two conformations of apigenin molecule were considered in this work. The following results were found. (1) For apigenin monomer, the molecular structure is non-planar, and all of the hydrogen and oxygen atoms can be hydrogen-bonding sites. (2) Eight and seven optimized geometries are obtained for apigenin (I)-H2O/CH3CH2OH and apigenin (II)-H2O/CH3CH2OH complexes, respectively. In apigenin, excluding the aromatic hydrogen atoms in the phenyl substituent, all other hydrogen atoms and the oxygen atoms form hydrogen-bonds with H2O and CH3CH2OH. (3) In apigenin-H2O/CH3CH2OH complexes, the electron density and the E(2) in the related localized anti-bonding orbital are increased upon hydrogen-bond formation. These are the cause of the elongation and red-shift of the X-H bond. The sum of the charge change transfers from the hydrogen-bond acceptor to donor. The stronger interaction makes the charge change more intense than in the less stable structures. (4) Most of the hydrogen-bonds in the complexes are electrostatic in nature. However, the C4-O5···H, C9-O4···H and C13-O2···H hydrogen-bonds have some degree of covalent character. Furthermore, the hydroxyl groups of the apigenin molecule are the preferred hydrogen-bonding sites.

Formulation and characterization of an apigenin-phospholipid phytosome (APLC) for improved solubility, in vivo bioavailability, and antioxidant potential.

PubMed

Telange, Darshan R; Patil, Arun T; Pethe, Anil M; Fegade, Harshal; Anand, Sridhar; Dave, Vivek S

2017-10-15

The apigenin-phospholipid phytosome (APLC) was developed to improve the aqueous solubility, dissolution, in vivo bioavailability, and antioxidant activity of apigenin. The APLC synthesis was guided by a full factorial design strategy, incorporating specific formulation and process variables to deliver an optimized product. The design-optimized formulation was assayed for aqueous solubility, in vitro dissolution, pharmacokinetics, and antioxidant activity. The pharmacological evaluation was carried out by assessing its effects on carbon tetrachloride-induced elevation of liver function marker enzymes in a rat model. The antioxidant activity was assessed by studying its effects on the liver antioxidant marker enzymes. The developed model was validated using the design-optimized levels of formulation and process variables. The physical-chemical characterization confirmed the formation of phytosomes. The optimized formulation demonstrated over 36-fold higher aqueous solubility of apigenin, compared to that of pure apigenin. The formulation also exhibited a significantly higher rate and extent of apigenin release in dissolution studies. The pharmacokinetic analysis revealed a significant enhancement in the oral bioavailability of apigenin from the prepared formulation, compared to pure apigenin. The liver function tests indicated that the prepared phytosome showed a significantly improved restoration of all carbon tetrachloride-elevated rat liver function marker enzymes. The prepared formulation also exhibited antioxidant potential by significantly increasing the levels of glutathione, superoxide dismutase, catalase, and decreasing the levels of lipid peroxidase. The study shows that phospholipid-based phytosome is a promising and viable strategy for improving the delivery of apigenin and similar phytoconstituents with low aqueous solubility. Copyright © 2016 Elsevier B.V. All rights reserved.

Induction of caspase-dependent extrinsic apoptosis by apigenin through inhibition of signal transducer and activator of transcription 3 (STAT3) signalling in HER2-overexpressing BT-474 breast cancer cells.

PubMed

Seo, Hye-Sook; Jo, Jae Kyung; Ku, Jin Mo; Choi, Han-Seok; Choi, Youn Kyung; Woo, Jong-Kyu; Kim, Hyo In; Kang, Soo-Yeon; Lee, Kang Min; Nam, Koong Won; Park, Namkyu; Jang, Bo-Hyoung; Shin, Yong Cheol; Ko, Seong-Gyu

2015-10-23

Phytoestrogen intake is known to be beneficial to decrease breast cancer incidence and progression. But its molecular mechanisms of action are still unknown. The present study aimed to examine the effect of apigenin on proliferation and apoptosis in HER2-expressing breast cancer cells. In our experiments, apigenin inhibited the proliferation of BT-474 cells in a dose- and time-dependent manner. Apigenin also inhibited clonogenic survival (anchorage-dependent and -independent) of BT-474 cells in a dose-dependent manner. These growth inhibitions were accompanied with an increase in sub-G0/G1 apoptotic populations. Apigenin-induced extrinsic a caspase-dependent apoptosis up-regulating the levels of cleaved caspase-8 and cleaved caspase-3, and inducing the cleavage of poly (ADP-ribose) polymerase (PARP). Whereas, apigenin did not induce apoptosis via intrinsic mitochondrial apoptosis pathway since this compound did not decrease mitochondrial membrane potential without affecting the levels of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (BAX). Apigenin reduced the expression of phospho-JAK1, phospho-JAK2 and phospho-STAT3 and decreased signal transducer and activator of transcription 3 (STAT3) dependent luciferase reporter gene activity in BT-474 cells. Apigenin inhibited CoCl2-induced VEGF secretion and decreased the nuclear translocation of STAT3. Our study indicates that apigenin induces apoptosis through inhibition of STAT3 signalling and could serve as a useful compound to prevent or treat HER2-overexpressing breast cancer. © 2015 Authors.

Induction of caspase-dependent extrinsic apoptosis by apigenin through inhibition of signal transducer and activator of transcription 3 (STAT3) signalling in HER2-overexpressing BT-474 breast cancer cells

PubMed Central

Seo, Hye-Sook; Jo, Jae Kyung; Ku, Jin Mo; Choi, Han-Seok; Choi, Youn Kyung; Woo, Jong-Kyu; in Kim, Hyo; Kang, Soo-yeon; Lee, Kang min; Nam, Koong Won; Park, Namkyu; Jang, Bo-Hyoung; Shin, Yong Cheol; Ko, Seong-Gyu

2015-01-01

Phytoestrogen intake is known to be beneficial to decrease breast cancer incidence and progression. But its molecular mechanisms of action are still unknown. The present study aimed to examine the effect of apigenin on proliferation and apoptosis in HER2-expressing breast cancer cells. In our experiments, apigenin inhibited the proliferation of BT-474 cells in a dose- and time-dependent manner. Apigenin also inhibited clonogenic survival (anchorage-dependent and -independent) of BT-474 cells in a dose-dependent manner. These growth inhibitions were accompanied with an increase in sub-G0/G1 apoptotic populations. Apigenin-induced extrinsic a caspase-dependent apoptosis up-regulating the levels of cleaved caspase-8 and cleaved caspase-3, and inducing the cleavage of poly (ADP-ribose) polymerase (PARP). Whereas, apigenin did not induce apoptosis via intrinsic mitochondrial apoptosis pathway since this compound did not decrease mitochondrial membrane potential without affecting the levels of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (BAX). Apigenin reduced the expression of phospho-JAK1, phospho-JAK2 and phospho-STAT3 and decreased signal transducer and activator of transcription 3 (STAT3) dependent luciferase reporter gene activity in BT-474 cells. Apigenin inhibited CoCl2-induced VEGF secretion and decreased the nuclear translocation of STAT3. Our study indicates that apigenin induces apoptosis through inhibition of STAT3 signalling and could serve as a useful compound to prevent or treat HER2-overexpressing breast cancer. PMID:26500281

Advantages of Molecular Weight Identification during Native MS Screening.

PubMed

Khan, Ahad; Bresnick, Anne; Cahill, Sean; Girvin, Mark; Almo, Steve; Quinn, Ronald

2018-05-09

Native mass spectrometry detection of ligand-protein complexes allowed rapid detection of natural product binders of apo and calcium-bound S100A4 (a member of the metal binding protein S100 family), T cell/transmembrane, immunoglobulin (Ig), and mucin protein 3, and T cell immunoreceptor with Ig and ITIM (immunoreceptor tyrosine-based inhibitory motif) domains precursor protein from extracts and fractions. Based on molecular weight common hits were detected binding to all four proteins. Seven common hits were identified as apigenin 6- C - β - D -glucoside 8- C - α - L -arabinoside, sweroside, 4',5-dihydroxy-7-methoxyflavanone-6- C -rutinoside, loganin acid, 6- C -glucosylnaringenin, biochanin A 7- O -rutinoside and quercetin 3- O -rutinoside. Mass guided isolation and NMR identification of hits confirmed the mass accuracy of the ligand in the ligand-protein MS complexes. Thus, molecular weight ID from ligand-protein complexes by electrospray ionization Fourier transform mass spectrometry allowed rapid dereplication. Native mass spectrometry using electrospray ionization Fourier transform mass spectrometry is a tool for dereplication and metabolomics analysis. Georg Thieme Verlag KG Stuttgart · New York.

Use of apigenin from Cordia dichotoma in the treatment of colitis.

PubMed

Ganjare, Anjali B; Nirmal, Sunil A; Patil, Anuja N

2011-10-01

Cordia dichotoma f. (Boraginaceae) is a small deciduous tree from India. The bark of was used in the treatment of ulcerative colitis (UC) and colic pain traditionally hence present work was undertaken to identify the phytoconstituent responsible for this activity. Apigenin is isolated by column chromatography from methanol fraction of crude methanol extract of C. dichotoma bark. Structure of apigenin is established by various spectroscopic studies. Apigenin (5mg/kg, p.o.) showed significant healing and reduction in inflammatory enzymes when screened for UC. It can be concluded that apigenin from C. dichotoma bark may be responsible for the treatment of UC. Copyright © 2011 Elsevier B.V. All rights reserved.

Apigenin Induces the Apoptosis and Regulates MAPK Signaling Pathways in Mouse Macrophage ANA-1 Cells

PubMed Central

Liao, Yuexia; Shen, Weigan; Kong, Guimei; Lv, Houning; Tao, Wenhua; Bo, Ping

2014-01-01

Apigenin is a naturally occurring plant flavonoid that possesses antioxidant, anti-cancer and anti-inflammatory properties. However, there are few reports has been done on the ability of apigenin to induce apoptosis in macrophages. In this study, mouse macrophage ANA-1 cells were incubated with different concentrations of apigenin. The cell viability was determined by an MTT assay. The cell apoptosis were analyzed by flow cytometric analysis. Apoptosis were also analyzed using a TUNEL assay and a DNA ladder. The level of intracellular ROS was detected using a dichlorofluorescein -diacetate probe. The expression levels of apoptosis-related proteins were detected by western blot analysis. The results showed that apigenin decreased the viability of ANA-1 cells and induced apoptosis in a dose- and time-dependent manner. Apigenin increased the level of intracellular ROS, downregulated the expression of Bcl-2 and upregulated the expression of caspase-3 and caspase-8 in ANA-1 cells. Furthermore, apigenin downregulated the expression of phospho-ERK and phospho-JNK, upregulated the expression of phospho-p38 and had no significant effect on the expression of Bax, ERK, JNK and p38. The results suggested that apigenin induced cell apoptosis in mouse macrophage ANA-1 cells may via increasing intracellular ROS, regulating the MAPK pathway, and then inhibiting Bcl-2 expression. PMID:24646936

AgFNS overexpression increase apigenin and decrease anthocyanins in petioles of transgenic celery.

PubMed

Tan, Guo-Fei; Ma, Jing; Zhang, Xin-Yue; Xu, Zhi-Sheng; Xiong, Ai-Sheng

2017-10-01

Apigenin and anthocyanin biosyntheses share common precursors in plants. Flavone synthase (FNS) converts naringenin into apigenin in higher plants. Celery is an important edible and medical vegetable crop that contains apigenin in its tissues. However, the effect of high AgFNS gene expression on the apigenin and anthocyanins contents of purple celery remains to be elucidated. In this study, the AgFNS gene was cloned from purple celery ('Nanxuan liuhe purple celery') and overexpressed in this purple celery to determine its influence on anthocyanins and apigenin contents. Results showed that the AgFNS gene was 1068bp, which encodes 355 amino acid residues. Evolution analysis showed that the AgFNS protein belongs to the FSN I type. In AgFNS transgenic celery, the anthocyanins content in petioles was lower than that wild-type celery plants. Apigenin content increased in the petioles of AgFNS transgenic celery. The transcript levels of the AgPAL, AgC4H, AgCHS, and AgCHI genes were up-regulated, whereas those of the AgF3H, AgF3'H, AgDFR, AgANS, and Ag3GT genes were down-regulated in the petioles of AgFNS transgenic plants compared with wild-type celery plants. This work provides basic knowledge about the function of the AgFNS gene in the anthocyanin and apigenin biosyntheses of celery. Copyright © 2017 Elsevier B.V. All rights reserved.

Apigenin induces both intrinsic and extrinsic pathways of apoptosis in human colon carcinoma HCT-116 cells.

PubMed

Wang, Bo; Zhao, Xin-Huai

2017-02-01

Apigenin is one of the plant-originated flavones with anticancer activities. In this study, apigenin was assessed for its in vitro effects on a human colon carcinoma line (HCT‑116 cells) in terms of anti-proliferation, cell cycle progression arrest, apoptosis and intracellular reactive oxygen species (ROS) generation, and then outlined its possible apoptotic mechanism for the cells. Apigenin exerted cytotoxic effect on the cells via inhibiting cell growth in a dose-time-dependent manner and causing morphological changes, arrested cell cycle progression at G0/G1 phase, and decreased mitochondrial membrane potential of the treated cells. Apigenin increased respective ROS generation and Ca2+ release and thereby, caused ER stress in the treated cells. Apigenin shows apoptosis induction towards the cells, resulting in enhanced portion of apoptotic cells. A mechanism involved ROS generation and endoplasmic reticulum stress was outlined for the apigenin-mediated apoptosis via both intrinsic mitochondrial and extrinsic pathways, based on the assayed mRNA and protein expression levels in the cells. With this mechanism, apigenin resulted in the HCT-116 cells with enhanced intracellular ROS generation and Ca2+ release together with damaged mitochondrial membrane, and upregulated protein expression of CHOP, DR5, cleaved BID, Bax, cytochrome c, cleaved caspase-3, cleaved caspase-8 and cleaved caspase-9, which triggered apoptosis of the cells.

Oxidative Stress Triggered by Apigenin Induces Apoptosis in a Comprehensive Panel of Human Cervical Cancer-Derived Cell Lines.

PubMed

Souza, Raquel P; Bonfim-Mendonça, Patrícia de S; Gimenes, Fabrícia; Ratti, Bianca A; Kaplum, Vanessa; Bruschi, Marcos L; Nakamura, Celso V; Silva, Sueli O; Maria-Engler, Silvya S; Consolaro, Marcia E L

2017-01-01

Recently, the cytotoxic effects of apigenin (4',5,7-trihydroxyflavone), particularly its marked inhibition of cancer cell viability both in vitro and in vivo, have attracted the attention of the anticancer drug discovery field. Despite this, there are few studies of apigenin in cervical cancer, and these studies have mostly been conducted using HeLa cells. To evaluate the possibility of apigenin as a new therapeutic candidate for cervical cancer, we evaluated its cytotoxic effects in a comprehensive panel of human cervical cancer-derived cell lines including HeLa (human papillomavirus/HPV 18-positive), SiHa (HPV 16-positive), CaSki (HPV 16 and HPV 18-positive), and C33A (HPV-negative) cells in comparison to a nontumorigenic spontaneously immortalized human epithelial cell line (HaCaT). Our results demonstrated that apigenin had a selective cytotoxic effect and could induce apoptosis in all cervical cancer cell lines which were positively marked with Annexin V, but not in HaCaT (control cells). Additionally, apigenin was able to induce mitochondrial redox impairment, once it increased ROS levels and H 2 O 2 , decreased the Δ ψm , and increased LPO. Still, apigenin was able to inhibit migration and invasion of cancer cells. Thus, apigenin appears to be a promising new candidate as an anticancer drug for cervical cancer induced by different HPV genotypes.

Oxidative Stress Triggered by Apigenin Induces Apoptosis in a Comprehensive Panel of Human Cervical Cancer-Derived Cell Lines

PubMed Central

Souza, Raquel P.; Gimenes, Fabrícia; Ratti, Bianca A.; Kaplum, Vanessa; Bruschi, Marcos L.; Nakamura, Celso V.; Maria-Engler, Silvya S.

2017-01-01

Recently, the cytotoxic effects of apigenin (4′,5,7-trihydroxyflavone), particularly its marked inhibition of cancer cell viability both in vitro and in vivo, have attracted the attention of the anticancer drug discovery field. Despite this, there are few studies of apigenin in cervical cancer, and these studies have mostly been conducted using HeLa cells. To evaluate the possibility of apigenin as a new therapeutic candidate for cervical cancer, we evaluated its cytotoxic effects in a comprehensive panel of human cervical cancer-derived cell lines including HeLa (human papillomavirus/HPV 18-positive), SiHa (HPV 16-positive), CaSki (HPV 16 and HPV 18-positive), and C33A (HPV-negative) cells in comparison to a nontumorigenic spontaneously immortalized human epithelial cell line (HaCaT). Our results demonstrated that apigenin had a selective cytotoxic effect and could induce apoptosis in all cervical cancer cell lines which were positively marked with Annexin V, but not in HaCaT (control cells). Additionally, apigenin was able to induce mitochondrial redox impairment, once it increased ROS levels and H2O2, decreased the Δψm, and increased LPO. Still, apigenin was able to inhibit migration and invasion of cancer cells. Thus, apigenin appears to be a promising new candidate as an anticancer drug for cervical cancer induced by different HPV genotypes. PMID:28191273

The antiproliferative and apoptotic effects of apigenin on glioblastoma cells.

PubMed

Stump, Trevor A; Santee, Brittany N; Williams, Lauren P; Kunze, Rachel A; Heinze, Chelsae E; Huseman, Eric D; Gryka, Rebecca J; Simpson, Denise S; Amos, Samson

2017-07-01

Glioblastoma (GBM) is highly proliferative, infiltrative, malignant and the most deadly form of brain tumour. The epidermal growth factor receptor (EGFR) is overexpressed, amplified and mutated in GBM and has been shown to play key and important roles in the proliferation, growth and survival of this tumour. The goal of our study was to investigate the antiproliferative, apoptotic and molecular effects of apigenin in GBM. Proliferation and viability tests were carried out using the trypan blue exclusion, MTT and lactate dehydrogenase (LDH) assays. Flow cytometry was used to examine the effects of apigenin on the cell cycle check-points. In addition, we determined the effects of apigenin on EGFR-mediated signalling pathways by Western blot analyses. Our results showed that apigenin reduced cell viability and proliferation in a dose- and time-dependent manner while increasing cytotoxicity in GBM cells. Treatment with apigenin-induced is poly ADP-ribose polymerase (PARP) cleavage and caused cell cycle arrest at the G2M checkpoint. Furthermore, our data revealed that apigenin inhibited EGFR-mediated phosphorylation of mitogen-activated protein kinase (MAPK), AKT and mammalian target of rapamycin (mTOR) signalling pathways and attenuated the expression of Bcl-xL. Our results demonstrated that apigenin has potent inhibitory effects on pathways involved in GBM proliferation and survival and could potentially be used as a therapeutic agent for GBM. © 2017 Royal Pharmaceutical Society.

Apigenin Alleviates Endotoxin-Induced Myocardial Toxicity by Modulating Inflammation, Oxidative Stress, and Autophagy

PubMed Central

Li, Fang; Lang, Fangfang; Zhang, Huilin; Xu, Liangdong; Wang, Yidan; Zhai, Chunxiao

2017-01-01

Apigenin, a component in daily diets, demonstrates antioxidant and anti-inflammatory properties. Here, we intended to explore the mechanism of apigenin-mediated endotoxin-induced myocardial injury and its role in the interplay among inflammation, oxidative stress, and autophagy. In our lipopolysaccharide- (LPS-) induced myocardial injury model, apigenin ameliorated cardiac injury (lactate dehydrogenase (LDH) and creatine kinase (CK)), cell death (TUNEL staining, DNA fragmentation, and PARP activity), and tissue damage (cardiac troponin I (cTnI) and cardiac myosin light chain-1 (cMLC1)) and improved cardiac function (ejection fraction (EF) and end diastolic left ventricular inner dimension (LVID)). Apigenin also alleviated endotoxin-induced myocardial injury by modulating oxidative stress (nitrotyrosine and protein carbonyl) and inflammatory cytokines (TNF-α, IL-1β, MIP-1α, and MIP-2) along with their master regulator NFκB. Apigenin modulated redox homeostasis, and its anti-inflammatory role might be associated with its ability to control autophagy. Autophagy (determined by LAMP1, ATG5, and p62), its transcriptional regulator transcription factor EB (TFEB), and downstream target genes including vacuolar protein sorting-associated protein 11 (Vps11) and microtubule-associated proteins 1A/1B light chain 3B (Map1lc3) were modulated by apigenin. Thus, our study demonstrated that apigenin may lead to potential development of new target in sepsis treatment or other myocardial oxidative and/or inflammation-induced injuries. PMID:28828145

Inhibition of mTOR by apigenin in UVB-irradiated keratinocytes: A new implication of skin cancer prevention.

PubMed

Bridgeman, Bryan B; Wang, Pu; Ye, Boping; Pelling, Jill C; Volpert, Olga V; Tong, Xin

2016-05-01

Ultraviolet B (UVB) radiation is the major environmental risk factor for developing skin cancer, the most common cancer worldwide, which is characterized by aberrant activation of Akt/mTOR (mammalian target of rapamycin). Importantly, the link between UV irradiation and mTOR signaling has not been fully established. Apigenin is a naturally occurring flavonoid that has been shown to inhibit UV-induced skin cancer. Previously, we have demonstrated that apigenin activates AMP-activated protein kinase (AMPK), which leads to suppression of basal mTOR activity in cultured keratinocytes. Here, we demonstrated that apigenin inhibited UVB-induced mTOR activation, cell proliferation and cell cycle progression in mouse skin and in mouse epidermal keratinocytes. Interestingly, UVB induced mTOR signaling via PI3K/Akt pathway, however, the inhibition of UVB-induced mTOR signaling by apigenin was not Akt-dependent. Instead, it was driven by AMPK activation. In addition, mTOR inhibition by apigenin in keratinocytes enhanced autophagy, which was responsible, at least in part, for the decreased proliferation in keratinocytes. In contrast, apigenin did not alter UVB-induced apoptosis. Taken together, our results indicate the important role of mTOR inhibition in UVB protection by apigenin, and provide a new target and strategy for better prevention of UV-induced skin cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Angiogenic effects of apigenin on endothelial cells after hypoxia-reoxygenation via the caveolin-1 pathway

PubMed Central

Tu, Fengxia; Pang, Qiongyi; Chen, Xiang; Huang, Tingting; Liu, Meixia; Zhai, Qiongxiang

2017-01-01

In the present study, we aimed to elucidate whether apigenin contributes to the induction of angiogenesis and the related mechanisms in cell hypoxia-reoxygenation injury. The role of apigenin was examined in human umbilical vein endothelial cell (HUVEC) viability, migration and tube formation in vitro. To investigate the related mechanisms, we used caveolin-1 short interfering RNA. The viability of HUVECs was measured using Cell Counting Kit-8 assays, HUVEC migration was analyzed by crystal violet staining, and a tube formation assay was performed using the branch point method. Expression of caveolin-1, vascular endothelial growth factor (VEGF), and endothelial nitric oxide synthase (eNOS) in HUVECs was examined by polymerase chain reaction and western blotting. Our data revealed that apigenin induced angiogenesis in vitro by increasing the tube formation ability of HUVECs, which was counteracted by caveolin-1 silencing. Compared to the NC group, Caveolin-1 and eNOS expression was upregulated by apigenin, whereas compared to the NC group, eNOS expression was increased upon caveolin-1 silencing. The expression of VEGF was increased by treatment with apigenin; however, compared to the NC group, caveolin-1 silencing did not affect VEGF expression, and apigenin did not increase VEGF expression in HUVECs after caveolin-1 silencing. These data suggest that apigenin may be a candidate therapeutic target for stroke recovery by promoting angiogenesis via the caveolin-1 signaling pathway. PMID:29039442

The Protective Effect of Apigenin on Myocardial Injury in Diabetic Rats mediating Activation of the PPAR-γ Pathway.

PubMed

Mahajan, Umesh B; Chandrayan, Govind; Patil, Chandragouda R; Arya, Dharamvir Singh; Suchal, Kapil; Agrawal, Yogeeta O; Ojha, Shreesh; Goyal, Sameer N

2017-04-04

We substantiated the role of peroxisome proliferator-activated receptor-γ (PPAR-γ) activation in the protective effect of apigenin against the myocardial infarction (MI) in diabetic rats. Diabetes was induced by intraperitoneal administration of a single dose of streptozotocin (55 mg/kg). The study groups included diabetic rats receiving vehicle, apigenin (75 mg/kg/day, orally), GW9662 (1 mg/kg/day, intraperitoneally), and a combination of apigenin and GW9662 for 14 days. The MI was induced in all the study groups except the diabetic control group by subcutaneous injection of 100 mg/kg/day of isoproterenol on the two terminal days. The diabetes and isoproterenol-induced MI was evident as a reduction in the maximal positive and negative rate of developed left ventricular pressure and an increase in the left ventricular end-diastolic pressure. The activities of creatine kinase on myocardial bundle (CK-MB) and lactate dehydrogenase (LDH) were also reduced. Apigenin treatment prevented the hemodynamic perturbations, restored the left ventricular function and reinstated a balanced redox status. It protected rats against an MI by attenuating myonecrosis, edema, cell death, and oxidative stress. GW9662, a PPAR-γ antagonist reversed the myocardial protection conferred by apigenin. Further, an increase in the PPAR-γ expression in the myocardium of the rats receiving apigenin reinforces the role of PPAR-γ pathway activation in the cardioprotective effects of apigenin.

Apigenin Alleviates Endotoxin-Induced Myocardial Toxicity by Modulating Inflammation, Oxidative Stress, and Autophagy.

PubMed

Li, Fang; Lang, Fangfang; Zhang, Huilin; Xu, Liangdong; Wang, Yidan; Zhai, Chunxiao; Hao, Enkui

2017-01-01

Apigenin, a component in daily diets, demonstrates antioxidant and anti-inflammatory properties. Here, we intended to explore the mechanism of apigenin-mediated endotoxin-induced myocardial injury and its role in the interplay among inflammation, oxidative stress, and autophagy. In our lipopolysaccharide- (LPS-) induced myocardial injury model, apigenin ameliorated cardiac injury (lactate dehydrogenase (LDH) and creatine kinase (CK)), cell death (TUNEL staining, DNA fragmentation, and PARP activity), and tissue damage (cardiac troponin I (cTnI) and cardiac myosin light chain-1 (cMLC1)) and improved cardiac function (ejection fraction (EF) and end diastolic left ventricular inner dimension (LVID)). Apigenin also alleviated endotoxin-induced myocardial injury by modulating oxidative stress (nitrotyrosine and protein carbonyl) and inflammatory cytokines (TNF- α , IL-1 β , MIP-1 α , and MIP-2) along with their master regulator NF κ B. Apigenin modulated redox homeostasis, and its anti-inflammatory role might be associated with its ability to control autophagy. Autophagy (determined by LAMP1, ATG5, and p62), its transcriptional regulator transcription factor EB (TFEB), and downstream target genes including vacuolar protein sorting-associated protein 11 (Vps11) and microtubule-associated proteins 1A/1B light chain 3B (Map1lc3) were modulated by apigenin. Thus, our study demonstrated that apigenin may lead to potential development of new target in sepsis treatment or other myocardial oxidative and/or inflammation-induced injuries.

Apigenin shows synergistic anticancer activity with curcumin by binding at different sites of tubulin.

PubMed

Choudhury, Diptiman; Ganguli, Arnab; Dastidar, Debabrata Ghosh; Acharya, Bipul R; Das, Amlan; Chakrabarti, Gopal

2013-06-01

Apigenin, a natural flavone, present in many plants sources, induced apoptosis and cell death in lung epithelium cancer (A549) cells with an IC50 value of 93.7 ± 3.7 μM for 48 h treatment. Target identification investigations using A549 cells and also in cell-free system demonstrated that apigenin depolymerized microtubules and inhibited reassembly of cold depolymerized microtubules of A549 cells. Again apigenin inhibited polymerization of purified tubulin with an IC50 value of 79.8 ± 2.4 μM. It bounds to tubulin in cell-free system and quenched the intrinsic fluorescence of tubulin in a concentration- and time-dependent manner. The interaction was temperature-dependent and kinetics of binding was biphasic in nature with binding rate constants of 11.5 × 10(-7) M(-1) s(-1) and 4.0 × 10(-9) M(-1) s(-1) for fast and slow phases at 37 °C, respectively. The stoichiometry of tubulin-apigenin binding was 1:1 and binding the binding constant (Kd) was 6.08 ± 0.096 μM. Interestingly, apigenin showed synergistic anti-cancer effect with another natural anti-tubulin agent curcumin. Apigenin and curcumin synergistically induced cell death and apoptosis and also blocked cell cycle progression at G2/M phase of A549 cells. The synergistic activity of apigenin and curcumin was also apparent from their strong depolymerizing effects on interphase microtubules and inhibitory effect of reassembly of cold depolymerized microtubules when used in combinations, indicating that these ligands bind to tubulin at different sites. In silico modeling suggested apigenin bounds at the interphase of α-β-subunit of tubulin. The binding site is 19 Å in distance from the previously predicted curcumin binding site. Binding studies with purified protein also showed both apigenin and curcumin can simultaneously bind to purified tubulin. Understanding the mechanism of synergistic effect of apigenin and curcumin could be helped to develop anti-cancer combination drugs from cheap and readily available nutraceuticals. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

In vitro antioxidant properties, free radicals scavenging activities of extracts and polyphenol composition of a non-timber forest product used as spice: Monodora myristica.

PubMed

Moukette, Bruno Moukette; Pieme, Constant Anatole; Njimou, Jacques Romain; Biapa, Cabral Prosper Nya; Marco, Bravi; Ngogang, Jeanne Yonkeu

2015-03-14

Excessive production of free radicals causes direct damage to biological molecules such as DNA, proteins, lipids, carbohydrates leading to tumor development and progression. Natural antioxidant molecules from phytochemicals of plant origin may directly inhibit either their production or limit their propagation or destroy them to protect the system. In the present study, Monodora myristica a non-timber forest product consumed in Cameroon as spice was screened for its free radical scavenging properties, antioxidant and enzymes protective activities. Its phenolic compound profile was also realized by HPLC. This study demonstrated that M. myristica has scavenging properties against DPPH(•), OH(•), NO(•), and ABTS(•) radicals which vary in a dose depending manner. It also showed an antioxidant potential that was comparable with that of Butylated Hydroxytoluene (BHT) and vitamin C used as standard. The aqueous ethanol extract of M. myristica barks (AEH); showed a significantly higher content in polyphenolic compounds (21.44 ± 0.24 mg caffeic acid/g dried extract) and flavonoid (5.69 ± 0.07 quercetin equivalent mg/g of dried weight) as compared to the other studied extracts. The HPLC analysis of the barks and leaves revealed the presence of several polyphenols. The acids (3,4-OH-benzoic, caffeic, gallic, O- and P- coumaric, syringic, vanillic), alcohols (tyrosol and OH-tyrosol), theobromine, quercetin, rutin, catechine and apigenin were the identified and quantified polyphenols. All the tested extracts demonstrated a high protective potential on the superoxide dismutase (SOD), catalase and peroxidase activities. Finally, the different extracts from M. myristica and specifically the aqueous ethanol extract reveal several properties such as higher free radical scavenging properties, significant antioxidant capacities and protective potential effects on liver enzymes.

Liquid chromatography-tandem mass spectrometry analysis allows the simultaneous characterization of C-glycosyl and O-glycosyl flavonoids in stingless bee honeys.

PubMed

Truchado, Pilar; Vit, Patricia; Ferreres, Federico; Tomas-Barberan, Francisco

2011-10-21

The analysis of the phytochemicals present in stingless bee honey samples has been a difficult task due to the small amounts of samples available and to the complexity of the phytochemical composition that often combines flavonoid glycosides and aglycones. Honey samples produced in Venezuela from Melipona species were analyzed using a combination of solid-phase extraction and HPLC-DAD-MSn/ESI methodologies with specific study of the fragment ions produced from flavonoid glycosides. The analyses revealed that flavonoid glycosides were the main constituents. The honey samples analyzed contained a consistent flavonoid pattern composed of flavone-C-glycosides, flavonol-O-glycosides and flavonoid aglycones. The HPLC-DAD-MSn/ESI analysis and the study of the fragment ions obtained allowed the characterization and quantification for the first time of five apigenin-di-C-glycosides, and ten quercetin, kaempferol and isorhamnetin O-glycosides (di- and tri- glycosides), and the aglycones pinobanksin, quercetin, kaempferol and isorhamnetin in the different samples. This is the first report of flavonoid-C-glycosides in honey. The results show that the content of flavonoid-glycosides (mean values of 2712 μg/100 g) in stingless bee honeys is considerably higher than the content of flavonoid aglycones (mean values of 315 μg/100 g). This differs from previous studies on Apis mellifera honeys that consistently showed much higher aglycone content and smaller flavonoid glycoside content. The occurrence of relevant amounts of flavonoid glycosides, and particularly C-glycosides, in stingless bee honeys could be associated with their putative anticataract properties. Copyright © 2011 Elsevier B.V. All rights reserved.

Luteolin reduces inflammation in Staphylococcus aureus-induced mastitis by inhibiting NF-kB activation and MMPs expression.

PubMed

Guo, Ying-Fang; Xu, Nian-Nian; Sun, Weijing; Zhao, Yifan; Li, Cheng-Ye; Guo, Meng-Yao

2017-04-25

Mastitis is a serious and prevalent disease caused by infection by pathogens such as Staphylococcus aureus. We evaluated the anti-inflammatory effects and mechanism of luteolin, a natural flavonoid with a wide range of pharmacological activities, in a mouse model of S. aureus mastitis. We also treated cultured mouse mammary epithelial cells (mMECs) with S. aureus and luteolin. Histopathological changes were examined by H&E staining and the levels of inflammatory cytokine proteins were analyzed using ELISAs. We determined mRNA levels with qPCR and the level of NF-κB and matrix metalloproteinase (MMP) proteins by Western blotting. The observed histopathological changes showed that luteolin protected mammary glands with S. aureus infection from tissue destruction and inflammatory cell infiltration. Luteolin inhibited the expression of TNF-α, IL-1β, and IL-6, all of which were increased with S. aureus infection of mammary tissues and mMECs. S. aureus-induced TLR2 and TLR4 was suppressed by luteolin, as were levels of IκBα and NF-κB p65 phosphorylation and expression of MMP-2 and MMP-9. Levels of tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2 were enhanced. These findings suggest luteolin is a potentially effective new treatment to reduce tissue damage and inflammation from S. aureus-induced mastitis.

Luteolin, a novel natural inhibitor of tumor progression locus 2 serine/threonine kinase, inhibits tumor necrosis factor-alpha-induced cyclooxygenase-2 expression in JB6 mouse epidermis cells.

PubMed

Kim, Jong-Eun; Son, Joe Eun; Jang, Young Jin; Lee, Dong Eun; Kang, Nam Joo; Jung, Sung Keun; Heo, Yong-Seok; Lee, Ki Won; Lee, Hyong Joo

2011-09-01

Targeting tumor necrosis factor (TNF)-α-mediated signal pathways may be a promising strategy for developing chemopreventive agents, because TNF-α-mediated cyclooxygenase (COX)-2 expression plays a key role in inflammation and carcinogenesis. Luteolin [2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-chromenone] exerts anticarcinogenic effects, although little is known about the underlying molecular mechanisms and specific targets of this compound. In the present study, we found that luteolin inhibited TNF-α-induced COX-2 expression by down-regulating the transactivation of nuclear factor-κB and activator protein-1. Furthermore, luteolin inhibited TNF-α-induced phosphorylation of mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase 1/ERK/p90(RSK), mitogen-activated protein kinase kinase 4/c-Jun N-terminal kinase/c-Jun, and Akt/p70(S6K). However, it had no effect on the phosphorylation of p38. These effects of luteolin on TNF-α-mediated signaling pathways and COX-2 expression are similar to those achieved by blocking tumor progression locus 2 serine/threonine kinase (TPL2) using pharmacologic inhibitors and small interfering RNAs. Luteolin inhibited TPL2 activity in vitro and in TPL2 immunoprecipitation kinase assays by binding directly in an ATP-competitive manner. Overall, these results indicate that luteolin exerts potent chemopreventive activities, which primarily target TPL2.

The Flavone Luteolin Suppresses SREBP-2 Expression and Post-Translational Activation in Hepatic Cells

PubMed Central

Wong, Tsz Yan; Lin, Shu-mei; Leung, Lai K.

2015-01-01

High blood cholesterol has been associated with cardiovascular diseases. The enzyme HMG CoA reductase (HMGCR) is responsible for cholesterol synthesis, and inhibitors of this enzyme (statins) have been used clinically to control blood cholesterol. Sterol regulatory element binding protein (SREBP) -2 is a key transcription factor in cholesterol metabolism, and HMGCR is a target gene of SREBP-2. Attenuating SREBP-2 activity could potentially minimize the expression of HMGCR. Luteolin is a flavone that is commonly detected in plant foods. In the present study, Luteolin suppressed the expression of SREBP-2 at concentrations as low as 1 μM in the hepatic cell lines WRL and HepG2. This flavone also prevented the nuclear translocation of SREBP-2. Post-translational processing of SREBP-2 protein was required for nuclear translocation. Luteolin partially blocked this activation route through increased AMP kinase (AMPK) activation. At the transcriptional level, the mRNA and protein expression of SREBP-2 were reduced through luteolin. A reporter gene assay also verified that the transcription of SREBF2 was weakened in response to this flavone. The reduced expression and protein processing of SREBP-2 resulted in decreased nuclear translocation. Thus, the transcription of HMGCR was also decreased after luteolin treatment. In summary, the results of the present study showed that luteolin modulates HMGCR transcription by decreasing the expression and nuclear translocation of SREBP-2. PMID:26302339

Apigenin Inhibits Enterovirus-71 Infection by Disrupting Viral RNA Association with trans-Acting Factors

PubMed Central

Zhang, Wei; Qiao, Haishi; Lv, Yuanzi; Wang, Jingjing; Chen, Xiaoqing; Hou, Yayi; Tan, Renxiang; Li, Erguang

2014-01-01

Flavonoids are widely distributed natural products with broad biological activities. Apigenin is a dietary flavonoid that has recently been demonstrated to interact with heterogeneous nuclear ribonucleoproteins (hnRNPs) and interferes with their RNA editing activity. We investigated whether apigenin possessed antiviral activity against enterovirus-71 (EV71) infection since EV71 infection requires of hnRNP proteins. We found that apigenin selectively blocks EV71 infection by disrupting viral RNA association with hnRNP A1 and A2 proteins. The estimated EC50 value for apigenin to block EV71 infection was determined at 10.3 µM, while the CC50 was estimated at 79.0 µM. The anti-EV71 activity was selective since no activity was detected against several DNA and RNA viruses. Although flavonoids in general share similar structural features, apigenin and kaempferol were among tested compounds with significant activity against EV71 infection. hnRNP proteins function as trans-acting factors regulating EV71 translation. We found that apigenin treatment did not affect EV71-induced nucleocytoplasmic redistribution of hnRNP A1 and A2 proteins. Instead, it prevented EV71 RNA association with hnRNP A1 and A2 proteins. Accordingly, suppression of hnRNP A1 and A2 expression markedly reduced EV71 infection. As a positive sense, single strand RNA virus, EV71 has a type I internal ribosome entry site (IRES) that cooperates with host factors and regulates EV71 translation. The effect of apigenin on EV71 infection was further demonstrated using a bicistronic vector that has the expression of a GFP protein under the control of EV71 5′-UTR. We found that apigenin treatment selectively suppressed the expression of GFP, but not a control gene. In addition to identification of apigenin as an antiviral agent against EV71 infection, this study also exemplifies the significance in antiviral agent discovery by targeting host factors essential for viral replication. PMID:25330384

Apigenin potentiates the antitumor activity of 5-FU on solid Ehrlich carcinoma: Crosstalk between apoptotic and JNK-mediated autophagic cell death platforms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gaballah, Hanaa H., E-mail: hanaahibishy@hotmail.c

Background: Although 5- Fluorouracil (5-FU) has exhibited effectiveness against cancer, novel therapeutic strategies are needed to enhance its antitumor efficiency and modulate its cytotoxity. Apigenin, a flavonoid present in fruits and vegetables, is a potent dietary phytochemical effective in cancer chemoprevention. Aim: This study was undertaken to investigate the potential synergistic antitumor activity of apigenin and 5-FU on Solid Ehrlich carcinoma (SEC). Methods: Eighty Swiss albino male mice were divided into four equal groups: vehicle treated control SEC, SEC + 5-FU, SEC + apigenin, SEC + 5-FU + apigenin. Beclin-1 and caspases 3, 9 and JNK activities were estimated bymore » ELISA; mRNA expression levels of the antiapoptotic gene Mcl-1 were estimated using quantitative real-time RT-PCR, while tissue malondialdehyde (MDA), glutathione peroxidase and total antioxidant capacity were evaluated spectrophotometrically. A part of the tumor was examined for histopathological and Ki-67 immunohistochemistry analysis. Results: 5-FU and/or apigenin caused significant increase in tissue levels of Beclin-1, caspases 3, 9 and JNK activities, MDA with significant decrease in tumor volume, Mcl-1expression, tissue glutathione peroxidase and total antioxidant capacity and alleviated the histopathological changes with significant decrease of Ki-67 proliferation index compared to vehicle treated SEC control group. In conclusion: The combination of 5-FU and apigenin had a greater effect than each of 5-FU or apigenin alone against solid Ehrlich carcinoma in mice. - Highlights: • Apigenin potentiated 5-FU cytotoxicity in EAC solid tumor models in vivo. • It acted via autophagy stimulation, downregulating MCL-1 and Ki-67 expression. • It caused JNK activation and ROS accumulation; resulted in tumor growth inhibition. • Apigenin can be used as a co-adjuvant agent in cancer therapy.« less

Activation of TRPV4 by dietary apigenin antagonizes renal fibrosis in deoxycorticosterone acetate (DOCA)-salt-induced hypertension.

PubMed

Wei, Xing; Gao, Peng; Pu, Yunfei; Li, Qiang; Yang, Tao; Zhang, Hexuan; Xiong, Shiqiang; Cui, Yuanting; Li, Li; Ma, Xin; Liu, Daoyan; Zhu, Zhiming

2017-04-01

Hypertension-induced renal fibrosis contributes to the progression of chronic kidney disease, and apigenin, an anti-hypertensive flavone that is abundant in celery, acts as an agonist of transient receptor potential vanilloid 4 (TRPV4). However, whether apigenin reduces hypertension-induced renal fibrosis, as well as the underlying mechanism, remains elusive. In the present study, the deoxycorticosterone acetate (DOCA)-salt hypertension model was established in male Sprague-Dawley rats that were treated with apigenin or vehicle for 4 weeks. Apigenin significantly attenuated the DOCA-salt-induced structural and functional damage to the kidney, which was accompanied by reduced expression of transforming growth factor-β1 (TGF-β1)/Smad2/3 signaling pathway and extracellular matrix proteins. Immunochemistry, cell-attached patch clamp and fluorescent Ca 2+ imaging results indicated that TRPV4 was expressed and activated by apigenin in both the kidney and renal cells. Importantly, knockout of TRPV4 in mice abolished the beneficial effects of apigenin that were observed in the DOCA-salt hypertensive rats. Additionally, apigenin directly inhibited activation of the TGF-β1/Smad2/3 signaling pathway in different renal tissues through activation of TRPV4 regardless of the type of pro-fibrotic stimulus. Moreover, the TRPV4-mediated intracellular Ca 2+ influx activated the AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) pathway, which inhibited the TGF-β1/Smad2/3 signaling pathway. In summary, dietary apigenin has beneficial effects on hypertension-induced renal fibrosis through the TRPV4-mediated activation of AMPK/SIRT1 and inhibition of the TGF-β1/Smad2/3 signaling pathway. This work suggests that dietary apigenin may represent a promising lifestyle modification for the prevention of hypertension-induced renal damage in populations that consume a high-sodium diet. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Apigenin and tangeretin enhance gap junctional intercellular communication in rat liver epithelial cells.

PubMed

Chaumontet, C; Bex, V; Gaillard-Sanchez, I; Seillan-Heberden, C; Suschetet, M; Martel, P

1994-10-01

Two flavones, apigenin and tangeretin, were studied for their ability to modulate gap junctional intercellular communication (GJIC) in the rat liver epithelial cell line REL. Their cytotoxicity was first determined by cell density and neutral red uptake assays: neither apigenin nor tangeretin are cytotoxic at 10 and 25 microM, the concentrations used in our experiments. We then studied GJIC using the dye transfer assay and we observed that both apigenin and tangeretin enhance it, the maximum stimulation (x 1.7-1.8) being achieved at 25 microM for 24 h. When the dye transfer was enhanced, the amount of connexin 43 increased, which was demonstrated by Western blot and immunofluorescence analysis. For apigenin only, Northern blot analysis showed an accumulation of connexin 43 mRNA. In addition, the incubation of REL cells with the two compounds, for 1 or 24 h, prevented the inhibition of dye transfer by 12-O-tetradecanoylphorbol-13-acetate (1 or 10 ng/ml). The enhancement of GJIC by apigenin could be one of the major mechanisms responsible for apigenin's anti-tumour promoting action in vivo. As for tangeretin, its capacity to enhance GJIC completes its potential protective properties towards the post-initiation process.

Dietary Apigenin Exerts Immune-Regulatory Activity in Vivo by Reducing NF-κB Activity, Halting Leukocyte Infiltration and Restoring Normal Metabolic Function

PubMed Central

Cardenas, Horacio; Arango, Daniel; Nicholas, Courtney; Duarte, Silvia; Nuovo, Gerard J.; He, Wei; Voss, Oliver H.; Gonzalez-Mejia, M. Elba; Guttridge, Denis C.; Grotewold, Erich; Doseff, Andrea I.

2016-01-01

The increasing prevalence of inflammatory diseases and the adverse effects associated with the long-term use of current anti-inflammatory therapies prompt the identification of alternative approaches to reestablish immune balance. Apigenin, an abundant dietary flavonoid, is emerging as a potential regulator of inflammation. Here, we show that apigenin has immune-regulatory activity in vivo. Apigenin conferred survival to mice treated with a lethal dose of Lipopolysaccharide (LPS) restoring normal cardiac function and heart mitochondrial Complex I activity. Despite the adverse effects associated with high levels of splenocyte apoptosis in septic models, apigenin had no effect on reducing cell death. However, we found that apigenin decreased LPS-induced apoptosis in lungs, infiltration of inflammatory cells and chemotactic factors’ accumulation, re-establishing normal lung architecture. Using NF-κB luciferase transgenic mice, we found that apigenin effectively modulated NF-κB activity in the lungs, suggesting the ability of dietary compounds to exert immune-regulatory activity in an organ-specific manner. Collectively, these findings provide novel insights into the underlying immune-regulatory mechanisms of dietary nutraceuticals in vivo. PMID:26938530

Apigenin inhibits proliferation and invasion, and induces apoptosis and cell cycle arrest in human melanoma cells.

PubMed

Zhao, Guangming; Han, Xiaodong; Cheng, Wei; Ni, Jing; Zhang, Yunfei; Lin, Jingrong; Song, Zhiqi

2017-04-01

Malignant melanoma is the most invasive and fatal form of cutaneous cancer. Moreover it is extremely resistant to conventional chemotherapy and radiotherapy. Apigenin, a non-mutagenic flavonoid, has been found to exhibit chemopreventive and/or anticancerogenic properties in many different types of human cancer cells. Therefore, apigenin may have particular relevance for development as a chemotherapeutic agent for cancer treatment. In the present study, we investigated the effects of apigenin on the viability, migration and invasion potential, dendrite morphology, cell cycle distribution, apoptosis, phosphorylation of the extracellular signal-regulated protein kinase (ERK) and the AKT/mTOR signaling pathway in human melanoma A375 and C8161 cell lines in vitro. Apigenin effectively suppressed the proliferation of melanoma cells in vitro. Moreover, it inhibited cell migration and invasion, lengthened the dendrites, and induced G2/M phase arrest and apoptosis. Furthermore, apigenin promoted the activation of cleaved caspase-3 and cleaved PARP proteins and decreased the expression of phosphorylated (p)‑ERK1/2 proteins, p-AKT and p-mTOR. Consequently, apigenin is a novel therapeutic candidate for melanoma.

The effects of apigenin on lipopolysaccharide-induced depressive-like behavior in mice.

PubMed

Li, Ruipeng; Zhao, Di; Qu, Rong; Fu, Qiang; Ma, Shiping

2015-05-06

Increasing evidence shows that inflammation may contribute to the pathophysiology of depression. Apigenin, one type of natural flavone, has a number of biological actions including anti-inflammatory effects. Although it has potential antidepressant activity in a chronic mild stress model, the mechanisms of antidepressant effect for apigenin remain unclear. Here, we examined the effects of apigenin on lipopolysaccharide (LPS)-induced depressive-like behavior in male mice. A single administration of LPS (0.5mg/kg, i.p.) increased the immobility time in the tail suspension test (TST) and reduced sucrose preference without changing spontaneous locomotor activity in open field test (OFT). Pre-treatment with apigenin (25, 50mg/kg, i.p.) or fluoxetine (positive control drug, 20mg/kg, i.p.) once daily for 7 consecutive days prevented the abnormal behavior induced by LPS. Apigenin or fluoxetine also effectively attenuated LPS-induced production of pro-inflammatory cytokines IL-1β (interleukin-1β) and TNF-α (tumor necrosis factor-α). Moreover, apigenin or fluoxetine significantly suppressed the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression at both the mRNA and protein level via the modulation of nuclear factor-κB (NF-κB) activation in the prefrontal cortex. Additionally, apigenin (50mg/kg, i.p.) or fluoxetine (20mg/kg, i.p.) effectively reversed the depressive-like behavior induced by TNF-α (0.1fg/site, i.c.v.) without altering the locomotor activity. These results demonstrate that apigenin exhibits antidepressant-like effects in LPS treated mice, partially due to its anti-inflammatory properties. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Apigenin inhibits glioma cell growth through promoting microRNA-16 and suppression of BCL-2 and nuclear factor-κB/MMP‑9.

PubMed

Chen, Xin-Jun; Wu, Mian-Yun; Li, Deng-Hui; You, Jin

2016-09-01

The present study aimed to investigate the effect of apigenin on glioma cells and to explore its potential mechanism. U87 human glioma cells treated with apigenin were used in the current study. Cell Counting Kit‑8 solution and Annexin V-fluorescein isothiocyanate/propidium iodide Apoptosis Detection kit were used to analyze the effect of apigenin on U87 cell viability and apoptotic cell death. Reverse transcription‑quantitative polymerase chain reaction analysis was also used to determine microRNA‑16 (miR‑16) and MMP‑9 gene expression levels. Nuclear factor‑κB (NF‑κB) and B‑cell CLL/lymphoma 2 (BCL2) protein expression levels were determined using western blot analysis. An anti‑miR‑16 plasmid was constructed and transfected into U87 cells. The current study demonstrated that apigenin significantly decreased cell viability and induced apoptotic cell death of U87 cells in a dose‑dependent manner. Additionally, it was demonstrated that apigenin significantly increased miR‑16 levels, suppressed BCL2 protein expression and suppressed the NF‑κB/MMP9 signaling pathway in U87 cells. Furthermore, downregulation of miR‑16 using the anti‑miR‑16 plasmid reversed the effect of apigenin on cell viability, BCL2 protein expression and the NF‑κB/MMP‑9 pathway in U87 cells. The results of the present study suggested that apigenin inhibits glioma cell growth through promoting miR‑16 and suppression of BCL2 and NF-κB/MMP-9. In conclusion, the present study demonstrated the potential anticancer effects of apigenin on glioma cells.

Apigenin and naringenin regulate glucose and lipid metabolism, and ameliorate vascular dysfunction in type 2 diabetic rats.

PubMed

Ren, Bei; Qin, Weiwei; Wu, Feihua; Wang, Shanshan; Pan, Cheng; Wang, Liying; Zeng, Biao; Ma, Shiping; Liang, Jingyu

2016-02-15

Vascular endothelial dysfunction is regarded as the initial step of vascular complications in diabetes mellitus. This study investigated the amelioration of apigenin and naringenin in type 2 diabetic (T2D) rats induced by high-fat diet and streptozotocin and explored the underlying mechanism. Apigenin or naringenin was intragastrically administered at 50 or 100mg/kg once a day for 6 weeks. Biochemical parameters including blood glucose, glycated serum protein, serum lipid, insulin, superoxide dismutase (SOD), malonaldehyde and intercellular adhesion molecule-1 (ICAM-1) were measured. Vascular reactivity in isolated thoracic aortic rings was examined. Pathological features of the thoracic aorta were further observed through optical microscopy and transmission electron microscopy. Lastly, we evaluated their effects on insulin resistance of palmitic acid (PA)-induced endothelial cells. Compared with diabetic control group, apigenin and naringenin significantly decreased the levels of blood glucose, serum lipid, malonaldehyde, ICAM-1 and insulin resistance index, increased SOD activity and improved impaired glucose tolerance. Apigenin and naringenin restored phenylephrine-mediated contractions and acetylcholine or insulin-induced relaxations in aortic tissues. Furthermore, pathological damage in the thoracic aorta of apigenin and naringenin groups was more remissive than diabetic control group. In vitro, apigenin and naringenin inhibited NF-κB activation and ICAM-1 mRNA expression in PA-treated endothelial cells and improved nitric oxide production in the presence of insulin. In conclusion, both apigenin and naringenin can ameliorate glucose and lipid metabolism, as well as endothelial dysfunction in T2D rats at least in part by down-regulating oxidative stress and inflammation. In general, apigenin showed greater potency than naringenin equivalent. Copyright © 2016 Elsevier B.V. All rights reserved.

Apigenin inhibits proliferation and induces apoptosis in human multiple myeloma cells through targeting the trinity of CK2, Cdc37 and Hsp90

PubMed Central

2011-01-01

Background Multiple myeloma (MM) is a B-cell malignancy that is largely incurable and is characterized by the accumulation of malignant plasma cells in the bone marrow. Apigenin, a common flavonoid, has been reported to suppress proliferation in a wide variety of solid tumors and hematological cancers; however its mechanism is not well understood and its effect on MM cells has not been determined. Results In this study, we investigated the effects of apigenin on MM cell lines and on primary MM cells. Cell viability assays demonstrated that apigenin exhibited cytotoxicity against both MM cell lines and primary MM cells but not against normal peripheral blood mononuclear cells. Together, kinase assays, immunoprecipitation and western blot analysis showed that apigenin inhibited CK2 kinase activity, decreased phosphorylation of Cdc37, disassociated the Hsp90/Cdc37/client complex and induced the degradation of multiple kinase clients, including RIP1, Src, Raf-1, Cdk4 and AKT. By depleting these kinases, apigenin suppressed both constitutive and inducible activation of STAT3, ERK, AKT and NF-κB. The treatment also downregulated the expression of the antiapoptotic proteins Mcl-1, Bcl-2, Bcl-xL, XIAP and Survivin, which ultimately induced apoptosis in MM cells. In addition, apigenin had a greater effects in depleting Hsp90 clients when used in combination with the Hsp90 inhibitor geldanamycin and the histone deacetylase inhibitor vorinostat. Conclusions Our results suggest that the primary mechanisms by which apigenin kill MM cells is by targeting the trinity of CK2-Cdc37-Hsp90, and this observation reveals the therapeutic potential of apigenin in treating multiple myeloma. PMID:21871133

The flavonoid apigenin from Croton betulaster Mull inhibits proliferation, induces differentiation and regulates the inflammatory profile of glioma cells.

PubMed

Coelho, Paulo L C; Oliveira, Mona N; da Silva, Alessandra B; Pitanga, Bruno P S; Silva, Victor D A; Faria, Giselle P; Sampaio, Geraldo P; Costa, Maria de Fatima D; Braga-de-Souza, Suzana; Costa, Silvia L

2016-11-01

This study aimed to investigate the antitumor and immunomodulatory properties of the flavonoid apigenin (5,7,4'-trihydroxyflavone), which was extracted from Croton betulaster Mull, in glioma cell culture using the high-proliferative rat C6 glioma cell line as a model. Apigenin was found to have the ability to reduce the viability and proliferation of C6 cells in a time-dependent and dose-dependent manner, with an IC50 of 22.8 µmol/l, 40 times lower than that of temozolomide (1000 µmol/l), after 72 h of apigenin treatment. Even after C6 cells were treated with apigenin for 48 h, high proportions of C6 cells entered apoptosis (39.56%) and autophagy (22%) as shown by flow cytometry using annexin V/propidium iodide and acridine orange staining, respectively. In addition, the flavonoid apigenin induced cell accumulation in the G0/G1 phase of the cell cycle and inhibited glioma cell migration efficiently. Moreover, apigenin induced astroglial differentiation and morphological changes in C6 cells, characterized by increased expression of glial fibrillary acidic protein and decreased expression of nestin protein, a typical marker of neuronal precursors. The immunomodulating effects of apigenin were also characterized by a change in the inflammatory profile as evidenced by a significant decrease in interleukin-10 and tumor necrosis factor production and increased nitric oxide levels. Because apigenin can induce differentiation, apoptosis, and autophagy, can alter the profile of cytokines involved in regulating the immune response, and can reduce the survival, growth, proliferation, and migration of C6 cells, this flavonoid may be considered a potential antitumor drug for the adjuvant treatment of malignant gliomas.

Inhibitory Effect of Apigenin on Losartan Metabolism and CYP2C9 Activity in vitro.

PubMed

Wang, Zhe; Gong, Yun; Zeng, Da-Li; Chen, Lian-Guo; Lin, Gao-Tong; Huang, Cheng-Ke; Sun, Wei; Chen, Meng-Chun; Hu, Guo-Xin; Chen, Rui-Jie

2016-01-01

CYP2C9 is one of the most important phase I drug-metabolizing enzymes in liver. The objective of this work was to investigate the effects of apigenin on the metabolism of losartan and human CYP2C9 and rat CYP2C11 activity in vitro. Different concentrations of apigenin were added to a 100 mmol/l Tris-HCl reaction mixture containing 2 pmol/ml recombinant human CYP2C9.1, 0.25 mg/ml human liver microsomes or 0.5 mg/ml rat liver microsomes to determine the half maximal inhibition or a half-maximal inhibitory concentration (IC50) on the metabolism of losartan. In addition, diclofenac used as CYP2C9 substrate was performed to determine the effects of apigenin on CYP2C9. The results showed that apigenin has the inhibitory effect on the metabolism of losartan in vitro, the IC50 was 7.61, 4.10 and 11.07 μmol/l on recombinant CYP2C9 microsomes, human liver microsomes and rat liver microsomes, respectively. Meanwhile, apigenin's mode of action on human CYP2C9 activity was competitive for the substrate diclofenac. In contrast to its potent inhibition of CYP2C9 in humans (9.51 μmol/l), apigenin had lesser effects on CYP2C11 in rat (IC50 = 15.51 μmol/l). The observations imply that apigenin has the inhibitory effect on the metabolism of losartan and CYP2C9 activity in vitro. More attention should be paid as to when losartan should be administrated combined with apigenin. © 2016 S. Karger AG, Basel.

Apigenin enhances skeletal muscle hypertrophy and myoblast differentiation by regulating Prmt7

PubMed Central

Jang, Young Jin; Son, Hyo Jeong; Choi, Yong Min; Ahn, Jiyun; Jung, Chang Hwa; Ha, Tae Youl

2017-01-01

Apigenin, a natural flavone abundant in various plant-derived foods including parsley and celery, has been shown to prevent inflammation and inflammatory diseases. However, the effect of apigenin on skeletal muscle hypertrophy and myogenic differentiation has not previously been elucidated. Here, we investigated the effects of apigenin on quadricep muscle weight and running distance using C57BL/6 mice on an accelerating treadmill. Apigenin stimulated mRNA expression of MHC (myosin heavy chain) 1, MHC2A, and MHC2B in the quadricep muscles of these animals. GPR56 (G protein-coupled receptor 56) and its ligand collagen III were upregulated by apigenin supplementation, together with enhanced PGC-1α, PGC-1α1, PGC-1α4, IGF1, and IGF2 expression. Prmt7 protein expression increased in conjunction with Akt and mTORC1 activation. Apigenin treatment also upregulated FNDC5 (fibronectin type III domain containing 5) mRNA expression and serum irisin levels. Furthermore, apigenin stimulated C2C12 myogenic differentiation and upregulated total MHC, MHC2A, and MHC2B expression. These events were attributable to an increase in Prmt7-p38-myoD expression and Akt and S6K1 phosphorylation. We also observed that Prmt7 regulates both PGC-1α1 and PGC-1α4 expression, resulting in a subsequent increase in GPR56 expression and mTORC1 activation. Taken together, these findings suggest that apigenin supplementation can promote skeletal muscle hypertrophy and myogenic differentiation by regulating the Prmt7-PGC-1α-GPR56 pathway, as well as the Prmt7-p38-myoD pathway, which may contribute toward the prevention of skeletal muscle weakness. PMID:29108230

Apigenin enhances skeletal muscle hypertrophy and myoblast differentiation by regulating Prmt7.

PubMed

Jang, Young Jin; Son, Hyo Jeong; Choi, Yong Min; Ahn, Jiyun; Jung, Chang Hwa; Ha, Tae Youl

2017-10-03

Apigenin, a natural flavone abundant in various plant-derived foods including parsley and celery, has been shown to prevent inflammation and inflammatory diseases. However, the effect of apigenin on skeletal muscle hypertrophy and myogenic differentiation has not previously been elucidated. Here, we investigated the effects of apigenin on quadricep muscle weight and running distance using C57BL/6 mice on an accelerating treadmill. Apigenin stimulated mRNA expression of MHC (myosin heavy chain) 1, MHC2A, and MHC2B in the quadricep muscles of these animals. GPR56 (G protein-coupled receptor 56) and its ligand collagen III were upregulated by apigenin supplementation, together with enhanced PGC-1α, PGC-1α1, PGC-1α4, IGF1, and IGF2 expression. Prmt7 protein expression increased in conjunction with Akt and mTORC1 activation. Apigenin treatment also upregulated FNDC5 (fibronectin type III domain containing 5) mRNA expression and serum irisin levels. Furthermore, apigenin stimulated C2C12 myogenic differentiation and upregulated total MHC, MHC2A, and MHC2B expression. These events were attributable to an increase in Prmt7-p38-myoD expression and Akt and S6K1 phosphorylation. We also observed that Prmt7 regulates both PGC-1α1 and PGC-1α4 expression, resulting in a subsequent increase in GPR56 expression and mTORC1 activation. Taken together, these findings suggest that apigenin supplementation can promote skeletal muscle hypertrophy and myogenic differentiation by regulating the Prmt7-PGC-1α-GPR56 pathway, as well as the Prmt7-p38-myoD pathway, which may contribute toward the prevention of skeletal muscle weakness.

The Protective Effect of Apigenin on Myocardial Injury in Diabetic Rats mediating Activation of the PPAR-γ Pathway

PubMed Central

Mahajan, Umesh B.; Chandrayan, Govind; Patil, Chandragouda R.; Arya, Dharamvir Singh; Suchal, Kapil; Agrawal, Yogeeta O.; Ojha, Shreesh; Goyal, Sameer N.

2017-01-01

We substantiated the role of peroxisome proliferator-activated receptor-γ (PPAR-γ) activation in the protective effect of apigenin against the myocardial infarction (MI) in diabetic rats. Diabetes was induced by intraperitoneal administration of a single dose of streptozotocin (55 mg/kg). The study groups included diabetic rats receiving vehicle, apigenin (75 mg/kg/day, orally), GW9662 (1 mg/kg/day, intraperitoneally), and a combination of apigenin and GW9662 for 14 days. The MI was induced in all the study groups except the diabetic control group by subcutaneous injection of 100 mg/kg/day of isoproterenol on the two terminal days. The diabetes and isoproterenol-induced MI was evident as a reduction in the maximal positive and negative rate of developed left ventricular pressure and an increase in the left ventricular end-diastolic pressure. The activities of creatine kinase on myocardial bundle (CK-MB) and lactate dehydrogenase (LDH) were also reduced. Apigenin treatment prevented the hemodynamic perturbations, restored the left ventricular function and reinstated a balanced redox status. It protected rats against an MI by attenuating myonecrosis, edema, cell death, and oxidative stress. GW9662, a PPAR-γ antagonist reversed the myocardial protection conferred by apigenin. Further, an increase in the PPAR-γ expression in the myocardium of the rats receiving apigenin reinforces the role of PPAR-γ pathway activation in the cardioprotective effects of apigenin. PMID:28375162

Apigenin Reduces Proteasome Inhibition-Induced Neuronal Apoptosis by Suppressing the Cell Death Process.

PubMed

Kim, Arum; Nam, Yoon Jeong; Lee, Min Sung; Shin, Yong Kyoo; Sohn, Dong Suep; Lee, Chung Soo

2016-11-01

Impairment of proteasomal function has been shown to be implicated in neuronal cell degeneration. The compounds which have antioxidant and anti-inflammatory abilities appear to provide a neuroprotective effect. Flavone apigenin is known to exhibits antioxidant and anti-inflammatory effects. Nevertheless, the effect of apigenin on the proteasome inhibition-induced neuronal apoptosis has not been studied. Therefore, we assessed the effect of apigenin on the proteasome inhibition-induced apoptotic neuronal cell death using differentiated PC12 cells and human neuroblastoma SH-SY5Y cells. Apigenin attenuated the proteasome inhibitors (MG132 and MG115)-induced decrease in the levels of Bid and Bcl-2, increase in the levels of Bax and p53, loss of the mitochondrial transmembrane potential, release of cytochrome c, activation of caspases (-8, -9 and -3), cleavage of PARP-1 and cell death in both cell lines. Apigenin attenuated the production of reactive oxygen species, the depletion and oxidation of glutathione, the formations of malondialdehyde and carbonyls in cell lines treated with proteasome inhibitors. The results show that apigenin appears to attenuate the proteasome inhibitor-induced apoptosis in differentiated PC12 cells and SH-SY5Y cells by suppressing the activation of the mitochondrial pathway, and of the caspase-8- and Bid-dependent pathways. The inhibitory effect of apigenin on the proteasome inhibitor-induced apoptosis appears to be attributed to the suppressive effect on the production of reactive oxygen species, the depletion and oxidation of glutathione and the formations of malondialdehyde and carbonyls.

Angiogenic effects of apigenin on endothelial cells after hypoxia-reoxygenation via the caveolin-1 pathway.

PubMed

Tu, Fengxia; Pang, Qiongyi; Chen, Xiang; Huang, Tingting; Liu, Meixia; Zhai, Qiongxiang

2017-12-01

In the present study, we aimed to elucidate whether apigenin contributes to the induction of angiogenesis and the related mechanisms in cell hypoxia-reoxygenation injury. The role of apigenin was examined in human umbilical vein endothelial cell (HUVEC) viability, migration and tube formation in vitro. To investigate the related mechanisms, we used caveolin-1 short interfering RNA. The viability of HUVECs was measured using Cell Counting Kit-8 assays, HUVEC migration was analyzed by crystal violet staining, and a tube formation assay was performed using the branch point method. Expression of caveolin-1, vascular endothelial growth factor (VEGF), and endothelial nitric oxide synthase (eNOS) in HUVECs was examined by polymerase chain reaction and western blotting. Our data revealed that apigenin induced angiogenesis in vitro by increasing the tube formation ability of HUVECs, which was counteracted by caveolin-1 silencing. Compared to the NC group, Caveolin-1 and eNOS expression was upregulated by apigenin, whereas compared to the NC group, eNOS expression was increased upon caveolin-1 silencing. The expression of VEGF was increased by treatment with apigenin; however, compared to the NC group, caveolin-1 silencing did not affect VEGF expression, and apigenin did not increase VEGF expression in HUVECs after caveolin-1 silencing. These data suggest that apigenin may be a candidate therapeutic target for stroke recovery by promoting angiogenesis via the caveolin-1 signaling pathway.

Apigenin potentiates the antitumor activity of 5-FU on solid Ehrlich carcinoma: Crosstalk between apoptotic and JNK-mediated autophagic cell death platforms.

PubMed

Gaballah, Hanaa H; Gaber, Rasha A; Mohamed, Darin A

2017-02-01

Although 5- Fluorouracil (5-FU) has exhibited effectiveness against cancer, novel therapeutic strategies are needed to enhance its antitumor efficiency and modulate its cytotoxity. Apigenin, a flavonoid present in fruits and vegetables, is a potent dietary phytochemical effective in cancer chemoprevention. This study was undertaken to investigate the potential synergistic antitumor activity of apigenin and 5-FU on Solid Ehrlich carcinoma (SEC). Eighty Swiss albino male mice were divided into four equal groups: vehicle treated control SEC, SEC+5-FU, SEC+apigenin, SEC+ 5-FU+apigenin. Beclin-1 and caspases 3, 9 and JNK activities were estimated by ELISA; mRNA expression levels of the antiapoptotic gene Mcl-1 were estimated using quantitative real-time RT-PCR, while tissue malondialdehyde (MDA), glutathione peroxidase and total antioxidant capacity were evaluated spectrophotometrically. A part of the tumor was examined for histopathological and Ki-67 immunohistochemistry analysis. 5-FU and/or apigenin caused significant increase in tissue levels of Beclin-1, caspases 3, 9 and JNK activities, MDA with significant decrease in tumor volume, Mcl-1expression, tissue glutathione peroxidase and total antioxidant capacity and alleviated the histopathological changes with significant decrease of Ki-67 proliferation index compared to vehicle treated SEC control group. The combination of 5-FU and apigenin had a greater effect than each of 5-FU or apigenin alone against solid Ehrlich carcinoma in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

Vernonia condensata Baker (Asteraceae): A Promising Source of Antioxidants

PubMed Central

da Silva, Jucélia Barbosa; Temponi, Vanessa dos Santos; Gasparetto, Carolina Miranda; Fabri, Rodrigo Luiz; Aragão, Danielle Maria de Oliveira; Pinto, Nícolas de Castro Campos; Ribeiro, Antônia; Scio, Elita; Del-Vechio-Vieira, Glauciemar; de Sousa, Orlando Vieira

2013-01-01

The present study evaluated the antioxidant potential of Vernonia condensata Baker (Asteraceae). Dried and powdered leaves were exhaustively extracted with ethanol by static maceration followed by partition to obtain the hexane, dichloromethane, ethyl acetate, and butanol fractions. Total phenols and flavonoids contents were determined through spectrophotometry and flavonoids were identified by HPLC-DAD system. The antioxidant activity was assessed by DPPH radical scavenging activity, TLC-bioautography, reducing power of Fe+3, phosphomolybdenum, and TBA assays. The total phenolic content and total flavonoids ranged from 0.19 to 23.11 g/100 g and from 0.13 to 4.10 g/100 g, respectively. The flavonoids apigenin and luteolin were identified in the ethyl acetate fraction. The IC50 of DPPH assay varied from 4.28 to 75.10 µg/mL and TLC-bioautography detected the antioxidant compounds. The reducing power of Fe+3 was 19.98 to 336.48 μg/mL, while the reaction with phosphomolybdenum ranged from 13.54% to 32.63% and 56.02% to 135.00% considering ascorbic acid and rutin as reference, respectively. At 30 mg/mL, the ethanolic extract and fractions revealed significant effect against lipid peroxidation. All these data sustain that V. condensata is an important and promising source of bioactive substances with antioxidant activity. PMID:24489987

Identification of the compositional changes in Orthosiphon stamineus leaves triggered by different drying techniques using 1 H NMR metabolomics.

PubMed

Pariyani, Raghunath; Ismail, Intan Safinar; Ahmad Azam, Amalina; Abas, Faridah; Shaari, Khozirah

2017-09-01

Java tea is a well-known herbal infusion prepared from the leaves of Orthosiphon stamineus (OS). The biological properties of tea are in direct correlation with the primary and secondary metabolite composition, which in turn largely depends on the choice of drying method. Herein, the impact of three commonly used drying methods, i.e. shade, microwave and freeze drying, on the metabolite composition and antioxidant activity of OS leaves was investigated using proton nuclear magnetic resonance ( 1 H NMR) spectroscopy combined with multivariate classification and regression analysis tools. A total of 31 constituents comprising primary and secondary metabolites belonging to the chemical classes of fatty acids, amino acids, sugars, terpenoids and phenolic compounds were identified. Shade-dried leaves were identified to possess the highest concentrations of bioactive secondary metabolites such as chlorogenic acid, caffeic acid, luteolin, orthosiphol and apigenin, followed by microwave-dried samples. Freeze-dried leaves had higher concentrations of choline, amino acids leucine, alanine and glutamine and sugars such as fructose and α-glucose, but contained the lowest levels of secondary metabolites. Metabolite profiling coupled with multivariate analysis identified shade drying as the best method to prepare OS leaves as Java tea or to include in traditional medicine preparation. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Chemical Composition and Antioxidant Activity of Euterpe oleracea Roots and Leaflets.

PubMed

Brunschwig, Christel; Leba, Louis-Jérôme; Saout, Mona; Martial, Karine; Bereau, Didier; Robinson, Jean-Charles

2016-12-29

Euterpe oleracea (açaí) is a palm tree well known for the high antioxidant activity of its berries used as dietary supplements. Little is known about the biological activity and the composition of its vegetative organs. The objective of this study was to investigate the antioxidant activity of root and leaflet extracts of Euterpe oleracea ( E . oleracea ) and characterize their phytochemicals. E . oleracea roots and leaflets extracts were screened in different chemical antioxidant assays (DPPH-2,2-diphenyl-1-picrylhydrazyl, FRAP-ferric feducing antioxidant power, and ORAC-oxygen radical absorbance capacity), in a DNA nicking assay and in a cellular antioxidant activity assay. Their polyphenolic profiles were determined by UV and LC-MS/MS. E . oleracea leaflets had higher antioxidant activity than E . oleracea berries, and leaflets of Oenocarpus bacaba and Oenocarpus bataua , as well as similar antioxidant activity to green tea. E. oleracea leaflet extracts were more complex than root extracts, with fourteen compounds, including caffeoylquinic acids and C -glycosyl derivatives of apigenin and luteolin. In the roots, six caffeoylquinic and caffeoylshikimic acids were identified. Qualitative compositions of E. oleracea , Oenocarpus bacaba and Oenocarpus bataua leaflets were quite similar, whereas the quantitative compositions were quite different. These results provide new prospects for the valorization of roots and leaflets of E. oleracea in the pharmaceutical, food or cosmetic industry, as they are currently by-products of the açaí industry.

Antioxidative Activities and Active Compounds of Extracts from Catalpa Plant Leaves

PubMed Central

Xu, Hongyu; Hu, Gege; Dong, Juane; Wei, Qin; Shao, Hongbo; Lei, Ming

2014-01-01

In order to screen the Catalpa plant with high antioxidant activity and confirm the corresponding active fractions from Catalpa ovata G. Don, C. fargesii Bur., and C. bungei C. A. Mey., total flavonoid contents and antioxidant activities of the extracts/fractions of Catalpa plant leaves were determined. The determined total flavonoid content and antioxidant activity were used as assessment criteria. Those compounds with antioxidant activity were isolated with silica gel column chromatography and ODS column chromatography. Our results showed that the total flavonoid content in C. bungei C. A. Mey. (30.07 mg/g·DW) was the highest, followed by those in C. fargesii Bur. (25.55 mg/g·DW) and C. ovata G. Don (24.96 mg/g·DW). According to the determination results of total flavonoid content and antioxidant activity in 3 clones of leaves of C. bungei C. A. Mey., the total flavonoid content and antioxidant activity in crude extracts from C. bungei C. A. Mey. 6 (CA6) leaves were the highest. Moreover, the results showed that the total flavonoid content and antioxidant activities of ethyl acetate (EA) fraction in ethanol crude extracts in CA6 leaves were the highest, followed by n-butanol, petroleum ether (PE), and water fractions. Two flavonoid compounds with antioxidant activity were firstly isolated based on EA fraction. The two compounds were luteolin (1) and apigenin (2), respectively. PMID:25431795

Chemical Composition and Antioxidant Activity of Euterpe oleracea Roots and Leaflets

PubMed Central

Brunschwig, Christel; Leba, Louis-Jérôme; Saout, Mona; Martial, Karine; Bereau, Didier; Robinson, Jean-Charles

2016-01-01

Euterpe oleracea (açaí) is a palm tree well known for the high antioxidant activity of its berries used as dietary supplements. Little is known about the biological activity and the composition of its vegetative organs. The objective of this study was to investigate the antioxidant activity of root and leaflet extracts of Euterpe oleracea (E. oleracea) and characterize their phytochemicals. E. oleracea roots and leaflets extracts were screened in different chemical antioxidant assays (DPPH—2,2-diphenyl-1-picrylhydrazyl, FRAP—ferric feducing antioxidant power, and ORAC—oxygen radical absorbance capacity), in a DNA nicking assay and in a cellular antioxidant activity assay. Their polyphenolic profiles were determined by UV and LC-MS/MS. E. oleracea leaflets had higher antioxidant activity than E. oleracea berries, and leaflets of Oenocarpus bacaba and Oenocarpus bataua, as well as similar antioxidant activity to green tea. E. oleracea leaflet extracts were more complex than root extracts, with fourteen compounds, including caffeoylquinic acids and C-glycosyl derivatives of apigenin and luteolin. In the roots, six caffeoylquinic and caffeoylshikimic acids were identified. Qualitative compositions of E. oleracea, Oenocarpus bacaba and Oenocarpus bataua leaflets were quite similar, whereas the quantitative compositions were quite different. These results provide new prospects for the valorization of roots and leaflets of E. oleracea in the pharmaceutical, food or cosmetic industry, as they are currently by-products of the açaí industry. PMID:28036089

Leaf polyphenol profile and SSR-based fingerprinting of new segregant Cynara cardunculus genotypes

PubMed Central

Pandino, Gaetano; Lombardo, Sara; Moglia, Andrea; Portis, Ezio; Lanteri, Sergio; Mauromicale, Giovanni

2015-01-01

The dietary value of many plant polyphenols lies in the protection given against degenerative pathologies. Their in planta role is associated with the host's defense response against biotic and abiotic stress. The polyphenol content of a given plant tissue is strongly influenced by the growing environment, but is also genetically determined. Plants belonging to the Cynara cardunculus species (globe artichoke and the cultivated and wild cardoon) accumulate substantial quantities of polyphenols mainly mono and di-caffeoylquinic acid (CQA) in their foliage. Transgressive segregation for CQA content in an F1 population bred from a cross between a globe artichoke and a cultivated cardoon led to the selection of eight segregants which accumulated more CQA in their leaves than did those of either of their parental genotypes. The selections were grown over two seasons to assess their polyphenol profile (CQAs, apigenin and luteolin derivatives and narirutin), and were also fingerprinted using a set of 217 microsatellite markers. The growing environment exerted a strong effect on polyphenol content, but two of the selections were able to accumulate up to an order of magnitude more CQA than either parent in both growing seasons. Since the species is readily vegetatively propagable, such genotypes can be straightforwardly exploited as a source of pharmaceutically valuable compounds, while their SSR-based fingerprinting will allow the genetic identity of clonally propagated material to be easily verified. PMID:25653660

Novel methodology for the extraction and identification of natural dyestuffs in historical textiles by HPLC-UV-Vis-ESI MS. Case study: chasubles from the Wawel Cathedral collection.

PubMed

Lech, Katarzyna; Jarosz, Maciej

2011-03-01

High-performance liquid chromatography coupled with spectrophotometric and electrospray mass spectrometric detection (HPLC-UV-Vis-ESI MS) was used for characterization of natural dyes present in historical art works. The gradient program was developed for identification of 29 colorants of various polarities. Dual detection system (UV-Vis and ESI MS) allowed differentiation of all compounds, even if they were not completely separated. This enabled examination of more color compounds over a substantially shorter time in comparison with previously recommended methods. Moreover, for extraction of colorants from historical textiles a two-step sequential procedure was proposed, excluding evaporation used in earlier procedures. The developed method was successfully applied to identification of indigotin, carminic, kermesic, flavokermesic, dcII, dcIV, dcVII, and ellagic acids as well as luteolin, apigenin, and genistein in red, violet, and green fibers taken from three selected historical chasubles which belong to the collection of the Wawel Cathedral treasury (Cracow, Poland). Italian textiles from the fifteenth and sixteenth centuries, of which chasubles were made, were dyed with a limited number of dyestuffs, consistently used for all batches of fabrics. The obtained results also allowed confirmation of the structure of the so-called "dcII" component of cochineal as a C-glucose derivative of flavokermesic acid.

Evidence of Bioactive Compounds from Vernonia polyanthes Leaves with Topical Anti-Inflammatory Potential

PubMed Central

Rodrigues, Kamilla C. M.; Chibli, Lucas A.; Santos, Bruna C. S.; Temponi, Vanessa S.; Pinto, Nícolas C. C.; Scio, Elita; Del-Vechio-Vieira, Glauciemar; Alves, Maria S.; Sousa, Orlando V.

2016-01-01

Vernonia polyanthes Less. (Asteraceae), popularly known as “assa-peixe”, is a plant species used in Brazilian traditional medicine for the treatment of cutaneous damage, cicatrization, inflammation, and rheumatism. Based on these ethnopharmacological findings, the current study evaluated the topical anti-inflammatory effects of the hexane (HEVP) and ethyl acetate (EAEVP) extracts from V. polyanthes leaves in experimental models of skin inflammation. Chemical characterization was carried out by HPLC–UV/DAD analysis. Anti-inflammatory activity was evaluated using Croton oil-, arachidonic acid (AA)-, phenol-, ethyl phenylpropiolate (EPP)-, and capsaicin-induced ear edema models in mice. Histopathological evaluation and measurements of myeloperoxidase (MPO) and N-acetyl-β-d-glucosaminidase (NAG) enzymes were also performed. Rutin, luteolin, and apigenin were identified in EAEVP. Topically applied HEVP and EAEVP significantly (p < 0.05, p < 0.01 or p < 0.001) reduced edema induced by five different irritants at the doses tested (0.1, 0.5 and 1.0 mg/ear). Histopathological analysis revealed a reduction of edema, inflammatory cell infiltration, and vasodilation. In addition, the enzymes activity (MPO and NAG) in the ear tissues was reduced by the topical treatment of HEVP and EAEVP (p < 0.05, p < 0.01 or p < 0.001). The results suggest that V. polyanthes leaves are effective against cutaneous damage, which support its traditional use and open up new possibilities for the treatment of skin disorders. PMID:27916942

Antioxidative activities and active compounds of extracts from Catalpa plant leaves.

PubMed

Xu, Hongyu; Hu, Gege; Dong, Juane; Wei, Qin; Shao, Hongbo; Lei, Ming

2014-01-01

In order to screen the Catalpa plant with high antioxidant activity and confirm the corresponding active fractions from Catalpa ovata G. Don, C. fargesii Bur., and C. bungei C. A. Mey., total flavonoid contents and antioxidant activities of the extracts/fractions of Catalpa plant leaves were determined. The determined total flavonoid content and antioxidant activity were used as assessment criteria. Those compounds with antioxidant activity were isolated with silica gel column chromatography and ODS column chromatography. Our results showed that the total flavonoid content in C. bungei C. A. Mey. (30.07 mg/g · DW) was the highest, followed by those in C. fargesii Bur. (25.55 mg/g · DW) and C. ovata G. Don (24.96 mg/g · DW). According to the determination results of total flavonoid content and antioxidant activity in 3 clones of leaves of C. bungei C. A. Mey., the total flavonoid content and antioxidant activity in crude extracts from C. bungei C. A. Mey. 6 (CA6) leaves were the highest. Moreover, the results showed that the total flavonoid content and antioxidant activities of ethyl acetate (EA) fraction in ethanol crude extracts in CA6 leaves were the highest, followed by n-butanol, petroleum ether (PE), and water fractions. Two flavonoid compounds with antioxidant activity were firstly isolated based on EA fraction. The two compounds were luteolin (1) and apigenin (2), respectively.

Effects of palmitoylethanolamide and luteolin in an animal model of anxiety/depression.

PubMed

Crupi, Rosalia; Paterniti, Irene; Ahmad, Akbar; Campolo, Michela; Esposito, Emanuela; Cuzzocrea, Salvatore

2013-11-01

The antidepressant effect of a compound formed by co-ultramicronized palmitoylethanolamide (PEA) and luteolin (PEA+luteolin) was investigated in a mouse model of anxiety/depressive-like behavior. 129Sv/Ev mice were subjected to 6 weeks of corticosterone administration, and then behavior, neurogenesis, neuroplasticity, neurotrophic and apoptotic proteins expression were evaluated. The effect of PEA+luteolin compound treatment (1mg/kg, i.p.), on depression-like behaviour was assessed using different paradigms such as open field, novelty suppressed feeding, forced swim test and elevated plus maze. In particular in the open field, novelty suppressed feeding and elevated plus maze the time spent in the open arm was employed as an indicator of anxiety; forced swim test was used to evaluate the antidepressant capacity of PEA+luteolin on immobility time as an indicator of depression. Adult hippocampal neurogenesis and neuroplasticity were evaluated by immunohistochemical techniques; brain-derived neurotrophic factor and apoptotic protein (Bax and Bcl2) expression were studied by immunostaining and Western blot analysis. For the first time we demonstrated that PEA+luteolin compound exerts a significant antidepressant effect a low dose and may be considered as a novel therapeutic strategy in depression.

Exploiting genes and functional diversity of chlorogenic acid and luteolin biosyntheses in Lonicera japonica and their substitutes.

PubMed

Yuan, Yuan; Wang, Zhouyong; Jiang, Chao; Wang, Xumin; Huang, Luqi

2014-01-25

Chlorogenic acids (CGAs) and luteolin are active compounds in Lonicera japonica, a plant of high medicinal value in traditional Chinese medicine. This study provides a comprehensive overview of gene families involved in chlorogenic acid and luteolin biosynthesis in L. japonica, as well as its substitutes Lonicera hypoglauca and Lonicera macranthoides. The gene sequence feature and gene expression patterns in various tissues and buds of the species were characterized. Bioinformatics analysis revealed that 14 chlorogenic acid and luteolin biosynthesis-related genes were identified from the L. japonica transcriptome assembly. Phylogenetic analyses suggested that the function of individual gene could be differentiation and induce active compound diversity. Their orthologous genes were also recognized in L. hypoglauca and L. macranthoides genomic datasets, except for LHCHS1 and LMC4H2. The expression patterns of these genes are different in the tissues of L. japonica, L. hypoglauca and L. macranthoides. Results also showed that CGAs were controlled in the first step of biosynthesis, whereas both steps controlled luteolin in the bud of L. japonica. The expression of LJFNS2 exhibited positive correlation with luteolin levels in L. japonica. This study provides significant information for understanding the functional diversity of gene families involved in chlorogenic acid and the luteolin biosynthesis, active compound diversity of L. japonica and its substitutes, and the different usages of the three species. Copyright © 2012. Published by Elsevier B.V.

[Protective effects of luteolin on neurons against oxygen-glucose deprivation/reperfusion injury via improving Na+/K+ -ATPase activity].

PubMed

Fang, Lumei; Zhang, Mingming; Ding, Yuemin; Fang, Yuting; Yao, Chunlei; Zhang, Xiong

2010-04-01

Luteolin, a flavone, has considerable neuroprotective effects by its anti-oxidative mechanism. However, it is still unclear whether luteolin can protect neurons against oxygen-glucose deprivation/reperfusion (OGD/R) induced injury. After 2 hours oxygen-glucose deprivation and 24 hours reperfusion treatment in primary cultured hippocampal neurons, the neuron viability, survival rate and apoptosis rate were evaluated by MTT assay, lactate dehydrogenase (LDH) leakage assay and Hoechst staining, respectively. The activity of Na+/K+ -ATPase was examined in cultured neurons or in the hippocampus of SD rats treated by 10 minutes global cerebral ischemia and followed 24 hours reperfusion. Treatment by OGD/R markedly reduced neuronal viability, increased LDH leakage rate and increased apoptosis rate. Application of luteolin (10-100 micromol x L(-1)) during OGD inhibited OGD/R induced neuron injury and apoptosis in a dose-dependent manner. Compared to the control group or OGP/R-treated neurons, the activity of Na+/K+ -ATPase was significantly suppressed in global ischemia/reperfusion group or OGD/R-treated neurons. Application of luteolin during ischemia or OGD preserved the Na+/K+ -ATPase activity. Furthermore, inhibition of Na+/K+ -ATPase with ouabain attenuated the protective effect afforded by luteolin. The data provide the evidence that luteolin has neuroprotective effect against OGD/R induced injury and the protective effect may be associated with its ability to improve Na+/K+ -ATPase activity after OGD/R.

Apigenin Attenuates Experimental Autoimmune Myocarditis by Modulating Th1/Th2 Cytokine Balance in Mice.

PubMed

Zhang, Shouxin; Liu, Xiaoyan; Sun, Chengming; Yang, Jun; Wang, Lihong; Liu, Jie; Gong, Lei; Jing, Yanyan

2016-04-01

This study aims to investigate the protective effect of apigenin on the development of experimental autoimmune myocarditis (EAM) and the underlying mechanisms. An EAM model was induced in BALB/c mice by the injection of porcine cardiac myosin. Apigenin was orally administered from day 1 to 21. The severity of myocarditis was assessed by determination of heart weight/body weight ratio (HW/BW) and histopathological evaluation. Echocardiography was conducted to evaluate the cardiac function and heart structure. Antigen-specific T cell proliferation responses to cardiac myosin were evaluated by the lymphocyte proliferation assay. ELISA was used to determine serum levels of type 1 helper (Th1) and Th2 cytokines. Apigenin treatment significantly decreased HW/BW. Histopathologic analysis showed that the infiltration of inflammatory cells was reduced significantly by apigenin treatment. Meanwhile, apigenin administration effectively ameliorated autoimmune myocarditis-induced cardiac hypertrophy and cardiac dysfunction as well as inhibited lymphocyte proliferation in mice immunized with myosin. Furthermore, Th1 cytokines tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and interleukin-2 (IL-2) were significantly downregulated, while Th2 cytokines IL-4 and IL-10 were markedly upregulated. The results indicated that apigenin can alleviate EAM due to its immunomodulatory reactions in modification of helper T cell balance.

Propolis Extracted from the Stingless Bee Trigona sirindhornae Inhibited S. mutans Activity In Vitro.

PubMed

Utispan, Kusumawadee; Chitkul, Bordin; Monthanapisut, Paopanga; Meesuk, Ladda; Pugdee, Kamolparn; Koontongkaew, Sittichai

The aim of this study was to determine the antimicrobial effects of propolis extracted from an endemic species of stingless bee, T. sirindhornae, on the cariogenic bacterium Streptococcus mutans. Dichloromethane extracts (DME) of propolis (DMEP) were prepared and analysed by reverse-phase high-performance liquid chromatography. The antibacterial growth and antibiofilm formation effects of DMEP on S. mutans were compared with those of apigenin, a commercial propolis product. The effects of DMEP and apigenin on glucosyltransferase (gtf) B expression in S. mutans were investigated using real-time polymerase chain reaction. Chlorhexidine (CHX) was used as a positive control in the experiments. Apigenin, pinocembrin, p-coumaric acid, and caffeic acid were not detected in the propolis extracts. DMEP and apigenin significantly inhibited S. mutans growth (IC50 = 43.5 and 17.36 mg/ml, respectively). DMEP and apigenin also exhibited antiadherence effects on S. mutans as shown by reduced biofilm formation. Furthermore, a significant inhibition in gtfB expression was observed in DMEP and apigenin treated S. mutans. Propolis produced by T. sirindhornae demonstrated antibacterial and antibiofilm effects, and reduced gtfB expression in S. mutans. The antibacterial activities of propolis observed were not due to apigenin, pinocembrin, p-coumaric acid, or caffeic acid.

[Inhibitory effects of luteolin on human gastric carcinoma xenografts in nude mice and its mechanism].

PubMed

Lu, Xue-ying; Li, Yan-hong; Xiao, Xiang-wen; Li, Xiao-bo

2013-01-08

To explore the in vivo anticancer effects of luteolin with BGC-823 gastric carcinoma xenografts in nude mice and elucidate its mechanism. After modeling of gastric carcinoma xenografts in nude mice, 40 BALB/c (nu/nu) nude mice were randomly divided into 5 groups (n = 8 each). And an intraperitoneal injection of luteolin was administered at 10 mg/kg (low-dose), 20 mg/kg (middle-dose) and 40 mg/kg (high-dose) groups. And 5-fluorouracil (30 mg/kg) and control groups were also established. The growth curves of xenografts in nude mice were drawn and weight inhibition rates measured. The morphological features were detected by hematoxylin and eosin staining. And the protein expression levels of vascular endothelial growth factor A (VEGF-A) and matrix metalloproteinase 9 (MMP-9) were measured by immunohistochemistry. In vivo tumor formation test showed that tumor volume in nude mice treated with luteolin was smaller than that of control group. Tumor weights of high-dose luteolin group were lighter than those of the control ((0.29 ± 0.01) vs (0.38 ± 0.03) g). And the difference was statistically significant (P < 0.01). The rate of tumor inhibition in high-dose luteolin group was up to 24.87%. Lymphocytic invasion of tumor tissue was observed under light microscope in the treatment groups. Results of immunohistochemistry showed the positive cell integral of VEGF in middle and high-dose luteolin groups were 1.25 ± 0.17 and 1.00 ± 0.07 respectively. Both were significantly lower than that of control group (1.50 ± 0.15, both P < 0.05). The positive cell integral of MMP-9 in high-dose luteolin group was markedly lower than that of control group (3.75 ± 1.43 vs 9.00 ± 1.08, P < 0.01). Luteolin can effectively inhibit the in vivo growth of gastric tumor. The mechanism may be correlated with the stimulation of immune response and the down-regulated expressions of VEGF-A and MMP-9.

Synergistic antibacterial effect of apigenin with β-lactam antibiotics and modulation of bacterial resistance by a possible membrane effect against methicillin resistant Staphylococcus aureus.

PubMed

Akilandeswari, K; Ruckmani, K

2016-12-30

Methicillin-resistant Staphylococcus aureus (MRSA) infections are easily spread among infected patients, where resistance has dramatically increased resulted in serious health issues. Therefore, there is a need to develop alternative natural or combination drug therapies. Apigenin (AP) is a natural poly phenolic flavonoid has been found to possess many beneficial biological actions. The aim of this study was to investigate the anti-MRSA efficacy and synergistic effect of apigenin (AP) and in combination with ampicillin (AM) and ceftriaxone (CEF). The antibacterial activity of apigenin was assessed by the broth macro dilution, checkerboard micro dilution method and time-kill assay.  The mode of action was studied by outer and inner membrane permeabilisation assays, scanning electron microscopy and transmission electron microscopy. The minimum inhibitory concentration (MIC) of apigenin against gram positive and gram negative strain ranged from 32.5 to 62.5µg/ml. In checkerboard method apigenin markedly reduced the MIC of the antibiotics ampicillin 800 µg/ml shifted to 107 µg/ml (AM+AP) and ceftriaxone 58 µg/ml shifted to 2.6 µg/ml (CEF+AP) against MRSA. The synergistic activity of ampicillin and ceftriaxone plus apigenin combinations with FIC indices (CI) between 0.18-0.47. The modulation of methicillin-resistance by apigenin significantly enhanced the activities of ampicillin and ceftriaxone. The result of time-kill assays of the two drug combinations AM +AP and CEF+AP against MRSA showed significant inhibitory effect and reduced the colony count by approximately 99% after 8 h The results for outer membrane (OM) and inner membrane (IM) permeabilization showed that ampicillin and ceftriaxone in combination with apigenin damaged MRSA cytoplasmic membrane and caused subsequent leakage of intracellular constituents. Electron microscopy clearly showed that the above said combination also caused marked morphological damage of cell wall, cell shape and plasma membrane of this strain. From these results, it can be concluded that apigenin has the synergistic effect with ampicillin and ceftriaxone to reverse bacterial resistance against MRSA.

Apigenin alleviates STZ-induced diabetic cardiomyopathy.

PubMed

Liu, Huang-Jun; Fan, Yun-Lin; Liao, Hai-Han; Liu, Yuan; Chen, Si; Ma, Zhen-Guo; Zhang, Ning; Yang, Zheng; Deng, Wei; Tang, Qi-Zhu

2017-04-01

Apigenin is an important component of fruits and vegetables in human daily diets. Several cellular and animal models have been performed to demonstrate its anti-oxidant and anti-inflammatory bioactivities. However, the cardioprotective effects of apigenin in diabetic cardiomyopathy (DCM) remain unclear. In this study, we intended to explore the roles of apigenin in cardiac remodeling of DCM. Male C57BL/6 J mice were treated with streptozotocin (STZ, 50 mg/kg) for 5 consecutive days to induce DCM. The echocardiography and catheter-based measurements of hemodynamic parameters were performed to evaluate the cardiac function. Paraffin slices of harvested hearts were prepared for histological pathological analysis and TUNEL assay. Oxidative assay kits were used to detect Glutathione Peroxidase (GPx), Lipid Peroxidation Malondialdehyde (MDA), and Superoxide Dismutase (SOD). Western blot and real-time PCR were used for accessing the expressions of protein and mRNA. Diabetes mellitus exacerbated the cardiac dysfunction, fibrosis, and overaccumulation of 4-hydroxynonenal accompanying with down-regulation of Bcl2, GPx, and SOD, up-regulation of MDA, cleaved caspase3, and pro-apoptotic protein Bax, and contribution to the translocation of NF-κB. All these pathological changes could be effectively blunted by treatment of apigenin in vivo. Finally, H9c2 treated with high glucose or apigenin was used for further investigation of these effects in vitro; what is more, we also compared the effects between apigenin and Resveratrol in in vitro experiments. Our experiments have demonstrated that apigenin may be a potential drug for diabetic patients suffering from DCM.

Preliminary enrichment and separation of genistein and apigenin from extracts of pigeon pea roots by macroporous resins.

PubMed

Liu, Wei; Zhang, Su; Zu, Yuan-Gang; Fu, Yu-Jie; Ma, Wei; Zhang, Dong-Yang; Kong, Yu; Li, Xiao-Juan

2010-06-01

Enrichment and separation of genistein and apigenin from extracts of pigeon pea roots were studied using eleven macroporous resins with different physical and chemical properties. ADS-5 resin showed the maximum effectiveness among the tested resins. The solute affinity towards ADS-5 resin at different temperatures was described in terms of Langmuir and Freundlich isotherms, and the equilibrium experimental data were well-fitted to the two isotherms. In order to optimize the operating parameters for separating genistein and apigenin, dynamic adsorption and desorption tests were carried out. After one run treatment with ADS-5 resin, the contents of genistein and apigenin in the product were 9.36-fold and 11.09-fold increased with recovery yields of 89.78% and 93.41%, respectively. The process achieved easy and effective enrichment and separation of genistein and apigenin by using ADS-5 resin, and it is a promising basis for large-scale preparation of genistein and apigenin from pigeon pea or other plants extracts. (c) 2010 Elsevier Ltd. All rights reserved.

Apigenin sensitizes hepatocellular carcinoma cells to doxorubic through regulating miR-520b/ATG7 axis.

PubMed

Gao, Ai-Mei; Zhang, Xiao-Yu; Hu, Juan-Ni; Ke, Zun-Ping

2018-01-25

Chemo-resistance is a serious obstacle for successful treatment of cancer. Apigenin, a dietary flavonoid, has been reported as an anticancer drug in various malignant cancers. This study aimed to investigate the potential chemo-sensitization effect of apigenin in doxorubicin-resistant hepatocellular carcinoma cell line BEL-7402/ADM. We observed that apigenin significantly enhanced doxorubicin sensitivity, induced miR-520b expression and inhibited ATG7-dependent autophagy in BEL-7402/ADM cells. In addition, we also showed that miR-520b mimics increased doxorubicin sensitivity and inhibited ATG7-dependent autophagy. Meanwhile, we indicated that ATG7 was a potential target of miR-520b. Furthermore, APG inhibited the growth of hepatocellar carcinoma xenografts in nude mice by up-regulating miR-520b and inhibiting ATG7. Our finding provides evidence that apigenin sensitizes BEL-7402/ADM cells to doxorubicin through miR-520b/ATG7 pathway, which furtherly supports apigenin as a potential chemo-sensitizer for hepatocellular carcinoma. Copyright © 2017 Elsevier B.V. All rights reserved.

Synergistic apoptotic effects of apigenin TPGS liposomes and tyroservatide: implications for effective treatment of lung cancer

PubMed Central

Jin, Xin; Yang, Qing; Zhang, Youwen

2017-01-01

To develop an alternative treatment for lung cancer, a combination of two potent chemotherapeutic agents – liposomal apigenin and tyroservatide – was developed. The therapeutic potential of this combination was investigated using A549 cells. Apigenin and tocopherol derivative-containing D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) liposomes might improve the delivery of apigenin to tumor cells, both in vitro and in vivo. Importantly, compared to either agent alone, the combination of apigenin TPGS liposomes and tyroservatide exhibited superior cytotoxicity, induced stronger G2 arrest, and suppressed A549 cancer cell invasion at a lower dose. The proapoptotic synergistic effects were also observed in A549 cells using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, flow cytometry, and Western blot analysis. More importantly, in vivo results showed that the combination of apigenin TPGS liposomes and tyroservatide exhibited tumor-growth inhibitory effects in A549 cell-bearing mice. In conclusion, our study showed that this combination therapy could serve as a promising synergistic therapeutic approach to improve outcomes in patients with lung cancer. PMID:28761344

Synergistic apoptotic effects of apigenin TPGS liposomes and tyroservatide: implications for effective treatment of lung cancer.

PubMed

Jin, Xin; Yang, Qing; Zhang, Youwen

2017-01-01

To develop an alternative treatment for lung cancer, a combination of two potent chemotherapeutic agents - liposomal apigenin and tyroservatide - was developed. The therapeutic potential of this combination was investigated using A549 cells. Apigenin and tocopherol derivative-containing D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) liposomes might improve the delivery of apigenin to tumor cells, both in vitro and in vivo. Importantly, compared to either agent alone, the combination of apigenin TPGS liposomes and tyroservatide exhibited superior cytotoxicity, induced stronger G2 arrest, and suppressed A549 cancer cell invasion at a lower dose. The proapoptotic synergistic effects were also observed in A549 cells using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, flow cytometry, and Western blot analysis. More importantly, in vivo results showed that the combination of apigenin TPGS liposomes and tyroservatide exhibited tumor-growth inhibitory effects in A549 cell-bearing mice. In conclusion, our study showed that this combination therapy could serve as a promising synergistic therapeutic approach to improve outcomes in patients with lung cancer.

Apigenin reduce lipoteichoic acid-induced inflammatory response in rat cardiomyoblast cells.

PubMed

Gutiérrez-Venegas, Gloria; González-Rosas, Zeltzin

2017-02-01

Infective endocarditis is caused by Streptococcus sanguinis present in dental plaque, which can induce inflammatory responses in the endocardium. The present study depicts research on the properties of apigenin in embryonic mouse heart cells (H9c2) treated with lipoteichoic acid (LTA) obtained from S. sanguinis. Interleukin-1β and cyclooxygenase (COX)-2 expression were detected by reverse transcriptase polymerase chain reaction. In addition, western blot assays and immuno-fluorescence staining were used to assess translocation of nuclear factor kappa beta (NF-κB), degradation of IκB, as well as activity of the mitogen activated protein kinases: extracellular signal-regulated kinase (ERK)1/2, p38, and c-Jun N-terminal kinase (JNK). Effect of apigenin on cell viability was equally assessed in other experimental series. Our results showed that apigenin blocked activation of ERK, JNK, and p38 in cardiomyocytes treated with LTA in a dose-dependent fashion. Moreover, apigenin showed no cytotoxic effects; it blocked NF-κB translocation and IκB degradation. Our findings suggested that apigenin possessed potential value in the treatment of infectious endocarditis.

Anti-Inflammatory Effect of Apigenin on LPS-Induced Pro-Inflammatory Mediators and AP-1 Factors in Human Lung Epithelial Cells.

PubMed

Patil, Rajeshwari H; Babu, R L; Naveen Kumar, M; Kiran Kumar, K M; Hegde, Shubha M; Nagesh, Rashmi; Ramesh, Govindarajan T; Sharma, S Chidananda

2016-02-01

Apigenin is one of the plant flavonoids present in fruits and vegetables, acting as an important nutraceutical component. It is recognized as a potential antioxidant, antimicrobial, and anti-inflammatory molecule. In the present study, the mechanism of anti-inflammatory action of apigenin on lipopolysaccharide (LPS)-induced pro-inflammatory cytokines and activator protein-1 (AP-1) factors in human lung A549 cells was investigated. The anti-inflammatory activity of apigenin on LPS-induced inflammation was determined by analyzing the expression of pro-inflammatory cytokines, nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and different AP-1 factors. Apigenin significantly inhibited the LPS-induced expression of iNOS, COX-2, expression of pro-inflammatory cytokines (IL-1β, IL-2, IL-6, IL-8, and TNF-α), and AP-1 proteins (c-Jun, c-Fos, and JunB) including nitric oxide production. Study confirms the anti-inflammatory effect of apigenin by inhibiting the expression of inflammatory mediators and AP-1 factors involved in the inflammation and its importance in the treatment of lung inflammatory diseases.

Apigenin Attenuates Inflammation in Experimentally Induced Acute Pancreatitis-Associated Lung Injury.

PubMed

Basios, Neofitos; Lampropoulos, Pavlos; Papalois, Apostolos; Lambropoulou, Maria; Pitiakoudis, Michael K; Kotini, Athanasia; Simopoulos, Constantinos; Tsaroucha, Alexandra K

2016-06-01

Acute pancreatitis is associated with acute lung injury. The aim of the present study is to evaluate alterations of lungs in an experimental model of acute pancreatitis (AP) following both bilio-pancreatic duct obstruction close to the duodenum. Acute pancreatitis is a common disease with significant mortality. This situation makes the need of finding protective factors for the lung parenchyma, imperative. In the present study there is an effort to clarify the role of apigenin, a substance which is well known for its antioxidant and anti-inflammatory effects, on lung injury, following acute pancreatitis in rats. In the present study, 126 male Wistar-type rats 3-4 months old and 220-350 g weight were used. At time 0 we randomly assigned the following groups: Group Sham: Rats were subjected to virtual surgery. Group Control: Rats were subjected to surgery for induction of acute pancreatitis. Group Apigenin: Rats were subjected to surgery for induction of acute pancreatitis and enteral feeding with apigenin. Immunochemistry for TNF-α and IL-6 as well as MPO activity were measured at predetermined time intervals 6, 12, 24, 48, and 72 h, in order to evaluate architectural disturbances of the lung tissue. From the pathological reports we realized that comparing the control group with the apigenin group, there is an improvement of lung tissue damage following apigenin administration, with statistical significance. Apigenin reduces most histopathological alterations of the pulmonary tissue, reduces MPO and TNF-α activity at 48 hours and, furthermore, reduces IL-6 activity at 72 hours post-administration. Oral Apigenin administration in rats, following experimental induced acute pancreatitis, seems to be protective on the lung tissue. Apigenin administration to humans could potentially ameliorate acute lung injuries. However, special caution is required for humans' use, as more detailed studies are needed.

Apigenin inhibits prostate cancer progression in TRAMP mice via targeting PI3K/Akt/FoxO pathway

PubMed Central

Gupta, Sanjay

2014-01-01

Forkhead box O (FoxO) transcription factors play an important role as tumor suppressor in several human malignancies. Disruption of FoxO activity due to loss of phosphatase and tensin homolog and activation of phosphatidylinositol-3 kinase (PI3K)/Akt are frequently observed in prostate cancer. Apigenin, a naturally occurring plant flavone, exhibits antiproliferative and anticarcinogenic activities through mechanisms, which are not fully defined. In the present study, we show that apigenin suppressed prostate tumorigenesis in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice through the PI3K/Akt/FoxO-signaling pathway. Apigenin-treated TRAMP mice (20 and 50 μg/mouse/day, 6 days/week for 20 weeks) exhibited significant decrease in tumor volumes of the prostate as well as completely abolished distant organ metastasis. Apigenin treatment resulted in significant decrease in the weight of genitourinary apparatus (P < 0.0001), dorsolateral (P < 0.0001) and ventral prostate (P < 0.028), compared with the control group. Apigenin-treated mice showed reduced phosphorylation of Akt (Ser473) and FoxO3a (Ser253), which correlated with its increased nuclear retention and decreased binding of FoxO3a with 14-3-3. These events lead to reduced proliferation as assessed by Ki-67 and cyclin D1, along with upregulation of FoxO-responsive proteins BIM and p27/Kip1. Complementing in vivo results, similar observations were noted in human prostate cancer LNCaP and PC-3 cells after apigenin treatment. Furthermore, binding of FoxO3a with p27/Kip1 was markedly increased after 10 and 20 μM apigenin treatment resulting in G0/G1-phase cell cycle arrest, which was consistent with the effects elicited by PI3K/Akt inhibitor, LY294002. These results provide convincing evidence that apigenin effectively suppressed prostate cancer progression, at least in part, by targeting the PI3K/Akt/FoxO-signaling pathway. PMID:24067903

Apigenin suppresses migration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4 expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Lei; Kuang, Lisha; Hitron, John Andrew

Environmental exposure to arsenic is known to cause various cancers. There are some potential relationships between cell malignant transformation and C-X-C chemokine receptor type 4 (CXCR4) expressions. Metastasis, one of the major characteristics of malignantly transformed cells, contributes to the high mortality of cells. CXCR4 and its natural chemokine ligand C-X-C motif ligand 12 (CXCL12) play a critical role in metastasis. Therefore, identification of nutritional factors which are able to inhibit CXCR4 is important for protection from environmental arsenic-induced carcinogenesis and for abolishing metastasis of malignantly transformed cells. The present study demonstrates that apigenin (4′,5,7-trihydroxyflavone), a natural dietary flavonoid, suppressedmore » CXCR4 expression in arsenic-transformed Beas-2B cells (B-AsT) and several other types of transformed/cancer cells in a dose- and time-dependent manner. Neither proteasome nor lysosome inhibitor had any effect in reducing the apigenin-induced down-regulation of CXCR4, indicating that apigenin-induced down-regulation of CXCR4 is not due to proteolytic degradation. The down-regulation of CXCR4 is mainly due to the inhibition of nuclear factor κB (NF-κB) transcriptional activity. Apigenin also abolished migration and invasion of transformed cells induced by CXCL12. In a xenograft mouse model, apigenin down-regulated CXCR4 expression and suppressed tumor growth. Taken together, our results show that apigenin is a novel inhibitor of CXCR4 expression. This dietary flavonoid has the potential to suppress migration and invasion of transformed cells and prevent environmental arsenic-induced carcinogenesis. - Highlights: • Apigenin has a potential in preventing environmental arsenic induced carcinogenesis. • Apigenin suppresses CXCR4 in malignant transformed cells in vitro and in vivo. • The down-regulation of CXCR4 is mainly due to inhibition of NF-κB activity.« less

Insight into the novel inhibition mechanism of apigenin to Pneumolysin by molecular modeling

NASA Astrophysics Data System (ADS)

Niu, Xiaodi; Yang, Yanan; Song, Meng; Wang, Guizhen; Sun, Lin; Gao, Yawen; Wang, Hongsu

2017-11-01

In this study, the mechanism of apigenin inhibition was explored using molecular modelling, binding energy calculation, and mutagenesis assays. Energy decomposition analysis indicated that apigenin binds in the gap between domains 3 and 4 of PLY. Using principal component analysis, we found that binding of apigenin to PLY weakens the motion of domains 3 and 4. Consequently, these domains cannot complete the transition from monomer to oligomer, thereby blocking oligomerisation of PLY and counteracting its haemolytic activity. This inhibitory mechanism was confirmed by haemolysis assays, and these findings will promote the future development of an antimicrobial agent.

Coadministrating luteolin minimizes the side effects of the aromatase inhibitor letrozole.

PubMed

Li, Fengjuan; Wong, Tsz Yan; Lin, Shu-mei; Chow, Simon; Cheung, Wing-hoi; Chan, Franky L; Chen, Shiuan; Leung, Lai K

2014-11-01

Aromatase inhibitors (AIs) have been used as adjuvant therapeutic agents for breast cancer. Their adverse side effect on blood lipid is well documented. Some natural compounds have been shown to be potential AIs. In the present study, we compared the efficacy of the flavonoid luteolin to the clinically approved AI letrozole (Femara; Novartis Pharmaceuticals, East Hanover, NJ) in a cell and a mouse model. In the in vitro experimental results for aromatase inhibition, the Ki values of luteolin and letrozole were estimated to be 2.44 µM and 0.41 nM, respectively. Both letrozole and luteolin appeared to be competitive inhibitors. Subsequently, an animal model was used for the comparison. Aromatase-expressing MCF-7 cells were transplanted into ovariectomized athymic mice. Luteolin was given by mouth at 5, 20, and 50 mg/kg, whereas letrozole was administered by intravenous injection. Similar to letrozole, luteolin administration reduced plasma estrogen concentrations and suppressed the xenograft proliferation. The regulation of cell cycle and apoptotic proteins-such as a decrease in the expression of Bcl-xL, cyclin-A/D1/E, CDK2/4, and increase in that of Bax-was about the same in both treatments. The most significant disparity was on blood lipids. In contrast to letrozole, luteolin increased fasting plasma high-density lipoprotein concentrations and produced a desirable blood lipid profile. These results suggested that the flavonoid could be a coadjuvant therapeutic agent without impairing the action of AIs. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

Extraction process optimization of polyphenols from Indian Citrus sinensis – as novel antiglycative agents in the management of diabetes mellitus

PubMed Central

2014-01-01

Background Diabetes mellitus is a chronic metabolic disorder characterized by increased blood glucose level. It has become an epidemic disease in the 21st century where, India leads the world with largest number of diabetic subjects. Non-enzymatic glycosylation (glycation) is severe form of diabetes, occurs between reducing sugar and proteins which results in the formation of advanced glycation end products (AGEs) that leads to the other complicated secondary disorders. In this context, Mangifera indica (Mango), Syzygium cumini (Jambul), Vitis vinifera (Grapes), Citrus sinensis (Orange), Artocarpus heterophyllus (Jackfruit), Manilkara zapota (Sapodilla) seeds were evaluated for their antiglyation activity. Attempts were made to isolate the polyphenols in the seeds that have recorded the maximum activity. Methods Different extraction methods (shake flask, centrifugation and pressurized hot water) using various extractants (organic solvents, hot water and pressurized hot water) were adopted to investigate the in vitro antiglycation activity. Central composite (CCD) design based Response Surface Methodology (RSM) was espoused to optimize the extraction process of polyphenols from the fruit seeds that have recorded poor antiglycation activity. The PTLC analysis was performed to isolate the polyphenols (Flavonoids and phenolic acids) and LC-PDA-MS analysis was done for structure prediction. Results Pressurized hot water extraction of Artocarpus heterophyllus (87.52%) and Citrus sinensis seeds (74.79%) was found to possess high and low antiglycation activity, respectively. The RSM mediated optimization process adopted for the Citrus sinensis seeds have revealed that 1:15 solvent ratio (hexane to heptane), 6 minutes and 1:20 solid to liquid ratio as the optimal conditions for the extraction of polyphenols with a maximum antiglycation activity (89.79%). The LC-PDA-MS analysis of preparative thin layer chromatography (PTLC) eluates of Artocarpus heterophyllus seed has showed the presence of compounds like quercetin (301.2), 4-hydroxy phenyl acetic acid (149.0), rhamnosyl-di-hexosyl quercetin sulphate (857.6), quercetin-3-O-xyloside (428.2), rutin (613.4), diosmetin (298.1) and luteolin (283.0). Conclusion The Artocarpus heterophyllus was observed to possess a significant antiglycation activity and the activity of Citrus sinensis was improved after the optimization process, which proved that both the seeds may be used as a traditional medicine in the management of chronic diabetes mellitus. PMID:24397983

Extraction process optimization of polyphenols from Indian Citrus sinensis - as novel antiglycative agents in the management of diabetes mellitus.

PubMed

Shakthi Deve, Asaithambi; Sathish Kumar, Thiyagarajan; Kumaresan, Kuppamuthu; Rapheal, Vinohar Stephen

2014-01-07

Diabetes mellitus is a chronic metabolic disorder characterized by increased blood glucose level. It has become an epidemic disease in the 21st century where, India leads the world with largest number of diabetic subjects. Non-enzymatic glycosylation (glycation) is severe form of diabetes, occurs between reducing sugar and proteins which results in the formation of advanced glycation end products (AGEs) that leads to the other complicated secondary disorders. In this context, Mangifera indica (Mango), Syzygium cumini (Jambul), Vitis vinifera (Grapes), Citrus sinensis (Orange), Artocarpus heterophyllus (Jackfruit), Manilkara zapota (Sapodilla) seeds were evaluated for their antiglyation activity. Attempts were made to isolate the polyphenols in the seeds that have recorded the maximum activity. Different extraction methods (shake flask, centrifugation and pressurized hot water) using various extractants (organic solvents, hot water and pressurized hot water) were adopted to investigate the in vitro antiglycation activity. Central composite (CCD) design based Response Surface Methodology (RSM) was espoused to optimize the extraction process of polyphenols from the fruit seeds that have recorded poor antiglycation activity. The PTLC analysis was performed to isolate the polyphenols (Flavonoids and phenolic acids) and LC-PDA-MS analysis was done for structure prediction. Pressurized hot water extraction of Artocarpus heterophyllus (87.52%) and Citrus sinensis seeds (74.79%) was found to possess high and low antiglycation activity, respectively. The RSM mediated optimization process adopted for the Citrus sinensis seeds have revealed that 1:15 solvent ratio (hexane to heptane), 6 minutes and 1:20 solid to liquid ratio as the optimal conditions for the extraction of polyphenols with a maximum antiglycation activity (89.79%). The LC-PDA-MS analysis of preparative thin layer chromatography (PTLC) eluates of Artocarpus heterophyllus seed has showed the presence of compounds like quercetin (301.2), 4-hydroxy phenyl acetic acid (149.0), rhamnosyl-di-hexosyl quercetin sulphate (857.6), quercetin-3-O-xyloside (428.2), rutin (613.4), diosmetin (298.1) and luteolin (283.0). The Artocarpus heterophyllus was observed to possess a significant antiglycation activity and the activity of Citrus sinensis was improved after the optimization process, which proved that both the seeds may be used as a traditional medicine in the management of chronic diabetes mellitus.

Suppression by apigenin of peritoneal metastasis of intestinal adenocarcinomas induced by azoxymethane in Wistar rats.

PubMed

Tatsuta, A; Iishi, H; Baba, M; Yano, H; Murata, K; Mukai, M; Akedo, H

2000-01-01

The effect of a naturally occurring flavonoid apigenin on the development of bombesin-enhanced peritoneal metastasis from intestinal adenocarcinomas induced by azoxymethane was investigated in male Wistar rats. From the start of the experiment, rats were given weekly s.c. injections of azoxymethane (7.4 mg/kg body weight) for 10 weeks and s.c. injection of bombesin (40 microg/kg body weight) every other day, and from week 16, s.c. injections of apigenin (0.75 or 1.5 mg/kg body weight) every other day until the end of the experiment in week 45. Bombesin significantly increased the incidence of intestinal tumors and cancer metastasis to the peritoneum in week 45. It also significantly increased the labeling index of intestinal cancers. Although administration of apigenin at either dose with bombesin had little or no effect on the enhancement of intestinal carcinogenesis by bombesin, the location, histologic type, depth of involvement, infiltrating growth patterns and labeling index, it was found to decrease significantly the incidence of cancer metastasis. Apigenin significantly decreased the incidence of lymphatic vessel invasion of adenocarcinomas, which was enhanced by bombesin. In vitro experiments revealed that apigenin inhibited bombesin-enhanced phosphorylation of mitogen-activated protein kinase (MAPK), but not matrix metalloprotease (MMP)-9 expression. Our findings indicate that apigenin inhibits cancer metastasis through inhibition of phosphorylation of MAPK.

Quantification of phytoprostanes - bioactive oxylipins - and phenolic compounds of Passiflora edulis Sims shell using UHPLC-QqQ-MS/MS and LC-IT-DAD-MS/MS.

PubMed

Medina, Sonia; Collado-González, Jacinta; Ferreres, Federico; Londoño-Londoño, Julián; Jiménez-Cartagena, Claudio; Guy, Alexandre; Durand, Thierry; Galano, Jean-Marie; Gil-Izquierdo, Angel

2017-08-15

The genus Passiflora, comprising about 500 species, is the largest in the Passion flower family. Passiflora edulis Sims f. edulis (gulupa) is one of the most important fruits cultivated in Colombia. In recent years and due to its organoleptic and bioactive properties, its exports have significantly increased. In this work, six new bioactive oxylipins -phytoprostanes - were detected in gulupa shell by a UHPLC-QqQ-MS/MS method: F 1t -phytoprostanes and D 1t -phytoprostanes were the predominant and minor classes, respectively. Moreover, the polyphenol profile of the shell was investigated and we were able to detect and quantify phenolic compounds that have not been described previously, like luteolin-8-C-(2-O-rhamnosyl)hexoside and quercetin-3-O-(6″-acetyl)glucosyl-2″-sinapic acid. Consequently, this study provides new insights into the importance of gulupa shell as a valuable option in the design of new beverages rich in antioxidant phytochemicals, as part of a well-balanced diet, and in the process and quality control of such products. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dereplication of antioxidant compounds in Bene (Pistacia atlantica subsp. mutica) hull using a multiplex approach of HPLC-DAD, LC-MS and (1)H NMR techniques.

PubMed

Rezaie, Mitra; Farhoosh, Reza; Pham, Ngoc; Quinn, Ronald J; Iranshahi, Mehrdad

2016-01-05

Bene is an edible fruit from the tree Pistacia atlantica subsp. mutica, and is of steadily growing interest in recent years due to its significant antioxidant properties and potential health benefits. An antioxidant activity-guided fractionation of the methanol extract from Bene hull together with an integrated approach of HPLC-DAD, LC-MS and (1)H NMR techniques led to the identification of main antioxidant phenolic compounds for the first time. Radical scavenging activity of each fraction/compound was tested using DPPH and FRAP assays. The phenolic content of the fractions was also determined by Folin-Ciocalteu's method. The main identified antioxidant compounds were luteolin (46.53% w/w of total extract), gallic acid (9.84% w/w), 2″-O-galloylisoquercitrin (0.53% w/w), quercetin 3-rutinoside (0.34% w/w) and 2″-O-cis-caffeoylquercitrin (0.26% w/w). The minor antioxidant compounds were also identified by liquid chromatography-positive/negative electrospray ionization tandem mass spectrometry. The structure-antioxidant activity relationship of identified phenolics are also discussed in this paper. Copyright © 2015 Elsevier B.V. All rights reserved.

Comparison of five agro-industrial waste-based composts as growing media for lettuce: Effect on yield, phenolic compounds and vitamin C.

PubMed

Santos, Francielly T; Goufo, Piebiep; Santos, Cátia; Botelho, Donzilia; Fonseca, João; Queirós, Aurea; Costa, Mônica S S M; Trindade, Henrique

2016-10-15

Overall phenolic content in plants is on average higher in organic farming, including when renewable resources such as composts are used as soil amendments. In most cases, however, the composting process needs to be optimized to reach the desired outcome. Using composts obtained from chestnut, red and white grapes, olive and broccoli wastes, the relative antioxidative abilities of lettuces cultivated in greenhouse were examined. Results clearly coupled high phenolic levels with high yield in lettuce grown on the chestnut-based compost. A huge accumulation of phenolics was observed with the white grape-based compost, but this coincided with low yield. Three compounds were identified as discriminating factors between treated samples, namely quercetin 3-O-glucoside, luteolin 7-O-glucoside, and cyanidin 3-O-(6″-malonyl)-β-d-glucoside; these are also some of the compounds receiving health claims on lettuce consumption. On a negative note, all composts led to decreased vitamin C levels. Collectively, the data suggest that compost amendments can help add value to lettuce by increasing its antioxidant activity as compared to other organic resources. Copyright © 2016 Elsevier Ltd. All rights reserved.

Apigenin protects against alcohol-induced liver injury in mice by regulating hepatic CYP2E1-mediated oxidative stress and PPARα-mediated lipogenic gene expression.

PubMed

Wang, Feng; Liu, Jin-Cheng; Zhou, Rui-Jun; Zhao, Xi; Liu, Mei; Ye, Hua; Xie, Mei-Lin

2017-09-25

Alcohol is a major cause of liver injury, and there are currently no ideal pharmacological reagents that can prevent or reverse this disease. Apigenin is one of the most common flavonoids present in numerous plants and has many beneficial effects. But whether or not apigenin may protect against alcohol-induced liver injury remains unknown. Our aim was to examine the effect and potential mechanisms. The experimental mice were given 56% erguotou wine or simultaneously given apigenin 150-300 mg/kg by gavage for 30 days. The results showed that in the apigenin-treated mice, the expression of hepatic cytochrome P450 2E1 (CYP2E1) and nuclear factor kappa B proteins as well as contents of hepatic malondialdehyde and tumor necrosis factor-alpha were reduced, while the levels of hepatic reduced glutathione, glutathione reductase, glutathione peroxidase, and glutathione S-transferase were increased, especially in the 300 mg/kg group. A significant change in hepatic steatosis was also observed in the apigenin 300 mg/kg group. Apigenin pretreatment could increase the expression of hepatic peroxisome proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase-1 proteins, and decrease the expression of hepatic sterol regulatory element binding protein-1c, fatty acid synthase, and diacylglycerol acyltransferase proteins. These findings demonstrated that apigenin might exert a protective effect on alcohol-induced liver injury, and its mechanisms might be related to the regulations of hepatic CYP2E1-mediated oxidative stress and PPARα-mediated lipogenic gene expression. Copyright © 2017 Elsevier B.V. All rights reserved.

Suppression of rat and human androgen biosynthetic enzymes by apigenin: Possible use for the treatment of prostate cancer.

PubMed

Wang, Xiudi; Wang, Guimin; Li, Xiaoheng; Liu, Jianpeng; Hong, Tingting; Zhu, Qiqi; Huang, Ping; Ge, Ren-Shan

2016-06-01

Apigenin is a natural flavone. It has recently been used as a chemopreventive agent. It may also have some beneficial effects to treat prostate cancer by inhibiting androgen production. The objective of the present study was to investigate the effects of apigenin on the steroidogenesis of rat immature Leydig cells and some human testosterone biosynthetic enzyme activities. Rat immature Leydig cells were incubated for 3h with 100μM apigenin without (basal) or with 1ng/ml luteinizing hormone (LH), 10mM 8-bromoadenosine 3',5'-cyclic monophosphate (8BR), and 20μM of the following steroid substrates: 22R-hydroxychloesterol (22R), pregnenolone (P5), progesterone (P4), and androstenedione (D4). The medium levels of 5α-androstane-3α, 17β-diol (DIOL), the primary androgen produced by rat immature Leydig cells, were measured. Apigenin significantly inhibited basal, 8BR, 22R, PREG, P4, and D4 stimulated DIOL production in rat immature Leydig cells. Further study showed that apigenin inhibited rat 3β-hydroxysteroid dehydrogenase, 17α-hydroxylase/17, 20-lyase, and 17β-hydroxysteroid dehydrogenase 3 with IC50 values of 11.41±0.7, 8.98±0.10, and 9.37±0.07μM, respectively. Apigenin inhibited human 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase 3 with IC50 values of 2.17±0.04 and 1.31±0.09μM, respectively. Apigenin is a potent inhibitor of rat and human steroidogenic enzymes, being possible use for the treatment of prostate cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

Apigenin Ameliorates Post-Stroke Cognitive Deficits in Rats Through Histone Acetylation-Mediated Neurochemical Alterations.

PubMed

Tu, Fengxia; Pang, Qiongyi; Huang, Tingting; Zhao, Yun; Liu, Meixia; Chen, Xiang

2017-08-19

BACKGROUND To identify the effect of apigenin on cognitive deficits of rats after cerebral ischemia and reperfusion injury, and to investigate the potential molecular mechanisms. MATERIAL AND METHODS The rats were given sodium butyrate (NaB) or apigenin (20 or 40 mg/kg) for 28 days. Cognition was investigated by the Morris water maze (MWM) test. On day 28, the rats were euthanized and their hippocampal brain regions were used to identify biochemical and neurochemical alterations. The content of histone deacetylase (HDAC) was measured by enzyme-linked immunosorbent assay (ELISA). Western blot analysis was performed to determine the levels of BDNF, phosphorylated cAMP response element-binding protein (pCREB), acetylated H3, and acetylated H4. The mRNA expressions of brain-derived neurotrophic factor (BDNF) and synapsin-I (Syn-I) were examined by polymerase chain reaction (PCR). RESULTS The rats with chronic administration of apigenin (20 and 40 mg/kg) showed better performance in the MWM task than the model rats; there was no significant difference between the apigenin-treated and NaB-treated rats. At the higher apigenin dose of 40 mg/kg, the HDAC content was decreased, the BDNF level was markedly increased, and acetylated H3 and acetylated H4 expressions and Syn-I expressions in the hippocampus was upregulated compared with the model group. Apigenin at 20 mg/kg did not show reversal of the neurochemical alterations. CONCLUSIONS The improvement effect of apigenin on cognitive impairments after cerebral ischemia and reperfusion injury may involve multiple mechanisms, such as the inhibition of HDAC, induction of BDNF and Syn-I expression, and regulation of histone acetylation.

Intestinal anti-inflammatory activity of apigenin K in two rat colitis models induced by trinitrobenzenesulfonic acid and dextran sulphate sodium.

PubMed

Mascaraque, Cristina; González, Raquel; Suárez, María Dolores; Zarzuelo, Antonio; Sánchez de Medina, Fermín; Martínez-Augustin, Olga

2015-02-28

Flavonoids are polyphenolic compounds that are widespread in nature, and consumed as part of the human diet in significant amounts. The aim of the present study was to test the intestinal anti-inflammatory activity of apigenin K, a soluble form of apigenin, in two models of rat colitis, namely the trinitrobenzenesulfonic acid (TNBS) model and the dextran sulphate sodium (DSS) model. Apigenin K (1, 3 and 10 mg/kg; by the oral route; n 4-6 per group) was administered as a pre-treatment to rats with TNBS and DSS colitis, and colonic status was checked by macroscopic and biochemical examination. Apigenin K pre-treatment resulted in the amelioration of morphological signs and biochemical markers in the TNBS model. The results demonstrated a reduction in the inflamed area, as well as lower values of score and colonic weight:length ratio compared with the TNBS group. Myeloperoxidase (MPO) activity was reduced by 30 % (P< 0·05). Moreover, apigenin K pre-treatment ameliorated morphological signs and biochemical markers in the DSS model. Thus, macroscopic damage was significantly reduced and the colonic weight:length ratio was lowered by approximately 10 %, while colonic MPO and alkaline phosphatase activities were decreased by 35 and 21 %, respectively (P< 0·05). Apigenin K pre-treatment also tended to normalise the expression of a number of colonic inflammatory markers (e.g. TNF-α, transforming growth factor-β, IL-6, intercellular adhesion molecule 1 or chemokine (C-C motif) ligand 2). In conclusion, apigenin K is found to have anti-inflammatory effects in two preclinical models of inflammatory bowel disease.

[Pharmaceutical and formulation aspects of Petroselinum crispum extract].

PubMed

Pápay, Zsófia Edit; Kósa, Annamária; Boldizsár, Imre; Ruszkai, Akos; Balogh, Emese; Klebovich, Imre; Antal, István

2012-01-01

Parsley (Petroselinum crispum L.) is a very popular spice and vegetable in Europe, it is widely spread and easy to grow. It's herb and fruits are known to be diuretic, smooth muscle relaxant and hepatoprotective. The most important identified active ingredients are flavonoids, cumarins and vitamin C. Apigenin and its glycosides are the main flavonoids in parsley, it can be found relatively large amounts in the leaves. The bioactive flavonoid apigenin has antiinflammatory, antioxidant and anticancer activities. The objectives of this study were the preparation and detemination of the apigenin content of the parsley extract and the formulation using inert pellets by layering the apigenin in fluid-bed process.

Apigenin inhibits d-galactosamine/LPS-induced liver injury through upregulation of hepatic Nrf-2 and PPARγ expressions in mice.

PubMed

Zhou, Rui-Jun; Ye, Hua; Wang, Feng; Wang, Jun-Long; Xie, Mei-Lin

2017-11-04

Apigenin is a natural flavonoid compound widely distributed in a variety of vegetables, medicinal plants and health foods. This study aimed to examine the protective effect of apigenin against d-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced mouse liver injury and to investigate the potential biochemical mechanisms. The results showed that after oral administration of apigenin 100-200 mg/kg for 7 days, the levels of serum alanine aminotransferase and aspartate aminotransferase were decreased, and the severity of liver injury was alleviated. Importantly, apigenin pretreatment increased the levels of hepatic nuclear factor erythroid 2-related factor 2 (Nrf-2) and peroxisome proliferator-activated receptor γ (PPARγ) protein expressions as well as superoxide dismutase, catalase, glutathione S-transferase and glutathione reductase activities, decreased the levels of hepatic nuclear factor-κB (NF-κB) protein expression and tumor necrosis factor-α. These findings demonstrated that apigenin could prevent the D-GalN/LPS-induced liver injury in mice, and its mechanisms might be associated with the increments of Nrf-2-mediated antioxidative enzymes and modulation of PPARγ/NF-κB-mediated inflammation. Copyright © 2017 Elsevier Inc. All rights reserved.

Apigenin attenuates isoflurane-induced cognitive dysfunction via epigenetic regulation and neuroinflammation in aged rats.

PubMed

Chen, Lin; Xie, Wenji; Xie, Wenqin; Zhuang, Weiqiang; Jiang, Changcheng; Liu, Naizhen

2017-11-01

Post operational cognitive dysfunction (POCD) occurs in patients after anesthesia and surgery. Abnormal histone acetylation and neuroinflammation are key factors in the pathogenesis of cognitive impairment. Apigenin not only has an anti-inflammatory activity but also modifies histone acetylation. We aimed to investigate whether apigenin can attenuate isoflurane exposure-induced cognitive decline by regulating histone acetylation and inflammatory signaling. Spatial learning and memory were assessed by Morris water maze test. Levels of histone acetylation, BDNF and downstream signaling, and inflammatory components were analyzed. Isoflurane exposure in aged rats lead to impaired spatial learning and memory. These rats exhibited dysregulated histone H3K9 and H4K12 acetylation, which was accompanied by reduced BDNF expression and suppressed BDNF downstream signaling pathway. Apigenin restored histone acetylation and BDNF signaling. Apigenin also suppressed isoflurane exposure induced upregulation of proinflammatory cytokines and NFκB signaling pathway. Memory impairment induced by isoflurane exposure is associated with dysregulated histone acetylation in the hippocampus, which affects BDNF expression and hence BDNF downstream signaling pathway. Apigenin recovers cognitive function by restoring histone acetylation and suppressing neuroinflammation. Copyright © 2017 Elsevier B.V. All rights reserved.

Flavonoids of Cynara scolymus possess potent xanthinoxidase inhibitory activity in vitro but are devoid of hypouricemic effects in rats after oral application.

PubMed

Sarawek, Sasiporn; Feistel, Bjoern; Pischel, Ivo; Butterweck, Veronika

2008-02-01

Artichoke (Cynara scolymus L.) leaves have been historically used for the treatment of hyperuricemia and gout, however whether artichoke is truly efficacious for this indication, is still a matter of debate. Thus, the goal of the present study was first to examine the xanthine oxidase (XO) inhibitory activity of an artichoke leaf extract (ALE) and some of its main compounds in vitro and then further test potentially active substances for possible hypouricemic effects using an in vivo rat model. The in vitro study showed that ALE inhibited XO with only minimal inhibitory action (< 5 %) at 100 microg/mL. However, when selected compounds were tested, the caffeic acid derivatives revealed a weak XO inhibitory effect with IC (50) > 100 microM. From the tested flavones the aglycone luteolin potently inhibited XO with an IC (50) value of 1.49 microM. Luteolin 7-O-glucoside and luteolin 7-O-glucuronide showed lower XO inhibition activities with IC (50) values of 19.90 microM and 20.24 microM, respectively. However, oral administration of an aqueous ALE, luteolin, and luteolin 7-O-glucoside did not produce any observable hypouricemic effects after acute oral treatment in potassium oxonate-treated rats. After intraperitoneal injection of luteolin a decrease in uric acid levels was detected suggesting that the hypouricemic effects of luteolin are due to its original form rather than its metabolites produced by the gut flora. In conclusion, an aqueous ALE, caffeic acid derivatives and flavones exerted XO inhibitory effects in vitro but a hypouricemic activity could not be confirmed after oral administration.

Luteolin as reactive oxygen generator by X-ray and UV irradiation

NASA Astrophysics Data System (ADS)

Toyama, Michiru; Mori, Takashi; Takahashi, Junko; Iwahashi, Hitoshi

2018-05-01

Non-toxic X-ray-responsive substances can be used in the radiosensitization of cancer, like porphyrin mediated radiotherapy. However, most X-ray-responsive substances are toxic. To find novel non-toxic X-ray-responsive substances, we studied the X-ray and UV reactivity of 40 non-toxic compounds extracted from plants. Dihydroethidium was used as an indicator to detect reactive oxygen species (ROS) generated by the compounds under X-ray or UV irradiation. We found that 13 of the investigated compounds generated ROS under X-ray irradiation and 17 generated ROS under UV irradiation. Only 4 substances generated ROS under both X-ray and UV. In particular, luteolin exhibited the highest activity among the investigated compounds; therefore, the ROS generated by luteolin were thoroughly characterized. To identify the ROS, we employed a combination of ROS detection reagents and their quenchers. O2·- generation by luteolin was monitored using dihydroethidium and superoxide dismutase (as an O2·- quencher). OH· and 1O2 generation was determined using aminophenyl fluorescein with ethanol (OH· quencher) and Singlet Oxygen Sensor Green® with NaN3 (1O2 quencher), respectively. Generation of O2·- under X-ray and UV irradiation was observed; however, no OH· or 1O2 was detected. The production of ROS from luteolin is surprising, because luteolin is a well-known antioxidant.

Apigenin blocks IKKα activation and suppresses prostate cancer progression

PubMed Central

Shukla, Sanjeev; Kanwal, Rajnee; Shankar, Eswar; Datt, Manish; Chance, Mark R.; Fu, Pingfu; MacLennan, Gregory T.; Gupta, Sanjay

2015-01-01

IKKα has been implicated as a key regulator of oncogenesis and driver of the metastatic process; therefore is regarded as a promising therapeutic target in anticancer drug development. In spite of the progress made in the development of IKK inhibitors, no potent IKKα inhibitor(s) have been identified. Our multistep approach of molecular modeling and direct binding has led to the identification of plant flavone apigenin as a specific IKKα inhibitor. Here we report apigenin, in micro molar range, inhibits IKKα kinase activity, demonstrates anti-proliferative and anti-invasive activities in functional cell based assays and exhibits anticancer efficacy in experimental tumor model. We found that apigenin directly binds with IKKα, attenuates IKKα kinase activity and suppresses NF-ĸB/p65 activation in human prostate cancer PC-3 and 22Rv1 cells much more effectively than IKK inhibitor, PS1145. We also showed that apigenin caused cell cycle arrest similar to knockdown of IKKα in prostate cancer cells. Studies in xenograft mouse model indicate that apigenin feeding suppresses tumor growth, lowers proliferation and enhances apoptosis. These effects correlated with inhibition of p-IKKα, NF-ĸB/p65, proliferating cell nuclear antigen and increase in cleaved caspase 3 expression in a dose-dependent manner. Overall, our results suggest that inhibition of cell proliferation, invasiveness and decrease in tumor growth by apigenin are mediated by its ability to suppress IKKα and downstream targets affecting NF-ĸB signaling pathways. PMID:26435478

Apigenin blocks IKKα activation and suppresses prostate cancer progression.

PubMed

Shukla, Sanjeev; Kanwal, Rajnee; Shankar, Eswar; Datt, Manish; Chance, Mark R; Fu, Pingfu; MacLennan, Gregory T; Gupta, Sanjay

2015-10-13

IKKα has been implicated as a key regulator of oncogenesis and driver of the metastatic process; therefore is regarded as a promising therapeutic target in anticancer drug development. In spite of the progress made in the development of IKK inhibitors, no potent IKKα inhibitor(s) have been identified. Our multistep approach of molecular modeling and direct binding has led to the identification of plant flavone apigenin as a specific IKKα inhibitor. Here we report apigenin, in micro molar range, inhibits IKKα kinase activity, demonstrates anti-proliferative and anti-invasive activities in functional cell based assays and exhibits anticancer efficacy in experimental tumor model. We found that apigenin directly binds with IKKα, attenuates IKKα kinase activity and suppresses NF-ĸB/p65 activation in human prostate cancer PC-3 and 22Rv1 cells much more effectively than IKK inhibitor, PS1145. We also showed that apigenin caused cell cycle arrest similar to knockdown of IKKα in prostate cancer cells. Studies in xenograft mouse model indicate that apigenin feeding suppresses tumor growth, lowers proliferation and enhances apoptosis. These effects correlated with inhibition of p-IKKα, NF-ĸB/p65, proliferating cell nuclear antigen and increase in cleaved caspase 3 expression in a dose-dependent manner. Overall, our results suggest that inhibition of cell proliferation, invasiveness and decrease in tumor growth by apigenin are mediated by its ability to suppress IKKα and downstream targets affecting NF-ĸB signaling pathways.

Apigenin in Combination with Akt Inhibition Significantly Enhances Thyrotropin-Stimulated Radioiodide Accumulation in Thyroid Cells

PubMed Central

Lakshmanan, Aparna; Doseff, Andrea I.; Ringel, Matthew D.; Saji, Motoyasu; Rousset, Bernard; Zhang, Xiaoli

2014-01-01

Background: Selectively increased radioiodine accumulation in thyroid cells by thyrotropin (TSH) allows targeted treatment of thyroid cancer. However, the extent of TSH-stimulated radioiodine accumulation in some thyroid tumors is not sufficient to confer therapeutic efficacy. Hence, it is of clinical importance to identify novel strategies to selectively further enhance TSH-stimulated thyroidal radioiodine accumulation. Methods: PCCl3 rat thyroid cells, PCCl3 cells overexpressing BRAFV600E, or primary cultured tumor cells from a thyroid cancer mouse model, under TSH stimulation were treated with various reagents for 24 hours. Cells were then subjected to radioactive iodide uptake, kinetics, efflux assays, and protein extraction followed by Western blotting against selected antibodies. Results: We previously reported that Akt inhibition increased radioiodine accumulation in thyroid cells under chronic TSH stimulation. Here, we identified Apigenin, a plant-derived flavonoid, as a reagent to further enhance the iodide influx rate increased by Akt inhibition in thyroid cells under acute TSH stimulation. Akt inhibition is permissive for Apigenin's action, as Apigenin alone had little effect. This action of Apigenin requires p38 MAPK activity but not PKC-δ. The increase in radioiodide accumulation by Apigenin with Akt inhibition was also observed in thyroid cells expressing BRAFV600E and in primary cultured thyroid tumor cells from TRβPV/PV mice. Conclusion: Taken together, Apigenin may serve as a dietary supplement in combination with Akt inhibitors to enhance therapeutic efficacy of radioiodine for thyroid cancer. PMID:24400871

Enhancing oral bioavailability using preparations of apigenin-loaded W/O/W emulsions: In vitro and in vivo evaluations.

PubMed

Kim, Bum-Keun; Cho, Ah-Ra; Park, Dong-June

2016-09-01

We analyzed the physical properties and digestibility of apigenin-loaded emulsions as they passed through a simulated digestion model. As the emulsion passed through the simulated stages of digestion, the particle size and zeta potential of all the samples changed, except for the soybean oil-Tween 80 emulsion, in which zeta potential remained constant, through all stages, indicating that soybean oil-Tween 80 emulsions may have an effect on stability during all stages of digestion. Fluorescence microscopy was used to observe the morphology of the emulsions at each step. The in vivo pharmacokinetics revealed that apigenin-loaded soybean oil-Tween 80 emulsions had a higher oral bioavailability than did the orally administrated apigenin suspensions. These results suggest that W/O/W multiple emulsions formulated with soybean oil and tween 80 have great potential as targeted delivery systems for apigenin, and may enhance in vitro and in vivo bioavailability when they pass through the digestive tract. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Flavonoid Apigenin Downregulates CDK1 by Directly Targeting Ribosomal Protein S9

PubMed Central

Iizumi, Yosuke; Oishi, Masakatsu; Taniguchi, Tomoyuki; Goi, Wakana; Sowa, Yoshihiro; Sakai, Toshiyuki

2013-01-01

Flavonoids have been reported to inhibit tumor growth by causing cell cycle arrest. However, little is known about the direct targets of flavonoids in tumor growth inhibition. In the present study, we developed a novel method using magnetic FG beads to purify flavonoid-binding proteins, and identified ribosomal protein S9 (RPS9) as a binding partner of the flavonoid apigenin. Similar to treatment with apigenin, knockdown of RPS9 inhibited the growth of human colon cancer cells at the G2/M phase by downregulating cyclin-dependent kinase 1 (CDK1) expression at the promoter level. Furthermore, knockdown of RPS9 suppressed G2/M arrest caused by apigenin. These results suggest that apigenin induces G2/M arrest at least partially by directly binding and inhibiting RPS9 which enhances CDK1 expression. We therefore raise the possibility that identification of the direct targets of flavonoids may contribute to the discovery of novel molecular mechanisms governing tumor growth. PMID:24009741

Inhibitory Mechanism of Apigenin on α-Glucosidase and Synergy Analysis of Flavonoids.

PubMed

Zeng, Li; Zhang, Guowen; Lin, Suyun; Gong, Deming

2016-09-21

Inhibition of α-glucosidase activity may suppress postprandial hyperglycemia. The inhibition kinetic analysis showed that apigenin reversibly inhibited α-glucosidase activity with an IC50 value of (10.5 ± 0.05) × 10(-6) mol L(-1), and the inhibition was in a noncompetitive manner through a monophasic kinetic process. The fluorescence quenching and conformational changes determined by fluorescence and circular dichroism were due to the formation of an α-glucosidase-apigenin complex, and the binding was mainly driven by hydrophobic interactions and hydrogen bonding. The molecular simulation showed that apigenin bound to a site close to the active site of α-glucosidase, which may induce the channel closure to prevent the access of substrate, eventually leading to the inhibition of α-glucosidase. Isobolographic analysis of the interaction between myricetin and apigenin or morin showed that both of them exhibited synergistic effects at low concentrations and tended to exhibit additive or antagonistic interaction at high concentrations.

Phenolic chemical composition of Petroselinum crispum extract and its effect on haemostasis.

PubMed

Chaves, Douglas S A; Frattani, Flávia S; Assafim, Mariane; de Almeida, Ana Paula; de Zingali, Russolina B; Costa, Sônia S

2011-07-01

From the aqueous extract (Pc) of Petroselinum crispum (Mill) flat leaves specimens were isolated and identified the flavonoids apigenin (1), apigenin-7-O-glucoside or cosmosiin (2), apigenin-7-O-apiosyl-(1 --> 2)-O-glucoside or apiin (3) and the coumarin 2",3"-dihydroxyfuranocoumarin or oxypeucedanin hydrate (4). The inhibitory activity toward clotting formation and platelet aggregation was assessed for Pc flavonoids (1) and (2), and the coumarin (4). Pc showed no inhibition on clotting activity when compared with the control. On the other hand, a strong antiplatelet aggregation activity was observed for Pc (IC50 = 1.81 mg/mL), apigenin (IC50 = 0.036 mg/mL) and cosmosiin (IC50 = 0.18 mg/mL). In all cases ADP was used as inductor of platelet aggregation. Our results showed that Pc, apigenin and cosmosiin interfere on haemostasis inhibiting platelet aggregation. To the best of our knowledge this is the first report for the cosmosiin antiplatelet aggregation in vitro activity.

Anti-oxidant and anti-inflammatory effects of apigenin in a rat model of sepsis: an immunological, biochemical, and histopathological study.

PubMed

Karamese, Murat; Erol, Huseyin Serkan; Albayrak, Mevlut; Findik Guvendi, Gulname; Aydin, Emsal; Aksak Karamese, Selina

2016-06-01

We hypothesize that apigenin may inhibit some cellular process of sepsis-induced spleen injury and simultaneously improve inflammation and oxidative stress. Therefore, the aim of this study was to investigate the potential protective effects of apigenin in a polymicrobial sepsis rat model of by cecal ligation and puncture. 64 female Wistar albino rats were divided into 8 groups. The pro-inflammatory (tumor necrosis factor-alpha, interleukin-6, and interleukin-1-beta) and anti-inflammatory (tumor growth factor-beta and interleukin-10) cytokine levels were measured by enzyme-linked immunosorbent assay. CD3, CD68, and nuclear factor kappa B (NF-κB) positivity rates were detected by immunohistochemical methods. Oxidative stress parameters were measured by tissue biochemistry. Sepsis caused a significant increase in TNF-alpha, IL-1-beta, IL-6, and TGF-beta levels whereas it reduced IL-10 level. Additionally, it led to an increase in CD3, CD68, and NF-κB positivity rates as well as oxidative stress parameters levels. However, apigenin inhibited the inflammation process, increased the IL-10 level and normalized the oxidative stress parameters. Pretreatment with apigenin results in a significant reduction in the amount of inflammatory cells. The beneficial effect of apigenin on spleen injury also involved inhibition of NF-κB pathway, suppression of proinflammatory cytokines, and induction of anti-inflammatory cytokine production. Additionally, it led to a decrease in oxidative stress in spleen tissue. Taking everything into account, apigenin may be an alternative therapeutic option for prevention of sepsis-induced organ.

Apigenin induces DNA damage through the PKCδ-dependent activation of ATM and H2AX causing down-regulation of genes involved in cell cycle control and DNA repair

PubMed Central

Arango, Daniel; Parihar, Arti; Villamena, Frederick A.; Wang, Liwen; Freitas, Michael A.; Grotewold, Erich; Doseff, Andrea I.

2014-01-01

Apigenin, an abundant plant flavonoid, exhibits anti-proliferative and anti-carcinogenic activities through mechanisms yet not fully defined. In the present study, we show that the treatment of leukemia cells with apigenin resulted in the induction of DNA damage preceding the activation of the apoptotic program. Apigenin-induced DNA damage was mediated by p38 and protein kinase C-delta (PKCδ), yet was independent of reactive oxygen species or caspase activity. Treatment of monocytic leukemia cells with apigenin induced the phosphorylation of the ataxia-telangiectasia mutated (ATM) kinase and histone H2AX, two key regulators of the DNA damage response, without affecting the ataxia-telangiectasia mutated and Rad-3-related (ATR) kinase. Silencing and pharmacological inhibition of PKCδ abrogated ATM and H2AX phosphorylation, whereas inhibition of p38 reduced H2AX phosphorylation independently of ATM. We established that apigenin delayed cell cycle progression at G1/S and increased the number of apoptotic cells. In addition, genome-wide mRNA analyses showed that apigenin-induced DNA damage led to down-regulation of genes involved in cell-cycle control and DNA repair. Taken together, the present results show that the PKCδ-dependent activation of ATM and H2AX define the signaling networks responsible for the regulation of DNA damage promoting genome-wide mRNA alterations that result in cell cycle arrest, hence contributing to the anti-carcinogenic activities of this flavonoid. PMID:22985621

Suppression of NF-κB and NF-κB-Regulated Gene Expression by Apigenin through IκBα and IKK Pathway in TRAMP Mice

PubMed Central

Shukla, Sanjeev; Shankar, Eswar; Fu, Pingfu; MacLennan, Gregory T.; Gupta, Sanjay

2015-01-01

Aberrant Nuclear Factor-κappaB (NF-κB) activation due to rapid IκBα turnover and high basal IκBα kinase (IKK) activity has been frequently observed in prostate cancer. Apigenin, a naturally occurring plant flavone, exhibits anti-proliferative, anti-inflammatory and anti-carcinogenic activities by inhibiting NF-κB pathway, through a mechanism not fully understood. We found that apigenin feeding in microgram doses (bioavailable in humans) inhibited prostate tumorigenesis in TRAMP mice by interfering with NF-κB signaling. Apigenin feeding to TRAMP mice (20 and 50 μg/mouse/day, 6 days/week for 20 weeks) exhibited significant decrease in tumor volumes of the prostate and completely abolished metastasis, which correlated with inhibition of NF-κB activation and binding to the DNA. Apigenin intake blocked phosphorylation and degradation of IκBα by inhibiting IKK activation, which in turn led to suppression of NF-κB activation. The expression of NF-κB-regulated gene products involved in proliferation (cyclin D1, and COX-2), anti-apoptosis (Bcl-2 and Bcl-xL), and angiogenesis (vascular endothelial growth factor) were also downregulated after apigenin feeding. These events correlated with the induction of apoptosis in tumor cells, as evident by increased cleaved caspase-3 labeling index in the dorsolateral prostate. Our results provide convincing evidence that apigenin inhibits IKK activation and restores the expression of IκBα, preventing it’s phosphorylation in a fashion similar to that elicited by IKK and proteasomal inhibitors through suppression of NF-κB signaling pathway. PMID:26379052

The therapeutic effects of apigenin and dexamethasone on 5-fluorouracil-induced oral mucositis - a pilot study using a Syrian hamster model.

PubMed

Molina Prats, Patricia; Gómez Garcia, Francisco; Martinez Diaz, Francisco; Amaral Mendes, Rui; Lopez-Jornet, Pia

2017-02-01

Oral mucositis (OM) is a common complication of chemotherapy and radiotherapy. The aim of this study was to evaluate the effects of treating 5-fluorouracil-induced OM with apigenin and dexamethasone. Thirty-six male Syrian hamsters were randomly assigned to one of three groups: control (50% acetic acid + 5-FU), 50% acetic acid + 5-FU + potassium Apigenin (KA), and 50% acetic acid + 5-FU + dexamethasone. The animals from each group were sacrificed 5, 7, 10, and 14 days after inducing the mucositis, and two samples collected from each animal, accounting a total of 72 samples. Macroscopic changes were assessed by histomorphometric analysis, with ulcers being assessed by imaging analysis and the number of inflammatory cells in the ulcerated region quantified in all periods through histomorphometric analysis (H&E). Furthermore, immunohistochemical changes were evaluated by proliferating cell nuclear antigen. All groups presented an increased inflammatory infiltrate after 7 days, compared to other evaluation times (P ≥ 0.05). There was significant difference between apigenin and control group in the 10-days period. Lower quantity of inflammatory cells in the apigenin-treated group in comparison with control group in the 7- and 10-days periods was observed (P < 0.05). No statistically significant difference was verified among the groups in 5- and 14-days periods. The healing process of the control group was slower than that of apigenin and dexamethasone-treated groups, with an overall significant difference between apigenin and the control group in the 10-days period. Apigenin treatment may enhance healing of OM induced by 5-fluorouracil, thus suggesting that more extensive research in this area may be useful to assess the role of agents of natural origin capable of preventing OM. Hence, further studies involving broader samples are need to confirm the therapeutic potential shown by this study. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The flavonoid compound apigenin prevents colonic inflammation and motor dysfunctions associated with high fat diet-induced obesity.

PubMed

Gentile, Daniela; Fornai, Matteo; Colucci, Rocchina; Pellegrini, Carolina; Tirotta, Erika; Benvenuti, Laura; Segnani, Cristina; Ippolito, Chiara; Duranti, Emiliano; Virdis, Agostino; Carpi, Sara; Nieri, Paola; Németh, Zoltán H; Pistelli, Laura; Bernardini, Nunzia; Blandizzi, Corrado; Antonioli, Luca

2018-01-01

Apigenin can exert beneficial actions in the prevention of obesity. However, its putative action on obesity-associated bowel motor dysfunctions is unknown. This study examined the effects of apigenin on colonic inflammatory and motor abnormalities in a mouse model of diet-induced obesity. Male C57BL/6J mice were fed with standard diet (SD) or high-fat diet (HFD). SD or HFD mice were treated with apigenin (10 mg/Kg/day). After 8 weeks, body and epididymal fat weight, as well as cholesterol, triglycerides and glucose levels were evaluated. Malondialdehyde (MDA), IL-1β and IL-6 levels, and let-7f expression were also examined. Colonic infiltration by eosinophils, as well as substance P (SP) and inducible nitric oxide synthase (iNOS) expressions were evaluated. Motor responses elicited under blockade of NOS and tachykininergic contractions were recorded in vitro from colonic longitudinal muscle preparations. When compared to SD mice, HFD animals displayed increased body weight, epididymal fat weight and metabolic indexes. HFD mice showed increments in colonic MDA, IL-1β and IL-6 levels, as well as a decrease in let-7f expression in both colonic and epididymal tissues. HFD mice displayed an increase in colonic eosinophil infiltration. Immunohistochemistry revealed an increase in SP and iNOS expression in myenteric ganglia of HFD mice. In preparations from HFD mice, electrically evoked contractions upon NOS blockade or mediated by tachykininergic stimulation were enhanced. In HFD mice, Apigenin counteracted the increase in body and epididymal fat weight, as well as the alterations of metabolic indexes. Apigenin reduced also MDA, IL-1β and IL-6 colonic levels as well as eosinophil infiltration, SP and iNOS expression, along with a normalization of electrically evoked tachykininergic and nitrergic contractions. In addition, apigenin normalized let-7f expression in epididymal fat tissues, but not in colonic specimens. Apigenin prevents systemic metabolic alterations, counteracts enteric inflammation and normalizes colonic dysmotility associated with obesity.

Phenolic compounds apigenin, hesperidin and kaempferol reduce in vitro lipid accumulation in human adipocytes.

PubMed

Gómez-Zorita, Saioa; Lasa, Arrate; Abendaño, Naiara; Fernández-Quintela, Alfredo; Mosqueda-Solís, Andrea; Garcia-Sobreviela, Maria Pilar; Arbonés-Mainar, Jose M; Portillo, Maria P

2017-11-21

Adipocytes derived from human mesenchymal stem cells (MSCs) are widely used to investigate adipogenesis. Taking into account both the novelty of these MSCs and the scarcity of studies focused on the effects of phenolic compounds, the aim of the present study was to analyze the effect of apigenin, hesperidin and kaempferol on pre-adipocyte and mature adipocytes derived from this type of cells. In addition, the expression of genes involved in TG accumulation was also measured. Pre-adipocytes were cultured from day 0 to day 8 and mature adipocytes for 48 h with the polyphenols at doses of 1, 10 and 25 µM. Apigenin did not show an anti-adipogenic action. Pre-adipocytes treated with hesperidin and kaempferol showed reduced TG content at the three experimental doses. Apigenin did not modify the expression of the main adipogenic genes (c/ebpβ, c/ebpα, pparγ and srebp1c), hesperidin inhibited genes involved in the three phases of adipogenesis (c/ebpβ, srebp1c and perilipin) and kaempferol reduced c/ebpβ. In mature adipocytes, the three polyphenols reduced TG accumulation at the dose of 25 µM, but not at lower doses. All compounds increased mRNA levels of atgl. Apigenin and hesperidin decreased fasn expression. The present study shows the anti-adipogenic effect and delipidating effects of apigenin, hesperidin and kaempferol in human adipocytes derived from hMSCs. While hesperidin blocks all the stages of adipogenesis, kaempferol only inhibits the early stage. Regarding mature adipocytes, the three compounds reduce TG accumulation by activating, at least in part, lipolysis, and in the case of hesperidin and apigenin, also by reducing lipogenesis. The present study shows for the first time the anti-adipogenic effect and delipidating effect of apigenin, hesperidin and kaempferol in human adipocytes derived from MSCs for the first time.

Effects of apigenin on the expression levels of B-cell lymphoma-2, Fas and Fas ligand in renal ischemia-reperfusion injury in rats.

PubMed

Liu, Yang; Liu, Xiuheng; Wang, Lei; Du, Yang; Chen, Zhiyuan; Chen, Hui; Guo, Jia; Weng, Xiaodong; Wang, Xiao; Wang, Ming; Wang, Zhishun

2017-12-01

The aim of the present study was to investigate the effect and possible mechanism of apigenin on renal ischemia-reperfusion (I/R) injury in rats, as well as in in vitro experiments. In total, 36 rats were subjected to 45 min of renal ischemia, with or without treatment prior to ischemia with different concentrations of apigenin (2, 10 and 50 mg/kg) administered intravenously. All rats were sacrificed at 24 h after I/R injury. The serum creatinine (Cr) and blood urea nitrogen (BUN) levels were analyzed, and histological examination was conducted. In addition, the expression levels of B-cell lymphoma 2 (Bcl-2) and Fas/Fas ligand (FasL) were detected by immunohistochemistry, reverse transcription-quantitative polymerase chain reaction and western blot analysis. For in vitro experiments, the NRK-52E cell line was employed. The viability, apoptosis and expression levels of Fas, FasL and Bcl-2 were examined in the culture of NRK-52E cells following the I/R. The results indicated that apigenin significantly decreased the levels of serum Cr and BUN induced by renal I/R, demonstrating an improvement in renal function. The histological evidence of renal damage associated with I/R was also mitigated by apigenin in vivo . Furthermore, apigenin increased the cell viability and decreased cell apoptosis in the culture of NRK52E after I/R in vitro . Compared with the I/R group, the expression of Bcl-2 was upregulated and the expression levels of Fas and FasL were downregulated by apigenin at the mRNA and protein levels in vivo and in vitro . In conclusion, apigenin appeared to increase the expression of Bcl-2 and reduce Fas/FasL expression in renal I/R injury, providing evident protection against renal I/R injury in rats.

Effects of apigenin on the expression levels of B-cell lymphoma-2, Fas and Fas ligand in renal ischemia-reperfusion injury in rats

PubMed Central

Liu, Yang; Liu, Xiuheng; Wang, Lei; Du, Yang; Chen, Zhiyuan; Chen, Hui; Guo, Jia; Weng, Xiaodong; Wang, Xiao; Wang, Ming; Wang, Zhishun

2017-01-01

The aim of the present study was to investigate the effect and possible mechanism of apigenin on renal ischemia-reperfusion (I/R) injury in rats, as well as in in vitro experiments. In total, 36 rats were subjected to 45 min of renal ischemia, with or without treatment prior to ischemia with different concentrations of apigenin (2, 10 and 50 mg/kg) administered intravenously. All rats were sacrificed at 24 h after I/R injury. The serum creatinine (Cr) and blood urea nitrogen (BUN) levels were analyzed, and histological examination was conducted. In addition, the expression levels of B-cell lymphoma 2 (Bcl-2) and Fas/Fas ligand (FasL) were detected by immunohistochemistry, reverse transcription-quantitative polymerase chain reaction and western blot analysis. For in vitro experiments, the NRK-52E cell line was employed. The viability, apoptosis and expression levels of Fas, FasL and Bcl-2 were examined in the culture of NRK-52E cells following the I/R. The results indicated that apigenin significantly decreased the levels of serum Cr and BUN induced by renal I/R, demonstrating an improvement in renal function. The histological evidence of renal damage associated with I/R was also mitigated by apigenin in vivo. Furthermore, apigenin increased the cell viability and decreased cell apoptosis in the culture of NRK52E after I/R in vitro. Compared with the I/R group, the expression of Bcl-2 was upregulated and the expression levels of Fas and FasL were downregulated by apigenin at the mRNA and protein levels in vivo and in vitro. In conclusion, apigenin appeared to increase the expression of Bcl-2 and reduce Fas/FasL expression in renal I/R injury, providing evident protection against renal I/R injury in rats. PMID:29285062

Effect of apigenin, kaempferol and resveratrol on the gene expression and protein secretion of tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) in RAW-264.7 macrophages.

PubMed

Palacz-Wrobel, Marta; Borkowska, Paulina; Paul-Samojedny, Monika; Kowalczyk, Malgorzata; Fila-Danilow, Anna; Suchanek-Raif, Renata; Kowalski, Jan

2017-09-01

Polyphenols such as apigenin, kaempferol or resveratrol are typically found in plants, including fruits, vegetables, herbs and spices, which have a wide range of biological functions such as antioxidative, anti-inflammatory, vasodilative, anticoagulative and proapoptotic. Discovering such multifunctional compounds in widely consumed plant-based products - ones that both inhibit the release of TNF-α from tissue macrophages and at the same time enhance the secretion of IL-10 - would be an important signpost in the quest for effective pharmacological treatment of numerous diseases that have an inflammatory etiology. The aim of the study is to investigate the impact of biologically active polyphenols such as apigenin, resveratrol and kaempferol on gene expression and protein secretion of IL-10 and TNF-α in line RAW-264.7. Cells were cultured under standard conditions. IL-10 and TNF-α genes expression were examined using QRT-PCR and to assess cytokines concentration ELISA have been used. Apigenin, kaempferol and resveratrol at a dose 30μM significantly decrease the TNF-α expression and secretion. Apigenin decrease the IL-10 expression and secretion. Furthermore, increase in IL-10 secretion after administration of kaempferol and resveratrol were observed. In the process of administration of tested compounds before LPS, which activate macrophages, decrease of TNF-α secretion after apigenin and kaempferol and increase of IL-10 secretion after resveratrol were observed. The results of present work indicate that 1) apigenin, resveratrol and kaempferol may reduce the intensity of inflammatory processes by inhibiting the secretion of proinflammatory cytokine TNF-α, and resveratrol and kaempferol additionally by increasing the secretion of anti-inflammatory cytokine IL-10 2) the studies indicate the potentially beneficial - anti-inflammatory - impact of diet rich in products including apigenin, resveratrol and kaempferol. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Piper betle leaves: profiling phenolic compounds by HPLC/DAD-ESI/MS(n) and anti-cholinesterase activity.

PubMed

Ferreres, Federico; Oliveira, Andreia P; Gil-Izquierdo, Angel; Valentão, Patrícia; Andrade, Paula B

2014-01-01

Piper betle L. is a widely distributed plant in the tropical and subtropical regions, its leaves being largely consumed as a masticator and mouth freshener. The purposes of this work were to characterise the phenolic profile of this species and to improve knowledge of its anti-cholinesterase properties. The phenolic composition of P. betle leaf aqueous and ethanol extracts was characterised by HPLC coupled with a diode-array detector and combined with electrospray ionisation tandem MS, and in vitro cholinesterase inhibitory capacity of both extracts was assessed by spectrophotometric microassays. The effect on neuronal cells (SH-SY5Y) viability was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction and lactate dehydrogenase leakage. Twelve phenolic compounds, comprising a phenylpropanoid, five cinnamoyl and six flavonoids derivatives were identified in P. betle leaves. Hydroxychavicol was the major compound in both extracts; however, the aqueous extract presented a greater diversity of compounds. Both extracts showed strong activity against both acetyl- and butyrylcholinesterase, which can be due, at least partially, to the phenolic composition. Furthermore, the aqueous extract proved to be cytotoxic to human neuroblastoma cells at concentrations higher than 500 µg/mL. The results suggest that the consumption of P. betle leaves as an infusion can have a positive impact in the prevention and treatment of neurodegenerative diseases. Apigenin and luteolin derivatives are reported for the first time in this species. Copyright © 2014 John Wiley & Sons, Ltd.

Identification of Predominant Phytochemical Compounds and Cytotoxic Activity of Wild Olive Leaves (Olea europaea L. ssp. sylvestris) Harvested in South Portugal.

PubMed

Makowska-Wąs, Justyna; Galanty, Agnieszka; Gdula-Argasińska, Joanna; Tyszka-Czochara, Małgorzata; Szewczyk, Agnieszka; Nunes, Ricardo; Carvalho, Isabel S; Michalik, Marta; Paśko, Paweł

2017-03-01

This study has been aimed at providing a qualitative and quantitative evaluation of selected phytochemicals such as phenolic acids, flavonoids, oleuropein, fatty acids profile, and volatile oil compounds, present in wild olive leaves harvested in Portugal, as well as at determining their antioxidant and cytotoxic potential against human melanoma HTB-140 and WM793, prostate cancer DU-145 and PC-3, hepatocellular carcinoma Hep G2 cell lines, as well as normal human skin fibroblasts BJ and prostate epithelial cells PNT2. Gallic, protocatechuic, p-hydroxybenzoic, vanillic acids, apigenin 7-O-glucoside, luteolin 7-O-glucoside, and rutin were identified in olive leaves. The amount of oleuropein was equal to 22.64 g/kg dry weight. (E)-Anethole (32.35%), fenchone (11.89%), and (Z)-3-nonen-1-ol (8%) were found to be the main constituents of the oil volatile fraction, whereas palmitic, oleic, and alpha-linolenic acid were determined to be dominating fatty acids. Olive leaves methanol extract was observed to exerted a significant, selective cytotoxic effect on DU-145 and PC-3 cell lines. Except the essential oil composition, evaluated wild olive leaves, with regard to their quantitative and qualitative composition, do not substantially differ from the leaves of other cultivars grown for industrial purposes and they reveal considerable antioxidant and cytotoxic properties. Thus, the wild species may prove to be suitable for use in traditional medicine as cancer chemoprevention. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Achillea millefolium L. hydroethanolic extract inhibits growth of human tumor cell lines by interfering with cell cycle and inducing apoptosis.

PubMed

Pereira, Joana M; Peixoto, Vanessa; Teixeira, Alexandra; Sousa, Diana; Barros, Lillian; Ferreira, Isabel C F R; Vasconcelos, M Helena

2018-06-05

The cell growth inhibitory activity of the hydroethanolic extract of Achillea millefolium was studied in human tumor cell lines (NCI-H460 and HCT-15) and its mechanism of action was investigated. The GI 50 concentration was determined with the sulforhodamine B assay and cell cycle and apoptosis were analyzed by flow cytometry following incubation with PI or Annexin V FITC/PI, respectively. The expression levels of proteins involved in cell cycle and apoptosis were analyzed by Western blot. The extracts were characterized regarding their phenolic composition by LC-DAD-ESI/MS. 3,5-O-Dicaffeoylquinic acid, followed by 5-O-caffeoylquinic acid, were the main phenolic acids, while, luteolin-O-acetylhexoside and apigenin-O-acetylhexoside were the main flavonoids. This extract decreased the growth of the tested cell lines, being more potent in HCT-15 and then in NCI-H460 cells. Two different concentrations of the extract (75 and 100 μg/mL) caused alterations in cell cycle profile and increased apoptosis levels in HCT-15 and NCI-H460 cells. Moreover, the extract caused an increase in p53 and p21 expression in NCI-H460 cells (which have wt p53), and reduced XIAP levels in HCT-15 cells (with mutant p53). This work enhances the importance of A. millefolium as source of bioactive phenolic compounds, particularly of XIAP inhibitors. Copyright © 2018 Elsevier Ltd. All rights reserved.

Identification of Phenolic Compounds from Seed Coats of Differently Colored European Varieties of Pea (Pisum sativum L.) and Characterization of Their Antioxidant and In Vitro Anticancer Activities.

PubMed

Stanisavljević, Nemanja S; Ilić, Marija D; Matić, Ivana Z; Jovanović, Živko S; Čupić, Tihomir; Dabić, Dragana Č; Natić, Maja M; Tešić, Živoslav Lj

2016-01-01

To date little has been done on identification of major phenolic compounds responsible for anticancer and antioxidant properties of pea (Pisum sativum L.) seed coat extracts. In the present study, phenolic profile of the seed coat extracts from 10 differently colored European varieties has been determined using ultrahigh-performance liquid chromatography-linear trap quadrupole orbitrap mass spectrometer technique. Extracts of dark colored varieties with high total phenolic content (up to 46.56 mg GAE/g) exhibited strong antioxidant activities (measured by 2,2-diphenyl-1-picrylhydrazyl or DPPH assay, and ferric ion reducing and ferrous ion chelating capacity assays) which could be attributed to presence of gallic acid, epigallocatechin, naringenin, and apigenin. The aqueous extracts of dark colored varieties exert concentration-dependent cytotoxic effects on all tested malignant cell lines (human colon adenocarcinoma LS174, human breast carcinoma MDA-MB-453, human lung carcinoma A594, and myelogenous leukemia K562). Correlation analysis revealed that intensities of cytotoxic activity of the extracts strongly correlated with contents of epigallocatechin and luteolin. Cell cycle analysis on LS174 cells in the presence of caspase-3 inhibitor points out that extracts may activate other cell death modalities besides caspase-3-dependent apoptosis. The study provides evidence that seed coat extracts of dark colored pea varieties might be used as potential cancer-chemopreventive and complementary agents in cancer therapy.

A NodD-like protein activates transcription of genes involved with naringenin degradation in a flavonoid-dependent manner in Herbaspirillum seropedicae.

PubMed

Wassem, R; Marin, A M; Daddaoua, A; Monteiro, R A; Chubatsu, L S; Ramos, J L; Deakin, W J; Broughton, W J; Pedrosa, F O; Souza, E M

2017-03-01

Herbaspirillum seropedicae is an associative, endophytic non-nodulating diazotrophic bacterium that colonises several grasses. An ORF encoding a LysR-type transcriptional regulator, very similar to NodD proteins of rhizobia, was identified in its genome. This nodD-like gene, named fdeR, is divergently transcribed from an operon encoding enzymes involved in flavonoid degradation (fde operon). Apigenin, chrysin, luteolin and naringenin strongly induce transcription of the fde operon, but not that of the fdeR, in an FdeR-dependent manner. The intergenic region between fdeR and fdeA contains several generic LysR consensus sequences (T-N 11 -A) and we propose a binding site for FdeR, which is conserved in other bacteria. DNase I foot-printing revealed that the interaction with the FdeR binding site is modified by the four flavonoids that stimulate transcription of the fde operon. Moreover, FdeR binds naringenin and chrysin as shown by isothermal titration calorimetry. Interestingly, FdeR also binds in vitro to the nod-box from the nodABC operon of Rhizobium sp. NGR234 and is able to activate its transcription in vivo. These results show that FdeR exhibits two features of rhizobial NodD proteins: nod-box recognition and flavonoid-dependent transcription activation, but its role in H. seropedicae and related organisms seems to have evolved to control flavonoid metabolism. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

Contrast agent-free sonoporation: The use of an ultrasonic standing wave microfluidic system for the delivery of pharmaceutical agents

PubMed Central

Carugo, Dario; Ankrett, Dyan N.; Glynne-Jones, Peter; Capretto, Lorenzo; Boltryk, Rosemary J.; Zhang, Xunli; Townsend, Paul A.; Hill, Martyn

2011-01-01

Sonoporation is a useful biophysical mechanism for facilitating the transmembrane delivery of therapeutic agents from the extracellular to the intracellular milieu. Conventionally, sonoporation is carried out in the presence of ultrasound contrast agents, which are known to greatly enhance transient poration of biological cell membranes. However, in vivo contrast agents have been observed to induce capillary rupture and haemorrhage due to endothelial cell damage and to greatly increase the potential for cell lysis in vitro. Here, we demonstrate sonoporation of cardiac myoblasts in the absence of contrast agent (CA-free sonoporation) using a low-cost ultrasound-microfluidic device. Within this device an ultrasonic standing wave was generated, allowing control over the position of the cells and the strength of the acoustic radiation forces. Real-time single-cell analysis and retrospective post-sonication analysis of insonated cardiac myoblasts showed that CA-free sonoporation induced transmembrane transfer of fluorescent probes (CMFDA and FITC-dextran) and that different mechanisms potentially contribute to membrane poration in the presence of an ultrasonic wave. Additionally, to the best of our knowledge, we have shown for the first time that sonoporation induces increased cell cytotoxicity as a consequence of CA-free ultrasound-facilitated uptake of pharmaceutical agents (doxorubicin, luteolin, and apigenin). The US-microfluidic device designed here provides an in vitro alternative to expensive and controversial in vivo models used for early stage drug discovery, and drug delivery programs and toxicity measurements. PMID:22662060

Comparative Studies on Phenolic Composition, Antioxidant, Wound Healing and Cytotoxic Activities of Selected Achillea L. Species Growing in Turkey.

PubMed

Agar, Osman Tuncay; Dikmen, Miris; Ozturk, Nilgun; Yilmaz, Mustafa Abdullah; Temel, Hamdi; Turkmenoglu, Fatma Pinar

2015-09-30

Turkey is one of the most important centers of diversity for the genus Achillea L. in the world. Keeping in mind the immense medicinal importance of phenols, in this study, three species growing in Turkey, A. coarctata Poir. (AC), A. kotschyi Boiss. subsp. kotschyi (AK) and A. lycaonica Boiss. & Heldr. (AL) were evaluated for their phenolic compositions, total phenolic contents (TPC), antioxidant properties, wound healing potencies on NIH-3T3 fibroblasts and cytotoxic effects on MCF-7 human breast cancer cells. Comprehensive LC-MS/MS analysis revealed that AK was distinctively rich in chlorogenic acid, hyperoside, apigenin, hesperidin, rutin, kaempferol and luteolin (2890.6, 987.3, 797.0, 422.5, 188.1, 159.4 and 121.2 µg analyte/g extract, respectively). The findings exhibited a strong correlation between TPC and both free radical scavenging activity and total antioxidant capacity (TAC). Among studied species, the highest TPC (148.00 mg GAE/g extract) and TAC (2.080 UAE), the strongest radical scavenging (EC50 = 32.63 μg/mL), the most prominent wound healing and most abundant cytotoxic activities were observed with AK. The results suggested that AK is a valuable source of flavonoids and chlorogenic acid with important antioxidant, wound healing and cytotoxic activities. These findings warrant further studies to assess the potential of AK as a bioactive source that could be exploited in pharmaceutical, cosmetics and food industries.

Phytochemical analysis of Passiflora loefgrenii Vitta, a rich source of luteolin-derived flavonoids with antioxidant properties.

PubMed

Argentieri, Maria Pia; Levi, Marisa; Guzzo, Flavia; Avato, Pinarosa

2015-11-01

The paper describes the flavonoid composition of the aerial parts (young leaves, YL; adult leaves, AL; stems, ST) of Passiflora loefgrenii Vitta, a rare species native to Brazil, where it is traditionally used as food. Antioxidant potential has also been evaluated. To the best of our knowledge, no phytochemical and biological study on this species has been reported previously. Compositional data have been acquired combining HPLC-diode array detector (DAD) and Electrospary ionization-tandem mass spectrometry (ESI-MS/MS) analyses. Antioxidant activity has been evaluated by the 2,2'-di-phenyl-1-picrylhydrazyl method. Glycosylated flavones, with luteolin as the main aglycone, can be regarded as biomarkers for this drug. Qualitative composition of the extracts from YL, AL and ST was similar. The bulk of the constituents was made up by 8-C-ß-glucosyl luteolin (orientin), 7-O-α-rhamnosyl-6-C-ß-glucosyl luteolin and 6-C-α-rhamnosyl luteolin, which totally amounted to 16.57 (73%), 10.77 (74%) and 5.07 (77%) μg/mg in YL, AL and ST, respectively. P. loefgrenii showed a good antioxidant activity (IC50 of 350 μg/ml), higher than generally reported for other passifloras. P. loefgrenii, rich in luteolin glycosides, can be regarded as a good candidate to be explored for therapeutic properties other than the sedative one since it represents a rich source of valuable flavonoids with antioxidant potential. © 2015 Royal Pharmaceutical Society.