Savinin, a lignan from Pterocarpus santalinus inhibits tumor necrosis factor-alpha production and T cell proliferation.

PubMed

Cho, J Y; Park, J; Kim, P S; Yoo, E S; Baik, K U; Park, M H

2001-02-01

Two lignans were isolated from the heartwood of Pterocarpus santalinus by activity-guided fractionation and investigated for their biological properties and molecular mechanism of action. On the basis of their spectroscopic data, these compounds were identified as savinin (1) and calocedrin (2), dibenzyl butyrolactone-type lignan compounds having an alpha-arylidene gamma-lactone structure. These lignans significantly inhibited tumor necrosis factor (TNF)-a production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and T cell proliferation elicited by concanavalin (Con A), without displaying cytotoxicity. The molecular inhibitory mechanism of compound 1 was confirmed to be mediated by the non-polar butyrolactone ring, according to a structure-relationship study with structurally related and unrelated compounds, such as arctigenin (a dibenzyl butyrolactone type lignan), eudesmin (a furofuran type lignan), isolariciresinol (a dibenzylbutane type lignan), and cynaropicrin (a sesquiterpene lactone). The results suggest that savinin may act as an active principle in the reported biological activities of P. santalinus, such as antiinflammatory effect, by mediation of the butyrolactone ring as a valuable pharmacophore.

Four new sesqui-lignans isolated from Acanthopanax senticosus and their diacylglycerol acyltransferase (DGAT) inhibitory activity.

PubMed

Li, Jia-Lin; Li, Na; Lee, Hyun-Sun; Xing, Shan-Shan; Qi, Shi-Zhou; Tuo, Zhen-Dong; Zhang, Le; Li, Ban-Ban; Chen, Jian-Guang; Cui, Long

2016-03-01

Four new sesqui-lignans, (7R, 7'R, 7″S, 8S, 8'S, 8″S)-4',5″-dihydroxy-3,5,3',4″-tetramethoxy-7,9':7',9-diepoxy-4,8″-oxy-8,8'-sesquineo-lignan-7″,9″-diol (1), (7R, 7'R, 7″S, 8S, 8'S, 8″S)-4',3″-dihydroxy-3,5,3',5',4″-pentamethoxy-7,9':7',9-diepoxy-4,8″-oxy-8,8'-sesquineo-lignan-7″,9″-diol (2), (7R, 7'R, 7″S, 8S, 8'S, 8″S)-3',4″-dihydroxy-3,5,4',5″-tetramethoxy-7,9':7',9-diepoxy-4,8″-oxy-8,8'-sesquineo-lignan-7″,9″-diol (3) and acanthopanax A (7) together with three known compounds (4-6) were isolated from the EtOAc-soluble extract of Acanthopanax senticosus. Their structures were elucidated on the basis of spectroscopic and physicochemical analyses. All the isolates were evaluated for in vitro inhibitory activity against DGAT1 and DGAT2. Among them, compounds 1-6 were found to exhibit selective inhibitory activity on DGAT1 with IC50 values ranging from 61.1 ± 1.3 to 97.7 ± 1.1 μM and compound 7 showed selective inhibition of DGAT2 with IC50 value 93.2 ± 1.2. Copyright © 2016 Elsevier B.V. All rights reserved.

Podophyllotoxin and other aryltetralin lignans from Eriope latifolia and Eriope blanchetii.

PubMed

Santos, Edlene O; Lima, Luciano S; David, Jorge M; Martins, Lidiane C; Guedes, Maria Lenise S; David, Juceni P

2011-09-01

Phytochemical investigation of the aerial parts of Eriope blanchetii and E. latifolia (Lamiaceae) yielded podophyllotoxin, as well as the aryltetralin lignans α- and β-peltatin and yatein. Oleanolic, ursolic and epikatonic acids were also isolated. This is the first occurrence of podophyllotoxin in the family.

Lignans from the roots of Urtica dioica and their metabolites bind to human sex hormone binding globulin (SHBG).

PubMed

Schöttner, M; Gansser, D; Spiteller, G

1997-12-01

Polar extracts of the stinging nettle (Urtica dioica L.) roots contain the ligans (+)-neoolivil, (-)-secoisolariciresinol, dehydrodiconiferyl alcohol, isolariciresinol, pinoresinol, and 3,4-divanillyltetrahydrofuran. These compounds were either isolated from Urtica roots, or obtained semisynthetically. Their affinity to human sex hormone binding globulin (SHBG) was tested in an in vitro assay. In addition, the main intestinal transformation products of plant lignans in humans, enterodiol and enterolactone, together with enterofuran were checked for their activity. All lignans except (-)-pinoresinol developed a binding affinity to SHBG in the in vitro assay. The affinity of (-)-3,4-divanillyltetrahydrofuran was outstandingly high. These findings are discussed with respect to potential beneficial effects of plant lignans on benign prostatic hyperplasia (BPH).

(−) Arctigenin and (+) Pinoresinol Are Antagonists of the Human Thyroid Hormone Receptor β

PubMed Central

2015-01-01

Lignans are important biologically active dietary polyphenolic compounds. Consumption of foods that are rich in lignans is associated with positive health effects. Using modeling tools to probe the ligand-binding pockets of molecular receptors, we found that lignans have high docking affinity for the human thyroid hormone receptor β. Follow-up experimental results show that lignans (−) arctigenin and (+) pinoresinol are antagonists of the human thyroid hormone receptor β. The modeled complexes show key plausible interactions between the two ligands and important amino acid residues of the receptor. PMID:25383984

Two new lignans from Saururus chinensis and their DGAT inhibitory activity.

PubMed

Li, Na; Tuo, Zhen-Dong; Qi, Shi-Zhou; Xing, Shan-Shan; Lee, Hyun-Sun; Chen, Jian-Guang; Cui, Long

2015-03-01

Two new lignans were isolated from Saururus chinensis, along with eight known compounds. Their structures were elucidated on the basis of spectroscopic and physico-chemical analyses. All the isolates were evaluated for in vitro inhibitory activity against DGAT1 and DGAT2. Among them, compounds 2, 3, 5 and 7 were found to exhibit selective inhibitory activity on DGAT1 with IC50 values ranging from 44.3±1.5 to 87.5±1.3μM. Copyright © 2014 Elsevier B.V. All rights reserved.

AP2/ERF Transcription Factor, Ii049, Positively Regulates Lignan Biosynthesis in Isatis indigotica through Activating Salicylic Acid Signaling and Lignan/Lignin Pathway Genes

PubMed Central

Ma, Ruifang; Xiao, Ying; Lv, Zongyou; Tan, Hexin; Chen, Ruibing; Li, Qing; Chen, Junfeng; Wang, Yun; Yin, Jun; Zhang, Lei; Chen, Wansheng

2017-01-01

Lignans, such as lariciresinol and its derivatives, have been identified as effective antiviral ingredients in Isatis indigotica. Evidence suggests that the APETALA2/ethylene response factor (AP2/ERF) family might be related to the biosynthesis of lignans in I. indigotica. However, the special role played by the AP2/ERF family in the metabolism and its underlying putative mechanism still need to be elucidated. One novel AP2/ERF gene, named Ii049, was isolated and characterized from I. indigotica in this study. The quantitative real-time PCR analysis revealed that Ii049 was expressed highest in the root and responded to methyl jasmonate, salicylic acid (SA) and abscisic acid treatments to various degrees. Subcellular localization analysis indicated that Ii049 protein was localized in the nucleus. Knocking-down the expression of Ii049 caused a remarkable reduction of lignan/lignin contents and transcript levels of genes involved in the lignan/lignin biosynthetic pathway. Ii049 bound to the coupled element 1, RAV1AAT and CRTAREHVCBF2 motifs of genes IiPAL and IiCCR, the key structural genes in the lignan/lignin pathway. Furthermore, Ii049 was also essential for SA biosynthesis, and SA induced lignan accumulation in I. indigotica. Notably, the transgenic I. indigotica hairy roots overexpressing Ii049 showed high expression levels of lignan/lignin biosynthetic genes and SA content, resulting in significant accumulation of lignan/lignin. The best-engineered line (OVX049-10) produced 425.60 μg·g−1 lariciresinol, an 8.3-fold increase compared with the wild type production. This study revealed the function of Ii049 in regulating lignan/lignin biosynthesis, which had the potential to increase the content of valuable lignan/lignin in economically significant medicinal plants. PMID:28824690

[Alkaloids and lignans from stems of Piper betle].

PubMed

Huang, Xiangzhong; Yin, Yan; Huang, Wenquan; Sun, Kuizong; Cheng, Chunmei; Bai, Lian; Dai, Yun

2010-09-01

Alkaloids and lignans from the stems of Piper betle were studied. Compounds were isolated and purified by repeated silica gel, reverse phase silica gel, Sephadex LH-20 column chromatography and preparative thin layer chromatography. The structures were elucidated on the basis of spectral analysis. From the ethyl acetate soluble fractions of the 70% acetone extract, ten compounds were isolated and identified as piperine (1), pellitorine (2), N-isobutyl-2E,4E-dodecadienamide (3), dehydropipernonaline (4), piperdardine (5), piperolein-B (6), guineensine (7), (2E,4E)-N-isobutyl-7-(3',4'-methylenedioxyphenyl)-2,4-heptadienamide (8), syringaresinol-O-beta-D-glucopyranoside (9),pinoresinol (10). All Compounds were isolated from the plant for the first time, and compounds 9 and 10 were isolated firstly from the genus.

Effects of phytoestrogen extracts isolated from rye, green and yellow pea seeds on hormone production and proliferation of trophoblast tumor cells Jeg3.

PubMed

Matscheski, A; Richter, D-U; Hartmann, A-M; Effmert, U; Jeschke, U; Kupka, M S; Abarzua, S; Briese, V; Ruth, W; Kragl, U; Piechulla, B

2006-01-01

Phytoestrogens are a diverse group of non-steroidal plant compounds. Because they have chemical structures similar to estrogens they are able to bind on estrogen receptors in humans. In this study, we tested the effects of crude phytoestrogen extracts from rye (Secale cereale), green pea (Pisum sativum) and yellow pea seeds (Pisum sativum cv.) on cell proliferation and the production of progesterone in trophoblast tumor cells of the cell line Jeg3. Isoflavone extracts from green and yellow pea seeds and lignan extracts from rye seeds were obtained, using different extraction methods. Isolated extracts were incubated in different concentrations with trophoblast tumor cells. Untreated cells were used as controls. At designated times, aliquots were removed and tested for estradiol and progesterone production. In addition, we tested the effects of the phytoestrogen extracts on cell proliferation. Cell proliferation is significantly inhibited by potential phytoestrogens isolated from rye, green and yellow pea seeds in trophoblast tumor cells of the cell line Jeg3. We found a correlation between the effects of proliferation and production of estradiol in isoflavone extracts from green and yellow pea seeds in Jeg3 cells. In addition, higher concentrations of isoflavones isolated from green pea seeds and lignans from rye showed also a inhibition of progesterone production whereas higher concentrations of rye lignans elevated estradiol production in Jeg3 cells. A useful indicator test system for potential phytoestrogens could be established. Based on the obtained results it is proposed that green and yellow pea seeds contain measurable concentrations of isoflavones and rye seeds contain lignans which can be isolated and used for special human diet programs. Copyright 2006 S. Karger AG, Basel.

Bioactive Lignans from Zanthoxylum alatum Roxb. stem bark with cytotoxic potential.

PubMed

Mukhija, Minky; Lal Dhar, Kanaya; Nath Kalia, Ajudhia

2014-02-27

Zanthoxylum alatum is used in traditional medicinal systems for number of disorders like cholera, diabetes, cough, diarrhea, fever, headache, microbial infections, toothache, inflammation and cancer. The aim of the present study was to evaluate Zanthoxylum alatum stem bark for its cytotoxic potential and to isolate the bioactive constituents. Cytotoxicity of the different extracts and isolated compounds was studied on lung carcinoma cell line (A549) and pancreatic carcinoma cell line (MIA-PaCa) using MTT assay. Isolation of compounds from most active extract (petroleum ether) was done on silica gel column. Structure elucidation was done by using various spectrophotometric techniques like UV, IR, (1)H NMR, (13)C NMR and mass spectroscopy. The type of cell death caused by most active compound C was explored by fluorescence microscopy using the acridine orange/ethidium bromide method. Petroleum ether extract of plant has shown significant cytotoxic potential. Three lignans sesamin (A), kobusin (B), and 4'O demethyl magnolin (C) has been isolated. All lignans showed cytotoxic activities in different ranges. Compound C was the novel bioactive compound from a plant source and found to be most active. In apoptosis study, treatment caused typical apoptotic morphological changes. It enhances the apoptosis at IC50 dose (21.72 µg/mL) however showing necrotic cell death at higher dose after 24h on MIA-PaCa cell lines. Petroleum ether extract (60-80 °C) of Zanthoxylum alatum has cytotoxic potential. The lignans isolated from the petroleum ether extract were responsible for the cytotoxic potential of the extract. 4'O demethyl magnolin was novel compound from Zanthoxylum alatum. Hence the Zanthoxylum alatum can be further explored for the development of anticancer drug. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Development and UFLC-MS/MS Characterization of a Product-Specific Standard for Phenolic Quantification of Maple-Derived Foods.

PubMed

Liu, Yongqiang; Ma, Hang; Seeram, Navindra P

2016-05-04

The phenolic contents of plant foods are commonly quantified by the Folin-Ciocalteu assay based on gallic acid equivalents (GAEs). However, this may lead to inaccuracies because gallic acid is not always representative of the structural heterogeneity of plant phenolics. Therefore, product-specific standards have been developed for the phenolic quantification of several foods. Currently, maple-derived foods (syrup, sugar, sap/water, and extracts) are quantified for phenolic contents based on GAEs. Because lignans are the predominant phenolics present in maple, herein, a maple phenolic lignan-enriched standard (MaPLES) was purified (by chromatography) and characterized (by UFLC-MS/MS with lignans previously isolated from maple syrup). Using MaPLES and secoisolariciresinol (a commercially available lignan), the phenolic contents of the maple-derived foods increased 3-fold compared to GAEs. Therefore, lignan-based standards are more appropriate for phenolic quantification of maple-derived foods versus GAEs. Also, MaPLES can be utilized for the authentication and detection of fake label claims on maple products.

A new lignan glycoside from the rhizomes of Imperata cylindrica.

PubMed

Lee, Dae-Young; Han, Kyung-Min; Song, Myoung-Chong; Lee, Do-Gyeong; Rho, Yeong-Deok; Baek, Nam-In

2008-01-01

A new lignan glycoside, 6-acetyl-1-[1,3-(4,4'-dihydroxy-3,3'-dimethoxy-beta-truxinyl)-beta-d-fructofuranosyl]-alpha-d-glucopyranoside (1), named impecyloside, was isolated from the rhizomes of Imperata cylindrica. The structure of the compound was determined by spectroscopic data including FABMS, UV, IR, 1H NMR and 13C NMR (DEPT) and 2D NMR (COSY, HSQC, HMBC).

Vitexins, nature-derived lignan compounds, induce apoptosis and suppress tumor growth

PubMed Central

Zhou, YingJun; Liu, Yiliang Ellie; Cao, JianGuo; Zeng, GuangYao; Shen, Cui; Li, YanLan; Zhou, MeiChen; Chen, Yiding; Pu, Weiping; Potters, Louis; Shi, Eric Y.

2009-01-01

Purpose Lignans such as secoisolariciresinol diglucoside (SDG) in flaxseed, are metabolizes to bioactive mammalian lignans of END and ENL. Because mammalian lignans have chemical structural similarity to the natural estrogen, they are thought to behave like selective estrogen receptor modulators (SERM) and therefore have anticancer effect against hormone-related cancers. We isolated a series of lignan compounds, named as Vitexins, from the seed of Chinese herb Vitex Negundo. Experimental Design We purified several Vitexin lignan compounds. Cytotoxic and antitumor effects were analyzed in cancer cells and in tumor xenograft models. In vivo metabolism of Vitexins was determined in rat. Results Contrasts to the classical lignans, Vitexins were not metabolized to END and ENL. A mixture of Vitexins EVn-50 and purified Vitexin compound VB1 have cytotoxic effect on breast, prostate, and ovarian cancer cells and induces apoptosis with cleavage in PARP protein, up-regulation of Bax, and down-regulation of Bcl-2. This induction of apoptosis seems to be mediated by activation of caspases because inhibition of caspases activity significantly reduced induced apoptosis. We demonstrated a broad antitumor activity of EVn-50 on seven tumor xenograft models including breast, prostate, liver, and cervical cancers. Consistent with in vitro data, EVn-50 treatment induced apoptosis, down-regulated of Bcl-2, and up-regulated Bax in tumor xenografts. Conclusion Vitexin is a class of nature lignan compounds, whose action and anticancer effect is mediated by the mechanisms different from the classical lignans. Vitexin induced antitumor effect and cytotoxic activity is exerted through proapoptotic process, which is mediated by a decreased Bcl-2/Bax ratio and activation of caspases. PMID:19671865

A new furofuran lignan from Piper terminaliflorum Tseng.

PubMed

Liu, Tie; Liang, Qian; Zhang, Xin-Min; Huang, Shen-Yang; Xu, Wen-Hui

2018-02-01

The chemical investigation of whole plants Piper terminaliflorum Tseng led to the isolation of one new furofuran lignan, 7-methoxyasarinin (1), along with three known amide alkaloids (2-4) as N-3,5-dimethoxy-4-hydroxycinnamoylpyrrole (2), dihydropipercide (3) and 1-[(2E,4E,9E)-10-(3,4-Methylenedioxyphenyl)-2,4,9-undecatrienoyl]pyrrolidine (4). Their structures were elucidated by extensive spectroscopic analyses, including 1D, 2D NMR and HR-ESI-MS, and by comparison with the literature. Compounds (2-4) were isolated from Piper terminaliflorum Tseng for the first time. All isolated compounds (1-4) were evaluated for their cytotoxic activities against five human cancer cell lines (including A-549, SMMC-7721, HL-60, MCF-7 and SW-480).

Antiausterity activity of arctigenin enantiomers: importance of (2R,3R)-absolute configuration.

PubMed

Awale, Suresh; Kato, Mamoru; Dibwe, Dya Fita; Li, Feng; Miyoshi, Chika; Esumi, Hiroyasu; Kadota, Shigetoshi; Tezuka, Yasuhiro

2014-01-01

From a MeOH extract of powdered roots of Wikstroemia indica, six dibenzyl-gamma-butyrolactone-type lignans with (2S,3S)-absolute configuration [(+)-arctigenin (1), (+)-matairesinol (2), (+)-trachelogenin (3), (+)-nortrachelogenin (4), (+)-hinokinin (5), and (+)-kusunokinin (6)] were isolated, whereas three dibenzyl-gamma-butyrolactone-type lignans with (2R,3R)-absolute configuration [(-)-arctigenin (1*), (-)-matairesinol (2*), (-)-trachelogenin (3*)] were isolated from Trachelospermum asiaticum. The in vitro preferential cytotoxic activity of the nine compounds was evaluated against human pancreatic PANC-1 cancer cells in nutrient-deprived medium (NDM), but none of the six lignans (1-6) with (2S,3S)-absolute configuration showed preferential cytotoxicity. On the other hand, three lignans (1*-3*) with (2R,3R)-absolute configuration exhibited preferential cytotoxicity in a concentration-dependent manner with PC50 values of 0.54, 6.82, and 5.85 microM, respectively. Furthermore, the effect of (-)- and (+)-arctigenin was evaluated against the activation of Akt, which is a key process in the tolerance to nutrition starvation. Interestingly, only (-)-arctigenin (1*) strongly suppressed the activation of Akt. These results indicate that the (2R,3R)-absolute configuration of (-)-enantiomers should be required for the preferential cytotoxicity through the inhibition of Akt activation.

Lignans from the stems and leaves of Brandisia hancei and their effects on VEGF-induced vascular permeability and migration of HRECs and DLAV formation in zebrafish.

PubMed

Lee, Ik-Soo; Kim, Young Sook; Jung, Seung-Hyun; Yu, Song Yi; Kim, Joo-Hwan; Sun, Hang; Kim, Jin Sook

2015-01-01

In our continuing search for novel antiangiogenic agents, a new lignan glycoside, (7R,8R)-1-(4-O-β-d-glucopyranosyl-3-methoxyphenyl)-2-{2-methoxy-4-[1-(E)-propene-3-ol]-phenoxyl}-propane-1,3-diol (1), along with three known lignans (2-4), were isolated from the 80% EtOH extract of Brandisia hancei stems and leaves. These isolates (1-4) were subjected to an in vitro bioassay to evaluate their effects on vascular endothelial growth factor (VEGF)-induced vascular permeability and migration of human retinal endothelial cells (HRECs). Of the compounds tested, compound 1 resulted in the greatest reduction in VEGF-induced vascular permeability by about 31.5% at 10 μM compared to the VEGF-treated control. In the migration assay, compounds 1 and 2 significantly decreased VEGF-induced HREC migration. Furthermore, zebrafish embryos treated with compounds 1 and 2 showed mild reductions of dorsal longitudinal anastomotic vessel (DLAV) formation.

Three new cytotoxic aryltetralin lignans from Sinopodophyllum emodi.

PubMed

Sun, Yan-Jun; Li, Zhan-Lin; Chen, Hong; Liu, Xiao-Qiu; Zhou, Wei; Hua, Hui-Ming

2011-06-15

Three new aryltetralin lignans, 4-acetyl-4-demethyl-podophyllotoxin (1) and sinolignans A, B (2-3), and two new natural products (4-5), were isolated from the roots and rhizomes of Sinopodophyllum emodi together with twelve known lignans (6-17). Their structures and stereochemistry were elucidated on the basis of spectroscopic evidence, and circular dichroism (CD) method. The cytotoxic activities of all isolated compounds were evaluated against HeLa and KB cell lines. Compared with etoposide, compounds 1, 6-9, and 13 showed more potent cytotoxicities against two tumor cell lines. On the basis of IC(50) values, deoxypodophyllotoxin (7) was about 579 and 1123 times more toxic than etoposide in HeLa and KB cell lines, respectively. The preliminary SAR study indicated that an oxygenated group at C-7' might decrease cytotoxicity against two cell lines, which was different from most previous studies. However, this needs to be systematically verified by extensive pharmacological experiments. Copyright © 2011 Elsevier Ltd. All rights reserved.

Antiproliferative and apoptotic effects of butyrolactone lignans from Arctium lappa on leukemic cells.

PubMed

Matsumoto, T; Hosono-Nishiyama, K; Yamada, H

2006-02-01

In the course of screening for pharmacologically active substances from extracts of crude drugs used traditionally in Sino-Japanese herbal medicines, it was found that the 70 % ethanol extract from the fruits of Arctium lappa L. (Compositae) showed potent antiproliferative activity against B cell hybridoma cell, MH60. By bioassay-guided purification, a new lignan, (+)-7,8-didehydroarctigenin, together with the known lignans (-)-arctigenin and (-)-matairesinol were isolated as the active ingredients from an aqueous ethanolic extract of the fruits of A. lappa. Of these active compounds, (-)-arctigenin showed the most potent antiproliferative activity against MH60 cells (IC (50) : 1.0 microM), and the activity was suggested to be due to apoptosis.

An unusual caffeic acid derived bicyclic [2.2.2] octane lignan and other constituents from Cordia rufescens.

PubMed

do Vale, Ademir E; David, Jorge M; dos Santos, Edlene O; David, Juceni P; e Silva, Lidercia C R C; Bahia, Marcus V; Brandão, Hugo N

2012-04-01

This work reports isolation of an unusual lignan with a bicyclic [2.2.2] octene skeleton, named rufescenolide (1), from stems of Cordia rufescens, along with β-sitosterol, stigmasterol, syringaldehyde, 3-β-O-D-glucopyranosyl-sitosterol, methyl caffeate, 4-methoxy-protocatechuic acid and methyl rosmarinate. Structural characterizations employed IR spectroscopic, ESIHRMS and mono and dimensional NMR spectroscopy. Copyright © 2011 Elsevier Ltd. All rights reserved.

Food Byproducts as a New and Cheap Source of Bioactive Compounds: Lignans with Antioxidant and Anti-inflammatory Properties from Crataegus pinnatifida Seeds.

PubMed

Huang, Xiao-Xiao; Bai, Ming; Zhou, Le; Lou, Li-Li; Liu, Qing-Bo; Zhang, Yan; Li, Ling-Zhi; Song, Shao-Jiang

2015-08-19

During the process of manufacturing hawthorn (Crataegus pinnatifida) juice and jam, a significant quantity of byproducts (leaves, seeds) is generated. The antioxidant and anti-inflammatory bioassay-guided fractionation of the extract of hawthorn seeds has led to the isolation of eight new lignans, hawthornnins A-H (1-8), and seven known analogues (9-15). Their structures were elucidated by spectroscopic techniques, including 1D and 2D NMR and CD spectra. The radical-scavenging effects of all isolated compounds were investigated. 1-6 and 8 showed moderate activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH), whereas 1-6 and 14 displayed good 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical-scavenging activities that were even more potent than that of trolox. In addition, all isolates were evaluated for their anti-inflammatory activities by detecting the nitric oxide (NO) and tumor necrosis factor α (TNF-α) production by the LPS-induced murine macrophage cell line RAW264.7, and compounds 1-7, 13, and 14 exhibited potent inhibition of NO and TNF-α production. The structure-activity relationships of isolated lignans were also examined, and the results obtained show that C. pinnatifida seeds can be regarded as a potential new and cheap source of antioxidants and inflammation inhibitors.

Cytotoxic arylnaphthalene lignans from a Vietnamese acanthaceae, Justicia patentiflora.

PubMed

Susplugas, Sophie; Hung, Nguyen Van; Bignon, Jérôme; Thoison, Odile; Kruczynski, Anna; Sévenet, Thierry; Guéritte, Françoise

2005-05-01

One new norlignan (1) and five new lignans (2-6) were isolated from the leaves and stems of Justicia patentiflora by a bioassay-guided purification. Five known compounds, carinatone, diphyllin, justicidin A, taiwanin E, and tuberculatin, were also found in J. patentiflora. Most of the new compounds display significant activity in in vitro cytotoxic assays against KB, HCT116, and MCF-7 cancer cell lines and arrest the cell cycle in the G0/G1 phase.

Lignans from Arctium lappa and their inhibition of LPS-induced nitric oxide production.

PubMed

Park, So Young; Hong, Seong Su; Han, Xiang Hua; Hwang, Ji Sang; Lee, Dongho; Ro, Jai Seup; Hwang, Bang Yeon

2007-01-01

A new butyrolactone sesquilignan, isolappaol C (1), together with four known lignans, lappaol C (2), lappaol D (3), lappaol F (4), and diarctigenin (5), were isolated from the methanolic extract of the seeds from the Arctium lappa plant. The structure of isolappaol C (1) was determined by spectral analysis including 1D- and 2D-NMR. All the isolates were evaluated for their inhibitory effects on the LPS-induced nitric oxide production using murine macrophage RAW264.7 cells. Lappaol F (4) and diarctigenin (5) strongly inhibited NO production in the LPS-stimulated RAW264.7 cells with IC(50) values of 9.5 and 9.6 microM, respectively.

[Study on Megastigmane Glycosides and Lignan Constituents from Leaves of Psidium littorale].

PubMed

Peng, Cai-ying; Liu, Jian-qun; Shu, Ji-cheng; Zhang, Rui

2014-12-01

To study the chemical constituents of the leaves of Psidium littorale. The constituents were isolated with silica gel column chromatography and the structures of these compounds were elucidated on the basis of spectral analysis. Four megastigmane glycosides and three lignans were isolated and their structures were identified as Bridelionoside B(1), Euodinoside E(2), (3S,5R,6R,7E,9S)-Megastignan-7-ene-3,5,6,9-tetrol 9-O-β-D-glucopyranoside (3), Bridelionoside C(4), (--)-Isolaricires-inol 3-α-O-β-D-glucopyranoside (5), (--)-5'-methoxy-Isolariciresinol 3-α-O-β-D-glucopyranoside (6) and dihydrodehydrodiconiferyl alcohol 4-O-β-D-glucopyranoside(7). Compounds 1-7 are isolated from this plant for the first time. The results have provided the scientific basis for further exploitation of Psidium littoratle.

Radioprotective Role in Lung of the Flaxseed Lignan Complex Enriched in the Phenolic Secoisolariciresinol Diglucoside (SDG)

PubMed Central

Christofidou-Solomidou, Melpo; Tyagi, Sonia; Pietrofesa, Ralph; Dukes, Floyd; Arguiri, Evguenia; Turowski, Jason; Grieshaber, Philip A.; Solomides, Charalambos C.; Cengel, Keith A.

2012-01-01

While dietary wholegrain Flaxseed (FS) has potent anti-inflammatory, anti-fibrotic and antioxidant properties in murine models of acute and chronic lung injury, the main bioactive ingredient that contributes to these protective effects remains unknown. This study evaluated the lignan complex of FS (FLC) enriched in secoisolariciresinol diglucoside with respect to lung radioprotective and tumor radiosensitizing efficacy using a mouse model of thoracic radiation-induced pneumonopathy. C57/Bl6 mice were fed 0% FS, 10% FS, 10% FLC or 20% FLC for 3 weeks, then irradiated with a single fraction (13.5 Gy) of X-ray radiation treatment (XRT). Mouse survival was monitored for 4 months after irradiation and inflammatory lung parameters were evaluated in bronchoalveolar lavage (BAL) fluid. Gene and protein levels of protective antioxidant and phase II enzymes were evaluated in lung tissue using qPCR and protein levels were verified by immunoblotting. Prolonged administration of the FLC diet was well tolerated and was not associated with any toxicity. Importantly, comparable to the whole grain 10% FS diet, irradiated mice fed 10% and 20% FLC diets displayed improved survival. Improved hemodynamic measurements were also recorded in irradiated mice fed 10% FS or 10% FLC diet compared to irradiated 0% FS fed mice. Flaxseed lignan complex diet also attenuated polymorphonuclear infiltration and overall lung inflammation to levels comparable to those in nonirradiated mice. Flaxseed lignan complex, similarly to FS, up-regulated gene expression as well as protein levels of protective antioxidant enzymes such as heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). Dietary FLC induced radiosensitizing effects in our murine model of metastatic lung cancer. Importantly, protection of normal tissue does not thwart tumor cell death by radiation treatment. The dietary lignan complex of FS, mainly consisting of the phenolic secoisolariciresinol, is protective against radiation pneumonopathy in vivo while not hindering the tumoricidal effects of radiotherapy. PMID:23106213

Radioprotective role in lung of the flaxseed lignan complex enriched in the phenolic secoisolariciresinol diglucoside (SDG).

PubMed

Christofidou-Solomidou, Melpo; Tyagi, Sonia; Pietrofesa, Ralph; Dukes, Floyd; Arguiri, Evguenia; Turowski, Jason; Grieshaber, Philip A; Solomides, Charalambos C; Cengel, Keith A

2012-12-01

While dietary wholegrain Flaxseed (FS) has potent anti-inflammatory, anti-fibrotic and antioxidant properties in murine models of acute and chronic lung injury, the main bioactive ingredient that contributes to these protective effects remains unknown. This study evaluated the lignan complex of FS (FLC) enriched in secoisolariciresinol diglucoside with respect to lung radioprotective and tumor radiosensitizing efficacy using a mouse model of thoracic radiation-induced pneumonopathy. C57/Bl6 mice were fed 0% FS, 10% FS, 10% FLC or 20% FLC for 3 weeks, then irradiated with a single fraction (13.5 Gy) of X-ray radiation treatment (XRT). Mouse survival was monitored for 4 months after irradiation and inflammatory lung parameters were evaluated in bronchoalveolar lavage (BAL) fluid. Gene and protein levels of protective antioxidant and phase II enzymes were evaluated in lung tissue using qPCR and protein levels were verified by immunoblotting. Prolonged administration of the FLC diet was well tolerated and was not associated with any toxicity. Importantly, comparable to the whole grain 10% FS diet, irradiated mice fed 10% and 20% FLC diets displayed improved survival. Improved hemodynamic measurements were also recorded in irradiated mice fed 10% FS or 10% FLC diet compared to irradiated 0% FS fed mice. Flaxseed lignan complex diet also attenuated polymorphonuclear infiltration and overall lung inflammation to levels comparable to those in nonirradiated mice. Flaxseed lignan complex, similarly to FS, up-regulated gene expression as well as protein levels of protective antioxidant enzymes such as heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). Dietary FLC induced radiosensitizing effects in our murine model of metastatic lung cancer. Importantly, protection of normal tissue does not thwart tumor cell death by radiation treatment. The dietary lignan complex of FS, mainly consisting of the phenolic secoisolariciresinol, is protective against radiation pneumonopathy in vivo while not hindering the tumoricidal effects of radiotherapy.

Antioxidant and Anti-Osteoporosis Activities of Chemical Constituents of the Stems of Zanthoxylum piperitum.

PubMed

Yang, Seo Young; Lee, Sang-Hyun; Tai, Bui Huu; Jang, Hae-Dong; Kim, Young Ho

2018-02-18

Two new lignans, zanthoxyloside C ( 1 ) and zanthoxyloside D ( 2 ), together with nine known compounds comprising lignans ( 3 - 5 ), flavonoids ( 6 - 8 ), and phenolics ( 9 - 11 ), were isolated from the methanol extract of the stems of Zanthoxylum piperitum. All isolates were evaluated for their antioxidant and anti-osteoporotic activities using oxygen radical absorbance capacity (ORAC), cupric reducing antioxidant capacity (CUPRAC), and tartrate-resistant acid phosphatase (TRAP) assays. Compounds 7 - 10 showed peroxyl radical-scavenging capacities and 4 , 6 - 7 , and 9 showed reducing capacities. Moreover, compounds 3 , 6 - 9 , and 11 significantly suppressed TRAP activities. These results indicated that the stems of Z. piperitum could be an excellent source for natural antioxidant and anti-osteoporosis.

One-step separation and purification of three lignans and one flavonol from Sinopodophyllum emodi by medium-pressure liquid chromatography and high-speed counter-current chromatography.

PubMed

Wang, Ping; Liu, Yongling; Chen, Tao; Xu, Wenhua; You, Jinmao; Liu, Yongjun; Li, Yulin

2013-01-01

Lignans and flavonols are the primary constituents of Sinopodophyllum emodi and have been used as cathartic, anthelmintic, chemotherapeutic and anti-hypertensive compounds. Although these compounds have been isolated, there have been no reports on the separation of 4'-demethyl podophyllotoxin, podophyllotoxin, deoxypodophyllotoxin and kaempferol in one step by medium-pressure liquid chromatography (MPLC) and high-speed counter-current chromatography (HSCCC). Development of an efficient method for the preparative separation and purification of three lignans and one flavonol from S. emodi. The precipitate of crude extracts was first separated by MPLC into four parts, numbered GJ-1, GJ-2, GJ-3 and GJ-4. GJ-1 was separated and purified by HSCCC using a solvent system composed of n-hexane:ethyl acetate:methanol:water (1.75:1.5:1:0.75, v/v/v/v). The purities of the target compounds were assessed using high-performance liquid chromatography (HPLC) and chemical structures were identified by (1) H-NMR and (13) C-NMR. The HSCCC and MPLC methods were successfully used for the preparative separation and purification of 4'-demethyl podophyllotoxin (8.5 mg, 92.4%), podophyllotoxin (40.1 mg, 92.1%), deoxypodophyllotoxin (4.6 mg, 98.1%), and kaempferol (1.6 mg, 96.7%) from a 100 mg sample. Three lignans (4'-demethyl podophyllotoxin, podophyllotoxin, deoxypodophyllotoxin) and one flavonol (kaempferol) were successfully isolated by HSCCC and MPLC in one step. Copyright © 2013 John Wiley & Sons, Ltd.

Lignans from Carthamus tinctorius suppress tryptophan breakdown via indoleamine 2,3-dioxygenase

PubMed Central

Kuehnl, Susanne; Schroecksnadel, Sebastian; Temml, Veronika; Gostner, Johanna M.; Schennach, Harald; Schuster, Daniela; Schwaiger, Stefan; Rollinger, Judith M.; Fuchs, Dietmar; Stuppner, Hermann

2013-01-01

Seed extracts of Carthamus tinctorius L. (Asteraceae), safflower, have been traditionally used to treat coronary disease, thrombotic disorders, and menstrual problems but also against cancer and depression. A possible effect of C. tinctorius compounds on tryptophan-degrading activity of enzyme indoleamine 2,3-dioxygenase (IDO) could explain many of its activities. To test for an effect of C. tinctorius extracts and isolated compounds on cytokine-induced IDO activity in immunocompetent cells in vitro methanol and ethylacetate seed extracts were prepared from cold pressed seed cakes of C. tinctorius and three lignan derivatives, trachelogenin, arctigenin and matairesinol were isolated. The influence on tryptophan breakdown was investigated in peripheral blood mononuclear cells (PBMCs). Effects were compared to neopterin production in the same cellular assay. Both seed extracts suppressed tryptophan breakdown in stimulated PBMC. The three structurally closely related isolates exerted differing suppressive activity on PBMC: arctigenin (IC50 26.5 μM) and trachelogenin (IC50 of 57.4 μM) showed higher activity than matairesinol (IC50 >200 μM) to inhibit tryptophan breakdown. Effects on neopterin production were similar albeit generally less strong. Data show an immunosuppressive property of compounds which slows down IDO activity. The in vitro results support the view that some of the anti-inflammatory, anti-cancer and antidepressant properties of C. tinctorius lignans might relate to their suppressive influence on tryptophan breakdown. PMID:23867649

Lignans and aromatic glycosides from Piper wallichii and their antithrombotic activities.

PubMed

Shi, Yan-Ni; Shi, Yi-Ming; Yang, Lian; Li, Xing-Cong; Zhao, Jin-Hua; Qu, Yan; Zhu, Hong-Tao; Wang, Dong; Cheng, Rong-Rong; Yang, Chong-Ren; Xu, Min; Zhang, Ying-Jun

2015-03-13

Piper wallichii (Miq.) Hand.-Mazz. is a medicinal plant used widely for the treatment of rheumatoid arthritis, inflammatory diseases, cerebral infarction and angina in China. Previous study showed that lignans and neolignans from Piper spp. had potential inhibitory activities on platelet aggregation. In the present study, we investigated the chemical constituents of Piper wallichii and their antithrombotic activities, to support its traditional uses. The methanolic extract of the air-dried stems of Piper wallichii was separated and purified using various chromatographic methods, including semi-preparative HPLC. The chemical structures of the isolates were determined by detailed spectroscopic analysis, and acidic hydrolysis in case of the new glycoside 2. Determination of absolute configurations of the new compound 1 was facilitated by calculated electronic circular dichroism using time-dependent density-functional theory. All compounds were tested for their inhibitory effects on platelet aggregation induced by platelet activating factor (PAF) in rabbits׳ blood model, from which the active ones were further evaluated the in vivo antithrombotic activity in zebrafish model. A new neolignan, piperwalliol A (1), and four new aromatic glycosides, piperwalliosides A-D (2-5) were isolated from the stems of Piper wallichii, along with 25 known compounds, including 13 lignans, six aromatic glycosides, two phenylpropyl aldehydes, and four biphenyls. Five known compounds (6-10) showed in vitro antiplatelet aggregation activities. Among them, (-)-syringaresinol (6) was the most active compound with an IC50 value of 0.52 mM. It is noted that in zebrafish model, the known lignan 6 showed good in vivo antithrombotic effect with a value of 37% at a concentration of 30 μM, compared with the positive control aspirin with the inhibitory value of 74% at a concentration of 125μM. This study demonstrated that lignans, phenylpropanoid and biphenyl found in Piper wallichii may be responsible for antithrombotic effect of the titled plant. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Analysis of lignans in Magnoliae Flos by turbulent flow chromatography with online solid-phase extraction and high-performance liquid chromatography with tandem mass spectrometry.

PubMed

Zhou, Xuan; Chen, Cen; Ye, Xiaolan; Song, Fenyun; Fan, Guorong; Wu, Fuhai

2016-04-01

In this study, a method coupling turbulent flow chromatography with online solid-phase extraction and high-performance liquid chromatography with tandem mass spectrometry was developed for analyzing the lignans in Magnoliae Flos. By the online pretreatment of turbulent flow chromatography solid-phase extraction, the impurities removal and analytes concentration were automatically processed, and the lignans were separated rapidly and well. Seven lignans of Magnoliae Flos including epieudesmin, magnolin, 1-irioresinol-B-dimethyl ether, epi-magnolin, fargesin aschantin, and demethoxyaschantin were identified by comparing their retention behavior, UV spectra, and mass spectra with those of reference substances or literature data. The developed method was validated, and the good results showed that the method was not only automatic and rapid, but also accurate and reliable. The turbulent flow chromatography with online solid-phase extraction and high-performance liquid chromatography with tandem mass spectrometry method holds a high potential to become an effective method for the quality control of lignans in Magnoliae Flos and a useful tool for the analysis of other complex mixtures. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Inhibitory effects of Morinda citrifolia extract and its constituents on melanogenesis in murine B16 melanoma cells.

PubMed

Masuda, Megumi; Itoh, Kimihisa; Murata, Kazuya; Naruto, Shunsuke; Uwaya, Akemi; Isami, Fumiyuki; Matsuda, Hideaki

2012-01-01

The objective of this study was to examine the effects of Morinda citrifolia (noni) extract and its constituents on α-melanocyte stimulating hormone (α-MSH)-stimulated melanogenesis in cultured murine B16 melanoma cells (B16 cells). A 50% ethanolic extract of noni seeds (MCS-ext) showed significant inhibition of melanogenesis with no effect on cell proliferation. MCS-ext was more active than noni leaf and fruit flesh extracts. Activity guided fractionation of MCS-ext led to the isolation of two lignans, 3,3'-bisdemethylpinoresinol (1) and americanin A (2), as active constituents. To elucidate the mechanism of melanogenesis inhibition by the lignans, α-MSH-stimulated B16 cells were treated with 1 (5 μM) and 2 (200 μM). Time-dependent increases of intracellular melanin content and tyrosinase activity, during 24 to 72 h, were inhibited significantly by treatment with the lignans. The activity of 1 was greater than that of 2. Western blot analysis suggested that the lignans inhibited melanogenesis by down regulation of the levels of phosphorylation of p38 mitogen-activated protein kinase, resulting in suppression of tyrosinase expression.

A simple and rapid electrophoretic method to characterize simple phenols, lignans, complex phenols, phenolic acids, and flavonoids in extra-virgin olive oil.

PubMed

Carrasco-Pancorbo, Alegria; Gómez-Caravaca, Ana Maria; Cerretani, Lorenzo; Bendini, Alessandra; Segura-Carretero, Antonio; Fernández-Gutiérrez, Alberto

2006-09-01

We have devised a simple and rapid capillary electrophoretic method which provides the analyst with a useful tool for the characterization of the polyphenolic fraction of extra-virgin olive oil. This method that uses a capillary with 50 microm id and a total length of 47 cm (40 cm to the detector) with a detection window of 100 x 200 microm, and a buffer solution containing 45 mM of sodium tetraborate pH 9.3 offers valuable information about all the families of compounds present in the polar fraction of the olive oil. The detection was carried out by UV absorption at 200, 240, 280, and 330 nm in order to facilitate the identification of the compounds. Concretely, the method permits the identification of simple phenols, lignans, complex phenols (isomeric forms of secoiridoids), phenolic acids, and flavonoids in the SPE-Diol extracts from extra-virgin olive oil in a short time (less than 10 min) and provides a satisfactory resolution. Peak identification was done by comparing both migration time and spectral data obtained from olive oil samples and standards (commercial or isolated (by HPLC-MS) standards), with spiked methanol-water extracts of olive oil with HPLC-collected compounds and commercially available standards at several concentration levels, studying the information of the electropherograms obtained at several wavelengths and also using the information previously reported.

Lignans isolated from Campylotropis hirtella (Franch.) Schindl. decreased prostate specific antigen and androgen receptor expression in LNCaP cells.

PubMed

Han, Hui-Ying; Wang, Xiang-Hong; Wang, Nai-Li; Ling, Ming-Tat; Wong, Yong-Chuan; Yao, Xin-Sheng

2008-08-27

Accumulating epidemiological data suggest that Asian men have lower incidences of prostate cancer and benign prostate hyperplasia (BPH) compared with American and European populations and may have benefited from their higher intake of phytoestrogens in their diet. However, how these phytochemicals affect prostatic diseases is still unclear. In this study, we isolated six lignans from a plant, Campylotropis hirtella (Franch.) Schindl., which has been used as a folk medicine for treatment of BPH in China, through bioassay guided fractionation. They were dehydrodiconiferyl alcohol (C1), 4-[(-6-hydroxy-2,3-dihydro-1-benzofuran-3-yl)methyl]-5-methoxybenzene-1,3-diol (C2), erythro-guaiacylglycerol-beta-O-4'-coniferyl ether (C3), threo-guaiacylglycerol-beta-O-4'-coniferyl ether (C4), secoisolariciresinol (C5), and prupaside (C6), where C2 was identified as a new lignan analog. Their IC50 values for inhibition of prostate specific antigen (PSA) secretion were 19, 45, 110, 128, 137, and 186 microM, respectively, from C1 to C6 in LNCaP cells. Further study showed that C1-5 down-regulated cellular PSA expression and C1-4 also decreased androgen receptor (AR) expression in LNCaP cells. Furthermore, we investigated the proapoptotic effect of C1 on LNCaP cells. The active forms of caspase 3 associated with the specific proteolysis of poly (ADP-ribose) polymerase (PARP) were detected, and the antiapoptotic protein Bcl-2 was down-regulated after the treatment with C1. These results collectively indicated that these lignans may have chemopreventive or therapeutic actions for prostate cancer through suppressing AR signaling pathway and inducing apoptosis.

Phenylpropanoid, sapnol A, lignan and neolignan sophorosides, saposides A and B, isolated from Canadian sugar maple sap.

PubMed

Yoshikawa, Kazuko; Tani, Sakiko; Baba, Chihiro; Hashimoto, Toshihiro

2013-08-12

One new phenolic compound, sapnol A (1), and two new aromatic sophorosides, named saposides A (2) and B (3) were isolated from sugar maple sap. In addition, seven known phenolic compounds 4-10 were isolated. These structures were determined on the basis of NMR experiments as well as chemical evidence. Furthermore, all the isolated compounds 1-10 were tested for antioxidative activity by the superoxide dismutase (SOD)-like assay.

Lignans and secoiridoid glycosides from the stem barks of Jasminum tortuosum.

PubMed

Tomassini, Lamberto; Ventrone, Antonio; Frezza, Claudio; Serafini, Ilaria; Bianco, Armandodoriano; Cometa, Maria Francesca

2018-08-01

This paper reports on the first phytochemical analysis ever performed on Jasminum tortuosum Willd. This analysis, mainly carried out by means of column chromatography separation, NMR spectroscopy and mass spectrometry, led to the isolation and the identification of four compounds, namely the lignans ginkgool (1) and olivil-4'-O-β-glucopyranoside (2) and the secoiridoids oleoside dimethyl ester (3) and oleoside 11-methyl ester (4). The presence of these compounds is significant from a chemotaxonomic point of view, confirming the correct botanical classification of the species and, from a phytochemical standpoint, may suggest its possible use in the ethno-medicinal field.

New Butyrolactone Type Lignans from Arctii Fructus and Their Anti-inflammatory Activities.

PubMed

Yang, Ya-Nan; Huang, Xiao-Ying; Feng, Zi-Ming; Jiang, Jian-Shuang; Zhang, Pei-Cheng

2015-09-16

Arctiidilactone (1), a novel rare butyrolactone lignan with a 6-carboxyl-2-pyrone moiety, and 11 new butyrolactone lignans (2-12) were isolated from the fruits of Arctium lappa L., together with 5 known compounds (13-17). Their structures were elucidated by interpretation of their spectroscopic data (1D and 2D NMR, UV, IR, ORD, and HRESIMS) and comparison to literature data. The absolute configurations of compounds 1-12 were determined by a combination of rotating-frame nuclear Overhauser effect spectroscopy (ROESY), circular dichroism (CD) spectroscopy, and Rh2(OCOCF3)4-induced CD spectroscopy. All of the compounds were tested for their anti-inflammatory properties in terms of suppressing the production of NO in lipopolysaccharide-induced BV2 cells. Compounds 1, 6, 8, and 10 exhibited stronger anti-inflammatory effects than the positive control curcumin, particularly 1, which exhibited 75.51, 70.72, and 61.17% inhibition at 10, 1, and 0.1 μM, respectively.

Simultaneous quantification and identification of flavonoids, lignans, coumarin and amides in leaves of Zanthoxylum armatum using UPLC-DAD-ESI-QTOF-MS/MS.

PubMed

Bhatt, Vinod; Sharma, Sushila; Kumar, Neeraj; Sharma, Upendra; Singh, Bikram

2017-01-05

The current study presents isolation and characterization of twelve compounds including catechin (1), isovitexin (2), hesperidin (3), psoralin (4), eudesmin (5), kobusin (6), fargesin (7), sesamin (8), asarinin (9), planispine-A (10), α-sanshool (11) and vitexin (12), from the leaves of Zanthoxylum armatum. Further, two rapid and simple ultra performance liquid chromatography-diode array detection (UPLC-DAD) methods were developed for the simultaneous quantitative determination of isolated compounds from Z. armatum leaves. These analytical methods were validated for linearity, precision, accuracy, limit of detection (LOD) and limit of quantification (LOQ). The LOD and LOQ were in the range of 0.06-0.21μg/mL and 0.19-0.69μg/mL, respectively. The validated method was linear (R 2 ≥0.9906), precise in terms of peak area (intra-day RSDs <3.8% and inter-day RSDs <2.7%), and accurate (109.6-92.5%). This is the first report on the isolation and quantification of 1, 2, 4 and 12 in Z. armatum and 3 in Zanthoxylum genus. The methods: were successfully applied to assess the quality of samples collected from different locations of Himachal Pradesh during summer and winter season. The results demonstrated that flavonoids and furofuran lignans were the major constituents in Z. armatum leaves. The developed methods: were further applied for tandem electrospray ionization-mass spectrometry (UPLC-DAD-ESI-MS/MS) and total eighteen compounds were identified including phenolic acid, flavonoids, furofuran lignans, coumarin and isobutyl amides. Copyright © 2016 Elsevier B.V. All rights reserved.

Larvicidal activity of lignans and alkaloid identified in Zanthoxylum piperitum bark toward insecticide-susceptible and wild Culex pipiens pallens and Aedes aegypti.

PubMed

Kim, Soon-Il; Ahn, Young-Joon

2017-05-04

The yellow fever mosquito, Aedes aegypti, and the common house mosquito, Culex pipiens pallens, transmit dengue fever and West Nile virus diseases, respectively. This study was conducted to determine the toxicity of the three lignans (-)-asarinin, sesamin and (+)-xanthoxylol-γ,γ-dimethylallylether (XDA), and the alkaloid pellitorine from Zanthoxylum piperitum (Rutaceae) bark to third-instar larvae from insecticide-susceptible C. pipiens pallens and Ae. aegypti as well as wild C. pipiens pallens resistant to deltamethrin, cyfluthrin, fenthion, and temephos. The toxicities of all isolates were compared with those of mosquito larvicide temephos. LC 50 values for each species and their treatments were significantly different from one another when their 95% confidence intervals did not overlap. XDA was isolated from Z. piperitum as a new larvicidal principle. XDA (LC 50 , 0.27 and 0.24 mg/l) was 4, 53, and 144 times and 4, 100, and 117 times more toxic than pellitorine, sesamin, and asarinin toward larvae from susceptible C. pipiens pallens and Ae. aegypti, respectively. Overall, all the isolates were less toxic than temephos (LC 50 , 0.006 and 0.009 mg/l). These constituents did not differ in toxicity to larvae from the two Culex strains. The present finding indicates that the lignans and alkaloid and the insecticides do not share a common mode of larvicidal action or elicit cross-resistance. Naturally occurring Z. piperitum bark-derived compounds, particularly XDA, merit further study as potential mosquito larval control agents or as lead compounds for the control of insecticide-resistant mosquito populations.

Isolation of a dihydrobenzofuran lignan from South American dragon's blood (Croton spp.) as an inhibitor of cell proliferation.

PubMed

Pieters, L; de Bruyne, T; Claeys, M; Vlietinck, A; Calomme, M; vanden Berghe, D

1993-06-01

Dragon's blood is a red viscous latex extracted from the cortex of various Croton spp. (Euphorbiaceae), most commonly Croton lechleri, Croton draconoides (or Croton palanostigma), and Croton erythrochilus. It is used in South American popular medicine for several purposes, including wound healing. Bioassay-guided fractionation of dragon's blood, using an in vitro test system for the stimulation of human umbilical vein endothelial cells, has resulted in the isolation of a dihydrobenzofuran lignan, 3',4-O-dimethylcedrusin or 4-O-methyldihydrodehydrodiconiferyl alcohol [2-(3',4'-dimethoxyphenyl)-3-hydroxymethyl-2,3-dihydro-7-methoxybenzo furan-5- propan-1-ol] [1] as the biologically active principle. A related compound, 4-O-methylcedrusin [2-(3',4'-dimethoxyphenyl)-3-hydroxymethyl-2,3-dihydro-7-hydroxybenzo furan-5- propan-1-ol] [2], and the alkaloid taspine [3], also isolated from dragon's blood, were not active in the same assay. A cell proliferation assay, measuring the incorporation of tritiated thymidine in endothelial cells, showed that compound 1 did not stimulate cell proliferation, but rather inhibited thymidine incorporation, while protecting cells against degradation in a starvation medium.

Prenylated flavonol glycosides Epimedium grandiflorum: Cytotoxicity and evaluation against inflammation and metabolic disorders

USDA-ARS?s Scientific Manuscript database

Two new prenylated flavonol glycosides, epimedigrandiosides A and B (1 and 2), and 28 previously known compounds including prenylated flavonol derivatives, flavonol glycoside, megastigmanes, phenyl alkanoids, sesquiterpenoid glycoside, lignan, and hexene glucoside were isolated from the methanol ext...

Recent advances in the metabolic engineering of lignan biosynthesis pathways for the production of transgenic plant-based foods and supplements.

PubMed

Satake, Honoo; Ono, Eiichiro; Murata, Jun

2013-12-04

Plant physiological, epidemiological, and food science studies have shed light on lignans as healthy diets for the reduction of the risk of lifestyle-related noncommunicable diseases and, thus, the demand for lignans has been rapidly increasing. However, the low efficiency and instability of lignan production via extraction from plant resources remain to be resolved, indicating the requirement for the development of new procedures for lignan production. The metabolic engineering of lignan-biosynthesizing plants is expected to be most promising for efficient, sustainable, and stable lignan production. This is supported by the recent verification of biosynthetic pathways of major dietary lignans and the exploration of lignan production via metabolic engineering using transiently gene-transfected or transgenic plants. The aim of this review is to present an overview of the biosynthetic pathways, biological activities, and metabolic engineering of lignans and also perspectives in metabolic engineering-based lignan production using transgenic plants for practical application.

Dietary intake and urinary excretion of lignans in Finnish men.

PubMed

Nurmi, Tarja; Mursu, Jaakko; Peñalvo, José L; Poulsen, Henrik E; Voutilainen, Sari

2010-03-01

Intake of lignans has been assessed in different study populations, but so far none of the studies has compared the daily intake of lignans and the urinary excretion of plant and enterolignans. We assessed the intake of lariciresinol, pinoresinol, secoisolariciresinol and matairesinol in 100 Finnish men consuming their habitual omnivorous diet, and measured the 24 h urinary excretion of plant and enterolignans to compare the intake and metabolism. Dietary determinants of lignan intake and their urinary excretion were also determined. The mean intake of lignans was 1224 (sd 539) mug/d, of which lariciresinol and pinoresinol covered 78 %. Almost half (47 %) of the intake of lignans was explained by the intake of rye products, berries, coffee, tea and roots. The urinary excretion of plant lignans corresponded to 17 % and enterolignans to 92 % of the intake of lignans. The urinary excretion of plant lignans was explained 14 % by the intake of rye products and intake of coffee, and consequently 3-7 % by the intake of water-insoluble fibre. The urinary excretion of enterolactone was explained 11 % by the intake of vegetables and rye products, 14 % by the intake of water-soluble fibre and only 4 % by the intake of lariciresinol. Although the assessed intake of lignans corresponded well with the urinary excretion of lignans, the enterolactone production in the human body depended more on the dietary sources of lignans than the absolute intake of lignans.

A new pair of enantiomeric lignans from the fruits of Morinda citrifolia and their absolute configuration.

PubMed

Liu, Wen-Jian; Chen, Yue-Juan; Chen, Dan-Na; Wu, Ya-Ping; Gao, Yu-Jie; Li, Jing; Zhong, Wen-Jun; Jiang, Lin

2018-04-01

A new pair of sesamin-type lignan enantiomers (±)-morifolia A (1a/1b) together with eight known analogues (2-9) were isolated from the fruits of Morinda citrifolia. Their structures were established by spectroscopic data and the absolute configurations of 1a/1b were determined by ECD calculation. All compounds were examined for their inhibitory effects on the nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages, and compounds 1a, 1b, 2-4 and 7-9 exhibited pronounced inhibition with IC 50 values in the range of 1.97-8.01 (μM, being more active than the positive control, quercetin (IC 50  = 15.32 (M).

Isolation, characterization and antihyperlipidemic activity of secoisolariciresinol diglucoside in poloxamer-407-induced experimental hyperlipidemia.

PubMed

Zanwar, Anand A; Hegde, Mahabaleshwar V; Rojatkar, Supada R; Sonawane, Kiran B; Rajamohanan, P R; Bodhankar, Subhash L

2014-09-01

Linum usitatissimum L. (Linaceae), commonly known as flaxseed, is a good source of dietary fiber and lignans. Earlier we reported cardioprotective, antihyperlipidemic, and in vitro antioxidant activity of flax lignan concentrate (FLC) obtained from flaxseed. To isolate secoisolariciresinol diglucoside (SDG) from FLC and to evaluate the antihyperlipidemic activity of SDG in poloxamer-407 (P-407)-induced hyperlipidaemic mice. FLC was subjected to column chromatography and further subjected to preparative HPTLC to isolate SDG. The chemical structure of the isolated compound was elucidated by UV, IR, (1)H NMR, (13)C NMR, DEPT, COSY, HSQC, HMBC, ROESY, MS, and specific optical rotation was recorded. Further, we have investigated the antihyperlipidaemic effect of SDG (20 mg/kg) in P-407-induced hyperlipidaemic rats. Hyperlipidaemia was induced by intraperitoneal administration of P-407 (30% w/v). Serum lipid parameters such as total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) levels were measured. The structure and stereochemistry of the isolated compound were confirmed on the basis of 1D and 2D spectral data and characterized as SDG. Finally, isolated pure SDG was screened using a P-407-induced mice model for its antihyperlipidemic action using serum lipid parameters. The isolated SDG (20 mg/kg) significantly reduced serum cholesterol, triglyceride (p < 0.001), very low-density lipoprotein (p < 0.05), and non-significantly increased HDL-C. Finally, it was concluded unequivocally that SDG showed antihyperlipidaemic effects in P-407-induced hyperlipidaemic mice. Isolated pure SDG confirms that SDG is beneficial in the prevention of experimental hyperlipidemia in laboratory animals.

Dietary intake and main sources of plant lignans in five European countries

PubMed Central

Tetens, Inge; Turrini, Aida; Tapanainen, Heli; Christensen, Tue; Lampe, Johanna W.; Fagt, Sisse; Håkansson, Niclas; Lundquist, Annamari; Hallund, Jesper; Valsta, Liisa M.

2013-01-01

Background Dietary intakes of plant lignans have been hypothesized to be inversely associated with the risk of developing cardiovascular disease and cancer. Earlier studies were based on a Finnish lignan database (Fineli®) with two lignan precursors, secoisolariciresinol (SECO) and matairesinol (MAT). More recently, a Dutch database, including SECO and MAT and the newly recognized lignan precursors lariciresinol (LARI) and pinoresinol (PINO), was compiled. The objective was to re-estimate and re-evaluate plant lignan intakes and to identify the main sources of plant lignans in five European countries using the Finnish and Dutch lignan databases, respectively. Methods Forty-two food groups known to contribute to the total lignan intake were selected and attributed a value for SECO and MAT from the Finnish lignan database (Fineli®) or for SECO, MAT, LARI, and PINO from the Dutch database. Total intake of lignans was estimated from food consumption data for adult men and women (19–79 years) from Denmark, Finland, Italy, Sweden, United Kingdom, and the contribution of aggregated food groups calculated using the Dutch lignin database. Results Mean dietary lignan intakes estimated using the Dutch database ranged from 1 to 2 mg/day, which was approximately four-fold higher than the intakes estimated from the Fineli® database. When LARI and PINO were included in the estimation of the total lignan intakes, cereals, grain products, vegetables, fruit and berries were the most important dietary sources of lignans. Conclusion Total lignin intake was approximately four-fold higher in the Dutch lignin database, which includes the lignin precursors LARI and PINO, compared to estimates based on the Finnish database based only on SECO and MAT. The main sources of lignans according to the Dutch database in the five countries studied were cereals and grain products, vegetables, fruit, berries, and beverages. PMID:23766759

Neolignans from the Leaves of Casearia sylvestris Swartz

USDA-ARS?s Scientific Manuscript database

Six new neolignans, casearialignans A-F (1-6) and one known lignan syringaresinol-ß-D-glucoside were isolated from the leaves of Casearia sylvestris. Their structures were determined on the basis of 1D and 2 D NMR and high resolution ESI-MS spectroscopic analyses. The relative and absolute configura...

High throughput screening and antioxidant assay of dibenzo[a,c]cyclooctadiene lignans in modified-ultrasonic and supercritical fluid extracts of Schisandra chinensis Baill by liquid chromatography--mass spectrometry and a free radical-scavenging method.

PubMed

Wang, Ming-Chih; Lai, Yih-Cherng; Chang, Chia-Lin

2008-05-01

Dibenzo[a,c]cyclooctadiene lignans of Schisandra chinensis Baill are well known because of their hepatoprotective activity, antioxidant activity, and anticancer effect. For the isolation of the dibenzo[a,c]cyclooctadiene lignans of Schisandra chinensis Baill two extraction methods were used: modified-ultrasonic extraction and supercritical fluid extraction. A specific and fast analytical method for structure identification is established for quality control because structure elucidation could be accomplished by means of liquid chromatography-mass spectrometry (LC-MS) technologies. The separation and identification of the compounds were completed by: (i) a water-acetonitrile gradient system using a C18 reversed-phase column; (ii) UV detection at 225 nm; (iii) MS/MS experiments with electrospray ionization interface (ESI) ion trap mass spectrometry in the positive mode. Normalized collision energy was used to obtain fragment ions of structural relevance in the LC-MS/MS. These results provided a reliable LC-MS/MS method for the determination of the dibenzo[a,c]cyclooctadiene lignans from Schisandra chinensis Baill. Finally, we also detected 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging effects (%) of the modified-ultrasonic and supercritical fluid extracts of Schisandra chinensis Baill compared with 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox). The antioxidant activities of the modified-ultrasonic and supercritical fluid extracts were lower than that of trolox.

Dietary lignans: physiology and potential for cardiovascular disease risk reduction

PubMed Central

Peterson, Julia; Dwyer, Johanna; Adlercreutz, Herman; Scalbert, Augustin; Jacques, Paul; McCullough, Marjorie L

2010-01-01

We reviewed lignan physiology and lignan intervention and epidemiological studies to determine if they decreased the risks of cardiovascular disease in Western populations. Five intervention studies using flaxseed lignan supplements indicated beneficial associations with C-reactive protein and a meta-analysis, which included these studies, also suggested a lowering effect on plasma total and low-density lipoprotein cholesterol. Three intervention studies using sesamin supplements indicated possible lipid and blood pressure lowering associations. Eleven human observational epidemiological studies examined dietary intakes of lignans in relation to cardiovascular disease risk. Five showed decreased risk with either increasing dietary intakes of lignans or increased levels of serum enterolactone (an enterolignan used as a biomarker of lignan intake), five studies were of borderline significance, and one was null. The associations between lignans and decreased risk of cardiovascular disease are promising, but are yet not well established, perhaps due to low lignan intakes in habitual Western diets. At the higher doses used in intervention studies, associations were more evident. PMID:20883417

Development of an extraction method for the quantification of lignans in espresso coffee by using HPLC-MS/MS triple quadrupole.

PubMed

Angeloni, Simone; Navarini, Luciano; Sagratini, Gianni; Torregiani, Elisabetta; Vittori, Sauro; Caprioli, Giovanni

2018-06-20

Lignans are polyphenolic compounds that are considered phytoestrogens for their plant origins and they possess different biological activities. Three different extraction methods, i.e., 'dilute and shoot', acidic hydrolysis and enzymatic digestion, have been compared for extracting lignans (secoisolariciresinol, SECO, matairesinol, MAT and lariciresinol LARI) from espresso coffee (EC) by using high performance liquid chromatography (HPLC) tandem mass spectrometry (MS/MS). The best recovery values (SECO: 97%, LARI: 98% and MAT: 93%) were obtained by using enzymatic hydrolysis with Clara-Diastase at 10% (w/v), keeping the sample at 37 °C for 3 hours. For this reason, this method has been chosen and then applied to quantify lignans in nine different EC samples from five different geographical origins (Brazil, Colombia, El Salvador, Ethiopia and India). SECO and LARI were found in all EC samples from 27.9 to 52.0 μg l -1 and from 5.3 to 27.8 μg l -1 , respectively, contrary to MAT that it was not possible to detect it in each type of coffee. This method confirms the high specificity and sensitivity of MS/MS system for detecting bioactives in complex matrix such as coffee. This article is protected by copyright. All rights reserved.

Potential protective properties of flax lignan secoisolariciresinol diglucoside.

PubMed

Imran, Muhammad; Ahmad, Nazir; Anjum, Faqir Muhammad; Khan, Muhammad Kamran; Mushtaq, Zarina; Nadeem, Muhammad; Hussain, Shahzad

2015-07-28

Lignans are a group of phytonutrients which are widely distributed in the plant kingdom. Flaxseed is the richest source of providing lignan precursor such as secoisolariciresinol diglucoside (SDG). This article reviews the studies relevant to experimental models in animals and humans demonstrating the possible nutraceutical actions of SDG to prevent and alleviate lifestyle-related diseases. A local and international web-based literature review for this project was carried out to provide information relating to the study. The major key word "SDG" was selected to gather information using the electronic databases pertaining to the current state of flaxseed lignans composition, bioactive compounds, metabolism and to find out their role in terms of chemopreventive action. The extraction methods vary from simple to complex depending on separation, fractionation, identification and detection of the analytes. The majority of studies demonstrate that SDG interferes with the development of different types of diseases like cardiovascular, diabetic, lupus nephritis, bone, kidney, menopause, reproduction, mental stress, immunity, atherosclerosis, hemopoietic, liver necrosis and urinary disorders due to its various biological properties including anti-inflammatory, antioxidant, antimutagenic, antimicrobial, antiobesity, antihypolipidemic and neuroprotective effects. Moreover, SDG has a defending mediator against various cancers by modulating multiple cell signaling pathways. As discussed in this review, SDG has shown therapeutic potential against a number of human diseases and can be recommended for discerning consumers.

The lignan niranthin poisons Leishmania donovani topoisomerase IB and favours a Th1 immune response in mice

PubMed Central

Chowdhury, Sayan; Mukherjee, Tulika; Mukhopadhyay, Rupkatha; Mukherjee, Budhaditya; Sengupta, Souvik; Chattopadhyay, Sharmila; Jaisankar, Parasuraman; Roy, Syamal; Majumder, Hemanta K

2012-01-01

Niranthin, a lignan isolated from the aerial parts of the plant Phyllanthus amarus, exhibits a wide spectrum of pharmacological activities. In the present study, we have shown for the first time that niranthin is a potent anti-leishmanial agent. The compound induces topoisomerase I-mediated DNA–protein adduct formation inside Leishmania cells and triggers apoptosis by activation of cellular nucleases. We also show that niranthin inhibits the relaxation activity of heterodimeric type IB topoisomerase of L. donovani and acts as a non-competitive inhibitor interacting with both subunits of the enzyme. Niranthin interacts with DNA–protein binary complexes and thus stabilizes the ‘cleavable complex’ formation and subsequently inhibits the religation of cleaved strand. The compound inhibits the proliferation of Leishmania amastigotes in infected cultured murine macrophages with limited cytotoxicity to the host cells and is effective against antimony-resistant Leishmania parasites by modulating upregulated P-glycoprotein on host macrophages. Importantly, besides its in vitro efficacy, niranthin treatment leads to a switch from a Th2- to a Th1-type immune response in infected BALB/c mice. The immune response causes production of nitric oxide, which results in almost complete clearance of the liver and splenic parasite burden after intraperitoneal or intramuscular administration of the drug. These findings can be exploited to develop niranthin as a new drug candidate against drug-resistant leishmaniasis. PMID:23027614

The lignan glycosides lyoniside and saracoside poison the unusual type IB topoisomerase of Leishmania donovani and kill the parasite both in vitro and in vivo.

PubMed

Saha, Sourav; Mukherjee, Tulika; Chowdhury, Sayan; Mishra, Amartya; Chowdhury, Somenath Roy; Jaisankar, Parasuraman; Mukhopadhyay, Sibabrata; Majumder, Hemanta K

2013-12-15

Lignans are diphenyl propanoids with vast range of biological activities. The present study provides an important insight into the anti-leishmanial activities of two lignan glycosides, viz. lyoniside and saracoside. These compounds inhibit catalytic activities of topoisomerase IB (LdTopIB) of Leishmania donovani in non-competitive manner and stabilize the LdTopIB mediated cleavage complex formation both in vitro and in Leishmania promastigotes and subsequently inhibit the religation of cleaved strand. These two compounds not only poison LdTopIB but also can interact with the free enzyme LdTopIB. We have also shown that lyoniside and saracoside are cytotoxic to promastigotes and intracellular amastigotes. The protein-DNA complex formation leads to double strand breaks in DNA which ultimately triggers apoptosis-like cell death in the parasite. Along with their cytotoxicity towards sodium antimony gluconate (SAG) sensitive AG83 strain, their ability to kill SAG resistant GE1 strain makes these two compounds potential anti-leishmanial candidates. Not only they effectively kill L. donovani amastigotes inside macrophages in vitro, lyoniside and saracoside demonstrated strong anti-leishmanial efficacies in BALB/c mice model of leishmaniasis. Treatment with these lignan glycosides produce nitric oxide and reactive oxygen species which result in almost complete clearance of the liver and splenic parasite burden. These compounds do not inhibit human topoisomerase IB upto 200μM concentrations and had poor cytotoxic effect on uninfected cultured murine peritoneal macrophages upto 100μM concentrations. Taken together it can be concluded that these compounds can be developed into excellent therapeutic agent against deadly disease leishmaniasis. Copyright © 2013 Elsevier Inc. All rights reserved.

Evaluation and structure-activity relationship analysis of a new series of arylnaphthalene lignans as potential anti-tumor agents.

PubMed

Luo, Jiaoyang; Hu, Yichen; Kong, Weijun; Yang, Meihua

2014-01-01

Arylnaphthalene lignan lactones have attracted considerable interest because of their anti-tumor and anti-hyperlipidimic activities. However, to our knowledge, few studies have explored the effects of these compounds on human leukemia cell lines. In this study, five arylnaphthalene lignans including 6'-hydroxy justicidin A (HJA), 6'-hydroxy justicidin B (HJB), justicidin B (JB), chinensinaphthol methyl ether (CME) and Taiwanin E methyl ether (TEME) were isolated from Justicia procumbens and their effects on the proliferation and apoptosis of the human leukemia K562 cell line were investigated then used to assess structure-activity relationships. To achieve these aims, cytotoxicity was assayed using the MTT assay, while intracellular SOD activity was detected using the SOD Activity Assay kit. Apoptosis was measured by both the using a cycle TEST PLUS DNA reagent kit as well as the FITC Annexin V apoptosis detection kit in combination with flow cytometry. Activation of caspase-mediated apoptosis was evaluated using a FITC active Caspase-3 apoptosis kit and flow cytometry. The results indicated that HJB, HJA and JB significantly inhibited the growth of K562 cells by decreasing both proliferation and SOD activity and inducing apoptosis. The sequence of anti-proliferative activity induced by the five tested arylnaphthalenes by decreasing strength was HJB > HJA > JB > CME > TEME. HJB, HJA and JB also decreased SOD activity and induced apoptosis in a dose-dependent manner. Activation of caspase-3 further indicated that HJB, HJA and JB induced caspase-dependent intrinsic and/or extrinsic apoptosis pathways. Together, these assays suggest that arylnaphthalene lignans derived from Justicia procumbens induce apoptosis to varying degrees, through a caspase-dependent pathway in human leukemia K562 cells. Furthermore, analysis of structure-activity relationships suggest that hydroxyl substitution at C-1 and C-6' significantly increased the antiproliferative activity of arylnaphthalene lignans while a methoxyl at C-1 significantly decreased the effect.

Hepatoprotective triterpenoids and lignans from the stems of Schisandra pubescens.

PubMed

Wang, Guo-Wei; Deng, Li-Qing; Luo, You-Ping; Liao, Zhi-Hua; Chen, Min

2017-08-01

One new triterpenoid (1) and 13 known compounds (2-14) were isolated from Schisandra pubescens stems. The structure of the new compound was established on the basis of 1D/2D NMR and HRESIMS spectroscopic analyses. The isolated compounds were evaluated for their hepatoprotective activities against D-GalN-induced cell injury in QSG7701 cells. Compounds 1, 13 and 14 at 10 μM showed hepatoprotective activities, with survival rates of 60.5, 50.4 and 48.9%, respectively.

Dietary Lignan Intake and Androgen Receptor Expression in Breast Tumors

PubMed Central

Williams, AnnaLynn M.; Bonner, Matthew; Ochs-Balcom, Heather M.; Hwang, Helena; Morrison, Carl; McCann, Susan E.

2014-01-01

Purpose Lignans, a class of phytoestrogen commonly found in the Western diet, have been linked to decreased breast cancer risks in epidemiologic studies. Similar to estrogen receptors, the androgen receptor (AR), a prognostic factor in breast tumors, may be affected by lignans. However, few studies have investigated this link in the context of breast cancer etiology. We evaluated the relationship between dietary lignan intake and androgen receptor expression in incident breast tumors. Methods Tumor tissue, epidemiological, and clinical data were collected from 216 women with incident, primary, histologically-confirmed breast cancer enrolled in the Roswell Park Cancer Institute (RPCI) Data Bank and BioRepository (DBBR). On average, three tumor cores from each participant were assembled into a Tissue MicroArray (TMA). After immunohistochemical staining, a trained RPCI pathologist determined AR status of each core. Lignan intake was calculated from a food frequency questionnaire collected upon enrollment into the DBBR. Results We observed a weak positive association between dietary lignans and AR expression (β (SE) 27.6 (17.0), p 0.10) and there was no significant difference in lignan intake across categories of AR expression (p=0.09, R2 =0.35). Conclusion Our results do not support a clear relationship between dietary lignan intake and AR expression. This investigation is the first, to our knowledge, to examine dietary lignan intake and AR expression in breast tumors. Further research is needed within a larger, more representative sample to determine if lignan intake is truly associated with androgen receptor expression. PMID:25471060

Dietary lignan intake and androgen receptor expression in breast tumors.

PubMed

Williams, AnnaLynn M; Bonner, Matthew; Ochs-Balcom, Heather M; Hwang, Helena; Morrison, Carl; McCann, Susan E

2015-02-01

Lignans, a class of phytoestrogen commonly found in the Western diet, have been linked to decreased breast cancer risks in epidemiologic studies. Similar to estrogen receptors, the androgen receptor (AR), a prognostic factor in breast tumors, may be affected by lignans. However, few studies have investigated this link in the context of breast cancer etiology. We evaluated the relationship between dietary lignan intake and AR expression in incident breast tumors. Tumor tissue, epidemiological, and clinical data were collected from 216 women with incident, primary, histologically confirmed breast cancer enrolled in the Roswell Park Cancer Institute (RPCI) Data Bank and BioRepository (DBBR). On average, three tumor cores from each participant were assembled into a tissue micro array. After immunohistochemical staining, a trained RPCI pathologist determined AR status of each core. Lignan intake was calculated from a food frequency questionnaire collected upon enrollment into the DBBR. We observed a weak positive association between dietary lignans and AR expression [β (SE) 27.6 (17.0), p 0.10], and there was no significant difference in lignan intake across categories of AR expression (p = 0.09, R (2) = 0.35). Our results do not support a clear relationship between dietary lignan intake and AR expression. This investigation is the first, to our knowledge, to examine dietary lignan intake and AR expression in breast tumors. Further research is needed within a larger, more representative sample to determine whether lignan intake is truly associated with AR expression.

Optimum yields of dibenzylbutyrolactone-type lignans from Cynareae fruits, during their ripening, germination and enzymatic hydrolysis processes, determined by on-line chromatographic methods.

PubMed

Szokol-Borsodi, Lilla; Sólyomváry, Anna; Molnár-Perl, Ibolya; Boldizsár, Imre

2012-01-01

Dibenzylbutyrolactone-type lignans are the physiologically active constituents of the achene fruits of Cynareae. These lignans occur in glycoside/aglycone forms: in the highest quantity of the arctiin/arctigenin, matairesinoside/matairesinol and tracheloside/trachelogenin pairs found in the fruits of Arctium lappa L., Centaurea scabiosa L. and Cirsium arvense (L.) Scop. To optimise the extraction yield of the arctiin/arctigenin, matairesinoside/matairesinol and tracheloside/trachelogenin glycoside/aglycone pairs, from the fruits of Arctium lappa, Centaurea scabiosa and Cirsium arvense, under the ripening, germination and enzymatic hydrolysis processes of the fruits. Identification and quantification of lignans were performed with on-line gas chromatography-mass spectrometry (GC-MS) and with high performance liquid chromatography (HPLC), both with UV and mass selective detections (HPLC-UV/MS). As novelties to the field it was confirmed that: (i) the unripe fruits provide a high amount of lignans, similar to the ripe fruit; (ii) the fruits of Arctium lappa and Cirsium arvense do have glycosidase activity to hydrolyse their lignan glycosides into free lignans; (iii) the glycosidase of Centaurea scabiosa fruit becomes activated under its germination process only; and (iv) the overwhelming part of the fruits lignan contents (80-94%) in all three species are accumulated in the embryo. The best sources of (i) lignan aglycones are the enzyme-hydrolysed embryos, separating spontaneously during the germination process, and (ii) lignan glycosides are the unripe fruits. Copyright © 2012 John Wiley & Sons, Ltd.

Lignans From Forsythia x Intermedia Leaves and Flowers Attenuate the Pro-inflammatory Function of Leukocytes and Their Interaction With Endothelial Cells

PubMed Central

Michalak, Barbara; Filipek, Agnieszka; Chomicki, Piotr; Pyza, Małgorzata; Woźniak, Marta; Żyżyńska-Granica, Barbara; Piwowarski, Jakub P.; Kicel, Agnieszka; Olszewska, Monika A.; Kiss, Anna K.

2018-01-01

Aim of the study: Taking into account that overactivated leukocytes are an important factor in the development of many chronic diseases, we investigated the activity of phytochemically characterized (HPLC-DAD-MSn) extracts from forsythia leaves and flowers on the pro- and anti-inflammatory functions of leukocytes (effects on IL-1β, IL-8, TNF-α, and TGFβ release) and their adherence to endothelial cells. Using bio-guided fractionation, we isolated the active compounds and determined their biological activity, and we included the positive control quercetin. Methods: The effect on IL-1β, TNF-α, IL-8, and TGF-α production by leukocytes was measured by enzyme-linked immunosorbent assay (ELISA). The surface expression of adhesion molecules was analyzed with flow cytometry, and the neutrophil attachment to the endothelial cells was assessed fluorimetrically. The effects on p38MAPK, ERK1/2 and JNK phosphorylation were determined using western blots. Results: Leaf extracts had the effect of decreasing TNF-α production in neutrophils and monocyte/macrophage cells. The bio-guided fractionation led to the isolation of the following lignan aglycones: (+)-pinoresinol, (+)-epipinoresinol, (−)-matairesinol, (+)-phillygenin, and (−)-arctigenin. Only phillygenin was able to stimulate the anti-inflammatory function of macrophages by inducing TGF-β release and IL-10 receptor surface expression. Arctigenin, phillygenin, and a metabolite produced by the gut microbiota, enterolactone, decreased TNF-α and IL-1β production and neutrophil adhesion to endothelial cells, probably by attenuating the p38 and ERK kinase pathways. Conclusion: Forsythia x intermedia is a valuable source of active lignans, which may be potential candidates for treating inflammatory diseases that are associated with the excessive production of cytokines such as TNF-α and IL-1β. PMID:29740324

Lignans From Forsythia x Intermedia Leaves and Flowers Attenuate the Pro-inflammatory Function of Leukocytes and Their Interaction With Endothelial Cells.

PubMed

Michalak, Barbara; Filipek, Agnieszka; Chomicki, Piotr; Pyza, Małgorzata; Woźniak, Marta; Żyżyńska-Granica, Barbara; Piwowarski, Jakub P; Kicel, Agnieszka; Olszewska, Monika A; Kiss, Anna K

2018-01-01

Aim of the study: Taking into account that overactivated leukocytes are an important factor in the development of many chronic diseases, we investigated the activity of phytochemically characterized (HPLC-DAD-MS n ) extracts from forsythia leaves and flowers on the pro- and anti-inflammatory functions of leukocytes (effects on IL-1β, IL-8, TNF-α, and TGFβ release) and their adherence to endothelial cells. Using bio-guided fractionation, we isolated the active compounds and determined their biological activity, and we included the positive control quercetin. Methods: The effect on IL-1β, TNF-α, IL-8, and TGF-α production by leukocytes was measured by enzyme-linked immunosorbent assay (ELISA). The surface expression of adhesion molecules was analyzed with flow cytometry, and the neutrophil attachment to the endothelial cells was assessed fluorimetrically. The effects on p38MAPK, ERK1/2 and JNK phosphorylation were determined using western blots. Results: Leaf extracts had the effect of decreasing TNF-α production in neutrophils and monocyte/macrophage cells. The bio-guided fractionation led to the isolation of the following lignan aglycones: (+)-pinoresinol, (+)-epipinoresinol, (-)-matairesinol, (+)-phillygenin, and (-)-arctigenin. Only phillygenin was able to stimulate the anti-inflammatory function of macrophages by inducing TGF-β release and IL-10 receptor surface expression. Arctigenin, phillygenin, and a metabolite produced by the gut microbiota, enterolactone, decreased TNF-α and IL-1β production and neutrophil adhesion to endothelial cells, probably by attenuating the p38 and ERK kinase pathways. Conclusion: Forsythia x intermedia is a valuable source of active lignans, which may be potential candidates for treating inflammatory diseases that are associated with the excessive production of cytokines such as TNF-α and IL-1β.

Activity in vitro and in vivo against Trypanosoma cruzi of a furofuran lignan isolated from Piper jericoense.

PubMed

García-Huertas, Paola; Olmo, Francisco; Sánchez-Moreno, Manuel; Dominguez, Jorge; Chahboun, Rachid; Triana-Chávez, Omar

2018-06-01

Piperaceae species are abundant in the tropics and are important components of secondary vegetation. Many of these plants have received considerable attention due to their wide range of biological activities. Here, the trypanocidal activity of extracts and fractions with different polarities obtained from Colombian Piper jericoense plant was evaluated. A furofuran lignan, (1S,3aS,4S,6aS)-1-(3',4'-dimethoxyphenyl)-4-(3″,4″-methylendioxyphenyl)hexahydrofuro[3,4-c]furan, (1), was isolated from Colombian Piper jericoense leaves ethyl acetate extract. Its relative configuration at the stereogenic centers was established on the basis of various spectroscopic analyses, including 1D- (1H, 13C, and DEPT) and 2D-NMR (COSY, NOESY, HMQC and HMBC) and a 2D INADEQUATE NMR experiment as well as by comparison of their spectral data with those of related compounds such as (+)-Kobusin (2). The activity against Trypanosoma cruzi indicated that compound 1 was active against all parasite forms (epimastigote, amastigote and trypomastigote) and presented lower toxicity than the reference drug, benznidazole (Bz), evidenced by a selective index of 18.4 compared to that of Bz, which was 6.7. Moreover, this compound inhibited the infectious process, and it was active in infected mice in the acute phase. This compound significantly inhibited the T. cruzi Fe-SOD enzyme, whereas Cu/Zn-SOD from human cells was not affected. Ultrastructural analyses, together with metabolism-excretion studies in the parasite, were also performed to identify the possible mechanism of action of the tested compound. Interestingly, the lignan affected the parasite structure, but it did not alter the energetic metabolism. Copyright © 2018 Elsevier Inc. All rights reserved.

Abscisic acid related compounds and lignans in prunes (Prunus domestica L.) and their oxygen radical absorbance capacity (ORAC).

PubMed

Kikuzaki, Hiroe; Kayano, Shin-ichi; Fukutsuka, Naoko; Aoki, Asuka; Kasamatsu, Kumi; Yamasaki, Yuka; Mitani, Takahiko; Nakatani, Nobuji

2004-01-28

Four new abscisic acid related compounds (1-4), together with (+)-abscisic acid (5), (+)-beta-D-glucopyranosyl abscisate (6), (6S,9R)-roseoside (7), and two lignan glucosides ((+)-pinoresinol mono-beta-D-glucopyranoside (8) and 3-(beta-D-glucopyranosyloxymethyl)-2- (4-hydroxy-3-methoxyphenyl)-5-(3-hydroxypropyl)-7-methoxy-(2R,3S)-dihydrobenzofuran (9)) were isolated from the antioxidative ethanol extract of prunes (Prunus domestica L.). The structures of 1-4 were elucidated on the basis of NMR and MS spectrometric data to be rel-5-(3S,8S-dihydroxy-1R,5S-dimethyl-7-oxa-6-oxobicyclo[3,2,1]oct-8-yl)-3-methyl-2Z,4E-pentadienoic acid (1), rel-5-(3S,8S-dihydroxy-1R,5S-dimethyl-7-oxa-6-oxobicyclo[3,2,1]oct-8-yl)-3-methyl-2Z,4E-pentadienoic acid 3'-O-beta-d-glucopyranoside (2), rel-5-(1R,5S-dimethyl-3R,4R,8S-trihydroxy-7-oxa-6-oxobicyclo[3,2,1]oct-8-yl)-3-methyl-2Z,4E-pentadienoic acid (3), and rel-5-(1R,5S-dimethyl-3R,4R,8S-trihydroxy-7-oxabicyclo[3,2,1]- oct-8-yl)-3-methyl-2Z,4E-pentadienoic acid (4). The antioxidant activities of these isolated compounds were evaluated on the basis of oxygen radical absorbance capacity (ORAC). The ORAC values of abscisic acid related compounds (1-7) were very low. Two lignans (8 and 9) were more effective antioxidants whose ORAC values were 1.09 and 2.33 micromol of Trolox equiv/micromol, respectively.

Isolation, Identification, and Biological Evaluation of Phenolic Compounds from a Traditional North American Confectionery, Maple Sugar.

PubMed

Liu, Yongqiang; Rose, Kenneth N; DaSilva, Nicholas A; Johnson, Shelby L; Seeram, Navindra P

2017-05-31

Maple sap, collected from the sugar maple (Acer saccharum) tree, is boiled to produce the popular plant-derived sweetener, maple syrup, which can then be further evaporated to yield a traditional North American confectionery, maple sugar. Although maple sap and maple syrup have been previously studied, the phytochemical constituents of maple sugar are unknown. Herein, 30 phenolic compounds, 1-30, primarily lignans, were isolated and identified (by HRESIMS and NMR) from maple sugar. The isolates included the phenylpropanoid-based lignan tetramers (erythro,erythro)-4″,4‴-dihydroxy-3,3',3″,3‴,5,5'-hexamethoxy-7,9';7',9-diepoxy-4,8″;4',8‴-bisoxy-8,8'-dineolignan-7″,7‴,9″,9‴-tetraol, 29, and (threo,erythro)-4″,4‴-dihydroxy-3,3',3″,3‴,5,5'-hexamethoxy-7,9';7',9-diepoxy-4,8″;4',8‴-bisoxy-8,8'-dineolignan-7″,7‴,9″,9‴-tetraol, 30, neither of which have been identified from maple sap or maple syrup before. Twenty of the isolates (selected on the basis of sample quantity available) were evaluated for their potential biological effects against lipopolysaccharide-induced inflammation in BV-2 microglia in vitro and juglone-induced oxidative stress in Caenorhabditis elegans in vivo. The current study increases scientific knowledge of possible bioactive compounds present in maple-derived foods including maple sugar.

Seasonal alteration in amounts of lignans and their glucosides and gene expression of the relevant biosynthetic enzymes in the Forsythia suspense leaf.

PubMed

Morimoto, Kinuyo; Satake, Honoo

2013-01-01

Lignans of Forsythia spp. are essential components of various Chinese medicines and health diets. However, the seasonal alteration in lignan amounts and the gene expression profile of lignan-biosynthetic enzymes has yet to be investigated. In this study, we have assessed seasonal alteration in amounts of major lignans, such as pinoresinol, matairesinol, and arctigenin, and examined the gene expression profile of pinoresinol/lariciresinol reductase (PLR), pinoresinol-glucosylating enzyme (UGT71A18), and secoisolariciresinol dehydrogenase (SIRD) in the leaf of Forsythia suspense from April to November. All of the lignans in the leaf continuously increased from April to June, reached the maximal level in June, and then decreased. Ninety percent of pinoresinol and matairesinol was converted into glucosides, while approximately 50% of arctigenin was aglycone. PLR was stably expressed from April to August, whereas the PLR expression was not detected from September to November. In contrast, the UGT71A18 expression was found from August to November, but not from April to July. The SIRD expression was prominent from April to May, not detected in June to July, and then increased again from September to November. These expression profiles of the lignan-synthetic enzymes are largely compatible with the alteration in lignan contents. Furthermore, such seasonal lignan profiles are in good agreement with the fact that the Forsythia leaves for Chinese medicinal tea are harvested in June. This is the first report on seasonal alteration in lignans and the relevant biosynthetic enzyme genes in the leaf of Forsythia species.

Dietary Intakes of Total and Specific Lignans Are Associated with Clinical Breast Tumor Characteristics123

PubMed Central

McCann, Susan E.; Hootman, Katie C.; Weaver, Anne M.; Thompson, Lilian U.; Morrison, Carl; Hwang, Helena; Edge, Stephen B.; Ambrosone, Christine B.; Horvath, Peter J.; Kulkarni, Swati A.

2012-01-01

Dietary lignans may affect breast cancer by modifying tumor characteristics likely to affect prognosis. We investigated usual dietary intakes of total and specific lignans with tumor characteristics in 683 women with breast cancer and 611 healthy women without breast cancer enrolled in the Data Bank and BioRepository at Roswell Park Cancer Institute (RPCI). Clinicopathologic data were abstracted from the RPCI breast cancer database. Dietary lignan intakes were calculated from FFQ. OR and 95% CI were estimated with logistic regression adjusting for potential confounders and stratified by menopausal status. Women in the highest compared to the lowest tertile of total lignan intakes had a 40–50% lower odds of breast cancer regardless of menopausal status and substantially reduced odds of an invasive tumor, especially among premenopausal women [OR 0.48 (95% CI 0.26–0.86)]. Lignan intakes were inversely associated with odds of grade 3 tumors among premenopausal women. Lignan intakes were inversely associated with risk of estrogen receptor (ER) negative (ER−) breast cancer among premenopausal women [OR 0.16 (95% CI 0.03–0.44)] and particularly triple negative tumors [ER−, progesterone receptor negative, HER2 negative; OR 0.16 (95% CI 0.04–0.62)]. There were significant differences in the contribution to these effects by specific lignans, especially matairesinol and lariciresinol. In summary, in this case-control study of dietary lignan intakes and breast cancer, we found that higher lignan intakes were associated with lower risks of breast cancer with more favorable prognostic characteristics. Future investigations are warranted to explore the strong associations observed with ER− cancer in premenopausal women. PMID:22113872

Two new lignan glycosides from the seeds of Cuscuta chinensis.

PubMed

He, Xiang-Hui; Yang, Wen-Zhi; Meng, A-Hui; He, Wen-Ni; Guo, De-An; Ye, Min

2010-11-01

Two new lignan glycosides, 2'-hydroxyl asarinin 2'-O-β-D-glucopyranoside (cuscutoside C, 1) and 2'-hydroxyl asarinin 2'-O-β-D-apiofuranosyl-(1 → 2)-[β-D-glucopyranosyl-(1 → 6)]-β-D-glucopyranoside (cuscutoside D, 2), were isolated from the seeds of Cuscuta chinensis Lam., along with six known compounds, 2'-hydroxyl asarinin 2'-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (3), 2'-hydroxyl asarinin 2'-O-β-D-apiofuranosyl-(1 → 2)-β-D-glucopyranoside (cuscutoside A, 4), kaempferol 3,7-di-O-β-D-glucopyranoside (5), 5-caffeoyl quinic acid (6), 4-caffeoyl quinic acid (7), and cinnamic acid (8). Their structures were elucidated on the basis of spectroscopic analyses including HR-ESI-MS, ESI-MS/MS, (1)H and (13)C NMR, HSQC, HMBC, and TOCSY.

Dietary lignan intakes and risk of pre- and postmenopausal breast cancer.

PubMed

McCann, Susan E; Muti, Paola; Vito, Dominica; Edge, Stephen B; Trevisan, Maurizio; Freudenheim, Jo L

2004-09-01

Lignans are plant compounds metabolized in the mammalian gut to produce the phytoestrogens enterolactone and enterodiol. Because estrogens have been linked to breast cancer etiology, lignans could affect breast cancer risk through modulation of endogenous estrogen metabolism or competitive inhibition with estrogen receptors. We examined breast cancer risk and dietary lignan intake in a population-based case-control study of 1,122 women with primary, incident, histologically confirmed breast cancer and 2,036 controls frequency matched to cases on age and county of residence as part of the Western New York Exposures and Breast Cancer (WEB) Study. Diet was assessed with a self-administered 104-item food frequency questionnaire and other relevant data were collected by detailed in-person interviews. Lignans were expressed as the sum of the dietary precursors secoisolariciresinol and matairesinol. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression, adjusting for age, total energy and other breast cancer risk factors. Premenopausal women in the highest quartile of dietary lignan intake had reduced breast cancer risk (OR = 0.66; 95% CI = 0.44-0.98). No association was observed between lignan intakes and postmenopausal breast cancer. Our results suggest that dietary lignans may be important in the etiology of breast cancer, particularly among premenopausal women. Copyright 2004 Wiley-Liss, Inc.

Insecticidal defenses of Piperaceae from the neotropics.

PubMed

Bernard, C B; Krishanmurty, H G; Chauret, D; Durst, T; Philogène, B J; Sánchez-Vindas, P; Hasbun, C; Poveda, L; San Román, L; Arnason, J T

1995-06-01

Insecticidal and growth-reducing properties of extracts of 14 species of American neotropical Piperaceae were investigated by inclusion in diets of a polyphagous lepidopteran, the European corn borer,Ostrinia nubilalis. Nutritional indices suggested most extracts acted by postdigestive toxicity.Piper aduncum, P. tuberculatum, andP. decurrens were among the most active species and were subjected to bioassay-guided isolation of the active components. Dillapiol was isolated from the active fraction ofP. aduncum, piperlonguminine was isolated fromP. tuberculatum, and a novel neolignan fromP. decurrens. The results support other studies on Asian and AfricanPiper species, which suggest that lignans and isobutyl amides are the active defence compounds in this family.

Protective Role of Flaxseed Oil and Flaxseed Lignan Secoisolariciresinol Diglucoside Against Oxidative Stress in Rats with Metabolic Syndrome.

PubMed

Pilar, Bruna; Güllich, Angélica; Oliveira, Patrícia; Ströher, Deise; Piccoli, Jacqueline; Manfredini, Vanusa

2017-12-01

This study evaluated the protective effect of flaxseed oil (FO) and flaxseed lignan secoisolariciresinol diglucoside (SDG) against oxidative stress in rats with metabolic syndrome (MS). 48 rats were allocated into the following 6 groups: Groups 1 (control), 5 (FO), and 6 (SDG) received water and were treated daily orally with saline, FO, and SDG, respectively. Groups 2 (MS), 3 (MS+FO), and 4 (MS+SDG) received 30% fructose in drinking water for MS induction and were treated daily orally with saline, FO, and SDG, respectively. After 30 d, animals were sacrificed, and blood was collected for biochemical and oxidative analysis. Body weight was recorded weekly. Systolic blood pressure (SBP) was measured before and after treatment. Fructose could produce MS and oxidative stress. FO and SDG prevented changes in SBP, lipids, and glucose. FO and SDG prevented oxidative damage to lipids, and only FO prevented oxidative damage to proteins associated to MS. FO and SDG improved enzymatic antioxidants defenses and reduced glutathione levels, which was greater with SDG. Total polyphenol levels were enhanced in groups that received SDG. Thus, the results of this study demonstrated that treatment with a 30% fructose solution for 30 d is effective for MS induction and the oxidative stress is involved in the pathophysiology of MS induced by fructose-rich diets. Furthermore, we demonstrated that the antioxidant effects attributed to flaxseed are mainly due to its high lignan content especially that of SDG, suggesting that this compound can be used in isolation to prevent oxidative stress associated with MS. We report that the antioxidant effects attributed to flaxseed are mainly due to its high lignan content, especially that of secoisolariciresinol diglucoside. This is significant because suggests that this compound can be used in isolation to prevent oxidative stress associated with MS. Furthermore, this study was the only one to perform a comparison of the abilities of 2 components of flaxseed to protect against oxidative stress in an MS model, which brings a great advance in the medicine's field, since it indicates another alternative for improve the health and the quality of life of patients with this disorder. © 2017 Institute of Food Technologists®.

[Determination of podophyllotoxin and total lignans in Sinopodophyllum emodi].

PubMed

Huang, Kun; Jiang, Wei; Zhao, Jifeng; Wang, Changhua; Liu, Xiang; Zhang, Zhiwei; Qin, Songyun; Zhong, Guoyue

2012-05-01

To determine the content of podophyllotoxin and total lignans in Sinopodophyllum emodi Ying from different areas and evaluate the resource utilization of this endangered medicinal plant. HPLC and UV spectrophotometry were used to determine the content of podophyllotoxin and total lignans in 126 samples from different habitats and the total lignans content was determined by the reference wavelength method. According to the results, the highest content was determined from the samples from Yongdeng Nature Reserve in Gansu province, and the lowest ones was found in the samples from Tibet. The former's podophyllotoxin and total lignans contents were 7.40% and 20.66%, respectively, which were 19 times and 4 times more than those of the latter. The content of podophyllotoxin and total lignans in S. emodi were significantly positively related, meanwhile, samples from both low altitude and high latitude showed the higher content. The two determination methods are simple, rapid, accurate and repeatable. It is more scientific and rational to evaluate the resource utilization of S. emodi with two indicators, those are the content of podophyllotoxin and the content of total lignans. This paper is instructive to the collection of wild resources and the establishment of production bases.

Comparative pharmacokinetics of purified flaxseed and associated mammalian lignans in male Wistar rats.

PubMed

Mukker, Jatinder Kaur; Singh, Ravi Shankar Prasad; Muir, Alister D; Krol, Ed S; Alcorn, Jane

2015-03-14

Consumption of flaxseed lignans is associated with various health benefits; however, little is known about the bioavailability of purified lignans in flaxseed. Data on their bioavailability and hence pharmacokinetics (PK) are necessary to better understand their role in putative health benefits. In the present study, we conducted a comparative PK analysis of the principal lignan of flaxseed, secoisolariciresinol diglucoside (SDG), and its primary metabolites, secoisolariciresinol (SECO), enterodiol (ED) and enterolactone (EL) in rats. Purified lignans were intravenously or orally administered to each male Wistar rat. SDG and its primary metabolites SECO, ED and EL were administered orally at doses of 40, 40, 10 and 10 mg/kg, respectively, and intravenously at doses of 20, 20, 5 and 1 mg/kg, respectively. Blood samples were collected at 0 (pre-dose), 5, 10, 15, 20, 30 and 45 min, and at 1, 2, 4, 6, 8, 12 and 24 h post-dosing, and serum samples were analysed. PK parameters and oral bioavailability of purified lignans were determined by non-compartmental methods. In general, administration of the flaxseed lignans SDG, SECO and ED demonstrated a high systemic clearance, a large volume of distribution and short half-lives, whereas administration of EL at the doses of 1 mg/kg (intravenously) and 10 mg/kg (orally administered) killed the rats within a few hours of dosing, precluding a PK analysis of this lignan. PK parameters of flaxseed lignans exhibited the following order: systemic clearance, SDG < SECO < ED; volume of distribution, SDG < SECO < ED; half-life, SDG < ED < SECO. The percentage of oral bioavailability was 0, 25 and < 1 % for SDG, SECO and ED, respectively.

Two new compounds from Xanthium strumarium.

PubMed

Yin, Rong-Hua; Bai, Xue; Feng, Tao; Dong, Ze-Jun; Li, Zheng-Hui; Liu, Ji-Kai

2016-01-01

One new lignan, fructusol A (1), and one new thiazine derivative, 2-hydroxy-xanthiazone (2), along with eight known ones, were isolated from the seeds of Xanthium strumarium. The structures of new compounds were elucidated on the basis of extensive spectroscopic methods. Meanwhile, compounds 1-3 were tested for their antifungal activities against Candida albicans (ATCC 10231) in vitro. No one showed obvious inhibitions (MIC90 > 128 μg/ml).

The cellular distribution of lignans in Tsuga heterophylla wood

Treesearch

R.l. Krahmer; Richard W. Hemingway; W.E. Hillis

1970-01-01

Western hemlock heartwood contains patches of tracheids with large amounts of cellular inclusions. Microscopic and chemical examination of the wood showed several types of deposits containing the lignans matairesinol, hydroxymatairesinol and conidendrin. The deposits, which were often relatively pure individual lignans, frequently assumed different physical forms and...

Effect of Antibiotics and Diet on Enterolactone Concentration and Metabolome Studied by Targeted and Nontargeted LC-MS Metabolomics.

PubMed

Bolvig, Anne K; Nørskov, Natalja P; Hedemann, Mette S; Foldager, Leslie; McCarthy-Sinclair, Brendan; Marco, Maria L; Lærke, Helle N; Bach Knudsen, Knud E

2017-06-02

High plant lignan intake is associated with a number of health benefits, possibly induced by the lignan metabolite enterolactone (ENL). The gut microbiota plays a crucial role in converting dietary lignans into ENL, and epidemiological studies have shown that use of antibiotics is associated with lower levels of ENL. Here we investigate the link between antibiotic use and lignan metabolism in pigs using LC-MS/MS. The effect of lignan intake and antibiotic use on the gut microbial community and the pig metabolome is studied by 16S rRNA sequencing and nontargeted LC-MS. Treatment with antibiotics resulted in substantially lower concentrations of ENL compared with concentrations detected in untreated animals, whereas the plasma concentrations of plant lignans were unchanged. Both diet and antibiotic treatment affected the clustering of urinary metabolites and significantly altered the proportions of taxa in the gut microbiota. Diet, but not antibiotic treatment, affected the plasma lipid profile, and a lower concentration of LDL cholesterol was observed in the pigs fed a high lignan diet. This study provides solid support for the associations between ENL concentrations and use of antibiotics found in humans and indicates that the lower ENL concentration may be a consequence of the ecological changes in the microbiota.

Dietary lignan intakes in relation to survival among women with breast cancer: the Western New York Exposures and Breast Cancer (WEB) Study.

PubMed

McCann, Susan E; Thompson, Lilian U; Nie, Jing; Dorn, Joan; Trevisan, Maurizio; Shields, Peter G; Ambrosone, Christine B; Edge, Stephen B; Li, Hsin-Fang; Kasprzak, Christina; Freudenheim, Jo L

2010-07-01

Dietary lignan intakes have been associated with reduced breast cancer risks; however, no previous studies have investigated whether lignan intake might be associated with breast cancer survival. We examined the association of dietary lignan intakes with survival in 1122 women with primary, incident, histologically confirmed breast cancer identified between 1996 and 2001, and with vital status determined through December 31, 2006. Diet in the 12-24 months before diagnosis was assessed with an extensive food frequency questionnaire, and potential confounders assessed from an extensive epidemiologic interview and abstracted clinical data. Lignan intake was calculated using published food composition data. Hazard ratios (HR), and 95% confidence intervals (CIs) for dietary lignan intakes with all cause, and breast cancer mortality were estimated using Cox proportional hazards adjusting for age, education, race, total energy intake, tumor stage, and body mass index. Of the 1122 women with complete dietary data, 160 had died by the end of follow-up. Among postmenopausal women only, those in the highest versus lowest quartile of lignan intakes had a statistically significant reduction in the risk of all cause mortality (HR 0.49, 95% CI 0.26-0.91) and a significantly reduced risk of breast cancer mortality (HR 0.29, 95% CI 0.11-0.76). Higher intakes of dried beans (HR 0.61, 95% CI 0.36-1.03), but not fruits, vegetables, or grains, were also weakly associated with overall mortality. In summary, our results suggest that higher lignan intakes may be associated with improved survival among postmenopausal women with breast cancer.

Comparative analysis of caffeoylquinic acids and lignans in roots and seeds among various burdock (Arctium lappa) genotypes with high antioxidant activity.

PubMed

Liu, Jingyi; Cai, Yi-Zhong; Wong, Ricky Ngok Shun; Lee, Calvin Kai-Fai; Tang, Sydney Chi Wai; Sze, Stephen Cho Wing; Tong, Yao; Zhang, Yanbo

2012-04-25

Caffeoylquinic acids and lignans in the crude extracts of both roots and seeds from different burdock ( Arctium lappa L.) genotypes were simultaneously characterized and systematically compared by LC-MS and matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight mass spectrometry (MALDI-QIT-TOF MS), and their antioxidant activities were also investigated. A total of 14 lignans were identified in burdock seeds and 12 caffeoylquinic acids in burdock roots. High levels of caffeoylquinic acids were also detected in burdock seeds, but only trace amounts of lignans were found in burdock roots. Burdock seeds contained higher concentrations of lignans and caffeoylquinic acids than burdock roots. Quantitative analysis of caffeoylquinic acids and lignans in roots and seeds of various burdock genotypes was reported for the first time. Great variations in contents of both individual and total phenolic compounds as well as antioxidant activities were found among different genotypes. Burdock as a root vegetable or medicinal plants possessed considerably stronger antioxidant activity than common vegetables and fruits.

Boehmenan, a lignan from Hibiscus ficulneus, showed Wnt signal inhibitory activity.

PubMed

Shono, Takumi; Ishikawa, Naoki; Toume, Kazufumi; Arai, Midori A; Ahmed, Firoj; Sadhu, Samir K; Ishibashi, Masami

2015-07-15

The Wnt signal pathway modulates numerous biological processes, and its aberrant activation is related to various diseases. Therefore, inhibition of the Wnt signal may provide an effective (or efficient) strategy for these diseases. Cell-based luciferase assay targeting the Wnt signal (TOP assay) revealed that Hibiscus ficulneus extract inhibited the Wnt signal. The activity-guided isolation of the MeOH extract of H. ficulneus stems yielded four known (1-4) lignans along with myriceric acid (5). Compounds 1-4 potently inhibited the Wnt signal with TOPflash IC50 values of 1.0, 4.5, 6.3, and 1.9 μM, respectively. Compound 1 exhibited cytotoxicity against both Wnt-dependent (HCT116) and Wnt-independent (RKO) cells. Western blot analysis showed that 1 decreased the expression of full, cytosolic and nuclear β-catenin along with c-myc in STF/293 cells. Our results suggested that 1 may have inhibited the Wnt signal by decreasing β-catenin levels. Copyright © 2015 Elsevier Ltd. All rights reserved.

Associations between Both Lignan and Yogurt Consumption and Cardiovascular Risk Parameters in an Elderly Population: Observations from a Cross-Sectional Approach in the PREDIMED Study.

PubMed

Creus-Cuadros, Anna; Tresserra-Rimbau, Anna; Quifer-Rada, Paola; Martínez-González, Miguel Angel; Corella, Dolores; Salas-Salvadó, Jordi; Fitó, Montse; Estruch, Ramon; Gómez-Gracia, Enrique; Lapetra, José; Arós, Fernando; Fiol, Miquel; Ros, Emili; Serra-Majem, Lluís; Pintó, Xavier; Moreno, Juan José; Ruiz-Canela, Miguel; Sorli, Jose Vicente; Basora, Josep; Schröder, Helmut; Lamuela-Raventós, Rosa Maria

2017-04-01

The study of dietary patterns is gaining interest. Although the health benefits of yogurt and lignans have been investigated separately, to our knowledge there are no studies on their associative effects. The aim of this study was to evaluate a possible association between yogurt and lignans using biomarkers of cardiovascular disease risk in an elderly population. We conducted a cross-sectional analysis of the association between baseline dietary information and cardiovascular risk parameters using food frequency questionnaires. We enrolled 7,169 Spanish participants of the PREDIMED (Prevención con Dieta Mediterránea) study (elderly men and women at high cardiovascular risk) from June 2003 to June 2009. Cardiovascular risk parameters, including cholesterol, triglycerides, glucose, body mass index, weight, waist circumference, and blood pressure were measured. General linear models were used to assess the relationship between categorical variables (yogurt, total dairy intake, lignans, and yogurt plus lignans) and cardiovascular risk parameters. The consumption of either yogurt or lignans seems to have beneficial effects on human health, but the consumption of both showed greater improvement in some cardiovascular health parameters. Indeed, participants with a higher consumption of both yogurt and lignans showed lower total cholesterol (estimated β-coefficients=-6.18; P=0.001) and low-density lipoprotein cholesterol levels (β=-4.92; P=0.005). In contrast, participants with lower yogurt and lignan consumption had a higher body mass index (β=0.28; P=0.007) and weight (β=1.20; P=0.008). High lignan and yogurt consumption is associated with a better cardiovascular risk parameters profile in an elderly Mediterranean population. Further research is warranted to determine the mechanisms and consequences of this potential effect. Copyright © 2017 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Simultaneous determination of seven lignans in Justicia procumbens by high performance liquid chromatography-photodiode array detection using relative response factors.

PubMed

Luo, Zuliang; Kong, Weijun; Qiu, Feng; Yang, Meihua; Li, Qian; Wei, Riwei; Yang, Xiaoli; Qin, Jieping

2013-02-01

A simple and sensitive HPLC coupled with photodiode array (HPLC-PDA) method was developed for simultaneous determination of seven lignans in Justicia procumbens using relative response factors (RRFs). The chromatographic separation was performed on a Shiseido Capcell Pak C(18) column (250 × 4.6 mm id, 5 μm), a gradient elution of acetonitrile/water, and a photodiode array detector. The column temperature was maintained at 35°C and the detection wavelength was set at 256 nm. Chinensinaphthol methyl ether was selected as the reference compound for calculating the relative response factors of the lignans. It has shown that the RRFs for lignans are quite similar at 256 nm of detection under different analytical conditions (different columns and HPLC instruments). Using RRFs, not every lignan is needed as a reference standard, making the method ideal for rapid, routine analysis, especially for those laboratories where lignans standards are not readily available. An economic and practicable HPLC method using RRFs was established for the determination of seven lignans in J. procumbens. This method not only can determine multiple indexes in traditional Chinese medicines (TCMs) simultaneously, but also resolve the problem of lacking of chemical standards. It will be a good quality evaluation method and pattern for TCMs. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Phytotoxic properties of nordihydroguaiaretic acid, a lignan fromLarrea tridentata (Creosote bush).

PubMed

Elakovich, S D; Stevens, K L

1985-01-01

The phytotoxic properties of nordihydroguaiaretic acid (NDGA) isolated from creosote bush,Larrea tridentata (Zygophyllaceae), were examined. NDGA dramatically reduces the seedling root growth of barnyard grass, green foxtail, perennial ryegrass, annual ryegrass, red millet, lambsquarter, lettuce, and alfalfa, and reduces the hypocotyl growth of lettuce and green foxtail. It has no effect on the germination of lettuce seeds. NDGA almost certainly contributes to the observed allelopathic nature of creosote bush.

Rapid analysis of lignans from leaves of Podophyllum peltatum l. samples using UPLC-UV-MS

USDA-ARS?s Scientific Manuscript database

A new rapid UPLC-UV-MS method has been developed that permits the analysis of four lignans in P. peltatum L. Podophyllotoxin is a natural lignan that is being used as a precursor for the semi-synthetic anti-cancer drugs etoposide, teniposide and etopophos. The chromatographic separation was achieved...

Rapid analysis of lignans from leaves of Podophyllum peltatum L samples using UPLC-UV-MS

USDA-ARS?s Scientific Manuscript database

A new rapid UPLC-UV-MS method has been developed that permits the analysis of four lignans in P. peltatum L. Podophyllotoxin is a natural lignan that is being used as a precursor for the semi-synthetic anti-cancer drugs etoposide, teniposide and etopophos. The chromatographic separation was achieved...

Investigation of the Lignan Content in Extracts from Linum, Callitris and Juniperus Species in Relation to Their In Vitro Antiproliferative Activities.

PubMed

Doussot, Joël; Mathieu, Véronique; Colas, Cyril; Molinié, Roland; Corbin, Cyrielle; Montguillon, Josiane; Moreno Y Banuls, Laeticia; Renouard, Sullivan; Lamblin, Frédéric; Dupré, Patricia; Maunit, Benoit; Kiss, Robert; Hano, Christophe; Lainé, Eric

2017-04-01

Podophyllotoxin, a lignan still extracted from the rhizomes of Podophyllum hexandrum (Berberidaceae), is the starting molecule for the semisynthesis of widely used anticancer drugs such as etoposide. However, this source is threatened by the over-collection of P. hexandrum . Plants belonging to the Linaceae and Cupressaceae families could be attractive alternative sources with species that contain the lignan podophyllotoxin or its precursors and derivatives. Wild flax species, such as Linum flavum , as well as some Juniperus and Callitris species were investigated for their lignan content, and the in vitro antiproliferative capacity of their extracts was assayed on four tumor cell lines. Some of the lignans were detected by LC-HRMS for the first time in these extracts.In addition, lignans purified from these plants and compounds semisynthesized from commercially available podophyllotoxin were tested in terms of their in vitro antiproliferative activity. The genus Juniperus was the most promising given its in vitro antiproliferative effects, which were also observed with extracts from L. flavum and Callitris species.The in vitro antiproliferative effect of the plant extracts studied here appears to correlate well with the contents of the aryltetralin lignan podophyllotoxin and its glycoside as well as with deoxypodophyllotoxin and 6-methoxypodophyllotoxin. The strongest correlation between the lignan content of the extracts and the antiproliferative activity was observed for 6-methoxypodophyllotoxin. Regarding the possibility of producing large renewable amounts of 6-methoxypodophyllotoxin, this molecule could be of interest to produce new anticancer drugs and to bypass the resistance mechanisms against podophyllotoxin-derived drugs. Georg Thieme Verlag KG Stuttgart · New York.

Natural Hypolignification Is Associated with Extensive Oligolignol Accumulation in Flax Stems1[C][W

PubMed Central

Huis, Rudy; Morreel, Kris; Fliniaux, Ophélie; Lucau-Danila, Anca; Fénart, Stéphane; Grec, Sébastien; Neutelings, Godfrey; Chabbert, Brigitte; Mesnard, François; Boerjan, Wout; Hawkins, Simon

2012-01-01

Flax (Linum usitatissimum) stems contain cells showing contrasting cell wall structure: lignified in inner stem xylem tissue and hypolignified in outer stem bast fibers. We hypothesized that stem hypolignification should be associated with extensive phenolic accumulation and used metabolomics and transcriptomics to characterize these two tissues. 1H nuclear magnetic resonance clearly distinguished inner and outer stem tissues and identified different primary and secondary metabolites, including coniferin and p-coumaryl alcohol glucoside. Ultrahigh-performance liquid chromatography-Fourier transform ion cyclotron resonance-mass spectrometry aromatic profiling (lignomics) identified 81 phenolic compounds, of which 65 were identified, to our knowledge, for the first time in flax and 11 for the first time in higher plants. Both aglycone forms and glycosides of monolignols, lignin oligomers, and (neo)lignans were identified in both inner and outer stem tissues, with a preponderance of glycosides in the hypolignified outer stem, indicating the existence of a complex monolignol metabolism. The presence of coniferin-containing secondary metabolites suggested that coniferyl alcohol, in addition to being used in lignin and (neo)lignan formation, was also utilized in a third, partially uncharacterized metabolic pathway. Hypolignification of bast fibers in outer stem tissues was correlated with the low transcript abundance of monolignol biosynthetic genes, laccase genes, and certain peroxidase genes, suggesting that flax hypolignification is transcriptionally regulated. Transcripts of the key lignan genes Pinoresinol-Lariciresinol Reductase and Phenylcoumaran Benzylic Ether Reductase were also highly abundant in flax inner stem tissues. Expression profiling allowed the identification of NAC (NAM, ATAF1/2, CUC2) and MYB transcription factors that are likely involved in regulating both monolignol production and polymerization as well as (neo)lignan production. PMID:22331411

Pre-diagnostic polyphenol intake and breast cancer survival: the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

PubMed

Kyrø, Cecilie; Zamora-Ros, Raul; Scalbert, Augustin; Tjønneland, Anne; Dossus, Laure; Johansen, Christoffer; Bidstrup, Pernille Envold; Weiderpass, Elisabete; Christensen, Jane; Ward, Heather; Aune, Dagfinn; Riboli, Elio; His, Mathilde; Clavel-Chapelon, Françoise; Baglietto, Laura; Katzke, Verena; Kühn, Tilman; Boeing, Heiner; Floegel, Anna; Overvad, Kim; Lasheras, Cristina; Travier, Noémie; Sánchez, Maria-José; Amiano, Pilar; Chirlaque, Maria-Dolores; Ardanaz, Eva; Khaw, Kay-Tee; Wareham, Nick; Perez-Cornago, Aurora; Trichopoulou, Antonia; Lagiou, Pagona; Vasilopoulou, Effie; Masala, Giovanna; Grioni, Sara; Berrino, Franco; Tumino, Rosario; Sacerdote, Carlotta; Mattiello, Amalia; Bueno-de-Mesquita, H Bas; Peeters, Petra H; van Gils, Carla; Borgquist, Signe; Butt, Salma; Zeleniuch-Jacquotte, Anne; Sund, Malin; Hjartåker, Anette; Skeie, Guri; Olsen, Anja; Romieu, Isabelle

2015-11-01

The aim was to investigate the association between pre-diagnostic intakes of polyphenol classes (flavonoids, lignans, phenolic acids, stilbenes, and other polyphenols) in relation to breast cancer survival (all-cause and breast cancer-specific mortality). We used data from the European Prospective Investigation into Cancer and Nutrition cohort. Pre-diagnostic usual diet was assessed using dietary questionnaires, and polyphenol intakes were estimated using the Phenol-Explorer database. We followed 11,782 breast cancer cases from time of diagnosis until death, end of follow-up or last day of contact. During a median of 6 years, 1482 women died (753 of breast cancer). We related polyphenol intake to all-cause and breast cancer-specific mortality using Cox proportional hazard models with time since diagnosis as underlying time and strata for age and country. Among postmenopausal women, an intake of lignans in the highest versus lowest quartile was related to a 28 % lower risk of dying from breast (adjusted model: HR, quartile 4 vs. quartile 1, 0.72, 95 % CI 0.53; 0.98). In contrast, in premenopausal women, a positive association between lignan intake and all-cause mortality was found (adjusted model: HR, quartile 4 vs. quartile 1, 1.63, 95 % CI 1.03; 2.57). We found no association for other polyphenol classes. Intake of lignans before breast cancer diagnosis may be related to improved survival among postmenopausal women, but may on the contrary worsen the survival for premenopausal women. This suggests that the role of phytoestrogens in breast cancer survival is complex and may be dependent of menopausal status.

Versatile peroxidase as a valuable tool for generating new biomolecules by homogeneous and heterogeneous cross-linking.

PubMed

Salvachúa, Davinia; Prieto, Alicia; Mattinen, Maija-Liisa; Tamminen, Tarja; Liitiä, Tiina; Lille, Martina; Willför, Stefan; Martínez, Angel T; Martínez, María Jesús; Faulds, Craig B

2013-05-10

The modification and generation of new biomolecules intended to give higher molecular-mass species for biotechnological purposes, can be achieved by enzymatic cross-linking. The versatile peroxidase (VP) from Pleurotus eryngii is a high redox-potential enzyme with oxidative activity on a wide variety of substrates. In this study, VP was successfully used to catalyze the polymerization of low molecular mass compounds, such as lignans and peptides, as well as larger macromolecules, such as protein and complex polysaccharides. Different analytical, spectroscopic, and rheological techniques were used to determine structural changes and/or variations of the physicochemical properties of the reaction products. The lignans secoisolariciresinol and hydroxymatairesinol were condensed by VP forming up to 8 unit polymers in the presence of organic co-solvents and Mn(2+). Moreover, 11 unit of the peptides YIGSR and VYV were homogeneously cross-linked. The heterogeneous cross-linking of one unit of the peptide YIGSR and several lignan units was also achieved. VP could also induce gelation of feruloylated arabinoxylan and the polymerization of β-casein. These results demonstrate the efficacy of VP to catalyze homo- and hetero-condensation reactions, and reveal its potential exploitation for polymerizing different types of compounds. Copyright © 2013 Elsevier Inc. All rights reserved.

Micro-matrix solid-phase dispersion coupled with MEEKC for quantitative analysis of lignans in Schisandrae Chinensis Fructus using molecular sieve TS-1 as a sorbent.

PubMed

Chu, Chu; Wei, Mengmeng; Wang, Shan; Zheng, Liqiong; He, Zheng; Cao, Jun; Yan, Jizhong

2017-09-15

A simple and effective method was developed for determining lignans in Schisandrae Chinensis Fructus by using a micro-matrix solid phase dispersion (MSPD) technique coupled with microemulsion electrokinetic chromatography (MEEKC). Molecular sieve, TS-1, was applied as a solid supporting material in micro MSPD extraction for the first time. Parameters that affect extraction efficiency, such as type of dispersant, mass ratio of the sample to the dispersant, grinding time, elution solvent and volume were optimized. The optimal extraction conditions involve dispersing 25mg of powdered Schisandrae samples with 50mg of TS-1 by a mortar and pestle. A grinding time of 150s was adopted. The blend was then transferred to a solid-phase extraction cartridge and the target analytes were eluted with 500μL of methanol. Moreover, several parameters affecting MEEKC separation were studied, including the type of oil, SDS concentration, type and concentration of cosurfactant, and concentration of organic modifier. A satisfactory linearity (R>0.9998) was obtained, and the calculated limits of quantitation were less than 2.77μg/mL. Finally, the micro MSPD-MEEKC method was successfully applied to the analysis of lignans in complex Schisandrae fructus samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Cytotoxic cardiac glycosides and other compounds from Asclepias syriaca.

PubMed

Araya, Juan J; Kindscher, Kelly; Timmermann, Barbara N

2012-03-23

Phytochemical investigation of the dried biomass of Asclepias syriaca afforded five new compounds (1-5), along with 19 known structures. Overall, the secondary metabolites isolated and identified from this plant showed a wide structural diversity including pentacyclic triterpenes, cardiac glycosides, flavonoid glycosides, lignans, a phenylethanoid, and a glycosylated megastigmane. In addition, the isolates were tested against the cancer breast cell line Hs578T, and those showing IC(50) values lower than 50 μM (1 and 6-9) were further investigated in three additional breast cancer cell lines (MCF-7, T47D, and Sk-Br-3) and the normal breast cell line Hs578Bst.

Two-steps extraction of essential oil, polysaccharides and biphenyl cyclooctene lignans from Schisandra chinensis Baill fruits.

PubMed

Cheng, Zhenyu; Yang, Yingjie; Liu, Yan; Liu, Zhigang; Zhou, Hongli; Hu, Haobin

2014-08-05

A method for two-steps extraction of essential oil, polysaccharides and lignans from Schisandra chinensis Baill had been established. Firstly, S. chinensis was extracted by hydro-distillation, the extracted solution was separated from the water-insoluble residue and precipitated by adding dehydrated alcohol after the essential oil was collected, and then the precipitate as polysaccharide was collected. Finally, second extraction was performed to obtained lignans from the water-insoluble residue with ultrasonic-microwave assisted extraction (UMAE) method. Response surface methodology was employed to optimize the UMAE parameters, the optimal conditions were as follows: microwave power 430W, ethanol concentration 84%, particle size of sample 120-mesh sieves, ratio of water to raw material 15 and extraction time 2.1min. Under these optimized conditions, the total extraction yields of five lignans (Schisandrol A, Schisantherin A, Deoxyschisandrin, Schisandrin B and Schisandrin C) had reached 14.22±0.135mg/g. Compared with the traditional method of direct extraction of different bioactive components in respective procedure, the extraction yields of polysaccharides and the five lignans had reached 99% and 95%, respectively. The mean recoveries of the 5 lignan compounds and polysaccharides were 97.75-101.08% and their RSD value was less than 3.88%.The approach proposed in this study not only improved the extraction yield of lignans, but also elevated the utilization of Schisandra resources. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of abomasal infusion of flaxseed (Linum usitatissimum) oil on microbial β-glucuronidase activity and concentration of the mammalian lignan enterolactone in ruminal fluid, plasma, urine and milk of dairy cows.

PubMed

Côrtes, Cristiano; da Silva-Kazama, Daniele; Kazama, Ricardo; Benchaar, Chaouki; dos Santos, Geraldo; Zeoula, Lucia M; Gagnon, N; Petit, Hélène V

2013-02-14

Ruminal microbiota plays an important role in the conversion of plant lignans into mammalian lignans. The main mammalian lignan present in the milk of dairy cows fed flax products is enterolactone (EL). The objectives of the present study were to investigate the effects of abomasal infusion of flax oil on the metabolism of flax lignans and concentrations of EL in biological fluids of dairy cows. A total of six rumen-cannulated dairy cows were assigned within a 2 × 3 factorial arrangement of six treatments utilising flax hulls (0 and 15·9 % of DM) and abomasal infusion of flax oil (0, 250 and 500 g/d). There were six periods of 21 d each. Samples were collected during the last 7 d of each period and subjected to chemical analysis. Flax hull supplementation increased concentrations of EL in ruminal fluid, plasma, urine and milk, while flax oil infusion had no effect. Post-feeding, β-glucuronidase activity in the ruminal fluid of cows infused with 250 g flax oil was significantly lower for cows fed hulls than for those fed the control diet. The present study demonstrated that the presence of a rich source of n-3 fatty acids such as flax oil in the small intestine does not interfere with the absorption of the mammalian lignan EL and that lower ruminal β-glucuronidase activity had no effect on the conversion of flax lignans into EL in the rumen of dairy cows.

The Cytochrome P450-Mediated Metabolism Alternation of Four Effective Lignans From Schisandra chinensis in Carbon Tetrachloride-Intoxicated Rats and Patients With Advanced Hepatocellular Carcinoma

PubMed Central

Wu, Rongrong; Xiao, Zhiyong; Zhang, Xiaorui; Liu, Feng; Zhou, Wenxia; Zhang, Yongxiang

2018-01-01

It is highly valuable to study the pharmacokinetics of herbal components under the pathological condition of liver dysfunction for safe and rational use of herbal medicines. In this study, the pharmacokinetic profiles of four effective lignans from Schisandra chinensis (SC), schisandrin, schisantherin A, deoxyshisandrin and γ-schisandrin, were investigated in carbon tetrachloride (CCl4)-intoxicated rats. The metabolism of the four lignans was also studied using microsomes from patients with advanced hepatocellular carcinoma. In situ intestinal and hepatic perfusions were conducted to clarify the contributions from impairments of gut and liver on the pharmacokinetics of the four schisandra lignans in CCl4-intoxicated rats. The metabolism in rat and human liver microsomes and transport in Caco-2 monolayer cell model were studied to reveal the key factors for the in vivo disposition of the four lignans. When SC alcoholic extract was orally administrated to CCl4-intoxicated rat for a short term (4 days), the pharmacokinetics of four active SC lignans was significantly changed while its hepatotherapeutic effect was not obviously observed. The plasma concentrations of the four schisandra lignans were dramatically elevated compared with the control. The Cmax, AUC and MRT were all increased or prolonged significantly while parameter CLz/F was obviously reduced in rat pretreated with CCl4. In hepatic perfusion study and liver microsomes incubation, it was found that the hepatic metabolism of the four lignans was markedly decreased mainly due to the activity reduction of multiple CYP450 isoenzymes involved the metabolism, which, eventually, might lead to the alternation of their pharmacokinetic profiles in CCl4-intoxicated rats or patients with advanced hepatocellular carcinoma. The pharmacokinetic studies of SC components in pathological situation of liver dysfunction are expected to provide useful data for rational and safe application of SC preparations in clinic or further pharmacological and toxicological research. PMID:29593545

The Cytochrome P450-Mediated Metabolism Alternation of Four Effective Lignans From Schisandra chinensis in Carbon Tetrachloride-Intoxicated Rats and Patients With Advanced Hepatocellular Carcinoma.

PubMed

Wu, Rongrong; Xiao, Zhiyong; Zhang, Xiaorui; Liu, Feng; Zhou, Wenxia; Zhang, Yongxiang

2018-01-01

It is highly valuable to study the pharmacokinetics of herbal components under the pathological condition of liver dysfunction for safe and rational use of herbal medicines. In this study, the pharmacokinetic profiles of four effective lignans from Schisandra chinensis (SC) , schisandrin, schisantherin A, deoxyshisandrin and γ-schisandrin, were investigated in carbon tetrachloride (CCl 4 )-intoxicated rats. The metabolism of the four lignans was also studied using microsomes from patients with advanced hepatocellular carcinoma. In situ intestinal and hepatic perfusions were conducted to clarify the contributions from impairments of gut and liver on the pharmacokinetics of the four schisandra lignans in CCl 4 -intoxicated rats. The metabolism in rat and human liver microsomes and transport in Caco-2 monolayer cell model were studied to reveal the key factors for the in vivo disposition of the four lignans. When SC alcoholic extract was orally administrated to CCl 4 -intoxicated rat for a short term (4 days), the pharmacokinetics of four active SC lignans was significantly changed while its hepatotherapeutic effect was not obviously observed. The plasma concentrations of the four schisandra lignans were dramatically elevated compared with the control. The Cmax, AUC and MRT were all increased or prolonged significantly while parameter CLz/F was obviously reduced in rat pretreated with CCl 4 . In hepatic perfusion study and liver microsomes incubation, it was found that the hepatic metabolism of the four lignans was markedly decreased mainly due to the activity reduction of multiple CYP450 isoenzymes involved the metabolism, which, eventually, might lead to the alternation of their pharmacokinetic profiles in CCl 4 -intoxicated rats or patients with advanced hepatocellular carcinoma. The pharmacokinetic studies of SC components in pathological situation of liver dysfunction are expected to provide useful data for rational and safe application of SC preparations in clinic or further pharmacological and toxicological research.

Terpene and lignan glycosides from the twigs and leaves of an endangered conifer, Cathaya argyrophylla.

PubMed

He, Wen-Jun; Fu, Zhao-Hui; Zeng, Guang-Zhi; Zhang, Yu-Mei; Han, Hong-Jin; Yan, He; Ji, Chang-Jiu; Chu, Hong-Biao; Tan, Ning-Hua

2012-11-01

Labdane diterpene glycosides cathargyroside A and cathargyroside B, monoterpene glycosides vervenone-10-O-β-D-glucopyranoside and vervenone-10-O-β-D-apiofuranosyl-(1″→6')-β-D-glucopyranoside, as well as lignan glycosides cedrusinin-4-O-α-L-rhamnopyranoside and (+)-cyclo-olivil-9'-O-β-D-xylopyranoside, along with 39 known compounds, were obtained from the methanol extract of the twigs and leaves of Cathaya argyrophylla. These compounds were identified mainly by analyzing their NMR and MS data. Almost all of these compounds were hitherto unknown in this genus. The isolated compounds were screened against Candida albicans and Staphylococcus aureus for antimicrobial assay, and against K562, HT-29, BEL-7402, SGC-7901, B16, BGC-823, U251 and A549 cancer cell lines for cytotoxic activities. One compound showed antimicrobial activity against C. albicans, and four of them displayed cytotoxicity. Similarity analysis on the chemical constituents of the genera Cathaya, Picea and Pinus supported their close phylogenetic relationships. Copyright © 2012 Elsevier Ltd. All rights reserved.

Phenolic and lignan glycosides from the butanol extract of Averrhoa carambola L. root.

PubMed

Wen, Qingwei; Lin, Xing; Liu, Yeqi; Xu, Xiaohui; Liang, Tao; Zheng, Ni; Kintoko; Huang, Renbin

2012-10-19

Fifteen compounds, which included six chiral lignans and nine phenolic glycosides, were separated from the butanol fraction of Averrhoa carambola L. root and identified. All of the compounds, namely 3,4,5-trimethoxyphenol-1-O-β-D-glucopyranoside, benzyl-1-O-β-D-glucopyranoside, (+)-5'-methoxyisolariciresinol 3α-O-β-D-gluco-pyranoside, (+)-isolariciresinol 3α-O-β-D-glucopyranoside, koaburaside, (+)-lyoniresinol 3α-O-β-D-glucopyranoside, (-)-lyoniresinol 3α-O-β-D-glucopyranoside, (-)-5'-methoxyisolariciresinol 3α-O-β-D-glucopyranoside, (-)-isolariciresinol 3α-O-β-D-glucopyranoside, 3,5-dimethoxy-4-hydroxyphenyl 1-O-β-apiofuranosyl (1''→6')-O-β-D-glucopyranoside, 3,4,5-trimethoxyphenyl 1-O-β-apiofuranosyl (1''→6')-β-gluco-pyranoside, methoxyhydroquinone-4-β-D-glucopyranoside, (2S)-2-O-β-D-gluco-pyranosyl-2-hydroxyphenylacetic acid, 3-hydroxy-4-methoxyphenol 1-O-β-D-apio-furanosyl-(1''→6')-O-β-D-glucopyranoside and 4-hydroxy-3-methoxyphenol 1-O-β-D-apiofuranosyl-(1''→6')-O-β-D-glucopyranoside were isolated from this plant for the first time.

New Thymoquinol Glycosides and Neuroprotective Dibenzocyclooctane Lignans from the Rattan Stems of Schisandra chinensis.

PubMed

Yang, Bing-You; Guo, Jiang-Tao; Li, Zu-Yi; Wang, Chang-Fu; Wang, Zhi-Bin; Wang, Qiu-Hong; Kuang, Hai-Xue

2016-09-01

Three new lignans (1 - 3), together with four new thymoquinol glycosides (4 - 7), were isolated from 70%-EtOH extract of the rattan stems of Schisandra chinensis. The structures of 1 - 7 were elucidated by detailed spectroscopic analyses, and these new compounds were identified as pinobatol-9-O-β-d-glucopyranoside (1), 1,2,13,14-tetramethoxydibenzocyclooctadiene 3,12-O-β-d-diglucopyranoside (2), 3,7-dihydroxy-1,2,13,14-tetramethoxydibenzocyclooctadiene 12-O-β-d-glucopyranoside (3), thymoquinol 2-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside (4), thymoquinol 2-O-α-d-arabinofuranosyl-(1→6)-β-d-glucopyranoside (5), thymoquinol 5-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside (6), and thymoquinol 5-O-α-d-arabinofuranosyl-(1→6)-β-d-glucopyranoside (7). The neuroprotective activity of 1 - 7 was evaluated on PC12 cells with neurotoxicity induced by amyloid-beta 1 - 42 (Aβ 1 - 42 ). Compounds 2 and 3 showed protecting activity against Aβ-induced toxicity in PC12 cells. © 2016 Wiley-VHCA AG, Zürich.

Bioactive Compounds from Vitex leptobotrys#

PubMed Central

Pan, Wenhui; Liu, Kanglun; Guan, Yifu; Tan, Ghee Teng; Hung, Nguyen Van; Cuong, Nguyen Manh; Soejarto, D. Doel; Pezzuto, John M.; Fong, Harry H.S.; Zhang, Hongjie

2014-01-01

A new lignan, vitexkarinol (1), as well as a known lignan, neopaulownin (2), a known chalcone, 3-(4-hydroxyphenyl)-1-(2,4,6-trimethoxyphenyl)-2-propen-1-one (3), two known dehydroflavones, tsugafolin (4) and alpinetin (5), two known dipeptides, aurantiamide and aurantiamide acetate, a known sesquiterpene, vemopolyanthofuran, and five known carotenoid metabolites, vomifoliol, dihydrovomifoliol, dehydrovomifoliol, loliolide and isololiolide, were isolated from the leaves and twigs of Vitex leptobotrys through bioassay-guided fractionation. The chalcone (3) was found to inhibit HIV-1 replication by 77% at 15.9 µM, and the two dehydroflavones (4 and 5) showed weak anti-HIV activity with IC50 values of 118 and 130 µM, respectively, while being devoid of cytotoxicity at 150 µM. A chlorophyll-enriched fraction of V. leptobotrys, containing pheophorbide a, was found to inhibit the replication of HIV-1 by 80% at a concentration of 10 µg/mL. Compounds 1 and 3 were further selected to be evaluated against 21 viral targets available at NIAID (National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD). PMID:24404757

Lignans from the root of Wikstroemia indica and their cytotoxic activity against PANC-1 human pancreatic cancer cells.

PubMed

Chang, Hang; Wang, Yuwei; Gao, Xue; Song, Zehai; Awale, Suresh; Han, Na; Liu, Zhihui; Yin, Jun

2017-09-01

Six new compounds, wikstronin A (1), wikstronin B (2), wikstresinol (3), acetylwikstresinol (4), bis-5',5'-(+)-matairesinol (5), bis-5,5'-(+)-matairesinol (6), together with 20 known compounds (7-26) were isolated from the CH 2 Cl 2 extract of roots of Wikstroemia indica. Structures of compounds 1-6 were determined by extensive NMR and CD spectroscopic analysis. In vitro preferential cytotoxicity of all the isolates was evaluated against a PANC-1 human pancreatic cell line. Compounds 8 and 12 displayed mild preferential cytotoxicity in the nutrient-deprived medium (NDM) and without causing toxicity in normal nutrient-rich conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

Enhancing lignan biosynthesis by over-expressing pinoresinol lariciresinol reductase in transgenic wheat.

PubMed

Ayella, Allan K; Trick, Harold N; Wang, Weiqun

2007-12-01

Lignans are phenylpropane dimers that are biosynthesized via the phenylpropanoid pathway, in which pinoresinol lariciresinol reductase (PLR) catalyzes the last steps of lignan production. Our previous studies demonstrated that the contents of lignans in various wheat cultivars were significantly associated with anti-tumor activities in APC(Min) mice. To enhance lignan biosynthesis, this study was conducted to transform wheat cultivars ('Bobwhite', 'Madison', and 'Fielder', respectively) with the Forsythia intermedia PLR gene under the regulatory control of maize ubiquitin promoter. Of 24 putative transgenic wheat lines, we successfully obtained 3 transformants with the inserted ubiquitin-PLR gene as screened by PCR. Southern blot analysis further demonstrated that different copies of the PLR gene up to 5 were carried out in their genomes. Furthermore, a real-time PCR indicated approximately 17% increase of PLR gene expression over the control in 2 of the 3 positive transformants at T(0) generation. The levels of secoisolariciresinol diglucoside, a prominent lignan in wheat as determined by HPLC-MS, were found to be 2.2-times higher in one of the three positive transgenic sub-lines at T(2 )than that in the wild-type (117.9 +/- 4.5 vs. 52.9 +/- 19.8 mug/g, p <0.005). To the best of our knowledge, this is the first study that elevated lignan levels in a transgenic wheat line has been successfully achieved through genetic engineering of over-expressed PLR gene. Although future studies are needed for a stably expression and more efficient transformants, the new wheat line with significantly higher SDG contents obtained from this study may have potential application in providing additive health benefits for cancer prevention.

Metabolism of Secoisolariciresinol-Diglycoside The Dietary Precursor to The Intestinally Derived Lignan Enterolactone in Humans

PubMed Central

Setchell, Kenneth D. R.; Brown, Nadine M.; Zimmer-Nechemias, Linda; Wolfe, Brian; Jha, Pinky; Heubi, James E.

2014-01-01

Secoisolariciresinol-diglycoside (SDG), a natural dietary lignan of flaxseeds now available in dietary supplements, is converted by intestinal bacteria to the mammalian lignans enterodiol and enterolactone. High levels of these lignans in blood and urine are associated with reduced risk of many chronic diseases. Our objective was to determine the bioavailability and pharmacokinetics of SDG in purified flaxseed extracts under dose-ranging and steady-state conditions, and to examine whether differences in secoisolariciresinol-diglycoside purity influence bioavailability. Pharmacokinetic studies were performed on healthy postmenopausal women after oral intake of 25, 50, 75, 86 and 172mg of secoisolariciresinol-diglycoside. Extracts differing in secoisolariciresinol-diglycoside purity were compared, and steady-state lignan concentrations measured after daily intake for one week. Blood and urine samples were collected at timed intervals and secoisolariciresinol, enterodiol and enterolactone concentrations measured by mass spectrometry. Secoisolariciresinol-diglycoside was efficiently hydrolyzed and converted to secoisolariciresinol. Serum concentrations increased rapidly after oral intake, peaking after 5-7h and disappearing with a plasma elimination half-life of 4.8h. Maximum serum concentrations of the biologically active metabolites, enterodiol and enterolactone were established after 12-24h and 24-36h, respectively, and the half-lives were 9.4h and 13.2h. Linear dose-responses were observed and secoisolariciresinol bioavailability correlated (r2=0.835) with cumulative lignan excretion. There were no significant differences in the pharmacokinetics of extracts differing in purity, and steady-state serum lignan concentrations were obtained after one-week of daily dosing. In conclusion, this study defines the pharmacokinetics of secoisolariciresinol-diglycoside and shows it is first hydrolyzed and then metabolized in a time-dependent sequence to secoisolariciresinol, enterodiol and ultimately enterolactone, and these metabolites are efficiently absorbed. PMID:24429845

Metabolism of secoisolariciresinol-diglycoside the dietary precursor to the intestinally derived lignan enterolactone in humans.

PubMed

Setchell, Kenneth D R; Brown, Nadine M; Zimmer-Nechemias, Linda; Wolfe, Brian; Jha, Pinky; Heubi, James E

2014-03-01

Secoisolariciresinol-diglycoside (SDG), a natural dietary lignan of flaxseeds now available in dietary supplements, is converted by intestinal bacteria to the mammalian lignans enterodiol and enterolactone. High levels of these lignans in blood and urine are associated with reduced risk of many chronic diseases. Our objective was to determine the bioavailability and pharmacokinetics of SDG in purified flaxseed extracts under dose-ranging and steady-state conditions, and to examine whether differences in secoisolariciresinol-diglycoside purity influence bioavailability. Pharmacokinetic studies were performed on healthy postmenopausal women after oral intake of 25, 50, 75, 86 and 172 mg of secoisolariciresinol-diglycoside. Extracts differing in secoisolariciresinol-diglycoside purity were compared, and steady-state lignan concentrations measured after daily intake for one week. Blood and urine samples were collected at timed intervals and secoisolariciresinol, enterodiol and enterolactone concentrations measured by mass spectrometry. Secoisolariciresinol-diglycoside was efficiently hydrolyzed and converted to secoisolariciresinol. Serum concentrations increased rapidly after oral intake, peaking after 5-7 h and disappearing with a plasma elimination half-life of 4.8 h. Maximum serum concentrations of the biologically active metabolites, enterodiol and enterolactone were attained after 12-24 h and 24-36 h, respectively, and the half-lives were 9.4 h and 13.2 h. Linear dose-responses were observed and secoisolariciresinol bioavailability correlated (r(2) = 0.835) with cumulative lignan excretion. There were no significant differences in the pharmacokinetics of extracts differing in purity, and steady-state serum lignan concentrations were obtained after one-week of daily dosing. In conclusion, this study defines the pharmacokinetics of secoisolariciresinol-diglycoside and shows it is first hydrolyzed and then metabolized in a time-dependent sequence to secoisolariciresinol, enterodiol and ultimately enterolactone, and these metabolites are efficiently absorbed.

Gene-to-metabolite network for biosynthesis of lignans in MeJA-elicited Isatis indigotica hairy root cultures

PubMed Central

Chen, Ruibing; Li, Qing; Tan, Hexin; Chen, Junfeng; Xiao, Ying; Ma, Ruifang; Gao, Shouhong; Zerbe, Philipp; Chen, Wansheng; Zhang, Lei

2015-01-01

Root and leaf tissue of Isatis indigotica shows notable anti-viral efficacy, and are widely used as “Banlangen” and “Daqingye” in traditional Chinese medicine. The plants' pharmacological activity is attributed to phenylpropanoids, especially a group of lignan metabolites. However, the biosynthesis of lignans in I. indigotica remains opaque. This study describes the discovery and analysis of biosynthetic genes and AP2/ERF-type transcription factors involved in lignan biosynthesis in I. indigotica. MeJA treatment revealed differential expression of three genes involved in phenylpropanoid backbone biosynthesis (IiPAL, IiC4H, Ii4CL), five genes involved in lignan biosynthesis (IiCAD, IiC3H, IiCCR, IiDIR, and IiPLR), and 112 putative AP2/ERF transcription factors. In addition, four intermediates of lariciresinol biosynthesis were found to be induced. Based on these results, a canonical correlation analysis using Pearson's correlation coefficient was performed to construct gene-to-metabolite networks and identify putative key genes and rate-limiting reactions in lignan biosynthesis. Over-expression of IiC3H, identified as a key pathway gene, was used for metabolic engineering of I. indigotica hairy roots, and resulted in an increase in lariciresinol production. These findings illustrate the utility of canonical correlation analysis for the discovery and metabolic engineering of key metabolic genes in plants. PMID:26579184

Schisandra lignans production regulated by different bioreactor type.

PubMed

Szopa, Agnieszka; Kokotkiewicz, Adam; Luczkiewicz, Maria; Ekiert, Halina

2017-04-10

Schisandra chinensis (Chinese magnolia vine) is a rich source of therapeutically relevant dibenzocyclooctadiene lignans with anticancer, immunostimulant and hepatoprotective activities. In this work, shoot cultures of S. chinensis were grown in different types of bioreactors with the aim to select a system suitable for the large scale in vitro production of schisandra lignans. The cultures were maintained in Murashige-Skoog (MS) medium supplemented with 3mg/l 6-benzylaminopurine (BA) and 1mg/l 1-naphthaleneacetic acid (NAA). Five bioreactors differing with respect to cultivation mode were tested: two liquid-phase systems (baloon-type bioreactor and bubble-column bioreactor with biomass immobilization), the gas-phase spray bioreactor and two commercially available temporary immersion systems: RITA ® and Plantform. The experiments were run for 30 and 60 days in batch mode. The harvested shoots were evaluated for growth and lignan content determined by LC-DAD and LC-DAD-ESI-MS. Of the tested bioreactors, temporary immersion systems provided the best results with respect to biomass production and lignan accumulation: RITA ® bioreactor yielded 17.86g/l (dry weight) during 60 day growth period whereas shoots grown for 30 days in Plantform bioreactor contained the highest amount of lignans (546.98mg/100g dry weight), with schisandrin, deoxyschisandrin and gomisin A as the major constituents (118.59, 77.66 and 67.86mg/100g dry weight, respectively). Copyright © 2017 Elsevier B.V. All rights reserved.

Regiochemical control of monolignol radical coupling: a new paradigm for lignin and lignan biosynthesis

NASA Technical Reports Server (NTRS)

Gang, D. R.; Costa, M. A.; Fujita, M.; Dinkova-Kostova, A. T.; Wang, H. B.; Burlat, V.; Martin, W.; Sarkanen, S.; Davin, L. B.; Lewis, N. G.

1999-01-01

BACKGROUND: Although the lignins and lignans, both monolignol-derived coupling products, account for nearly 30% of the organic carbon circulating in the biosphere, the biosynthetic mechanism of their formation has been poorly understood. The prevailing view has been that lignins and lignans are produced by random free-radical polymerization and coupling, respectively. This view is challenged, mechanistically, by the recent discovery of dirigent proteins that precisely determine both the regiochemical and stereoselective outcome of monolignol radical coupling. RESULTS: To understand further the regulation and control of monolignol coupling, leading to both lignan and lignin formation, we sought to clone the first genes encoding dirigent proteins from several species. The encoding genes, described here, have no sequence homology with any other protein of known function. When expressed in a heterologous system, the recombinant protein was able to confer strict regiochemical and stereochemical control on monolignol free-radical coupling. The expression in plants of dirigent proteins and proposed dirigent protein arrays in developing xylem and in other lignified tissues indicates roles for these proteins in both lignan formation and lignification. CONCLUSIONS: The first understanding of regiochemical and stereochemical control of monolignol coupling in lignan biosynthesis has been established via the participation of a new class of dirigent proteins. Immunological studies have also implicated the involvement of potential corresponding arrays of dirigent protein sites in controlling lignin biopolymer assembly.

Stereoselectivity in Polyphenol Biosynthesis

NASA Technical Reports Server (NTRS)

Lewis, Norman G.; Davin, Laurence B.

1992-01-01

Stereoselectivity plays an important role in the late stages of phenyl-propanoid metabolism, affording lignins, lignans, and neolignans. Stereoselectivity is manifested during monolignol (glucoside) synthesis, e.g., where the geometry (E or Z) of the pendant double bond affects the specificity of UDPG:coniferyl alcohol glucosyltransferases in different species. Such findings are viewed to have important ramifications in monolignol transport and storage processes, with roles for both E- and Z-monolignols and their glucosides in lignin/lignan biosynthesis being envisaged. Stereoselectivity is also of great importance in enantiose-lective enzymatic processes affording optically active lignans. Thus, cell-free extracts from Forsythia species were demonstrated to synthesize the enantiomerically pure lignans, (-)-secoisolariciresinol, and (-)-pinoresinol, when NAD(P)H, H2O2 and E-coniferyl alcohol were added. Progress toward elucidating the enzymatic steps involved in such highly stereoselective processes is discussed. Also described are preliminary studies aimed at developing methodologies to determine the subcellular location of late-stage phenylpropanoid metabolites (e.g., coniferyl alcohol) and key enzymes thereof, in intact tissue or cells. This knowledge is essential if questions regarding lignin and lignan tissue specificity and regulation of these processes are to be deciphered.

Regioselective alkali metal reduction of dibenzocyclooctadiene lignan derivatives, demethoxylation followed by dehalogenation.

PubMed

Wang, Qing-Yao; Fang, Jia-Qi; Deng, Lu-Lu; Hao, Xiao-Jiang; Mu, Shu-Zhen

2017-12-27

The regioselective demethoxylation and dehalogenation of dihalogenated dibenzocyclooctadiene lignans derivatives were realized in a one-step reaction with excellent yields in the sodium and t-butanol reaction system.

Chemical and biological evaluation on scopadulane-type diterpenoids from Scoparia dulcis of Vietnamese origin.

PubMed

Phan, Minh Giang; Phan, Tong Son; Matsunami, Katsuyoshi; Otsuka, Hideaki

2006-04-01

From the aerial parts of Scoparia dulcis L. (Scrophulariaceae) grown in Vietnam, four scopadulane-type diterpenoids (4-7), of which 7 is new and was given the trivial name scopadulcic acid C, together with nine known compounds were isolated. Their structures were elucidated by spectroscopic analyses. The absolute configurations of 4-7 were ascertained by applying the modified Mosher's method to iso-dulcinol (6). The isolation of the lignans nirtetralin and niranthin for the first time from S. dulcis is also of chemotaxonomic interest. The cytotoxic activity in KB cells, inhibitory effect on LPS/IFNgamma-induced NO production, inhibition of multidrug resistance (MDR), and antibacterial and antifungal activities of the scopadulane-type diterpenoids 4-7 were examined in this study.

Antibacterial Compounds from Propolis of Tetragonula laeviceps and Tetrigona melanoleuca (Hymenoptera: Apidae) from Thailand

PubMed Central

Sanpa, Sirikarn; Popova, Milena; Bankova, Vassya; Tunkasiri, Tawee; Eitssayeam, Sukum; Chantawannakul, Panuwan

2015-01-01

This study investigated the chemical composition and antimicrobial activity of propolis collected from two stingless bee species Tetragonula laeviceps and Tetrigona melanoleuca (Hymenoptera: Apidae). Six xanthones, one triterpene and one lignane were isolated from Tetragonula laeviceps propolis. Triterpenes were the main constituents in T. melanoleuca propolis. The ethanol extract and isolated compounds from T. laeviceps propolis showed a higher antibacterial activity than those of T. melanoleuca propolis as the constituent α-mangostin exhibited the strongest activity. Xanthones were found in propolis for the first time; Garcinia mangostana (Mangosteen) was the most probable plant source. In addition, this is the first report on the chemical composition and bioactivity of propolis from T. melanoleuca. PMID:25992582

Lignans from the seeds of Chinese hawthorn (Crataegus pinnatifida var. major N.E.Br.) against β-amyloid aggregation.

PubMed

Huang, Xiao-Xiao; Xu, Yang; Bai, Ming; Zhou, Le; Song, Shao-Jiang; Wang, Xiao-Bo

2017-11-08

Phytochemical investigation on the seeds of hawthorn (Crataegus spp.) led to the isolation of a new compound, (7'R, 8'R, 8S)-isolariciresinol (1), along with six known compounds (2-7). The structures of all compounds were determined based on spectroscopic data interpretation. The Aβ 1-42 inhibition activity of all isolated compounds was evaluated in vitro. As a result, compounds 5 and 6 showed stronger inhibition of Aβ 1-42 aggregation than curcumin, with inhibition rates of 70.59 and 68.14% at 20 μM. The possible mechanism of interaction between Aβ 1-42 and the active compounds 5 and 6 was also investigated by molecular docking.

Comparative pharmacokinetics and tissue distribution profiles of lignan components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe.

PubMed

Yang, Tao; Liu, Shan; Zheng, Tian-Hui; Tao, Yan-Yan; Liu, Cheng-Hai

2015-05-26

Fuzheng Huayu recipe (FZHY) is formulated on the basis of Chinese medicine theory in treating liver fibrosis. To illuminate the influence of the pathological state of liver fibrosis on the pharmacokinetics and tissue distribution profiles of lignan components from FZHY. Male Wistar rats were randomly divided into normal group and Hepatic fibrosis group (induced by dimethylnitrosamine). Six lignan components were detected and quantified by ultrahigh performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)in the plasma and tissue of normal and hepatic fibrosis rats. A rapid, sensitive and convenient UHPLC-MS/MS method has been developed for the simultaneous determination of six lignan components in different rat biological samples successfully. After oral administration of FZHY at a dose of 15g/kg, the pharmacokinetic behaviors of schizandrin A (SIA), schizandrin B (SIB), schizandrin C (SIC), schisandrol A (SOA), Schisandrol B (SOB) and schisantherin A (STA) have been significantly changed in hepatic fibrosis rats compared with the normal rats, and their AUC(0-t) values were increased by 235.09%, 388.44%, 223.30%, 669.30%, 295.08% and 267.63% orderly (P<0.05). Tissue distribution results showed the amount of SIA, SIB, SOA and SOB were significant increased in heart, lung, spleen and kidney of hepatic fibrosis rats compared with normal rats at most of the time point (P<0.05). Meanwhile, the result also reveals that the hepatic fibrosis could delay the peak time of lignans in liver. The results proved that the established UHPLC-MS/MS method could be applied to the comparative study on pharmacokinetics and tissue distribution of lignan components in normal and hepatic fibrosis rats. The hepatic fibrosis could alter the pharmacokinetics and tissue distribution properties of lignan components in rats after administration of FZHY. The results might be helpful for guide the clinical application of this medicine. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Impact of a lignan-rich diet on adiposity and insulin sensitivity in post-menopausal women.

PubMed

Morisset, Anne-Sophie; Lemieux, Simone; Veilleux, Alain; Bergeron, Jean; John Weisnagel, S; Tchernof, André

2009-07-01

There has been a growing interest in lignans, a class of phyto-oestrogens, because of their potentially favourable effects on human health. The aim of the present study was to compare the metabolic profile of post-menopausal women consuming various amounts of dietary lignans. Phyto-oestrogen intake was assessed using a 3-d dietary record analysed with a Canadian food phyto-oestrogen content data table in 115 post-menopausal women (age 56.8 (SD 4.4) years and BMI 28.5 (SD 5.9) kg/m(2)). Plasma enterolactone (ENL), the major biologically active metabolite of dietary lignans, was determined by time-resolved fluoroimmunoassay. Anthropometrics, abdominal adipose tissue areas (computed tomography), body composition (hydrostatic weighing) and insulin sensitivity (hyperinsulinaemic-euglycaemic clamp) were measured in all women. Women in the high dietary lignan intake subgroup (n 29) had a significantly lower BMI and total body fat mass, as well as a better glucose disposal rate (GDR; P < 0.05), compared with women in the low lignan intake subgroup (n 28). The majority of women with the highest dietary lignan intake were also in the highest quartile of plasma ENL (59 %). Women in the highest ENL quartile had a significantly lower BMI (26.1 (SD 4.4) v. 30.4 (SD 6.9) kg/m(2), P < 0.05), total body fat mass (24.8 (SD 9.8) v. 33.3 (SD 13.3) kg, P < 0.05), 2 h postload glycaemia (5.5 (SD 0.9) v. 5.7 (sd 0.8) nmol/l, P < 0.05) and a higher GDR (8.3 (SD 2.7) v. 5.5 (SD 2.8), P < 0.01) compared with women in the lowest ENL quartile. In conclusion, women with the highest ENL concentrations had a better metabolic profile including higher insulin sensitivity and lower adiposity measures.

Furanolabdane diterpenes from Hypoestes purpurea.

PubMed

Shen, Chien-Chang; Ni, Ching-Li; Huang, Yu-Ling; Huang, Ray-Ling; Chen, Chien-Chih

2004-11-01

Four new furanolabdane diterpenes, hypopurin A (1), hypopurin B (2), hypopurin C (3), and hypopurin D (4), together with eight lignans, alpha-O-methylcubebin, beta-O-methylcubebin, hinoquinin, helioxanthin, 7-hydroxyhinokinin, dehydroxycubebin, justicidine E, and (-)-hibalactone, as well as two triterpenes, lupeol and betulin, were isolated from the dried aerial part of Hypoestes purpurea. The structures of 1-4 were elucidated mainly on the basis of NMR and MS. Compound 1 was found to be moderately cytotoxic toward the KB cell line with an IC(50) value of 9.4 microM.

Potential Mechanism of Action of 3'-Demethoxy-6-O-demethyl-isoguaiacin on Methicillin Resistant Staphylococcus aureus.

PubMed

Favela-Hernández, Juan Manuel J; Clemente-Soto, Aldo F; Balderas-Rentería, Isaías; Garza-González, Elvira; Camacho-Corona, María del Rayo

2015-07-08

Bacterial infections represent one of the main threats to global public health. One of the major causative agents associated with high morbidity and mortality infections in hospitals worldwide is methicillin-resistant Staphylococcus aureus. Therefore, there is a need to develop new antibacterial agents to treat these infections, and natural products are a rich source of them. In previous studies, we reported that lignan 3'-demethoxy-6-O-demethylisoguaiacin, isolated and characterized from Larrea tridentate, showed the best activity towards methicillin-resistant S. aureus. Thus, the aim of this study was to determine the potential molecular mechanism of the antibacterial activity of 3'-demethoxy-6-O-demethylisoguaiacin against methicillin-resistant S. aureus using microarray technology. Results of microarray genome expression were validated by real-time polymerase chain reaction (RT-PCR). The genetic profile expression results showed that lignan 3'-demethoxy-6-O-demethylisoguaiacin had activity on cell membrane affecting proteins of the ATP-binding cassette (ABC) transport system causing bacteria death. This molecular mechanism is not present in any antibacterial commercial drug and could be a new target for the development of novel antibacterial agents.

Potential mechanism of action of 3'-demethoxy-6-O-demethyl-isoguaiacin on methicillin resistant Staphylococcus aureus.

PubMed

Favela-Hernández, Juan Manuel J; Clemente-Soto, Aldo F; Balderas-Rentería, Isaías; Garza-González, Elvira; Camacho-Corona, María Del Rayo

2015-07-08

Bacterial infections represent one of the main threats to global public health. One of the major causative agents associated with high morbidity and mortality infections in hospitals worldwide is methicillin-resistant Staphylococcus aureus. Therefore, there is a need to develop new antibacterial agents to treat these infections, and natural products are a rich source of them. In previous studies, we reported that lignan 3'-demethoxy-6-O-demethylisoguaiacin, isolated and characterized from Larrea tridentate, showed the best activity towards methicillin-resistant S. aureus. Thus, the aim of this study was to determine the potential molecular mechanism of the antibacterial activity of 3'-demethoxy-6-O-demethylisoguaiacin against methicillin-resistant S. aureus using microarray technology. Results of microarray genome expression were validated by real-time polymerase chain reaction (RT-PCR). The genetic profile expression results showed that lignan 3'-demethoxy-6-O-demethylisoguaiacin had activity on cell membrane affecting proteins of the ATP-binding cassette (ABC) transport system causing bacteria death. This molecular mechanism is not present in any antibacterial commercial drug and could be a new target for the development of novel antibacterial agents.

The western red cedar (Thuja plicata) 8-8' DIRIGENT family displays diverse expression patterns and conserved monolignol coupling specificity

NASA Technical Reports Server (NTRS)

Kim, Myoung K.; Jeon, Jae-Heung; Fujita, Masayuki; Davin, Laurence B.; Lewis, Norman G.

2002-01-01

The isolation and characterization of a multigene family of the first class of dirigent proteins (namely that mainly involved in 8-8' coupling leading to (+)-pinoresinol in this case) is reported, this comprising of nine western red cedar (Thuja plicata) DIRIGENT genes (DIR1-9) of 72-99.5% identity to each other. Their corresponding cDNA clones had coding regions for 180-183 amino acids with each having a predicted molecular mass of ca. 20 kDa including the signal peptide. Real time-PCR established that the DIRIGENT isovariants were differentially expressed during growth and development of T. plicata (P < 0.05). The phylogenetic relationships and the rates and patterns of nucleotide substitution suggest that the DIRIGENT gene may have evolved via paralogous expansion at an early stage of vascular plant diversification. Thereafter, western red cedar paralogues have maintained an high homogeneity presumably via a concerted evolutionary mode. This, in turn, is assumed to be the driving force for the differential formation of 8-8'-linked pinoresinol derived (poly)lignans in the needles, stems, bark and branches, as well as for massive accumulation of 8-8'-linked plicatic acid-derived (poly)lignans in heartwood.

Mechanism of oil-pulling therapy - in vitro study.

PubMed

Asokan, Sharath; Rathinasamy, T K; Inbamani, N; Menon, Thangam; Kumar, S Senthil; Emmadi, Pamela; Raghuraman, R

2011-01-01

Oil pulling has been used extensively as a traditional Indian folk remedy without scientific proof for many years for strengthening teeth, gums and jaws and to prevent decay, oral malodor, bleeding gums and dryness of throat and cracked lips. The aim of this study was to evaluate the antibacterial activity of sesame oil and lignans isolated from sesame oil on oral microorganisms and to check whether saponification or emulsification occurs during oil-pulling therapy. The in vitro study was carried out in three different phases: (1) Antibacterial activity of the lignans and sesame oil were tested by minimum inhibitory concentration assay by agar dilution method and agar well diffusion method, respectively. (2) Increase in free fatty acid level of oil and the quantity of sodium hydroxide (NaOH) used up in the titration are good indicators of saponification process. This was assessed using analytical tests for vegetable oils. (3) Swished oil was observed under light microscope to assess the status of the oil, presence of microorganisms, oral debris and foreign bodies. Sesamin and sesamolin isolated from sesame oil did not have any antibacterial effect against oral microorganisms like Streptococcus mutans, Streptococcus mitis and Streptococcus viridans. Emulsification of sesame oil occurs during oil-pulling therapy. Increased consumption of NaOH in titration is a definite indication of a possible saponification process. The myth that the effect of oil-pulling therapy on oral health was just a placebo effect has been broken and there are clear indications of possible saponification and emulsification process, which enhances its mechanical cleaning action.

Flavonoid and lignan intake in relation to bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

PubMed

Zamora-Ros, R; Sacerdote, C; Ricceri, F; Weiderpass, E; Roswall, N; Buckland, G; St-Jules, D E; Overvad, K; Kyrø, C; Fagherazzi, G; Kvaskoff, M; Severi, G; Chang-Claude, J; Kaaks, R; Nöthlings, U; Trichopoulou, A; Naska, A; Trichopoulos, D; Palli, D; Grioni, S; Mattiello, A; Tumino, R; Gram, I T; Engeset, D; Huerta, J M; Molina-Montes, E; Argüelles, M; Amiano, P; Ardanaz, E; Ericson, U; Lindkvist, B; Nilsson, L M; Kiemeney, L A; Ros, M; Bueno-de-Mesquita, H B; Peeters, P H M; Khaw, K-T; Wareham, N J; Knaze, V; Romieu, I; Scalbert, A; Brennan, P; Wark, P; Vineis, P; Riboli, E; González, C A

2014-10-28

There is growing evidence of the protective role of dietary intake of flavonoids and lignans on cancer, but the association with bladder cancer has not been thoroughly investigated in epidemiological studies. We evaluated the association between dietary intakes of total and subclasses of flavonoids and lignans and risk of bladder cancer and its main morphological type, urothelial cell carcinoma (UCC), within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. A cohort of 477 312 men and women mostly aged 35-70 years, were recruited in 10 European countries. At baseline, dietary flavonoid and lignan intakes were estimated using centre-specific validated questionnaires and a food composition database based on the Phenol-Explorer, the UK Food Standards Agency and the US Department of Agriculture databases. During an average of 11 years of follow-up, 1575 new cases of primary bladder cancer were identified, of which 1425 were UCC (classified into aggressive (n=430) and non-aggressive (n=413) UCC). No association was found between total flavonoid intake and bladder cancer risk. Among flavonoid subclasses, significant inverse associations with bladder cancer risk were found for intakes of flavonol (hazard ratio comparing fifth with first quintile (HRQ5-Q1) 0.74, 95% confidence interval (CI): 0.61-0.91; P-trend=0.009) and lignans (HRQ5-Q1 0.78, 95% CI: 0.62-0.96; P-trend=0.046). Similar results were observed for overall UCC and aggressive UCC, but not for non-aggressive UCC. Our study suggests an inverse association between the dietary intakes of flavonols and lignans and risk of bladder cancer, particularly aggressive UCC.

Flavonoid and lignan intake and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort.

PubMed

Molina-Montes, Esther; Sánchez, María-José; Zamora-Ros, Raul; Bueno-de-Mesquita, H B As; Wark, Petra A; Obon-Santacana, Mireia; Kühn, Tilman; Katzke, Verena; Travis, Ruth C; Ye, Weimin; Sund, Malin; Naccarati, Alessio; Mattiello, Amalia; Krogh, Vittorio; Martorana, Caterina; Masala, Giovanna; Amiano, Pilar; Huerta, José-María; Barricarte, Aurelio; Quirós, José-Ramón; Weiderpass, Elisabete; Angell Åsli, Lene; Skeie, Guri; Ericson, Ulrika; Sonestedt, Emily; Peeters, Petra H; Romieu, Isabelle; Scalbert, Augustin; Overvad, Kim; Clemens, Matthias; Boeing, Heiner; Trichopoulou, Antonia; Peppa, Eleni; Vidalis, Pavlos; Khaw, Kay-Tee; Wareham, Nick; Olsen, Anja; Tjønneland, Anne; Boutroun-Rualt, Marie-Christine; Clavel-Chapelon, Françoise; Cross, Amanda J; Lu, Yunxia; Riboli, Elio; Duell, Eric J

2016-10-01

Despite the potential cancer preventive effects of flavonoids and lignans, their ability to reduce pancreatic cancer risk has not been demonstrated in epidemiological studies. Our aim was to examine the association between dietary intakes of flavonoids and lignans and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 865 exocrine pancreatic cancer cases occurred after 11.3 years of follow-up of 477,309 cohort members. Dietary flavonoid and lignan intake was estimated through validated dietary questionnaires and the US Department of Agriculture (USDA) and Phenol Explorer databases. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated using age, sex and center-stratified Cox proportional hazards models, adjusted for energy intake, body mass index (BMI), smoking, alcohol and diabetes status. Our results showed that neither overall dietary intake of flavonoids nor of lignans were associated with pancreatic cancer risk (multivariable-adjusted HR for a doubling of intake = 1.03, 95% CI: 0.95-1.11 and 1.02; 95% CI: 0.89-1.17, respectively). Statistically significant associations were also not observed by flavonoid subclasses. An inverse association between intake of flavanones and pancreatic cancer risk was apparent, without reaching statistical significance, in microscopically confirmed cases (HR for a doubling of intake = 0.96, 95% CI: 0.91-1.00). In conclusion, we did not observe an association between intake of flavonoids, flavonoid subclasses or lignans and pancreatic cancer risk in the EPIC cohort. © 2016 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

Urinary composition and postprandial blood changes in H-secoisolariciresinol diglycoside (SDG) metabolites in rats do not differ between acute and chronic SDG treatments.

PubMed

Rickard, S E; Thompson, L U

2000-09-01

Although chronic exposure to secoisolariciresinol diglycoside (SDG) was shown to alter (3)H-SDG metabolite disposition in rats, the proportion of measured radioactivity attributed to known or unknown SDG metabolites was not determined. Using HPLC and GC-MS, two experiments were conducted to determine the effect of acute (1 d) vs. chronic (10 d) SDG treatment on major urinary metabolites of (3)H-SDG in female, Sprague-Dawley rats (70-72-d-old) over a 48-h period and if new urinary metabolites were detectable in rats fed nonradioactive flaxseed or SDG. A third experiment was conducted to determine changes in postprandial blood levels of (3)H-SDG metabolites over a 24-h period with acute or chronic SDG treatment. Regardless of treatment, enterodiol, enterolactone and secoisolariciresinol accounted for 75-80% of urine radioactivity. Four potential new lignan metabolites, two of which were detected in the urine of rats fed nonradioactive flaxseed or SDG, were found. Type of treatment had no effect on levels of individual urinary metabolites of (3)H-SDG. As observed for plasma lignans in women fed flaxseed, blood radioactivity peaked at 9 h and remained high until 24 h in both treatment groups, suggesting that blood lignan kinetics might be similar with flaxseed or SDG consumption and that they were comparable between humans and rats. In conclusion, the main urinary lignan metabolites were enterodiol, enterolactone and secoisolariciresinol. Urinary composition or blood levels of radioactive lignans were not affected by the duration of SDG exposure. Thus, while chronic SDG exposure alters lignan disposition in rats, it does not change the metabolite profile.

[Correlation research on contents of podophyllotoxin and total lignans in Sinopodophyllum hexandrum and ecological factors].

PubMed

Li, Min; Zhong, Guo-yue; Wu, Ao-lin; Zhang, Shou-wen; Jiang, Wei; Liang, Jian

2015-05-01

To explore the correlation between the ecological factors and the contents of podophyllotoxin and total lignans in root and rhizome of Sinopodophyllum hexandrum, podophyllotoxin in 87 samples (from 5 provinces) was determined by HPLC and total lignans by UV. A correlation and regression analysis was made by software SPSS 16.0 in combination with ecological factors (terrain, soil and climate). The content determination results showed a great difference between podophyllotoxin and total lignans, attaining 1.001%-6.230% and 5.350%-16.34%, respective. The correlation and regression analysis by SPSS showed a positive linear correlation between their contents, strong positive correlation between their contents, latitude and annual average rainfall within the sampling area, weak negative correlation with pH value and organic material in soil, weaker and stronger positive correlations with soil potassium, weak negative correlation with slope and annual average temperature and weaker positive correlation between the podophyllotoxin content and soil potassium.

Phytochemical and cytotoxic studies on the leaves of Calotropis gigantea.

PubMed

Nguyen, Khang D H; Dang, Phu H; Nguyen, Hai X; Nguyen, Mai T T; Awale, Suresh; Nguyen, Nhan T

2017-07-01

A new lignan, 9'-methoxypinoresinol (1), and two new glycosylated 5-hydroxymethylfurfurals, calofurfuralside A (2), and calofurfuralside B (3), together with nine known compounds (4-12) have been isolated from the active fractions, CHCl 3 (IC 50 , 0.32μgmL -1 ) and EtOAc (IC 50 , 0.55μgmL -1 ) fractions of the leaves of Calotropis gigantea. Their structures were elucidated based on NMR and MS data. Among the isolated compounds, compounds 1 and 9 exhibited potent cytotoxicity against PANC-1 human pancreatic cancer cell line under the normoglycemic condition with IC 50 values of 3.7 and 3.3μM, respectively. 9'-Methoxypinoresinol (1) significantly inhibited the colony formation of PANC-1 cells in a concentration-dependent manner. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ionic liquid-based microwave-assisted extraction of essential oil and biphenyl cyclooctene lignans from Schisandra chinensis Baill fruits.

PubMed

Ma, Chun-hui; Liu, Ting-ting; Yang, Lei; Zu, Yuan-gang; Chen, Xiaoqiang; Zhang, Lin; Zhang, Ying; Zhao, Chunjian

2011-12-02

Ionic liquid-based microwave-assisted extraction (ILMAE) has been successfully applied in extracting essential oil and four kinds of biphenyl cyclooctene lignans from Schisandra chinensis Baill. 0.25 M 1-lauryl-3-methylimidazolium bromide ionic liquid is selected as solvent. The optimum parameters of dealing with 25.0 g sample are 385 W irradiation power, 40 min microwave extraction time and 1:12 solid-liquid ratio. The yields of essential oil and lignans are 12.12±0.37 ml/kg and 250.2±38.2 mg/kg under the optimum conditions. The composition of the essential oil extracted by hydro-distillation, steam-distillation and ILMAE is analyzed by GC-MS. With ILMAE method, the energy consumption time has not only been shortened to 40 min (hydro-distillation 3.0 h for extracting essential oil and reflux extraction 4.0 h for extracting lignans, respectively), but also the extraction efficiency has been improved (extraction of lignans and distillation of essential oil at the same time) and reduces the environmental pollution. S. chinensis materials treated by different methods are observed by scanning electronic microscopy. Micrographs provide more evidence to prove that ILMAE is a better and faster method. The experimental results also indicate that ILMAE is a simple and efficient technique for sample preparation. Copyright © 2011 Elsevier B.V. All rights reserved.

Constituents of the leaves of Magnolia ovata.

PubMed

Barros, Letícia Ferrari L; Barison, Andersson; Salvador, Marcos José; de Mello-Silva, Renato; Cabral, Elaine C; Eberlin, Marcos N; Stefanello, Maria Elida A

2009-08-01

Two new lignans, magnovatins A (1) and B (2), along with nine known compounds, were isolated from the leaves of Magnolia ovata. The known compounds were identified as acuminatin (3), licarin A (4), kadsurenin M, 4-O-demethylkadsurenin M, oleiferin A, oleiferin C, spathulenol, parthenolide, and 11,13-dehydrocompressanolide. In addition, compounds 1 and 2 yielded four new derivatives (1a, 1b, 2a, and 2b). The structures of the new compounds were established on the basis of spectrometric data evaluation. Free-radical scavenging and antimicrobial activities of the major compunds 1, 3, and 4 were investigated.

New cardenolide and acylated lignan glycosides from the aerial parts of Asclepias curassavica.

PubMed

Warashina, Tsutomu; Shikata, Kimiko; Miyase, Toshio; Fujii, Satoshi; Noro, Tadataka

2008-08-01

Three new cardenolide glycosides and six new acylated lignan glycosides were obtained along with nineteen known compounds from the aerial parts of Asclepias curassavica L. (Asclepiadaceae). The structure of each compound was determined based on interpretations of NMR and MS measurements and chemical evidence.

Comparative effects of sesame seed lignan and flaxseed lignan in reducing the growth of human breast tumors (MCF-7) at high levels of circulating estrogen in athymic mice.

PubMed

Truan, Jennifer S; Chen, Jian-Min; Thompson, Lilian U

2012-01-01

Flaxseed (FS) has a breast tumor-reducing effect, possibly because of its high content of secoisolariciresinol diglucoside (SDG) lignan. Sesame seed (SS) is rich in the lignan sesamin (SES) but is non-protective. Both lignans are metabolized to estrogen-like enterodiol and enterolactone. The objective of this study was to differentiate the effects of SDG and SES on established human estrogen receptor-positive breast tumors (MCF-7) in athymic mice with high serum estrogen to help explain the different effects of FS and SS. Mice were fed for 8 wk the basal diet (BD, control) or BD supplemented with 1 g/kg SDG or SES. SES reduced palpable tumor size by 23% compared to control, whereas SDG did not differ from SES or control. Both treatments reduced tumor cell proliferation, but only SES increased apoptosis. SDG and SES reduced human epidermal growth factor receptor 2 and endothelial growth factor receptor expressions, but only SES reduced downstream pMAPK. Neither treatment affected IGF-1R, vascular endothelial growth factor receptor-2, Akt, pAkt, or MAPK of the growth factor signaling pathway. Thus, at high serum estrogen levels, SDG may not account for the tumor reducing effect of FS. SES was more effective than SDG in reducing breast tumor growth, but its effect may have been lost when consumed as a component of SS.

Health effects with consumption of the flax lignan secoisolariciresinol diglucoside.

PubMed

Adolphe, Jennifer L; Whiting, Susan J; Juurlink, Bernhard H J; Thorpe, Lilian U; Alcorn, Jane

2010-04-01

Flaxseed is the richest source of the lignan secoisolariciresinol diglucoside (SDG). After ingestion, SDG is converted to secoisolariciresinol, which is further metabolised to the mammalian lignans enterodiol and enterolactone. A growing body of evidence suggests that SDG metabolites may provide health benefits due to their weak oestrogenic or anti-oestrogenic effects, antioxidant activity, ability to induce phase 2 proteins and/or inhibit the activity of certain enzymes, or by mechanisms yet unidentified. Human and animal studies identify the benefits of SDG consumption. SDG metabolites may protect against CVD and the metabolic syndrome by reducing lipid and glucose concentrations, lowering blood pressure, and decreasing oxidative stress and inflammation. Flax lignans may also reduce cancer risk by preventing pre-cancerous cellular changes and by reducing angiogenesis and metastasis. Thus, dietary SDG has the potential to decrease the incidence of several chronic diseases that result in significant morbidity and mortality in industrialised countries. The available literature, though, makes it difficult to clearly identify SDG health effects because of the wide variability in study methods. However, the current evidence suggests that a dose of at least 500 mg SDG/d for approximately 8 weeks is needed to observe positive effects on cardiovascular risk factors in human patients. Flaxseed and its lignan extracts appear to be safe for most adult populations, though animal studies suggest that pregnant women should limit their exposure. The present review discusses the potential health benefits of SDG in humans, with supporting evidence from animal studies, and offers suggestions for future research.

Cistanches Herba: An overview of its chemistry, pharmacology, and pharmacokinetics property.

PubMed

Fu, Zhifei; Fan, Xiang; Wang, Xiaoying; Gao, Xiumei

2018-06-12

Cistanches Herba is an Orobanchaceae parasitic plant. As a commonly used Traditional Chinese Medicine (TCM), its traditional functions include treating kidney deficiency, impotence, female infertility and senile constipation. Chemical analysis of Cistanches Herba revealed that phenylethanoid glycosides, iridoids, lignans, oligosaccharides, and polysaccharides were the main constituents. Pharmacological studies demonstrated that Cistanches Herba exhibited neuroprotective, immunomodulatory, hormonal balancing, anti-fatigue, anti-inflammatory, hepatoprotection, anti-oxidative, anti-bacterial, anti-viral, and anti-tumor effects, etc. The aim of this review is to provide updated, comprehensive and categorized information on the phytochemistry, pharmacological research and pharmacokinetics studies of the major constituents of Cistanches Herba. The literature search was conducted by systematic searching multiple electronic databases including SciFinder, ISI Web of Science, PubMed, Google Scholar and CNKI. Information was also collected from journals, local magazines, books, monographs. To date, more than 100 compounds have been isolated from this genus, include phenylethanoid glycosides, carbohydrates, lignans, iridoids, etc. The crude extracts and isolated compounds have exhibited a wide range of in vitro and in vivo pharmacologic effects, such as neuroprotective, immunomodulatory, anti-inflammatory, hepatoprotection, anti-oxidative, anti-bacterial, and anti-tumor effects. The phenylethanoid glycosides, echinacoside and acteoside have attracted the most attention for their significantly neuropharmacology effects. Pharmacokinetic studies of echinacoside and acteoside also have also been summarized. Phenylethanoid glycosides have demonstrated wide pharmacological actions and have great clinical value if challenges such as poor bioavailability, fast and extensive metabolism are addressed. Apart from phenylethanoid glycosides, other constituents of Cistanches Herba, their pharmacological activities and underlying mechanisms are also need to be studied further. Copyright © 2017. Published by Elsevier B.V.

Role of protein farnesylation events in the ABA-mediated regulation of the Pinoresinol-Lariciresinol Reductase 1 (LuPLR1) gene expression and lignan biosynthesis in flax (Linum usitatissimum L.).

PubMed

Corbin, Cyrielle; Decourtil, Cédric; Marosevic, Djurdjica; Bailly, Marlène; Lopez, Tatiana; Renouard, Sullivan; Doussot, Joël; Dutilleul, Christelle; Auguin, Daniel; Giglioli-Guivarc'h, Nathalie; Lainé, Eric; Lamblin, Frédéric; Hano, Christophe

2013-11-01

A Linum usitatissimum LuERA1 gene encoding a putative ortholog of the ERA1 (Enhanced Response to ABA 1) gene of Arabidopsis thaliana (encoding the beta subunit of a farnesyltransferase) was analyzed in silico and for its expression in flax. The gene and the protein sequences are highly similar to other sequences already characterized in plants and all the features of a farnesyltransferase were detected. Molecular modeling of LuERA1 protein confirmed its farnesyltransferase nature. LuERA1 is expressed in the vegetative organs and also in the outer seedcoat of the flaxseed, where it could modulate the previously observed regulation operated by ABA on lignan synthesis. This effect could be mediated by the regulation of the transcription of a key gene for lignan synthesis in flax, the LuPLR1 gene, encoding a pinoresinol lariciresinol reductase. The positive effect of manumycin A, a specific inhibitor of farnesyltransferase, on lignan biosynthesis in flax cell suspension systems supports the hypothesis of the involvement of such an enzyme in the negative regulation of ABA action. In Arabidopsis, ERA1 is able to negatively regulate the ABA effects and the mutant era1 has an enhanced sensitivity to ABA. When expressed in an Arabidopsis cell suspension (heterologous system) LuERA1 is able to reverse the effect of the era1 mutation. RNAi experiments in flax targeting the farnesyltransferase β-subunit encoded by the LuERA1 gene led to an increase LuPLR1 expression level associated with an increased content of lignan in transgenic calli. Altogether these results strongly suggest a role of the product of this LuERA1 gene in the ABA-mediated upregulation of lignan biosynthesis in flax cells through the activation of LuPLR1 promoter. This ABA signaling pathway involving ERA1 probably acts through the ABRE box found in the promoter sequence of LuPLR1, a key gene for lignan synthesis in flax, as demonstrated by LuPLR1 gene promoter-reporter experiments in flax cells using wild type and mutated promoter sequences. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

LC-DAD-MS-based metabolite profiling of three species of Justicia (Acanthaceae).

PubMed

Calderón, Angela I; Hodel, Adam; Wolfender, Jean-Luc; Gupta, Mahabir P; Correa, Mireya; Hostettmann, Kurt

2013-08-01

Olean-12-en-3β-24 diol (A), auranamide (B), aurantiamide acetate (C), 2α,3β-dihydroxy-olean-12-en-28-oic acid (D) and quindoline (E) were isolated from the dichloromethane (CH2Cl2) extract of the stems of Justicia secunda (Acanthaceae). Liquid chromatography with ultraviolet and mass spectrometric detection was used to acquire more knowledge of the chemical composition of this extract and to monitor variations in profiles of both the isolated and the other non-identified compounds in Justicia refractifolia and Justicia graciliflora. The compound classes, phenolic and olefinic amides, feruloyltyramine amides, 2,5-diaryl-3,4-dimethyltetrahydrofuranoid lignans, peptide alkaloids, phenylalanine derivatives, conjugated ynones, indolquinoline alkaloids, triterpenes and pigments, were tentatively identified based on the LC-DAD-APCI-MS analysis. The most frequently encountered compound among the species was auranamide while the distribution of quindoline was limited to J. secunda. Moreover, the acetylcholinesterase inhibitory activity of the isolated compounds was determined.

Flaxseed lignan and visceral obesity: a closer look at its chemical properties, absorption, metabolism, bioavailability and effects on visceral fat, lipid profile, systemic inflammation and hypertension

USDA-ARS?s Scientific Manuscript database

Linum usitatissimum (Flax) is an important flowering crop plant cultivated world-wide. Particularly, flaxseeds have been cherished as a valuable agricultural commodity for many years, because they contain fiber, protein, oil, lignan and others. Secoisolariciresinol diglucoside (SDG) is a major lign...

Antioxidant lipoxygenase inhibitors from the leaf extracts of Simmondsia chinensis.

PubMed

Abdel-Mageed, Wael Mostafa; Bayoumi, Soad Abdel Latief Hassan; Salama, Awwad Abdoh Radwan; Salem-Bekhit, Mounir Mohamed; Abd-Alrahman, Sherif Hussein; Sayed, Hanaa Mohamed

2014-09-01

To isolate and identify chemical constituents with antioxidant and lipoxygenase inhibitory effects of the ethanolic extract of Simmondsia chinensis (Jojoba) leaves. The alcoholic extract was subjected to successive solvent fractionation. The antioxidant active fractions (chloroform, ethyl acetate and aqueous fractions) were subjected to a combination of different chromatographic techniques guided by the antioxidant assay with DPPH. The structures of the isolated compounds were elucidated on the basis of spectroscopic evidences and correlated with known compounds. The antioxidant activity was assessed quantitively using DPPH and β-carotene methods. The inhibitory potential against enzyme lipoxygenase was assessed on soybean lipoxygenase enzyme. Ten flavonoids and four lignans were isolated. Flavonoid aglycones showed stronger antioxidant and lipoxygenase inhibitory effects than their glycosides. Lignoid glycosides showed moderate to weak antioxidant and lipoxygenase inhibitory effects. A total of 14 compounds were isolated and identified from Simmondsia chinensis; 12 of them were isolated for the first time. This is the first report that highlights deeply on the phenolic content of jojoba and their potential biological activities and shows the importance of this plant as a good source of phenolics in particular the flavonoid content. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Reduction in Ki-67 in Benign Breast Tissue of High Risk Women with the Lignan Secoisolariciresinol Diglycoside (SDG)

PubMed Central

Fabian, Carol J.; Kimler, Bruce F.; Zalles, Carola M.; Klemp, Jennifer R.; Petroff, Brian K.; Khan, Qamar J.; Sharma, Priyanka; Setchell, Kenneth D. R.; Zhao, Xueheng; Phillips, Teresa A.; Metheny, Trina; Hughes, Jennifer R.; Yeh, Hung-Wen; Johnson, Karen A.

2010-01-01

Preclinical and correlative studies suggest reduced breast cancer with higher lignan intake or blood levels. We conducted a pilot study of modulation of risk biomarkers for breast cancer in premenopausal women after administration of the plant lignan secoisolariciresinol given as the diglycoside (SDG). Eligibility criteria included regular menstrual cycles, no oral contraceptives, a greater than 3-fold increase in 5 year risk, and baseline Ki-67 ≥2% in areas of hyperplasia in breast tissue sampled by random periareolar fine needle aspiration (RPFNA) during the follicular phase of the menstrual cycle. SDG 50 mg daily was given for 12 months, followed by repeat RPFNA. The primary endpoint was change in Ki-67. Secondary endpoints included change in cytomorphology, mammographic breast density, serum bioavailable estradiol, and testosterone IGF-I and IGFBP-3, and plasma lignan levels. Forty-five of 49 eligible women completed the study with excellent compliance (median = 96%) and few serious side effects (4% grade 3). Median plasma enterolactone increased ~ 9-fold, and total lignans 16 fold. Thirty-six (80%) of the 45 evaluable subjects demonstrated a decrease in Ki-67, from a median of 4% (range 2–16.8 %) to 2% (range 0–15.2%) (p<0.001 by Wilcoxon signed rank test). A decrease from baseline in the proportion of women with atypical cytology (p=0.035) was also observed. Based on favorable risk biomarker modulation and lack of adverse events, we are initiating a randomized trial of SDG vs. placebo in premenopausal women. PMID:20724470

Dietary Flavonoid and Lignan Intake and Mortality in Prospective Cohort Studies: Systematic Review and Dose-Response Meta-Analysis.

PubMed

Grosso, Giuseppe; Micek, Agnieszka; Godos, Justyna; Pajak, Andrzej; Sciacca, Salvatore; Galvano, Fabio; Giovannucci, Edward L

2017-06-15

Recent evidence has suggested that flavonoid and lignan intake may be associated with decreased risk of chronic and degenerative diseases. The aim of this meta-analysis was to assess the association between dietary flavonoid and lignan intake and all-cause and cardiovascular disease (CVD) mortality in prospective cohort studies. A systematic search was conducted in electronic databases to identify studies published from January 1996 to December 2015 that satisfied inclusion/exclusion criteria. Risk ratios and 95% confidence intervals were extracted and analyzed using a random-effects model. Nonlinear dose-response analysis was modeled by using restricted cubic splines. The inclusion criteria were met by 22 prospective studies exploring various flavonoid and lignan classes. Compared with lower intake, high consumption of total flavonoids was associated with decreased risk of all-cause mortality (risk ratio = 0.74, 95% confidence intervals: 0.55, 0.99), while a 100-mg/day increment in intake led to a (linear) decreased risk of 6% and 4% of all-cause and CVD mortality, respectively. Among flavonoid classes, significant results were obtained for intakes of flavonols, flavones, flavanones, anthocyanidins, and proanthocyanidins. Only limited evidence was available on flavonoid classes and lignans and all-cause mortality. Findings from this meta-analysis indicated that dietary flavonoids are associated with decreased risk of all-cause and CVD mortality. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Differential and directional estrogenic signaling pathways induced by enterolignans and their precursors

PubMed Central

Zhu, Yun; Kawaguchi, Kayoko; Kiyama, Ryoiti

2017-01-01

Mammalian lignans or enterolignans are metabolites of plant lignans, an important category of phytochemicals. Although they are known to be associated with estrogenic activity, cell signaling pathways leading to specific cell functions, and especially the differences among lignans, have not been explored. We examined the estrogenic activity of enterolignans and their precursor plant lignans and cell signaling pathways for some cell functions, cell cycle and chemokine secretion. We used DNA microarray-based gene expression profiling in human breast cancer MCF-7 cells to examine the similarities, as well as the differences, among enterolignans, enterolactone and enterodiol, and their precursors, matairesinol, pinoresinol and sesamin. The profiles showed moderate to high levels of correlation (R values: 0.44 to 0.81) with that of estrogen (17β-estradiol or E2). Significant correlations were observed among lignans (R values: 0.77 to 0.97), and the correlations were higher for cell functions related to enzymes, signaling, proliferation and transport. All the enterolignans/precursors examined showed activation of the Erk1/2 and PI3K/Akt pathways, indicating the involvement of rapid signaling through the non-genomic estrogen signaling pathway. However, when their effects on specific cell functions, cell cycle progression and chemokine (MCP-1) secretion were examined, positive effects were observed only for enterolactone, suggesting that signals are given in certain directions at a position closer to cell functions. We hypothesized that, while estrogen signaling is initiated by the enterolignans/precursors examined, their signals are differentially and directionally modulated later in the pathways, resulting in the differences at the cell function level. PMID:28152041

[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.

RNAi-mediated pinoresinol lariciresinol reductase gene silencing in flax (Linum usitatissimum L.) seed coat: consequences on lignans and neolignans accumulation.

PubMed

Renouard, Sullivan; Tribalatc, Marie-Aude; Lamblin, Frederic; Mongelard, Gaëlle; Fliniaux, Ophélie; Corbin, Cyrielle; Marosevic, Djurdjica; Pilard, Serge; Demailly, Hervé; Gutierrez, Laurent; Hano, Christophe; Mesnard, François; Lainé, Eric

2014-09-15

RNAi technology was applied to down regulate LuPLR1 gene expression in flax (Linum usitatissimum L.) seeds. This gene encodes a pinoresinol lariciresinol reductase responsible for the synthesis of (+)-secoisolariciresinol diglucoside (SDG), the major lignan accumulated in the seed coat. If flax lignans biological properties and health benefits are well documented their roles in planta remain unclear. This loss of function strategy was developed to better understand the implication of the PLR1 enzyme in the lignan biosynthetic pathway and to provide new insights on the functions of these compounds. RNAi plants generated exhibited LuPLR1 gene silencing as demonstrated by quantitative RT-PCR experiments and the failed to accumulate SDG. The accumulation of pinoresinol the substrate of the PLR1 enzyme under its diglucosylated form (PDG) was increased in transgenic seeds but did not compensate the overall loss of SDG. The monolignol flux was also deviated through the synthesis of 8-5' linked neolignans dehydrodiconiferyl alcohol glucoside (DCG) and dihydro-dehydrodiconiferyl alcohol glucoside (DDCG) which were observed for the first time in flax seeds. Copyright © 2014 Elsevier GmbH. All rights reserved.

Simultaneous determination of three major lignans in rat plasma by LC-MS/MS and its application to a pharmacokinetic study after oral administration of Diphylleia sinensis extract.

PubMed

Zhao, Chengliang; Zhang, Nan; He, Weiyan; Li, Rui; Shi, Dan; Pang, Li; Dong, Ning; Xu, Hong; Ji, Honglei

2014-04-01

A sensitive and selective liquid chromatography tandem mass spectrometry was developed and validated for the simultaneous determination of three major lignans (podophyllotoxin, epipodophyllotoxin, and 4'-demethylpodophyllotoxin) in rat plasma using diphenhydramine as the internal standard. The analytes were detected using a triple quadrupole mass spectrometer that was equipped with an electrospray ionization source in the positive ion and selected reaction monitoring modes. The linearity of the calibration curve was good, with coefficients of determination (r(2) ) >0.9914 for all of the analytes. The developed method was successfully applied for the simultaneous determination of the three lignans in rat plasma following oral administration of Diphylleia sinensis extract to rats. Copyright © 2013 John Wiley & Sons, Ltd.

Isolation and identification of arctiin and arctigenin in leaves of burdock (Arctium lappa L.) by polyamide column chromatography in combination with HPLC-ESI/MS.

PubMed

Liu, Shiming; Chen, Kaoshan; Schliemann, Willibald; Strack, Dieter

2005-01-01

A simple method involving polyamide column chromatography in combination with HPLC-PAD and HPLC-ESI/MS for isolating and identifying two kinds of lignans, arctiin and arctigenin, in the leaves of burdock (Arctium lappa L.) has been established. After extraction of burdock leaves with 80% methanol, the aqueous phase of crude extracts was partitioned between water and chloroform and the aqueous phase was fractionated on a polyamide glass column. The fraction, eluting with 100% methanol, was concentrated and gave a white precipitate at 4 degrees C from which two main compounds were purified by semi-preparative HPLC. In comparison with the UV and ESI-MS spectra and the HPLC retention time of authentic standards, the compounds were determined to be arctiin and arctigenin. The extraction/separation technique was validated using an internal standard method.

Effects of secoisolariciresinol diglucoside lignan-enriched flaxseed powder on body weight, visceral fat, lipid profile, adipokines, and blood pressure in rats fed a high-fructose and high-fat diet

USDA-ARS?s Scientific Manuscript database

The potential effects of secoisolariciresinol diglucoside (SDG) lignan-enriched flaxseed powder LEFP) on body weight, visceral fat, lipid profile, adipokines, and blood pressure were investigated using Sprague-Dawley rats. The animals were divided into three groups (n=8) that were fed either a norm...

Arctigenin, a lignan from Arctium lappa L., inhibits metastasis of human breast cancer cells through the downregulation of MMP-2/-9 and heparanase in MDA-MB-231 cells.

PubMed

Lou, Chenghua; Zhu, Zhihui; Zhao, Yaping; Zhu, Rui; Zhao, Huajun

2017-01-01

Arctigenin is a bioactive lignan isolated from the seeds of Arctium lappa L. which has been widely used as a diuretic and a diaphoretic in Traditional Chinese Medicine. In the present study, the authors investigated the effects of arctigenin on tumor migration and invasion in aggressive human breast cancer cells. The MTT assay results showed that arctigenin did not show a significant cytotoxic effect on the cell viability of MDA-MB-231 cells. However, wound healing migration and Boyden chamber invasion assays demonstrated that arctigenin significantly inhibited in vitro migration and invasion of the MDA-MB-231 cells. Furthermore, gelatin zymography results showed that arctigenin reduced the activity of MMP-2 and MMP-9. Western blot analysis results demonstrated that the expression of MMP-2, MMP-9 and heparanase proteins was significantly downregulated following the treatment of arctigenin. Finally, the antiangiogenic activity of arctigenin was also examined by the chick embryo chorioallantoic membrane (CAM) assay. Arctigenin treatment significantly inhibited angiogenesis in the CAM. In conclusion, the results revealed that arctigenin significantly inhibited the migration and invasion of MDA-MB-231 cells by downregulating MMP-2, MMP-9 and heparanase expression. However, further studies are still necessary to investigate the exact mechanisms involved and to explore signal transduction pathways to better understand the biological mechanisms.

Arctigenin, a phenylpropanoid dibenzylbutyrolactone lignan, inhibits type I-IV allergic inflammation and pro-inflammatory enzymes.

PubMed

Lee, Ji Yun; Kim, Chang Jong

2010-06-01

We previously reported that arctigenin, a phenylpropanoid dibenzylbutyrolactone lignan isolated from Forsythia koreana, exhibits anti-inflammatory, antioxidant, and analgesic effects in animal models. In addition, arctigenin inhibited eosinophil peroxidase and activated myeloperoxidase in inflamed tissues. In this study, we tested the effects of arctigenin on type I-IV allergic inflammation and pro-inflammatory enzymes in vitro and in vivo. Arctigenin significantly inhibited the heterologous passive cutaneous anaphylaxis induced by ovalbumin in mice at 15 mg/kg, p.o., and compound 48/80-induced histamine release from rat peritoneal mast cells at 10 microM. Arctigenin (15 mg/kg, p.o.) significantly inhibited reversed cutaneous anaphylaxis. Further, arctigenin (15 mg/kg, p.o.) significantly inhibited the Arthus reaction to sheep's red blood cells, decreasing the hemolysis titer, the hemagglutination titer, and the plaque-forming cell number for SRBCs. In addition, arctigenin significantly inhibited delayed type hypersensitivity at 15 mg/kg, p.o. and the formation of rosette-forming cells at 45 mg/kg, p.o. Contact dermatitis induced by picrylchloride and dinitrofluorobenzene was significantly (p < 0.05) inhibited by surface treatment with arctigenin (0.3 mg/ear). Furthermore, arctigenin dose-dependently inhibited pro-inflammatory enzymes, such as cyclooxygenase-1 and 2, 5-lipoxygenase, phospholipase A2, and phosphodiesterase. Our results show that arctigenin significantly inhibited B- and T-cell mediated allergic inflammation as well as pro-inflammatory enzymes.

Preventive effects of lignan extract from flax hulls on experimentally induced benign prostate hyperplasia.

PubMed

Bisson, Jean-François; Hidalgo, Sophie; Simons, Rudy; Verbruggen, Marian

2014-06-01

Consumption of diet rich in lignans may decrease the risk of some chronic hormonal conditions such as benign prostatic hyperplasia (BPH). This study investigated whether a lignan-rich extract from flaxseed hulls, LinumLife EXTRA (LLE), could prevent BPH using the testosterone propionate (TP)-induced BPH rat model. Male Wistar-Unilever rats were randomly divided into four groups of 12 rats each: a negative control group fed with control diet and receiving daily subcutaneous injections of corn oil without TP, and three groups fed with control diet (positive control), diet containing 0.5% LLE (LLE 0.5) or 1.0% LLE (LLE 1.0) and receiving daily subcutaneous injections of TP in corn oil. Treatments with diets started 2 weeks before the induction of BPH and were carried out for 5 consecutive weeks. The influence of TP and LLE on body weight (BW), food and water consumptions, and enterolactone (ENL) levels in serum and urine of rats was examined at the end of the 5-week treatment period. TP significantly diminished the mean body weight gain (MBWG) of positive control rats and their food and water consumptions while LLE reduced significantly this MBWG reduction in a dose-dependent manner. The lignan-rich extract significantly inhibited TP-induced prostate size ratio (prostate weight/rat BW) increase in comparison with positive controls (P<.001). This effect was dose dependent. Higher serum and urine levels of ENL correlated well with the dose of extract provided to rats. It was concluded that the lignan-rich flaxseed hull extract prevented the TP-induced BPH indicating it might be beneficial in the prevention of BPH.

Ruminal Prevotella spp. May Play an Important Role in the Conversion of Plant Lignans into Human Health Beneficial Antioxidants

PubMed Central

Schogor, Ana L. B.; Huws, Sharon A.; Santos, Geraldo T. D.; Scollan, Nigel D.; Hauck, Barbara D.; Winters, Ana L.; Kim, Eun J.; Petit, Hélène V.

2014-01-01

Secoisolariciresinol diglucoside (SDG), the most abundant lignan in flaxseed, is metabolized by the ruminal microbiota into enterolignans, which are strong antioxidants. Enterolactone (EL), the main mammalian enterolignan produced in the rumen, is transferred into physiological fluids, with potentially human health benefits with respect to menopausal symptoms, hormone-dependent cancers, cardiovascular diseases, osteoporosis and diabetes. However, no information exists to our knowledge on bacterial taxa that play a role in converting plant lignans into EL in ruminants. In order to investigate this, eight rumen cannulated cows were used in a double 4×4 Latin square design and fed with four treatments: control with no flax meal (FM), or 5%, 10% and 15% FM (on a dry matter basis). Concentration of EL in the rumen increased linearly with increasing FM inclusion. Total rumen bacterial 16S rRNA concentration obtained using Q-PCR did not differ among treatments. PCR-T-RFLP based dendrograms revealed no global clustering based on diet indicating between animal variation. PCR-DGGE showed a clustering by diet effect within four cows that had similar basal ruminal microbiota. DNA extracted from bands present following feeding 15% FM and absent with no FM supplementation were sequenced and it showed that many genera, in particular Prevotella spp., contributed to the metabolism of lignans. A subsequent in vitro study using selected pure cultures of ruminal bacteria incubated with SDG indicated that 11 ruminal bacteria were able to convert SDG into secoisolariciresinol (SECO), with Prevotella spp. being the main converters. These data suggest that Prevotella spp. is one genus playing an important role in the conversion of plant lignans to human health beneficial antioxidants in the rumen. PMID:24709940

[Dynamic study on two lignans contents in different parts of Sinopodophyllum hexandrum].

PubMed

Li, Yan-ling; Ning, Yi; Xu, Wen-hua; Zhou, Guo-ying

2015-05-01

The contents of two lignans, namely 4'-demethylpodophyllotoxin and podophyllotoxin in cultivated and wild Sinopodophyllum hexandrum plants were extracted by ultrasonicaction and determined by HPLC. According to the result showed, the order of parts of cultivated plants containing 4'-demethylpodophyllotoxin from high to low is as follows: stem > root, no 4'-demethypodophyllotoxin was detected in leaves of cultivated plants; The order of parts of wild plants 4'-demethylpodophyllotoxin from high to low is as follows: lateral root > petiole > rhizome > leaf, no 4'-demethypodophyllotoxin was detected in fruit. The order of parts of cultivated and wild S. hexandrum containing podophyllotoxin from high to low is as follows: root > petiole > leaf ( > fruit). Both of the lignan contents in different parts of cultivated plant varied in a " W" curve with the changes in seasons, with the highest content in July.

Theagalloflavic Acid, a New Pigment Derived from Hexahydroxydiphenoyl Group, and Lignan Oxidation Products Produced by Aerobic Microbial Fermentation of Green Tea.

PubMed

Matsuo, Yosuke; Matsuda, Tomoko; Sugihara, Keisuke; Saito, Yoshinori; Zhang, Ying-Jun; Yang, Chong-Ren; Tanaka, Takashi

2016-01-01

Chinese ripe pu-erh tea is produced by aerobic microbial fermentation of green tea. To clarify the microbial degradation of tea polyphenols, Japanese commercial green tea was mixed with Chinese ripe pu-erh tea, which retains microorganisms, and fermented for 5 d. Chromatographic separation yielded a novel water-soluble yellow pigment termed theagalloflavic acid. Spectroscopic and chemical evidence suggested that this pigment was produced by oxidative ring cleavage of hexahydroxydiphenoyl esters. In addition, two new oxygenated lignin metabolites, (+)-5,5'-dihydroxypinoresinol and 5-hydroxydihydrodehydrodiconiferyl alcohol, were also isolated together with known degradation products of quercetin and tea catechins.

Annonaceae: Breaking the Wall of Inflammation

PubMed Central

Attiq, Ali; Jalil, Juriyati; Husain, Khairana

2017-01-01

Inventories of tropical forests have listed Annonaceae as one of the most diverse plant families. For centuries, it is employed in traditional medicines to cure various pathological conditions including snakebite, analgesic, astringent, diarrhea, dysentery, arthritis pain, rheumatism, neuralgia, and weight loss etc. Phytochemical analysis of Annonaceae family have reported the occurrence of alkaloids, flavonoids, triterpenes, diterpenes and diterpene flavone glycosides, sterols, lignans, and annonaceous acetogenin characteristically affiliated with Annonaceae sp. Numerous past studies have underlined the pleotropic pharmacological activities of the crude extracts and isolated compounds from Annonaceae species. This review is an effort to abridge the ethnobotany, morphology, phytochemistry, toxicity, and particularly focusing on the anti-inflammatory activity of the Annonaceae species. PMID:29104539

Spectroscopic identification and anti-biofilm properties of polar metabolites from the medicinal plant Helichrysum italicum against Pseudomonas aeruginosa.

PubMed

D'Abrosca, Brigida; Buommino, Elisabetta; D'Angelo, Grazia; Coretti, Lorena; Scognamiglio, Monica; Severino, Valeria; Pacifico, Severina; Donnarumma, Giovanna; Fiorentino, Antonio

2013-11-15

Two new acylated styrylpyrones, one 5-methoxy-1(3H)-isobenzofuranone glucoside and a hydroxymethyl-orcinol derivative, along with sixteen known aromatic metabolites, including lignans, quinic acid derivatives low-molecular weight phenol glucosides, have been isolated from the methanol extract of Helichrysum italicum, a medicinal plant typical of the Mediterranean vegetation. The structures of these compounds have been elucidated on the basis of extensive 2D-NMR spectroscopic analyses, including COSY, TOCSY, HSQC, CIGAR-HMBC, H2BC and HSQC-TOCSY, along with Q-TOF HRMS(2) analysis. Selected compounds were evaluated for their anti-biofilm properties against Pseudomonas aeruginosa. Copyright © 2013. Published by Elsevier Ltd.

Deoxypodophyllotoxin: a promising therapeutic agent from herbal medicine.

PubMed

Khaled, Meyada; Jiang, Zhen-Zhou; Zhang, Lu-Yong

2013-08-26

Recently, biologically active compounds isolated from plants used in herbal medicine have been the center of interest. Deoxypodophyllotoxin (DPT), structurally closely related to the lignan podophyllotoxin, is a potent antitumor and anti-inflammatory agent. However, DPT has not been used clinically yet. Also, DPT from natural sources seems to be unavailable. Hence, it is important to establish alternative resources for the production of such lignan; especially that it is used as a precursor for the semi-synthesis of the cytostatic drugs etoposide phosphate and teniposide. The update paper provides an overview of DPT as an effective anticancer natural compound and a leader for cytotoxic drugs synthesis and development in order to highlight the gaps in our knowledge and explore future research needs. The present review covers the literature available from 1877 to 2012. The information was collected via electronic search using Chinese papers and the major scientific databases including PubMed, Sciencedirect, Web of Science and Google Scholar using the keywords. All abstracts and full-text articles reporting database on the history and current status of DPT were gathered and analyzed. Plants containing DPT have played an important role in traditional medicine. In light of the in vitro pharmacological investigations, DPT is a high valuable medicinal agent that has anti-tumor, anti-proliferative, anti-inflammatory and anti-allergic properties. Further, DPT is an important precursor for the cytotoxic aryltetralin lignan, podophyllotoxin, which is used to obtain semisynthetic derivatives like etoposide and teniposide used in cancer therapy. However, most studies have focused on the in vitro data. Therefore, DPT has not been used clinically yet. DPT has emerged as a potent chemical agent from herbal medicine. Therefore, in vivo studies are needed to carry out clinical trials in humans and enable the development of new anti-cancer agents. In addition, DPT from commercial sources seems to be unavailable due to its rarity from natural sources and cumbersome extraction procedures. Hence, it is important to establish alternative, cost-effective and renewable resources, such plant cell cultures and (semi-) synthesis strategies for the production of DPT. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Lignans, bacteriocides and organochlorine compounds activate the human pregnane X receptor (PXR)

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

Jacobs, Miriam N.; Nolan, Gail T.; Hood, Steven R.

2005-12-01

The pregnane X receptor (PXR) mediates the induction of enzymes involved in steroid metabolism and xenobiotic detoxification. The receptor is expressed in liver and intestinal tissues and is activated by a wide range of compounds. The ability of a diverse range of dietary compounds to activate PXR-mediated transcription was assayed in HuH7 cells following transient transfection with human PXR (hPXR). The compounds investigated included phytochemicals such as lignans and phytoestrogens, organochlorine dietary contaminants such as polychlorinated biphenyls (PCBs) and triclosan and selected steroid, drug and herbal compounds. The hPXR activation at the top concentrations tested (10 {mu}M) relative to themore » positive control 10 {mu}M rifampicin ranged from 1.3% (trans-resveratrol) to 152% (ICI 182780). Hydroxylated compounds were marginally more potent than the parent compounds (tamoxifen activation was 74.6% whereas 4 hydroxytamoxifen activation was 84.2%) or significantly greater (vitamin D{sub 3} activation was 1.6%, while hydroxylated vitamin D{sub 3} activation was 55.6%). Enterolactone, the metabolite of common dietary lignans, was a medium activator of PXR (35.6%), compared to the lower activation of a parent lignan, secoisolariciresinol (20%). Two non-hydroxylated PCB congeners (PCB 118 and 153), which present a larger fraction of the PCB contamination of fatty foods, activated hPXR by 26.6% and 17%, respectively. The pesticide trans-nonachlor activation was 53.8%, while the widely used bacteriocide triclosan was a medium activator of hPXR at 46.2%. The responsiveness of PXR to activation by lignan metabolites suggests that dietary intake of these compounds may affect the metabolism of drugs that are CYP3A substrates. Additionally, the evidence that organochlorine chemicals, particularly the ubiquitous triclosan, activate hPXR suggests that these environmental chemicals may, in part, exhibit their endocrine disruptor activities by altering PXR-regulated steroid hormone metabolism with potential adverse health effects in exposed individuals.« less

Flavonoid and lignan intake in a Mediterranean population: proposal for a holistic approach in polyphenol dietary analysis, the Moli-sani Study.

PubMed

Pounis, G; Di Castelnuovo, A; Bonaccio, M; Costanzo, S; Persichillo, M; Krogh, V; Donati, M B; de Gaetano, G; Iacoviello, L

2016-03-01

The objective of this study is to extract and assess data on the dietary intake of flavonoids and lignans in a healthy free-living Mediterranean population, using newly updated harmonized European Union food composition data. This work also aimed at analyzing in a holistic way the total content of the diet in major classes of polyphenols. Six thousand nine hundred and eighty-one men and 7048 women (aged ⩾ 35 years) of the Moli-sani cohort, randomly recruited from the general population, were analyzed. The European Prospective Investigation into Cancer (EPIC) and Nutrition-Food Frequency Questionnaire was used for dietary assessment. The polyphenol content of each food group was evaluated using Eurofir BioActive Substances in Food Information System and the United States Department of Agriculture food composition tables (FCTs), when data were missing. Flavonol, flavone, flavanone, flavanol, anthocyanin, isoflavone and lignan intakes were calculated and polyphenol antioxidant content (PAC) score (-28, 28) constructed, to assess the total content of the diet in these nutrients. Seasonal and citrus fruits, leafy, grain, pod and root vegetables, and onions and garlic accounted for different proportions (11-70%) of the total intake of different polyphenols. Within the Moli-sani population, men or older, or no/former smokers, or physically active or obese/overweight individuals presented higher consumption of flavonoids, lignans and PAC score (P for all <0.01). Multiple regression analysis showed that PAC score and its seven components were positively associated with Mediterranean diet (MeD) adherence in both genders (β-coefficient >0, P<0.001). In addition, 1 unit increase in PAC score was associated with 7.1-7.8% increase in the likelihood of high MeD adherence (P<0.001). The intake of flavonoids and lignans in an European Union population was calculated using harmonized European Union FCT data. In addition, a holistic approach in dietary analysis of polyphenol intake was proposed.

Kinetics and molecular docking studies of cholinesterase inhibitors derived from water layer of Lycopodiella cernua (L.) Pic. Serm. (II).

PubMed

Hung, Tran Manh; Lee, Joo Sang; Chuong, Nguyen Ngoc; Kim, Jeong Ah; Oh, Sang Ho; Woo, Mi Hee; Choi, Jae Sue; Min, Byung Sun

2015-10-05

Acetylcholinesterase (AChE) inhibitors increase the availability of acetylcholine in central cholinergic synapses and are the most promising drugs currently available for the treatment of Alzheimer's disease (AD). Our screening study indicated that the water fraction of the methanolic extract of Lycopodiella cernua (L.) Pic. Serm. significantly inhibited AChE in vitro. Bioassay-guided fractionation led to the isolation of a new lignan glycoside, lycocernuaside A (12), and fourteen known compounds (1-11 and 13-15). Compound 7 exhibited the most potent AChE inhibitory activity with an IC50 value of 0.23 μM. Compound 15 had the most potent inhibitory activity against BChE and BACE1 with IC50 values of 0.62 and 2.16 μM, respectively. Compounds 4 and 7 showed mixed- and competitive-type AChE inhibition. Compound 7 noncompetitively inhibited BChE whereas 15 showed competitive and 8, 13, and 14 showed mixed-type inhibition. The docking results for complexes with AChE or BChE revealed that inhibitors 4, 7, and 15 stably positioned themselves in several pocket/catalytic domains of the AChE and BChE residues. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Nine Different Chemical Species and Action Mechanisms of Pancreatic Lipase Ligands Screened Out from Forsythia suspensa Leaves All at One Time.

PubMed

Chen, Tinggui; Li, Yayun; Zhang, Liwei

2017-05-12

It is difficult to screen out as many active components as possible from natural plants all at one time. In this study, subfractions of Forsythia suspensa leaves were firstly prepared; then, their inhibitive abilities on pancreatic lipase were tested; finally, the highest inhibiting subfraction was screened by self-made immobilized pancreatic lipase. Results showed that nine ligands, including eight inhibitors and one promotor, were screened out all at one time. They were three flavonoids (rutin, IC 50 : 149 ± 6.0 μmol/L; hesperidin, 52.4 μmol/L; kaempferol-3- O -rutinoside, isolated from F. suspensa leaves for the first time, IC 50 notably reached 2.9 ± 0.5 μmol/L), two polyphenols (chlorogenic acid, 3150 ± 120 μmol/L; caffeic acid, 1394 ± 52 μmol/L), two lignans (phillyrin, promoter; arctigenin, 2129 ± 10.5 μmol/L), and two phenethyl alcohol (forsythiaside A, 2155 ± 8.5 μmol/L; its isomer). Their action mechanisms included competitive inhibition, competitive promotion, noncompetitive inhibition, and uncompetitive inhibition. In sum, using the appropriate methods, more active ingredients can be simply and quickly screened out all at one time from a complex natural product system. In addition, F. suspensa leaves contain numerous inhibitors of pancreatic lipase.

Novel linear and step-gradient counter-current chromatography for bio-guided isolation and purification of cytotoxic podophyllotoxins from Dysosma versipellis (Hance).

PubMed

Yang, Zhi; Liu, Xiaoman; Wang, Kuiwu; Cao, Xiaoji; Wu, Shihua

2013-03-01

Dysosma versipellis (Hance) is a famous traditional Chinese medicine for the treatment of snakebite, weakness, condyloma accuminata, lymphadenopathy, and tumors for thousands of years. In this work, four podophyllotoxin-like lignans including 4'-demethylpodophyllotoxin (1), α-peltatin (2), podophyllotoxin (3), β-peltatin (4) as major cytotoxic principles of D. versipellis were successfully isolated and purified by several novel linear and step gradient counter-current chromatography methods using the systems of hexane/ethyl acetate/methanol/water (4:6:3:7 and 4:6:4:6, v/v/v/v). Compared with isocratic elution, linear and step-gradient elution can provide better resolution and save more time for the separation of photophyllotoxin and its congeners. Their cytotoxicities were further evaluated and their structures were validated by high-resolution electrospray TOF MS and nuclear magnetic resonance spectra. All components showed potent anticancer activity against human hepatoma cells HepG2. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

New phytochemicals as potential human anti-aging compounds: Reality, promise, and challenges.

PubMed

Corrêa, Rúbia C G; Peralta, Rosane M; Haminiuk, Charles W I; Maciel, Giselle Maria; Bracht, Adelar; Ferreira, Isabel C F R

2018-04-13

Aging is an inevitable process influenced by genetic, lifestyle, and environmental factors. Indirect evidence shows that several phytochemicals can have anti-aging capabilities, although direct evidence in this field is still limited. This report aims to provide a critical review on aspects related to the use of novel phytochemicals as anti-aging agents, to discuss the obstacles found when performing most anti-aging study protocols in humans, and to analyze future perspectives. In addition to the extensively studied resveratrol, epicatechin, quercetin, and curcumin, new phytochemicals have been reported to act as anti-aging agents, such as the amino acid L-theanine isolated from green tea, and the lignans arctigenin and matairesinol isolated from Arctium lappa seeds. Furthermore, this review discusses the application of several new extracts rich in phytochemicals with potential use in anti-aging therapies. Finally, this review also discusses the most important biomarkers to test anti-aging interventions, the necessity of conducting epidemiological studies and the need of clinical trials with adequate study protocols for humans.

Endophytic Fungus from Sinopodophyllum emodi (Wall.) Ying that Produces Podophyllotoxin.

PubMed

Liang, Zizhen; Zhang, Jia; Zhang, Xuan; Li, Jinjie; Zhang, Xiaoqian; Zhao, Changqi

2016-02-01

The aryltetralin lactone podophyllotoxin, which exhibits pronounced antineoplastic activity, is used as the precursor of the following three clinical anticancer drugs: Etoposide™, Etopophos™ and Teniposide™. The natural occurrence of this arylnaphthalene lignan is scarce and unable to meet the ever-rising demand in the medical industry. Thus, developing alternative sources for the production of podophyllotoxin is extremely urgent. This is the first report of the production of podophyllotoxin from endophytic Alternaria tenuissima isolated from Sinopodophyllum emodi (Wall.) Ying. The identification of podophyllotoxin was performed using high-performance liquid chromatography and liquid chromatography-mass spectrometry (MS)-MS and confirmed by comparison with authentic standards. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Regularity of changes in main active components of Schisandra chinensis before and after being processed with vinegar].

PubMed

Li, Li; Xiao, Yong-Qing; Yu, Ding-Rong; Ma, Yin-Lian; Zhu, Ming-Gui; Chen, Liang

2012-12-01

To investigate the regularity of changes in the main active components of Schisandra chinensis preparations before and after being processed with vinegar. High performance liquid chromatography was used to analyze the changes in the content of lignans and organic acids in S. chinensis preparations before and after being processed with vinegar. After being processed with vinegar, the content of lignans in S. chinensis preparations significantly reduced, while that of organic acids significantly increased. The ratio between them reduced from 1:16 (raw product) to 1:21 (vinegar products). The changes in the main pharmacological effects of S. chinensis are related to not only the changes in the contents of lignan and organic acids, but also the significant changes in the ratio relations between the two components. This is of great significance to the correlation among the principle of S. chinensis processed with vinegar and material basis and the changes in pharmacological effects.

Lignan enhancement in hairy root cultures of Linum album using coniferaldehyde and methylenedioxycinnamic acid.

PubMed

Ahmadian Chashmi, Najmeh; Sharifi, Mohsen; Behmanesh, Mehrdad

2016-07-03

Feeding experiments with hairy root cultures of Linum album have established that the extracellular coniferaldehyde is a good precursor for production of two lignans: lariciresinol (LARI) and pinoresinol (PINO). The accumulation of the LARI, PINO, and podophyllotoxin (PTOX) in hairy roots were enhanced about 14.8-, 8.7-, and 1.5-fold (107.61, 8.7 and 6.42 µg g(-1) Fresh Wight), respectively, by the addition of coniferaldehyde (2 mM) to the culture media (after 24 hr). This result was correlated with an increase pinoresinol/lariciresinol reductase (PLR) expression gene and cinnamyl alcohol dehydrogenase (CAD) activity in the fed hairy roots. Adding 3,4-(methylendioxy)cinnamic acid (MDCA) precursor did not influence on the lignans accumulation, but the lignin content of the hairy roots was increased. Moreover, the expression genes of phenylalanine ammonialyase (PAL), CAD, and cinnamoyl-CoA reductase (CCR) were influenced after feeding hairy roots with MDCA.

Concentration of the mammalian lignans enterolactone and enterodiol in milk of cows fed diets containing different concentrations of whole flaxseed.

PubMed

Petit, H V; Gagnon, N

2009-10-01

A total of 32 lactating Holstein cows with mean body weight of 622 kg (s.e. = 24) were allotted, at week 25 of lactation, to eight groups of four cows blocked for similar days in milk. The objective of the experiment was to determine the effect of feeding four dietary concentrations (0, 50, 100 or 150 g/kg of dry matter) of whole flaxseed, which contains the plant lignan precursor secoisolariciresinol diglucoside (SDG), on concentrations of two mammalian lignans (enterodiol and enterolactone) in milk. The effects of the four diets on feed intake, milk production, milk composition and digestion were also studied. Cows within each block were assigned to one of the four isonitrogenous and isoenergetic total mixed diets and the experiment was carried out from week 25 to 29 of lactation. Diets were fed for ad libitum intake. Enterolactone was the mammalian lignan, of the two metabolites studied, detected in the milk of cows and its concentration in milk tended (P = 0.08) to increase linearly with higher intake of SDG in the diet. Feed intake, milk yield and milk composition were similar among diets. Milk fatty acid profile was slightly improved by feeding flaxseed, as shown by higher concentrations of fatty acids (e.g. n-3) recognized as being beneficial for human health. Those results suggest that feeding of whole flaxseed may result in changes in milk fatty acid composition and enterolactone content, which offer benefits for consumers.

Formation of Lignans(-)-Secoisolariciresinol and (-)-Matairesinol with Forsythia intermedia Cell-Free Extracts

NASA Technical Reports Server (NTRS)

Umezawa, Toshiaki; Davin, Laurence B.; Lewis, Norman G.

1991-01-01

In vivo labeling experiments of Forsythia intermedia plant tissue with [8-(C-14)]- and [9,9-(2)H2,OC(2)H3]coniferyl alcohols revealed that the lignans, (-)-secoisolariciresinol and (-)-matairesinol, were derived from two coniferyl alcohol molecules; no evidence for the formation of the corresponding (+)-enantiomers was found. Administration of (+/-)-[Ar-(H-3)] secoisolariciresinols to excised shoots of F.intermedia resulted in a significant conversion into (-)-matairesinol; again, the (+)-antipode was not detected. Experiments using cell-free extracts of F.intermedia confirmed and extended these findings. In the presence of NAD(P)H and H2O2, the cell-free extracts catalyzed the formation of (-)- secoisolariciresinol, with either [8-(C-14)]- or [9,9-(2)H2,OC(2)H3]coniferyl alcohols as substrates. The (+)- enantiomer was not formed. Finally, when either (-)-[Ar-(H-3)] or (+/-)-[Ar-(H-2)]secoisolariciresinols were used as substrates, in the presence of NAD(P), only (-)- and not (+)-matairesinol formation occurred. The other antipode, (+)-secoisolariciresinol, did not serve as a substrate for the formation of either (+)- or (-)-matairesinol. Thus, in F.intermedia, the formation of the lignan, (-)-secoisolariciresinol, occurs under strict stereochemical control, in a reaction or reactions requiring NAD(P)H and H2O2 as cofactors. This stereoselectivity is retained in the subsequent conversion into (-)-matairesinol, since (+)-secoisolariciresinol is not a substrate. These are the first two enzymes to be discovered in lignan formation.

Role of bifidobacteria in the activation of the lignan secoisolariciresinol diglucoside.

PubMed

Roncaglia, Lucia; Amaretti, Alberto; Raimondi, Stefano; Leonardi, Alan; Rossi, Maddalena

2011-10-01

Lignans are ubiquitous plant polyphenols, which have relevant health properties being the major phytoestrogens occurring in Western diets. Secoisolariciresinol (SECO) is the major dietary lignan mostly found in plants as secoisolariciresinol diglucoside (SDG). To exert biological activity, SDG requires being deglycosylated to SECO and transformed to enterodiol (ED) and enterolactone (EL) by the intestinal microbes. The involvement of bifidobacteria in the transformation of lignans glucosides has been investigated for the first time in this study. Twenty-eight strains were assayed for SDG and SECO activation. They all failed to transform SECO into reduced metabolites, excluding any role in ED and EL production. Ten Bifidobacterium cultures partially hydrolyzed SDG, giving both SECO and the monoglucoside with yields < 25%. When the cell-free extracts were assayed in SDG transformation, seven additional strains were active in the hydrolysis. Cellobiose induced β-glucosidase activity and caused the enhancement of both the rate of SDG hydrolysis and the final yield of SECO only in the strains capable of SDG bioconversion. The highest SDG conversion to SECO was achieved by Bifidobacterium pseudocatenulatum WC 401, which exhibited 75% yield in cellobiose-based medium after 48 h. These results indicate that SDG hydrolysis is not a common feature in Bifidobacterium genus, but selected probiotic strains can be combined to β-glucoside-based prebiotics to enhance the release of SECO, thus improving its bioavailability for absorption by colonic mucosa and/or the biotransformation to ED and EL by other intestinal microorganisms.

AAPH-mediated antioxidant reactions of secoisolariciresinol and SDG.

PubMed

Hosseinian, Farah S; Muir, Alister D; Westcott, Neil D; Krol, Ed S

2007-02-21

Secoisolariciresinol (SECO ) is the major lignan found in flaxseed (Linum usitatissimum L.) and is present in a polymer that contains secoisolariciresinol diglucoside (SDG ). SECO, SDG and the polymer are known to have a number of health benefits, including reduction of serum cholesterol levels, delay in the onset of type II diabetes and decreased formation of breast, prostate and colon cancers. The health benefits of SECO and SDG may be partially attributed to their antioxidant properties. To better understand their antioxidant properties, SECO and SDG were oxidized using 2,2'-azobis(2-amidinopropane), an in vitro model of radical scavenging. The major lignan radical-scavenging oxidation products and their formation over time were determined. SDG was converted to four major products, which were the result of a phenoxyl radical intermediate. One of these products, a dimer of SDG, decomposed under the reaction conditions to form two of the other major products, and . SECO was converted to five major products, two of which were also the result of a phenoxyl radical intermediate. The remaining products were the result of an unexpected alkoxyl radical intermediate. The phenol oxidation products were stable under the reaction conditions, whereas two of the alcohol oxidation products decomposed. In general, only one phenol group on the lignans was oxidized, suggesting that the number of phenols per molecule may not predict radical scavenging antioxidant ability of lignans. Finally, SECO is a superior antioxidant to SDG, and it may be that the additional alcohol oxidation pathway contributes to its greater antioxidant ability.

Identification and characterization of cis-acting elements involved in the regulation of ABA- and/or GA-mediated LuPLR1 gene expression and lignan biosynthesis in flax (Linum usitatissimum L.) cell cultures.

PubMed

Corbin, Cyrielle; Renouard, Sullivan; Lopez, Tatiana; Lamblin, Frédéric; Lainé, Eric; Hano, Christophe

2013-03-15

Pinoresinol lariciresinol reductase 1, encoded by the LuPLR1 gene in flax (Linum usitatissimum L.), is responsible for the biosynthesis of (+)-secoisolariciresinol, a cancer chemopreventive phytoestrogenic lignan accumulated in high amount in the hull of flaxseed. Our recent studies have demonstrated a key role of abscisic acid (ABA) in the regulation of LuPLR1 gene expression and thus of the (+)-secoisolariciresinol synthesis during the flax seedcoat development. It is well accepted that gibberellins (GA) and ABA play antagonistic roles in the regulation of numerous developmental processes; therefore it is of interest to clarify their respective effects on lignan biosynthesis. Herein, using flax cell suspension cultures, we demonstrate that LuPLR1 gene expression and (+)-secoisolariciresinol synthesis are up-regulated by ABA and down-regulated by GA. The LuPLR1 gene promoter analysis and mutation experiments allow us to identify and characterize two important cis-acting sequences (ABRE and MYB2) required for these regulations. These results imply that a cross-talk between ABA and GA signaling orchestrated by transcription factors is involved in the regulation of lignan biosynthesis. This is particularly evidenced in the case of the ABRE cis-regulatory sequence of LuPLR1 gene promoter that appears to be a common target sequence of GA and ABA signals. Copyright © 2012 Elsevier GmbH. All rights reserved.

Reductive Bis-addition of Aromatic Aldehydes to α,β-Unsaturated Esters via the Use of Sm/Cu(I) in Air: A Route to the Construction of Furofuran Lignans.

PubMed

Liu, Yongjun; Tian, Guang; Li, Jingjing; Qi, Yan; Wen, Yonghong; Du, Feng

2017-06-02

The novel bis-addition of benzaldehydes to acrylates or maleates was achieved by the direct use of samarium metal with the assistance of CuI under mild conditions under dry air, and the useful 2-hydroxylalkyl-γ-butyrolactons and lignan derivatives were thus constructed with high efficiency. The key factors that influence the reaction efficiency were investigated. The use of potassium iodide and molecular sieves as additives can improve the reaction efficiency remarkably.

Novel Derivative of Benzofuran Induces Cell Death Mostly by G2/M Cell Cycle Arrest through p53-dependent Pathway but Partially by Inhibition of NF-κB*

PubMed Central

Manna, Sunil K.; Bose, Julie S.; Gangan, Vijay; Raviprakash, Nune; Navaneetha, Thota; Raghavendra, Pongali B.; Babajan, Banaganapalli; Kumar, Chitta S.; Jain, Swatantra K.

2010-01-01

The Dracaena resin is widely used in traditional medicine as an anticancer agent, and benzofuran lignan is the active component. In this report, we provide evidence that the synthetic derivative of benzofuran lignan (Benfur) showed antitumor activities. It induced apoptosis in p53-positive cells. Though it inhibited endotoxin-induced nuclear factor κB (NF-κB) activation in both p53-positive and -negative cells, the activation of caspase 3 was observed in p53-positive cells. It showed partial cell death effect in both p53-positive and -negative cells through inhibition of NF-κB. Cell cycle analysis using flow cytometry showed that treatment with this novel benozofuran lignan derivative to Jurkat T-cells, but not U-937 cells, resulted in a G2/M arrest in a dose- and time-dependent manner. It increased amounts of p21, p27, and cyclin B, but not phospho-Rb through p53 nuclear translocation in Jurkat T-cells, but not in U-937 cells. It inhibited amounts of MDM2 (murine double minute 2) by repressing the transcription factor Sp1, which was also proved in silico. It induced cell death in tumor cells, but not in primary T-cells. Overall, our data suggest that Benfur-mediated cell death is partially dependent upon NF-κB, but predominantly dependent on p53. Thus, this novel benzofuran lignan derivative can be effective chemopreventive or chemotherapeutic agent against malignant T-cells. PMID:20472557

Flaxseed and cardiovascular health.

PubMed

Prasad, Kailash

2009-11-01

Flaxseed and its components may improve cardiovascular health because of their numerous attributes. Flaxseed contains 35% of its mass as oil, of which 55% is alpha-linolenic acid (ALA). Flax meal, which is devoid of oil, contains the lignan secoisolariciresinol diglucoside (SDG). Flaxseed, flaxseed with very low ALA, flaxseed oil, flax lignan complex (FLC), and SDG reduce the development of hypercholesterolemic atherosclerosis by 46%, 69%, 0%, 73%, and 34%, respectively, in the rabbit model. FLC and SDG slow the progression of atherosclerosis but have no effect in regression of atherosclerosis. Suppression of atherosclerosis by flaxseed is the result of its lignan content and not the result of ALA content. Suppression of atherosclerosis is associated with lowering of serum lipids and antioxidant activity. Effects of flaxseed on serum lipids in experimental animals are variable from no change to slight reduction. Flaxseed oil does not affect serum lipids, except for a slight reduction in serum triglycerides. Lignan in general reduces serum total cholesterol and low-density lipoprotein cholesterol and raises serum high-density lipoprotein cholesterol. SDG and its metabolites have antioxidant activity. Flaxseed and flaxseed oil do not have antioxidant activity except they suppress oxygen radical production by white blood cells. Flaxseed oil/ALA has variable effects on inflammatory mediators/markers (interleukin [IL]-1beta, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor-alpha, interferon-gamma, C-reactive protein, and serum amyloid A). Doses of ALA less than 14 g/d do not affect inflammatory mediators/markers, but 14 g/d or greater reduce inflammatory mediators/markers. Flaxseed oil decreases soluble vascular cell adhesion molecule-1 but has no effect on soluble intracellular adhesion molecule-1, soluble E-selectin, and monocyte colony-stimulating factor. Flaxseed has variable effects on IL-6, high-sensitivity C-reactive protein, and soluble vascular cell adhesion molecule-1. FLC reduces plasma levels of C-reactive protein but has no effects on IL-6, tumor necrosis factor-alpha, soluble intracellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, or monocyte chemoattractant protein. Flaxseed has a very small hypotensive effect, but flaxseed oil does not lower blood pressure. However, SDG is a very potent hypotensive agent. Flaxseed oil decreases platelet aggregation and increases platelet activating inhibitor-1 and bleeding time. Flaxseed and FLC have no effect on the hemopoietic system. SDG is a potent angiogenic and antiapoptotic agent that may have a role in cardioprotection in ischemic heart disease. In conclusion, flaxseed, FLC, and SDG, but not flaxseed oil, suppress atherosclerosis, and FLC and SDG slow progression of atherosclerosis but have no effect on regression. Flaxseed oil suppresses oxygen radical production by white blood cells, prolongs bleeding time, and in higher doses suppresses serum levels of inflammatory mediators and does not lower serum lipids.

(+)-rumphiin and polyalthurea, new compounds from the stems of Polyalthia rumphii.

PubMed

Wang, Tian-Shan; Luo, You-Ping; Wang, Jing; He, Meng-Xiong; Zhong, Ming-Guo; Li, Ying; Song, Xiao-Ping

2013-10-01

Two new compounds, (+)-rumphiin (3) and polyalthurea (7), together with seven known ones, 3,4,5-trimethoxy benzoic acid (1), (-)-seselinone (2), cannabisin D (4), allantoin (5), oxostephanine (6) and a mixture of beta-sitosterol (8) and stigmasterol (9) were isolated from the stems of Polyalthia rumphii. The chemical structures of 3 and 7 were elucidated by the combination of spectroscopic data, and the absolute configuration of 3 at C-2 was determined by the matrix method to be R. All compounds were evaluated for their cytotoxicity on four human cancer cell lines, which demonstrated that 3 was a moderate bioactive lignan, and 6 showed significant anticancer activity against SPC-A-1 and BEL-7402 cell lines with IC50 values of 1.47 and 1.73 microg/mL, respectively.

Sesquiterpenoids and lignans from the roots of Valeriana officinalis L.

PubMed

Wang, Peng-Cheng; Ran, Xin-Hui; Chen, Rui; Luo, Huai-Rong; Ma, Qing-Yun; Liu, Yu-Qing; Hu, Jiang-Miao; Huang, Sheng-Zhuo; Jiang, He-Zhong; Chen, Zhong-Quan; Zhou, Jun; Zhao, You-Xing

2011-10-01

Two new guaiane-type sesquiterpenoids, valerol A (1) and kessyl 3-acetate (2), together with nine known compounds, valeracetate (3), anismol A (4), orientalol C (5), spatulenol (6), 4α,10α-epoxyaromadendrane (7), (+)-8-hydroxypinoresinol (8), pinorespiol (9), pinoresinol 4-O-β-D-glucopyranoside (10), and 8-hydroxypinoresinol 4'-O-β-D-glucopyranoside (11) were isolated from the roots of Valeriana officinalis. The structures and relative configurations of 1 and 2 were elucidated on the basis of spectroscopic methods (1D- and 2D-NMR, MS, UV, and IR). These compounds were evaluated for inhibitory activity on acetylcholinesterase (AChE) and enhancing activity on nerve growth factor (NGF)-mediated neurite outgrowth in PC12 cells. Copyright © 2011 Verlag Helvetica Chimica Acta AG, Zürich.

Current knowledge of Schisandra chinensis (Turcz.) Baill. (Chinese magnolia vine) as a medicinal plant species: a review on the bioactive components, pharmacological properties, analytical and biotechnological studies.

PubMed

Szopa, Agnieszka; Ekiert, Radosław; Ekiert, Halina

2017-01-01

Schisandra chinensis Turcz. (Baill.) is a plant species whose fruits have been well known in Far Eastern medicine for a long time. However, schisandra seems to be a plant still underestimated in contemporary therapy still in the countries of East Asia. The article presents latest available information on the chemical composition of this plant species. Special attention is given to dibenzo cyclooctadiene lignans. In addition, recent studies of the biological activity of dibenzocyclooctadiene lignans and schisandra fruit extracts are recapitulated. The paper gives a short resume of their beneficial effects in biological systems in vitro, in animals, and in humans, thus underlining their medicinal potential. The cosmetic properties are depicted, too. The analytical methods used for assaying schisandra lignans in the scientific studies and also in industry are also presented. Moreover, special attention is given to the information on the latest biotechnological studies of this plant species. The intention of this review is to contribute to a better understanding of the huge potential of the pharmacological relevance of S. chinensis.

Plant constituents interfering with human sex hormone-binding globulin. Evaluation of a test method and its application to Urtica dioica root extracts.

PubMed

Gansser, D; Spiteller, G

1995-01-01

A test system is described, which allows the search for compounds interfering with human sex hormone-binding globulin (SHBG) even in complex plant extracts. The method has been evaluated and applied to Urtica dioica root extracts. The lignan secoisolariciresinol (5) as well as a mixture of isomeric (11 E)-9,10,13-trihydroxy-11-octadecenoic and (10 E)-9,12,13-trihydroxy-10-octadecenoic acids (3 and 4, resp.) were demonstrated to reduce binding activity of human SHBG. Methylation of the mixture of 3 and 4 increased its activity about 10-fold.

Process-induced compositional changes of flaxseed.

PubMed

Wanasundara, P K; Shahidi, F

1998-01-01

Flaxseed has been used as an edible grain in different parts of the world since ancient times. However, use of flaxseed oil has been limited due to its high content of polyunsaturated fatty acids. Nonetheless, alpha-linolenic acid, dietary fiber and lignans of flaxseed have regained attention. New varieties of flaxseed containing low levels of alpha-linolenic acid are available for edible oil extraction. Use of whole flaxseed in foods provides a means to utilise all of its nutrients and require minimum processing steps. However, the presence of cyanogenic glucosides and diglucosides in the seeds is a concern as they may release cyanide upon hydrolysis. In addition, the polyunsaturated fatty acids may undergo thermal or autooxidation when exposed to air or high temperatures that are used in food preparation. Studies todate on oxidation products of intact flaxseed lipids have not shown any harmful effects when flaxseed is included, up to 28%, in the baked products. Furthermore, cyanide levels produced as a result of autolysis are below the harmful limits to humans. However, the meals left after oil extraction require detoxification but, by solvent extraction, to reduce the harmful effects of cyanide when used in animal rations. Flaxseed meal is a good source of proteins; these could be isolated by complexation with sodium hexametaphosphate without changing their nutritional value or composition. In addition, the effect of germination on proteins, lipids, cyanogenic glycosides, and other minor constituents of flaxseed is discussed.

Cytotoxic and potential anticancer constituents from the stems of Schisandra pubescens.

PubMed

Lu, Yan; Li, Yu-Quan; Liu, Yi-Nan; Lee, Kuo-Hsiung; Chen, Dao-Feng

2013-09-01

The diethyl ether extract of the stems of Schisandra pubescens Hemsl. et Wils. (Schisandraceae) was found to exhibit cytotoxic activity in vitro. However, investigations of the bioactive constituents of this plant have been very limited. Elucidation of the cytotoxic constituents of S. pubescens was performed. Repeated silica gel column chromatography and preparative TLC were used for the chemical investigation of the diethyl ether extract of S. pubescens stems. All isolates were evaluated for their in vitro cytotoxicity against A549, PC-3, KB and KBvin human cancer cell lines. Nine known compounds were obtained, including four lignans, epischisandrone (1), tigloylgomisin P (2), cagayanone (3) and (-)-gomisin L₂ (4), together with five triterpenoids, micranoic acid B (5), lancifodilactone H (6), coccinic acid (7), schisanlactone B (8) and anwuweizonic acid (9). Compounds 2-6 and 8 showed moderate to marginal cytotoxicity, with GI₅₀ values of 11.83-35.65 μM. The isolation of 1-9 from S. pubescens and the cytotoxicities of 3-6 are first reported. Compounds 2-6 and 8 could be the active principles responsible for the anticancer effects of S. pubescens.

Deoxypodophyllotoxin isolated from Juniperus communis induces apoptosis in breast cancer cells.

PubMed

Benzina, Sami; Harquail, Jason; Jean, Stephanie; Beauregard, Annie-Pier; Colquhoun, Caitlyn D; Carroll, Madison; Bos, Allyson; Gray, Christopher A; Robichaud, Gilles A

2015-01-01

The study of anticancer properties from natural products has regained popularity as natural molecules provide a high diversity of chemical structures with specific biological and medicinal activity. Based on a documented library of the most common medicinal plants used by the indigenous people of North America, we screened and isolated compounds with anti-breast cancer properties from Juniperus communis (common Juniper). Using bioassay-guided fractionation of a crude plant extract, we identified the diterpene isocupressic acid and the aryltetralin lignan deoxypodophyllotoxin (DPT) as potent inducers of caspase-dependent programmed cell death (apoptosis) in malignant MB231 breast cancer cells. Further elucidation revealed that DPT, in contrast to isocupressic acid, also concomitantly inhibited cell survival pathways mediated by the MAPK/ERK and NFκB signaling pathways within hours of treatment. Our findings emphasize the potential and importance of natural product screening for new chemical entities with novel anticancer activities. Natural products research complemented with the wealth of information available through the ethnobotanical and ethnopharmacological knowledge of the indigenous peoples of North America can provide new candidate entities with desirable bioactivities to develop new cancer therapies.

Anti-Inflammatory and Neuroprotective Constituents from the Peels of Citrus grandis.

PubMed

Kuo, Ping-Chung; Liao, Yu-Ren; Hung, Hsin-Yi; Chuang, Chia-Wei; Hwang, Tsong-Long; Huang, Shiow-Chyn; Shiao, Young-Ji; Kuo, Daih-Huang; Wu, Tian-Shung

2017-06-09

A series of chromatographic separations performed on the ethanol extracts of the peels of Citrus grandis has led to the characterization of forty compounds, including seventeen coumarins, eight flavonoids, two triterpenoids, four benzenoids, two steroids, one lignan, one amide, and five other compounds, respectively. The chemical structures of the purified constituents were identified on the basis of spectroscopic elucidation, including 1D- and 2D-NMR, UV, IR, and mass spectrometric analysis. Most of the isolated compounds were examined for their inhibition of superoxide anion generation and elastase release by human neutrophils. Among the isolates, isomeranzin ( 3 ), 17,18-dihydroxybergamottin ( 12 ), epoxybergamottin ( 13 ), rhoifolin ( 19 ), vitexicarpin ( 22 ) and 4-hydroxybenzaldehyde ( 29 ) displayed the most significant inhibition of superoxide anion generation and elastase release with IC 50 values ranged from 0.54 to 7.57 μM, and 0.43 to 4.33 μM, respectively. In addition, 7-hydroxy-8-(2'-hydroxy-3'-methylbut-3'-enyl)coumarin ( 8 ) and 17,18-dihydroxybergamottin ( 12 ) also exhibited the protection of neurons against A-mediated neurotoxicity at 50 μM.

Study on human intestinal bacterium Blautia sp. AUH-JLD56 for the conversion of arctigenin to (-)-3'-desmethylarctigenin.

PubMed

Liu, Ming-Yue; Li, Meng; Wang, Xiu-Ling; Liu, Peng; Hao, Qing-Hong; Yu, Xiu-Mei

2013-12-11

Arctium lappa L. (A. lappa) is a popularly used vegetable as well as herbal medicine. Human intestinal microflora was reported to convert arctiin, the lignan compound with highest content in the dried fruits of Arctium lappa, to a series of metabolites. However, the specific bacterium responsible for the formation of 3'-desmethylarctigenin (3'-DMAG), the most predominant metabolite of arctiin by rat or human intestinal microflora, has not been isolated yet. In the present study, we isolated one single bacterium, which we named Blautia sp. AUH-JLD56, capable of solely biotransforming arctiin or arctigenin to (-)-3'-DMAG. The structure of the metabolite 3'-DMAG was elucidated by electrospray ionization mass spectrometry (ESI-MS) and (1)H and (13)C nuclear magnetic resonance spectroscopy. The biotransforming kinetics and maximum biotransforming capacity of strain AUH-JLD56 was investigated. In addition, the metabolite 3'-DMAG showed significantly higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity than that of the substrate arctigenin at the concentrations tested.

Bioactivation of Phytoestrogens: Intestinal Bacteria and Health.

PubMed

Landete, J M; Arqués, J; Medina, M; Gaya, P; de Las Rivas, B; Muñoz, R

2016-08-17

Phytoestrogens are polyphenols similar to human estrogens found in plants or derived from plant precursors. Phytoestrogens are found in high concentration in soya, flaxseed and other seeds, fruits, vegetables, cereals, tea, chocolate, etc. They comprise several classes of chemical compounds (stilbenes, coumestans, isoflavones, ellagitannins, and lignans) which are structurally similar to endogenous estrogens but which can have both estrogenic and antiestrogenic effects. Although epidemiological and experimental evidence indicates that intake of phytoestrogens in foods may be protective against certain chronic diseases, discrepancies have been observed between in vivo and in vitro experiments. The microbial transformations have not been reported so far in stilbenes and coumestans. However, isoflavones, ellagitanins, and lignans are metabolized by intestinal bacteria to produce equol, urolithins, and enterolignans, respectively. Equol, urolithin, and enterolignans are more bioavailable, and have more estrogenic/antiestrogenic and antioxidant activity than their precursors. Moreover, equol, urolithins and enterolignans have anti-inflammatory effects and induce antiproliferative and apoptosis-inducing activities. The transformation of isoflavones, ellagitanins, and lignans by intestinal microbiota is essential to be protective against certain chronic diseases, as cancer, cardiovascular disease, osteoporosis, and menopausal symptoms. Bioavailability, bioactivity, and health effects of dietary phytoestrogens are strongly determined by the intestinal bacteria of each individual.

Imbricatolic acid from Juniperus communis L. prevents cell cycle progression in CaLu-6 cells.

PubMed

De Marino, Simona; Cattaneo, Fabio; Festa, Carmen; Zollo, Franco; Iaccio, Annalisa; Ammendola, Rosario; Incollingo, Filomena; Iorizzi, Maria

2011-11-01

Imbricatolic acid was isolated from the methanolic extract of the fresh ripe berries of Juniperus communis (Cupressaceae) together with sixteen known compounds and a new dihydrobenzofuran lignan glycoside named juniperoside A. Their structures were determined by spectroscopic methods and by comparison with the spectral data reported in literature. Imbricatolic acid was evaluated for its ability to prevent cell cycle progression in p53-null CaLu-6 cells. This compound induces the upregulation of cyclin-dependent kinase inhibitors and their accumulation in the G1 phase of the cell cycle, as well as the degradation of cyclins A, D1, and E1. Furthermore, no significant imbricatolic acid-induced apoptosis was observed. Therefore, this plant-derived compound may play a role in the control of cell cycle. © Georg Thieme Verlag KG Stuttgart · New York.

Transcriptome-wide identification and characterization of CAD isoforms specific for podophyllotoxin biosynthesis from Podophyllum hexandrum.

PubMed

Bhattacharyya, Dipto; Hazra, Saptarshi; Banerjee, Anindyajit; Datta, Riddhi; Kumar, Deepak; Chakrabarti, Saikat; Chattopadhyay, Sharmila

2016-09-01

Podophyllotoxin (ptox) is a therapeutically important lignan derived from Podophyllum hexandrum and is used as a precursor for the synthesis of anticancer drugs etoposide, teniposide and etopophose. In spite of its enormous economic significance, genomic information on this endangered medicinal herb is scarce. We have performed de novo transcriptome analysis of methyl jasmonate (MeJA)-treated P. hexandrum cell cultures exhibiting enhanced ptox accumulation. The results revealed the maximum up-regulation of several isoforms of cinnamyl alcohol dehydrogenase (CAD). CAD catalyzes the synthesis of coniferyl alcohol and sinapyl alcohol from coniferaldehyde (CAld) and sinapaldehyde respectively. Coniferyl alcohol can produce both lignin and lignan while sinapyl alcohol produces only lignin. To isolate the CAD isoforms favoring ptox, we deduced full length cDNA sequences of four CAD isoforms: PhCAD1, PhCAD2, PhCAD3 and PhCAD4 from the contigs of the transcriptome data. In vitro enzyme assays indicated a higher affinity for CAld over sinapaldehyde for each isoform. In silico molecular docking analyses also suggested that PhCAD3 has a higher binding preference with CAld over sinapaldehyde, followed by PhCAD4, PhCAD2, and PhCAD1, respectively. The transgenic cell cultures overexpressing these isoforms independently revealed that PhCAD3 favored the maximum accumulation of ptox as compared to lignin followed by PhCAD4 and PhCAD2, whereas, PhCAD1 favored both equally. Together, our study reveals transcriptome-wide identification and characterization of ptox specific CAD isoforms from P. hexandrum. It provides a useful resource for future research not only on the ptox biosynthetic pathway but on overall P. hexandrum, an endangered medicinal herb with immense therapeutic importance.

Mass spectrometry-based analysis of whole-grain phytochemicals.

PubMed

Koistinen, Ville Mikael; Hanhineva, Kati

2017-05-24

Whole grains are a rich source of several classes of phytochemicals, such as alkylresorcinols, benzoxazinoids, flavonoids, lignans, and phytosterols. A high intake of whole grains has been linked to a reduced risk of some major noncommunicable diseases, and it has been postulated that a complex mixture of phytochemicals works in synergy to generate beneficial health effects. Mass spectrometry, especially when coupled with liquid chromatography, is a widely used method for the analysis of phytochemicals owing to its high sensitivity and dynamic range. In this review, the current knowledge of the mass spectral properties of the most important classes of phytochemicals found in cereals of common wheat, barley, oats, and rye is discussed.

Hepatocyte-protective effect of nectandrin B, a nutmeg lignan, against oxidative stress: Role of Nrf2 activation through ERK phosphorylation and AMPK-dependent inhibition of GSK-3β

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

Song, Jae-Sook; Kim, Eun-Kyung; Choi, Yong-Won

Oxidative stress can contribute to the development and progression of liver diseases, such as drug-induced or alcoholic liver injury, nonalcoholic fatty liver disease, and nonalcoholic steatohepatitis. Nectandrin B is a bioactive lignan isolated from nutmeg extract. To date, little information is available about its pharmacological activities in the liver. This study investigated the hepatocyte-protective effect of nectandrin B against tert-butylhydroperoxide-induced oxidative injury and the underlying molecular mechanism. The cell viability assay revealed that nectandrin B prevents apoptosis stimulated by tert-butylhydroperoxide in both HepG2 cells and primary mouse hepatocytes. Nectandrin B also attenuated ROS production and restored the depleted glutathione level.more » Real-time PCR and immunoblot analyses showed that the expression of glutamate-cysteine ligase, an enzyme responsible for the glutathione biosynthesis, was induced by nectandrin B, indicating its indirect antioxidative effect. The NF-E2-related factor-2 (Nrf2) regulates gene expression of an array of antioxidant enzymes in hepatocytes. Nectandrin B stimulated Nrf2 activation as evidenced by its enhanced nuclear accumulation and increased antioxidant response element (ARE)-luciferase activity. Intriguingly, the hepatocyte-protective effect of nectandrin B against oxidative damage was completely abrogated by Nrf2 knockdown using Nrf2 specific siRNA. Nectandrin B promoted ERK activation, but inactivated GSK-3β through the AMPK-mediated inhibitory phosphorylation. The enforced overexpression of dominant-negative mutant of MEK1 or AMPKα, or wild-type GSK-3β inhibited the increase in the NQO1-ARE-luciferase activity stimulated by nectandrin B, suggesting that both ERK and AMPK-GSK-3β signalings are involved in the activation of Nrf2/ARE pathway by nectandrin B. Consistent with this, cytoprotection and restoration of glutathione level by nectandrin B was also blocked by the overexpression of dominant-negative MEK1 or wild-type GSK-3β. Finally, our data demonstrate that nectandrin B has the ability to protect hepatocytes against oxidative injury through the activation of Nrf2/ARE pathway mediated by ERK phosphorylation and AMPK-dependent inactivation of GSK-3β. - Highlight: • Nectandrin B, a nutmeg lignan protects hepatocytes against oxidative damage. • Nectandrin B exerts an indirect antioxidative effect via the activation of Nrf2. • Both ERK and GSK-3β pathways contribute to the activation of Nrf2 and hepatocyte-protection by nectandrin B. • Nectandrin B can inactivate GSK-3β through the activation of AMPK in HepG2 cells.« less

Synergistic mutual potentiation of antifungal activity of Zuccagnia punctata Cav. and Larrea nitida Cav. extracts in clinical isolates of Candida albicans and Candida glabrata.

PubMed

Butassi, Estefanía; Svetaz, Laura A; Ivancovich, Juan J; Feresin, Gabriela E; Tapia, Alejandro; Zacchino, Susana A

2015-06-01

Zuccagnia punctata Cav. (Fabaceae) and Larrea nitida Cav. (Zygophyllaceae) are indistinctly or jointly used in traditional medicine for the treatment of fungal-related infections. Although their dichloromethane (DCM) extract have demonstrated moderate antifungal activities when tested on their own, antifungal properties of combinations of both plants have not been assessed previously. The aim of this study was to establish with statistical rigor whether Z. punctata (ZpE) and L. nitida DCM extract (LnE) interact synergistically against the clinically important fungi Candida albicans and Candida glabrata and to characterize the most synergistic combinations. For synergism assessment, the statistical-based Boik's design was applied. Eight ZpE-LnE fixed-ratio mixtures were prepared from four different months of 1 year and tested against Candida strains. Lϕ (Loewe index) of each mixture at different fractions affected (ϕ) allowed for the finding of the most synergistic combinations, which were characterized by HPLC fingerprint and by the quantitation of the selected marker compounds. Lϕ and confidence intervals were determined in vitro with the MixLow method, once the estimated parameters from the dose-response curves of independent extracts and mixtures, were obtained. Markers (four flavonoids for ZpE and three lignans for LnE) were quantified in each extract and their combinations, with a valid HPLC-UV method. The 3D-HPLC profiles of the most synergistic mixtures were obtained by HPLC-DAD. Three over four IC50ZpE/IC50LnE fixed-ratio mixtures displayed synergistic interactions at effect levels ϕ > 0.5 against C. albicans. The dosis of the most synergistic (Lϕ = 0.62) mixture was 65.96 µg/ml (ZpE = 28%; LnE = 72%) containing 8 and 36% of flavonoids and lignans respectively. On the other hand, one over four IC50ZpE/IC50LnE mixtures displays synergistic interactions at ϕ > 0.5 against C. glabrata. The dosis of the most synergistic (Lϕ = 0.67) mixture was 168.23 µg/ml (ZpE = 27%; LnE = 73%) with 9.7 and 31.6% of flavonoids and lignans respectively. Studies with the statistical-based MixLow method, allowed for the finding of the most ZpE-LnE synergistic mixtures, giving support to a proper joint use of both antifungal herbs in traditional medicine. Copyright © 2015 Elsevier GmbH. All rights reserved.

Chemical Constituents from Cimicifuga dahurica and Their Anti-Proliferative Effects on MCF-7 Breast Cancer Cells.

PubMed

Huyen, Chu Thi Thanh; Luyen, Bui Thi Thuy; Khan, Ghulam Jilany; Oanh, Ha Van; Hung, Ta Manh; Li, Hui-Jun; Li, Ping

2018-05-04

This study was designed to search for novel anti-cancer compounds from natural plants. The 70% ethanolic extract from the rizhomes of Cimicifuga dahurica (Turcz.) Maxim. (Ranunculaceae) was found to possess significant in vitro anti-proliferative effects on MCF-7 breast cancer cells. A phytochemical investigation using assay-guided fractionation of the ethanolic extract of C. dahurica resulted in the isolation of one new phenolic amide glycoside 3 , two new lignan glycosides 4 and 7 , one new 9,19-cycloartane triterpenoid glycoside 6 , and thirteen known constituents 1 , 2 , 5 , and 8 ⁻ 17 . The structures of 3 , 4 , 6 , and 7 were established using contemporary NMR methods and from their HRESIMS data. The anti-proliferative effects of isolated compounds were evaluated using the BrdU-proliferation kit. Five among the 17 isolated compounds showed significant anti-proliferative effects ( p ≤ 0.05), wherein compound 7 showed the most significant anti-proliferative and cell cycle arresting effect ( p ≤ 0.05) which followed a dose dependent manner. Western blot protein expression analysis showed a down expression of c-Myc and cyclin D1 which further elucidated the anti-proliferation mechanism of compound 7 while apoptotic effects were found in association with Bcl-2 family protein expression variations. Conclusively this study reports the isolation and identification of 17 compounds from C. dahurica , including four novel molecules, in addition to the fact that compound 7 possesses significant anti-proliferative and apoptotic effects in vitro that may require further exploration.

The association between dietary lignans, phytoestrogen-rich foods, and fiber intake and postmenopausal breast cancer risk: a German case-control study.

PubMed

Zaineddin, Aida Karina; Buck, Katharina; Vrieling, Alina; Heinz, Judith; Flesch-Janys, Dieter; Linseisen, Jakob; Chang-Claude, Jenny

2012-01-01

Phytoestrogens are structurally similar to estrogens and may affect breast cancer risk by mimicking estrogenic/antiestrogenic properties. In Western societies, whole grains and possibly soy foods are rich sources of phytoestrogens. A population-based case-control study in German postmenopausal women was used to evaluate the association of phytoestrogen-rich foods and dietary lignans with breast cancer risk. Dietary data were collected from 2,884 cases and 5,509 controls using a validated food-frequency questionnaire, which included additional questions phytoestrogen-rich foods. Associations were assessed using conditional logistic regression. All analyses were adjusted for relevant risk and confounding factors. Polytomous logistic regression analysis was performed to evaluate the associations by estrogen receptor (ER) status. High and low consumption of soybeans as well as of sunflower and pumpkin seeds were associated with significantly reduced breast cancer risk compared to no consumption (OR = 0.83, 95% CI = 0.70-0.97; and OR = 0.66, 95% CI = 0.77-0.97, respectively). The observed associations were not differential by ER status. No statistically significant associations were found for dietary intake of plant lignans, fiber, or the calculated enterolignans. Our results provide evidence for a reduced postmenopausal breast cancer risk associated with increased consumption of sunflower and pumpkin seeds and soybeans.

Effects of flaxseed lignan secoisolariciresinol diglucoside on preneoplastic biomarkers of cancer progression in a model of simultaneous breast and ovarian cancer development

PubMed Central

Delman, Devora M.; Fabian, Carol J.; Kimler, Bruce F.; Yeh, Henry; Petroff, Brian K.

2016-01-01

Breast cancer prevention efforts are focused increasingly on potentially beneficial dietary modifications due to their ease of implementation and wide acceptance. Secoisolariciresinol diglucoside (SDG) is a lignan found in high concentration in flaxseed that may have selective estrogen receptor modulator (SERM)-like effects resulting in antiestrogenic activity in a high estrogen environment. In parallel with a human phase II prevention trial, female ACI rats (n=8–10/group) received 0, 10 or 100 ppm SDG in the feed. The 100 ppm SDG treatment produced similar blood lignan levels as those observed in our human pilot study. Mammary and ovarian cancer progression were induced using local ovarian DMBA treatment and subcutaneous sustained release 17β-estradiol administered starting at 7 weeks of age. Mammary gland and ovarian tissues were collected at 3 months after initiation of treatment and examined for changes in epithelial cell proliferation (Ki-67, cell counts), histopathology and dysplasia scores as well as expression of selected genes involved in proliferation, estrogen signaling and cell adhesion. Treatment with SDG normalized several biomarkers in mammary gland tissue (dysplasia, cell number, and expression of several genes) that had been altered by carcinogen. There is no indication that SDG promotes pre-neoplastic progression in the ovarian epithelium. PMID:26010915

Cytotoxicity of arctigenin and matairesinol against the T-cell lymphoma cell line CCRF-CEM.

PubMed

Su, Shan; Cheng, Xinlai; Wink, Michael

2015-09-01

Arctigenin and matairesinol possess a diversity of bioactivities. Here we investigated the cytotoxicity of arctigenin and matairesinol against a T-cell lymphoma cell line CCRF-CEM and the underlying mechanisms that have not been explored before. The cytotoxic activity was investigated using MTT assay. The cell cycle arrest and reactive oxygen species (ROS) accumulation were determined by flow cytometric analysis. The apoptosis induction was assessed using Annexin V/Propidium Iodide assay. The gene quantification analysis was measured through real-time polymerase chain reaction. Arctigenin and matairesinol exhibited significant antiproliferative activity against CCRF-CEM cells after 72 h treatment with IC50 values of 1.21 ± 0.15 μm and 4.27 ± 0.41 μm, respectively. In addition, both lignans arrest CCRF-CEM cells in the S phase. Furthermore, they could induce apoptosis in CCRF-CEM cells in a concentration- and time-dependent manner. Interestingly, the lignans differentially regulated the expression of several key genes involved in apoptosis pathways, including Bax, Bad and caspase-9. Moreover, both lignans could increase ROS levels in CCRF-CEM cells. Our study provides an insight into the potential of arctigenin and matairesinol as good candidates for the development of novel agents against T-cell lymphoma. © 2015 Royal Pharmaceutical Society.

A genome-wide analysis of the flax (Linum usitatissimum L.) dirigent protein family: from gene identification and evolution to differential regulation

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

Corbin, Cyrielle; Drouet, Samantha; Markulin, Lucija

Identification of DIR encoding genes in flax genome. Analysis of phylogeny, gene/protein structures and evolution. Identification of new conserved motifs linked to biochemical functions. Investigation of spatio-temporal gene expression and response to stress. Dirigent proteins (DIRs) were discovered during 8-8' lignan biosynthesis studies, through identification of stereoselective coupling to afford either (+)- or (-)-pinoresinols from E-coniferyl alcohol. DIRs are also involved or potentially involved in terpenoid, allyl/propenyl phenol lignan, pterocarpan and lignin biosynthesis. DIRs have very large multigene families in different vascular plants including flax, with most still of unknown function. DIR studies typically focus on a small subset ofmore » genes and identification of biochemical/physiological functions. Herein, a genome-wide analysis and characterization of the predicted flax DIR 44-membered multigene family was performed, this species being a rich natural grain source of 8-8' linked secoisolariciresinol-derived lignan oligomers. All predicted DIR sequences, including their promoters, were analyzed together with their public gene expression datasets. Expression patterns of selected DIRs were examined using qPCR, as well as through clustering analysis of DIR gene expression. These analyses further implicated roles for specific DIRs in (-)-pinoresinol formation in seed-coats, as well as (+)-pinoresinol in vegetative organs and/or specific responses to stress. Phylogeny and gene expression analysis segregated flax DIRs into six distinct clusters with new cluster-specific motifs identified. We propose that these findings can serve as a foundation to further systematically determine functions of DIRs, i.e. other than those already known in lignan biosynthesis in flax and other species. Given the differential expression profiles and inducibility of the flax DIR family, we provisionally propose that some DIR genes of unknown function could be involved in different aspects of secondary cell wall biosynthesis and plant defense.« less

Urine phyto-oestrogen metabolites are not significantly associated with risk of type 2 diabetes: the Singapore Chinese health study.

PubMed

Talaei, Mohammad; Lee, Bee L; Ong, Choon N; van Dam, Rob M; Yuan, Jian M; Koh, Woon P; Pan, An

2016-05-01

We evaluated the relationship between urine concentrations of phyto-oestrogens (isoflavones and lignans) and risk of incident type 2 diabetes in middle-aged and elderly Chinese residing in Singapore. Urine metabolites of isoflavones and lignans were assayed by HPLC among 564 diabetes cases and 564 matched controls in a case-control study nested within the Singapore Chinese Health Study cohort. Participants were free of diagnosed diabetes, CVD and cancer at morning urine collections during 1999-2004. Cases were participants who reported to have physician-diagnosed diabetes at follow-up visits during 2006-2010, whereas controls were randomly selected among those who remained free of diabetes and were matched to the index cases by age, sex, dialect group and date of urine collection. Conditional logistic regression models were used to calculate OR and 95 % CI with adjustment for potential confounders. The mean age of the participants at the time of urine collection was 59·8 years, and the average interval between urine collection and diabetes diagnosis was 4·0 years. The multivariate-adjusted OR for diabetes were 1·00 (reference), 0·76 (95 % CI 0·52, 1·11), 0·78 (95 % CI 0·53, 1·14) and 0·79 (95 % CI 0·54, 1·15) across quartiles of urine isoflavones (P for trend=0·54), and were 1·00 (reference), 0·87 (95 % CI 0·60, 1·27), 1·10 (95 % CI 0·77, 1·56) and 0·93 (95 % CI 0·63, 1·37) for lignans (P for trend=0·93). The results were similar in men and women, as well as for individual metabolites of isoflavones (genistein, daidzein, glycitin and equol) or lignans (enterodiol and enterolactone). The present study did not find a significant association between urine phyto-oestrogen metabolites and risk of type 2 diabetes in Chinese adults.

Effects of photoperiod regimes and ultraviolet-C radiations on biosynthesis of industrially important lignans and neolignans in cell cultures of Linum usitatissimum L. (Flax).

PubMed

Anjum, Sumaira; Abbasi, Bilal Haider; Doussot, Joël; Favre-Réguillon, Alain; Hano, Christophe

2017-02-01

Lignans and neolignans are principal bioactive components of Linum usitatissimum L. (Flax), having multiple pharmacological activities. In present study, we are reporting an authoritative abiotic elicitation strategy of photoperiod regimes along with UV-C radiations. Cell cultures were grown in different photoperiod regimes (24h-dark, 24h-light and 16L/8D h photoperiod) either alone or in combination with various doses (1.8-10.8kJ/m 2 ) of ultraviolet-C (UV-C) radiations. Secoisolariciresinol diglucoside (SDG), lariciresinol diglucoside (LDG), dehydrodiconiferyl alcohol glucoside (DCG), and guaiacylglycerol-β-coniferyl alcohol ether glucoside (GGCG) were quantified by using reverse phase-high performance liquid chromatography (RP-HPLC). Results showed that the cultures exposed to UV-C radiations, accumulated higher levels of lignans, neolignans and other biochemical markers than cultures grown under different photoperiod regimes. 3.6kJ/m 2 dose of UV-C radiations resulted in 1.86-fold (7.1mg/g DW) increase in accumulation of SDG, 2.25-fold (21.6mg/g DW) in LDG, and 1.33-fold (9.2mg/g DW) in GGCG in cell cultures grown under UV+photoperiod than their respective controls. Furthermore, cell cultures grown under UV+dark showed 1.36-fold (60.0mg/g DW) increase in accumulation of DCG in response to 1.8kJ/m 2 dose of UV-C radiations. Smilar trends were observed in productivity of SDG, LDG and GGCG. Additionally, 3.6kJ/m 2 dose of UV-C radiations also resulted in 2.82-fold (195.65mg/l) increase in total phenolic production, 2.94-fold (98.9mg/l) in total flavonoid production and 1.04-fold (95%) in antioxidant activity of cell cultures grown under UV+photoperiod. These findings open new dimensions for feasible production of biologically active lignans and neolignans by Flax cell cultures. Copyright © 2017 Elsevier B.V. All rights reserved.

A genome-wide analysis of the flax (Linum usitatissimum L.) dirigent protein family: from gene identification and evolution to differential regulation.

PubMed

Corbin, Cyrielle; Drouet, Samantha; Markulin, Lucija; Auguin, Daniel; Lainé, Éric; Davin, Laurence B; Cort, John R; Lewis, Norman G; Hano, Christophe

2018-05-01

Identification of DIR encoding genes in flax genome. Analysis of phylogeny, gene/protein structures and evolution. Identification of new conserved motifs linked to biochemical functions. Investigation of spatio-temporal gene expression and response to stress. Dirigent proteins (DIRs) were discovered during 8-8' lignan biosynthesis studies, through identification of stereoselective coupling to afford either (+)- or (-)-pinoresinols from E-coniferyl alcohol. DIRs are also involved or potentially involved in terpenoid, allyl/propenyl phenol lignan, pterocarpan and lignin biosynthesis. DIRs have very large multigene families in different vascular plants including flax, with most still of unknown function. DIR studies typically focus on a small subset of genes and identification of biochemical/physiological functions. Herein, a genome-wide analysis and characterization of the predicted flax DIR 44-membered multigene family was performed, this species being a rich natural grain source of 8-8' linked secoisolariciresinol-derived lignan oligomers. All predicted DIR sequences, including their promoters, were analyzed together with their public gene expression datasets. Expression patterns of selected DIRs were examined using qPCR, as well as through clustering analysis of DIR gene expression. These analyses further implicated roles for specific DIRs in (-)-pinoresinol formation in seed-coats, as well as (+)-pinoresinol in vegetative organs and/or specific responses to stress. Phylogeny and gene expression analysis segregated flax DIRs into six distinct clusters with new cluster-specific motifs identified. We propose that these findings can serve as a foundation to further systematically determine functions of DIRs, i.e. other than those already known in lignan biosynthesis in flax and other species. Given the differential expression profiles and inducibility of the flax DIR family, we provisionally propose that some DIR genes of unknown function could be involved in different aspects of secondary cell wall biosynthesis and plant defense.

Replacement of the lactone moiety on podophyllotoxin and steganacin analogues with a 1,5-disubstituted 1,2,3-triazole via ruthenium-catalyzed click chemistry.

PubMed

Imperio, Daniela; Pirali, Tracey; Galli, Ubaldina; Pagliai, Francesca; Cafici, Laura; Canonico, Pier Luigi; Sorba, Giovanni; Genazzani, Armando A; Tron, Gian Cesare

2007-11-01

Steganacin and podophyllotoxin are two naturally occurring lignans first isolated from plant sources, which share the capability to disrupt tubulin assembly. Although not strictly essential for its activity, the lactone ring on both structures represents Achilles' heel, as it is a potential site of metabolic degradation and epimerization on its C2 carbon brings about a significant loss in potency. In the present manuscript, we have used the ruthenium-catalyzed [3+2] azide-alkyne cycloaddition, a click-chemistry reaction, to replace the lactone ring with a 1,5-disubstituted triazole in few synthetic steps. The compounds were cytotoxic, although to a lesser degree compared to podophyllotoxin, while retaining antitubulin activity. The present structures might therefore represent a good platform for the fast generation of metabolically stable compounds with few stereogenic centers that might be of value from a medicinal chemistry point of view.

Radix Bupleuri: A Review of Traditional Uses, Botany, Phytochemistry, Pharmacology, and Toxicology.

PubMed

Yang, Fude; Dong, Xiaoxv; Yin, Xingbin; Wang, Wenping; You, Longtai; Ni, Jian

2017-01-01

Radix Bupleuri (Chaihu) has been used as a traditional medicine for more than 2000 years in China, Japan, Korea, and other Asian countries. Phytochemical studies demonstrated that this plant contains essential oils, triterpenoid saponins, polyacetylenes, flavonoids, lignans, fatty acids, and sterols. Crude extracts and pure compounds isolated from Radix Bupleuri exhibited various biological activities, such as anti-inflammatory, anticancer, antipyretic, antimicrobial, antiviral, hepatoprotective, neuroprotective, and immunomodulatory effects. However, Radix Bupleuri could also lead to hepatotoxicity, particularly in high doses and with long-term use. Pharmacokinetic studies have demonstrated that the major bioactive compounds (saikosaponins a, b 2 , c, and d) were absorbed rapidly in rats after oral administration of the extract of Radix Bupleuri . This review aims to comprehensively summarize the traditional uses, botany, phytochemistry, pharmacology, toxicology, and pharmacokinetics of Radix Bupleuri reported to date with an emphasis on its biological properties and mechanisms of action.

Identification of minor secondary metabolites from the latex of Croton lechleri (Muell-Arg) and evaluation of their antioxidant activity.

PubMed

De Marino, Simona; Gala, Fulvio; Zollo, Franco; Vitalini, Sara; Fico, Gelsomina; Visioli, Francesco; Iorizzi, Maria

2008-06-01

Dragon's blood (Sangre de drago), a viscous red sap derived from Croton lechleri Muell-Arg (Euphorbiaceae), is extensively used by indigenous cultures of the Amazonian basin for its wound healing properties. The aim of this study was to identify the minor secondary metabolites and test the antioxidant activity of this sustance. A bioguided fractionation of the n-hexane, chloroform, n-butanol, and aqueous extracts led to the isolation of 15 compounds: three megastigmanes, four flavan-3-ols, three phenylpropanoids, three lignans, a clerodane, and the alkaloid taspine. In addition to these known molecules, six compounds were isolated and identified for the first time in the latex: blumenol B, blumenol C, 4,5-dihydroblumenol A, erythro-guaiacyl-glyceryl-beta-O-4'- dihydroconiferyl ether, 2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-propane-1,3-diol and floribundic acid glucoside. Combinations of spectroscopic methods ((1)H-, (13)C- NMR and 2D-NMR experiments), ESI-MS, and literature comparisons were used for compound identification. In vitro antioxidant activities were assessed by DPPH, total antioxidant capacity and lipid peroxidation assays. Flavan-3-ols derivatives (as major phenolic compounds in the latex) exhibited the highest antioxidant activity.

Biotransformation of lignan glycoside to its aglycone by Woodfordia fruticosa flowers: quantification of compounds using a validated HPTLC method.

PubMed

Mishra, Shikha; Aeri, Vidhu

2017-12-01

Saraca asoca Linn. (Caesalpiniaceae) is an important traditional remedy for gynaecological disorders and it contains lyoniside, an aryl tetralin lignan glycoside. The aglycone of lyoniside, lyoniresinol possesses structural similarity to enterolignan precursors which are established phytoestrogens. This work illustrates biotransformation of lyoniside to lyoniresinol using Woodfordia fruticosa Kurz. (Lythraceae) flowers and simultaneous quantification of lyoniside and lyoniresinol using a validated HPTLC method. The aqueous extract prepared from S. asoca bark was fermented using W. fruticosa flowers. The substrate and fermented product both were simultaneously analyzed using solvent system:toluene:ethyl acetate:formic acid (4:3:0.4) at 254 nm. The method was validated for specificity, accuracy, precision, linearity, sensitivity and robustness as per ICH guidelines. The substrate showed the presence of lyoniside, however, it decreased as the fermentation proceeded. On 3rd day, lyoniresinol starts appearing in the medium. In 8 days duration most of the lyoniside converted to lyoniresinol. The developed method was specific for lyoniside and lyoniresinol. Lyoniside and lyoniresinol showed linearity in the range of 250-3000 and 500-2500 ng. The method was accurate as resulted in 99.84% and 99.83% recovery, respectively, for lyoniside and lyoniresinol. Aryl tetralin lignan glycoside, lyoniside was successfully transformed into lyoniresinol using W. fruticosa flowers and their contents were simultaneously analyzed using developed validated HPTLC method.

Extraction, identification, fractionation and isolation of phenolic compounds in plants with hepatoprotective effects.

PubMed

Pereira, Carla; Barros, Lillian; Ferreira, Isabel C F R

2016-03-15

The liver is one of the most important organs of human body, being involved in several vital functions and regulation of physiological processes. Given its pivotal role in the excretion of waste metabolites and drugs detoxification, the liver is often subjected to oxidative stress that leads to lipid peroxidation and severe cellular damage. The conventional treatments of liver diseases such as cirrhosis, fatty liver and chronic hepatitis are frequently inadequate due to side effects caused by hepatotoxic chemical drugs. To overcome this problematic paradox, medicinal plants, owing to their natural richness in phenolic compounds, have been intensively exploited concerning their extracts and fraction composition in order to find bioactive compounds that could be isolated and applied in the treatment of liver ailments. The present review aimed to collect the main results of recent studies carried out in this field and systematize the information for a better understanding of the hepatoprotective capacity of medicinal plants in in vitro and in vivo systems. Generally, the assessed plant extracts revealed good hepatoprotective properties, justifying the fractionation and further isolation of phenolic compounds from different parts of the plant. Twenty-five phenolic compounds, including flavonoids, lignan compounds, phenolic acids and other phenolic compounds, have been isolated and identified, and proved to be effective in the prevention and/or treatment of chemically induced liver damage. In this perspective, the use of medicinal plant extracts, fractions and phenolic compounds seems to be a promising strategy to avoid side effects caused by hepatotoxic chemicals. © 2015 Society of Chemical Industry.

Effects of A Breast-Health Herbal Formula Supplement on Estrogen Metabolism in Pre- and Post-Menopausal Women not Taking Hormonal Contraceptives or Supplements: A Randomized Controlled Trial

PubMed Central

Laidlaw, Maggie; Cockerline, Carla A.; Sepkovic, Daniel W.

2010-01-01

Introduction Both indole-3-carbinol and dietary lignans have beneficial effects on estrogen metabolism and breast cancer risk. There is no published literature on the effects of a combination product. This study was designed to investigate the impact of a combination product on estrogen metabolism. The major trial objective was to determine whether a breast health supplement containing indole-3-carbinol and hydroxymatairesinol lignan would alter estrogen metabolism to favour C-2 hydroxylation and reduce C-16 hydroxylation. Higher concentrations of C-2 metabolites and lower concentrations of C-16 metabolites may reduce breast cancer risk and risk for other hormonally-related cancers. Methods Forty-seven pre-menopausal and forty-nine post-menopausal women were recruited for this study, and were divided by random allocation into treatment and placebo group. The treatment supplement contained HMR lignan, indole-3-carbinol, calcium glucarate, milk thistle, Schisandra chinesis and stinging nettle, and each woman consumed either treatment or placebo for 28 days. At day 0 and day 28, blood samples were analysed for serum enterolactone concentrations, and first morning random urine samples were assessed for estrogen metabolites. Repeated measures ANOVA statistical testing was performed. Results In pre-menopausal women, treatment supplementation resulted in a significant increase (P < 0.05) in urinary 2-OHE concentrations and in the 2:16α-OHE ratio. In post-menopausal women, treatment supplementation resulted in a significant increase in urinary 2-OHE concentrations. In pre- and post-menopausal women combined, treatment supplementation produced a significant increase in urinary 2-OHE concentration and a trend (P = 0.074) toward an increased 2:16α-OHE ratio. There were no significant increases in serum enterolactone concentrations in the treatment or placebo groups. Conclusions Supplementation with a mixture of indole-3-carbinol and HMR lignan in women significantly increased estrogen C-2 hydroxylation. This may constitute a mechanism for the reduction of breast cancer risk as well as risk for other estrogen-related cancers. Further studies with higher numbers of subjects are indicated. Trial registration ClinicalTrials.gov registration #NCT01089049. PMID:21234288

Reprogramming of gene expression during compression wood formation in pine: Coordinated modulation of S-adenosylmethionine, lignin and lignan related genes

PubMed Central

2012-01-01

Background Transcript profiling of differentiating secondary xylem has allowed us to draw a general picture of the genes involved in wood formation. However, our knowledge is still limited about the regulatory mechanisms that coordinate and modulate the different pathways providing substrates during xylogenesis. The development of compression wood in conifers constitutes an exceptional model for these studies. Although differential expression of a few genes in differentiating compression wood compared to normal or opposite wood has been reported, the broad range of features that distinguish this reaction wood suggest that the expression of a larger set of genes would be modified. Results By combining the construction of different cDNA libraries with microarray analyses we have identified a total of 496 genes in maritime pine (Pinus pinaster, Ait.) that change in expression during differentiation of compression wood (331 up-regulated and 165 down-regulated compared to opposite wood). Samples from different provenances collected in different years and geographic locations were integrated into the analyses to mitigate the effects of multiple sources of variability. This strategy allowed us to define a group of genes that are consistently associated with compression wood formation. Correlating with the deposition of a thicker secondary cell wall that characterizes compression wood development, the expression of a number of genes involved in synthesis of cellulose, hemicellulose, lignin and lignans was up-regulated. Further analysis of a set of these genes involved in S-adenosylmethionine metabolism, ammonium recycling, and lignin and lignans biosynthesis showed changes in expression levels in parallel to the levels of lignin accumulation in cells undergoing xylogenesis in vivo and in vitro. Conclusions The comparative transcriptomic analysis reported here have revealed a broad spectrum of coordinated transcriptional modulation of genes involved in biosynthesis of different cell wall polymers associated with within-tree variations in pine wood structure and composition. In particular, we demonstrate the coordinated modulation at transcriptional level of a gene set involved in S-adenosylmethionine synthesis and ammonium assimilation with increased demand for coniferyl alcohol for lignin and lignan synthesis, enabling a better understanding of the metabolic requirements in cells undergoing lignification. PMID:22747794

Investigation of Linum flavum (L.) Hairy Root Cultures for the Production of Anticancer Aryltetralin Lignans.

PubMed

Renouard, Sullivan; Corbin, Cyrielle; Drouet, Samantha; Medvedec, Barbara; Doussot, Joël; Colas, Cyril; Maunit, Benoit; Bhambra, Avninder S; Gontier, Eric; Jullian, Nathalie; Mesnard, François; Boitel, Michèle; Abbasi, Bilal Haider; Arroo, Randolph R J; Lainé, Eric; Hano, Christophe

2018-03-26

Linum flavum hairy root lines were established from hypocotyl pieces using Agrobacterium rhizogenes strains LBA 9402 and ATCC 15834. Both strains were effective for transformation but induction of hairy root phenotype was more stable with strain ATCC 15834. Whereas similar accumulation patterns were observed in podophyllotoxin-related compounds (6-methoxy-podophyllotoxin, podophyllotoxin and deoxypodophyllotoxin), significant quantitative variations were noted between root lines. The influence of culture medium and various treatments (hormone, elicitation and precursor feeding) were evaluated. The highest accumulation was obtained in Gamborg B5 medium. Treatment with methyl jasmonate, and feeding using ferulic acid increased the accumulation of aryltetralin lignans. These results point to the use of hairy root culture lines of Linum flavum as potential sources for these valuable metabolites as an alternative, or as a complement to Podophyllum collected from wild stands.

Interaction of Carthamus tinctorius lignan arctigenin with the binding site of tryptophan-degrading enzyme indoleamine 2,3-dioxygenase☆

PubMed Central

Temml, Veronika; Kuehnl, Susanne; Schuster, Daniela; Schwaiger, Stefan; Stuppner, Hermann; Fuchs, Dietmar

2013-01-01

Mediterranean Carthamus tinctorius (Safflower) is used for treatment of inflammatory conditions and neuropsychiatric disorders. Recently C. tinctorius lignans arctigenin and trachelogenin but not matairesinol were described to interfere with the activity of tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) in peripheral blood mononuclear cells in vitro. We examined a potential direct influence of compounds on IDO enzyme activity applying computational calculations based on 3D geometry of the compounds. The interaction pattern analysis and force field-based minimization was performed within LigandScout 3.03, the docking simulation with MOE 2011.10 using the X-ray crystal structure of IDO. Results confirm the possibility of an intense interaction of arctigenin and trachelogenin with the binding site of the enzyme, while matairesinol had no such effect. PMID:24251110

Enterolactone induces G1-phase cell cycle arrest in non-small cell lung cancer cells by down-regulating cyclins and cyclin-dependent kinases

PubMed Central

Chikara, Shireen; Lindsey, Kaitlin; Dhillon, Harsharan; Mamidi, Sujan; Kittilson, Jeffrey; Christofidou-Solomidou, Melpo; Reindl, Katie M.

2017-01-01

Flaxseed is a rich source of the plant lignan secoisolariciresinol diglucoside (SDG) which is metabolized into mammalian lignans enterodiol (ED) and enterolactone (EL) in the digestive tract. The anti-cancer properties of these lignans have been demonstrated for various cancer types, but have not been studied for lung cancer. In this study we investigated the anti-cancer effects of EL for several non-small cell lung cancer (NSCLC) cell lines of various genetic backgrounds. EL inhibited the growth of A549, H441, and H520 lung cancer cells in concentration- and time-dependent manners. The anti-proliferative effects of EL for lung cancer cells were not due to enhanced cell death, but rather due to G1-phase cell cycle arrest. Molecular studies revealed that EL- decreased mRNA or protein expression levels of the G1-phase promoters cyclin D1, cyclin E, cyclin-dependent kinases (CDK)-2, -4, and -6, and p-cdc25A; decreased phosphorylated retinoblastoma (p-pRb) protein levels; and simultaneously increased levels of p21WAF1/CIP1, a negative regulator of the G1-phase. The results suggest that EL inhibits the growth of NSCLC cell lines by down-regulating G1-phase cyclins and CDKs, and up-regulating p21WAF1/CIP1, which leads to G1-phase cell cycle arrest. Therefore, EL may hold promise as an adjuvant treatment for lung cancer therapy. PMID:28323486

Enterolactone Induces G1-phase Cell Cycle Arrest in Nonsmall Cell Lung Cancer Cells by Downregulating Cyclins and Cyclin-dependent Kinases.

PubMed

Chikara, Shireen; Lindsey, Kaitlin; Dhillon, Harsharan; Mamidi, Sujan; Kittilson, Jeffrey; Christofidou-Solomidou, Melpo; Reindl, Katie M

2017-01-01

Flaxseed is a rich source of the plant lignan secoisolariciresinol diglucoside (SDG), which is metabolized into mammalian lignans enterodiol (ED) and enterolactone (EL) in the digestive tract. The anticancer properties of these lignans have been demonstrated for various cancer types, but have not been studied for lung cancer. In this study, we investigated the anticancer effects of EL for several nonsmall cell lung cancer (NSCLC) cell lines of various genetic backgrounds. EL inhibited the growth of A549, H441, and H520 lung cancer cells in concentration- and time-dependent manners. The antiproliferative effects of EL for lung cancer cells were not due to enhanced cell death, but rather due to G 1 -phase cell cycle arrest. Molecular studies revealed that EL decreased mRNA or protein expression levels of the G 1 -phase promoters cyclin D1, cyclin E, cyclin-dependent kinases (CDK)-2, -4, and -6, and p-cdc25A; decreased phosphorylated retinoblastoma (p-pRb) protein levels; and simultaneously increased levels of p21 WAF1/CIP1 , a negative regulator of the G 1 phase. The results suggest that EL inhibits the growth of NSCLC cell lines by downregulating G 1 -phase cyclins and CDKs, and upregulating p21 WAF1/CIP1 , which leads to G 1 -phase cell cycle arrest. Therefore, EL may hold promise as an adjuvant treatment for lung cancer therapy.

Antioxidative and Chemopreventive Properties of Vernonia amygdalina and Garcinia biflavonoid

PubMed Central

Farombi, Ebenezer O.; Owoeye, Olatunde

2011-01-01

Recently, considerable attention has been focused on dietary and medicinal phytochemicals that inhibit, reverse or retard diseases caused by oxidative and inflammatory processes. Vernonia amygdalina is a perennial herb belonging to the Asteraceae family. Extracts of the plant have been used in various folk medicines as remedies against helminthic, protozoal and bacterial infections with scientific support for these claims. Phytochemicals such as saponins and alkaloids, terpenes, steroids, coumarins, flavonoids, phenolic acids, lignans, xanthones, anthraquinones, edotides and sesquiterpenes have been extracted and isolated from Vernonia amygdalina. These compounds elicit various biological effects including cancer chemoprevention. Garcinia kola (Guttiferae) seed, known as “bitter kola”, plays an important role in African ethnomedicine and traditional hospitality. It is used locally to treat illnesses like colds, bronchitis, bacterial and viral infections and liver diseases. A number of useful phytochemicals have been isolated from the seed and the most prominent of them is the Garcinia bioflavonoids mixture called kolaviron. It has well-defined structure and an array of biological activities including antioxidant, antidiabetic, antigenotoxic and hepatoprotective properties. The chemopreventive properties of Vernonia amygdalina and Garcinia biflavonoids have been attributed to their abilities to scavenge free radicals, induce detoxification, inhibit stress response proteins and interfere with DNA binding activities of some transcription factors. PMID:21776245

Trimeric Structure of (+)-Pinoresinol-forming Dirigent Protein at 1.95 Å Resolution with Three Isolated Active Sites

DOE PAGES

Kim, Kye-Won; Smith, Clyde A.; Daily, Michael D.; ...

2014-11-19

Control over phenoxy radical-radical coupling reactions in vivo in vascular plants was enigmatic until our discovery of dirigent proteins (DPs, from the Latin dirigere, to guide or align). The first three-dimensional structure of a DP ((+)-pinoresinol-forming DP, 1.95 Å resolution, rhombohedral space group H32)) is reported herein. It has a tightly packed trimeric structure with an eight-stranded β-barrel topology for each DP monomer. Each putative substrate binding and orientation coupling site is located on the trimer surface but too far apart for intermolecular coupling between sites. It is proposed that each site enables stereoselective coupling (using either two coniferyl alcoholmore » radicals or a radical and a monolignol). Interestingly, there are six differentially conserved residues in DPs affording either the (+)- or (₋)-antipodes in the vicinity of the putative binding site and region known to control stereoselectivity. We find DPs are involved in lignan biosynthesis, whereas dirigent domains/sites have been implicated in lignin deposition.« less

Arctigenin inhibits STAT3 and exhibits anticancer potential in human triple-negative breast cancer therapy

PubMed Central

Shen, Wanxiang; Zhang, Liang; Gu, Xinsheng; Guo, Yang; Tsai, Hsiang-i; Liu, Xuewen; Li, Jian; Zhang, Jingxuan; Li, Shan; Wu, Fuyun; Liu, Ying

2017-01-01

Triple-negative breast cancers (TNBCs) are the most aggressive and hard-to-treat breast tumors with poor prognosis, and exploration for novel therapeutic drugs is impending. Arctigenin (Atn), a bioactive lignan isolated from seeds of Arctium lappa L, has been reported to inhibit many cancer types; however, the effect of Atn on TNBC remains unclear. In this study, we demonstrated that Atn decreased proliferation, and induced apoptosis in TNBC cells. Furthermore, we explored the underlying mechanism of Atn inhibition on TNBC cells. Computational docking and affinity assay showed that Atn bound to the SH2 domain of STAT3. Atn inhibited STAT3 binding to genomic DNA by disrupting hydrogen bond linking between DNA and STAT3. In addition, Atn augmented Taxotere®-induced TNBC cell cytotoxicity. TNBC xenograft tests also confirmed the antitumor effect of Atn in vivo. These characteristics render Atn as a promising candidate drug for further development and for designing new effective STAT3 inhibitors. PMID:27861147

Arctigenin inhibits STAT3 and exhibits anticancer potential in human triple-negative breast cancer therapy.

PubMed

Feng, Tingting; Cao, Wei; Shen, Wanxiang; Zhang, Liang; Gu, Xinsheng; Guo, Yang; Tsai, Hsiang-I; Liu, Xuewen; Li, Jian; Zhang, Jingxuan; Li, Shan; Wu, Fuyun; Liu, Ying

2017-01-03

Triple-negative breast cancers (TNBCs) are the most aggressive and hard-to-treat breast tumors with poor prognosis, and exploration for novel therapeutic drugs is impending. Arctigenin (Atn), a bioactive lignan isolated from seeds of Arctium lappa L, has been reported to inhibit many cancer types; however, the effect of Atn on TNBC remains unclear. In this study, we demonstrated that Atn decreased proliferation, and induced apoptosis in TNBC cells. Furthermore, we explored the underlying mechanism of Atn inhibition on TNBC cells. Computational docking and affinity assay showed that Atn bound to the SH2 domain of STAT3. Atn inhibited STAT3 binding to genomic DNA by disrupting hydrogen bond linking between DNA and STAT3. In addition, Atn augmented Taxotere®-induced TNBC cell cytotoxicity. TNBC xenograft tests also confirmed the antitumor effect of Atn in vivo. These characteristics render Atn as a promising candidate drug for further development and for designing new effective STAT3 inhibitors.

Bioactive phytochemicals in wheat: Extraction, analysis, processing, and functional properties

USDA-ARS?s Scientific Manuscript database

Whole wheat provides a rich source of bioactive phytochemicals namely, phenolic acids, carotenoids, tocopherols, alkylresorcinols, arabinoxylans, benzoxazinoids, phytosterols, and lignans. This review provides information on the distribution, extractability, analysis, and nutraceutical properties of...

Sesquiterpene lactones from Centaurea tweediei.

PubMed

Fortuna, A M.; de Riscala, E C.; Catalan, C A.N.; Gedris, T E.; Herz, W

2001-10-01

Aerial parts of Centaurea tweediei from Argentina afforded as the main constituent the sesquiterpene lactone onopordopicrin and minor amounts of a new heliangolide, a new guaianolide, a new eudesmanolide, a new eudesmane acid and the lignans arctigenin and matairesinol.

Differentiation of Cuscuta chinensis and Cuscuta australis by HPLC-DAD-MS analysis and HPLC-UV quantitation.

PubMed

He, Xianghui; Yang, Wenzhi; Ye, Min; Wang, Qing; Guo, Dean

2011-11-01

Cuscuta chinensis and Cuscuta australis, the two botanical sources of the Chinese herbal medicine Tu-Si-Zi, were distinguished from each other based on qualitative and quantitative chemical analysis. By HPLC‑DAD‑MS, a total of 36 compounds were characterized from these two Cuscuta species, including 14 flavonoids, 17 quinic acid derivatives, and 5 lignans. In addition, HPLC‑UV was applied to determine seven major compounds (6 flavonoids plus chlorogenic acid) in 27 batches of Tu-Si-Zi. The results revealed that the amounts of the three classes of compounds varied significantly between the species. C. australis contained more flavonoids but less quinic acid derivatives and lignans than C. chinensis. Particularly, the amounts of kaempferol and astragalin in C. australis were remarkably higher than in C. chinensis. This finding could be valuable for the quality control of Tu-Si-Zi. © Georg Thieme Verlag KG Stuttgart · New York.

Quantitative analysis of major dibenzocyclooctane lignans in Schisandrae fructus by online TLC-DART-MS.

PubMed

Kim, Hye Jin; Oh, Myung Sook; Hong, Jongki; Jang, Young Pyo

2011-01-01

Direct analysis in real time (DART) ion source is a powerful ionising technique for the quick and easy detection of various organic molecules without any sample preparation steps, but the lack of quantitation capacity limits its extensive use in the field of phytochemical analysis. To improvise a new system which utilize DART-MS as a hyphenated detector for quantitation. A total extract of Schisandra chinensis fruit was analyzed on a TLC plate and three major lignan compounds were quantitated by three different methods of UV densitometry, TLC-DART-MS and HPLC-UV to compare the efficiency of each method. To introduce the TLC plate into the DART ion source at a constant velocity, a syringe pump was employed. The DART-MS total ion current chromatogram was recorded for the entire TLC plate. The concentration of each lignan compound was calculated from the calibration curve established with standard compound. Gomisin A, gomisin N and schisandrin were well separated on a silica-coated TLC plate and the specific ion current chromatograms were successfully acquired from the TLC-DART-MS system. The TLC-DART-MS system for the quantitation of natural products showed better linearity and specificity than TLC densitometry, and consumed less time and solvent than conventional HPLC method. A hyphenated system for the quantitation of phytochemicals from crude herbal drugs was successfully established. This system was shown to have a powerful analytical capacity for the prompt and efficient quantitation of natural products from crude drugs. Copyright © 2010 John Wiley & Sons, Ltd.

Gastrointestinal microflora, food components and colon cancer prevention

PubMed Central

Davis, Cindy D.; Milner, John A.

2009-01-01

Evidence is emerging that the intestinal microbiota is intrinsically linked with overall health, including cancer risk. Moreover, its composition is not fixed, but can be influenced by several dietary components. Dietary modifiers, including the consumption of live bacteria (probiotics), nondigestible or limited digestible food constituents such as oligosaccharides (prebiotics) and polyphenols, or both (synbiotics), are recognized modifiers of the numbers and types of microbes and have been reported to reduce colon cancer risk experimentally. Microorganisms also have the ability to generate bioactive compounds from food components. Examples include equol from isoflavones, enterodiol and enterolactone from lignans, and urolithins from ellagic acid, which have also been demonstrated to retard experimentally induced cancers. The gastrointestinal microbiota can also influence both sides of the energy balance equation; namely, as a factor influencing energy utilization from the diet and as a factor that influences host genes that regulate energy expenditure and storage. Because of the link between obesity and cancer incidence and mortality, this complex relationship deserves greater attention. Thus, a complex interrelationship exists between the intestinal microbiota and colon cancer risk which can be modified by dietary components and eating behaviors. PMID:19716282

A new lignan from the seeds of Arctium lappa.

PubMed

Yong, Min; Kun, Gu; Qiu, Min-Hua

2007-01-01

A new compound, neoarctin A (1), together with nine known compounds (2-10), were obtained from the ethanolic extract of the seeds of Arctium lappa. The structure of 1 was elucidated on the basis of spectral and chemical evidence.

Testosterone 5alpha-reductase inhibitory active constituents of Piper nigrum leaf.

PubMed

Hirata, Noriko; Tokunaga, Masashi; Naruto, Shunsuke; Iinuma, Munekazu; Matsuda, Hideaki

2007-12-01

Previously we reported that Piper nigrum leaf extract showed a potent stimulation effect on melanogenesis and that (-)-cubebin (1) and (-)-3,4-dimethoxy-3,4-desmethylenedioxycubebin (2) were isolated as active constituents. As a part of our continuous studies on Piper species for the development of cosmetic hair-care agents, testosterone 5alpha-reductase inhibitory activity of aqueous ethanolic extracts obtained from several different parts of six Piper species, namely Piper nigrum, P. methysticum, P. betle, P. kadsura, P. longum, and P. cubeba, were examined. Among them, the extracts of P. nigrum leaf, P. nigrum fruit and P. cubeba fruit showed potent inhibitory activity. Activity-guided fractionation of P. nigrum leaf extract led to the isolation of 1 and 2. Fruits of P. cubeba contain 1 as a major lignan, thus inhibitory activity of the fruit may be attributable to 1. As a result of further assay on other known constituents of the cited Piper species, it was found that piperine, a major alkaloid amide of P. nigrum fruit, showed potent inhibitory activity, thus a part of the inhibitory activity of P. nigrum fruit may depend on piperine. The 5alpha-reductase inhibitory activities of 1 and piperine were found for the first time. In addition, the P. nigrum leaf extract showed in vivo anti-androgenic activity using the hair regrowth assay in testosterone sensitive male C57Black/6CrSlc strain mice.

Commiphora leptophloeos Phytochemical and Antimicrobial Characterization

PubMed Central

de Souza Pereira, Jorge J.; Pereira, Aline de P. C.; Jandú, Jannyson J. B.; da Paz, Josinete A.; Crovella, Sergio; dos Santos Correia, Maria T.; de Azevêdo Silva, Jaqueline

2017-01-01

Commiphora leptophloeos is a plant specie usually known for its medicinal purposes in local communities in Northeast Brazil. In order to evaluate its therapeutic potential, we aimed to determine the phytochemical and antimicrobial properties of C. leptophloeos extracts. Thin Layer Chromatography (TLC) was able to detect the presence of phenolic compounds, flavonoids and reducing sugars. Three phenolic compounds were identified by HPLC and described as Gallic, Chlorogenic and Protocatechuic acids. On the other hand, H1NMR analysis revealed the presence of hinokinin, a bioactive lignan further characterized in the present work. The minimum inhibitory concentration (MIC) values for hinokinin ranged from 0.0485 to 3.125 mg/mL in different S. aureus clinical isolates and showed a bactericidal activity against MRSA isolated from blood (MMC 0.40 mg/mL) and postoperative secretion (MMC = 3.125 mg/mL). C. leptophloeos extracts also showed antimicrobial activity against Mycobacterium species such as M. smegmatis (MIC = 12.5 mg/mL) and M. tuberculosis (MIC = 52 mg/mL). Additionally, we determined the toxicity of C. leptophloeos by in vitro HC50 tests with hemolytic activity detected of 313 ± 0.5 μg/mL. Our results showed that C. leptophloeos possesses inhibitory properties against MRSA as well as several other clinically important microorganisms. Furthermore, the present work is the first report of the presence of hinokinin in Commiphora genus. PMID:28174564

Effects of an equol-producing bacterium isolated from human faeces on isoflavone and lignan metabolism in mice.

PubMed

Tamura, Motoi; Hori, Sachiko; Nakagawa, Hiroyuki; Yamauchi, Satoshi; Sugahara, Takuya

2016-07-01

Equol is a metabolite of daidzein that is produced by intestinal microbiota. The oestrogenic activity of equol is stronger than daidzein. Equol-producing bacteria are believed to play an important role in the gut. The rod-shaped and Gram-positive anaerobic equol-producing intestinal bacterium Slackia TM-30 was isolated from healthy human faeces and its effects on urinary phyto-oestrogen, plasma and faecal lipids were assessed in adult mice. The urinary amounts of equol in urine were significantly higher in mice receiving the equol-producing bacterium TM-30 (BAC) group than in the control (CO) group (P < 0.05). However, no significant differences were observed between the urinary amounts of daidzein, dihydrodaidzein, enterodiol, and enterolactone between the BAC and CO groups. No significant differences in the plasma lipids were observed between the two groups. The lipid content (% dry weight) in the faeces sampled on the final day of the experiment tended to be higher in the BAC group than in the CO group (P = 0.07). Administration of equol-producing bacterium TM-30 affected the urinary amounts of phyto-oestrogens and the faecal lipid contents of mice. The equol-producing bacterium TM-30 likely influences the metabolism of phyto-oestrogen via changes in the gastrointestinal environment. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

An integrated strategy using UPLC-QTOF-MSE and UPLC-QTOF-MRM (enhanced target) for pharmacokinetics study of wine processed Schisandra Chinensis fructus in rats.

PubMed

Liu, Kuangyi; Song, Yonggui; Liu, Yali; Peng, Mi; Li, Hanyun; Li, Xueliang; Feng, Bingwei; Xu, Pengfei; Su, Dan

2017-05-30

Currently the pharmacokinetic (PK) research of herbal medicines is still limited and facing critical technical challenges on quantitative analysis of multi-components from biological matrices which often accompanied by lacking of authentic standards and low concentration. This present work contributes to the development of an integrated strategy for extensive pharmacokinetics assessments, and a selective and sensitive method independent of authentic standards for multi-components analysis based on the use of ultra-performance liquid chromatography/quadrupole-time-of-flight/MS E (UPLC-TOF-MS E ) and UPLC-TOF-MRM (rnhanced target). Initially, phytochemicals were identified by UPLC-TOF-MS E analysis, subsequently the identified components were matched with authentic standards and pre-classified, and UPLC-QTOF-MRM method optimized and developed. To guarantee reliable results, three rules are necessary: (1) detection with a mass error of less than 5ppm; (2) same class chemical compositions with structural high similarity between analytes with and without authentic reference substance; (3) a matching retention time between TOF-MRM mode and TOF-MS E within 0.2min. The developed and validated method was applied for the simultaneous determination of 12 lignans in rat plasma after administered with wine processed Schisandra Chinensis fructus (WPSCF) extract. Such an approach was found capable of providing extensive pharmacokinetic profiles of multi-components absorbed into blood after oral administrated with WPSCF extract. The results also indicated that significant difference in pharmacokinetics parameters of dibenzocyclooctadiene lignans was observed between schizandrin and gomisin compounds. For lignans, the absorption via gastrointestinal tract were all rapid and maintained relatively long retention time, especially for schisantherin A and schisantherin B with higher plasma exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

Cytostatic inhibition of cancer cell growth by lignan secoisolariciresinol diglucoside.

PubMed

Ayella, Allan; Lim, Soyoung; Jiang, Yu; Iwamoto, Takeo; Lin, Dingbo; Tomich, John; Wang, Weiqun

2010-11-01

Our previous study demonstrated that lignan metabolites enterolactone and enterodiol inhibited colonic cancer cell growth by inducing cell cycle arrest and apoptosis. However, the dietary lignans are naturally present as glycoside precursors, such as secoisolariciresinol diglucoside (SDG), which have not been evaluated yet. This study tested the hypothesis that dietary SDG might have a different effect than its metabolites in human colonic SW480 cancer cells. Treatment with SDG at 0 to 40 μmol/L for up to 48 hours resulted in a dose- and time-dependent decrease in cell numbers, which was comparable to enterolactone. The inhibition of cell growth by SDG did not appear to be mediated by cytotoxicity, but by a cytostatic mechanism associated with an increase of cyclin A expression. Furthermore, high-performance liquid chromatography analysis indicated that SDG in the media was much more stable than enterolactone (95% of SDG survival vs 57% of enterolactone after 48-hour treatment). When the cells were treated with either enterolactone or SDG at 40 μmol/L for 48 hours, the intracellular levels of enterolactone, as measured by high-performance liquid chromatography-mass spectrometry/electron spray ionization, were about 8.3 × 10(-8) nmol per cell; but intracellular SDG or potential metabolites were undetectable. Taken together, SDG demonstrated similar effects on cell growth, cytotoxicity, and cell cycle arrest when compared with its metabolite enterolactone. However, the reliable stability and undetectable intracellular SDG in treated cells may suggest that metabolism of SDG, if exposed directly to the colonic cells, could be different from the known degradation by microorganisms in human gut. Copyright © 2010 Elsevier Inc. All rights reserved.

Flaxseed lignans enriched in secoisolariciresinol diglucoside prevent acute asbestos-induced peritoneal inflammation in mice

PubMed Central

Pietrofesa, Ralph A.; Velalopoulou, Anastasia; Arguiri, Evguenia; Menges, Craig W.; Testa, Joseph R.; Hwang, Wei-Ting; Albelda, Steven M.

2016-01-01

Malignant mesothelioma (MM), linked to asbestos exposure, is a highly lethal form of thoracic cancer with a long latency period, high mortality and poor treatment options. Chronic inflammation and oxidative tissue damage caused by asbestos fibers are linked to MM development. Flaxseed lignans, enriched in secoisolariciresinol diglucoside (SDG), have antioxidant, anti-inflammatory and cancer chemopreventive properties. As a prelude to chronic chemoprevention studies for MM development, we tested the ability of flaxseed lignan component (FLC) to prevent acute asbestos-induced inflammation in MM-prone Nf2+/mu mice. Mice (n = 16–17 per group) were placed on control (CTL) or FLC-supplemented diets initiated 7 days prior to a single intraperitoneal bolus of 400 µg of crocidolite asbestos. Three days post asbestos exposure, mice were evaluated for abdominal inflammation, proinflammatory/profibrogenic cytokine release, WBC gene expression changes and oxidative and nitrosative stress in peritoneal lavage fluid (PLF). Asbestos-exposed mice fed CTL diet developed acute inflammation, with significant (P < 0.0001) elevations in WBCs and proinflammatory/profibrogenic cytokines (IL-1ß, IL-6, TNFα, HMGB1 and active TGFß1) relative to baseline (BL) levels. Alternatively, asbestos-exposed FLC-fed mice had a significant (P < 0.0001) decrease in PLF WBCs and proinflammatory/profibrogenic cytokine levels relative to CTL-fed mice. Importantly, PLF WBC gene expression of cytokines (IL-1ß, IL-6, TNFα, HMGB1 and TGFß1) and cytokine receptors (TNFαR1 and TGFßR1) were also downregulated by FLC. FLC also significantly (P < 0.0001) blunted asbestos-induced nitrosative and oxidative stress. FLC reduces acute asbestos-induced peritoneal inflammation, nitrosative and oxidative stress and may thus prove to be a promising agent in the chemoprevention of MM. PMID:26678224

Further investigation into maple syrup yields 3 new lignans, a new phenylpropanoid, and 26 other phytochemicals.

PubMed

Li, Liya; Seeram, Navindra P

2011-07-27

Maple syrup is made by boiling the sap collected from certain maple ( Acer ) species. During this process, phytochemicals naturally present in tree sap are concentrated in maple syrup. Twenty-three phytochemicals from a butanol extract of Canadian maple syrup (MS-BuOH) had previously been reported; this paper reports the isolation and identification of 30 additional compounds (1-30) from its ethyl acetate extract (MS-EtOAc) not previously reported from MS-BuOH. Of these, 4 compounds are new (1-3, 18) and 20 compounds (4-7, 10-12, 14-17, 19, 20, 22-24, 26, and 28-30) are being reported from maple syrup for the first time. The new compounds include 3 lignans and 1 phenylpropanoid: 5-(3″,4″-dimethoxyphenyl)-3-hydroxy-3-(4'-hydroxy-3'-methoxybenzyl)-4-(hydroxymethyl)dihydrofuran-2-one (1), (erythro,erythro)-1-[4-[2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-1-(hydroxymethyl)ethoxy]-3,5-dimethoxyphenyl]-1,2,3-propanetriol (2), (erythro,threo)-1-[4-[2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-1-(hydroxymethyl)ethoxy]-3,5-dimethoxyphenyl]-1,2,3-propanetriol (3), and 2,3-dihydroxy-1-(3,4- dihydroxyphenyl)-1-propanone (18), respectively. In addition, 25 other phenolic compounds were isolated including (threo,erythro)-1-[4-[(2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-1-(hydroxymethyl)ethoxy]-3-methoxyphenyl]-1,2,3-propanetriol (4), (threo,threo)-1-[4-[(2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-1-(hydroxymethyl)ethoxy]-3-methoxyphenyl]-1,2,3-propanetriol (5), threo-guaiacylglycerol-β-O-4'-dihydroconiferyl alcohol (6), erythro-1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-hydroxypropyl)-2,6-dimethoxyphenoxy]-1,3-propanediol (7), 2-[4-[2,3-dihydro-3-(hydroxymethyl)-5-(3-hydroxypropyl)-7-methoxy-2-benzofuranyl]-2,6-dimethoxyphenoxy]-1-(4-hydroxy-3-methoxyphenyl)-1,3-propanediol (8), acernikol (9), leptolepisol D (10), buddlenol E (11), (1S,2R)-2-[2,6-dimethoxy-4-[(1S,3aR,4S,6aR)-tetrahydro-4-(4-hydroxy-3,5-dimethoxyphenyl)-1H,3H-furo[3,4-c]furan-1-yl]phenoxy]-1-(4-hydroxy-3-methoxyphenyl)-1,3-propanediol (12), syringaresinol (13), isolariciresinol (14), icariside E4 (15), sakuraresinol (16), 1,2-diguaiacyl-1,3-propanediol (17), 2,3-dihydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone (19), 3-hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)propan-1-one (20), dihydroconiferyl alcohol (21), 4-acetylcatechol (22), 3',4',5'-trihydroxyacetophenone (23), 3,4-dihydroxy-2-methylbenzaldehyde (24), protocatechuic acid (25), 4-(dimethoxymethyl)pyrocatechol (26), tyrosol (27), isofraxidin (28), and 4-hydroxycatechol (29). One sesquiterpene, phaseic acid (30), which is a known metabolite of the phytohormone abscisic acid, was also isolated from MS-EtOAc. The antioxidant activities of MS-EtOAc (IC(50) = 75.5 μg/mL) and the pure isolates (IC(50) ca. 68-3000 μM) were comparable to that of vitamin C (IC(50) = 40 μM) and the synthetic commercial antioxidant butylated hydroxytoluene (IC(50) = 3000 μM), in the diphenylpicrylhydrazyl radical scavenging assay. The current study advances scientific knowledge of maple syrup constituents and suggests that these diverse phytochemicals may impart potential health benefits to this natural sweetener.

Further Investigation Into Maple Syrup Yields Three New Lignans, a New Phenylpropanoid, and Twenty-Six Other Phytochemicals

PubMed Central

LI, LIYA; SEERAM, NAVINDRA P.

2011-01-01

Maple syrup is made by boiling the sap collected from certain maple (Acer) species. During this process, phytochemicals naturally present in tree sap are concentrated in maple syrup. We previously reported 23 phytochemicals from a butanol extract of Canadian maple syrup (MS-BuOH). Here we report the isolation and identification of 30 additional compounds (1–30) from its ethyl acetate extract (MS-EtOAc) not previously reported from MS-BuOH. Of these, 4 compounds are new (1–3, 18) and 20 compounds (4–7, 10–12, 14–17, 19–20, 22–24, 26, 28–30) are being reported from maple syrup for the first time. The new compounds include 3 lignans and 1 phenylpropanoid: 5-(3″,4″-dimethoxyphenyl)-3-hydroxy-3-(4′-hydroxy-3′-methoxybenzyl)-4-hydroxymethyl-dihydrofuran-2-one (1), (erythro, erythro)-1-[4-[2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-1-(hydroxymethyl)ethoxy]-3,5-dimethoxyphenyl]-1,2,3-propanetriol (2), (erythro, threo)-1-[4-[2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-1-(hydroxymethyl)ethoxy]-3,5-dimethoxyphenyl]-1,2,3-propanetriol (3) and 2,3-dihydroxy-1-(3,4-dihydroxyphenyl)-1-propanone (18), respectively. In addition, 25 other phenolic compounds were isolated including (threo, erythro)-1-[4-[(2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-1-(hydroxymethyl)ethoxy]-3-methoxyphenyl]-1,2,3-propanetriol (4), (threo, threo)-1-[4-[(2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-1-(hydroxymethyl)ethoxy]-3-methoxyphenyl]-1,2,3-propanetriol (5), threo-guaiacylglycerol-β-O-4′-dihydroconiferyl alcohol (6), erythro-1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-hydroxypropyl)-2,6-dimethoxyphenoxy]-1,3-propanediol (7), 2-[4-[2,3-dihydro-3-(hydroxymethyl)-5-(3-hydroxypropyl)-7-methoxy-2-benzofuranyl]-2,6-dimethoxyphenoxy]-1-(4-hydroxy-3-methoxyphenyl)-1,3-propanediol (8), acernikol (9), leptolepisol D (10), buddlenol E (11), (1S,2R)-2-[2,6-dimethoxy-4-[(1S,3aR,4S,6aR)-tetrahydro-4-(4-hydroxy-3,5-dimethoxyphenyl)-1H,3H-furo[3,4-c]furan-1-yl]phenoxy]-1-(4-hydroxy-3-methoxyphenyl)-1,3-propanediol (12), syringaresinol (13), isolariciresinol (14), icariside E4 (15), sakuraresinol (16), 1,2-diguaiacyl-1,3-propanediol (17), 2,3-dihydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone (19), 3-hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)propan-1-one (20), dihydroconiferyl alcohol (21), 4-acetylcatechol (22), 3′,4′,5′-trihydroxyacetophenone (23), 3,4-dihydroxy-2-methylbenzaldehyde (24), protocatechuic acid (25), 4-(dimethoxymethyl)-pyrocatechol (26), tyrosol (27), isofraxidin (28) and 4-hydroxycatechol (29). One sesquiterpene, phaseic acid (30), which is a known metabolite of the phytohormone, abscisic acid, was also isolated from MS-EtOAc. The antioxidant activities of MS-EtOAc (IC50 = 75.5 μg/mL), and the pure isolates (IC50 ca. 68–3000 μM) were comparable to vitamin C (IC50 = 40 μM) and the synthetic commercial antioxidant, butylated hydroxytoluene (IC50 = 3000 μM), in the diphenylpicrylhydrazyl radical scavenging assay. The current study advances scientific knowledge of maple syrup constituents and suggest that these diverse phytochemicals may impart potential health benefits to this natural sweetener. PMID:21675726

Reactivity of bacterial and fungal laccases with lignin under alkaline conditions.

PubMed

Moya, Raquel; Saastamoinen, Päivi; Hernández, Manuel; Suurnäkki, Anna; Arias, Enriqueta; Mattinen, Maija-Liisa

2011-11-01

The ability of Streptomyces ipomoea laccase to polymerize secoisolariciresinol lignan and technical lignins was assessed. The reactivity of S. ipomoea laccase was also compared to that of low redox fungal laccase from Melanocarpus albomyces using low molecular mass p-coumaric, ferulic and sinapic acid as well as natural (acetosyringone) and synthetic 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) mediators as substrates. Oxygen consumption measurement, MALDI-TOF MS and SEC were used to follow the enzymatic reactions at pH 7, 8, 9 and 10 at 30°C and 50°C. Polymerization of lignins and lignan by S. ipomoea laccase under alkaline reaction conditions was observed, and was enhanced in the presence of acetosyringone almost to the level obtained with M. albomyces laccase without mediator. Reactivities of the enzymes towards acetosyringone and TEMPO were similar, suggesting exploitation of the compounds and low redox laccase in lignin valorization under alkaline conditions. The results have scientific impact on basic research of laccases. Copyright © 2011 Elsevier Ltd. All rights reserved.

Phenolic Components and Antioxidant Activity of Wood Extracts from 10 Main Spanish Olive Cultivars.

PubMed

Salido, Sofía; Pérez-Bonilla, Mercedes; Adams, Robert P; Altarejos, Joaquín

2015-07-29

The chemical composition and radical-scavenging activity of wood samples from 10 main Spanish olive cultivars were studied. The wood samples were collected during the pruning works from trees growing under the same agronomical and environmental conditions. The 10 ethyl acetate extracts were submitted to HPLC-DAD/ESI-MS analysis to determine the phenolic constituents. Seventeen compounds were identified (10 secoiridoids, 3 lignans, 2 phenol alcohols, 1 iridoid, and 1 flavonoid) by comparison with authentic samples. Significant quantitative and qualitative differences were found among olive cultivars. The lignan (+)-1-hydroxypinoresinol 1-O-β-d-glucopyranoside was the major compound in all olive cultivars, except in cultivars 'Farga' and 'Picual'. The multivariate analysis of all data revealed three sets of cultivars with similar compositions. Cultivars 'Gordal sevillana' and 'Picual' had the most distinct chemical profiles. With regard to the radical-scavenging activity, cultivar 'Picual', with oleuropein as the major phenolic, showed the highest activity (91.4 versus 18.6-32.7%).

The occurrence of tricin and its derivatives in plants

DOE PAGES

Li, Mi; Pu, Yunqiao; Yoo, Chang Geun; ...

2016-02-02

Our understanding of the structure and biosynthetic pathway of lignin, a phenylpropanoid heteropolymer, continues to evolve, especially with the discovery of new lignin monomers/structural moieties such as monolignol acetate, hydroxycinnamyl aldehyde/alcohol, and p-hydroxybenzoate in the past decades. Recently, tricin has been reported as a component incorporated into monocot lignin. As a flavonoid compound widely distributed in herbaceous plants, tricin has been extensively studied due to its biological significance in plant growth as well as its potential for pharmaceutical importance. Tricin is biosynthesized as a constituent of plant secondary metabolites through a combination of phenylpropanoid and polyketide pathways. Tricin occurs inmore » plants in either free or conjugated forms such as tricin-glycosides, tricin-lignans, and tricin-lignan-glycosides.The emergence of tricin covalently incorporated with lignin biopolymer implies the possible association of lignification and tricin biosynthesis. This review summarizes the occurrence of tricin and its derivatives in plants. Additionally, synthesis, potential application, and characterization of tricin are discussed.« less

The occurrence of tricin and its derivatives in plants

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

Li, Mi; Pu, Yunqiao; Yoo, Chang Geun

Our understanding of the structure and biosynthetic pathway of lignin, a phenylpropanoid heteropolymer, continues to evolve, especially with the discovery of new lignin monomers/structural moieties such as monolignol acetate, hydroxycinnamyl aldehyde/alcohol, and p-hydroxybenzoate in the past decades. Recently, tricin has been reported as a component incorporated into monocot lignin. As a flavonoid compound widely distributed in herbaceous plants, tricin has been extensively studied due to its biological significance in plant growth as well as its potential for pharmaceutical importance. Tricin is biosynthesized as a constituent of plant secondary metabolites through a combination of phenylpropanoid and polyketide pathways. Tricin occurs inmore » plants in either free or conjugated forms such as tricin-glycosides, tricin-lignans, and tricin-lignan-glycosides.The emergence of tricin covalently incorporated with lignin biopolymer implies the possible association of lignification and tricin biosynthesis. This review summarizes the occurrence of tricin and its derivatives in plants. Additionally, synthesis, potential application, and characterization of tricin are discussed.« less

Chemical fingerprinting of valeriana species: simultaneous determination of valerenic acids, flavonoids, and phenylpropanoids using liquid chromatography with ultraviolet detection.

PubMed

Navarrete, Andres; Avula, Bharathi; Choi, Young-Whan; Khan, Ikhlas A

2006-01-01

The roots and rhizomes of various valeriana species are currently used as a sleeping aid or mild sedative. A liquid chromatography method has been developed that permits the analysis of chlorogenic acid, lignans, flavonoids, valerenic acids, and valpotrates in various valerian samples. The best results were obtained with a Phenomenex Luna C18(2) column using gradient elution with a mobile phase consisting of water and 0.05% phosphoric acid and 2-100% acetonitrile-methanol (1 + 1) with 0.05% phosphoric acid. The flow rate was 0.8 mL/min and ultraviolet detection was at 207, 225, 254, 280, and 325 nm. Different valerian species and commercial products showed remarkable quantitative variations. Chlorogenic acid (0.2-1.2%), 3 lignans, linarin (0.002-0.24%), and valepotriates were detected in all the valeriana species analyzed. Highest amounts of valerenic acids were detected in V. officinalis L., trace amounts in V. sitchensis, and none in the other species analyzed.

Cardioprotective activity of flax lignan concentrate extracted from seeds of Linum usitatissimum in isoprenalin induced myocardial necrosis in rats

PubMed Central

Zanwar, Anand A.; Hegde, Mahabaleshwar V.; Bodhankar, Subhash L.

2011-01-01

The objective of the study was to evaluate the cardioprotective activity of flax lignan concentrate (FLC) in isoprenalin (ISO) induced cardiotoxicity in rats. Male Wistar rats (200–230 g) were divided into three groups. Group I: control, Group II: isoprenalin, Group III: FLC (500 mg/kg, p.o.) orally for 8 days and in group II and III isoprenalin 5.25 mg/kg, s.c. on day 9 and 8.5 mg/kg on day 10. On day 10 estimation of marker enzymes in serum and haemodynamic parameters were recorded. Animals were sacrificed, histology of heart was performed. Isoprenalin showed cardiotoxicity, manifested by increased levels of marker enzymes and increased heart rate. FLC treatment reversed these biochemical changes significantly compared with ISO group. The cardiotoxic effect of isoprenalin was less in FLC pretreated animals, which was confirmed in histopathological alterations. Haemodynamic, biochemical alteration and histopathological results suggest a cardioprotective protective effect of FLC in isoprenalin induced cardiotoxicity. PMID:21753905

Trimeric structure of (+)-pinoresinol-forming dirigent protein at 1.95 Å resolution with three isolated active sites.

PubMed

Kim, Kye-Won; Smith, Clyde A; Daily, Michael D; Cort, John R; Davin, Laurence B; Lewis, Norman G

2015-01-16

Control over phenoxy radical-radical coupling reactions in vivo in vascular plants was enigmatic until our discovery of dirigent proteins (DPs, from the Latin dirigere, to guide or align). The first three-dimensional structure of a DP ((+)-pinoresinol-forming DP, 1.95 Å resolution, rhombohedral space group H32)) is reported herein. It has a tightly packed trimeric structure with an eight-stranded β-barrel topology for each DP monomer. Each putative substrate binding and orientation coupling site is located on the trimer surface but too far apart for intermolecular coupling between sites. It is proposed that each site enables stereoselective coupling (using either two coniferyl alcohol radicals or a radical and a monolignol). Interestingly, there are six differentially conserved residues in DPs affording either the (+)- or (-)-antipodes in the vicinity of the putative binding site and region known to control stereoselectivity. DPs are involved in lignan biosynthesis, whereas dirigent domains/sites have been implicated in lignin deposition. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Phytochemical pharmacokinetics and bioactivity of oat and barley flour: a randomized crossover trial

USDA-ARS?s Scientific Manuscript database

While dietary fiber plays an important role in the health benefits associated with whole grain consumption, other ingredients concentrated in the outer bran layer, including alkylresorcinols, lignans, phenolic acids, phytosterols, and tocols, may also contribute to these outcomes. To determine the a...

Anti-mycobacterial natural products from the Canadian medicinal plant Juniperus communis.

PubMed

Carpenter, Caitlyn D; O'Neill, Taryn; Picot, Nadia; Johnson, John A; Robichaud, Gilles A; Webster, Duncan; Gray, Christopher A

2012-09-28

Common juniper, Juniperus communis, is amongst the plants most frequently used by the indigenous peoples of North America for medicinal purposes. The First Nations of the Canadian Maritimes use infusions of juniper primarily as a tonic and for the treatment of tuberculosis. Previous investigations of extracts derived from the aerial parts of J. communis have shown it to possess anti-mycobacterial activity. The aim of the study is to isolate and identify anti-mycobacterial constituents from the aerial parts of J. communis. Methanolic extracts of J. communis needles and branches were subjected to bioassay guided fractionation using the microplate resazurin assay (MRA) to assess inhibitory activity against Mycobacterium tuberculosis strain H37Ra. The anti-mycobacterial constituents were identified by NMR, MS and polarimetry. The diterpenes isocupressic acid and communic acid and the aryltetralin lignan deoxypodophyllotoxin were isolated from the J. communis extract. Isocupressic acid and communic acid (isolated as an inseparable 3:2 mixture of cis and trans isomers) displayed MICs of 78 μM and 31 μM and IC(50)s of 46 μM and 15 μM against M. tuberculosis H37Ra respectively. Deoxypodophyllotoxin was less active, with a MIC of 1004 μM and an IC(50) of 287 μM. Isocupressic acid, communic acid and deoxypodophyllotoxin were identified as the principal constituents responsible for the anti-mycobacterial activity of the aerial parts of J. communis. Although further research will be required to evaluate the relative activities of the two communic acid isomers, this work validates an ethnopharmacological use of this plant by Canadian First Nations and Native American communities. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Natural compounds isolated from Brazilian plants are potent inhibitors of hepatitis C virus replication in vitro.

PubMed

Jardim, A C G; Igloi, Z; Shimizu, J F; Santos, V A F F M; Felippe, L G; Mazzeu, B F; Amako, Y; Furlan, M; Harris, M; Rahal, P

2015-03-01

Compounds extracted from plants can provide an alternative approach to new therapies. They present characteristics such as high chemical diversity, lower cost of production and milder or inexistent side effects compared with conventional treatment. The Brazilian flora represents a vast, largely untapped, resource of potential antiviral compounds. In this study, we investigate the antiviral effects of a panel of natural compounds isolated from Brazilian plants species on hepatitis C virus (HCV) genome replication. To do this we used firefly luciferase-based HCV sub-genomic replicons of genotypes 2a (JFH-1), 1b and 3a and the compounds were assessed for their effects on both HCV replication and cellular toxicity. Initial screening of compounds was performed using the maximum non-toxic concentration and 4 compounds that exhibited a useful therapeutic index (favourable ratio of cytotoxicity to antiviral potency) were selected for extra analysis. The compounds APS (EC50=2.3μM), a natural alkaloid isolated from Maytrenus ilicifolia, and the lignans 3(∗)43 (EC50=4.0μM), 3(∗)20 (EC50=8.2μM) and 5(∗)362 (EC50=38.9μM) from Peperomia blanda dramatically inhibited HCV replication as judged by reductions in luciferase activity and HCV protein expression in both the subgenomic and infectious systems. We further show that these compounds are active against a daclatasvir resistance mutant subgenomic replicon. Consistent with inhibition of genome replication, production of infectious JFH-1 virus was significantly reduced by all 4 compounds. These data are the first description of Brazilian natural compounds possessing anti-HCV activity and further analyses are being performed in order to investigate the mode of action of those compounds. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Impact of bran components on the quality of whole wheat bread

USDA-ARS?s Scientific Manuscript database

Whole grains contain components, such as dietary fiber, starch, fat, antioxidant nutrients, minerals, vitamin, lignans, and phenolic compounds, which are beneficial to human health. Most of the beneficial components are found in the germ and bran as part of a wheat kernel, which are reduced in the ...

A Commentary on Phytoestrogens and Disease

ERIC Educational Resources Information Center

Hard, Alison; Edelstein, Sari

2015-01-01

On the most basic level, phytoestrogens can be defined as compounds found in plants that exhibit estrogen-like activity in the human body. Phytoestrogens are considered functional foods because of their diverse physiological effects beyond basic nutritional functions. The 2 primary categories of phytoestrogens found in food are lignans and…

Enantiomeric Lignans and Neolignans from Phyllanthus glaucus: Enantioseparation and Their Absolute Configurations

NASA Astrophysics Data System (ADS)

Wu, Zhaodi; Lai, Yongji; Zhou, Lei; Wu, Ye; Zhu, Hucheng; Hu, Zhengxi; Yang, Jing; Zhang, Jinwen; Wang, Jianping; Luo, Zengwei; Xue, Yongbo; Zhang, Yonghui

2016-04-01

Eight pairs of enantiomeric neolignans, norlignans, and sesquineolignans (1a/1b-8a/8b), together with five known neolignans (9a/9b and 10-12), have been isolated from 70% acetone extract of the whole plants of Phyllanthus glaucus Wall. (Euphorbiaceae). The racemic or partial racemic mixtures were successfully separated by chiral HPLC using different types of chiral columns with various mobile phases. Their structures were elucidated on the basis of extensive spectroscopic data. The absolute configurations of 2a/2b were determined by computational analysis of their electronic circular dichroism (ECD) spectrum, and the absolute configurations of other isolates were ascertained by comparing their experimental ECD spectra and optical rotation values with those of structure-relevant compounds reported in literatures. Compounds 4a/4b featured unique sesquineolignan skeletons with a novel 7-4‧-epoxy-8‧-8‧‧/7‧-2‧‧ scaffold, consisting of an aryltetrahydronaphthalene and a dihydrobenzofuran moiety. The planar structures of compounds 2, 3, 7, and 8 were documented previously; however, their absolute configurations were established for the first time in this study. The antioxidant activities of 1a/1b-8a/8b were evaluated using DPPH free radical scavenging assay, and the results demonstrated that compounds 1b and 3b showed potent DPPH radical scavenging activities with IC50 values of 5.987 ± 1.212 and 9.641 ± 0.865 μg/mL, respectively.

Inhibition of β-catenin signaling involved in the biological activities of a lignan E2S isolated from Carya cathayensis fruits.

PubMed

Xia, Xichun; Bi, Xiuli; Wu, Wei; Mou, Yanhua; Hou, Yue; Zhang, Kaiqing; Zhao, Yuqing

2013-11-01

Carya cathayensis is a fruit-bearing plant that belongs to the Juglandaceae family and is widely distributed throughout the world. It possesses various important biological activities. We have previously isolated an antitumor compound from the shell of C. cathayensis fruits and named it E2S ((E)-3-[(2S,3R)-2,3-dihydro-2-(4'-hydroxy-3'-methoxyphenyl)-3-hydroxymethyl-7-methoxy-1-benzo[b]furan-5-yl]-2-propenal). In this study, we investigated the antitumor activity of E2S against various human colorectal cancer cell lines (HCT116, HT29, SW480, LoVo). The results showed that E2S could significantly inhibit the growth of cancer cells in a dose-dependent manner, as well as disrupt the progression of the cell cycle. Mechanistic study revealed that E2S could decrease the protein levels of β-catenin and its downstream targets (such as c-myc, a key transcriptional target of β-catenin) in the cells. In addition, it also significantly suppressed β-catenin/TCF transcriptional activity. Taken together, the results suggested that E2S might partially exert an antiproliferative effect on human colorectal cancer cells by targeting β-catenin signaling, a finding that might potentially translate into a chemotherapeutic strategy for the treatment of cancer. It might also have implications for cancer prevention strategies. Georg Thieme Verlag KG Stuttgart · New York.

Hessian fly larval attack triggers elevated expression of disease resistance dirigent-like protein-encoding gene, HfrDrd, in resistant wheat.

USDA-ARS?s Scientific Manuscript database

Dirigent proteins regulate coupling of monolignol plant phenols to generate the structural cell wall polymers lignins and lignans that are involved in structural fortification of cell wall and defense against pathogens and pests. Microarray expression profiling of resistant wheat (Triticum aestivum)...

Tree nut phytochemicals: composition, antioxidant capacity, bioactivity, impact factors. A systematic review of almonds, Brazils, cashews, hazelnuts, macadamias, pecans, pine nuts, pistachios and walnuts

USDA-ARS?s Scientific Manuscript database

Tree nuts contain an array of phytochemicals including carotenoids, phenolic acids, phytosterols and polyphenolic compounds such as flavonoids, proanthocyanidins (PAC) and stilbenes, all of which are included in nutrient databases, as well as phytates, sphingolipids, alkylphenols and lignans, which ...

Effects of UV-B radiation levels on concentrations of phytosterol, ergothioneine, and polyphenolic compounds in mushroom powder used as dietary supplements

USDA-ARS?s Scientific Manuscript database

Compositional changes of powder dietary supplement made from mushrooms previously exposed to different levels of UV-B irradiation were evaluated for the bioactive naturally occurring mushroom anti-oxidant, ergothioneine, other natural polyphenolic anti-oxidants: e.g. flavonoids, lignans, and others,...

Formation of Olelresin and Lignans in Sapwood of White Spruce in Response to Wounding

Treesearch

J.H. Hart; J.F. Wardell; Richard W. Hemingway

1975-01-01

Sapwood of white spruce (Picea glauca) was wounded in the spring with an increment borer. Tissue adjacent to the wound, collected 4-9 months after injury, was more decay resistant than uninjured tissue when exposed to Poria monticola or Coriolus versicolor. No significant quantitative or qualitative differences...

An efficient fermentation method for the degradation of cyanogenic glycosides in flaxseed.

PubMed

Wu, C-F; Xu, X-M; Huang, S-H; Deng, M-C; Feng, A-J; Peng, J; Yuan, J-P; Wang, J-H

2012-01-01

Recently, flaxseed has become increasingly popular in the health food market because it contains a considerable amount of specific beneficial nutrients such as lignans and omega-3 fatty acids. However, the presence of cyanogenic glycosides (CGs) in flaxseed severely limits the exploitation of its health benefits and nutritive value. We, therefore, developed an effective fermentation method, optimised by response surface methodology (RSM), for degrading CGs with an enzymatic preparation that includes 12.5% β-glucosidase and 8.9% cyanide hydratase. These optimised conditions resulted in a maximum CG degradation level of 99.3%, reducing the concentration of cyanide in the flaxseed power from 1.156 to 0.015 mg g(-1) after 48 h of fermentation. The avoidance of steam heat to evaporate hydrocyanic acid (HCN) results in lower energy consumption and no environmental pollution. In addition, the detoxified flaxseed retained the beneficial nutrients, lignans and fatty acids at the same level as untreated flaxseed, and this method could provide a new means of removing CGs from other edible plants, such as cassava, almond and sorghum by simultaneously expressing cyanide hydratase and β-glucosidase.

Arctigenin, a Natural Lignan Compound, Induces Apoptotic Death of Hepatocellular Carcinoma Cells via Suppression of PI3-K/Akt Signaling.

PubMed

Jiang, Xiaoxin; Zeng, Leping; Huang, Jufang; Zhou, Hui; Liu, Yubin

2015-04-28

In this study, we explored the cytotoxic effects of arctigenin, a natural lignan compound, on human hepatocellular carcinoma (HCC) cells and check the involvement of phosphatidylinositol 3-kinase (PI3-K)/Akt signaling. HCC cells were treated with different concentrations of arctigenin and cell viability and apoptosis were assessed. Manipulating Akt signaling was used to determine its role in the action of arctigenin. Arctigenin significantly inhibited the viability of HCC cells in a concentration-dependent manner. Arctigenin induced apoptosis and activation of caspase-9 and -3. Overexpression of a constitutively active Akt mutant blocked arctigenin-induced apoptosis. Combinational treatment with arctigenin and the PI3-K inhibitor LY294002 significantly enhanced apoptosis. Arctigenin reduced the expression of Bcl-xL, Mcl-1, and survivin and the phosphorylation of mTOR and S6K, which were significantly reversed by overexpression of constitutively active Akt. This is the first report about the anticancer activity of arctigenin in HCC cells, which is mediated by inactivation of PI3-K/Akt signaling. © 2015 Wiley Periodicals, Inc.

Intakes and sources of isoflavones, lignans, enterolignans, coumestrol and soya-containing foods in the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk), from 7 d food diaries, using a newly updated database.

PubMed

Mulligan, Angela A; Kuhnle, Gunter G C; Lentjes, Marleen A H; van Scheltinga, Veronica; Powell, Natasha A; McTaggart, Alison; Bhaniani, Amit; Khaw, Kay-Tee

2013-08-01

A diet rich in phyto-oestrogens has been suggested to protect against a variety of common diseases but UK intake data on phyto-oestrogens or their food sources are sparse. The present study estimates the average intakes of isoflavones, lignans, enterolignans and coumestrol from 7 d food diaries and provides data on total isoflavone, lignan and phyto-oestrogen consumption by food group. Development of a food composition database for twelve phyto-oestrogens and analysis of soya food and phyto-oestrogen consumption in a populationbased study. Men and women, aged 40–79 years, from the general population participating in the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk) between 1993 and 1997, with nutrient and food data from 7 d food diaries. A subset of 20 437 participants. The median daily phyto-oestrogen intake for all men was 1199 mg (interquartile range 934–1537mg; mean 1504mg, SD 1502mg) and 888mg for all women (interquartile range 710–1135 mg; mean 1205 mg, SD 1701mg). In soya consumers, median daily intakes were higher: 2861 mg in men (interquartile range 1304–7269mg; mean 5051mg, SD 5031mg) and 3142 mg in women (interquartile range 1089–7327mg; mean 5396 mg, SD 6092 mg). In both men and women, bread made the greatest contribution to phyto-oestrogen intake – 40?8% and 35?6%, respectively. In soya consumers, vegetable dishes and soya/goat’s/sheep’s milks were the main contributors – 45?7% and 21?3% in men and 38?4% and 33?7% in women, respectively. The ability to estimate phyto-oestrogen intake in Western populations more accurately will aid investigations into their suggested effects on health.

Pharmacokinetics and Bioavailability of Plant Lignan 7-Hydroxymatairesinol and Effects on Serum Enterolactone and Clinical Symptoms in Postmenopausal Women: A Single-Blinded, Parallel, Dose-Comparison Study

PubMed Central

Udani, Jay K.; Brown, Donald J.; Tan, Maria Olivia C.; Hardy, Mary

2013-01-01

Objective 7-Hydroxymaitairesinol (7-HMR) is a naturally occurring plant lignan found in whole grains and the Norway spruce (Piciea abies). The purpose of this study was to evaluate the bioavailability of a proprietary 7-HMR product (HMRlignan, Linnea SA, Locarno, Switzerland) through measurement of lignan metabolites and metabolic precursors. Methods A single-blind, parallel, pharmacokinetic and dose-comparison study was conducted on 22 post-menopausal females not receiving hormone replacement therapy. Subjects were enrolled in either a 36 mg/d (low-dose) or 72 mg/d dose (high-dose) regimen for 8 weeks. Primary measured outcomes included plasma levels of 7-HMR and enterolactone (ENL), and single-dose pharmacokinetic analysis was performed on a subset of subjects in the low-dose group. Safety data and adverse event reports were collected as well as data on hot flash frequency and severity. Results Pharmacokinetic studies demonstrated 7-HMR Cmax = 757.08 ng/ml at 1 hour and ENL Cmax = 4.8 ng/ml at 24 hours. From baseline to week 8, plasma 7-HMR levels increased by 191% in the low-dose group (p < 0.01) and by 1238% in the high-dose group (p < 0.05). Plasma ENL levels consistently increased as much as 157% from baseline in the low-dose group and 137% in the high-dose group. Additionally, the mean number of weekly hot flashes decreased by 50%, from 28.0/week to 14.3/week (p < 0.05) in the high-dose group. No significant safety issues were identified in this study. Conclusion The results demonstrate that HMRlignan is quickly absorbed into the plasma and is metabolized to ENL in healthy postmenopausal women. Clinically, the data demonstrate a statistically significant improvement in hot flash frequency. Doses up to 72 mg/d HMRlignan for 8 weeks were safe and well tolerated in this population. PMID:24606716

Pharmacokinetics and bioavailability of plant lignan 7-hydroxymatairesinol and effects on serum enterolactone and clinical symptoms in postmenopausal women: a single-blinded, parallel, dose-comparison study.

PubMed

Udani, Jay K; Brown, Donald J; Tan, Maria Olivia C; Hardy, Mary

2013-01-01

7-Hydroxymaitairesinol (7-HMR) is a naturally occurring plant lignan found in whole grains and the Norway spruce (Piciea abies). The purpose of this study was to evaluate the bioavailability of a proprietary 7-HMR product (HMRlignan, Linnea SA, Locarno, Switzerland) through measurement of lignan metabolites and metabolic precursors. A single-blind, parallel, pharmacokinetic and dose-comparison study was conducted on 22 postmenopausal females not receiving hormone replacement therapy. Subjects were enrolled in either a 36 mg/d (low-dose) or 72 mg/d dose (high-dose) regimen for 8 weeks. Primary measured outcomes included plasma levels of 7-HMR and enterolactone (ENL), and single-dose pharmacokinetic analysis was performed on a subset of subjects in the low-dose group. Safety data and adverse event reports were collected as well as data on hot flash frequency and severity. Pharmacokinetic studies demonstrated 7-HMR C max = 757.08 ng/ml at 1 hour and ENL C max = 4.8 ng/ml at 24 hours. From baseline to week 8, plasma 7-HMR levels increased by 191% in the low-dose group (p < 0.01) and by 1238% in the high-dose group (p < 0.05). Plasma ENL levels consistently increased as much as 157% from baseline in the low-dose group and 137% in the high-dose group. Additionally, the mean number of weekly hot flashes decreased by 50%, from 28.0/week to 14.3/week (p < 0.05) in the high-dose group. No significant safety issues were identified in this study. The results demonstrate that HMRlignan is quickly absorbed into the plasma and is metabolized to ENL in healthy postmenopausal women. Clinically, the data demonstrate a statistically significant improvement in hot flash frequency. Doses up to 72 mg/d HMRlignan for 8 weeks were safe and well tolerated in this population.

Identification and functional characterization of a flax UDP-glycosyltransferase glucosylating secoisolariciresinol (SECO) into secoisolariciresinol monoglucoside (SMG) and diglucoside (SDG).

PubMed

Ghose, Kaushik; Selvaraj, Kumarakurubaran; McCallum, Jason; Kirby, Chris W; Sweeney-Nixon, Marva; Cloutier, Sylvie J; Deyholos, Michael; Datla, Raju; Fofana, Bourlaye

2014-03-28

Lignans are a class of diphenolic nonsteroidal phytoestrogens often found glycosylated in planta. Flax seeds are a rich source of secoisolariciresinol diglucoside (SDG) lignans. Glycosylation is a process by which a glycosyl group is covalently attached to an aglycone substrate and is catalyzed by uridine diphosphate glycosyltransferases (UGTs). Until now, very little information was available on UGT genes that may play a role in flax SDG biosynthesis. Here we report on the identification, structural and functional characterization of 5 putative UGTs potentially involved in secoisolariciresinol (SECO) glucosylation in flax. Five UGT genes belonging to the glycosyltransferases' family 1 (EC 2.4.x.y) were cloned and characterized. They fall under four UGT families corresponding to five sub-families referred to as UGT74S1, UGT74T1, UGT89B3, UGT94H1, UGT712B1 that all display the characteristic plant secondary product glycosyltransferase (PSPG) conserved motif. However, diversity was observed within this 44 amino acid sequence, especially in the two peptide sequences WAPQV and HCGWNS known to play a key role in the recognition and binding of diverse aglycone substrates and in the sugar donor specificity. In developing flax seeds, UGT74S1 and UGT94H1 showed a coordinated gene expression with that of pinoresinol-lariciresinol reductase (PLR) and their gene expression patterns correlated with SDG biosynthesis. Enzyme assays of the five heterologously expressed UGTs identified UGT74S1 as the only one using SECO as substrate, forming SECO monoglucoside (SMG) and then SDG in a sequential manner. We have cloned and characterized five flax UGTs and provided evidence that UGT74S1 uses SECO as substrate to form SDG in vitro. This study allowed us to propose a model for the missing step in SDG lignan biosynthesis.

Identification and functional characterization of a flax UDP-glycosyltransferase glucosylating secoisolariciresinol (SECO) into secoisolariciresinol monoglucoside (SMG) and diglucoside (SDG)

PubMed Central

2014-01-01

Background Lignans are a class of diphenolic nonsteroidal phytoestrogens often found glycosylated in planta. Flax seeds are a rich source of secoisolariciresinol diglucoside (SDG) lignans. Glycosylation is a process by which a glycosyl group is covalently attached to an aglycone substrate and is catalyzed by uridine diphosphate glycosyltransferases (UGTs). Until now, very little information was available on UGT genes that may play a role in flax SDG biosynthesis. Here we report on the identification, structural and functional characterization of 5 putative UGTs potentially involved in secoisolariciresinol (SECO) glucosylation in flax. Results Five UGT genes belonging to the glycosyltransferases’ family 1 (EC 2.4.x.y) were cloned and characterized. They fall under four UGT families corresponding to five sub-families referred to as UGT74S1, UGT74T1, UGT89B3, UGT94H1, UGT712B1 that all display the characteristic plant secondary product glycosyltransferase (PSPG) conserved motif. However, diversity was observed within this 44 amino acid sequence, especially in the two peptide sequences WAPQV and HCGWNS known to play a key role in the recognition and binding of diverse aglycone substrates and in the sugar donor specificity. In developing flax seeds, UGT74S1 and UGT94H1 showed a coordinated gene expression with that of pinoresinol-lariciresinol reductase (PLR) and their gene expression patterns correlated with SDG biosynthesis. Enzyme assays of the five heterologously expressed UGTs identified UGT74S1 as the only one using SECO as substrate, forming SECO monoglucoside (SMG) and then SDG in a sequential manner. Conclusion We have cloned and characterized five flax UGTs and provided evidence that UGT74S1 uses SECO as substrate to form SDG in vitro. This study allowed us to propose a model for the missing step in SDG lignan biosynthesis. PMID:24678929

Mechanism and Anticancer Activity of the Metabolites of an Endophytic Fungi from Eucommia ulmoides Oliv.

PubMed

Li, Qi; Zhang, Yan; Shi, Jun-Ling; Wang, Yi-Lin; Zhao, Hao-Bin; Shao, Dong-Yan; Huang, Qing-Sheng; Yang, Hui; Jin, Ming-Liang

2017-01-01

Backgroud: Pinoresinol (Pin) and pinoresinol monoglucoside (PMG) are plant-derived lignan molecules with multiple functions. We showed previously that an endophytic fungus from Eucommia ulmoides Oliv., Phomopsis sp. XP-8 is able to produce Pin and PMG. This study was carried out to test the anti-tumor capability of the culture of XP-8 and identify the major effective compounds. The fungal culture was added in the culture of HepG2 and K562 cells, and the viabilities of these cells were detected and the possible mechanism was analyzed. The fungal culture showed significant capaiblity in decreasing the viability of tumor cells and induce apoptosis via up-regulation of the expression of apoptosis-related genes. It also significantly inhibited the adhesion and migration of HepG2 cells by blocking MMP-9 expression. Pin and PMG were isolated from the growth culture and shown to be the major effective components for inhibition. The study indicated the potential application of XP-8 in the production of anti-tumour products by the bioconversion of glucose. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Crataegus pinnatifida: chemical constituents, pharmacology, and potential applications.

PubMed

Wu, Jiaqi; Peng, Wei; Qin, Rongxin; Zhou, Hong

2014-01-30

Crataegus pinnatifida (Hawthorn) is widely distributed in China and has a long history of use as a traditional medicine. The fruit of C. pinnatifida has been used for the treatment of cardiodynia, hernia, dyspepsia, postpartum blood stasis, and hemafecia and thus increasing interest in this plant has emerged in recent years. Between 1966 and 2013, numerous articles have been published on the chemical constituents, pharmacology or pharmacologic effects and toxicology of C. pinnatifida. To review the pharmacologic advances and to discuss the potential perspective for future investigation, we have summarized the main literature findings of these publications. So far, over 150 compounds including flavonoids, triterpenoids, steroids, monoterpenoids, sesquiterpenoids, lignans, hydroxycinnamic acids, organic acids and nitrogen-containing compounds have been isolated and identified from C. pinnatifida. It has been found that these constituents and extracts of C. pinnatifida have broad pharmacological effects with low toxicity on, for example, the cardiovascular, digestive, and endocrine systems, and pathogenic microorganisms, supporting the view that C. pinnatifida has favorable therapeutic effects. Thus, although C. pinnatifida has already been widely used as pharmacological therapy, due to its various active compounds, further research is warranted to develop new drugs.

Bioactive compounds from Peperomia pellucida.

PubMed

Xu, Su; Li, Na; Ning, Meng-Meng; Zhou, Cai-Hong; Yang, Qiao-Rong; Wang, Ming-Wei

2006-02-01

Five new compounds (1-5), including two secolignans, two tetrahydrofuran lignans, and one highly methoxylated dihydronaphthalenone, were isolated from the whole plant of Peperomia pellucida. These compounds were accompanied by the known peperomins A, B, C, and E, 7,8-trans-8,8'-trans-7',8'-cis-7,7'-bis(5-methoxy-3,4-methylenedioxyphenyl)-8-acetoxymethyl-8'-hydroxymethyltetrahydrofuran, 7,8-trans-8,8'-trans-7',8'-cis-7-(5-methoxy-3,4-methylenedioxyphenyl)-7'-(4-hydroxy-3,5-dimethoxyphenyl)-8,8'-diacetoxymethyltetrahydrofuran, sesamin, and isoswertisin. New structures were elucidated mainly by NMR and MS techniques, and anticancer activities evaluated in HL-60, MCF-7, and HeLa cell lines. Compound 1 and peperomin E show growth inhibitory effects on the three cancer cell lines with IC(50) values ranging between 1.4 and 9.1 and between 1.8 and 11.1 microM, respectively. Compound 2 has a weak suppressive activity on HL-60 cells (IC(50) = 10.8 microM), while 7,8-trans-8,8'-trans-7',8'-cis-7,7'-bis(5-methoxy-3,4-methylenedioxyphenyl)-8-acetoxymethyl-8'-hydroxymethyltetrahydrofuran exhibits estrogen-like properties (EC(50) = 3.1 microM) in CV-1 cells transfected with human estrogen receptor (ERalpha).

Mechanism Underlying the Reversal of Drug Resistance in P-Glycoprotein-Expressing Leukemia Cells by Pinoresinol and the Study of a Derivative.

PubMed

González, María L; Vera, D Mariano A; Laiolo, Jerónimo; Joray, Mariana B; Maccioni, Mariana; Palacios, Sara M; Molina, Gabriela; Lanza, Priscila A; Gancedo, Samanta; Rumjanek, Vivian; Carpinella, María C

2017-01-01

P-glycoprotein (P-gp) is a membrane protein associated with multidrug resistance (MDR) due to its key role in mediating the traffic of chemotherapeutic drugs outside cancer cells, leading to a cellular response that hinders efforts toward successful therapy. With the aim of finding agents that circumvent the MDR phenotype mediated by P-gp, 15 compounds isolated from native and naturalized plants of Argentina were screened. Among these, the non-cytotoxic lignan (±) pinoresinol successfully restored sensitivity to doxorubicin from 7 μM in the P-gp overexpressed human myelogenous leukemia cells, Lucena 1. This resistance-reversing effect was confirmed by competitively increasing the intracellular doxorubicin accumulation and by significantly inhibiting the efflux of doxorubicin and, to a lesser extent, that of rhodamine 123. The activity obtained was similar to that observed with verapamil. No such results were observed in the sensitive parental K562 cell line. To gain deeper insight into the mode of action of pinoresinol, its effect on P-gp function and expression was examined. The docking simulations indicated that the lignan bound to P-gp at the apex of the V-shaped transmembrane cavity, involving transmembrane helices 4, 5, and 6, and partially overlapped the binding region of tariquidar, which was used as a positive control. These results would shed some light on the nature of its interaction with P-gp at molecular level and merit further mechanistic and kinetic studies. In addition, it showed a maximum 29% activation of ATP hydrolysis and antagonized verapamil-stimulated ATPase activity with an IC 50 of 20.9 μM. On the other hand, pinoresinol decreased the presence of P-gp in the cell surface. Derivatives of pinoresinol with improved activity were identified by docking studies. The most promising one, the non-cytotoxic 1-acetoxypinoresinol, caused a reversion of doxorubicin resistance from 0.11 μM and thus higher activity than the lead compound. It also caused a significant increase in doxorubicin accumulation. Results were similar to those observed with verapamil. The results obtained positioned these compounds as potential candidates for effective agents to overcome P-gp-mediated MDR, leading to better outcomes for leukemia chemotherapy.

Isolation of circulating immune complexes using Raji cells. Separation of antigens from immune complexes and production of antiserum.

PubMed Central

Theofilopoulos, A N; Eisenberg, R A; Dixon, F J

1978-01-01

Raji cells were used for the isolation of complement-fixing antigen-antibody complexes from serum. Immune complexes bound to these cells were radiolabeled at the cell surface with lactoperoxidase. The complexes were then eluted from the cells with isotonic citrate buffer pH 3.2 or recovered by immunoprecipitation of cell lysates. The antigen and antibody moieties of the complexes were isolated by dissociating sucrose density gradient centrifugation or by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A variety of preformed immune complexes were successfully isolated from serum with this approach. In addition, these techniques were used to isolate and identify the antigens in immune complexes in the serum of rabbits with chronic serum sickness and rats with Moloney virus-induced sarcomas. Methods were also developed for the production of antisera against the antigenic moiety of immune complexes isolated from serum. Repeated challenge of rabbits with whole Raji cells with bound complexes or eluates from such cells resulted in antibody production against the antigens of the immune complexes, although reactivity against cellular and serum components was also elicited. Monospecific antisera against the antigens in immune complexes were produced by immunizing rabbits with the alum-precipitated antigen isolated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These techniques may be useful in isolating antigens in immune complex-associated diseases of unknown etiology. Images PMID:659616

Coptidis rhizoma and its main bioactive components: recent advances in chemical investigation, quality evaluation and pharmacological activity.

PubMed

Meng, Fan-Cheng; Wu, Zheng-Feng; Yin, Zhi-Qi; Lin, Li-Gen; Wang, Ruibing; Zhang, Qing-Wen

2018-01-01

Coptidis rhizoma (CR) is the dried rhizome of Coptis chinensis Franch., C. deltoidea C. Y. Cheng et Hsiao or C. teeta Wall. (Ranunculaceae) and is commonly used in Traditional Chinese Medicine for the treatment of various diseases including bacillary dysentery, typhoid, tuberculosis, epidemic cerebrospinal meningitis, empyrosis, pertussis, and other illnesses. A literature survey was conducted via SciFinder, ScieneDirect, PubMed, Springer, and Wiley databases. A total of 139 selected references were classified on the basis of their research scopes, including chemical investigation, quality evaluation and pharmacological studies. Many types of secondary metabolites including alkaloids, lignans, phenylpropanoids, flavonoids, phenolic compounds, saccharides, and steroids have been isolated from CR. Among them, protoberberine-type alkaloids, such as berberine, palmatine, coptisine, epiberberine, jatrorrhizine, columamine, are the main components of CR. Quantitative determination of these alkaloids is a very important aspect in the quality evaluation of CR. In recent years, with the advances in isolation and detection technologies, many new instruments and methods have been developed for the quantitative and qualitative analysis of the main alkaloids from CR. The quality control of CR has provided safety for pharmacological applications. These quality evaluation methods are also frequently employed to screen the active components from CR. Various investigations have shown that CR and its main alkaloids exhibited many powerful pharmacological effects including anti-inflammatory, anti-cancer, anti-diabetic, neuroprotective, cardioprotective, hypoglycemic, anti-Alzheimer and hepatoprotective activities. This review summarizes the recent phytochemical investigations, quality evaluation methods, the biological studies focusing on CR as well as its main alkaloids.

Secoisolariciresinol Diglucoside (SDG) Isolated from Flaxseed, an Alternative to ACE Inhibitors in the Treatment of Hypertension

PubMed Central

Prasad, Kailash

2013-01-01

Secoisolariciresionol diglucoside (SDG) is a plant lignan isolated from flaxseed and is phytoestrogen. SDG is a potent and long-acting hypotensive agent. Plant phytoestrogens have inhibitory effects on angiotensin-converting enzyme (ACE). The hypotensive effects of SDG, a phytoestrogen, may be mediated through inhibition of ACE. The objective of this study was to investigate if SDG-induced hypotension is mediated through inhibition of ACE. The Sprague Dawley male rats were anesthetized and trachea was cannulated. The right jugular vein was cannulated to administer the drug and the carotid artery was cannulated to record arterial pressures using PIOEZ-1 miniature model transducer (Becton, Dickinson and Company, Franklin Lakes, NJ) and Beckman dynograph (Beckman Instruments, Inc., Schiller Park, IL). The effects of angiotensin I (0.2 µg/kg, intravenously [IV]) in the absence and presence of SDG (10 mg/kg, IV), and SDG alone on systolic, diastolic, and mean arterial pressures were measured before and after 15, 30, and 60 minutes of drug administration. SDG decreased the systolic, diastolic, and mean arterial pressure by 37, 47, and 43%, respectively, at 15 minutes and 18.8, 21.2, and 20.3%, respectively, at 60 minutes. Angiotensin I increased the arterial pressure. SDG decreased angiotensin I-induced rise in the systolic, diastolic, and mean arterial pressures by 60, 58, and 51%, respectively, at 15 minutes and 48, 46, and 30%, respectively, at 60 minutes. The data suggest that SDG reduced the angiotensin I-induced rise in the arterial pressures and hence SDG is a potent ACE inhibitor. PMID:24436618

Secoisolariciresinol Diglucoside (SDG) Isolated from Flaxseed, an Alternative to ACE Inhibitors in the Treatment of Hypertension.

PubMed

Prasad, Kailash

2013-12-01

Secoisolariciresionol diglucoside (SDG) is a plant lignan isolated from flaxseed and is phytoestrogen. SDG is a potent and long-acting hypotensive agent. Plant phytoestrogens have inhibitory effects on angiotensin-converting enzyme (ACE). The hypotensive effects of SDG, a phytoestrogen, may be mediated through inhibition of ACE. The objective of this study was to investigate if SDG-induced hypotension is mediated through inhibition of ACE. The Sprague Dawley male rats were anesthetized and trachea was cannulated. The right jugular vein was cannulated to administer the drug and the carotid artery was cannulated to record arterial pressures using PIOEZ-1 miniature model transducer (Becton, Dickinson and Company, Franklin Lakes, NJ) and Beckman dynograph (Beckman Instruments, Inc., Schiller Park, IL). The effects of angiotensin I (0.2 µg/kg, intravenously [IV]) in the absence and presence of SDG (10 mg/kg, IV), and SDG alone on systolic, diastolic, and mean arterial pressures were measured before and after 15, 30, and 60 minutes of drug administration. SDG decreased the systolic, diastolic, and mean arterial pressure by 37, 47, and 43%, respectively, at 15 minutes and 18.8, 21.2, and 20.3%, respectively, at 60 minutes. Angiotensin I increased the arterial pressure. SDG decreased angiotensin I-induced rise in the systolic, diastolic, and mean arterial pressures by 60, 58, and 51%, respectively, at 15 minutes and 48, 46, and 30%, respectively, at 60 minutes. The data suggest that SDG reduced the angiotensin I-induced rise in the arterial pressures and hence SDG is a potent ACE inhibitor.

Reactivity of lignin and lignans: Correlation with molecular orbital calculations

Treesearch

Thomas Elder

2010-01-01

To date, and as can be seen from the other chapters of this text, the structure and chemistry of lignin have been described in terms of results from a wide range of chemical or spectroscopic methods to construct a mosaic picture of the polymer. The current chapter continues this process by describing past, present and potential applications of electronic structure...

Analysis of sesquiterpene lactones, lignans, and flavonoids in wormwood (Artemisia absinthium L.) using high-performance liquid chromatography (HPLC)-mass spectrometry, reversed phase HPLC, and HPLC-solid phase extraction-nuclear magnetic resonance.

PubMed

Aberham, Anita; Cicek, Serhat Sezai; Schneider, Peter; Stuppner, Hermann

2010-10-27

Today, the medicinal use of wormwood (Artemisia absinthium) is enjoying a resurgence of popularity. This study presents a specific and validated high-performance liquid chromatography (HPLC)-diode array detection method for the simultaneous determination and quantification of bioactive compounds in wormwood and commercial preparations thereof. Five sesquiterpene lactones, two lignans, and a polymethoxylated flavonoid were baseline separated on RP-18 material, using a solvent gradient consisting of 0.085% (v/v) o-phosphoric acid and acetonitrile. The flow rate was 1.0 mL/min, and chromatograms were recorded at 205 nm. The stability of absinthin was tested exposing samples to light, moisture, and different temperatures. Methanolic and aqueous solutions of absinthin were found to be stable for up to 6 months. This was also the case when the solid compound was kept in the refrigerator at -35 °C. In contrast, the colorless needles, when stored at room temperature, turned yellow. Three degradation compounds (anabsin, anabsinthin, and the new dimer 3'-hydroxyanabsinthin) were identified by HPLC-mass spectrometry and HPLC-solid-phase extraction-nuclear magnetic resonance and quantified by the established HPLC method.

Evaluation of phenolic compounds in virgin olive oil by direct injection in high-performance liquid chromatography with fluorometric detection.

PubMed

Selvaggini, Roberto; Servili, Maurizio; Urbani, Stefania; Esposto, Sonia; Taticchi, Agnese; Montedoro, GianFrancesco

2006-04-19

Hydrophilic phenols are the most abundant natural antioxidants of virgin olive oil (VOO), in which tocopherols and carotenes are also present. The prevalent classes of hydrophilic phenols found in VOO are phenyl alcohols, phenolic acids, secoiridoids such as the dialdehydic form of decarboxymethyl elenolic acid linked to (3,4-dihydroxyphenyl)ethanol or (p-hydroxypheny1)ethanol (3,4-DHPEA-EDA or p-HPEA-EDA) and an isomer of the oleuropein aglycon (3,4-DHPEA-EA), lignans such as (+)-1-acetoxypinoresinol and (+)-pinoresinol, and flavonoids. A new method for the analysis of VOO hydrophilic phenols by direct injection in high-performance liquid chromatography (HPLC) with the use of a fluorescence detector (FLD) has been proposed and compared with the traditional liquid-liquid extraction technique followed by the HPLC analysis utilizing a diode array detector (DAD) and a FLD. Results show that the most important classes of phenolic compounds occurring in VOO can be evaluated using HPLC direct injection. The efficiency of the new method, as compared to the liquid-liquid extraction, was higher to quantify phenyl alcohols, lignans, and 3,4-DHPEA-EA and lower for the evaluation of 3,4-DHPEA-EDA and p-HPEA-EDA.

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.

An Extraordinary Accumulation of (-)-Pinoresinol in Cell-Free Extracts of Forsythia intermedia: Evidence for Enantiospecific Reduction of (+)-Pinoresinol

NASA Technical Reports Server (NTRS)

Katayama, Takeshi; Davin, Laurence B.; Lewis, Norman G.

1992-01-01

Stereoselective and enantiospecific transformation mechanisms in lignan biogenesis are only now yielding to scientific inquiry: it has been shown that soluble cell-free preparations from Forsythia intermedia catalysis the formation of the enantiomerically pure lignan, (-)-secoisolariciresinol, when incubated with coniferyl alcohol in the presence of NAD(P)H and H2O2. Surprisingly, (-)-pinoresinol also accumulates in this soluble cell-free assay mixture in greater than 96% enantiomeric excess, even though it is not the naturally occurring antipode present in Forsythia sp. But these soluble cell-free preparations do not engender stereoselective coupling; instead, racemic pinoresinols are first formed, catalysed by an H2O2-dependent peroxidase reaction. An enantiospecific NAD(P)H reductase then converts (+)- pinoresinol, and not the (-)-antipode, into (-)-secoisolariciresinol. Stereoselective syntheis of(+)-pinoresinol from E-coniferyl alcohol is, however, catalysed by an insoluble enzyme preparation in F. suspensa, obtained following removal of readily soluble and ionically bound enzymes; no exogenously supplied cofactors were required other than oxygen, although the reaction was stimulated by NAD-malate addition. Thus, the overall biochemical pathway to enantiomerically pure (-)-secoisolariciresinol has been delineated.

Biosynthesis of podophyllotoxin in Linum album cell cultures.

PubMed

Seidel, Véronique; Windhövel, Jörg; Eaton, Graham; Alfermann, A Wilhelm; Arroo, Randolph R J; Medarde, Manuel; Petersen, Maike; Woolley, Jack G

2002-10-01

Cell cultures of Linum album Kotschy ex Boiss. (Linaceae) showing high accumulation of the lignan podophyllotoxin (PTOX) were established. Enzymological studies revealed highest activities of phenylalanine ammonia-lyase, cinnamyl alcohol dehydrogenase, 4-hydroxycinnamate:CoA ligase and cinnamoyl-CoA:NADP oxidoreductase immediately prior to PTOX accumulation. To investigate PTOX biosynthesis, feeding experiments were performed with [2-(13)C]3',4'-dimethoxycinnamic acid, [2-(13)C]3',4'-methylenedioxycinnamic acid (MDCA), [2-(13)C]3',4',5'-trimethoxycinnamic acid, [2-(13)C]sinapic acid, [2-(13)C]- and [2,3-(13)C(2)]ferulic acid. Analysis of the metabolites by HPLC coupled to tandem mass spectrometry revealed incorporation of label from ferulic acid into PTOX and deoxypodophyllotoxin (DOP). In addition, MDCA was also unambiguously incorporated intact into PTOX. These observations suggest that in L. album both ferulic acid and methylenedioxy-substituted cinnamic acid can be incorporated into lignans. Furthermore, it appears that, in this species, the hydroxylation of DOP is a rate-limiting point in the pathway leading to PTOX. Electronic supplementary material to this paper can be obtained by using the Springer LINK server located at http://dx.doi.org/wo.1007/s00425-002-0834-1.

Interspecific comparison of constitutive ash phloem phenolic chemistry reveals compounds unique to manchurian ash, a species resistant to emerald ash borer.

PubMed

Whitehill, Justin G A; Opiyo, Stephen O; Koch, Jennifer L; Herms, Daniel A; Cipollini, Donald F; Bonello, Pierluigi

2012-05-01

The emerald ash borer (Agrilus planipennis, EAB) is an invasive wood-borer indigenous to Asia and is responsible for widespread ash (Fraxinus spp.) mortality in the U.S. and Canada. Resistance and susceptibility to EAB varies among Fraxinus spp., which is a result of their co-evolutionary history with the pest. We characterized constitutive phenolic profiles and lignin levels in the phloem of green, white, black, blue, European, and Manchurian ash. Phloem was sampled twice during the growing season, coinciding with phenology of early and late instar EAB. We identified 66 metabolites that displayed a pattern of variation, which corresponded strongly with phylogeny. Previously identified lignans and lignan derivatives were confirmed to be unique to Manchurian ash, and may contribute to its high level of resistance to EAB. Other compounds that had been considered unique to Manchurian ash, including hydroxycoumarins and the phenylethanoids calceolarioside A and B, were detected in closely related, but susceptible species, and thus are unlikely to contribute to EAB resistance of Manchurian ash. The distinct phenolic profile of blue ash may contribute to its relatively high resistance to EAB.

Quantity and quality of secoiridoids and lignans in extra virgin olive oils: the effect of two- and three-way decanters on Leccino and Raggiola olive cultivars.

PubMed

Antonini, Elena; Farina, Alfonso; Scarpa, Emanuele Salvatore; Frati, Alessandra; Ninfali, Paolino

2016-01-01

In this investigation, 14 extra virgin olive oils (EVOOs), produced with Leccino and Raggiola olive cultivars, by a new two-way (2W) decanter were compared with 14 EVOOs produced by means of a conventional three-way (3W) decanter. The 2W EVOOs had higher phenol concentrations, as shown by high-performance liquid chromatography/diode array detection (HPLC-DAD) analysis and yielded a higher extraction of the 3,4-DHPEA-EDA (oleacein), 3,4-DHPEA-EA (oleuropein aglycone) and p-HPEA-EDA (oleocanthal). The concentrations of lignans, (+)-pinoresinol and (+)-1-acetoxypinoresinol, detected by HPLC-FLD equipment, were higher in the 2W EVOOs than they were in EVOOs produced using the 3W system. Total phenols, detected by the Folin-Ciocalteu assay, were lower than those obtained by HPLC, but they significantly correlated (p < 0.05). The antioxidant capacity (ORAC) values of 2W EVOOs were higher than those of 3W EVOOs. In conclusion, the 2W system provided high-quality phenol EVOOs and became an indispensable tool when adverse climatic conditions reduced the olive secoiridoid concentration.

Retention of natural antioxidants of blends of groundnut and sunflower oils with minor oils during storage and frying.

PubMed

Sunil, L; Reddy, P Vanitha; Krishna, A G Gopala; Urooj, Asna

2015-02-01

Unrefined groundnut oil (GNO) and refined sunflower oil (SFO) were blended with four minor oils including laboratory refined red palmolein (RRPO), physically refined rice bran oil (RBO), unrefined sesame oil (SESO), and unrefined coconut oil (CNO) containing natural antioxidants viz., β-carotene, tocopherols, oryzanol and lignans. The five blends prepared were GNO + RRPO (80:20), GNO + RBO (80:20), GNO + SESO (80:20), SFO + RRPO (50:50) and SFO + CNO (60:40). Prepared blends contained saturated fatty acids (SFA) (16.7-53.3 %); monounsaturated fatty acids (MUFA) (16.0-45.5 %) and polyunsaturated fatty acids (PUFA) (29.2-37.8 %). GNO blends viz., GNO + RRPO, GNO + RBO and GNO + SESO contained β-carotene (10.7 mg/100 g), oryzanol (0.12 g/100 g) and lignans (0.35 g/100 g) respectively as natural antioxidants. SFO was enriched with β-carotene (28.7 mg/100 g) and medium chain fatty acids (34.2 %) by blending with RRPO and CNO respectively. The oil blends (200 ml) were packed and stored at 38 °C/90 % relative humidity (RH) and 27 °C/65 % RH and samples were withdrawn at fixed intervals for analysis. Freshly prepared blends were also investigated for their frying performance. During storage, GNO + RBO blend showed highest oxidative stability probably due to the presence of oryzanol in the order GNO + RBO > GNO + SESO > GNO + RRPO. During frying, the peroxide value of GNO blends with RBO (rich in oryzanol) and SESO (rich in lignans) was less while the free fatty acid value was less in SFO blends with RRPO and CNO. Hence, blending of natural antioxidants rich minor oils (RRPO, RBO and SESO) with the major vegetable oils (GNO and SFO) may preserve them by lowering their rate of oxidation during storage and frying.

Flavonoid engineering of flax potentiate its biotechnological application.

PubMed

Zuk, Magdalena; Kulma, Anna; Dymińska, Lucyna; Szołtysek, Katarzyna; Prescha, Anna; Hanuza, Jerzy; Szopa, Jan

2011-01-28

Flavonoids are a group of secondary plant metabolites important for plant growth and development. They show also a protective effect against colon and breast cancer, diabetes, hypercholesterolemic atherosclerosis, lupus nephritis, and immune and inflammatory reactions. Thus, overproduction of these compounds in flax by genetic engineering method might potentiate biotechnological application of these plant products. Flax plants of third generation overexpressing key genes of flavonoid pathway cultivated in field were used as plant material throughout this study. The biochemical properties of seed, oil and seedcake extracts and fibre from natural and transgenic flax plants were compared. The data obtained suggests that the introduced genes were stably inherited and expressed through plant generations. Overproduction of flavonoid compounds resulted in increase of fatty acids accumulation in oil from transgenic seeds due to protection from oxidation offered during synthesis and seed maturation. The biochemical analysis of seedcake extracts from seeds of transgenic flax revealed significant increase in flavonoids (kaempferol), phenolic acids (coumaric, ferulic, synapic acids) and lignan content. Fibres, another product of flax plant showed increase in the level of catechine and acetylvanillone and decrease in phenolic acids upon flax modification.Biochemical analysis results were confirmed using IR spectroscopy. The integral intensities of IR bands have been used for identification of the component of phenylpropanoid pathway in oil, seedcake extract and fibre from control and transgenic flax. It was shown that levels of flavonoids, phenolic acids and lignans in oil and seedcake extract was higher in transgenic flax products compared to control. An FT-IR study of fibres confirmed the biochemical data and revealed that the arrangement of the cellulose polymer in the transgenic fibres differs from the control; in particular a significant decrease in the number of hydrogen bonds was detected. All analysed products from generated transgenic plants were enriched with antioxidant compounds derived from phenylopropanoid pathway Thus the products provide valuable source of flavonoids, phenolic acids and lignan for biomedical application. The compounds composition and quantity from transgenic plants was confirmed by IR spectroscopy. Thus the infrared spectroscopy appeared to be suitable method for characterization of flax products.

Flavonoid engineering of flax potentiate its biotechnological application

PubMed Central

2011-01-01

Background Flavonoids are a group of secondary plant metabolites important for plant growth and development. They show also a protective effect against colon and breast cancer, diabetes, hypercholesterolemic atherosclerosis, lupus nephritis, and immune and inflammatory reactions. Thus, overproduction of these compounds in flax by genetic engineering method might potentiate biotechnological application of these plant products. Results Flax plants of third generation overexpressing key genes of flavonoid pathway cultivated in field were used as plant material throughout this study. The biochemical properties of seed, oil and seedcake extracts and fibre from natural and transgenic flax plants were compared. The data obtained suggests that the introduced genes were stably inherited and expressed through plant generations. Overproduction of flavonoid compounds resulted in increase of fatty acids accumulation in oil from transgenic seeds due to protection from oxidation offered during synthesis and seed maturation. The biochemical analysis of seedcake extracts from seeds of transgenic flax revealed significant increase in flavonoids (kaempferol), phenolic acids (coumaric, ferulic, synapic acids) and lignan content. Fibres, another product of flax plant showed increase in the level of catechine and acetylvanillone and decrease in phenolic acids upon flax modification. Biochemical analysis results were confirmed using IR spectroscopy. The integral intensities of IR bands have been used for identification of the component of phenylpropanoid pathway in oil, seedcake extract and fibre from control and transgenic flax. It was shown that levels of flavonoids, phenolic acids and lignans in oil and seedcake extract was higher in transgenic flax products compared to control. An FT-IR study of fibres confirmed the biochemical data and revealed that the arrangement of the cellulose polymer in the transgenic fibres differs from the control; in particular a significant decrease in the number of hydrogen bonds was detected. Conclusions All analysed products from generated transgenic plants were enriched with antioxidant compounds derived from phenylopropanoid pathway Thus the products provide valuable source of flavonoids, phenolic acids and lignan for biomedical application. The compounds composition and quantity from transgenic plants was confirmed by IR spectroscopy. Thus the infrared spectroscopy appeared to be suitable method for characterization of flax products. PMID:21276227

Ruminant Rhombencephalitis-Associated Listeria monocytogenes Alleles Linked to a Multilocus Variable-Number Tandem-Repeat Analysis Complex ▿ †

PubMed Central

Balandyté, Lina; Brodard, Isabelle; Frey, Joachim; Oevermann, Anna; Abril, Carlos

2011-01-01

Listeria monocytogenes is among the most important food-borne pathogens and is well adapted to persist in the environment. To gain insight into the genetic relatedness and potential virulence of L. monocytogenes strains causing central nervous system (CNS) infections, we used multilocus variable-number tandem-repeat analysis (MLVA) to subtype 183 L. monocytogenes isolates, most from ruminant rhombencephalitis and some from human patients, food, and the environment. Allelic-profile-based comparisons grouped L. monocytogenes strains mainly into three clonal complexes and linked single-locus variants (SLVs). Clonal complex A essentially consisted of isolates from human and ruminant brain samples. All but one rhombencephalitis isolate from cattle were located in clonal complex A. In contrast, food and environmental isolates mainly clustered into clonal complex C, and none was classified as clonal complex A. Isolates of the two main clonal complexes (A and C) obtained by MLVA were analyzed by PCR for the presence of 11 virulence-associated genes (prfA, actA, inlA, inlB, inlC, inlD, inlE, inlF, inlG, inlJ, and inlC2H). Virulence gene analysis revealed significant differences in the actA, inlF, inlG, and inlJ allelic profiles between clinical isolates (complex A) and nonclinical isolates (complex C). The association of particular alleles of actA, inlF, and newly described alleles of inlJ with isolates from CNS infections (particularly rhombencephalitis) suggests that these virulence genes participate in neurovirulence of L. monocytogenes. The overall absence of inlG in clinical complex A and its presence in complex C isolates suggests that the InlG protein is more relevant for the survival of L. monocytogenes in the environment. PMID:21984240

[Separation and purification of the components in Trachelospermum jasminoides by two dimensional hydrophilic interaction liquid chromatography- reversed-phase liquid chromatography].

PubMed

Jia, Youmei; Cai, Jianfeng; Xin, Huaxia; Feng, Jiatao; Fu, Yanhui; Fu, Qing; Jin, Yu

2017-06-08

A preparative two dimensional hydrophilic interaction liquid chromatography/reversed-phase liquid chromatography (Pre-2D-HILIC/RPLC) method was established to separate and purify the components in Trachelospermum jasminoides . The pigments and strongly polar components were removed from the crude extract after the active carbon decolorization and solid phase extraction processes. A Click XIon column (250 mm×20 mm, 10 μm) was selected as stationary phase and water-acetonitrile as mobile phases in the first dimensional HILIC. Finally, 15 fractions were collected under UV-triggered mode. In the second dimensional RPLC, a C18 column (250 mm×20 mm, 5 μm) was selected and water-acetonitrile was used as mobile phases. As a result, 14 compounds with high purity were obtained, which were further identified by mass spectrometry (MS) and nuclear magnetic resonance (NMR). Finally, 11 lignan compounds and three flavonoid compounds were obtained. The method has a good orthogonality, and can improve the resolution and the peak capacity. It is significant for the separation of complex components from Trachelospermum jasminoides .

Cytotoxic constituents from Brazilian red propolis and their structure-activity relationship.

PubMed

Li, Feng; Awale, Suresh; Tezuka, Yasuhiro; Kadota, Shigetoshi

2008-05-15

Several classes of flavonoids [flavanoids (1-10), flavonol (11), isoflavones (12-18), isoflavanones (19-22), isoflavans (23-26), chalcones (27-30), auronol (31), pterocarpans (32-37), 2-arylbenzofuran (38), and neoflavonoid (39)] and lignans (40-42) isolated from the MeOH extract of Brazilian red propolis were investigated for their cytotoxic activity against a panel of six different cancer cell lines including murine colon 26-L5 carcinoma, murine B16-BL6 melanoma, murine Lewis lung carcinoma, human lung A549 adenocarcinoma, human cervix HeLa adenocarcinoma, and human HT-1080 fibrosarcoma cell lines. Based on the observed results, structure-activity relationships were discussed. Among the tested compounds, 7-hydroxy-6-methoxyflavanone (3) exhibited the most potent activity against B16-BL6 (IC(50), 6.66microM), LLC (IC(50), 9.29microM), A549 (IC(50), 8.63microM), and HT-1080 (IC(50), 7.94microM) cancer cell lines, and mucronulatol (26) against LLC (IC(50), 8.38microM) and A549 (IC(50), 9.9microM) cancer cell lines. These activity data were comparable to those of the clinically used anticancer drugs, 5-fluorouracil and doxorubicin, against the tested cell lines, suggesting that 3 and 26 are the good candidates for future anticancer drug development.

Dehydrodiconiferyl alcohol suppresses monocyte adhesion to endothelial cells by attenuation of JNK signaling pathway.

PubMed

Tsuneyoshi, Tadamitsu; Kanamori, Yuta; Matsutomo, Toshiaki; Morihara, Naoaki

2015-09-25

Several clinical studies have shown that the intake of aged garlic extract improves endothelial dysfunction. Lignan compounds, (+)-(2S,3R)-dehydrodiconiferyl alcohol (DDC) and (-)-(2R,3S)-dihydrodehydrodiconiferyl alcohol (DDDC), have been isolated as antioxidants in aged garlic extract. There is evidence showing the importance of oxidative stress in endothelial dysfunction. In the present study, we examined whether DDC and DDDC enhance endothelial cell function in vitro. Cell adhesion assay was performed using THP-1 monocyte and human umbilical vein endothelial cells (HUVECs) which were activated by lipopolysaccharide (LPS) or advanced glycation end products (AGEs)-BSA. Cellular ELISA method was used for the evaluation of vascular cell adhesion molecule 1 (VCAM-1) expression on HUVECs. DDC and DDDC suppressed the adhesion of THP-1 to HUVECs which was activated by LPS or AGEs-BSA. DDC and DDDC also inhibited VCAM-1 expression induced by LPS or AGEs-BSA, but DDDC was less effective than DDC. In addition, the inhibitory effect of DDC on VCAM-1 expression involved suppressing JNK/c-Jun pathway rather than NF-κB pathway. DDC has an inhibitory effect on VCAM-1 expression via JNK pathway in endothelial cells and therefore may serve as a novel pharmacological agent to improve endothelial dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.

Dietary supplementation with secoisolariciresinol diglycoside (SDG) reduces experimental metastasis of melanoma cells in mice.

PubMed

Li, D; Yee, J A; Thompson, L U; Yan, L

1999-07-19

We investigated the effect of dietary supplementation with secoisolariciresinol diglycoside (SDG), a lignan precursor isolated from flaxseed, on experimental metastasis of B16BL6 murine melanoma cells in C57BL/6 mice. Four diets were compared: a basal diet (control group) and the basal diet supplemented with SDG at 73, 147 or 293 micromol/kg (equivalent to SDG provided in the 2.5, 5 or 10% flaxseed diet). Mice were fed the diet for 2 weeks before and after an intravenous injection of 0.6 x 10(5) tumor cells. At necropsy, the number and size of tumors that formed in the lungs were determined. The median number of tumors in the control group was 62, and those in the SDG-supplemented groups were 38, 36 and 29, respectively. The last was significantly different from the control (P < 0.01). Dietary supplementation with SDG at 73, 147 and 293 micromol/kg also decreased tumor size (tumor cross-sectional area and volume) in a dose-dependent manner compared with the control values. These results show that SDG reduced pulmonary metastasis of melanoma cells and inhibited the growth of metastatic tumors that formed in the lungs. It is concluded that dietary supplementation with SDG reduces experimental metastasis of melanoma cells in mice.

Efficacy of bioactive compounds from extra virgin olive oil to modulate atherosclerosis development.

PubMed

Lou-Bonafonte, José M; Arnal, Carmen; Navarro, María A; Osada, Jesús

2012-07-01

As olive oil is the main source of calories in the Mediterranean diet, a great deal of research has been devoted to characterizing its role in atherosclerosis. Virgin olive oil is an oily matrix that contains hydrocarbons, mainly squalene; triterpenes such as uvaol, erythrodiol, oleanolic, and maslinic acid; phytosterols; and a wide range of phenolic compounds comprising simple phenols, flavonoids, secoiridoids, and lignans. In this review, we analyze the studies dealing with atherosclerosis and olive oil in several species. A protective role of virgin olive oil against atherosclerosis has been shown in ApoE-deficient mice and hamsters. In the former animal, sex, dose, and dietary cholesterol are modulators of the outcome. Contradictory findings have been reported for rabbits, a circumstance that could be due to the profusion of experimental designs, differing in terms of doses and animal strains, as well as sources of olive oils. This role has yet to be fully validated in humans. Minor components of olive oil have been shown to be involved in atherosclerosis protection. Nevertheless, evidence of the potential of isolated compounds or the right combination of them to achieve the antiatherosclerotic effect of virgin olive oil is inconclusive and will undoubtedly require further experimental support. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Genus Luehea (Malvaceae-Tiliaceae): Review about Chemical and Pharmacological Aspects

PubMed Central

de Morais, Selene Maia; Colares, Aracélio Viana

2016-01-01

Popularly known as “açoita-cavalo” (whips-horse), Luehea species (Malvaceae-Tilioideae) are native to America and are used in folk medicine as anti-inflammatory, antidiarrheal, antiseptic, expectorant, and depurative and against skin infections. Although there are studies showing the chemical constituents of some species, the active substances have not been properly identified. A systematic study was carried out through a computer search of data on CAPES journals, SciELO, ISI Bireme, PubMed, ScienceDirect, ScienceDomain Medline, and Google Scholar from published articles using key words: Luehea, açoita-cavalo, and Malvaceae. Luehea divaricata was the species with the highest number of studies observed. Triterpenes (9), flavonoids (6), and steroids (4), including saponins, organic acids (4), and one lignan, are the main types of secondary metabolites registered and the most cited flavonoids were rutin and quercetin and among triterpenes there was maslinic acid, which might be associated with the popular indication of its anti-inflammatory action. The vitexin, a C-glycosylated flavone, isolated from three different species, is cited as a possible taxonomic marker of the genus. Studies confirm in part the medicinal uses of plants named as “açoita-cavalo” species. Some pharmacological activities, not assigned to the species of the genus Luehea by populations, were observed in laboratory experiments. PMID:27818835

The role of food supplements in the treatment of the infertile man.

PubMed

Comhaire, Frank H; Mahmoud, Ahmed

2003-01-01

Recently, concerns have been raised about the presumptive increased risk of serious undesirable side effects in children born after IVF and intracytoplasmic sperm injection (ICSI). These treatments must, therefore, be reserved as the ultimate option after evidence-based and cause-directed treatment of the male patient with deficient semen has been exhausted. The present authors found that sperm quality and function improved with the intake of complementary food supplementation using a combination of zinc and folic acid, or the antioxidant astaxanthin (Astacarox), or an energy-providing combination containing (actyl)-carnitine (Proxeed). Also, double blind trials showed that the latter two substances increase spontaneous or intrauterine insemination- (IUI-) assisted conception rates. Extracts of Pinus maritima bark (Pycnogenol), which inhibits the cyclo-oxygenase enzyme, reducing prostaglandin production and inflammatory reaction, and extracts of the Peruvian plant Lepidium meyenii were shown to improve sperm morphology and concentration, respectively, in uncontrolled trials. Linseed (flaxseed) oil contains alfa-linolenic acid and lignans. The former corrects the deficient intake of omega-3 essential fatty acids, which is correlated with impaired sperm motility among subfertile men. Lignans are precursors of enterolacton, which inhibits aromatase and reduces the ratio of 16-OH over 2-OH oestrogen metabolites. The resulting reduction in oestrogen load may favourably influence Sertoli cell function.

Therapeutic values, chemical constituents and toxicity of Taiwanese Dysosma pleiantha--a review.

PubMed

Karuppaiya, Palaniyandi; Tsay, Hsin Sheng

2015-07-16

Dysosma pleiantha (Hance) Woodson also called as Bajiaolian belongs to the family Berberidaceae, is widely used in Taiwan as traditional Chinese herbal medicine for more than thousands of years. It is usually recommended by various traditional Chinese medical doctors and herbal pharmacies for general remedies including postpartum recovery, treatment of weakness, neck mass, acne, hepatoma, lumbago, snakebite, tumor growth and dysmenorrhea. In the textbooks of traditional Chinese medicine, there is limited information about the toxicity of Bajiaolian. Podophyllotoxin, a lignan is the main toxic ingredient of Bajiaolian rhizome. Therefore, Bajiaolian is documented as the fifth highest cause of poisoning among the herbal medicine in Taiwan. Since the therapeutic and toxic doses are very close, Bajiaolian poisoning cases are frequently reported in Taiwan. Moreover, Dysosma poisoning cases are difficult to diagnosis because physicians are unfamiliar with this medicine's multiple clinical presentations in different stages of intoxication. Therefore, the objective of this review is to represent the collective information available in literatures regarding D. pleiantha, a cytotoxic lignan containing medicinal plant. Specifically, the literatures have been reviewed for articles pertaining to chemical constituents, properties, therapeutical benefits, toxicity, poisoning symptoms, toxic as well as therapeutic dose and medical management. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The Flaxseed-Derived Lignan Phenolic Secoisolariciresinol Diglucoside (SDG) Protects Non-Malignant Lung Cells from Radiation Damage

PubMed Central

Velalopoulou, Anastasia; Tyagi, Sonia; Pietrofesa, Ralph A.; Arguiri, Evguenia; Christofidou-Solomidou, Melpo

2015-01-01

Plant phenolic compounds are common dietary antioxidants that possess antioxidant and anti-inflammatory properties. Flaxseed (FS) has been reported to be radioprotective in murine models of oxidative lung damage. Flaxseed’s protective properties are attributed to its main biphenolic lignan, secoisolariciresinol diglucoside (SDG). SDG is a free radical scavenger, shown in cell free systems to protect DNA from radiation-induced damage. The objective of this study was to investigate the in vitro radioprotective efficacy of SDG in murine lung cells. Protection against irradiation (IR)-induced DNA double and single strand breaks was assessed by γ-H2AX labeling and alkaline comet assay, respectively. The role of SDG in modulating the levels of cytoprotective enzymes was evaluated by qPCR and confirmed by Western blotting. Additionally, effects of SDG on clonogenic survival of irradiated cells were evaluated. SDG protected cells from IR-induced death and ameliorated DNA damage by reducing mean comet tail length and percentage of γ-H2AX positive cells. Importantly, SDG significantly increased gene and protein levels of antioxidant HO-1, GSTM1 and NQO1. Our results identify the potent radioprotective properties of the synthetic biphenolic SDG, preventing DNA damage and enhancing the antioxidant capacity of normal lung cells; thus, rendering SDG a potential radioprotector against radiation exposure. PMID:26703588

The Flaxseed-Derived Lignan Phenolic Secoisolariciresinol Diglucoside (SDG) Protects Non-Malignant Lung Cells from Radiation Damage.

PubMed

Velalopoulou, Anastasia; Tyagi, Sonia; Pietrofesa, Ralph A; Arguiri, Evguenia; Christofidou-Solomidou, Melpo

2015-12-22

Plant phenolic compounds are common dietary antioxidants that possess antioxidant and anti-inflammatory properties. Flaxseed (FS) has been reported to be radioprotective in murine models of oxidative lung damage. Flaxseed's protective properties are attributed to its main biphenolic lignan, secoisolariciresinol diglucoside (SDG). SDG is a free radical scavenger, shown in cell free systems to protect DNA from radiation-induced damage. The objective of this study was to investigate the in vitro radioprotective efficacy of SDG in murine lung cells. Protection against irradiation (IR)-induced DNA double and single strand breaks was assessed by γ-H2AX labeling and alkaline comet assay, respectively. The role of SDG in modulating the levels of cytoprotective enzymes was evaluated by qPCR and confirmed by Western blotting. Additionally, effects of SDG on clonogenic survival of irradiated cells were evaluated. SDG protected cells from IR-induced death and ameliorated DNA damage by reducing mean comet tail length and percentage of γ-H2AX positive cells. Importantly, SDG significantly increased gene and protein levels of antioxidant HO-1, GSTM1 and NQO1. Our results identify the potent radioprotective properties of the synthetic biphenolic SDG, preventing DNA damage and enhancing the antioxidant capacity of normal lung cells; thus, rendering SDG a potential radioprotector against radiation exposure.

Design and synthesis of a new series of 3,5-disubstituted isoxazoles active against Trypanosoma cruzi and Leishmania amazonensis.

PubMed

da Rosa, Rafael; de Moraes, Milene Höehr; Zimmermann, Lara Almida; Schenkel, Eloir Paulo; Steindel, Mario; Bernardes, Lílian Sibelle Campos

2017-03-10

Chagas disease and leishmaniasis are neglected tropical diseases (NTDs) endemic in developing countries. Although there are drugs available for their treatment, efforts on finding new efficacious therapies are continuous. The natural lignans grandisin (1) and veraguensin (2) show activity against trypomastigote T. cruzi and their scaffold has been used as inspiration to design new derivatives with improved potency and chemical properties. We describe here the planning and microwave-irradiated synthesis of 26 isoxazole derivatives based on the structure of the lignans 1 and 2. In addition, the in vitro evaluation against culture trypomastigotes and intracellular amastigotes of T. cruzi and intracellular amastigotes of L. amazonensis and L. infantum is reported. Among the synthesized derivatives, compounds 17 (IC 50  = 5.26 μM for T. cruzi), 29 (IC 50  = 1.74 μM for T. cruzi) and 31 (IC 50  = 1.13 μM for T. cruzi and IC 50  = 5.08 μM for L. amazonensis) were the most active and were also evaluated against recombinant trypanothione reductase of T. cruzi in a preliminary study of their mechanism of action. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Leoligin, the major lignan from Edelweiss, inhibits intimal hyperplasia of venous bypass grafts

PubMed Central

Reisinger, Ute; Schwaiger, Stefan; Zeller, Iris; Messner, Barbara; Stigler, Robert; Wiedemann, Dominik; Mayr, Tobias; Seger, Christoph; Schachner, Thomas; Dirsch, Verena M.; Vollmar, Angelika M.; Bonatti, Johannes O.; Stuppner, Hermann; Laufer, Günther; Bernhard, David

2009-01-01

Aims Despite the lower patency of venous compared with arterial coronary artery bypass grafts, ∼50% of grafts used are saphenous vein conduits because of their easier accessibility. In a search for ways to increase venous graft patency, we applied the results of a previous pharmacological study screening for non-toxic compounds that inhibit intimal hyperplasia of saphenous vein conduits in organ cultures. Here we analyse the effects and mechanism of action of leoligin [(2S,3R,4R)-4-(3,4-dimethoxybenzyl)-2-(3,4-dimethoxyphenyl)tetrahydrofuran-3-yl]methyl (2Z)-2-methylbut-2-enoat, the major lignan from Edelweiss (Leontopodium alpinum Cass.). Methods and results We found that leoligin potently inhibits vascular smooth muscle cell (SMC) proliferation by inducing cell cycle arrest in the G1-phase. Leoligin induced cell death neither in SMCs nor, more importantly, in endothelial cells. In a human saphenous vein organ culture model for graft disease, leoligin potently inhibited intimal hyperplasia, and even reversed graft disease in pre-damaged vessels. Furthermore, in an in vivo mouse model for venous bypass graft disease, leoligin potently inhibited intimal hyperplasia. Conclusion Our data suggest that leoligin might represent a novel non-toxic, non-thrombogenic, endothelial integrity preserving candidate drug for the treatment of vein graft disease. PMID:19228707

Microwave-assisted extraction of herbacetin diglucoside from flax (Linum usitatissimum L.) seed cakes and its quantification using an RP-HPLC-UV system.

PubMed

Fliniaux, Ophélie; Corbin, Cyrielle; Ramsay, Aina; Renouard, Sullivan; Beejmohun, Vickram; Doussot, Joël; Falguières, Annie; Ferroud, Clotilde; Lamblin, Frédéric; Lainé, Eric; Roscher, Albrecht; Grand, Eric; Mesnard, François; Hano, Christophe

2014-03-10

Flax (Linum usitatissimum L.) seeds are widely used for oil extraction and the cold-pressed flaxseed (or linseed) cakes obtained during this process constitute a valuable by-product. The flavonol herbacetin diglucoside (HDG) has been previously reported as a constituent of the flaxseed lignan macromolecule linked through ester bonds to the linker molecule hydroxymethylglutaric acid. In this context, the development and validation of a new approach using microwave-assisted extraction (MAE) of HDG from flaxseed cakes followed by quantification with a reverse-phase HPLC system with UV detection was purposed. The experimental parameters affecting the HDG extraction yield, such as microwave power, extraction time and sodium hydroxide concentration, from the lignan macromolecule were optimized. A maximum HDG concentration of 5.76 mg/g DW in flaxseed cakes was measured following an irradiation time of 6 min, for a microwave power of 150 W using a direct extraction in 0.1 M NaOH in 70% (v/v) aqueous methanol. The optimized method was proven to be rapid and reliable in terms of precision, repeatability, stability and accuracy for the extraction of HDG. Comparison with a conventional extraction method demonstrated that MAE is more effective and less time-consuming.

Cell and nuclear enlargement of SW480 cells induced by a plant lignan, arctigenin: evaluation of cellular DNA content using fluorescence microscopy and flow cytometry.

PubMed

Kang, Kyungsu; Lee, Hee Ju; Yoo, Ji-Hye; Jho, Eun Hye; Kim, Chul Young; Kim, Minkyun; Nho, Chu Won

2011-08-01

Arctigenin is a natural plant lignan previously shown to induce G(2)/M arrest in SW480 human colon cancer cells as well as AGS human gastric cancer cells, suggesting its use as a possible cancer chemopreventive agent. Changes in cell and nuclear size often correlate with the functionality of cancer-treating agents. Here, we report that arctigenin induces cell and nuclear enlargement of SW480 cells. Arctigenin clearly induced the formation of giant nuclear shapes in SW480, as demonstrated by fluorescence microscopic observation and quantitative determination of nuclear size. Cell and nuclear size were further assessed by flow cytometric analysis of light scattering and fluorescence pulse width after propidium iodide staining. FSC-H and FL2-W values (parameters referring to cell and nuclear size, respectively) significantly increased after arctigenin treatment; the mean values of FSC-H and FL2-W in arctigenin-treated SW480 cells were 572.6 and 275.1, respectively, whereas those of control cells were 482.0 and 220.7, respectively. Our approach may provide insights into the mechanism behind phytochemical-induced cell and nuclear enlargement as well as functional studies on cancer-treating agents.

Arctigenin reduces neuronal responses in the somatosensory cortex via the inhibition of non-NMDA glutamate receptors.

PubMed

Borbély, Sándor; Jócsák, Gergely; Moldován, Kinga; Sedlák, Éva; Preininger, Éva; Boldizsár, Imre; Tóth, Attila; Atlason, Palmi T; Molnár, Elek; Világi, Ildikó

2016-07-01

Lignans are biologically active phenolic compounds related to lignin, produced in different plants. Arctigenin, a dibenzylbutyrolactone-type lignan, has been used as a neuroprotective agent for the treatment of encephalitis. Previous studies of cultured rat cerebral cortical neurones raised the possibility that arctigenin inhibits kainate-induced excitotoxicity. The aims of the present study were: 1) to analyse the effect of arctigenin on normal synaptic activity in ex vivo brain slices, 2) to determine its receptor binding properties and test the effect of arctigenin on AMPA/kainate receptor activation and 3) to establish its effects on neuronal activity in vivo. Arctigenin inhibited glutamatergic transmission and reduced the evoked field responses. The inhibitory effect of arctigenin on the evoked field responses proved to be substantially dose dependent. Our results indicate that arctigenin exerts its effects under physiological conditions and not only on hyper-excited neurons. Furthermore, arctigenin can cross the blood-brain barrier and in the brain it interacts with kainate sensitive ionotropic glutamate receptors. These results indicate that arctigenin is a potentially useful new pharmacological tool for the inhibition of glutamate-evoked responses in the central nervous system in vivo. Copyright © 2016 Elsevier Ltd. All rights reserved.

Phytochemicals prevent mitochondrial membrane permeabilization and protect SH-SY5Y cells against apoptosis induced by PK11195, a ligand for outer membrane translocator protein.

PubMed

Wu, Yuqiu; Shamoto-Nagai, Masayo; Maruyama, Wakako; Osawa, Toshihiko; Naoi, Makoto

2017-01-01

Epidemiological studies present the beneficial effects of dietary habits on prevention of aging-associated decline of brain function. Phytochemicals, the second metabolites of food, protect neuronal cells from cell death in cellular models of neurodegenerative disorders, and the neuroprotective activity has been ascribed to the anti-oxidant and anti-inflammatory functions. In this paper, the cellular mechanism of neuroprotection by phytochemicals was investigated, using the cellular model of mitochondrial apoptosis induced by PK11195, a ligand of outer membrane translocator protein, in SH-SY5Y cells. PK11195 induced mitochondrial membrane permeabilization with rapid transit production of superoxide (superoxide flashes) and calcium release from mitochondria, and activated apoptosis signal pathway. Study on the structure-activity relationship of astaxanthin, ferulic acid derivatives, and sesame lignans revealed that these phytochemicals inhibited mitochondrial membrane permeabilization and protected cells from apoptosis. Ferulic acid derivatives and sesame lignans inhibited or enhanced the mitochondrial pore formation and cell death by PK11195 according to their amphiphilic properties, not directly depending on the antioxidant activity. Regulation of pore formation at mitochondrial membrane is discussed as a novel mechanism behind neuroprotective activity of phytochemicals in aging and age-associated neurodegenerative disorders, and also behind dual functions of phytochemicals in neuronal and cancer cells.

Can supplementary dietary fibre suppress breast cancer growth?

PubMed Central

Stoll, B. A.

1996-01-01

Case-control studies in diverse populations around the world have reported a lower risk of breast cancer in association with higher intake of dietary fibre and complex carbohydrates. Although this has not been confirmed in prospective studies in the USA, the observations have prompted the hypothesis that prolonged use of dietary fibre supplements might reduce breast cancer risk in high-incidence populations. Several possible mechanisms of action have been suggested, all involving a reduction of bioactive oestrogen levels in the blood. The various mechanisms are not necessarily mutually exclusive. First, a high-fibre diet might reduce circulating oestrogen levels by reducing the enterohepatic recirculation of oestrogen. Second, many plants and vegetables contain isoflavones and lignans capable of conversion in the bowel into weak oestrogens that may compete with oestradiol for target binding-sites. Third, a high-fibre diet is less often associated with obesity, which tends to increase availability of the biologically active 16-alpha metabolites of oestrone. Fourth, a high-fibre diet usually has a lower content of fat and a higher content of antioxidant vitamins, which may protect against breast cancer risk. Finally, diets rich in fibre and complex carbohydrates have been shown to improve insulin sensitivity, with an associated reduction in circulating oestrogen levels. Synergism between these effects offers a possible mechanism by which a high fibre intake might suppress breast cancer growth in women. PMID:8605086

UPLC-MS-ELSD-PDA as a powerful dereplication tool to facilitate compound identification from small-molecule natural product libraries.

PubMed

Yang, Jin; Liang, Qian; Wang, Mei; Jeffries, Cynthia; Smithson, David; Tu, Ying; Boulos, Nidal; Jacob, Melissa R; Shelat, Anang A; Wu, Yunshan; Ravu, Ranga Rao; Gilbertson, Richard; Avery, Mitchell A; Khan, Ikhlas A; Walker, Larry A; Guy, R Kiplin; Li, Xing-Cong

2014-04-25

The generation of natural product libraries containing column fractions, each with only a few small molecules, using a high-throughput, automated fractionation system, has made it possible to implement an improved dereplication strategy for selection and prioritization of leads in a natural product discovery program. Analysis of databased UPLC-MS-ELSD-PDA information of three leads from a biological screen employing the ependymoma cell line EphB2-EPD generated details on the possible structures of active compounds present. The procedure allows the rapid identification of known compounds and guides the isolation of unknown compounds of interest. Three previously known flavanone-type compounds, homoeriodictyol (1), hesperetin (2), and sterubin (3), were identified in a selected fraction derived from the leaves of Eriodictyon angustifolium. The lignan compound deoxypodophyllotoxin (8) was confirmed to be an active constituent in two lead fractions derived from the bark and leaves of Thuja occidentalis. In addition, two new but inactive labdane-type diterpenoids with an uncommon triol side chain were also identified as coexisting with deoxypodophyllotoxin in a lead fraction from the bark of T. occidentalis. Both diterpenoids were isolated in acetylated form, and their structures were determined as 14S,15-diacetoxy-13R-hydroxylabd-8(17)-en-19-oic acid (9) and 14R,15-diacetoxy-13S-hydroxylabd-8(17)-en-19-oic acid (10), respectively, by spectroscopic data interpretation and X-ray crystallography. This work demonstrates that a UPLC-MS-ELSD-PDA database produced during fractionation may be used as a powerful dereplication tool to facilitate compound identification from chromatographically tractable small-molecule natural product libraries.

Trichosanthis Fructus: botany, traditional uses, phytochemistry and pharmacology.

PubMed

Yu, Xiankuo; Tang, Liying; Wu, Hongwei; Zhang, Xiao; Luo, Hanyan; Guo, Rixin; Xu, Mengying; Yang, Hongjun; Fan, Jianwei; Wang, Zhuju; Su, Ruiqiang

2018-05-26

Trichosanthis Fructus (ripe fruits of Trichosanthes kirilowii Maxim. and Trichosanthes rosthornii Harms) is an essential traditional Chinese medicine to treat thoracic obstruction, angina, cardiac failure, myocardial infarction, pulmonary heart disease, some cerebral ischaemic diseases, etc. The present report reviews the advancements in research on the botany, traditional uses, phytochemistry and pharmacology of Trichosanthis Fructus. Finally, perspectives on future research and its possible directions are discussed. This review provides up-to-date information about the botany, traditional uses, phytochemistry, pharmacology, toxicity and quality control of Trichosanthis Fructus and discusses the perspectives on future research and possible directions of this traditional Chinese Medicine and its origin plants. The information on Trichosanthes kirilowii Maxim. and Trichosanthes rosthornii Harms was collected from published scientific materials, including books; monographs on medicinal plants; pharmacopoeia and electronic databases such as SCI finder, PubMed, Web of Science, ACS, Science Direct, Wiley, Springer, Taylor, CNKI and Google Scholar. Approximately 162 compounds, including terpenoids, phytosterols, flavonoids, nitrogenous compounds and lignans, have been isolated and identified from Trichosanthes kirilowii Maxim. and Trichosanthes rosthornii Harms. Numerous studies have shown that the extracts and compounds isolated from these two plants exhibit pharmacological activities, including protection against myocardial ischaemia, calcium antagonist, endothelial cell protection, anti-hypoxic, anti-platelet aggregation, expectorant, anti-inflammatory, cytotoxic and antioxidant. Trichosanthis Fructus is an essential traditional Chinese medicine with pharmacological activities that mainly affect the cardiovascular system. This review summarises its botany, traditional uses, phytochemistry and pharmacology. Future research is needed to clarify the different uses of the seeds, pericarps and fruits. Quality control of investigations of the fruits should be improved, and the potential uses of the flesh, leaves and twigs should be further explored. Copyright © 2018 Elsevier B.V. All rights reserved.

Rheum australe D. Don: a review of its botany, ethnobotany, phytochemistry and pharmacology.

PubMed

Rokaya, Maan Bahadur; Münzbergová, Zuzana; Timsina, Binu; Bhattarai, Krishna Ram

2012-06-14

Rheum australe D. Don (Polygonaceae) has been commonly used in traditional medicine for a wide range of ailments related to the circulatory, digestive, endocrine, respiratory and skeletal systems as well as to infectious diseases. To provide the up-to-date information that is available on the botany, traditional uses, phytochemistry, pharmacology and toxicology of Rheum australe. Additionally, to highlight the possible uses of this species to treat different diseases and to provide a basis for future research. The present review covers the literature available from 1980 to 2011. The information was collected from scientific journals, books, theses and reports via a library and electronic search (Google Scholar, Web of Science and ScienceDirect). Ethnomedical uses of Rheum australe have been recorded from China, India, Nepal and Pakistan for 57 different types of ailments. The phytochemical studies have shown the presence of many secondary metabolites belonging to anthraquinones, stilbenes, anthrones, oxantrone ethers and esters, chromones, flavonoids, carbohydrate, lignans, phenols and sterols. Crude extracts and isolated compounds from Rheum australe show a wide spectrum of pharmacological activities, such as antidiabetic, anti-inflammatory, antifungal, antimicrobial, antioxidant, anticancer, hepatoprotective and immune-enhancing activities, as well as a usefulness for improving renal function. Rheum australe has been widely used source of medicine for years without any adverse effects. Many studies have provided evidence for various traditional uses. However, there is a need for additional studies of the isolated compounds to validate the traditional uses in human models. The present review on the botany, traditional uses, phytochemistry and toxicity has provided preliminary information for further studies and commercial exploitations of the plant. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Physicochemical characterization of phyllanthin from Phyllanthus amarus Schum. et Thonn.

PubMed

Hanh, Nguyen Duc; Sinchaipanid, Nuttanan; Mitrevej, Ampol

2014-06-01

Phyllanthin is a major bioactive lignan component of Phyllanthus amarus, with several known biological activities. This study dealt with the isolation and physicochemical characterization of phyllanthin. Phyllanthin was isolated from P. amarus leaves by column chromatography and purified by recrystallization to obtain phyllanthin crystals with a purity of more than 98%. UV, IR, MS, (1)H NMR and (13)C NMR spectra were employed to identify phyllanthin. The physicochemical properties of phyllanthin were characterized using differential scanning calorimetry, thermogravimetric analysis, X-ray diffraction, pH-solubility, ionization property and lipophilicity. The results indicated that phyllanthin crystals had the melting point and melting enthalpy range of 96.67-97.03 °C and 109.61-116.34 J/g, respectively. Three kinds of phyllanthin crystals, recrystallized by petroleum ether, absolute ethanol and 25% ethanol solution, showed only one polymorph and no polymorphic impurity. Phyllanthin in a solid state was found to undergo significant thermal decomposition above 200 °C. The compound demonstrated good stability in aqueous solution over a pH range of 1.07-10.02 for at least 4 h. The solubility of phyllanthin appeared to be pH-independent of pH range from 1.07 to 10.26. Ionization property studied by absorbance spectroscopy method was in agreement with the result of pH-solubility study, showing that phyllanthin has no pKa over a pH range of 1.12-10.02. The log Pow value of phyllanthin was found to be 3.30 ± 0.05 at pH 7.48, suggesting that phyllanthin may have good permeability through biological membranes. The findings could be useful tools for the development of stable and bioavailable oral dosage forms of phyllanthin.

Matrix isolation studies of hydrogen bonding - An historical perspective

NASA Astrophysics Data System (ADS)

Barnes, Austin J.

2018-07-01

An historical introduction sets matrix isolation in perspective with other spectroscopic techniques for studying hydrogen-bonded complexes. This is followed by detailed accounts of various aspects of hydrogen-bonded complexes that have been studied using matrix isolation spectroscopy: Matrix effects: stabilisation of complexes. Strongly hydrogen-bonded molecular complexes: the vibrational correlation diagram. Anomalous spectra: the Ratajczak-Yaremko model. Metastable complexes. Csbnd H hydrogen bonding and blue shifting hydrogen bonds.

Phenotypic and Genomic Analysis of Hypervirulent Human-associated Bordetella bronchiseptica

PubMed Central

2012-01-01

Background B. bronchiseptica infections are usually associated with wild or domesticated animals, but infrequently with humans. A recent phylogenetic analysis distinguished two distinct B. bronchiseptica subpopulations, designated complexes I and IV. Complex IV isolates appear to have a bias for infecting humans; however, little is known regarding their epidemiology, virulence properties, or comparative genomics. Results Here we report a characterization of the virulence of human-associated complex IV B. bronchiseptica strains. In in vitro cytotoxicity assays, complex IV strains showed increased cytotoxicity in comparison to a panel of complex I strains. Some complex IV isolates were remarkably cytotoxic, resulting in LDH release levels in A549 cells that were 10- to 20-fold greater than complex I strains. In vivo, a subset of complex IV strains was found to be hypervirulent, with an increased ability to cause lethal pulmonary infections in mice. Hypercytotoxicity in vitro and hypervirulence in vivo were both dependent on the activity of the bsc T3SS and the BteA effector. To clarify differences between lineages, representative complex IV isolates were sequenced and their genomes were compared to complex I isolates. Although our analysis showed there were no genomic sequences that can be considered unique to complex IV strains, there were several loci that were predominantly found in complex IV isolates. Conclusion Our observations reveal a T3SS-dependent hypervirulence phenotype in human-associated complex IV isolates, highlighting the need for further studies on the epidemiology and evolutionary dynamics of this B. bronchiseptica lineage. PMID:22863321

Sesquiterpenes from Centaurea aspera.

PubMed

Marco, J Alberto; Sanz-Cervera, Juan F; Yuste, Alberto; Sancenón, Félix; Carda, Miguel

2005-07-01

The aerial parts of two subspecies of Centaurea aspera L. (Asteraceae) yielded the germacranolides 1a-h, 2, 3, 4 and 5, the elemane derivatives 6d and 6f, the lignan matairesinol, the degraded terpene loliolide, and the onopordopicrin-valine dimeric adduct 7. From these, compounds 1e, 3 and 6d are natural products. The chemical composition of the two subspecies is very similar, a circumstance which does not support a taxonomic subdivision of the species.

Clonal spread and accumulation of β-lactam resistance determinants in Enterobacter aerogenes and Enterobacter cloacae complex isolates from infection and colonization in patients at a public hospital in Recife, Pernambuco, Brazil.

PubMed

Cabral, Adriane Borges; Maciel, Maria Amélia Vieira; Barros, Josineide Ferreira; Antunes, Marcelo Maranhão; Barbosa de Castro, Célia Maria Machado; Lopes, Ana Catarina Souza

2017-01-01

Enterobacter aerogenes and Enterobacter cloacae complex are the two species of this genus most involved in healthcare-associated infections that are ESBL and carbapenemase producers. This study characterized, phenotypically and genotypically, 51 isolates of E. aerogenes and E. cloacae complex originating from infection or colonization in patients admitted to a public hospital in Recife, Pernambuco, Brazil, by antimicrobial susceptibility profile, analysis of β-lactamase genes (blaTEM, blaSHV, blaCTX-M, blaKPC, blaVIM, blaIMP and blaSPM), PCR and DNA sequencing, plasmid profile and ERIC-PCR. In both species, the genes blaTEM, blaCTX-M and blaKPC were detected. The DNA sequencing confirmed the variants blaTEM-1, blaCTX-M-15 and blaKPC-2 in isolates. More than one gene conferring resistance in the isolates, including the detection of the three previously cited genes in strains isolated from infection sites, was observed. The detection of blaCTX-M was more frequent in isolates from infection sites than from colonization. The gene blaKPC predominated in E. cloacae complex isolates obtained from infections; however, in E. aerogenes isolates, it predominated in samples obtained from colonization. A clonal relationship among all of E. aerogenes isolates was detected by ERIC-PCR. The majority of E. cloacae complex isolates presented the same ERIC-PCR pattern. Despite the clonal relation presented by the isolates using ERIC-PCR, different plasmid and resistance profiles and several resistance genes were observed. The clonal dissemination and the accumulation of β-lactam resistance determinants presented by the isolates demonstrated the ability of E. aerogenes and E. cloacae complex, obtained from colonization and infection, to acquire and maintain different resistance genes.

Enantioselective α-Alkylation of Aldehydes via Photoredox Organocatalysis: Rapid Access to Pharmacophore Fragments from β-Cyanoaldehydes**

PubMed Central

Welin, Eric R.; Warkentin, Alexander A.; Conrad, Jay C.

2015-01-01

The combination of photoredox catalysis and enamine catalysis has enabled the development of an enantioselective α-cyanoalkylation of aldehydes. This synergistic catalysis protocol allows for the coupling of two highly versatile yet orthogonal functionalities, allowing rapid diversification of the oxonitrile products to a wide array of medicinally relevant derivatives and heterocycles. This methodology has also been applied to the total synthesis of the lignan natural product (−)-bursehernin. PMID:26130043

Dirigent proteins and dirigent sites in lignifying tissues

NASA Technical Reports Server (NTRS)

Burlat, V.; Kwon, M.; Davin, L. B.; Lewis, N. G.

2001-01-01

Tissue-specific dirigent protein gene expression and associated dirigent (site) localization were examined in various organs of Forsythia intermedia using tissue printing, in situ mRNA hybridization and immunolabeling techniques, respectively. Dirigent protein gene expression was primarily noted in the undifferentiated cambial regions of stem sections, whereas dirigent protein sites were detected mainly in the vascular cambium and ray parenchyma cell initials. Immunolocalization also revealed cross-reactivity with particular regions of the lignified cell walls, these being coincident with the known sites of initiation of lignin deposition. These latter regions are considered to harbor contiguous arrays of dirigent (monomer binding) sites for initiation of lignin biopolymer assembly. Dirigent protein mRNA expression was also localized in the vascular regions of roots and petioles, whereas in leaves the dirigent sites were primarily associated with the palisade layers and the vascular bundle. That is, dirigent protein mediated lignan biosynthesis was initiated primarily in the cambium and ray cell initial regions of stems as well as in the leaf palisade layers, this being in accordance with the occurrence of the lignans for defense purposes. Within lignified secondary xylem cell walls, however, dirigent sites were primarily localized in the S(1) sublayer and compound middle lamella, these being coincident with previously established sites for initiation of macromolecular lignin biosynthesis. Once initiation occurs, lignification is proposed to continue through template polymerization.

Sesamin and sesamolin as unexpected contaminants in various cold-pressed plant oils: NP-HPLC/FLD/DAD and RP-UPLC-ESI/MS(n) study.

PubMed

Górnaś, Paweł; Siger, Aleksander; Pugajeva, Iveta; Segliņa, Dalija

2014-04-01

Thirteen cold-pressed oils (Japanese quince seed, black caraway, flaxseed, rapeseed, hemp, peanut, sunflower, pumpkin, hazelnut, poppy, walnut, almond and sesame oil) manufactured by the same company over a 2-year period (2011-12) were assessed for lipophilic compounds. The presence of sesamin and sesamolin, two characteristic lignans of sesame oil, were detected in all tested plant oils. Both lignans were identified by NP-HPLC/FLD/DAD and confirmed by a RP-UPLC-ESI/MS(n) method. The lowest amount of sesamin and sesamolin was found for Japanese quince seed oil (0.10 and 0.27 mg/100 g), and the highest, excluding sesame oil, for almond oil (36.21 and 105.42 mg/100 g, respectively). The highly significant correlation between sesamolin and sesamin concentrations was found in all samples tested (r = 0.9999; p < 0.00001). These results indicate contamination of cold-pressed oils from the same source. This investigation highlights the fact that increasing the range of products manufactured by the same company can contribute to a lesser regard for the quality of the final product. Moreover, less attention paid to the quality of final product can be related to the health risks of consumers especially sensitive to allergens. Therefore, proper cleaning of processing equipment is needed to prevent cross-contact of cold-pressed oils.

Detection of novel metabolites of flaxseed lignans in vitro and in vivo.

PubMed

Quartieri, Andrea; García-Villalba, Rocío; Amaretti, Alberto; Raimondi, Stefano; Leonardi, Alan; Rossi, Maddalena; Tomàs-Barberàn, Francisco

2016-07-01

This study aimed to improve the knowledge of secoisolariciresinol diglucoside (SDG) transformation by human gut microbiota. SDG-supplemented microbiota cultures were inoculated with the feces of five subjects. The same volunteers received a flaxseed supplement for 7 days. SDG metabolites in cultures, feces, and urine were monitored by LC-ESI-QTOF and LC-DAD. In all cultures, SDG was deglycosylated to secoisolariciresinol (SECO) within 12 h. SECO underwent successive dehydroxylations and demethylations yielding enterodiol (4-18% conversion) and enterolactone (0.2-6%) after 24 h. Novel intermediates related to SECO, matairesinol (MATA), and anhydrosecoisolariciresinol (AHS) were identified in fecal cultures. These metabolites were also found after flaxseed consumption in feces and urine (in approximate amounts between 0.01-47.03 μg/g and 0.01-13.49 μg/mL, respectively) in their native form and/or modified by phase II human enzymes (glucuronide, sulfate and sulfoglucuronide conjugates). Derivatives of MATA and AHS are described for the first time as intermediates of SDG biotransformation by intestinal bacteria, providing a more comprehensive knowledge of lignan intestinal metabolism. The transformations observed in vitro seem to occur in vivo as well. The detection in urine of SDG intermediates indicates their gut absorption, opening new perspectives on the study of their systemic biological effects. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pinoresinol reductase 1 impacts lignin distribution during secondary cell wall biosynthesis in Arabidopsis

DOE PAGES

Zhao, Qiao; Zeng, Yining; Yin, Yanbin; ...

2014-08-05

In this paper, pinoresinol reductase (PrR) catalyzes the conversion of the lignan (-)-pinoresinol to (-)-lariciresinol in Arabidopsis thaliana, where it is encoded by two genes, PrR1 and PrR2, that appear to act redundantly. PrR1 is highly expressed in lignified inflorescence stem tissue, whereas PrR2 expression is barely detectable in stems. Co-expression analysis has indicated that PrR1 is co-expressed with many characterized genes involved in secondary cell wall biosynthesis, whereas PrR2 expression clusters with a different set of genes. The promoter of the PrR1 gene is regulated by the secondary cell wall related transcription factors SND1 and MYB46. The loss-of-function mutantmore » of PrR1 shows, in addition to elevated levels of pinoresinol, significantly decreased lignin content and a slightly altered lignin structure with lower abundance of cinnamyl alcohol end groups. Stimulated Raman scattering (SRS) microscopy analysis indicated that the lignin content of the prr1-1 loss-of-function mutant is similar to that of wild-type plants in xylem cells, which exhibit a normal phenotype, but is reduced in the fiber cells. Finally, together, these data suggest an association of the lignan biosynthetic enzyme encoded by PrR1 with secondary cell wall biosynthesis in fiber cells.« less

Contamination of soil and the medicinal plant Phyllanthus niruri Linn. with cadmium in ceramic industrial areas.

PubMed

Santos, Vanessa Santana Vieira; Arantes, Karen Magalhães; Gonçalves, Ester Luiza; Campos, Carlos Fernando; de Campos Júnior, Edimar Olegário; de Oliveira, Antônio Marcos Machado; Pereira, Boscolli Barbosa

2018-04-22

Phyllanthus niruri is a plant that is used to prevent calcium oxalate crystallisation and to block the stone formation in urolithiasis. Contaminants in the environment can be readily taken up by medicinal plants due to their ability to absorb chemicals into their tissues. If contaminated plants are ingested, they have the potential to negatively affect human and environmental health. The aim of this study was to assess contamination in the soil and the medicinal plant P. niruri by cadmium (Cd) in ceramic industrial areas of Monte Carmelo, Brazil. Soil samples and plant samples (divided in root, shoot and leaves) were collected from a contaminated monitoring site and from a rural area (which was used as a reference site for comparative purposes). The Cd concentrations of the samples were analysed with an atomic absorption spectrometer. P. niruri was found to be sensitive to soil contamination by Cd that was attributed to ceramic industrial emissions. The results revealed that Cd bioaccumulation in the roots and shoots of P. niruri was associated with a significant increase (p < 0.05) in the concentration of active lignan compounds (phyllanthin and hypophyllanthin) in the leaves. The identification of high concentrations of Cd and active lignan compounds suggests a risk of contamination of the site and the risk of a high dose of Cd to people exposed at the site.

Revealing hidden clonal complexity in Mycobacterium tuberculosis infection by qualitative and quantitative improvement of sampling.

PubMed

Pérez-Lago, L; Palacios, J J; Herranz, M; Ruiz Serrano, M J; Bouza, E; García-de-Viedma, D

2015-02-01

The analysis of microevolution events, its functional relevance and impact on molecular epidemiology strategies, constitutes one of the most challenging aspects of the study of clonal complexity in infection by Mycobacterium tuberculosis. In this study, we retrospectively evaluated whether two improved sampling schemes could provide access to the clonal complexity that is undetected by the current standards (analysis of one isolate from one sputum). We evaluated in 48 patients the analysis by mycobacterial interspersed repetitive unit-variable number tandem repeat of M. tuberculosis isolates cultured from bronchial aspirate (BAS) or bronchoalveolar lavage (BAL) and, in another 16 cases, the analysis of a higher number of isolates from independent sputum samples. Analysis of the isolates from BAS/BAL specimens revealed clonal complexity in a very high proportion of cases (5/48); in most of these cases, complexity was not detected when the isolates from sputum samples were analysed. Systematic analysis of isolates from multiple sputum samples also improved the detection of clonal complexity. We found coexisting clonal variants in two of 16 cases that would have gone undetected in the analysis of the isolate from a single sputum specimen. Our results suggest that analysis of isolates from BAS/BAL specimens is highly efficient for recording the true clonal composition of M. tuberculosis in the lungs. When these samples are not available, we recommend increasing the number of isolates from independent sputum specimens, because they might not harbour the same pool of bacteria. Our data suggest that the degree of clonal complexity in tuberculosis has been underestimated because of the deficiencies inherent in a simplified procedure. Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Distribution of Serogroups and Genotypes among Disease-Associated and Carried Isolates of Neisseria meningitidis from the Czech Republic, Greece, and Norway

PubMed Central

Yazdankhah, Siamak P.; Kriz, Paula; Tzanakaki, Georgina; Kremastinou, Jenny; Kalmusova, Jitka; Musilek, Martin; Alvestad, Torill; Jolley, Keith A.; Wilson, Daniel J.; McCarthy, Noel D.; Caugant, Dominique A.; Maiden, Martin C. J.

2004-01-01

The distribution of serogroups and multilocus sequence types (STs) in collections of disease-associated and carried meningococci from the period 1991 to 2000 in three European countries (the Czech Republic, Greece, and Norway) was investigated. A total of 314 patient isolates and 353 isolates from asymptomatic carriers were characterized. The frequency distributions of serogroups and clone complexes differed among countries and between disease and carrier isolate collections. Highly significant differentiation was seen at each housekeeping locus. A marked positive association of serogroup C with disease was evidenced. The ST-11 complex was strongly positively associated with disease; associations for other clone complexes were weaker. The genetic diversity of the clone complexes differed. A single ST dominated the ST-11 clone complex, while the ST-41/44 complex exhibited greater levels of diversity. These data robustly demonstrated differences in the distribution of meningococcal genotypes in disease and carrier isolates and among countries. Further, they indicated that differences in genotype diversity and pathogenicity exist between meningococcal clone complexes. PMID:15528708

[Study on molecular recognition technology in active constituents extracted and isolated from Aconitum pendulum].

PubMed

Ma, Xue-Qin; Li, Guo-Shan; Fu, Xue-Yan; Ma, Jing-Zu

2011-03-01

To investigate CD molecular recognition technology applied in active constituents extracted and isolated from traditional Chinese medicine--Aconitum pendulum. The inclusion constant and form probability of the inclusion complex of Aconitum pendulum with p-CD was calculated by UV spectra method. The active constituents of Aconitum pendulum were extracted and isolated by molecular recognition technology. The inclusion complex was identified by UV. The chemical constituents of Aconitum pendulum and inclusion complex was determined by HPLC. The analgesic effects of inclusion complex was investigated by experiment of intraperitoneal injection of acetic acid in rats. The inclusion complex was identified and confirmed by UV spectra method, the chemical components of inclusion complex were simple, and the content of active constituents increased significantly, the analgesic effects of inclusion complex was well. The molecular recognition technology can be used for extracting and isolating active constituents of Aconitum pendulum, and the effects are obvious.

Antifungal susceptibilities of Candida glabrata species complex, Candida krusei, Candida parapsilosis species complex and Candida tropicalis causing invasive candidiasis in China: 3 year national surveillance.

PubMed

Xiao, Meng; Fan, Xin; Chen, Sharon C-A; Wang, He; Sun, Zi-Yong; Liao, Kang; Chen, Shu-Lan; Yan, Yan; Kang, Mei; Hu, Zhi-Dong; Chu, Yun-Zhuo; Hu, Tie-Shi; Ni, Yu-Xing; Zou, Gui-Ling; Kong, Fanrong; Xu, Ying-Chun

2015-03-01

To define the antifungal susceptibility patterns of the most common non-albicans Candida spp. in China. We evaluated the susceptibilities to nine antifungal drugs of Candida parapsilosis species complex, Candida tropicalis, Candida glabrata species complex and Candida krusei isolates from patients with invasive candidiasis at 11 hospitals over 3 years. Isolates were identified by MALDI-TOF MS supplemented by DNA sequencing. MICs were determined by Sensititre YeastOne(TM) using current clinical breakpoints/epidemiological cut-off values to assign susceptibility (or WT), and by CLSI M44-A2 disc diffusion for fluconazole and voriconazole. Of 1072 isolates, 392 (36.6%) were C. parapsilosis species complex. C. tropicalis, C. glabrata species complex and C. krusei comprised 35.4%, 24.3% and 3.7% of the isolates, respectively. Over 99.3% of the isolates were of WT phenotype to amphotericin B and 5-flucytosine. Susceptibility/WT rates to azoles among C. parapsilosis species complex were ≥97.5%. However, 11.6% and 9.5% of C. tropicalis isolates were non-susceptible to fluconazole and voriconazole, respectively (7.1% were resistant to both). Approximately 14.3% of C. glabrata sensu stricto isolates (n = 258) were fluconazole resistant, and 11.6% of C. glabrata sensu stricto isolates were cross-resistant to fluconazole and voriconazole. All C. krusei isolates were susceptible/WT to voriconazole, posaconazole and itraconazole. Overall, 97.7%-100% of isolates were susceptible to caspofungin, micafungin and anidulafungin, but 2.3% of C. glabrata were non-susceptible to anidulafungin. There was no azole/echinocandin co-resistance. Disc diffusion and Sensititre YeastOne(TM) methods showed >95% categorical agreement for fluconazole and voriconazole. In summary, reduced azole susceptibility was seen among C. tropicalis. Resistance to echinocandins was uncommon. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Molecular screening of 246 Portuguese Aspergillus isolates among different clinical and environmental sources.

PubMed

Sabino, Raquel; Veríssimo, Cristina; Parada, Helena; Brandão, João; Viegas, Carla; Carolino, Elisabete; Clemons, Karl V; Stevens, David A

2014-07-01

Clinical and environmental samples from Portugal were screened for the presence of Aspergillus and the distributions of the species complexes were determined in order to understand how their distributions differ based on their source. Fifty-seven Aspergillus isolates from clinical samples were collected from 10 health institutions. Six species complexes were detected by internal transcribed spacer sequencing; Fumigati, Flavi, and Nigri were found most frequently (50.9%, 21.0%, and 15.8%, respectively). β-tubulin and calmodulin sequencing resulted in seven cryptic species (A. awamorii, A. brasiliensis, A. fructus, A. lentulus, A. sydowii, A. tubingensis, Emericella echinulata) being identified among the 57 isolates. Thirty-nine isolates of Aspergillus were recovered from beach sand and poultry farms, 31 from swine farms, and 80 from hospital environments, for a total 189 isolates. Eleven species complexes were found in these 189 isolates, and those belonging to the Versicolores species complex were found most frequently (23.8%). There was a significant association between the different environmental sources and distribution of the species complexes; the hospital environment had greater variability of species complexes than other environmental locations. A high prevalence of cryptic species within the Circumdati complex was detected in several environments; from the isolates analyzed, at least four cryptic species were identified, most of them growing at 37ºC. Because Aspergillus species complexes have different susceptibilities to antifungals, knowing the species-complex epidemiology for each setting, as well as the identification of cryptic species among the collected clinical isolates, is important. This may allow preventive and corrective measures to be taken, which may result in decreased exposure to those organisms and a better prognosis. © The Author 2014. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Development and validation of an efficient ultrasound assisted extraction of phenolic compounds from flax (Linum usitatissimum L.) seeds.

PubMed

Corbin, Cyrielle; Fidel, Thibaud; Leclerc, Emilie A; Barakzoy, Esmatullah; Sagot, Nadine; Falguiéres, Annie; Renouard, Sullivan; Blondeau, Jean-Philippe; Ferroud, Clotilde; Doussot, Joël; Lainé, Eric; Hano, Christophe

2015-09-01

Flaxseed accumulates in its seedcoat a macromolecular complex composed of lignan (secoisolariciresinol diglucoside, SDG), flavonol (herbacetin diglucoside, HDG) and hydroxycinnamic acids (p-couramic, caffeic and ferulic acid glucosides). Their antioxidant and/or cancer chemopreventive properties support their interest in human health and therefore, the demand for their extraction. In the present study, ultrasound-assisted extraction (UAE) of flaxseed phenolic compounds was investigated. Scanning Electron Microscopy imaging and histochemical analysis revealed the deep alteration of the seedcoat ultrastructure and the release of the mucilage following ultrasound treatment. Therefore, this method was found to be very efficient for the reduction of mucilage entrapment of flaxseed phenolics. The optimal conditions for UAE phenolic compounds extraction from flaxseeds were found to be: water as solvent supplemented with 0.2N of sodium hydroxide for alkaline hydrolysis of the SDG-HMG complex, an extraction time of 60 min at a temperature of 25°C and an ultrasound frequency of 30 kHz. Under these optimized and validated conditions, highest yields of SDG, HDG and hydroxycinnamic acid glucosides were detected in comparison to other published methods. Therefore, the procedure presented herein is a valuable method for efficient extraction and quantification of the main flaxseed phenolics. Moreover, this UAE is of particular interest within the context of green chemistry in terms of reducing energy consumption and valuation of flaxseed cakes as by-products resulting from the production of flax oil. Copyright © 2015 Elsevier B.V. All rights reserved.

Hemolysin as a Virulence Factor for Systemic Infection with Isolates of Mycobacterium avium Complex

PubMed Central

Maslow, Joel N.; Dawson, David; Carlin, Elizabeth A.; Holland, Steven M.

1999-01-01

Isolates of the Mycobacterium avium complex were examined for hemolysin expression. Only invasive isolates of M. avium were observed to be hemolytic (P < 0.001), with activity the greatest for isolates of serovars 4 and 8. Thus, M. avium hemolysin appears to represent a virulence factor necessary for invasive disease. PMID:9889239

Lyoniresinol 3α-O-β-D-glucopyranoside-mediated hypoglycaemia and its influence on apoptosis-regulatory protein expression in the injured kidneys of streptozotocin-induced mice.

PubMed

Wen, Qingwei; Liang, Tao; Qin, Feizhang; Wei, Jinbin; He, Qiaoling; Luo, Xiu; Chen, Xiaoyu; Zheng, Ni; Huang, Renbin

2013-01-01

Averrhoa carambola L. (Oxalidaceae) root (ACLR) has a long history of use in traditional Chinese medicine for treating diabetes and diabetic nephropathy (DN). (±)-Lyoniresinol 3α-O-β-D-glucopyranoside (LGP1, LGP2) were two chiral lignan glucosides that were isolated from the ACLR. The purpose of this study was to investigate the effect of LGP1 and LGP2-mediated hypoglycaemia on renal injury in streptozotocin (STZ)-induced diabetic mice. STZ-induced diabetic mice were administrated LGP1 and LGP2 orally (20, 40, 80 mg/kg body weight/d) for 14 days. Hyperglycaemia and the expression of related proteins such as nuclear factor-κB (NF-κB), caspase-3, -8, -9, and Bcl-associated X protein (Bax) were markedly decreased by LGP1 treatment. However, LGP2 treatment had no hypoglycaemic activity. Diabetes-dependent alterations in the kidney such as glomerular hypertrophy, excessive extracellular matrix amassing, and glomerular and tubular basement membrane thickening were improved after 14 days of LGP1 treatment. B cell lymphoma Leukaemia-2 (Bcl-2) expression was reduced in the STZ-induced diabetic mouse kidneys but was enhanced by LGP1 treatment. These findings suggest that LGP1 treatment may inhibit diabetic nephropathy progression and may regulate several pharmacological targets for treating or preventing diabetic nephropathy.

Lyoniresinol 3α-O-β-D-Glucopyranoside-Mediated Hypoglycaemia and Its Influence on Apoptosis-Regulatory Protein Expression in the Injured Kidneys of Streptozotocin-Induced Mice

PubMed Central

Wen, Qingwei; Liang, Tao; Qin, Feizhang; Wei, Jinbin; He, Qiaoling; Luo, Xiu; Chen, Xiaoyu; Zheng, Ni; Huang, Renbin

2013-01-01

Averrhoa carambola L. (Oxalidaceae) root (ACLR) has a long history of use in traditional Chinese medicine for treating diabetes and diabetic nephropathy (DN). (±)-Lyoniresinol 3α-O-β-D-glucopyranoside (LGP1, LGP2) were two chiral lignan glucosides that were isolated from the ACLR. The purpose of this study was to investigate the effect of LGP1 and LGP2-mediated hypoglycaemia on renal injury in streptozotocin (STZ)-induced diabetic mice. STZ-induced diabetic mice were administrated LGP1 and LGP2 orally (20, 40, 80 mg/kg body weight/d) for 14 days. Hyperglycaemia and the expression of related proteins such as nuclear factor-κB (NF-κB), caspase-3, -8, -9, and Bcl-associated X protein (Bax) were markedly decreased by LGP1 treatment. However, LGP2 treatment had no hypoglycaemic activity. Diabetes-dependent alterations in the kidney such as glomerular hypertrophy, excessive extracellular matrix amassing, and glomerular and tubular basement membrane thickening were improved after 14 days of LGP1 treatment. B cell lymphoma Leukaemia-2 (Bcl-2) expression was reduced in the STZ-induced diabetic mouse kidneys but was enhanced by LGP1 treatment. These findings suggest that LGP1 treatment may inhibit diabetic nephropathy progression and may regulate several pharmacological targets for treating or preventing diabetic nephropathy. PMID:24312585

Overview of Flaxseed Patent Applications for the Reduction of Cholesterol Levels.

PubMed

Ribas, Simone A; Grando, Rafaela L; Zago, Lilia; Carvajal, Elvira; Fierro, Iolanda M

2016-01-01

Flaxseed is becoming an increasingly widely used food ingredient. The rising interest of the food industry in this nutraceutical is primarily because of functional nutrients, such as alpha-linolenic acid and lignans, which have health benefits due to their lipid-lowering properties. The objective of this study was to provide an overview of the patenting of flaxseed products with cholesterol-lowering effects. Patent applications filed by country of origin were retrieved from the Derwent Innovations Index®database. A total of 307 patent documents were identified, of which 184 claim the use of flaxseed or parts of the flax plant in the product formulation, for their lipid-lowering effect when consumed by humans. A few of the patent applications contain claims for new products based on flaxseed in isolation, including the preparation of foods designed to inhibit the production of cholesterol. Most of the claims were for flaxseed in the form of oil and in association with other lipid-lowering compounds, mainly for the food industry, in the form of dietary supplements or baked products designed to raise their high-density lipoprotein content, and for treating heart problems. China and the United States are the leading countries of flax-related applications. These results may have important implications for the production of functional food products that meet specific societal demands. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

AMPK modulatory activity of olive-tree leaves phenolic compounds: Bioassay-guided isolation on adipocyte model and in silico approach.

PubMed

Jiménez-Sánchez, Cecilia; Olivares-Vicente, Mariló; Rodríguez-Pérez, Celia; Herranz-López, María; Lozano-Sánchez, Jesús; Segura-Carretero, Antonio; Fernández-Gutiérrez, Alberto; Encinar, José Antonio; Micol, Vicente

2017-01-01

Olive-tree polyphenols have demonstrated potential for the management of obesity-related pathologies. We aimed to explore the capacity of Olive-tree leaves extract to modulate triglyceride accumulation and AMP-activated protein kinase activity (AMPK) on a hypertrophic adipocyte model. Intracellular triglycerides and AMPK activity were measured on the hypertrophic 3T3-L1 adipocyte model by AdipoRed and immunofluorescence microscopy, respectively. Reverse phase high performance liquid chromatography coupled to time-of-flight mass detection with electrospray ionization (RP-HPLC-ESI-TOF/MS) was used for the fractionation of the extract and the identification of the compounds. In-silico molecular docking of the AMPK alpha-2, beta and gamma subunits with the identified compounds was performed. Olive-tree leaves extract decreased the intracellular lipid accumulation through AMPK-dependent mechanisms in hypertrophic adipocytes. Secoiridoids, cinnamic acids, phenylethanoids and phenylpropanoids, flavonoids and lignans were the candidates predicted to account for this effect. Molecular docking revealed that some compounds may be AMPK-gamma modulators. The modulatory effects of compounds over the alpha and beta AMPK subunits appear to be less probable. Olive-tree leaves polyphenols modulate AMPK activity, which may become a therapeutic aid in the management of obesity-associated disturbances. The natural occurrence of these compounds may have important nutritional implications for the design of functional ingredients.

Deoxyschizandrin, Isolated from Schisandra Berries, Induces Cell Cycle Arrest in Ovarian Cancer Cells and Inhibits the Protumoural Activation of Tumour-Associated Macrophages.

PubMed

Lee, Kijun; Ahn, Ji-Hye; Lee, Kyung-Tae; Jang, Dae Sik; Choi, Jung-Hye

2018-01-15

Deoxyschizandrin, a major lignan of Schisandra berries, has been demonstrated to have various biological activities such as antioxidant, hepatoprotective, and antidiabetic effects. However, the anti-cancer effects of deoxyschizandrin are poorly characterized. In the present study, we investigated the anti-cancer effect of deoxyschizandrin on human ovarian cancer cell lines and tumour-associated macrophages (TAMs). Deoxyschizandrin induced G₀/G₁ phase cell cycle arrest and inhibited cyclin E expression in human ovarian cancer cells. Overexpression of cyclin E significantly reversed the deoxyschizandrin-induced cell growth inhibition. Interestingly, increased production of reactive oxygen species and decreased activation of Akt were observed in A2780 cells treated with deoxyschizandrin, and the antioxidant compromised the deoxyschizandrin-induced cell growth inhibition and Akt inactivation. Moreover, deoxyschizandrin-induced cell growth inhibition was markedly suppressed by Akt overexpression. In addition, deoxyschizandrin was found to inhibit the expression of the M2 phenotype markers CD163 and CD209 in TAMs, macrophages stimulated by the ovarian cancer cells. Moreover, expression and production of the tumour-promoting factors MMP-9, RANTES, and VEGF, which are highly enhanced in TAMs, was significantly suppressed by deoxyschizandrin treatment. Taken together, these data suggest that deoxyschizandrin exerts anti-cancer effects by inducing G₀/G₁ cell cycle arrest in ovarian cancer cells and reducing the protumoural phenotype of TAMs.

The Genus Patrinia: A Review of Traditional Uses, Phytochemical and Pharmacological Studies.

PubMed

He, Xirui; Luan, Fei; Zhao, Zefeng; Ning, Ning; Li, Maoxing; Jin, Ling; Chang, Yu; Zhang, Qiang; Wu, Ni; Huang, Linhong

2017-01-01

The aim of the present review is to comprehensively outline the botanical description, traditional uses, phytochemistry, pharmacology and toxicology of Patrinia, and to discuss possible trends for the further study of medicinal plants from the genus Patrinia. The genus Patrinia plays an important role in Asian medicine for the treatment of erysipelas, conjunctival congestion with swelling and pain, peri-appendicular abscesses, lung carbuncle, dysentery, leucorrhea, and postpartum disease. More than 210 chemical constituents have been isolated and identified from Patrinia plants, especially P. scabiosaefolia Fisch., P. scabra Bunge, P. villosa Juss., P. heterophylla Bunge and P. rupestris(Pall.) Juss[Formula: see text] Of these compounds, triterpenoids and saponins, iridoids, flavonoids, and lignans are the major or active constituents. Both in vitro and in vivo studies have indicated that some monomer compounds and crude extracts from the genus Patrinia possess wide pharmacological activities, including antitumor, anti-inflammatory, antibacterial, and antiviral effects. In addition, they have been shown to have valuable and positive effects on the immune and nervous system in experimental animals. There are also some reports on the clinical uses and toxicity of these species. However, few reports have been published concerning the material identification or quality control of Patrinia species, and the clinical uses and toxic effects of these plants are relatively sparse. More attention must be given to these issues.

Phyllanthus amarus: ethnomedicinal uses, phytochemistry and pharmacology: a review.

PubMed

Patel, Jay Ram; Tripathi, Priyanka; Sharma, Vikas; Chauhan, Nagendra Singh; Dixit, Vinod Kumar

2011-11-18

Phyllanthus amarus Schum. & Thonn. belongs to the family Euphorbiaceae is a small herb well known for its medicinal properties and widely used worldwide. P. amarus is an important plant of Indian Ayurvedic system of medicine which is used in the problems of stomach, genitourinary system, liver, kidney and spleen. It is bitter, astringent, stomachic, diuretic, febrifuge and antiseptic. The whole plant is used in gonorrhea, menorrhagia and other genital affections. It is useful in gastropathy, diarrhoea, dysentery, intermittent fevers, ophthalmopathy, scabies, ulcers and wounds. The present review covers a literature across from 1980 to 2011. Some information collected from traditional Ayurvedic texts and published literature on ethanomedicinal uses of Phyllanthus amarus in different countries worldwide. Phytochemical studies have shown the presence of many valuable compounds such as lignans, flavonoids, hydrolysable tannins (ellagitannins), polyphenols, triterpenes, sterols and alkaloids. The extracts and the compounds isolated from P. amarus show a wide spectrum of pharmacological activities including antiviral, antibacterial, antiplasmodial, anti-inflammatory, antimalarial, antimicrobial, anticancer, antidiabetic, hypolipidemic, antioxidant, hepatoprotective nephroprotective and diurectic properties. The present review summarizes information concerning the morphology, ecology, ethnopharmacology, phytochemistry, biological activities, clinical applications and toxicological reports of P. amarus. This review aims at gathering the research work undertaken till date on this plant in order to provide sufficient baseline information for future works and commercial exploitation. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Antitumor effect of Deoxypodophyllotoxin on human breast cancer xenograft transplanted in BALB/c nude mice model.

PubMed

Khaled, Meyada; Belaaloui, Ghania; Jiang, Zhen-Zhou; Zhu, Xiong; Zhang, Lu-Yong

2016-10-01

Recently, biologically active compounds isolated from plants used in herbal medicine have been the center of interest. Deoxypodophyllotoxin (DPT), structurally closely related to the lignan podophyllotoxin, was found to be a potent antitumor and antiproliferative agent, in several tumor cells, in vitro. However, DPT has not been used clinically yet because of the lack of in vivo studies. This study is the first report demonstrating the antitumor effect of DPT on MDA-MB-231 human breast cancer xenografts in nude mice. DPT, significantly, inhibited the growth of MDA-MB-231 xenograft in BALB/c nude mice. The T/C value (the value of the relative tumor volume of treatment group compared to the control group) of groups treated with 5, 10, and 20 mg/kg of intravenous DPT-HP-β-CD was 42.87%, 34.04% and 9.63%, respectively, suggesting the positive antitumor activity of DPT. In addition, the antitumor effect of DPT-HP-β-CD (20 mg/kg) in human breast cancer MDA-MB-231 xenograft was more effective than etoposide (VP-16) (20 mg/kg) and docetaxel (20 mg/kg). These findings suggest that this drug is a promising chemotherapy candidate against human breast carcinoma. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

AMPK modulatory activity of olive–tree leaves phenolic compounds: Bioassay-guided isolation on adipocyte model and in silico approach

PubMed Central

Jiménez-Sánchez, Cecilia; Olivares-Vicente, Mariló; Rodríguez-Pérez, Celia; Herranz-López, María; Lozano-Sánchez, Jesús; Segura-Carretero, Antonio; Fernández-Gutiérrez, Alberto; Encinar, José Antonio; Micol, Vicente

2017-01-01

Scope Olive-tree polyphenols have demonstrated potential for the management of obesity-related pathologies. We aimed to explore the capacity of Olive-tree leaves extract to modulate triglyceride accumulation and AMP-activated protein kinase activity (AMPK) on a hypertrophic adipocyte model. Methods Intracellular triglycerides and AMPK activity were measured on the hypertrophic 3T3-L1 adipocyte model by AdipoRed and immunofluorescence microscopy, respectively. Reverse phase high performance liquid chromatography coupled to time-of-flight mass detection with electrospray ionization (RP-HPLC-ESI-TOF/MS) was used for the fractionation of the extract and the identification of the compounds. In-silico molecular docking of the AMPK alpha-2, beta and gamma subunits with the identified compounds was performed. Results Olive-tree leaves extract decreased the intracellular lipid accumulation through AMPK-dependent mechanisms in hypertrophic adipocytes. Secoiridoids, cinnamic acids, phenylethanoids and phenylpropanoids, flavonoids and lignans were the candidates predicted to account for this effect. Molecular docking revealed that some compounds may be AMPK-gamma modulators. The modulatory effects of compounds over the alpha and beta AMPK subunits appear to be less probable. Conclusions Olive-tree leaves polyphenols modulate AMPK activity, which may become a therapeutic aid in the management of obesity-associated disturbances. The natural occurrence of these compounds may have important nutritional implications for the design of functional ingredients. PMID:28278224

Enantioselective α-Alkylation of Aldehydes by Photoredox Organocatalysis: Rapid Access to Pharmacophore Fragments from β-Cyanoaldehydes.

PubMed

Welin, Eric R; Warkentin, Alexander A; Conrad, Jay C; MacMillan, David W C

2015-08-10

The combination of photoredox catalysis and enamine catalysis has enabled the development of an enantioselective α-cyanoalkylation of aldehydes. This synergistic catalysis protocol allows for the coupling of two highly versatile yet orthogonal functionalities, allowing rapid diversification of the oxonitrile products to a wide array of medicinally relevant derivatives and heterocycles. This methodology has also been applied to the total synthesis of the lignan natural product (-)-bursehernin. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multilocus Sequence Types of Campylobacter jejuni Isolates from Different Sources in Eastern China.

PubMed

Zhang, Gong; Zhang, Xiaoyan; Hu, Yuanqing; Jiao, Xin-An; Huang, Jinlin

2015-09-01

Campylobacter jejuni is a major food-borne pathogen that causes human gastroenteritis in many developed countries. In our study, we applied multilocus sequence typing (MLST) technology to 167 C. jejuni isolates from diverse sources in Eastern China to examine their genetic diversity. MLST defined 94 sequence types (STs) belonging to 18 clonal complexes (CCs). Forty-five STs from 60 isolates (36%) and 22 alleles have not been previously documented in an international database. One hundred and two isolates, accounting for 61.1% of all isolates, belonged to eight clonal complexes. The eight major CCs were also the most common complexes from different sources. The most common ST type of isolates from human and food was ST-353. The dominant ST type in chicken and foods was ST-354. Among 21 STs that contained two or more different sources isolates, 15 STs contained human isolates and isolates from other sources, suggesting that potentially pathogenic strains are not restricted to specific lineages.

Molecular identification and amphotericin B susceptibility testing of clinical isolates of Aspergillus from 11 hospitals in Korea.

PubMed

Heo, Min Seok; Shin, Jong Hee; Choi, Min Ji; Park, Yeon Joon; Lee, Hye Soo; Koo, Sun Hoe; Lee, Won Gil; Kim, Soo Hyun; Shin, Myung Geun; Suh, Soon Pal; Ryang, Dong Wook

2015-11-01

We investigated the species distribution and amphotericin B (AMB) susceptibility of Korean clinical Aspergillus isolates by using two Etests and the CLSI broth microdilution method. A total of 136 Aspergillus isolates obtained from 11 university hospitals were identified by sequencing the internal transcribed spacer (ITS) and β-tubulin genomic regions. Minimal inhibitory concentrations (MICs) of AMB were determined in Etests using Mueller-Hinton agar (Etest-MH) and RPMI agar (Etest-RPG), and categorical agreement with the CLSI method was assessed by using epidemiological cutoff values. ITS sequencing identified the following six Aspergillus species complexes: Aspergillus fumigatus (42.6% of the isolates), A. niger (23.5%), A. flavus (17.6%), A. terreus (11.0%), A. versicolor (4.4%), and A. ustus (0.7%). Cryptic species identifiable by β-tubulin sequencing accounted for 25.7% (35/136) of the isolates. Of all 136 isolates, 36 (26.5%) had AMB MICs of ≥2 μg/mL by the CLSI method. The categorical agreement of Etest-RPG with the CLSI method was 98% for the A. fumigatus, A. niger, and A. versicolor complexes, 87% for the A. terreus complex, and 37.5% for the A. flavus complex. That of Etest-MH was ≤75% for the A. niger, A. flavus, A. terreus, and A. versicolor complexes but was higher for the A. fumigatus complex (98.3%). Aspergillus species other than A. fumigatus constitute about 60% of clinical Aspergillus isolates, and reduced AMB susceptibility is common among clinical isolates of Aspergillus in Korea. Molecular identification and AMB susceptibility testing by Etest-RPG may be useful for characterizing Aspergillus isolates of clinical relevance.

Comparison of the Virulence-Associated Phenotypes of Five Species of Acinetobacter baumannii Complex.

PubMed

Na, In Young; Chung, Eun Seon; Jung, Chang-Yun; Kim, Dae Hun; Shin, Juyoun; Kang, KyeongJin; Kim, Seong-Tae; Ko, Kwan Soo

2016-01-01

In this study, we compared the virulence-associated factors of Acinetobacter baumannii complex species. Sixty-three isolates of five A. baumannii complex species, including 19 A. baumannii, 15 A. nosocomialis, 13 A. seifertii, 13 A. pittii, and 3 A. calcoaceticus isolates, were included in this study. For all isolates, biofilm formation, A549 cell adherence, resistance to normal human serum, and motility were evaluated. A. baumannii complex isolates showed diversity in biofilm formation, A549 cell adherence, and serum resistance, and no strong positive relationships among these virulence characteristics. However, A. seifertii showed relatively consistent virulence-associated phenotypes. In addition, A. baumannii clone ST110 exhibited consistently high virulence-associated phenotypes. Motility was observed in seven isolates, and all four A. baumannii ST110 isolates showed twitching motility. Although some inconsistencies in virulence-associated phenotypes were seen, high virulence characteristics were observed in A. seifertii, which has been mainly reported in Korea and shows high rates of colistin resistance.

Initial nitrogen enrichment conditions determines variations in nitrogen substrate utilization by heterotrophic bacterial isolates.

PubMed

Ghosh, Suchismita; Ayayee, Paul A; Valverde-Barrantes, Oscar J; Blackwood, Christopher B; Royer, Todd V; Leff, Laura G

2017-04-04

The nitrogen (N) cycle consists of complex microbe-mediated transformations driven by a variety of factors, including diversity and concentrations of N compounds. In this study, we examined taxonomic diversity and N substrate utilization by heterotrophic bacteria isolated from streams under complex and simple N-enrichment conditions. Diversity estimates differed among isolates from the enrichments, but no significant composition were detected. Substrate utilization and substrate range of bacterial assemblages differed within and among enrichments types, and not simply between simple and complex N-enrichments. N substrate use patterns differed between isolates from some complex and simple N-enrichments while others were unexpectedly similar. Taxonomic composition of isolates did not differ among enrichments and was unrelated to N use suggesting strong functional redundancy. Ultimately, our results imply that the available N pool influences physiology and selects for bacteria with various abilities that are unrelated to their taxonomic affiliation.

Genetic environment of metallo-β-lactamase genes in Pseudomonas aeruginosa isolates from the UK.

PubMed

Wright, Laura L; Turton, Jane F; Hopkins, Katie L; Livermore, David M; Woodford, Neil

2015-12-01

We sought to characterize the genetic environment of blaVIM and blaIMP genes in Pseudomonas aeruginosa isolates from the UK; these included members of six previously described prevalent complexes, A-F, which correspond to international 'high-risk clones', along with diverse strains. Metallo-β-lactamase (MBL)-encoding class 1 integrons were amplified by PCR from 218 P. aeruginosa isolates producing VIM-type (n = 196) or IMP-type (n = 22) enzymes, referred from UK hospital laboratories between 2003 and 2012. The variable regions of selected integrons were sequenced using a primer walking method. One-hundred-and-nineteen isolates had an MBL-encoding integron with the 3' conserved sequence (3'CS), 65 had Tn5090-like 3' regions and 17 had the sul1 gene, but lacked the qacEΔ1 gene; the 3' region could not be amplified using any primer combinations for the remaining 17 isolates. Six integron profiles were each seen in more than five isolates. Predominant integron types were seen amongst isolates belonging to STs 111, 233, 654/964 and 773 (complexes A, C, D and F, respectively), whereas diverse integron profiles were seen in isolates belonging to ST235 (complex B) and ST357 (complex E). In UK P. aeruginosa isolates, MBL genes occur in diverse class 1 integron structures, though commonly with 3' regions containing the classical 3'CS or Tn5090-like regions. Four of the six main clonal complexes, referred from multiple laboratories, carried a predominant integron type, whereas the remaining two had more diverse types. © Crown copyright 2015.

Synthesis and antiproliferative activity of two diastereomeric lignan amides serving as dimeric caffeic acid-l-DOPA hybrids.

PubMed

Magoulas, George E; Rigopoulos, Andreas; Piperigkou, Zoi; Gialeli, Chrysostomi; Karamanos, Nikos K; Takis, Panteleimon G; Troganis, Anastassios N; Chrissanthopoulos, Athanassios; Maroulis, George; Papaioannou, Dionissios

2016-06-01

Two new diastereomeric lignan amides (4 and 5) serving as dimeric caffeic acid-l-DOPA hybrids were synthesized. The synthesis involved the FeCl3-mediated phenol oxidative coupling of methyl caffeate to afford trans-diester 1a as a mixture of enantiomers, protection of the catechol units, regioselective saponification, coupling with a suitably protected l-DOPA derivative, separation of the two diastereomers thus obtained by flash column chromatography and finally global chemoselective deprotection of the catechol units. The effect of hybrids 4 and 5 and related compounds on the proliferation of two breast cancer cell lines with different metastatic potential and estrogen receptor status (MDA-MB-231 and MCF-7) and of one epithelial lung cancer cell line, namely A-549, was evaluated for concentrations ranging from 1 to 256μM and periods of treatment of 24, 48 and 72h. Both hybrids showed interesting and almost equipotent antiproliferative activities (IC50 64-70μM) for the MDA-MB-231 cell line after 24-48h of treatment, but they were more selective and much more potent (IC50 4-16μM) for the MCF-7 cells after 48h of treatment. The highest activity for both hybrids and both breast cancer lines was observed after 72h of treatment (IC50 1-2μM), probably as the result of slow hydrolysis of their methyl ester functions. Copyright © 2016 Elsevier Inc. All rights reserved.

Crystal structures of pinoresinol-lariciresinol and phenylcoumaran benzylic ether reductases and their relationship to isoflavone reductases

NASA Technical Reports Server (NTRS)

Min, Tongpil; Kasahara, Hiroyuki; Bedgar, Diana L.; Youn, Buhyun; Lawrence, Paulraj K.; Gang, David R.; Halls, Steven C.; Park, HaJeung; Hilsenbeck, Jacqueline L.; Davin, Laurence B.;

Association between dietary phytoestrogens intakes and prostate cancer risk in Sicily.

PubMed

Russo, Giorgio I; Di Mauro, Marina; Regis, Federica; Reale, Giulio; Campisi, Daniele; Marranzano, Marina; Lo Giudice, Arturo; Solinas, Tatiana; Madonia, Massimo; Cimino, Sebastiano; Morgia, Giuseppe

2018-03-01

In this study we aimed to investigate the association between dietary phytoestrogen consumption and prostate cancer in a sample of southern Italian individuals. A population-based case-control study on the association between prostate cancer and dietary factors was conducted from January 2015 to December 2016 in a single institution of the municipality of Catania, southern Italy (Registration number: 41/2015). A total of 118 histopathological-verified prostate cancer (PCa) cases and a total of 222 controls were collected. Dietary data was collected by using two food frequency questionnaires. Patients with PCa consumed significantly higher levels of phytoestrogens. Multivariate logistic regression showed that lignans (Q[quartile]4 vs. Q1, OR [odds ratio] = 4.72; p < .05) and specifically, lariciresinol (Q4 vs. Q1, OR = 4.60; p < .05), pinoresinol (Q4 vs. Q1, OR = 5.62; p < .05), matairesinol (Q4 vs. Q1, OR = 3.63; p < .05), secoisolariciresinol (Q4 vs. Q1, OR = 4.10; p < .05) were associated with increased risk of PCa. Furthermore, we found that isoflavones (Q3 vs. Q1, OR = 0.28; p < .05) and specifically, genistein (Q4 vs. Q1, OR = 0.40; p < .05) were associated with reduced risk of PCa. We found of an inverse association between dietary isoflavone intake and PCa, while a positive association was found with lignans intake.

Phytoestrogen consumption from foods and supplements and epithelial ovarian cancer risk: a population-based case control study

PubMed Central

2011-01-01

Background While there is extensive literature evaluating the impact of phytoestrogen consumption on breast cancer risk, its role on ovarian cancer has received little attention. Methods We conducted a population-based case-control study to evaluate phytoestrogen intake from foods and supplements and epithelial ovarian cancer risk. Cases were identified in six counties in New Jersey through the New Jersey State Cancer Registry. Controls were identified by random digit dialing, CMS (Centers for Medicare and Medicaid Service) lists, and area sampling. A total of 205 cases and 390 controls were included in analyses. Unconditional logistic regression analyses were conducted to examine associations with total phytoestrogens, as well as isoflavones (daidzein, genistein, formononetin, and glycitein), lignans (matairesinol, lariciresinol, pinoresinol, secoisolariciresinol), and coumestrol. Results No statistically significant associations were found with any of the phytoestrogens under evaluation. However, there was a suggestion of an inverse association with total phytoestrogen consumption (from foods and supplements), with an odds ratio (OR) of 0.62 (95% CI: 0.38-1.00; p for trend: 0.04) for the highest vs. lowest tertile of consumption, after adjusting for reproductive covariates, age, race, education, BMI, and total energy. Further adjustment for smoking and physical activity attenuated risk estimates (OR: 0.66; 95% CI: 0.41-1.08). There was little evidence of an inverse association for isoflavones, lignans, or coumestrol. Conclusions This study provided some suggestion that phytoestrogen consumption may decrease ovarian cancer risk, although results did not reach statistical significance. PMID:21943063

Lignan from Thyme Possesses Inhibitory Effect on ASIC3 Channel Current*

PubMed Central

Dubinnyi, Maxim A.; Osmakov, Dmitry I.; Koshelev, Sergey G.; Kozlov, Sergey A.; Andreev, Yaroslav A.; Zakaryan, Naira A.; Dyachenko, Igor A.; Bondarenko, Dmitry A.; Arseniev, Alexander S.; Grishin, Eugene V.

2012-01-01

A novel compound was identified in the acidic extract of Thymus armeniacus collected in the Lake Sevan region of Armenia. This compound, named “sevanol,” to our knowledge is the first low molecular weight natural molecule that has a reversible inhibition effect on both the transient and the sustained current of human ASIC3 channels expressed in Xenopus laevis oocytes. Sevanol completely blocked the transient component (IC50 353 ± 23 μm) and partially (∼45%) inhibited the amplitude of the sustained component (IC50 of 234 ± 53 μm). Other types of acid-sensing ion channel (ASIC) channels were intact to sevanol application, except ASIC1a, which showed more than six times less affinity to it as compared with the inhibitory action on the ASIC3 channel. To elucidate the structure of sevanol, the set of NMR spectra in two solvents (d6-DMSO and D2O) was collected, and the complete chemical structure was confirmed by liquid chromatography-mass spectrometry with electrospray ionization (LC-ESI+-MS) fragmentation. This compound is a new lignan built up of epiphyllic acid and two isocitryl esters in positions 9 and 10. In vivo administration of sevanol (1–10 mg/kg) significantly reversed thermal hyperalgesia induced by complete Freund's adjuvant injection and reduced response to acid in a writhing test. Thus, we assume the probable considerable role of sevanol in known analgesic and anti-inflammatory properties of thyme. PMID:22854960

Investigation of the profile of phenolic compounds in the leaves and stems of Pandiaka heudelotii using gas chromatography coupled with flame ionization detector.

PubMed

Ifeanacho, Mercy O; Ikewuchi, Catherine C; Ikewuchi, Jude C

2017-05-01

The profile of phenolic compounds in the leaves and stems of Pandiaka heudelotii was investigated using gas chromatography coupled with flame ionization detector. The leaves and stems had high flavonoids and benzoic acid derivatives content, and moderate levels of lignans and hydroxycinnamates. Twenty-eight known flavonoids were detected, which consisted mainly of kaempferol (41.93% in leaves and 47.97% in stems), (+)-catechin (17.12% in leaves and 16.11% in stems), quercetin (13.83% in leaves and 9.39% in stems), luteolin (7.34% in leaves and 7.71% in stems), and artemetin (6.53% in leaves and 4.83% in stems). Of the six known hydroxycinnamates detected, chlorogenic acid (80.79% in leaves and 87.56% in stems) and caffeic acid (18.98% in leaves and 12.30% in stems) were the most abundant, while arctigenin (77.81% in leaves and 83.40% in stems) and retusin (13.82% in leaves and 10.59% in stems) were the most abundant of the nine known lignans detected. Twelve known benzoic acid derivatives were detected, consisting mainly of ellagic acid (65.44% in leaves and 72.89% in stems), p-hydroxybenzoic acid (25.10% in leaves and 18.95% in stems), and vanillic acid (8.80% in leaves and 7.30% in stems). The rich phytochemical profile of the leaves and stems is an indication of their ability to serve as sources of nutraceuticals.

Leoligin, the major lignan from Edelweiss, activates cholesteryl ester transfer protein

PubMed Central

Duwensee, Kristina; Schwaiger, Stefan; Tancevski, Ivan; Eller, Kathrin; van Eck, Miranda; Markt, Patrick; Linder, Tobias; Stanzl, Ursula; Ritsch, Andreas; Patsch, Josef R.; Schuster, Daniela; Stuppner, Hermann; Bernhard, David; Eller, Philipp

2011-01-01

Objective Cholesteryl ester transfer protein (CETP) plays a central role in the metabolism of high-density lipoprotein particles. Therefore, we searched for new drugs that bind to CETP and modulate its activity. Methods A preliminary pharmacophore-based parallel screening approach indicated that leoligin, a major lignan of Edelweiss (Leontopodium alpinum Cass.), might bind to CETP. Therefore we incubated leoligin ex vivo at different concentrations with human (n = 20) and rabbit plasma (n = 3), and quantified the CETP activity by fluorimeter. Probucol served as positive control. Furthermore, we dosed CETP transgenic mice with leoligin and vehicle control by oral gavage for 7 days and measured subsequently the in vivo modulation of CETP activity (n = 5 for each treatment group). Results In vitro, leoligin significantly activated CETP in human plasma at 100 pM (p = 0.023) and 1 nM (p = 0.042), respectively, whereas leoligin concentrations of 1 mM inhibited CETP activity (p = 0.012). The observed CETP activation was not species specific, as it was similar in magnitude for rabbit CETP. In vivo, there was also a higher CETP activity after oral dosage of CETP transgenic mice with leoligin (p = 0.015). There was no short-term toxicity apparent in mice treated with leoligin. Conclusion CETP agonism by leoligin appears to be safe and effective, and may prove to be a useful modality to alter high-density lipoprotein metabolism. PMID:21820657

Environmental Screening for the Scedosporium apiospermum Species Complex in Public Parks in Bangkok, Thailand.

PubMed

Luplertlop, Natthanej; Pumeesat, Potjaman; Muangkaew, Watcharamat; Wongsuk, Thanwa; Alastruey-Izquierdo, Ana

2016-01-01

The Scedosporium apiospermum species complex, comprising filamentous fungal species S. apiospermum sensu stricto, S. boydii, S. aurantiacum, S. dehoogii and S. minutispora, are important pathogens that cause a wide variety of infections. Although some species (S. boydii and S. apiospermum) have been isolated from patients in Thailand, no environmental surveys of these fungi have been performed in Thailand or surrounding countries. In this study, we isolated and identified species of these fungi from 68 soil and 16 water samples randomly collected from 10 parks in Bangkok. After filtration and subsequent inoculation of samples on Scedo-Select III medium, colony morphological examinations and microscopic observations were performed. Scedosporium species were isolated from soil in 8 of the 10 parks, but were only detected in one water sample. Colony morphologies of isolates from 41 of 68 soil samples (60.29%) and 1 of 15 water samples (6.67%) were consistent with that of the S. apiospermum species complex. Each morphological type was selected for species identification based on DNA sequencing and phylogenetic analysis of the β-tubulin gene. Three species of the S. apiospermum species complex were identified: S. apiospermum (71 isolates), S. aurantiacum (6 isolates) and S. dehoogii (5 isolates). In addition, 16 sequences could not be assigned to an exact Scedosporium species. According to our environmental survey, the S. apiospermum species complex is widespread in soil in Bangkok, Thailand.

Environmental Screening for the Scedosporium apiospermum Species Complex in Public Parks in Bangkok, Thailand

PubMed Central

Pumeesat, Potjaman; Muangkaew, Watcharamat; Wongsuk, Thanwa; Alastruey-Izquierdo, Ana

2016-01-01

The Scedosporium apiospermum species complex, comprising filamentous fungal species S. apiospermum sensu stricto, S. boydii, S. aurantiacum, S. dehoogii and S. minutispora, are important pathogens that cause a wide variety of infections. Although some species (S. boydii and S. apiospermum) have been isolated from patients in Thailand, no environmental surveys of these fungi have been performed in Thailand or surrounding countries. In this study, we isolated and identified species of these fungi from 68 soil and 16 water samples randomly collected from 10 parks in Bangkok. After filtration and subsequent inoculation of samples on Scedo-Select III medium, colony morphological examinations and microscopic observations were performed. Scedosporium species were isolated from soil in 8 of the 10 parks, but were only detected in one water sample. Colony morphologies of isolates from 41 of 68 soil samples (60.29%) and 1 of 15 water samples (6.67%) were consistent with that of the S. apiospermum species complex. Each morphological type was selected for species identification based on DNA sequencing and phylogenetic analysis of the β-tubulin gene. Three species of the S. apiospermum species complex were identified: S. apiospermum (71 isolates), S. aurantiacum (6 isolates) and S. dehoogii (5 isolates). In addition, 16 sequences could not be assigned to an exact Scedosporium species. According to our environmental survey, the S. apiospermum species complex is widespread in soil in Bangkok, Thailand. PMID:27467209

Molecular Characterization of Invasive Meningococcal Isolates from Countries in the African Meningitis Belt before Introduction of a Serogroup A Conjugate Vaccine

PubMed Central

Caugant, Dominique A.; Kristiansen, Paul A.; Wang, Xin; Mayer, Leonard W.; Taha, Muhamed-Kheir; Ouédraogo, Rasmata; Kandolo, Denis; Bougoudogo, Flabou; Sow, Samba; Bonte, Laurence

2012-01-01

Background The serogroup A conjugate meningococcal vaccine, MenAfriVac, was introduced in mass vaccination campaigns in December 2010 in Burkina Faso, Mali and Niger. In the coming years, vaccination will be extended to other African countries at risk of epidemics. To document the molecular characteristics of disease-causing meningococcal strains circulating in the meningitis belt of Africa before vaccine introduction, the World Health Organization Collaborating Centers on Meningococci in Europe and United States established a common strain collection of 773 isolates from cases of invasive meningococcal disease collected between 2004 and 2010 from 13 sub-Saharan countries. Methodology All isolates were characterized by multilocus sequence typing, and 487 (62%) were also analyzed for genetic variation in the surface antigens PorA and FetA. Antibiotic susceptibility was tested for part of the collection. Principal Findings Only 19 sequence types (STs) belonging to 6 clonal complexes were revealed. ST-5 clonal complex dominated with 578 (74.8%) isolates. All ST-5 complex isolates were remarkably homogeneous in their PorA (P1.20,9) and FetA (F3-1) and characterized the serogroup A strains which have been responsible for most epidemics during this time period. Sixty-eight (8.8%) of the 773 isolates belonged to the ST-11 clonal complex which was mainly represented by serogroup W135, while an additional 38 (4.9%) W135 isolates belonged to the ST-175 complex. Forty-eight (6.2%) serogroup X isolates from West Africa belonged to the ST-181 complex, while serogroup X cases in Kenya and Uganda were caused by an unrelated clone, ST-5403. Serogroup X, ST-181, emerged in Burkina Faso before vaccine introduction. Conclusions In the seven years preceding introduction of a new serogroup A conjugate vaccine, serogroup A of the ST-5 clonal complex was identified as the predominant disease-causing strain. PMID:23029368

Comparative genomics of archived pyrazinamide resistant Mycobacterium tuberculosis complex isolates from Uganda

USDA-ARS?s Scientific Manuscript database

Bovine tuberculosis is a ‘neglected zoonosis’ and its contribution to the proportion of Mycobacterium tuberculosis complex infections in humans is unknown. A retrospective study on archived Mycobacterium tuberculosis complex (MTC) isolates from a reference laboratory in Uganda was undertaken to iden...

Composition of the Fusarium graminearum species complex populations in wheat cropping environments in Southern Brazil

USDA-ARS?s Scientific Manuscript database

The Fusarium graminearum species complex (FGSC) comprises several toxigenic species that cause Fusarium head blight (FHB) in wheat. In this study, high number (n=671 isolates) of pathogenic isolates (isolated from infected spikes) was obtained from a 3-year large-scale survey (2009-2011) conducted o...

Chapter 3: Isolation of Photosystem II Reaction Center Complexes from Plants

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

Seibert, M.; Picorel, R.

2011-01-01

Methods to isolate and purify 6- and 5-Chl D1/D2/Cyt b559 photosystem II (PSII) reaction center (RC) complexes from plants are presented, and the advantages and disadvantages of each procedure are discussed. One of the simpler 6-Chl procedures and a procedure for isolating 5-Chl complexes are described in detail. Furthermore, a rapid procedure that produces relatively large amounts of less pure 6-Chl material (i.e., more nonpigmented protein) is also described. Criteria to assess the purity of PSII RC preparations are presented, and problems associated with each of the isolation procedures are discussed.

Fitness cost: a bacteriological explanation for the demise of the first international methicillin-resistant Staphylococcus aureus epidemic.

PubMed

Nielsen, Karen L; Pedersen, Thomas M; Udekwu, Klas I; Petersen, Andreas; Skov, Robert L; Hansen, Lars H; Hughes, Diarmaid; Frimodt-Møller, Niels

2012-06-01

Denmark and several other countries experienced the first epidemic of methicillin-resistant Staphylococcus aureus (MRSA) during the period 1965-75, which was caused by multiresistant isolates of phage complex 83A. In Denmark these MRSA isolates disappeared almost completely, being replaced by other phage types, predominantly only penicillin resistant. We investigated whether isolates of this epidemic were associated with a fitness cost, and we employed a mathematical model to ask whether these fitness costs could have led to the observed reduction in frequency. Bacteraemia isolates of S. aureus from Denmark have been stored since 1957. We chose 40 S. aureus isolates belonging to phage complex 83A, clonal complex 8 based on spa type, ranging in time of isolation from 1957 to 1980 and with various antibiograms, including both methicillin-resistant and -susceptible isolates. The relative fitness of each isolate was determined in a growth competition assay with a reference isolate. Significant fitness costs of 2%-15% were determined for the MRSA isolates studied. There was a significant negative correlation between number of antibiotic resistances and relative fitness. Multiple regression analysis found significantly independent negative correlations between fitness and the presence of mecA or streptomycin resistance. Mathematical modelling confirmed that fitness costs of the magnitude carried by these isolates could result in the disappearance of MRSA prevalence during a time span similar to that seen in Denmark. We propose a significant fitness cost of resistance as the main bacteriological explanation for the disappearance of the multiresistant complex 83A MRSA in Denmark following a reduction in antibiotic usage.

[Sporothrix globosa isolation related to a case of lymphocutaneous sporotrichosis].

PubMed

Cruz, Rodrigo; Vieille, Peggy; Oschilewski, David

2012-08-01

Sporothrix schenckii complex comprises a group of environmental dimorphic fungi that cause sporotrichosis. In Chile, isolated cases have been reported in humans, though no environmental isolates have been described. To achieve isolation of Sporothrix complex from the soil where a 75 year old patient with lymphocutaneous sporotrichosis performs horticulture work. In March and July 2011 soil and plant debris from five sectors where the patient does his work in horticulture was extracted. The soil samples were diluted and inoculated in Sabouraud agar with cycloheximide and chloramphenicol at 26 °C. The plant debris was directly inoculated in the same medium. Colonies suggestive of Sporothrix complex were reseeded in PDA agar at 26 ° C and identified as recommended by Marimon et al. Of the 10 plates from the first sampling, one colony was identified as Sporothrix globosa. In the second sampling, Sporothrix globosa grew in two plates seeded with soil, with a total of 6 colonies. There was no growth of Sporothrix complex in plant debris. The isolate from the patient was also identified as Sporothrix globosa. For the first time in Chile a species of Sporothrix complex was isolated from the environment. Sporothrix globosa was the species identified both in the ground and from the patient with sporotrichosis.

Carbon as a source for yellow luminescence in GaN: Isolated C{sub N} defect or its complexes

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

Christenson, Sayre G.; Xie, Weiyu; Sun, Y. Y., E-mail: suny4@rpi.edu

2015-10-07

We study three carbon defects in GaN, isolated C{sub N} and its two complexes with donors C{sub N}–O{sub N}, and C{sub N}–Si{sub Ga}, as a cause of the yellow luminescence using accurate hybrid density functional calculation, which includes the semi-core Ga 3d electrons as valence electrons and uses a larger 300-atom supercell. We show that the isolated C{sub N} defect yields good agreement with experiment on the photoluminescence (PL) peak position, zero-phonon line, and thermodynamic defect transition level. We find that the defect state of the complexes that is involved in the PL process is the same as that ofmore » the C{sub N} defect. The role of the positively charged donors (O{sub N} or Si{sub Ga}) next to C{sub N} is to blue-shift the PL peak. Therefore, the complexes cannot be responsible for the same PL peak as isolated C{sub N}. Our detailed balance analysis further suggests that under thermal equilibrium at typical growth temperature, the concentration of isolated C{sub N} defect is orders of magnitude higher than the defect complexes, which is a result of the small binding energy in these complexes.« less

Chiral separation and chemical profile of Dengzhan Shengmai by integrating comprehensive with multiple heart-cutting two-dimensional liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

PubMed

Sheng, Ning; Zheng, Hao; Xiao, Yao; Wang, Zhe; Li, Menglin; Zhang, Jinlan

2017-09-29

Chemical profile for Chinese medicine formulas composed of several herbs is always a challenge due to a big array of small molecules with high chemical diversity so much as isomers. The present paper develops a feasible strategy to characterize and identify complex chemical constituents of a four-herb traditional Chinese medicine formula, Denzhan Shenmai (DZSM) by integrating comprehensive two-dimensional liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (LC×LC-qTOF-MS) with multiple heart-cutting two-dimensional liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (MHC-qTOF-MS). DZSM was separated by C8×C18 HPLC column system for comprehensive two-dimensional liquid chromatography system and 283 compounds most of which belonged to phenolic acid, flavonoid, saponin and lignan families were characterized and identified within 75min. Some isomers and compounds at low level were analyzed on C8×Chiral HPLC column system for multiple heart-cutting two-dimensional liquid chromatography system with 1D and 2D optimized gradient elution program. These 1D cutting fractions were successively separated on 2D chiral chromatographic column under extended the 2D gradient elution time from 30s to 5.0min. 12 pairs of isomer compounds were separated with good resolution. The combination of LC×LC and MHC system provides a powerful technique for global chemical profiling of DZSM and provided feasible strategy for other complex systems. Copyright © 2017 Elsevier B.V. All rights reserved.

STUDIES ON MAMMALIAN AND HUMAN PYRUVATE AND ALPHA-KETOGLUTARATE DEHYDROGENATION COMPLEXES.

DTIC Science & Technology

The pig heart pyruvate and alpha - ketoglutarate dehydrogenase complex were isolated in highly purified state as multienzyme units with molecular...weights of approximately 9 million and 2.8 million, respectively. The aims were to resolve the pig heart pyruvate and alpha - ketoglutarate dehydrogenase...complexes was isolated from three sources; (1) pyruvate dehydrogenase complex, (2) alpha - ketoglutarate dehydrogenase, and (3) amber-color extract free

The plastid ndh genes code for an NADH-specific dehydrogenase: Isolation of a complex I analogue from pea thylakoid membranes

PubMed Central

Sazanov, Leonid A.; Burrows, Paul A.; Nixon, Peter J.

1998-01-01

The plastid genomes of several plants contain ndh genes—homologues of genes encoding subunits of the proton-pumping NADH:ubiquinone oxidoreductase, or complex I, involved in respiration in mitochondria and eubacteria. From sequence similarities with these genes, the ndh gene products have been suggested to form a large protein complex (Ndh complex); however, the structure and function of this complex remains to be established. Herein we report the isolation of the Ndh complex from the chloroplasts of the higher plant Pisum sativum. The purification procedure involved selective solubilization of the thylakoid membrane with dodecyl maltoside, followed by two anion-exchange chromatography steps and one size-exclusion chromatography step. The isolated Ndh complex has an apparent total molecular mass of approximately 550 kDa and according to SDS/PAGE consists of at least 16 subunits including NdhA, NdhI, NdhJ, NdhK, and NdhH, which were identified by N-terminal sequencing and immunoblotting. The Ndh complex showed an NADH- and deamino-NADH-specific dehydrogenase activity, characteristic of complex I, when either ferricyanide or the quinones menadione and duroquinone were used as electron acceptors. This study describes the isolation of the chloroplast analogue of the respiratory complex I and provides direct evidence for the function of the plastid Ndh complex as an NADH:plastoquinone oxidoreductase. Our results are compatible with a dual role for the Ndh complex in the chlororespiratory and cyclic photophosphorylation pathways. PMID:9448329

[Isolation of Sporothrix pallida complex in clinical and environmental samples from Chile].

PubMed

Cruz Choappa, Rodrigo M; Vieille Oyarzo, Peggy I; Carvajal Silva, Laura C

2014-01-01

The isolation of S. pallida complex from medical samples and home garden soil of a patient in Chile is here in reported. Fungi of the Sporothrix schenckii complex can cause various infections. In Chile, the medical and environmental isolates of these this complex are rare. The aim of this study was to identify an unusual agent in a case of onychomycosis and to detect its presence in the patient's home garden. For this purpose, clinical samples were obtained by scraping the patient's subungueal first right toe nail as well as by taking soil samples from different areas of her home garden. Species identification was performed by morphophysiology and one of the strains isolated from the patient's toe nail was sent to CBS for molecular confirmation (14.062). S. pallida complex was identified both from the patient's toe nail and samples taken from her home garden. Copyright © 2014 Asociación Argentina de Microbiología. Publicado por Elsevier España. All rights reserved.

Morphological and molecular characterization of Cladosporium cladosporioides species complex causing pecan tree leaf spot.

PubMed

Walker, C; Muniz, M F B; Rolim, J M; Martins, R R O; Rosenthal, V C; Maciel, C G; Mezzomo, R; Reiniger, L R S

2016-09-16

The objective of this study was to characterize species of the Cladosporium cladosporioides complex isolated from pecan trees (Carya illinoinensis) with symptoms of leaf spot, based on morphological and molecular approaches. Morphological attributes were assessed using monosporic cultures on potato dextrose agar medium, which were examined for mycelial growth, sporulation, color, and conidia and ramoconidia size. Molecular characterization comprised isolation of DNA and subsequent amplification of the translation elongation factor 1α (TEF-1α) region. Three species of the C. cladosporioides complex were identified: C. cladosporioides, Cladosporium pseudocladosporioides, and Cladosporium subuliforme. Sporulation was the most important characteristic differentiating species of this genus. However, morphological features must be considered together with molecular analysis, as certain characters are indistinguishable between species. TEF-1αcan be effectively used to identify and group isolates belonging to the C. cladosporioides complex. The present study provides an important example of a methodology to ascertain similarity between isolates of this complex causing leaf spot in pecan trees, which should facilitate future pathogenicity studies.

Morphological and molecular characterization of Fusarium spp pathogenic to pecan tree in Brazil.

PubMed

Lazarotto, M; Milanesi, P M; Muniz, M F B; Reiniger, L R S; Beltrame, R; Harakava, R; Blume, E

2014-11-11

The occurrence of Fusarium spp associated with pecan tree (Carya illinoinensis) diseases in Brazil has been observed in recent laboratory analyses in Rio Grande do Sul State. Thus, in this study, we i) obtained Fusarium isolates from plants with disease symptoms; ii) tested the pathogenicity of these Fusarium isolates to pecan; iii) characterized and grouped Fusarium isolates that were pathogenic to the pecan tree based on morphological characteristics; iv) identified Fusarium spp to the species complex level through TEF-1α sequencing; and v) compared the identification methods used in the study. Fifteen isolates collected from the inflorescences, roots, and seeds of symptomatic plants (leaf necrosis or root rot) were used for pathogenicity tests. Morphological characterization was conducted using only pathogenic isolates, for a total of 11 isolates, based on the mycelial growth rate, sporulation, colony pigmentation, and conidial length and width variables. Pathogenic isolates were grouped based on morphological characteristics, and molecular characterization was performed by sequencing TEF-1α genes. Pathogenic isolates belonging to the Fusarium chlamydosporum species complex, Fusarium graminearum species complex, Fusarium proliferatum, and Fusarium oxysporum were identified based on the TEF-1α region. Morphological characteristics were used to effectively differentiate isolates and group the isolates according to genetic similarity, particularly conidial width, which emerged as a key morphological descriptor in this study.

Role of phytoestrogens in prevention and management of type 2 diabetes

PubMed Central

Talaei, Mohammad; Pan, An

2015-01-01

Type 2 diabetes (T2D) has become a major public health threat across the globe. It has been widely acknowledged that diet plays an important role in the development and management of T2D. Phytoestrogens are polyphenols that are structurally similar to endogenous estrogen and have weak estrogenic properties. Emerging evidence from pre-clinical models has suggested that phytoestrogens may have anti-diabetic function via both estrogen-dependent and estrogen-independent pathways. In the current review, we have summarized the evidence linking two major types of phytoestrogens, isoflavones and lignans, and T2D from epidemiological studies and clinical trials. The cross-sectional and prospective cohort studies have reported inconsistent results, which may due to the large variations in different populations and measurement errors in dietary intakes. Long-term intervention studies using isoflavone supplements have reported potential beneficial effects on glycemic parameters in postmenopausal women, while results from short-term small-size clinical trials are conflicting. Taken together, the current evidence from different study designs is complex and inconsistent. Although the widespread use of phytoestrogens could not be recommended yet, habitual consumption of phytoestrogens, particularly their intact food sources like soy and whole flaxseed, could be considered as a component of overall healthy dietary pattern for prevention and management of T2D. PMID:25789108

Recent developments in qualitative and quantitative analysis of phytochemical constituents and their metabolites using liquid chromatography-mass spectrometry.

PubMed

Wu, Haifeng; Guo, Jian; Chen, Shilin; Liu, Xin; Zhou, Yan; Zhang, Xiaopo; Xu, Xudong

2013-01-01

Over the past few years, the applications of liquid chromatography coupled with mass spectrometry (LC-MS) in natural product analysis have been dramatically growing because of the increasingly improved separation and detection capabilities of LC-MS instruments. In particular, novel high-resolution hybrid instruments linked to ultra-high-performance LC and the hyphenations of LC-MS with other separation or analytical techniques greatly aid unequivocal identification and highly sensitive quantification of natural products at trace concentrations in complex matrices. With the aim of providing an up-to-date overview of LC-MS applications on the analysis of plant-derived compounds, papers published within the latest years (2007-2012) involving qualitative and quantitative analysis of phytochemical constituents and their metabolites are summarized in the present review. After briefly describing the general characteristics of natural products analysis, the most remarkable features of LC-MS and sample preparation techniques, the present paper mainly focuses on screening and characterization of phenols (including flavonoids), alkaloids, terpenoids, steroids, coumarins, lignans, and miscellaneous compounds in respective herbs and biological samples, as well as traditional Chinese medicine (TCM) prescriptions using tandem mass spectrometer. Chemical fingerprinting analysis using LC-MS is also described. Meanwhile, instrumental peculiarities and methodological details are accentuated. Copyright © 2012 Elsevier B.V. All rights reserved.

Phytoceuticals in Acute Pancreatitis: Targeting the Balance between Apoptosis and Necrosis

PubMed Central

Gaman, Laura; Robu, Georgiana Catalina; Radoi, Mugurel Petrinel; Stroica, Laura; Badea, Mihaela

2018-01-01

Despite recent advances in understanding the complex pathogenesis of pancreatitis, the management of the disease remains suboptimal. The use of phytoceuticals (plant-derived pleiotropic multitarget molecules) represents a new research trend in pancreatology. The purpose of this review is to discuss the phytoceuticals with pancreatoprotective potential in acute pancreatitis and whose efficacy is based, at least in part, on their capacity to modulate the acinar cell death. The phytochemicals selected, belonging to such diverse classes as polyphenols, flavonoids, lignans, anthraquinones, sesquiterpene lactones, nitriles, and alkaloids, target the balance between apoptosis and necrosis. Activation of apoptosis via various mechanisms (e.g., inhibition of X-linked inhibitor of apoptosis proteins by embelin, upregulation of FasL gene expression by resveratrol) and/or inhibition of necrosis seem to represent the essential key for decreasing the severity of the disease. Apart from targeting the apoptosis/necrosis balance, the phytochemicals displayed other specific protective activities: inhibition of inflammasome (e.g., rutin), suppression of neutrophil infiltration (e.g., ligustrazine, resveratrol), and antioxidant activity. Even though many of the selected phytoceuticals represent a promising therapeutic alternative, there is a shortage of human evidence, and further studies are required to provide solid basis to justify their use in the treatment of pancreatitis. PMID:29686719

Optimization of microwave-assisted extraction conditions for preparing lignan-rich extract from Saraca asoca bark using Box-Behnken design.

PubMed

Mishra, Shikha; Aeri, Vidhu

2016-07-01

Lyoniside is the major constituent of Saraca asoca Linn. (Caesalpiniaceae) bark. There is an immediate need to develop an efficient method to isolate its chemical constituents, since it is a therapeutically important plant. A rapid extraction method for lyoniside based on microwave-assisted extraction of S. asoca bark was developed and optimized using response surface methodology (RSM). Lyoniside was analyzed and quantified by high-performance liquid chromatography coupled with ultraviolet detection (HPLC-UV). The extraction solvent ratio (%), material solvent ratio (g/ml) and extraction time (min) were optimized using Box-Behnken design (BBD) to obtain the highest extraction efficiency. The optimal conditions were the use of 1:30 material solvent ratio with 70:30 mixture of methanol:water for 10 min duration. The optimized microwave-assisted extraction yielded 9.4 mg/g of lyoniside content in comparison to reflux extraction under identical conditions which yielded 4.2 mg/g of lyoniside content. Under optimum conditions, the experimental values agreed closely with the predicted values. The analysis of variance (ANOVA) indicated a high goodness-of-fit model and the success of the RSM method for optimizing lyoniside extraction from the bark of S. asoca. All the three variables significantly affected the lyoniside content. Increased polarity of solvent medium enhances the lyoniside yield. The present study shows the applicability of microwave-assisted extraction in extraction of lyoniside from S. asoca bark.

Effects of Phytoestrogen Extracts Isolated from Elder Flower on Hormone Production and Receptor Expression of Trophoblast Tumor Cells JEG-3 and BeWo, as well as MCF7 Breast Cancer Cells

PubMed Central

Schröder, Lennard; Richter, Dagmar Ulrike; Piechulla, Birgit; Chrobak, Mareike; Kuhn, Christina; Schulze, Sandra; Abarzua, Sybille; Jeschke, Udo; Weissenbacher, Tobias

2016-01-01

Herein we investigated the effect of elderflower extracts (EFE) and of enterolactone/enterodiol on hormone production and proliferation of trophoblast tumor cell lines JEG-3 and BeWo, as well as MCF7 breast cancer cells. The EFE was analyzed by mass spectrometry. Cells were incubated with various concentrations of EFE. Untreated cells served as controls. Supernatants were tested for estradiol production with an ELISA method. Furthermore, the effect of the EFE on ERα/ERβ/PR expression was assessed by immunocytochemistry. EFE contains a substantial amount of lignans. Estradiol production was inhibited in all cells in a concentration-dependent manner. EFE upregulated ERα in JEG-3 cell lines. In MCF7 cells, a significant ERα downregulation and PR upregulation were observed. The control substances enterolactone and enterodiol in contrast inhibited the expression of both ER and of PR in MCF7 cells. In addition, the production of estradiol was upregulated in BeWo and MCF7 cells in a concentration dependent manner. The downregulating effect of EFE on ERα expression and the upregulation of the PR expression in MFC-7 cells are promising results. Therefore, additional unknown substances might be responsible for ERα downregulation and PR upregulation. These findings suggest potential use of EFE in breast cancer prevention and/or treatment and warrant further investigation. PMID:27740591

Analysis of kinetoplast cytochrome b gene of 16 Leishmania isolates from different foci of China: different species of Leishmania in China and their phylogenetic inference

PubMed Central

2013-01-01

Background Leishmania species belong to the family Trypanosomatidae and cause leishmaniasis, a geographically widespread disease that infects humans and other vertebrates. This disease remains endemic in China. Due to the large geographic area and complex ecological environment, the taxonomic position and phylogenetic relationship of Chinese Leishmania isolates remain uncertain. A recent internal transcribed spacer 1 and cytochrome oxidase II phylogeny of Chinese Leishmania isolates has challenged some aspects of their traditional taxonomy as well as cladistics hypotheses of their phylogeny. The current study was designed to provide further disease background and sequence analysis. Methods We systematically analyzed 50 cytochrome b (cyt b) gene sequences of 19 isolates (16 from China, 3 from other countries) sequenced after polymerase chain reaction (PCR) using a special primer for cyt b as well as 31 sequences downloaded from GenBank. After alignment, the data were analyzed using the maximum parsimony, Bayesian and netwok methods. Results Sequences of six haplotypes representing 10 Chinese isolates formed a monophyletic group and clustered with Leishmania tarentolae. The isolates GS1, GS7, XJ771 of this study from China clustered with other isolates of Leishmania donovani complex. The isolate JS1 was a sister to Leishmania tropica, which represented an L. tropica complex instead of clustering with L. donovani complex or with the other 10 Chinese isolates. The isolates KXG-2 and GS-GER20 formed a monophyletic group with Leishmania turanica from central Asia. In the different phylogenetic trees, all of the Chinese isolates occurred in at least four groups regardless of geographic distribution. Conclusions The undescribed Leishmania species of China, which are clearly causative agents of canine leishmaniasis and human visceral leishmaniasis and are related to Sauroleishmania, may have evolved from a common ancestral parasite that came from the Americas and may have split off earlier than the other old world Leishmania. Our results also suggest the following: the isolates GS7, GS1 and XJ771 occur as part of the L. donovani complex; the JS1 isolate is L. tropica; and the isolate GS-GER20 identified as Leishmania gerbilli is close to KXG-2 which is L. turanica. PMID:23383990

Co-complexes derived from alkene insertion to alkyne-dicobaltpentacarbonyl complexes: insight into the regioselectivity of pauson-khand reactions of cyclopropenes.

PubMed

Pallerla, Mahesh K; Yap, Glenn P A; Fox, Joseph M

2008-08-15

Described are the X-ray crystallographic and spectral properties of Co-complexes that were isolated from two Pauson-Khand reactions of chiral cyclopropenes. These are the first examples of isolated Co-complexes derived from the putative alkene-insertion intermediates of Pauson-Khand reactions. The binuclear Co-complexes are coordinated to mu-bonded, five-carbon "flyover" carbene ligands. It is proposed that the complexes result from cyclopropane fragmentation subsequent to alkene insertion. The observation of these metal complexes provides a rationale for the origin of regioselectivity in Pauson-Khand reactions of cyclopropenes.

Synthetic Lignan Secoisolariciresinol Diglucoside (LGM2605) Reduces Asbestos-Induced Cytotoxicity in an Nrf2-Dependent and -Independent Manner.

PubMed

Pietrofesa, Ralph A; Chatterjee, Shampa; Park, Kyewon; Arguiri, Evguenia; Albelda, Steven M; Christofidou-Solomidou, Melpo

2018-03-02

Asbestos exposure triggers inflammatory processes associated with oxidative stress and tissue damage linked to malignancy. LGM2605 is the synthetic lignan secoisolariciresinol diglucoside (SDG) with free radical scavenging, antioxidant, and anti-inflammatory properties in diverse inflammatory cell and mouse models, including exposure to asbestos fibers. Nuclear factor-E2 related factor 2 (Nrf2) activation and boosting of endogenous tissue defenses were associated with the protective action of LGM2605 from asbestos-induced cellular damage. To elucidate the role of Nrf2 induction by LGM2605 in protection from asbestos-induced cellular damage, we evaluated LGM2605 in asbestos-exposed macrophages from wild-type (WT) and Nrf2 disrupted (Nrf2 - / - ) mice. Cells were pretreated with LGM2605 (50 µM and 100 µM) and exposed to asbestos fibers (20 µg/cm²) and evaluated 8 h and 24 h later for inflammasome activation, secreted cytokine levels (interleukin-1β (IL-1β), interleukin-18 (IL-18), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFα)), cytotoxicity and cell death, nitrosative stress, and Nrf2-regulated enzyme levels. Asbestos exposure induced robust oxidative and nitrosative stress, cell death and cytotoxicity, which were equally mitigated by LGM2605. Inflammasome activation was significantly attenuated in Nrf2 -/- macrophages compared to WT, and the protective action of LGM2605 was seen only in WT cells. In conclusion, in a cell model of asbestos-induced toxicity, LGM2605 acts via protective mechanisms that may not involve Nrf2 activation.

Phytoestrogen Concentrations in Human Urine as Biomarkers for Dietary Phytoestrogen Intake in Mexican Women

PubMed Central

Chávez-Suárez, Karina M.; Ortega-Vélez, María I.; Valenzuela-Quintanar, Ana I.; Galván-Portillo, Marcia; López-Carrillo, Lizbeth; Esparza-Romero, Julián; Saucedo-Tamayo, María S.; Robles-Burgueño, María R.; Gutiérrez-Coronado, María L.; Campa-Siqueiros, Melissa M.; Grajeda-Cota, Patricia; Caire-Juvera, Graciela

2017-01-01

There has been substantial interest in phytoestrogens, because of their potential effect in reducing cancer and heart disease risk. Measuring concentrations of phytoestrogens in urine is an alternative method for conducting epidemiological studies. Our objective was to evaluate the urinary excretion of phytoestrogens as biomarkers for dietary phytoestrogen intake in Mexican women. Participants were 100 healthy women from 25 to 80 years of age. A food frequency questionnaire (FFQ) and a 24 h recall were used to estimate habitual and recent intakes of isoflavones, lignans, flavonols, coumestrol, resveratrol, naringenin, and luteolin. Urinary concentrations were measured by liquid chromatography (HPLC) coupled to mass spectrometry (MS) using the electrospray ionization interface (ESI) and diode array detector (DAD) (HPLC-DAD-ESI-MS). Spearman correlation coefficients were used to evaluate associations between dietary intake and urine concentrations. The habitual consumption (FFQ) of total phytoestrogens was 37.56 mg/day. In urine, the higher compounds were naringenin (60.1 µg/L) and enterolactone (41.7 µg/L). Recent intakes (24 h recall) of isoflavones (r = 0.460, p < 0.001), lignans (r = 0.550, p < 0.0001), flavonoids (r = 0.240, p < 0.05), and total phytoestrogens (r = 0.410, p < 0.001) were correlated to their urinary levels. Total phytoestrogen intakes estimated by the FFQ showed higher correlations to urinary levels (r = 0.730, p < 0.0001). Urinary phytoestrogens may be useful as biomarkers of phytoestrogen intake, and as a tool for evaluating the relationship of intake and disease risk in Mexican women. PMID:28961176

Uncovering potential anti-neuroinflammatory components of Modified Wuziyanzong Prescription through a target-directed molecular docking fingerprint strategy.

PubMed

Chen, Jinfeng; Wang, Jinlong; Lu, Yingyuan; Zhao, Shaoyang; Yu, Qian; Wang, Xuemei; Tu, Pengfei; Zeng, Kewu; Jiang, Yong

2018-05-01

Neuroinflammation is a main factor in the pathogenesis of neurodegenerative diseases, such as Alzheimer disease. Our previous studies indicated that the modified Wuziyanzong Prescription (MWP) can suppress neuroinflammatory responses via nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) signaling pathways. However, the anti-neuroinflammatory components of MWP remain unclear. Herein, a target-directed molecular docking fingerprint (TMDF) strategy, via integrating the chemical profiling and molecular docking approaches, was developed to identify the potential anti-neuroinflammatory components of MWP. First, as many as 120 possible structures, including 49 flavonoids, 28 phenylpropionic acids, 18 amides, 10 carotenoids, eight phenylethanoid glycosides, four lignans, two iridoids, and one triterpenoid were deduced by the source attribution and structural classification-assisted strategy. Then, their geometries were docked against five major targets of the NF-κB and MAPKs signaling cascades, including p38-α, IKKβ, ERK1, ERK2, and TRAF6. The docking results revealed diverse contributions of different components towards the protein targets. Collectively, prenylated flavonoids showed intensive or moderate anti-neuroinflammatory activities, while phenylpropanoids, amides, phenylethanoid glycosides, lignans, and triterpenoids exhibited moderate or weak anti-neuroinflammatory effects. The anti-neuroinflammatory activities of four retrieved prenylated flavonoids were tested by Western blotting assay, and the results mostly agreed with those predicted by the docking method. These gained information demonstrates that the established TMDF strategy could be a rapid and feasible methodology to investigate the potential active components in herbal compound prescriptions. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of flaxseed lignan and oil on bone health of breast-tumor-bearing mice treated with or without tamoxifen.

PubMed

Chen, Jianmin; Saggar, Jasdeep K; Ward, Wendy E; Thompson, Lilian U

2011-01-01

Previous studies showed that flaxseed lignan (secoisolariciresinol diglucoside, SDG) and oil (FO) inhibit established breast tumor growth in athymic mice with or without tamoxifen (TAM) treatment. TAM was found to increase bone mineral content (BMC) and density (BMD) in breast cancer patients. It is not known whether SDG or FO alone or combined with TAM affects bone health. Hence, the effects of SDG and FO, alone or in combination, on BMC, BMD, and biomechanical bone strength in ovariectomized athymic mice with established human breast tumors (MCF-7) treated with or without TAM were studied. In a factorial design, mice were divided into four non-TAM and four TAM groups. Each group consisted of mice fed a basal diet (BD), SDG (1 g/kg), FO (38.5 g/kg) or SDG + FO (combination) diets. The TAM group had TAM implants that provide a 5-mg TAM dose released over 60 d. TAM exerted an overall significant effect in increasing BMC, BMD, and biomechanical strength in femurs and lumbar vertebra. Without TAM treatment, SDG produced significant lower femur BMD (6%) while FO produced lower vertebrae BMC (8%) and BMD (6%). With TAM treatment, SDG and FO did not exert an effect on BMC and BMD at the femur or vertebra. SDG and FO produced no marked effect on biomechanical bone strength with or without TAM treatment. In conclusion, FS components did not significantly attenuate the positive effects on bone induced by TAM in this model system, indicating no apparent adverse effects on bone health.

Synthetic Lignan Secoisolariciresinol Diglucoside (LGM2605) Reduces Asbestos-Induced Cytotoxicity in an Nrf2-Dependent and -Independent Manner

PubMed Central

Pietrofesa, Ralph A.; Chatterjee, Shampa; Park, Kyewon; Arguiri, Evguenia; Albelda, Steven M.; Christofidou-Solomidou, Melpo

2018-01-01

Asbestos exposure triggers inflammatory processes associated with oxidative stress and tissue damage linked to malignancy. LGM2605 is the synthetic lignan secoisolariciresinol diglucoside (SDG) with free radical scavenging, antioxidant, and anti-inflammatory properties in diverse inflammatory cell and mouse models, including exposure to asbestos fibers. Nuclear factor-E2 related factor 2 (Nrf2) activation and boosting of endogenous tissue defenses were associated with the protective action of LGM2605 from asbestos-induced cellular damage. To elucidate the role of Nrf2 induction by LGM2605 in protection from asbestos-induced cellular damage, we evaluated LGM2605 in asbestos-exposed macrophages from wild-type (WT) and Nrf2 disrupted (Nrf2−/−) mice. Cells were pretreated with LGM2605 (50 µM and 100 µM) and exposed to asbestos fibers (20 µg/cm2) and evaluated 8 h and 24 h later for inflammasome activation, secreted cytokine levels (interleukin-1β (IL-1β), interleukin-18 (IL-18), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFα)), cytotoxicity and cell death, nitrosative stress, and Nrf2-regulated enzyme levels. Asbestos exposure induced robust oxidative and nitrosative stress, cell death and cytotoxicity, which were equally mitigated by LGM2605. Inflammasome activation was significantly attenuated in Nrf2−/− macrophages compared to WT, and the protective action of LGM2605 was seen only in WT cells. In conclusion, in a cell model of asbestos-induced toxicity, LGM2605 acts via protective mechanisms that may not involve Nrf2 activation. PMID:29498660

Accessibility of ³H-secoisolariciresinol diglycoside lignan metabolites in skeletal tissue of ovariectomized rats.

PubMed

Sacco, Sandra M; Thompson, Lilian U; Ganss, Bernhard; Ward, Wendy E

2011-10-01

Flaxseed, rich in the phytoestrogen lignan secoisolariciresinol diglycoside (SDG), provides protection against bone loss at the lumbar vertebrae primarily when combined with low-dose estrogen therapy in the ovariectomized rat model of postmenopausal osteoporosis. Whether SDG metabolites are accessible to skeletal tissue, and thus have the potential to interact with low-dose estrogen therapy to exert direct local action on bone metabolism, is unknown. The objective of this study was to determine whether metabolites of SDG are accessible to the skeleton of ovariectomized rats and to compare the distribution of SDG metabolites in skeletal tissue with that in other tissues. Rats were fed a 10% flaxseed diet and gavaged daily with tritium-labeled SDG (7.4 kBq/g of body weight) in deionized water (500 μL) (n=3) or deionized water alone (n=3) for 7 days, after which tissues were collected for liquid scintillation counting. Radioactivity was detected in similar concentrations in the lumbar vertebrae, femurs, and tibias. Compared with non-skeletal tissues, total radioactivity in the skeleton was significantly lower than in the liver, heart, kidney, thymus, and brain (P < .001). There were no significant differences in levels of radioactivity between skeletal tissue versus the spleen, lung, bladder, uterus, vagina, and mammary gland. In conclusion, SDG metabolites are accessible to skeletal tissue of ovariectomized rats. Thus, it is biologically plausible that SDG metabolites may play a direct role in the protective effects of flaxseed combined with low-dose estrogen therapy against the loss of bone mass and bone strength in the ovariectomized rat model of postmenopausal osteoporosis.

Abscisic acid regulates pinoresinol-lariciresinol reductase gene expression and secoisolariciresinol accumulation in developing flax (Linum usitatissimum L.) seeds.

PubMed

Renouard, Sullivan; Corbin, Cyrielle; Lopez, Tatiana; Montguillon, Josiane; Gutierrez, Laurent; Lamblin, Frédéric; Lainé, Eric; Hano, Christophe

2012-01-01

Secoisolariciresinol diglucoside (SDG), the main phytoestrogenic lignan of Linum usitatissimum, is accumulated in the seed coat of flax during its development and pinoresinol-lariciresinol reductase (PLR) is a key enzyme in flax for its synthesis. The promoter of LuPLR1, a flax gene encoding a pinoresinol lariciresinol reductase, contains putative regulatory boxes related to transcription activation by abscisic acid (ABA). Gel mobility shift experiments evidenced an interaction of nuclear proteins extracted from immature flax seed coat with a putative cis-acting element involved in ABA response. As ABA regulates a number of physiological events during seed development and maturation we have investigated its involvement in the regulation of this lignan synthesis by different means. ABA and SDG accumulation time courses in the seed as well as LuPLR1 expression were first determined in natural conditions. These results showed that ABA timing and localization of accumulation in the flax seed coat could be correlated with the LuPLR1 gene expression and SDG biosynthesis. Experimental modulations of ABA levels were performed by exogenous application of ABA or fluridone, an inhibitor of ABA synthesis. When submitted to exogenous ABA, immature seeds synthesized 3-times more SDG, whereas synthesis of SDG was reduced in immature seeds treated with fluridone. Similarly, the expression of LuPLR1 gene in the seed coat was up-regulated by exogenous ABA and down-regulated when fluridone was applied. These results demonstrate that SDG biosynthesis in the flax seed coat is positively controlled by ABA through the transcriptional regulation of LuPLR1 gene.

Tendency towards maximum complexity in a nonequilibrium isolated system

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

Calbet, Xavier; Lopez-Ruiz, Ricardo

2001-06-01

The time evolution equations of a simplified isolated ideal gas, the {open_quotes}tetrahedral{close_quotes} gas, are derived. The dynamical behavior of the Lopez-Ruiz{endash}Mancini{endash}Calbet complexity [R. Lopez-Ruiz, H. L. Mancini, and X. Calbet, Phys. Lett. A >209, 321 (1995)] is studied in this system. In general, it is shown that the complexity remains within the bounds of minimum and maximum complexity. We find that there are certain restrictions when the isolated {open_quotes}tetrahedral{close_quotes} gas evolves towards equilibrium. In addition to the well-known increase in entropy, the quantity called disequilibrium decreases monotonically with time. Furthermore, the trajectories of the system in phase space approach themore » maximum complexity path as it evolves toward equilibrium.« less

The mate recognition protein gene mediates reproductive isolation and speciation in the Brachionus plicatilis cryptic species complex.

PubMed

Gribble, Kristin E; Mark Welch, David B

2012-08-01

Chemically mediated prezygotic barriers to reproduction likely play an important role in speciation. In facultatively sexual monogonont rotifers from the Brachionus plicatilis cryptic species complex, mate recognition of females by males is mediated by the Mate Recognition Protein (MRP), a globular glycoprotein on the surface of females, encoded by the mmr-b gene family. In this study, we sequenced mmr-b copies from 27 isolates representing 11 phylotypes of the B. plicatilis species complex, examined the mode of evolution and selection of mmr-b, and determined the relationship between mmr-b genetic distance and mate recognition among isolates. Isolates of the B. plicatilis species complex have 1-4 copies of mmr-b, each composed of 2-9 nearly identical tandem repeats. The repeats within a gene copy are generally more similar than are gene copies among phylotypes, suggesting concerted evolution. Compared to housekeeping genes from the same isolates, mmr-b has accumulated only half as many synonymous differences but twice as many non-synonymous differences. Most of the amino acid differences between repeats appear to occur on the outer face of the protein, and these often result in changes in predicted patterns of phosphorylation. However, we found no evidence of positive selection driving these differences. Isolates with the most divergent copies were unable to mate with other isolates and rarely self-crossed. Overall the degree of mate recognition was significantly correlated with the genetic distance of mmr-b. Discrimination of compatible mates in the B. plicatilis species complex is determined by proteins encoded by closely related copies of a single gene, mmr-b. While concerted evolution of the tandem repeats in mmr-b may function to maintain identity, it can also lead to the rapid spread of a mutation through all copies in the genome and thus to reproductive isolation. The mmr-b gene is evolving rapidly, and novel alleles may be maintained and increase in frequency via asexual reproduction. Our analyses indicate that mate recognition, controlled by MMR-B, may drive reproductive isolation and allow saltational sympatric speciation within the B. plicatilis cryptic species complex, and that this process may be largely neutral.

Complex I-complex II ratio strongly differs in various organs of Arabidopsis thaliana.

PubMed

Peters, Katrin; Niessen, Markus; Peterhänsel, Christoph; Späth, Bettina; Hölzle, Angela; Binder, Stefan; Marchfelder, Anita; Braun, Hans-Peter

2012-06-01

In most studies, amounts of protein complexes of the oxidative phosphorylation (OXPHOS) system in different organs or tissues are quantified on the basis of isolated mitochondrial fractions. However, yield of mitochondrial isolations might differ with respect to tissue type due to varying efficiencies of cell disruption during organelle isolation procedures or due to tissue-specific properties of organelles. Here we report an immunological investigation on the ratio of the OXPHOS complexes in different tissues of Arabidopsis thaliana which is based on total protein fractions isolated from five Arabidopsis organs (leaves, stems, flowers, roots and seeds) and from callus. Antibodies were generated against one surface exposed subunit of each of the five OXPHOS complexes and used for systematic immunoblotting experiments. Amounts of all complexes are highest in flowers (likewise with respect to organ fresh weight or total protein content of the flower fraction). Relative amounts of protein complexes in all other fractions were determined with respect to their amounts in flowers. Our investigation reveals high relative amounts of complex I in green organs (leaves and stems) but much lower amounts in non-green organs (roots, callus tissue). In contrast, complex II only is represented by low relative amounts in green organs but by significantly higher amounts in non-green organs, especially in seeds. In fact, the complex I-complex II ratio differs by factor 37 between callus and leaf, indicating drastic differences in electron entry into the respiratory chain in these two fractions. Variation in amounts concerning complexes III, IV and V was less pronounced in different Arabidopsis tissues (quantification of complex V in leaves was not meaningful due to a cross-reaction of the antibody with the chloroplast form of this enzyme). Analyses were complemented by in gel activity measurements for the protein complexes of the OXPHOS system and comparative 2D blue native/SDS PAGE analyses using isolated mitochondria. We suggest that complex I has an especially important role in the context of photosynthesis which might be due to its indirect involvement in photorespiration and its numerous enzymatic side activities in plants.

A peptide affinity reagent for isolating an intact and catalytically active multi-protein complex from mammalian cells.

PubMed

Saathoff, Hinnerk; Brofelth, Mattias; Trinh, Anne; Parker, Benjamin L; Ryan, Daniel P; Low, Jason K K; Webb, Sarah R; Silva, Ana P G; Mackay, Joel P; Shepherd, Nicholas E

2015-03-01

We have developed an approach for directly isolating an intact multi-protein chromatin remodeling complex from mammalian cell extracts using synthetic peptide affinity reagent 4. FOG1(1-15), a short peptide sequence known to target subunits of the nucleosome remodeling and deacetylase (NuRD) complex, was joined via a 35-atom hydrophilic linker to the StreptagII peptide. Loading this peptide onto Streptactin beads enabled capture of the intact NuRD complex from MEL cell nuclear extract. Gentle biotin elution yielded the desired intact complex free of significant contaminants and in a form that was catalytically competent in a nucleosome remodeling assay. The efficiency of 4 in isolating the NuRD complex was comparable to other reported methods utilising recombinantly produced GST-FOG1(1-45). Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Characterization of Mediator Complex and its Associated Proteins from Rice.

PubMed

Samanta, Subhasis; Thakur, Jitendra Kumar

2017-01-01

The Mediator complex is a multi-protein complex that acts as a molecular bridge conveying transcriptional messages from the cis element-bound transcription factor to the RNA Polymerase II machinery. It is found in all eukaryotes including members of the plant kingdom. Increasing number of reports from plants regarding different Mediator subunits involved in a multitude of processes spanning from plant development to environmental interactions have firmly established it as a central hub of plant regulatory networks. Routine isolation of Mediator complex in a particular species is a necessity because of many reasons. First, composition of the Mediator complex varies from species to species. Second, the composition of the Mediator complex in a particular species is not static under all developmental and environmental conditions. Besides this, at times, Mediator complex is used in in vitro transcription systems. Rice, a staple food crop of the world, is used as a model monocot crop. Realizing the need of a reliable protocol for the isolation of Mediator complex from plants, we describe here the isolation of Mediator complex from rice.

Evaluation of the Sensititre MycoTB plate for susceptibility testing of the Mycobacterium tuberculosis complex against first- and second-line agents.

PubMed

Hall, Leslie; Jude, Kurt P; Clark, Shirley L; Dionne, Kim; Merson, Ryan; Boyer, Ana; Parrish, Nicole M; Wengenack, Nancy L

2012-11-01

The Sensititre MycoTB plate (TREK Diagnostic Systems, Cleveland, OH) uses a microtiter plate MIC format for susceptibility testing of Mycobacterium tuberculosis complex isolates against first- and second-line antituberculosis agents. Categorical agreement versus the agar proportion method for 122 M. tuberculosis complex isolates was 94% to 100%.

Isolation of integrin-based adhesion complexes.

PubMed

Jones, Matthew C; Humphries, Jonathan D; Byron, Adam; Millon-Frémillon, Angélique; Robertson, Joseph; Paul, Nikki R; Ng, Daniel H J; Askari, Janet A; Humphries, Martin J

2015-03-02

The integration of cells with their extracellular environment is facilitated by cell surface adhesion receptors, such as integrins, which play important roles in both normal development and the onset of pathologies. Engagement of integrins with their ligands in the extracellular matrix, or counter-receptors on other cells, initiates the intracellular assembly of a wide variety of proteins into adhesion complexes such as focal contacts, focal adhesions, and fibrillar adhesions. The proteins recruited to these complexes mediate bidirectional signaling across the plasma membrane, and, as such, help to coordinate and/or modulate the multitude of physical and chemical signals to which the cell is subjected. The protocols in this unit describe two approaches for the isolation or enrichment of proteins contained within integrin-associated adhesion complexes, together with their local plasma membrane/cytosolic environments, from cells in culture. In the first protocol, integrin-associated adhesion structures are affinity isolated using microbeads coated with extracellular ligands or antibodies. The second protocol describes the isolation of ventral membrane preparations that are enriched for adhesion complex structures. The protocols permit the determination of adhesion complex components via subsequent downstream analysis by western blotting or mass spectrometry. Copyright © 2015 John Wiley & Sons, Inc.

Distribution of the ACME-arcA gene among meticillin-resistant Staphylococcus haemolyticus and identification of a novel ccr allotype in ACME-arcA-positive isolates.

PubMed

Pi, Borui; Yu, Meihong; Chen, Yagang; Yu, Yunsong; Li, Lanjuan

2009-06-01

The aim of this study was to investigate the prevalence and characteristics of ACME (arginine catabolic mobile element)-arcA-positive isolates among meticillin-resistant Staphylococcus haemolyticus (MRSH). ACME-arcA, native arcA and SCCmec elements were detected by PCR. Susceptibilities to 10 antimicrobial agents were compared between ACME-arcA-positive and -negative isolates by chi-square test. PFGE was used to investigate the clonal relatedness of ACME-arcA-positive isolates. The phylogenetic relationships of ACME-arcA and native arcA were analysed using the neighbour-joining methods of mega software. A total of 42 (47.7 %) of 88 isolates distributed in 13 PFGE types were positive for the ACME-arcA gene. There were no significant differences in antimicrobial susceptibility between ACME-arcA-positive and -negative isolates. A novel ccr allotype (ccrAB(SHP)) was identified in ACME-arcA-positive isolates. Among 42 ACME-arcA-positive isolates: 8 isolates harboured SCCmec V, 8 isolates harboured class C1 mec complex and ccrAB(SHP); 22 isolates harbouring class C1 mec complex and 4 isolates harbouring class C2 mec complex were negative for all known ccr allotypes. The ACME-arcA-positive isolates were first found in MRSH with high prevalence and clonal diversity, which suggests a mobility of ACME within MRSH. The results from this study revealed that MRSH is likely to be one of the potential reservoirs of ACME for Staphylococcus aureus.

Co-complexes Derived from Alkene Insertion to Alkyne-dicobaltpentacarbonyl complexes: Insight into the Regioselectivity of Pauson-Khand Reactions of Cyclopropenes

PubMed Central

Pallerla, Mahesh K.; Yap, Glenn P. A.; Fox, Joseph M.

2009-01-01

Described are the X-ray crystallographic and spectral properties of Co-complexes that were isolated from two Pauson-Khand reactions of chiral cyclopropenes. These are the first examples of isolated Co-complexes derived from the putative alkene-insertion intermediates of Pauson-Khand reactions. The binuclear Co-complexes are coordinated to μ-bonded, five-carbon “flyover” carbene ligands. It is proposed that the complexes result from cyclopropane fragmentation subsequent to alkene insertion. The observation of these metal complexes provides a rationale for the origin of regioselectivity in Pauson-Khand reactions of cyclopropenes. PMID:18637694

Complex multifractal nature in Mycobacterium tuberculosis genome

PubMed Central

Mandal, Saurav; Roychowdhury, Tanmoy; Chirom, Keilash; Bhattacharya, Alok; Brojen Singh, R. K.

2017-01-01

The mutifractal and long range correlation (C(r)) properties of strings, such as nucleotide sequence can be a useful parameter for identification of underlying patterns and variations. In this study C(r) and multifractal singularity function f(α) have been used to study variations in the genomes of a pathogenic bacteria Mycobacterium tuberculosis. Genomic sequences of M. tuberculosis isolates displayed significant variations in C(r) and f(α) reflecting inherent differences in sequences among isolates. M. tuberculosis isolates can be categorised into different subgroups based on sensitivity to drugs, these are DS (drug sensitive isolates), MDR (multi-drug resistant isolates) and XDR (extremely drug resistant isolates). C(r) follows significantly different scaling rules in different subgroups of isolates, but all the isolates follow one parameter scaling law. The richness in complexity of each subgroup can be quantified by the measures of multifractal parameters displaying a pattern in which XDR isolates have highest value and lowest for drug sensitive isolates. Therefore C(r) and multifractal functions can be useful parameters for analysis of genomic sequences. PMID:28440326

Complex multifractal nature in Mycobacterium tuberculosis genome

NASA Astrophysics Data System (ADS)

Mandal, Saurav; Roychowdhury, Tanmoy; Chirom, Keilash; Bhattacharya, Alok; Brojen Singh, R. K.

2017-04-01

The mutifractal and long range correlation (C(r)) properties of strings, such as nucleotide sequence can be a useful parameter for identification of underlying patterns and variations. In this study C(r) and multifractal singularity function f(α) have been used to study variations in the genomes of a pathogenic bacteria Mycobacterium tuberculosis. Genomic sequences of M. tuberculosis isolates displayed significant variations in C(r) and f(α) reflecting inherent differences in sequences among isolates. M. tuberculosis isolates can be categorised into different subgroups based on sensitivity to drugs, these are DS (drug sensitive isolates), MDR (multi-drug resistant isolates) and XDR (extremely drug resistant isolates). C(r) follows significantly different scaling rules in different subgroups of isolates, but all the isolates follow one parameter scaling law. The richness in complexity of each subgroup can be quantified by the measures of multifractal parameters displaying a pattern in which XDR isolates have highest value and lowest for drug sensitive isolates. Therefore C(r) and multifractal functions can be useful parameters for analysis of genomic sequences.

Eucommia ulmoides Oliver: A Potential Feedstock for Bioactive Products.

PubMed

Zhu, Ming-Qiang; Sun, Run-Cang

2018-06-06

Eucommia ulmoides Oliver (EUO), a traditional Chinese herb, contains a variety of bioactive chemicals, including lignans, iridoids, phenolics, steroids, terpenoids, flavonoids, etc. These bioactive chemicals possess the effective function in nourishing the liver and kidneys and regulating blood pressure. The composition of bioactive chemicals extracted from EUO vary in the different functional parts (leaves, seeds, bark, and staminate flower) and planting models. The bioactive parts of EUO are widely used as raw materials for medicine and food, powdery extracts, herbal formulations, and tinctures. These capabilities hold potential for future development and commercial exploitation of the bioactive products from EUO.

Cytotoxic constituents of Achillea clavennae from Montenegro.

PubMed

Trifunović, Snezana; Vajs, Vlatka; Juranić, Zorica; Zizak, Zeljko; Tesević, Vele; Macura, Slobodan; Milosavljević, Slobodan

2006-05-01

Examination of the aerial parts of Achillea clavennae afforded eight guaianolides (1-8), three bisabolenes (9-11), four flavonols (12-15), sesamin (lignan) and isofraxidin (coumarin). The structures of the new compounds (2, 4, 5, 7 and 10) were determined by spectroscopic methods. The antiproliferative action of 2, 8, 9 and 12 were tested to HeLa, K562 and Fem-X human cancer cell lines. Guaianolides 2 (9alpha-acetoxyartecanin) and 8 (apressin) showed significant cytotoxic effects to all tested lines and inducumenone (9) exhibited a moderate activity. The most active was flavonol centaureidin (12), already known as cytotoxic compound.

Arctigenin: a lignan from Arctium lappa.

PubMed

Gao, Haiyan; Li, Guanglei; Zhang, Junhe; Zeng, Jie

2008-07-19

The title compound {systematic name: (3R-trans)-4-[(3,4-dimethoxy-phen-yl)meth-yl]-3-[(4-hydr-oxy-3-methoxy-phen-yl)meth-yl]-4,5-dihydrofuran-2(3H)-one}, C(21)H(24)O(6), has a dibenz-yl-butyrolactone skeleton. The two aromatic rings are inclined at a dihedral angle of 68.75 (7)° with respect to each other. The lactone ring adopts an envelope conformation. A series of O-H⋯O and C-H⋯O hydrogen bonds contribute to the stabilization of the crystal packing. The absolute configuration was assigned on the basis of the published literature.

Penicillium daejeonium sp. nov., a new species isolated from a grape and schisandra fruit in Korea.

PubMed

Sang, Hyunkyu; An, Tae-Jin; Kim, Chang Sun; Choi, Young Phil; Deng, Jian-Xin; Paul, Narayan Chandra; Sung, Gi-Ho; Yu, Seung Hun

2013-08-01

Two isolates of monoverticillate Penicillium species were collected from a grape and schisandra fruit in Korea. Multigene phylogenetic analyses with the nuclear ribosomal internal transcribed spacer (ITS) region and genes encoding β-tubulin (benA) and calmodulin (cmd), as well as morphological analyses revealed that the two isolates are members of the P. sclerotiorum complex in Penicillium subgenus Aspergilloides, but different from species of the P. sclerotiorum complex. The isolates are closely related to P. cainii, P. jacksonii, and P. viticola in terms of their multigene phylogeny, but their colony and conidiophore morphologies differ from those of closely related species. The name P. daejeonium is proposed for this unclassified new species belonging to the P. sclerotiorum complex in subgenus Aspergilloides.

Exhaustive oxidation of a nickel dithiolate complex: some mechanistic insights en route to sulfate formation.

PubMed

Hosler, Erik R; Herbst, Robert W; Maroney, Michael J; Chohan, Balwant S

2012-01-21

A study of the step-wise oxidation of a Ni(II) diaminodithiolate complex through the formation of sulfate, the ultimate sulfur oxygenate, is reported. Controlled oxygenations or peroxidations of a neutral, planar, tetracoordinate, low-spin Ni(II) complex of a N(2)S(2)-donor ligand, (N,N'-dimethyl-N-N'-bis(2-mecaptoethyl)-1,3-propanediaminato) nickel(ii) (1), led to a series of sulfur oxygenates that have been isolated and characterized by ESI-MS and single-crystal X-ray diffraction. A monosulfenate complex (2) was detected by ESI-MS as a product of oxidation with one equivalent of H(2)O(2). However, this complex proved too unstable to isolate. Reaction of the dithiolate (1) with two equivalents of H(2)O(2) or one O(2) molecule leads to the formation of a monosulfinate complex (3), which was isolated and fully characterized by crystallography. The oxidation product of the monosulfinate (3) produced with either O(2) or H(2)O(2) is an interesting dimeric complex containing both sulfonate and thiolate ligands (4), this complex was fully characterized by crystallography, details of which were reported earlier by us. A disulfonate complex (7) is produced by reaction of 1 in the presence of O(2) or by reaction with exactly six equivalents of H(2)O(2). This complex was isolated and also fully characterized by crystallography. Possible intermediates in the conversion of the monosulfinate complex (3) to the disulfonate complex (7) include complexes with mixed sulfonate/sulfenate (5) or sulfonate/sulfinate (6) ligands. Complex 5, a four-oxygen adduct of 1, was not detected, but the sulfonate/sulfinate complex (6) was isolated and characterized. The oxidation chemistry of 1 is very different from that reported for other planar cis-N(2)S(2) Ni(ii) complexes including N,N'-dimethyl-N-N'-bis(2-mecaptoethyl)-1,3-ethylenediaminato) nickel(II), (8), and N,N'-bis(mercaptoethyl)-1,5-diazacyclooctane nickel(II). To address the structural aspects of the reactivity differences, the crystal structure of 8 was also determined. A comparison of the structures of planar Ni(II) complexes containing cis-dithiolate ligands, strongly suggests that the differences in reactivity are determined in part by the degree of flexibility that is allowed by the NN' chelate ring.

Genotypic and Phenotypic Characterization of Carriage and Invasive Disease Isolates of Neisseria meningitidis in Finland

PubMed Central

Saukkoriipi, Annika; Bratcher, Holly B.; Bloigu, Aini; Juvonen, Raija; Silvennoinen-Kassinen, Sylvi; Peitso, Ari; Harju, Terttu; Vainio, Olli; Kuusi, Markku; Maiden, Martin C. J.; Leinonen, Maija; Käyhty, Helena; Toropainen, Maija

2012-01-01

The relationship between carriage and the development of invasive meningococcal disease is not fully understood. We investigated the changes in meningococcal carriage in 892 military recruits in Finland during a nonepidemic period (July 2004 to January 2006) and characterized all of the oropharyngeal meningococcal isolates obtained (n = 215) by using phenotypic (serogrouping and serotyping) and genotypic (porA typing and multilocus sequence typing) methods. For comparison, 84 invasive meningococcal disease strains isolated in Finland between January 2004 and February 2006 were also analyzed. The rate of meningococcal carriage was significantly higher at the end of military service than on arrival (18% versus 2.2%; P < 0.001). Seventy-four percent of serogroupable carriage isolates belonged to serogroup B, and 24% belonged to serogroup Y. Most carriage isolates belonged to the carriage-associated ST-60 clonal complex. However, 21.5% belonged to the hyperinvasive ST-41/44 clonal complex. Isolates belonging to the ST-23 clonal complex were cultured more often from oropharyngeal samples taken during the acute phase of respiratory infection than from samples taken at health examinations at the beginning and end of military service (odds ratio [OR], 6.7; 95% confidence interval [95% CI], 2.7 to 16.4). The ST-32 clonal complex was associated with meningococcal disease (OR, 17.8; 95% CI, 3.8 to 81.2), while the ST-60 clonal complex was associated with carriage (OR, 10.7; 95% CI, 3.3 to 35.2). These findings point to the importance of meningococcal vaccination for military recruits and also to the need for an efficacious vaccine against serogroup B isolates. PMID:22135261

Enterobacter cloacae Complex Isolates Harboring blaNMC-A or blaIMI-Type Class A Carbapenemase Genes on Novel Chromosomal Integrative Elements and Plasmids

PubMed Central

Boyd, David A.; Mataseje, Laura F.; Davidson, Ross; Delport, Johannes A.; Fuller, Jeff; Hoang, Linda; Lefebvre, Brigitte; Levett, Paul N.; Roscoe, Diane L.; Willey, Barbara M.

2017-01-01

ABSTRACT Carbapenem-resistant Enterobacter cloacae complex isolates submitted to a reference laboratory from 2010 to 2015 were screened by PCR for seven common carbapenemase gene groups, namely, KPC, NDM, OXA-48, VIM, IMP, GES, and NMC-A/IMI. Nineteen of the submitted isolates (1.7%) were found to harbor Ambler class A blaNMC-A or blaIMI-type carbapenemases. All 19 isolates were resistant to at least one carbapenem but susceptible to aminoglycosides, trimethoprim-sulfamethoxazole, tigecycline, and ciprofloxacin. Most isolates (17/19) gave positive results with the Carba-NP test for phenotypic carbapenemase detection. Isolates were genetically diverse by pulsed-field gel electrophoresis macrorestriction analysis, multilocus sequence typing, and hsp60 gene analysis. The genes were found in various Enterobacter cloacae complex species; however, blaNMC-A was highly associated with Enterobacter ludwigii. Whole-genome sequencing and bioinformatics analysis revealed that all NMC-A (n = 10), IMI-1 (n = 5), and IMI-9 (n = 2) producers harbored the carbapenemase gene on EludIMEX-1-like integrative mobile elements (EcloIMEXs) located in the identical chromosomal locus. Two novel genes, blaIMI-5 and blaIMI-6, were harbored on different IncFII-type plasmids. Enterobacter cloacae complex isolates harboring blaNMC-A/IMI-type carbapenemases are relatively rare in Canada. Though mostly found integrated into the chromosome, some variants are located on plasmids that may enhance their mobility potential. PMID:28223374

Enterobacter cloacae Complex Isolates Harboring blaNMC-A or blaIMI-Type Class A Carbapenemase Genes on Novel Chromosomal Integrative Elements and Plasmids.

PubMed

Boyd, David A; Mataseje, Laura F; Davidson, Ross; Delport, Johannes A; Fuller, Jeff; Hoang, Linda; Lefebvre, Brigitte; Levett, Paul N; Roscoe, Diane L; Willey, Barbara M; Mulvey, Michael R

2017-05-01

Carbapenem-resistant Enterobacter cloacae complex isolates submitted to a reference laboratory from 2010 to 2015 were screened by PCR for seven common carbapenemase gene groups, namely, KPC, NDM, OXA-48, VIM, IMP, GES, and NMC-A/IMI. Nineteen of the submitted isolates (1.7%) were found to harbor Ambler class A bla NMC-A or bla IMI -type carbapenemases. All 19 isolates were resistant to at least one carbapenem but susceptible to aminoglycosides, trimethoprim-sulfamethoxazole, tigecycline, and ciprofloxacin. Most isolates (17/19) gave positive results with the Carba-NP test for phenotypic carbapenemase detection. Isolates were genetically diverse by pulsed-field gel electrophoresis macrorestriction analysis, multilocus sequence typing, and hsp60 gene analysis. The genes were found in various Enterobacter cloacae complex species; however, bla NMC-A was highly associated with Enterobacter ludwigii Whole-genome sequencing and bioinformatics analysis revealed that all NMC-A ( n = 10), IMI-1 ( n = 5), and IMI-9 ( n = 2) producers harbored the carbapenemase gene on EludIMEX-1-like integrative mobile elements (EcloIMEXs) located in the identical chromosomal locus. Two novel genes, bla IMI-5 and bla IMI-6 , were harbored on different IncFII-type plasmids. Enterobacter cloacae complex isolates harboring bla NMC-A/IMI -type carbapenemases are relatively rare in Canada. Though mostly found integrated into the chromosome, some variants are located on plasmids that may enhance their mobility potential. © Crown copyright 2017.

In vitro antifungal activity of silver nanoparticles against ocular pathogenic filamentous fungi.

PubMed

Xu, Yan; Gao, Chuanwen; Li, Xiaohua; He, Yi; Zhou, Lutan; Pang, Guangren; Sun, Shengtao

2013-03-01

Fungal keratitis is emerging as a major cause of vision loss in a developing country such as China because of higher incidence and the unavailability of effective antifungals. It is urgent to explore broad-spectrum antifungals to effectively suppress ocular fungal pathogens, and to develop new antifungal eye drops to combat this vision-threatening infection. The aim of this study is to investigate the antifungal activity of silver nanoparticles (nano-Ag) in comparison with that of natamycin against ocular pathogenic filamentous fungi in vitro. Susceptibility tests were performed against 216 strains of fungi isolated from patients with fungal keratitis from the Henan Eye Institute in China by broth dilution antifungal susceptibility test of filamentous fungi approved by the Clinical and Laboratory Standards Institute M38-A document. The isolates included 112 Fusarium isolates (82 Fusarium solani species complex, 20 Fusarium verticillioides species complex, and 10 Fusarium oxysporum species complex), 94 Aspergillus isolates (61 Aspergillus flavus species complex, 11 Aspergillus fumigatus species complex, 12 Aspergillus versicolor species complex, and 10 Aspergillus niger species complex), and 10 Alternaria alternata isolates. The minimum inhibitory concentration (MIC) range and mode, the MIC for 50% of the strains tested (MIC50 value), and the MIC90 value were provided for the isolates with the SPSS statistical package. MIC50 value of nano-Ag were 1, 0.5, and 0.5 μg/mL for Fusarium spp., Aspergillus spp., and Al. alternata, respectively. MIC90 values of nano-Ag were 1, 1, and 1 μg/mL for Fusarium spp., Aspergillus spp., and Al. alternata, respectively. MIC50 values of natamycin were 4, 32, and 4 μg/mL for Fusarium spp., Aspergillus spp., and Al. alternata, respectively. MIC90 values of natamycin were 8, 32, and 4 μg/mL for Fusarium spp., Aspergillus spp., and Al. alternata, respectively. Nano-Ag, relative to natamycin, exhibits potent in vitro activity against ocular pathogenic filamentous fungi.

The mate recognition protein gene mediates reproductive isolation and speciation in the Brachionus plicatilis cryptic species complex

PubMed Central

2012-01-01

Background Chemically mediated prezygotic barriers to reproduction likely play an important role in speciation. In facultatively sexual monogonont rotifers from the Brachionus plicatilis cryptic species complex, mate recognition of females by males is mediated by the Mate Recognition Protein (MRP), a globular glycoprotein on the surface of females, encoded by the mmr-b gene family. In this study, we sequenced mmr-b copies from 27 isolates representing 11 phylotypes of the B. plicatilis species complex, examined the mode of evolution and selection of mmr-b, and determined the relationship between mmr-b genetic distance and mate recognition among isolates. Results Isolates of the B. plicatilis species complex have 1–4 copies of mmr-b, each composed of 2–9 nearly identical tandem repeats. The repeats within a gene copy are generally more similar than are gene copies among phylotypes, suggesting concerted evolution. Compared to housekeeping genes from the same isolates, mmr-b has accumulated only half as many synonymous differences but twice as many non-synonymous differences. Most of the amino acid differences between repeats appear to occur on the outer face of the protein, and these often result in changes in predicted patterns of phosphorylation. However, we found no evidence of positive selection driving these differences. Isolates with the most divergent copies were unable to mate with other isolates and rarely self-crossed. Overall the degree of mate recognition was significantly correlated with the genetic distance of mmr-b. Conclusions Discrimination of compatible mates in the B. plicatilis species complex is determined by proteins encoded by closely related copies of a single gene, mmr-b. While concerted evolution of the tandem repeats in mmr-b may function to maintain identity, it can also lead to the rapid spread of a mutation through all copies in the genome and thus to reproductive isolation. The mmr-b gene is evolving rapidly, and novel alleles may be maintained and increase in frequency via asexual reproduction. Our analyses indicate that mate recognition, controlled by MMR-B, may drive reproductive isolation and allow saltational sympatric speciation within the B. plicatilis cryptic species complex, and that this process may be largely neutral. PMID:22852831

Differential susceptibility of mitochondrial complex II to inhibition by oxaloacetate in brain and heart.

PubMed

Stepanova, Anna; Shurubor, Yevgeniya; Valsecchi, Federica; Manfredi, Giovanni; Galkin, Alexander

2016-09-01

Mitochondrial Complex II is a key mitochondrial enzyme connecting the tricarboxylic acid (TCA) cycle and the electron transport chain. Studies of complex II are clinically important since new roles for this enzyme have recently emerged in cell signalling, cancer biology, immune response and neurodegeneration. Oxaloacetate (OAA) is an intermediate of the TCA cycle and at the same time is an inhibitor of complex II with high affinity (Kd~10(-8)M). Whether or not OAA inhibition of complex II is a physiologically relevant process is a significant, but still controversial topic. We found that complex II from mouse heart and brain tissue has similar affinity to OAA and that only a fraction of the enzyme in isolated mitochondrial membranes (30.2±6.0% and 56.4±5.6% in the heart and brain, respectively) is in the free, active form. Since OAA could bind to complex II during isolation, we established a novel approach to deplete OAA in the homogenates at the early stages of isolation. In heart, this treatment significantly increased the fraction of free enzyme, indicating that OAA binds to complex II during isolation. In brain the OAA-depleting system did not significantly change the amount of free enzyme, indicating that a large fraction of complex II is already in the OAA-bound inactive form. Furthermore, short-term ischemia resulted in a dramatic decline of OAA in tissues, but it did not change the amount of free complex II. Our data show that in brain OAA is an endogenous effector of complex II, potentially capable of modulating the activity of the enzyme. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Fault detection and isolation for complex system

NASA Astrophysics Data System (ADS)

Jing, Chan Shi; Bayuaji, Luhur; Samad, R.; Mustafa, M.; Abdullah, N. R. H.; Zain, Z. M.; Pebrianti, Dwi

2017-07-01

Fault Detection and Isolation (FDI) is a method to monitor, identify, and pinpoint the type and location of system fault in a complex multiple input multiple output (MIMO) non-linear system. A two wheel robot is used as a complex system in this study. The aim of the research is to construct and design a Fault Detection and Isolation algorithm. The proposed method for the fault identification is using hybrid technique that combines Kalman filter and Artificial Neural Network (ANN). The Kalman filter is able to recognize the data from the sensors of the system and indicate the fault of the system in the sensor reading. Error prediction is based on the fault magnitude and the time occurrence of fault. Additionally, Artificial Neural Network (ANN) is another algorithm used to determine the type of fault and isolate the fault in the system.

Emulsifying and foaming properties of amaranth seed protein isolates.

PubMed

Fidantsi, A; Doxastakis, G

2001-07-01

The emulsifying and foaming properties of amaranth seed protein isolates prepared by wet extraction methods, such as isoelectric precipitation and dialysis, were investigated. The various isolates differ from each other in many ways. The isolate prepared by isoelectric precipitation mainly contains the globulin but not the albumin fraction and a considerable amount of polysaccharides, while the other isolate prepared by the dialysis method contains all the globulin and albumin fractions. The protein-polysaccharide complexes enhance emulsion stability due to steric repulsion effects. Measurements of the emulsion stability show that the studied protein isolates act as effective stabilizing agents. Foam expansion is dominated by the surface activity and availability of protein in the solution, while foam stability is determined by the properties of the interfacial layer. The results show that amaranth protein isolates act as an effective foaming agent. Both foaming properties intensified from the presence of protein-polysaccharide complexes.

Association between Dietary Share of Ultra-Processed Foods and Urinary Concentrations of Phytoestrogens in the US.

PubMed

Martínez Steele, Eurídice; Monteiro, Carlos A

2017-02-28

The aim of this study was to examine the relationship between dietary contribution of ultra-processed foods and urinary phytoestrogen concentrations in the US. Participants from cross-sectional 2009-2010 National Health and Nutrition Examination Survey aged 6+ years, selected to measure urinary phytoestrogens and with one 24-h dietary recall were evaluated (2692 participants). Food items were classified according to NOVA (a name, not an acronym), a four-group food classification based on the extent and purpose of industrial food processing. Ultra-processed foods are formulations manufactured using several ingredients and a series of processes (hence "ultra-processed"). Most of their ingredients are lower-cost industrial sources of dietary energy and nutrients, with additives used for the purpose of imitating sensorial qualities of minimally processed foods or of culinary preparations of these foods. Studied phytoestrogens included lignans (enterolactone and enterodiol) and isoflavones (genistein, daidzein, O -desmethylangolensin and equol). Gaussian regression was used to compare average urinary phytoestrogen concentrations (normalized by creatinine) across quintiles of energy share of ultra-processed foods. Models incorporated survey sample weights and were adjusted for age, sex, race/ethnicity, family income, and education, among other factors. Adjusted enterodiol geometric means decreased monotonically from 60.6 in the lowest quintile to 35.1 µg/g creatinine in the highest, while adjusted enterolactone geometric means dropped from 281.1 to 200.1 across the same quintiles, respectively. No significant linear trend was observed in the association between these quintiles and isoflavone concentrations. This finding reinforces the existing evidence regarding the negative impact of ultra-processed food consumption on the overall quality of the diet and expands it to include non-nutrients such as lignans.

Association between Dietary Share of Ultra-Processed Foods and Urinary Concentrations of Phytoestrogens in the US

PubMed Central

Martínez Steele, Eurídice; Monteiro, Carlos A.

2017-01-01

The aim of this study was to examine the relationship between dietary contribution of ultra-processed foods and urinary phytoestrogen concentrations in the US. Participants from cross-sectional 2009–2010 National Health and Nutrition Examination Survey aged 6+ years, selected to measure urinary phytoestrogens and with one 24-h dietary recall were evaluated (2692 participants). Food items were classified according to NOVA (a name, not an acronym), a four-group food classification based on the extent and purpose of industrial food processing. Ultra-processed foods are formulations manufactured using several ingredients and a series of processes (hence “ultra-processed”). Most of their ingredients are lower-cost industrial sources of dietary energy and nutrients, with additives used for the purpose of imitating sensorial qualities of minimally processed foods or of culinary preparations of these foods. Studied phytoestrogens included lignans (enterolactone and enterodiol) and isoflavones (genistein, daidzein, O-desmethylangolensin and equol). Gaussian regression was used to compare average urinary phytoestrogen concentrations (normalized by creatinine) across quintiles of energy share of ultra-processed foods. Models incorporated survey sample weights and were adjusted for age, sex, race/ethnicity, family income, and education, among other factors. Adjusted enterodiol geometric means decreased monotonically from 60.6 in the lowest quintile to 35.1 µg/g creatinine in the highest, while adjusted enterolactone geometric means dropped from 281.1 to 200.1 across the same quintiles, respectively. No significant linear trend was observed in the association between these quintiles and isoflavone concentrations. This finding reinforces the existing evidence regarding the negative impact of ultra-processed food consumption on the overall quality of the diet and expands it to include non-nutrients such as lignans. PMID:28264475

Extraction and Separation of Active Ingredients in Schisandra chinensis (Turcz.) Baill and the Study of their Antifungal Effects

PubMed Central

Liu, Jun; Zhang, Jie; Guo, Wei; Xiao, Weilie; Yao, Yuncong

2016-01-01

Schisandra chinensis extracts (SEs) have traditionally been used as an oriental medicine for the treatment of various human diseases, however, their further application in the biocontrol of plant disease remains poorly understood. This study was conducted to develop eco-friendly botanical pesticides from extracts of S. chinensis and assess whether they could play a key role in plant disease defense. Concentrated active fractions (SE-I, SE-II, and SE-III) were obtained from S. chinensis via specific extraction and separation. Then, lignan-like substances, such as Schisanhenol B, were detected via High-Performance Liquid Chromatography-ElectroSpray Ionization-Mass Spectrometry (HPLC-ESI-MS) analyses of the active fractions. Moreover, the results from biological tests on colony growth inhibition and spore germination indicated that SE-I, SE-II, and SE-III could inhibit hyphal growth and spore generation of three important plant pathogenic fungi (Monilinia fructicola, Fusarium oxysporum, and Botryosphaeria dothidea). The study of the mechanisms of resistant fungi revealed that the oxidation resistance system, including reactive oxygen species (ROS), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD), was activated. The expression of genes related to defense, such as pathogenesis-related protein (PR4), α-farnesene synthase (AFS), polyphenol oxidase (PPO), and phenylalanine ammonia lyase (PAL) were shown to be up-regulated after treatment with SEs, which suggested an increase in apple immunity and that fruits were induced to effectively defend against the infection of pathogenic fungi (B. dothidea). This study revealed that SEs and their lignans represent promising resources for the development of safe, effective, and multi-targeted agents against pathogenic fungi. PMID:27152614

Wounding response in xylem of Scots pine seedlings shows wide genetic variation and connection with the constitutive defence of heartwood.

PubMed

Harju, Anni M; Venäläinen, Martti; Laakso, Tapio; Saranpää, Pekka

2009-01-01

In this greenhouse experiment, 3-year-old Scots pine (Pinus sylvestris L.) seedlings were wounded by drilling holes through the stem. In the xylem next to the wound, the concentration of resin acids (RAC) increased, and the production of extractives typical for heartwood (stilbenes) and knotwood (stilbenes and lignans) of mature trees was induced. The induced stilbenes were pinosylvin (PS) and pinosylvin monomethyl ether (PSM), and the lignans nortrachelogenin (NTG) and matairesinol (MR). There was positive phenotypic correlation between concentrations of the different extractives. Except for the RAC, the extractive concentrations showed no correlation with the size of the seedlings. The treated seedlings belonged to half-sib families, which enabled the estimation of the genetic parameters for the response variables. The proportion of heritable variation (heritability, h(2)) in the concentration of PS, NTG and MR varied between 0.71 and 1.03, whereas for PSM and RAC the heritability was lower (0.35 and 0.31). Genetic correlation was significant between PS and PSM (r = 0.55, P = 0.018), and between NTG and MR (r = 0.50, P = 0.033). Heritabilities were also estimated on the basis of the regression of the offspring on their mothers h(2)(0P). These estimates were assessed for the concentration of PS, PSM and RAC in the wound response area of the seedlings and correspondingly in the heartwood of their mothers. The heritability was highest for the concentration of PS h(2)(0P). The findings of this study support the suggestion that the wounding of Scots pine seedlings may facilitate the development of an early testing method for breeding heartwood durability.

Characterisation of phenolic compounds by HPLC-TOF/IT/MS in buds and open flowers of 'Chemlali' olive cultivar.

PubMed

Taamalli, Amani; Abaza, Leila; Arráez Román, David; Segura Carretero, Antonio; Fernández Gutiérrez, Alberto; Zarrouk, Mokhtar; Nabil, Ben Youssef

2013-01-01

Plant phenolics are secondary metabolites that constitute one of the most widely occurring groups of phytochemicals that play several important functions in plants. In olive (Olea europaea L), there is not enough information about the occurrence of these compounds in buds and flowers. To conduct a comprehensive characterisation of buds and open flowers from the olive cultivar 'Chemlali'. The polar fraction of buds and open flowers was extracted using solid-liquid extraction with hydro-alcoholic solvent. Then extracts were analysed using high performance liquid chromatography (HPLC) coupled to electrospray ionisation time-of-flight mass spectrometry (ESI/TOF/MS) and electrospray ionisation ion-trap tandem mass spectrometry (ESI/IT/MS²) operating in negative ion mode. Phenolic compounds from different classes including secoiridoids, flavonoids, simple phenols, cinnamic acid derivatives and lignans were tentatively identified in both extracts. Qualitatively, no significant difference was observed between flower buds and open flowers extracts. However, quantitatively the secoiridoids presented higher percentage of total phenols in open flowers (41.7%) than in flower buds (30.5%) in contrast to flavonoids, which decreased slightly from 38.1 to 26.7%. Cinnamic acid derivatives and simple phenols did not show any change. Lignans presented the lowest percentage in both extracts with an increase during the development of the flower bud to open flower. The HPLC-TOF/IT/MS allowed the characterisation, for the first time, of the phenolic profile of extracts of 'Chemlali' olive buds and open flowers, proving to be a very useful technique for the characterisation and structure elucidation of phenolic compounds. Copyright © 2013 John Wiley & Sons, Ltd.

Effect of infrared heating on the formation of sesamol and quality of defatted flours from Sesamum indicum L.

PubMed

Kumar, C Mahendra; Appu Rao, A G; Singh, Sridevi Annapurna

2009-01-01

Infrared (IR) heating offers several advantages over conventional heating in terms of heat transfer efficiency, compactness of equipment, and quality of the products. Roasting of sesame seeds degrades the lignan sesamolin to sesamol, which increases the oxidative stability of sesame oil synergistically with tocopherols. IR (near infrared, 1.1 to 1.3 microm, 6 kW power) roasting conditions were optimized for the conversion of sesamolin to sesamol. The resultant oil was evaluated for sesamol and tocopherol content as well as oxidative stability. The defatted flours were evaluated for their nutritional content and functionality. IR roasting of sesame seeds at 200 degrees C for 30 min increased the efficiency of conversion of sesamolin to sesamol (51% to 82%) compared to conventional heating. The gamma-tocopherol content decreased by 17% and 25% in oils treated at 200 and 220 degrees C for 30 min, respectively. There were no significant differences in the tocopherol content and oxidative stability of the oil. Methionine and cysteine content of the flours remained unchanged due to roasting. The functional properties of defatted flours obtained from either IR roasted or conventionally roasted sesame seeds remained the same. Practical Applications: Sesame oil is stable to oxidation compared to other vegetable oils. This stability can be attributed to the presence of tocopherols and the formation of sesamol, the thermal degradation product of sesamolin-a lignan present in sesame. Roasting of sesame seeds before oil extraction increases sesamol content which is a more potent antioxidant than the parent molecule. The conversion efficiency of sesamolin to sesamol is increased by 31% by infrared roasting of seeds compared to electric drum roasting. This can be used industrially to obtain roasted oil with greater oxidative stability.

Secoisolariciresinol diglycoside, a flaxseed lignan, exerts analgesic effects in a mouse model of type 1 diabetes: Engagement of antioxidant mechanism.

PubMed

Hu, Pei; Mei, Qi-Yong; Ma, Li; Cui, Wu-Geng; Zhou, Wen-Hua; Zhou, Dong-Sheng; Zhao, Qing; Xu, Dong-Ying; Zhao, Xin; Lu, Qin; Hu, Zhen-Yu

2015-11-15

Peripheral painful neuropathy is one of the most common complications in diabetes and necessitates improved treatment. Secoisolariciresinol diglycoside (SDG), a predominant lignan in flaxseed, has been shown in our previous studies to exert antidepressant-like effect. As antidepressant drugs are clinically used to treat chronic neuropathic pain, this work aimed to investigate the potential analgesic efficacy of SDG against diabetic neuropathic pain in a mouse model of type 1 diabetes. We subjected mice to diabetes by a single intraperitoneal (i.p.) injection of streptozotocin (STZ, 200 mg/kg), and Hargreaves test or von Frey test was used to assess thermal hyperalgesia or mechanical allodynia, respectively. Chronic instead of acute SDG treatment (3, 10 or 30 mg/kg, p.o., twice per day for three weeks) ameliorated thermal hyperalgesia and mechanical allodynia in diabetic mice, and these analgesic actions persisted about three days when SDG treatment was terminated. Although chronic treatment of SDG to diabetic mice did not impact on the symptom of hyperglycemia, it greatly attenuated excessive oxidative stress in sciatic nerve and spinal cord tissues, and partially counteracted the condition of weight decrease. Furthermore, the analgesic actions of SDG were abolished by co-treatment with the reactive oxygen species donor tert-butyl hydroperoxide (t-BOOH), but potentiated by the reactive oxygen species scavenger phenyl-N-tert-butylnitrone (PBN). These findings indicate that chronic SDG treatment can correct neuropathic hyperalgesia and allodynia in mice with type 1 diabetes. Mechanistically, the analgesic actions of SDG in diabetic mice may be associated with its antioxidant activity. Copyright © 2015. Published by Elsevier B.V.

Flaxseed and pure secoisolariciresinol diglucoside, but not flaxseed hull, reduce human breast tumor growth (MCF-7) in athymic mice.

PubMed

Chen, Jianmin; Saggar, Jasdeep K; Corey, Paul; Thompson, Lilian U

2009-11-01

Previous studies have shown that dietary flaxseed (FS) can reduce the growth of established human breast tumors in athymic mice with low circulating estrogen concentrations. In this study, we determined the effect of FS compared with pure lignan at the level it is present in FS [secoisolariciresinol diglucoside (SDG)] and to the lignan-rich fraction [FS hull (FH)] on human breast tumor growth and their potential mechanisms of action. Ovariectomized, athymic mice, each with an implanted 17 beta-estradiol (E2) pellet (0.36 mg), were injected with human estrogen receptor (ER) positive breast cancer cells (MCF-7). When tumors were established, the E2 pellet was removed. Mice were fed either the control basal diet (BD), FS (100 g/kg diet), SDG (1 g/kg diet), or FH (18 g/kg diet) for 8 wk. Compared with the BD, FS and SDG significantly decreased the palpable tumor size, but effects of FS, SDG, and FH did not differ from one another. All treatments significantly inhibited cell proliferation, but only FS and SDG induced significantly higher apoptosis. Both FS and SDG significantly decreased mRNA expressions of Bcl2, cyclin D1, pS2, ERalpha, and ERbeta, epidermal growth factor receptor, and insulin-like growth factor receptor. FS also reduced human epidermal growth factor receptor 2 mRNA and SDG decreased phospho-specific mitogen-activated protein kinase expression. FH did not significantly reduce these biomarkers. In conclusion, pure SDG has a similar effect as FS in reducing tumor growth and in mechanisms of action, including downregulating ER- and growth factor-mediated cell signaling. The lesser effects of FH indicate a need for a higher dose to be more effective.

KIRKIA ACUMINATA OLIV.: A REVIEW OF ITS ETHNOBOTANY AND PHARMACOLOGY

PubMed Central

Maroyi, Alfred

2017-01-01

Background: Local communities in sub-Saharan Africa have a long history of medicinal plant usage. Like in other parts of the developing world, rural and urban communities are still dependent on herbal medicines for primary health care, and the use of herbal medicines is still an integral part of their daily life and socio-cultural life style. The objective of this paper is to summarise information on the ethnobotany and pharmacology of Kirkia acuminata Oliv. throughout its distributional range. Materials and Methods: The information documented in this article is derived from books, theses, scientific journals and reports obtained from library collections, Scopus, Pubmed, MEDLINE, ISI Web of Science, Google Scholar and Science Direct. Results: Kirkia acuminata is the most known and widely distributed Kirkia species in the genus and is one of the most popular and promising plant resources due to its several beneficial uses. Kirkia acuminata is used to treat abdominal pains, backache, cholera, constipation, cough, diarrhea, dysentery, snake bites, toothache and wounds. Other applications include its use as charcoal; hedge, ornamental or shade; stock feed, timber and source of water during drought periods. Preliminary phytochemical assessment of roots and stem bark of K. acuminata showed presence of lignans, neo-lignans, nor-carotinoids and other compounds. The extracts of K. acuminata exhibited antibacterial and antimycobacterial activities. These phytochemical compounds may be responsible for the medicinal uses and biological activities demonstrated by K. acuminata. Conclusion: Detailed research is required aimed at exploring mode of action of bioactive compounds of Kirkia acuminata that are responsible for the documented pharmacological effects. Kirkia acuminata is an important plant species that has potential to contribute to the primary health care and livelihood improvement of local communities in the geographical areas where it is indigenous and found in abundance. PMID:28573238

Inverse association between habitual polyphenol intake and incidence of cardiovascular events in the PREDIMED study.

PubMed

Tresserra-Rimbau, A; Rimm, E B; Medina-Remón, A; Martínez-González, M A; de la Torre, R; Corella, D; Salas-Salvadó, J; Gómez-Gracia, E; Lapetra, J; Arós, F; Fiol, M; Ros, E; Serra-Majem, L; Pintó, X; Saez, G T; Basora, J; Sorlí, J V; Martínez, J A; Vinyoles, E; Ruiz-Gutiérrez, V; Estruch, R; Lamuela-Raventós, R M

2014-06-01

Epidemiologic and biological evidence supports an inverse association between polyphenol consumption and the risk of cardiovascular disease (CVD). However, no previous studies have prospectively evaluated the relationship between polyphenol intake and the incidence of CVD in such a comprehensive way. The aim was to evaluate the association between intakes of total polyphenol and polyphenol subgroups, and the risk of major cardiovascular events (myocardial infarction, stroke or death from cardiovascular causes) in the PREDIMED study. The present work is an observational study within the PREDIMED trial. Over an average of 4.3 years of follow-up, there were 273 confirmed cases of CVD among the 7172 participants (96.3%) who completed a validated 137-item food frequency questionnaire (FFQ) at baseline. Polyphenol consumption was calculated by matching food consumption data from the FFQ with the Phenol-Explorer database on polyphenol content of each reported food. After multivariate adjustment, a 46% reduction in risk of CVD risk was observed comparing Q5 vs. Q1 of total polyphenol intake (HR = 0.54; 95% confidence interval [CI] = 0.33-0.91; P-trend = 0.04). The polyphenols with the strongest inverse associations were flavanols (HR = 0.40; CI 0.23-0.72; P-trend = 0.003), lignans (HR = 0.51; CI 0.30-0.86; P-trend = 0.007), and hydroxybenzoic acids (HR = 0.47; CI 0.26-0.86; P-trend 0.02). Greater intake of polyphenols, especially from lignans, flavanols, and hydroxybenzoic acids, was associated with decreased CVD risk. Clinical trials are needed to confirm this effect and establish accurate dietary recommendations. Copyright © 2014 Elsevier B.V. All rights reserved.

Association between Polyphenol Intake and Hypertension in Adults and Older Adults: A Population-Based Study in Brazil

PubMed Central

Miranda, Andreia Machado; Steluti, Josiane; Fisberg, Regina Mara; Marchioni, Dirce Maria

2016-01-01

Background/Objective Hypertension is an important risk factor for cardiovascular disease, and diet has been identified as a modifiable factor for preventing and controlling hypertension. Besides, epidemiological studies have suggested an inverse association between polyphenol intake and cardiovascular diseases. The aim of this study was to evaluate the association between the intake of polyphenols and hypertension in a general population of Sao Paulo. Methods Data came from the ‘Health Survey of Sao Paulo (ISA-Capital)’ among 550 adults and older adults in Sao Paulo, Brazil. Diet was assessed by two 24-hour dietary recalls (24HR). Usual intakes were calculated using the Multiple Source Method. Polyphenol intake was calculated by matching food consumption data from the 24HR with the Phenol-Explorer database. The associations between the hypertension and tertiles of the total and classes of polyphenols intake were tested by multivariate logistic regression analysis. Results After multivariate adjustment for potential confounding factors the findings showed an inverse and linearly association between the hypertension and highest tertiles of tyrosols (OR = 0.33; 95%CI 0.18, 0.64), alkylphenols (OR = 0.45; 95%CI 0.23, 0.87), lignans (OR = 0.49; 95%CI 0.25, 0.98), as well as stilbenes (OR = 0.60; 95%CI 0.36, 0.98), and other polyphenols (OR = 0.33; 95%CI 0.14, 0.74). However, total polyphenol intake, and phenolic acids were significantly associated only in the middle tertile with hypertension and flavonoids were not significant associated. Conclusion There is an inverse and linearly association between the highest tertile of some classes of polyphenols, such as, tyrosols, alkylphenols, lignans, stilbenes, other polyphenols and hypertension. PMID:27792767

Arctigenin, a natural lignan compound, induces G0/G1 cell cycle arrest and apoptosis in human glioma cells.

PubMed

Maimaitili, Aisha; Shu, Zunhua; Cheng, Xiaojiang; Kaheerman, Kadeer; Sikandeer, Alifu; Li, Weimin

2017-02-01

The aim of the current study was to investigate the anticancer potential of arctigenin, a natural lignan compound, in malignant gliomas. The U87MG and T98G human glioma cell lines were treated with various concentrations of arctigenin for 48 h and the effects of arctigenin on the aggressive phenotypes of glioma cells were assessed. The results demonstrated that arctigenin dose-dependently inhibited the growth of U87MG and T98G cells, as determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and bromodeoxyuridine incorporation assays. Arctigenin exposure also induced a 60-75% reduction in colony formation compared with vehicle-treated control cells. However, arctigenin was not observed to affect the invasiveness of glioma cells. Arctigenin significantly increased the proportion of cells in the G 0 /G 1 phase and reduced the number of cells in the S phase, as compared with the control group (P<0.05). Western blot analysis demonstrated that arctigenin increased the expression levels of p21, retinoblastoma and p53 proteins, and significantly decreased the expression levels of cyclin D1 and cyclin-dependent kinase 4 proteins. Additionally, arctigenin was able to induce apoptosis in glioma cells, coupled with increased expression levels of cleaved caspase-3 and the pro-apoptotic BCL2-associated X protein. Furthermore, arctigenin-induced apoptosis was significantly suppressed by the pretreatment of cells with Z-DEVD-FMK, a caspase-3 inhibitor. In conclusion, the results suggest that arctigenin is able to inhibit cell proliferation and may induce apoptosis and cell cycle arrest at the G 0 /G 1 phase in glioma cells. These results warrant further investigation of the anticancer effects of arctigenin in animal models of gliomas.

Arctigenin, a natural lignan compound, induces G0/G1 cell cycle arrest and apoptosis in human glioma cells

PubMed Central

Maimaitili, Aisha; Shu, Zunhua; Cheng, Xiaojiang; Kaheerman, Kadeer; Sikandeer, Alifu; Li, Weimin

2017-01-01

The aim of the current study was to investigate the anticancer potential of arctigenin, a natural lignan compound, in malignant gliomas. The U87MG and T98G human glioma cell lines were treated with various concentrations of arctigenin for 48 h and the effects of arctigenin on the aggressive phenotypes of glioma cells were assessed. The results demonstrated that arctigenin dose-dependently inhibited the growth of U87MG and T98G cells, as determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and bromodeoxyuridine incorporation assays. Arctigenin exposure also induced a 60–75% reduction in colony formation compared with vehicle-treated control cells. However, arctigenin was not observed to affect the invasiveness of glioma cells. Arctigenin significantly increased the proportion of cells in the G0/G1 phase and reduced the number of cells in the S phase, as compared with the control group (P<0.05). Western blot analysis demonstrated that arctigenin increased the expression levels of p21, retinoblastoma and p53 proteins, and significantly decreased the expression levels of cyclin D1 and cyclin-dependent kinase 4 proteins. Additionally, arctigenin was able to induce apoptosis in glioma cells, coupled with increased expression levels of cleaved caspase-3 and the pro-apoptotic BCL2-associated X protein. Furthermore, arctigenin-induced apoptosis was significantly suppressed by the pretreatment of cells with Z-DEVD-FMK, a caspase-3 inhibitor. In conclusion, the results suggest that arctigenin is able to inhibit cell proliferation and may induce apoptosis and cell cycle arrest at the G0/G1 phase in glioma cells. These results warrant further investigation of the anticancer effects of arctigenin in animal models of gliomas. PMID:28356992

ELECTROPHORETIC MOBILITY OF MYCOBACTERIUM AVIUM COMPLEX ORGANISMS

EPA Science Inventory

The electrophoretic mobilities (EPMs) of thirty Mycobacterium avium Complex (MAC) organisms isolated from clinical and environmental sources were measured in 9.15 mM KH2PO4 buffered water. The EPMs of fifteen clinical isolates ranged from -1.9 to -5.0 µm cm V^-1 ...

ELECTROPHORETIC MOBILITY OF MYCOBACTERIUM AVIUM COMPLEX ORGANISMS

EPA Science Inventory

The electrophoretic mobilities (EPMs) of thirty Mycobacterium avium Complex (MAC) organisms were measured. The EPMs of fifteen clinical isolates ranged from -1.9 to -5.0 µm cm V^-1s^-1, and the EPMs of fifteen environmental isolates ranged from -1...

Closed genomes of seven histophilus somni isolates from beef calves with bovine respiratory disease complex

USDA-ARS?s Scientific Manuscript database

Histophilus somni is a fastidious gram-negative opportunistic pathogenic Pasteurellacea that affects multiple organ systems and is one of the principle bacterial species contributing to bovine respiratory disease complex (BRDC) in feed yard cattle. Here we present seven closed genomes isolated from...

Staphylococcus argenteus from rabbits in Thailand.

PubMed

Indrawattana, Nitaya; Pumipuntu, Natapol; Suriyakhun, Nawarat; Jangsangthong, Arunee; Kulpeanprasit, Suphang; Chantratita, Narisara; Sookrung, Nitat; Chaicumpa, Wanpen; Buranasinsup, Shutipen

2018-06-21

Staphylococcus argenteus, a novel species of the genus Staphylococcus or a member of the S. aureus complex, is closely related to S. aureus and is usually misidentified. In this study, the presence of S. argenteus in isolated S. aureus was investigated in 67 rabbits with abscess lesions during 2014-2016. Among 19 S. aureus complex isolates, three were confirmed to be S. argenteus by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, nonribosomal peptide synthetase gene amplification, and multilocus sequence type. All S. aureus complex isolates, including the S. aureus isolates, were examined for their antimicrobial resistance phenotype by disk diffusion and for their resistance genotype by PCR assays. Among the S. argenteus isolates, one was susceptible to all antimicrobial drugs and the other two were resistant to penicillin and doxycycline. In contrast, most S. aureus isolates were resistant to penicillin (37.5%), and gentamicin (12.5%). Moreover, S. aureus isolates harbored the blaZ, mecA, aacA-aphD, and mrs(A) as well as mutations of gyrA and grlA, but S. argenteus isolates carried solely the blaZ. S. argenteus isolates were investigated for enterotoxin (sea-sed) and virulence genes by PCR. One isolate carried sea, sec, and sed, whereas the other two isolates carried only sea or sed. No isolate carried seb and see. All three S. argenteus isolates carried hla, hlb, and clfA, followed by pvl, whereas coa, spa (IgG-binding region), and spa (x region) were not detected in the three isolates. This paper presents the first identification of S. argenteus from rabbits in Thailand. S. argenteus might be pathogenic because the isolates carried virulence genes. Moreover, antimicrobial resistance was observed. Investigations of this new bacterial species should be conducted in other animal species as well as in humans. © 2018 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

Mouse Liver Mitochondria Isolation, Size Fractionation, and Real-time MOMP Measurement.

PubMed

Renault, Thibaud T; Luna-Vargas, Mark P A; Chipuk, Jerry E

2016-08-05

The mitochondrial pathway of apoptosis involves a complex interplay between dozens of proteins and lipids, and is also dependent on the shape and size of mitochondria. The use of cellular models in past studies has not been ideal for investigating how the complex multi-factor interplay regulates the molecular mechanisms of mitochondrial outer membrane permeabilization (MOMP). Isolated systems have proven to be a paradigm to deconstruct MOMP into individual steps and to study the behavior of each subset of MOMP regulators. In particular, isolated mitochondria are key to in vitro studies of the BCL-2 family proteins, a complex family of pro-survival and pro-apoptotic proteins that directly control the mitochondrial pathway of apoptosis (Renault et al ., 2013). In this protocol, we describe three complementary procedures for investigating in real-time the effects of MOMP regulators using isolated mitochondria. The first procedure is "Liver mitochondria isolation" in which the liver is dissected from mice to obtain mitochondria. "Mitochondria labeling with JC-1 and size fractionation" is the second procedure that describes a method to label, fractionate by size and standardize subpopulations of mitochondria. Finally, the "Real-time MOMP measurements" protocol allows to follow MOMP in real-time on isolated mitochondria. The aforementioned procedures were used to determine in vitro the role of mitochondrial membrane shape at the level of isolated cells and isolated mitochondria (Renault et al ., 2015).

Isolation, subunit composition and interaction of the NDH-1 complexes from Thermosynechococcus elongatus BP-1.

PubMed

Zhang, Pengpeng; Battchikova, Natalia; Paakkarinen, Virpi; Katoh, Hirokazu; Iwai, Masako; Ikeuchi, Masahiko; Pakrasi, Himadri B; Ogawa, Teruo; Aro, Eva-Mari

2005-09-01

NDH (NADH-quinone oxidoreductase)-1 complexes in cyanobacteria have specific functions in respiration and cyclic electron flow as well as in active CO2 uptake. In order to isolate NDH-1 complexes and to study complex-complex interactions, several strains of Thermosynechococcus elongatus were constructed by adding a His-tag (histidine tag) to different subunits of NDH-1. Two strains with His-tag on CupA and NdhL were successfully used to isolate NDH-1 complexes by one-step Ni2+ column chromatography. BN (blue-native)/SDS/PAGE analysis of the proteins eluted from the Ni2+ column revealed the presence of three complexes with molecular masses of about 450, 300 and 190 kDa, which were identified by MS to be NDH-1L, NDH-1M and NDH-1S respectively, previously found in Synechocystis sp. PCC 6803. A larger complex of about 490 kDa was also isolated from the NdhL-His strain. This complex, designated 'NDH-1MS', was composed of NDH-1M and NDH-1S. NDH-1L complex was recovered from WT (wild-type) cells of T. elongatus by Ni2+ column chromatography. NdhF1 subunit present only in NDH-1L has a sequence of -HHDHHSHH- internally, which appears to have an affinity for the Ni2+ column. NDH-1S or NDH-1M was not recovered from WT cells by chromatography of this kind. The BN/SDS/PAGE analysis of membranes solubilized by a low concentration of detergent indicated the presence of abundant NDH-1MS, but not NDH-1M or NDH-1S. These results clearly demonstrated that NDH-1S is associated with NDH-1M in vivo.

Whole-Genome Characterization of Epidemic Neisseria meningitidis Serogroup C and Resurgence of Serogroup W, Niger, 2015.

PubMed

Kretz, Cecilia B; Retchless, Adam C; Sidikou, Fati; Issaka, Bassira; Ousmane, Sani; Schwartz, Stephanie; Tate, Ashley H; Pana, Assimawè; Njanpop-Lafourcade, Berthe-Marie; Nzeyimana, Innocent; Nse, Ricardo Obama; Deghmane, Ala-Eddine; Hong, Eva; Brynildsrud, Ola Brønstad; Novak, Ryan T; Meyer, Sarah A; Oukem-Boyer, Odile Ouwe Missi; Ronveaux, Olivier; Caugant, Dominique A; Taha, Muhamed-Kheir; Wang, Xin

2016-10-01

In 2015, Niger reported the largest epidemic of Neisseria meningitidis serogroup C (NmC) meningitis in sub-Saharan Africa. The NmC epidemic coincided with serogroup W (NmW) cases during the epidemic season, resulting in a total of 9,367 meningococcal cases through June 2015. To clarify the phylogenetic association, genetic evolution, and antibiotic determinants of the meningococcal strains in Niger, we sequenced the genomes of 102 isolates from this epidemic, comprising 81 NmC and 21 NmW isolates. The genomes of 82 isolates were completed, and all 102 were included in the analysis. All NmC isolates had sequence type 10217, which caused the outbreaks in Nigeria during 2013-2014 and for which a clonal complex has not yet been defined. The NmC isolates from Niger were substantially different from other NmC isolates collected globally. All NmW isolates belonged to clonal complex 11 and were closely related to the isolates causing recent outbreaks in Africa.

Affinity proteomics to study endogenous protein complexes: Pointers, pitfalls, preferences and perspectives

PubMed Central

LaCava, John; Molloy, Kelly R.; Taylor, Martin S.; Domanski, Michal; Chait, Brian T.; Rout, Michael P.

2015-01-01

Dissecting and studying cellular systems requires the ability to specifically isolate distinct proteins along with the co-assembled constituents of their associated complexes. Affinity capture techniques leverage high affinity, high specificity reagents to target and capture proteins of interest along with specifically associated proteins from cell extracts. Affinity capture coupled to mass spectrometry (MS)-based proteomic analyses has enabled the isolation and characterization of a wide range of endogenous protein complexes. Here, we outline effective procedures for the affinity capture of protein complexes, highlighting best practices and common pitfalls. PMID:25757543

Dominance of international 'high-risk clones' among metallo-β-lactamase-producing Pseudomonas aeruginosa in the UK.

PubMed

Wright, Laura L; Turton, Jane F; Livermore, David M; Hopkins, Katie L; Woodford, Neil

2015-01-01

Carbapenem-resistant isolates of Pseudomonas aeruginosa producing metallo-β-lactamases (MBLs) are increasingly reported worldwide and often belong to particular 'high-risk clones'. This study aimed to characterize a comprehensive collection of MBL-producing P. aeruginosa isolates referred to the UK national reference laboratory from multiple UK laboratories over a 10 year period. Isolates were referred to the UK national reference laboratory between 2003 and 2012 for investigation of resistance mechanisms and/or outbreaks. MBL genes were detected by PCR. Typing was carried out by nine-locus variable-number tandem repeat (VNTR) analysis and MLST. MBL-producing P. aeruginosa isolates were referred from 267 source patients and 89 UK laboratories. The most common isolation sites were urine (24%), respiratory (18%), wounds (17%) and blood (13%). VIM-type MBLs predominated (91% of all MBLs found), but a few IMP- and NDM-type enzymes were also identified. Diverse VNTR types were seen, but 86% of isolates belonged to six major complexes. MLST of representative isolates from each complex showed that they corresponded to STs 111, 233, 235, 357, 654 and 773, respectively. Isolates belonging to these complexes were received from between 9 and 25 UK referring laboratories each. The incidence of MBL-producing P. aeruginosa is increasing in the UK. The majority of these isolates belong to several 'high-risk clones', which have been previously reported internationally as host clones of MBLs. © Crown copyright 2014.

[A preparative method for isolating the synaptonemal complexes from mammalian spermatocytes].

PubMed

Dadashev, S Ia; Bogdanov, Iu F; Gorach, G G; Kolomiets, O L; Karpova, O I

1993-01-01

A method of isolation of synaptonemal complexes (SC) from mouse, rat and Syrian hamster spermatocytes is described. A fraction of pachytene spermatocyte nuclei was obtained by centrifugation of the testis homogenate in stepwise sucrose gradient and then lysed. The resulting chromatine was hydrolysed with DNAse II, and a fraction of isolated SCs was obtained by ultracentrifugation of the hydrolysate. The method can be applied for obtaining the SC fraction from spermatocytes sufficient for cytological, biochemical and molecular biology studies.

Isolated lateral collateral ligament complex injury in rock climbing and Brazilian Jiu-jitsu.

PubMed

Davis, Bryan A; Hiller, Lucas P; Imbesi, Steven G; Chang, Eric Y

2015-08-01

We report two occurrences of high-grade tears of the lateral collateral ligament complex (LCLC), consisting of the anterolateral ligament (ALL) and fibular collateral ligament (FCL). One injury occurred in a rock climber and the other in a martial artist. Increasing awareness of isolated injuries of the LCLC will allow for appropriate diagnosis and management. We review and discuss the anatomy of the LCLC, the unique mechanism of isolated injury, as well as physical and imaging examination findings.

Characterization of Mycosphaerellaceae species associated with citrus greasy spot in Panama and Spain.

PubMed

Aguilera-Cogley, Vidal Antonio; Berbegal, Mónica; Català, Santiago; Brentu, Francis Collison; Armengol, Josep; Vicent, Antonio

2017-01-01

Greasy spot of citrus, caused by Zasmidium citri-griseum (= Mycosphaerella citri), is widely distributed in the Caribbean Basin, inducing leaf spots, premature defoliation, and yield loss. Greasy spot-like symptoms were frequently observed in humid citrus-growing regions in Panama as well as in semi-arid areas in Spain, but disease aetiology was unknown. Citrus-growing areas in Panama and Spain were surveyed and isolates of Mycosphaerellaceae were obtained from citrus greasy spot lesions. A selection of isolates from Panama (n = 22) and Spain (n = 16) was assembled based on their geographical origin, citrus species, and affected tissue. The isolates were characterized based on multi-locus DNA (ITS and EF-1α) sequence analyses, morphology, growth at different temperatures, and independent pathogenicity tests on the citrus species most affected in each country. Reference isolates and sequences were also included in the analysis. Isolates from Panama were identified as Z. citri-griseum complex, and others from Spain attributed to Amycosphaerella africana. Isolates of the Z. citri-griseum complex had a significantly higher optimal growth temperature (26.8°C) than those of A. africana (19.3°C), which corresponded well with their actual biogeographical range. The isolates of the Z. citri-griseum complex from Panama induced typical greasy spot symptoms in 'Valencia' sweet orange plants and the inoculated fungi were reisolated. No symptoms were observed in plants of the 'Ortanique' tangor inoculated with A. africana. These results demonstrate the presence of citrus greasy spot, caused by Z. citri-griseum complex, in Panama whereas A. africana was associated with greasy spot-like symptoms in Spain.

Photochemistry and reactivity of the phenyl radical-water system: a matrix isolation and computational study.

PubMed

Mardyukov, Artur; Crespo-Otero, Rachel; Sanchez-Garcia, Elsa; Sander, Wolfram

2010-08-02

The reaction of the phenyl radical 1 with water has been investigated by using matrix isolation spectroscopy and quantum chemical calculations. The primary thermal product of the reaction between 1 and water is a weakly bound complex stabilized by an OH...pi interaction. This complex is photolabile, and visible-light irradiation (lambda>420 nm) results in hydrogen atom transfer from water to radical 1 and the formation of a highly labile complex between benzene and the OH radical. This complex is stable under the conditions of matrix isolation, however, continuous irradiation with lambda>420 nm light results in the complete destruction of the aromatic system and formation of an acylic unsaturated ketene. The mechanisms of all reaction steps are discussed in the light of ab initio and DFT calculations.

Epidemiology, Antifungal Susceptibility, and Pathogenicity of Candida africana Isolates from the United Kingdom

PubMed Central

Szekely, Adrien; Linton, Chistopher J.; Palmer, Michael D.; Brown, Phillipa; Johnson, Elizabeth M.

2013-01-01

Candida africana was previously proposed as a new species within the Candida albicans species complex, together with C. albicans and C. dubliniensis, although further phylogenetic analyses better support its status as an unusual variant within C. albicans. Here we show that C. africana can be distinguished from C. albicans and C. dubliniensis by pyrosequencing of a short region of ITS2, and we have evaluated its occurrence in clinical samples by pyrosequencing all presumptive isolates of C. albicans submitted to the Mycology Reference Laboratory over a 9-month period. The C. albicans complex constituted 826/1,839 (44.9%) of yeast isolates received over the study period and included 783 isolates of C. albicans, 28 isolates of C. dubliniensis, and 15 isolates of C. africana. In agreement with previous reports, C. africana was isolated exclusively from genital specimens, in women in the 18-to-35-year age group. Indeed, C. africana constituted 15/251 (6%) of “C. albicans” isolates from female genital specimens during the study period. C. africana isolates were germ tube positive, grew significantly more slowly than C. albicans and C. dubliniensis on conventional mycological media, could be distinguished from the other members of the C. albicans complex by appearance on chromogenic agar, and were incapable of forming chlamydospores. Here we present the detailed evaluation of epidemiological, phenotypic, and clinical features and antifungal susceptibility profiles of United Kingdom isolates of C. africana. Furthermore, we demonstrate that C. africana is significantly less pathogenic than C. albicans and C. dubliniensis in the Galleria mellonella insect systemic infection model. PMID:23303503

Genetic variation among Staphylococcus aureus strains from Norwegian bulk milk.

PubMed

Jørgensen, H J; Mørk, T; Caugant, D A; Kearns, A; Rørvik, L M

2005-12-01

Strains of Staphylococcus aureus obtained from bovine (n = 117) and caprine (n = 114) bulk milk were characterized and compared with S. aureus strains from raw-milk products (n = 27), bovine mastitis specimens (n = 9), and human blood cultures (n = 39). All isolates were typed by pulsed-field gel electrophoresis (PFGE). In addition, subsets of isolates were characterized using multilocus sequence typing (MLST), multiplex PCR (m-PCR) for genes encoding nine of the staphylococcal enterotoxins (SE), and the cloverleaf method for penicillin resistance. A variety of genotypes were observed, and greater genetic diversity was found among bovine than caprine bulk milk isolates. Certain genotypes, with a wide geographic distribution, were common to bovine and caprine bulk milk and may represent ruminant-specialized S. aureus. Isolates with genotypes indistinguishable from those of strains from ruminant mastitis were frequently found in bulk milk, and strains with genotypes indistinguishable from those from bulk milk were observed in raw-milk products. This indicates that S. aureus from infected udders may contaminate bulk milk and, subsequently, raw-milk products. Human blood culture isolates were diverse and differed from isolates from other sources. Genotyping by PFGE, MLST, and m-PCR for SE genes largely corresponded. In general, isolates with indistinguishable PFGE banding patterns had the same SE gene profile and isolates with identical SE gene profiles were placed together in PFGE clusters. Phylogenetic analyses agreed with the division of MLST sequence types into clonal complexes, and isolates within the same clonal complex had the same SE gene profile. Furthermore, isolates within PFGE clusters generally belonged to the same clonal complex.

Genetic Variation among Staphylococcus aureus Strains from Norwegian Bulk Milk

PubMed Central

Jørgensen, H. J.; Mørk, T.; Caugant, D. A.; Kearns, A.; Rørvik, L. M.

2005-01-01

Strains of Staphylococcus aureus obtained from bovine (n = 117) and caprine (n = 114) bulk milk were characterized and compared with S. aureus strains from raw-milk products (n = 27), bovine mastitis specimens (n = 9), and human blood cultures (n = 39). All isolates were typed by pulsed-field gel electrophoresis (PFGE). In addition, subsets of isolates were characterized using multilocus sequence typing (MLST), multiplex PCR (m-PCR) for genes encoding nine of the staphylococcal enterotoxins (SE), and the cloverleaf method for penicillin resistance. A variety of genotypes were observed, and greater genetic diversity was found among bovine than caprine bulk milk isolates. Certain genotypes, with a wide geographic distribution, were common to bovine and caprine bulk milk and may represent ruminant-specialized S. aureus. Isolates with genotypes indistinguishable from those of strains from ruminant mastitis were frequently found in bulk milk, and strains with genotypes indistinguishable from those from bulk milk were observed in raw-milk products. This indicates that S. aureus from infected udders may contaminate bulk milk and, subsequently, raw-milk products. Human blood culture isolates were diverse and differed from isolates from other sources. Genotyping by PFGE, MLST, and m-PCR for SE genes largely corresponded. In general, isolates with indistinguishable PFGE banding patterns had the same SE gene profile and isolates with identical SE gene profiles were placed together in PFGE clusters. Phylogenetic analyses agreed with the division of MLST sequence types into clonal complexes, and isolates within the same clonal complex had the same SE gene profile. Furthermore, isolates within PFGE clusters generally belonged to the same clonal complex. PMID:16332822

Cuscuta chinensis Lam.: A systematic review on ethnopharmacology, phytochemistry and pharmacology of an important traditional herbal medicine.

PubMed

Donnapee, Sineeporn; Li, Jin; Yang, Xi; Ge, Ai-hua; Donkor, Paul Owusu; Gao, Xiu-mei; Chang, Yan-xu

2014-11-18

Cuscuta chinensis Lam. has found its use as a traditional medicine in China, Korea, Pakistan, Vietnam, India and Thailand. It is commonly used as an anti-aging agent, anti-inflammatory agent, pain reliever and aphrodisiac. To provide an overview of the ethnopharmacology, phytochemistry, pharmacokinetics, pharmacology and clinical applications of Cuscuta chinensis, as well as being an evidence base for further research works of the plant. The present review covers the literature available from 1985 to 2014. The information was collected from journals, books, theses and electronic search (Google Scholar, PubMed, ScienceDirect, ESBCO, Springerlink and CNKI). Literature abstracts and full-text articles were analyzed and included in the review. Many phytochemicals have been isolated, identified and published to date, including: at least 18 flavonoids; 13 phenolic acids; 2 steroids; 1 hydroquinone; 10 volatile oils; 22 lignans; 9 polysaccharides; 2 resin glycosides; 16 fatty acids. These phytochemicals and plant extracts exhibit a range of pharmacological activities that include hepatoprotective, renoprotective, antiosteoporotic, antioxidant, anti-aging, antimutagenic, antidepressant, improve sexual function, abortifacient effects, etc. This present review offers primary information for further studies of Cuscuta chinensis. The in vitro studies and in vivo models have provided a bioscientific explanation for its various ethnopharmacological uses and pharmacological activities (most notably antioxidant effects) especially in the prevention of hepatic disease and renal failure. It is necessary and important to do more pharmacokinetic and toxicological research works on human subjects in order to inform the possible active compounds in the body and validate its safety in clinical uses. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Multilocus Genotyping and Molecular Phylogenetics Resolve a Novel Head Blight Pathogen within the Fusarium graminearum Species Complex from Ethiopia

USDA-ARS?s Scientific Manuscript database

A survey of Fusarium head blight (FHB)-contaminated wheat in Ethiopia recovered 31 isolates resembling members of the Fusarium graminearum species complex. Results of a multilocus genotyping (MLGT) assay for FHB species and trichothecene chemotype determination suggested that 22 of these isolates m...

Novel Seimatosporium species from grapevine in northern California and their interactions with fungal pathogens involved in the trunk-disease complex

USDA-ARS?s Scientific Manuscript database

Seimatosporium species and closely related ‘pestalotioid fungi’ have been isolated from vineyards around the world, but their ecological status in grapevine wood is not equivocal. To determine their involvement in the grapevine trunk-disease complex, we tested the pathogenicity of California isolate...

Molecular analysis and distribution of multidrug-resistant Enterococcus faecium isolates belonging to clonal complex 17 in a tertiary care center in Mexico City

PubMed Central

2013-01-01

Background Enterococcus faecium has recently emerged as a multidrug-resistant nosocomial pathogen involved in outbreaks worldwide. A high rate of resistance to different antibiotics has been associated with virulent clonal complex 17 isolates carrying the esp and hyl genes and the purK1 allele. Results Twelve clinical vancomycin-resistant Enterococcus faecium (VREF) isolates were obtained from pediatric patients at the Hospital Infantil de México Federico Gómez (HIMFG). Among these VREF isolates, 58.3% (7/12) were recovered from urine, while 41.7% (5/12) were recovered from the bloodstream. The VREF isolates showed a 100% rate of resistance to ampicillin, amoxicillin-clavulanate, ciprofloxacin, clindamycin, chloramphenicol, streptomycin, gentamicin, rifampicin, erythromycin and teicoplanin. In addition, 16.7% (2/12) of the isolates were resistant to linezolid, and 66.7% (8/12) were resistant to tetracycline and doxycycline. PCR analysis revealed the presence of the vanA gene in all 12 VREF isolates, esp in 83.3% (10/12) of the isolates and hyl in 50% (6/12) of the isolates. Phylogenetic analysis via molecular typing was performed using pulsed-field gel electrophoresis (PFGE) and demonstrated 44% similarity among the VREF isolates. MLST analysis identified four different sequence types (ST412, ST757, ST203 and ST612). Conclusion This study provides the first report of multidrug-resistant VREF isolates belonging to clonal complex 17 from a tertiary care center in Mexico City. Multidrug resistance and genetic determinants of virulence confer advantages among VREF in the colonization of their host. Therefore, the prevention and control of the spread of nosocomial infections caused by VREF is crucial for identifying new emergent subclones that could be challenging to treat in subsequent years. PMID:24330424

Five-year National Surveillance of Invasive Candidiasis: Species Distribution and Azole Susceptibility from the China Hospital Invasive Fungal Surveillance Net (CHIF-NET) Study.

PubMed

Xiao, Meng; Sun, Zi-Yong; Kang, Mei; Guo, Da-Wen; Liao, Kang; Chen, Sharon C-A; Kong, Fanrong; Fan, Xin; Cheng, Jing-Wei; Hou, Xin; Zhou, Meng-Lan; Li, Ying; Yu, Shu-Ying; Huang, Jing-Jing; Wang, He; Xu, Ying-Chun

2018-05-09

Data on the epidemiology of invasive candidiasis (IC) and antifungal susceptibility of Candida isolates in China are still limited. Here we report surveillance for IC from the China Hospital Invasive Fungal Surveillance Net (CHIF-NET) Study. Sixty-five tertiary hospitals collected 8,829 Candida isolates from August 1, 2009 to July 31, 2014. Matrix-assisted laser desorption/ionization -time of flight mass spectrometry supplemented by rDNA sequencing was used to define species, and fluconazole and voriconazole susceptibilities determined by the Clinical and Laboratory Standards Institute disk diffusion method. A total of 32 Candida species were identified. C. albicans was the most common species (44.9%) followed by C. parapsilosis complex (20.0%), C. tropicalis (17.2%) and C. glabrata complex (10.8%), with other species comprising <3%. However, in candidemia, the proportion of cases caused by C. albicans was only 32.3%. C. albicans and C. parapsilosis complex isolates were susceptible to fluconazole and voriconazole (<6% resistance), while fluconazole- and azole cross-resistant rates were high in C. tropicalis (13.3% and 12.9%), C. glabrata complex (18.7% and 14%) and uncommon Candida species (44.1% and 10.3%) isolates. Moreover, from year 1 to 5 of the study, there was a significant increase in resistant rates amongst C. glabrata complex isolates to fluconazole (12.2% to 24.0%), and amongst C. tropicalis isolates to both fluconazole (5.7% to 21.0%) and voriconazole (5.7% to 21.4%) (all P<0.01). Geographic variations in causative species and susceptibilities were noted. Our findings indicated that antifungal resistance have become noteworthy in China, and enhanced surveillance is warranted. Copyright © 2018 American Society for Microbiology.

Scedosporium apiospermum complex in cystic fibrosis; should we treat?

PubMed

Noni, Maria; Katelari, Anna; Kapi, Aikaterini; Stathi, Angeliki; Dimopoulos, George; Doudounakis, Stavros-Eleftherios

2017-09-01

Species of the Scedosporium apiospermum complex are the second most frequent filamentous fungi after Aspergillus fumigatus that can be found in cystic fibrosis (CF). Mixed colonisation by S. apiospermum complex and A. fumigatus is also quite common. In this study we summarise all CF patients who were colonised by S. apiospermum complex during their childhood and we present two CF patients who were treated as fungal bronchitis due to S. apiospermum complex. The medical records of 400 CF patients were reviewed in order to identify those with positive respiratory cultures for S. apiospermum complex. Scedosporium apiospermum complex was isolated in 10 CF patients and six of them had more than two positive sputum cultures during the study period. By the time of first isolation, the median age was 14.5 years, the median BMI was 19.41 kg/m 2 , the median predicted FEV 1 % was 78.65% and six patients had a history of A. fumigatus isolation. Two patients presented symptoms of infection while they were colonised by S. apiospermum complex. A rapid remission of their symptoms was observed only when antifungal therapy was administered. Antifungal treatment should be considered in CF patients who present symptoms of infection not responding to antibacterial therapy and S. apiospermum complex is persistently growing in sputum cultures. © 2017 Blackwell Verlag GmbH.

Bacterial formate hydrogenlyase complex.

PubMed

McDowall, Jennifer S; Murphy, Bonnie J; Haumann, Michael; Palmer, Tracy; Armstrong, Fraser A; Sargent, Frank

2014-09-23

Under anaerobic conditions, Escherichia coli can carry out a mixed-acid fermentation that ultimately produces molecular hydrogen. The enzyme directly responsible for hydrogen production is the membrane-bound formate hydrogenlyase (FHL) complex, which links formate oxidation to proton reduction and has evolutionary links to Complex I, the NADH:quinone oxidoreductase. Although the genetics, maturation, and some biochemistry of FHL are understood, the protein complex has never been isolated in an intact form to allow biochemical analysis. In this work, genetic tools are reported that allow the facile isolation of FHL in a single chromatographic step. The core complex is shown to comprise HycE (a [NiFe] hydrogenase component termed Hyd-3), FdhF (the molybdenum-dependent formate dehydrogenase-H), and three iron-sulfur proteins: HycB, HycF, and HycG. A proportion of this core complex remains associated with HycC and HycD, which are polytopic integral membrane proteins believed to anchor the core complex to the cytoplasmic side of the membrane. As isolated, the FHL complex retains formate hydrogenlyase activity in vitro. Protein film electrochemistry experiments on Hyd-3 demonstrate that it has a unique ability among [NiFe] hydrogenases to catalyze production of H2 even at high partial pressures of H2. Understanding and harnessing the activity of the FHL complex is critical to advancing future biohydrogen research efforts.

Protein complex purification from Thermoplasma acidophilum using a phage display library.

PubMed

Hubert, Agnes; Mitani, Yasuo; Tamura, Tomohiro; Boicu, Marius; Nagy, István

2014-03-01

We developed a novel protein complex isolation method using a single-chain variable fragment (scFv) based phage display library in a two-step purification procedure. We adapted the antibody-based phage display technology which has been developed for single target proteins to a protein mixture containing about 300 proteins, mostly subunits of Thermoplasma acidophilum complexes. T. acidophilum protein specific phages were selected and corresponding scFvs were expressed in Escherichia coli. E. coli cell lysate containing the expressed His-tagged scFv specific against one antigen protein and T. acidophilum crude cell lysate containing intact target protein complexes were mixed, incubated and subjected to protein purification using affinity and size exclusion chromatography steps. This method was confirmed to isolate intact particles of thermosome and proteasome suitable for electron microscopy analysis and provides a novel protein complex isolation strategy applicable to organisms where no genetic tools are available. Copyright © 2013 Elsevier B.V. All rights reserved.

Live Cell Genomics: RNA Exon-Specific RNA-Binding Protein Isolation.

PubMed

Bell, Thomas J; Eberwine, James

2015-01-01

RNA-binding proteins (RBPs) are essential regulatory proteins that control all modes of RNA processing and regulation. New experimental approaches to isolate these indispensable proteins under in vivo conditions are needed to advance the field of RBP biology. Historically, in vitro biochemical approaches to isolate RBP complexes have been useful and productive, but biological relevance of the identified RBP complexes can be imprecise or erroneous. Here we review an inventive experimental to isolate RBPs under the in vivo conditions. The method is called peptide nucleic acid (PNA)-assisted identification of RBP (PAIR) technology and it uses cell-penetrating peptides (CPPs) to deliver photo-activatible RBP-capture molecule to the cytoplasm of the live cells. The PAIR methodology provides two significant advantages over the most commonly used approaches: (1) it overcomes the in vitro limitation of standard biochemical approaches and (2) the PAIR RBP-capture molecule is highly selective and adaptable which allows investigators to isolate exon-specific RBP complexes. Most importantly, the in vivo capture conditions and selectivity of the RBP-capture molecule yield biologically accurate and relevant RBP data.

Toxicity to Chicks of Aspergillus and Penicillium Species Isolated from Moldy Pecans 1

PubMed Central

Doupnik, Ben; Bell, D. K.

1971-01-01

Isolates of Aspergillus chevalieri, A. flavus, A. ochraceus, A. repens, and Penicillium funiculosum and complexes of P. citrinum-P. implicatum isolated from moldy pecan meats were toxic to chicks. PMID:5564681

OXA-Carbapenemases Present in Clinical Acinetobacter baumannii-calcoaceticus Complex Isolates from Patients in Kurdistan Region, Iraq.

PubMed

Ganjo, Aryann R; Maghdid, Delshad M; Mansoor, Isam Y; Kok, Dik J; Severin, Juliette A; Verbrugh, Henri A; Kreft, Deborah; Fatah, M H; Alnakshabandi, A A; Dlnya, Asad; Hammerum, Anette M; Ng, Kim; Goessens, Wil

2016-12-01

In addition to intrinsic resistance in Acinetobacter baumannii, many different types of acquired resistance mechanisms have been reported, including the presence of VIM and IMP metallo β-lactamases and also of bla OXA-23-like and bla OXA-58-like enzymes. In the Kurdistan region of Iraq, the multiresistant A. baumannii-calcoaceticus complex is prevalent. We characterized the different mechanisms of resistance present in clinical isolates collected from different wards and different hospitals from the Kurdistan region. One hundred twenty clinical nonduplicate A. baumannii-calcoaceticus complex isolates were collected from four hospitals between January 2012 and October 2013. The identification of the isolates was confirmed by MALDI-TOF. The susceptibility to different antibiotics was determined by disk diffusion and analyzed in accordance to EUCAST guidelines. By PCR, the presence of bla OXA-51-like , bla OXA-23-like , bla OXA-24-like , and bla OXA-58-like genes was determined as well as the presence of the insertion element ISAba1. Clonal diversity was analyzed by pulsed-field gel electrophoresis (PFGE) using the restriction enzyme ApaI and, in addition, multilocus sequence typing (MLST) was performed on a selected subset of 15 isolates. All 120 A. baumannii isolates harbored bla OXA-51-like genes. One hundred one out of 110 (92%) imipenem (IMP)-resistant A. baumannii-calcoaceticus complex isolates additionally carried the bla OXA-23-like gene and four isolates (3%) were positive for bla OXA-24-like. All 101 bla OXA-23-like -positive isolates had the ISAba1 insertion sequence, 1,600 bp upstream of the bla OXA-23-like gene. The bla OXA-58-like gene was not detected in any of the 110 IMP-resistant strains. Eight different PFGE clusters were identified and distributed over the different hospitals. MLST analysis performed on a subset of 15 representative isolates revealed the presence of the international clone ST2 (Pasteur). Besides ST2 (Pasteur), also many other STs (Pasteur) were encountered such as ST136, ST94, ST623, ST792, and ST793, all carrying the bla OXA-23 gene. In clinical A. baumannii-calcoaceticus complex isolates from Kurdistan-Iraq, the bla OXA-23 gene in combination with the upstream ISAba1 insertion element is largely responsible for carbapenem resistance. Several small clusters of identical genotypes were found from patients admitted to the same ward and during overlapping time periods, suggesting transmission within the hospital. Identification of source(s) and limiting the transmission of these strains to patients needs to be prioritized.

Control of epidemics on complex networks: Effectiveness of delayed isolation

NASA Astrophysics Data System (ADS)

Pereira, Tiago; Young, Lai-Sang

2015-08-01

We study isolation as a means to control epidemic outbreaks in complex networks, focusing on the consequences of delays in isolating infected nodes. Our analysis uncovers a tipping point: if infected nodes are isolated before a critical day dc, the disease is effectively controlled, whereas for longer delays the number of infected nodes climbs steeply. We show that dc can be estimated explicitly in terms of network properties and disease parameters, connecting lowered values of dc explicitly to heterogeneity in degree distribution. Our results reveal also that initial delays in the implementation of isolation protocols can have catastrophic consequences in heterogeneous networks. As our study is carried out in a general framework, it has the potential to offer insight and suggest proactive strategies for containing outbreaks of a range of serious infectious diseases.

Multilocus sequence type profiles of Bacillus cereus isolates from infant formula in China.

PubMed

Yang, Yong; Yu, Xiaofeng; Zhan, Li; Chen, Jiancai; Zhang, Yunyi; Zhang, Junyan; Chen, Honghu; Zhang, Zheng; Zhang, Yanjun; Lu, Yiyu; Mei, Lingling

2017-04-01

Bacillus cereus sensu stricto is an opportunistic foodborne pathogen. The multilocus sequence type (MLST) of 74 B. cereus isolated from 513 non-random infant formula in China was analyzed. Of 64 sequence types (STs) detected, 50 STs and 6 alleles were newly found in PubMLST database. All isolates except for one singleton (ST-1049), were classified into 7 clonal complexes (CC) by BURST (n-4), in which CC1 with core ancestral clone ST-26 was the largest group including 86% isolates, and CC2, 3, 9, 10 and 13 were first reported in China. MLST profiles of the isolates from 8 infant formula brands were compared. It was found the brands might be potentially tracked by the variety of STs, such as ST-1049 of singleton and ST-1062 of isolate from goat milk source, though they could not be easily tracked just by clonal complex types of the isolates. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genotypic and Phenotypic Correlations of Multidrug-Resistant Acinetobacter baumannii-A. calcoaceticus Complex Strains Isolated from Patients at the National Naval Medical Center

USDA-ARS?s Scientific Manuscript database

Acinetobacter baumannii-calcoaceticus complex (ABC) infections have complicated the care of U.S. combat casualties. In this study, 102 ABC isolates from wounded soldiers treated at National Naval Medical Center (NNMC) were characterized by phenotype and genotype to identify clones in this population...

Application of the Capilia TB assay for culture confirmation of Mycobacterium tuberculosis complex isolates.

PubMed

Hillemann, D; Rüsch-Gerdes, S; Richter, E

2005-12-01

The usefulness of a low-tech rapid test for culture confirmation of Mycobacterium tuberculosis complex, Capilia TB, was tested on 172 mycobacteria-positive clinical samples. The overall sensitivity and specificity were 92.4% and 100%, respectively. In three of nine false-negative isolates a mutation in the mpb64 gene could be detected.

Closed Genome Sequences of Seven Histophilus somni Isolates from Beef Calves with Bovine Respiratory Disease Complex.

PubMed

Harhay, Gregory P; Harhay, Dayna M; Bono, James L; Smith, Timothy P L; Capik, Sarah F; DeDonder, Keith D; Apley, Michael D; Lubbers, Brian V; White, Bradley J; Larson, Robert L

2017-10-05

Histophilus somni is a fastidious Gram-negative opportunistic pathogenic Pasteurellaceae that affects multiple organ systems and is one of the principal bacterial species contributing to bovine respiratory disease complex (BRDC) in feed yard cattle. Here, we present seven closed genome sequences isolated from three beef calves showing sign of BRDC.

Genetic Diversity of Human Pathogenic Members of the Fusarium oxysporum Complex Inferred from Multilocus DNA Sequence Data and Amplified Fragment Length Polymorphism Analyses: Evidence for the Recent Dispersion of a Geographically Widespread Clonal Lineage and Nosocomial Origin

PubMed Central

O'Donnell, Kerry; Sutton, Deanna A.; Rinaldi, Michael G.; Magnon, Karen C.; Cox, Patricia A.; Revankar, Sanjay G.; Sanche, Stephen; Geiser, David M.; Juba, Jean H.; van Burik, Jo-Anne H.; Padhye, Arvind; Anaissie, Elias J.; Francesconi, Andrea; Walsh, Thomas J.; Robinson, Jody S.

2004-01-01

Fusarium oxysporum is a phylogenetically diverse monophyletic complex of filamentous ascomycetous fungi that are responsible for localized and disseminated life-threatening opportunistic infections in immunocompetent and severely neutropenic patients, respectively. Although members of this complex were isolated from patients during a pseudoepidemic in San Antonio, Tex., and from patients and the water system in a Houston, Tex., hospital during the 1990s, little is known about their genetic relatedness and population structure. This study was conducted to investigate the global genetic diversity and population biology of a comprehensive set of clinically important members of the F. oxysporum complex, focusing on the 33 isolates from patients at the San Antonio hospital and on strains isolated in the United States from the water systems of geographically distant hospitals in Texas, Maryland, and Washington, which were suspected as reservoirs of nosocomial fusariosis. In all, 18 environmental isolates and 88 isolates from patients spanning four continents were genotyped. The major finding of this study, based on concordant results from phylogenetic analyses of multilocus DNA sequence data and amplified fragment length polymorphisms, is that a recently dispersed, geographically widespread clonal lineage is responsible for over 70% of all clinical isolates investigated, including all of those associated with the pseudoepidemic in San Antonio. Moreover, strains of the clonal lineage recovered from patients were conclusively shown to genetically match those isolated from the hospital water systems of three U.S. hospitals, providing support for the hypothesis that hospitals may serve as a reservoir for nosocomial fusarial infections. PMID:15528703

Characterization of Mycosphaerellaceae species associated with citrus greasy spot in Panama and Spain

PubMed Central

Aguilera-Cogley, Vidal Antonio; Berbegal, Mónica; Català, Santiago; Brentu, Francis Collison; Armengol, Josep

2017-01-01

Greasy spot of citrus, caused by Zasmidium citri-griseum (= Mycosphaerella citri), is widely distributed in the Caribbean Basin, inducing leaf spots, premature defoliation, and yield loss. Greasy spot-like symptoms were frequently observed in humid citrus-growing regions in Panama as well as in semi-arid areas in Spain, but disease aetiology was unknown. Citrus-growing areas in Panama and Spain were surveyed and isolates of Mycosphaerellaceae were obtained from citrus greasy spot lesions. A selection of isolates from Panama (n = 22) and Spain (n = 16) was assembled based on their geographical origin, citrus species, and affected tissue. The isolates were characterized based on multi-locus DNA (ITS and EF-1α) sequence analyses, morphology, growth at different temperatures, and independent pathogenicity tests on the citrus species most affected in each country. Reference isolates and sequences were also included in the analysis. Isolates from Panama were identified as Z. citri-griseum complex, and others from Spain attributed to Amycosphaerella africana. Isolates of the Z. citri-griseum complex had a significantly higher optimal growth temperature (26.8°C) than those of A. africana (19.3°C), which corresponded well with their actual biogeographical range. The isolates of the Z. citri-griseum complex from Panama induced typical greasy spot symptoms in ‘Valencia’ sweet orange plants and the inoculated fungi were reisolated. No symptoms were observed in plants of the ‘Ortanique’ tangor inoculated with A. africana. These results demonstrate the presence of citrus greasy spot, caused by Z. citri-griseum complex, in Panama whereas A. africana was associated with greasy spot-like symptoms in Spain. PMID:29236789

Isolation of homoleptic platinum oxyanionic complexes with doubly protonated diazacrown cation

NASA Astrophysics Data System (ADS)

Vasilchenko, Danila; Tkachev, Sergey; Baidina, Iraida; Romanenko, Galina; Korenev, Sergey

2017-02-01

Doubly protonated diazacrown ether cation (1,4,10,13-tetraoxa-7,16-diazoniacyclooctadecane DCH22+) was used for the efficient isolation of the homoleptic platinum complexes [Pt(NO3)6]2- and [Pt(C2O4)2]2- to crystalline solid phases from solutions containing mixtures of related platinum complexes. DCH22+ molecules in nitric acid solution were shown to prevent the condensation of mononuclear [Pt(H2O)n(NO3)6-n]n-2 species.

Subtyping of Clostridium difficile PCR ribotypes 591, 106 and 002, the dominant strain types circulating in Medellin, Colombia.

PubMed

Salazar, Clara Lina; Reyes, Catalina; Cienfuegos-Gallet, Astrid Vanessa; Best, Emma; Atehortua, Santiago; Sierra, Patricia; Correa, Margarita M; Fawley, Warren N; Paredes-Sabja, Daniel; Wilcox, Mark; Gonzalez, Angel

2018-01-01

We aimed to achieve a higher typing resolution within the three dominant Clostridium difficile ribotypes (591,106 and 002) circulating in Colombia. A total of 50 C. difficile isolates we had previously typed by PCR-ribotyping, representing the major three ribotypes circulating in Colombia, were analyzed. Twenty-seven isolates of ribotype 591, 12 of ribotype 106 and 11 of ribotype 002 were subtyped by multiple locus variable-number tandem-repeat analysis (MLVA). The presence of the PaLoc genes (tcdA/tcdB), toxin production in culture and antimicrobial susceptibility were also determined. From the total C. difficile ribotypes analyzed, 20 isolates (74%) of ribotype 591, nine (75%) of ribotype 106 and five (45.5%) of ribotype 002 were recovered from patients with Clostridium difficile infection (CDI). MLVA allowed us to recognize four and two different clonal complexes for ribotypes 591 and 002, respectively, having a summed tandem-repeat difference (STRD) <2, whereas none of the ribotype 106 isolates were grouped in a cluster or clonal complex having a STRD >10. Six ribotype 591 and three ribotype 002 isolates belonging to a defined clonal complex were isolated on the same week in two different hospitals. All ribotypes harbored either tcdA+/tcdB+ or tcdA-/tcdB+ PaLoc genes. Moreover, 94% of the isolates were positive for toxin in culture. All isolates were susceptible to vancomycin and metronidazole, while 75% to 100% of the isolates were resistant to clindamycin, and less than 14.8% of ribotype 591 isolates were resistant to moxifloxacina. No significant differences were found among ribotypes with respect to demographic and clinical patients' data; however, our results demonstrated a high molecular heterogeneity of C. difficile strains circulating in Colombia.

Subtyping of Clostridium difficile PCR ribotypes 591, 106 and 002, the dominant strain types circulating in Medellin, Colombia

PubMed Central

Salazar, Clara Lina; Reyes, Catalina; Cienfuegos-Gallet, Astrid Vanessa; Best, Emma; Atehortua, Santiago; Sierra, Patricia; Correa, Margarita M.; Fawley, Warren N.; Paredes-Sabja, Daniel; Wilcox, Mark

2018-01-01

We aimed to achieve a higher typing resolution within the three dominant Clostridium difficile ribotypes (591,106 and 002) circulating in Colombia. A total of 50 C. difficile isolates we had previously typed by PCR-ribotyping, representing the major three ribotypes circulating in Colombia, were analyzed. Twenty-seven isolates of ribotype 591, 12 of ribotype 106 and 11 of ribotype 002 were subtyped by multiple locus variable-number tandem-repeat analysis (MLVA). The presence of the PaLoc genes (tcdA/tcdB), toxin production in culture and antimicrobial susceptibility were also determined. From the total C. difficile ribotypes analyzed, 20 isolates (74%) of ribotype 591, nine (75%) of ribotype 106 and five (45.5%) of ribotype 002 were recovered from patients with Clostridium difficile infection (CDI). MLVA allowed us to recognize four and two different clonal complexes for ribotypes 591 and 002, respectively, having a summed tandem-repeat difference (STRD) <2, whereas none of the ribotype 106 isolates were grouped in a cluster or clonal complex having a STRD >10. Six ribotype 591 and three ribotype 002 isolates belonging to a defined clonal complex were isolated on the same week in two different hospitals. All ribotypes harbored either tcdA+/tcdB+ or tcdA-/tcdB+ PaLoc genes. Moreover, 94% of the isolates were positive for toxin in culture. All isolates were susceptible to vancomycin and metronidazole, while 75% to 100% of the isolates were resistant to clindamycin, and less than 14.8% of ribotype 591 isolates were resistant to moxifloxacina. No significant differences were found among ribotypes with respect to demographic and clinical patients’ data; however, our results demonstrated a high molecular heterogeneity of C. difficile strains circulating in Colombia. PMID:29649308

Presence and mechanisms of acquired antimicrobial resistance in Belgian Brachyspira hyodysenteriae isolates belonging to different clonal complexes.

PubMed

Mahu, M; Pasmans, F; Vranckx, K; De Pauw, N; Vande Maele, L; Vyt, Philip; Vandersmissen, Tamara; Martel, A; Haesebrouck, F; Boyen, F

2017-08-01

Swine dysentery (SD) is an economically important disease for which antimicrobial treatment still occupies an important place to control outbreaks. However, acquired antimicrobial resistance is increasingly observed in Brachyspira hyodysenteriae. In this study, the Minimal Inhibitory Concentrations (MIC) of six antimicrobial compounds for 30 recent Belgian B. hyodysenteriae isolates were determined using a broth microdilution method. In addition, relevant regions of the 16S rRNA, 23S rRNA and the L3 protein encoding genes were sequenced to reveal mutations associated with acquired resistance. Finally, a phylogeny was reconstructed using minimal spanning tree analysis of multi locus sequence typing of the isolates. For lincomycin, doxycycline, tylosin and tylvalosin, at least 70% of the isolates did not belong to the wild-type population and were considered to have acquired resistance. For valnemulin and tiamulin, this was over 50%. In all isolates with acquired resistance to doxycycline, the G1058C mutation was present in their 16S rRNA gene. All isolates showing acquired resistance to lincomycin and both macrolides displayed the A2058T mutation in their 23S rRNA gene. Other mutations in this gene and the N148S mutation in the L3 protein were present in both wild-type isolates and isolates considered to have acquired resistance. Multi locus sequence analysis revealed a previously undescribed clonal complex, with 4 novel sequence types in which the majority of isolates showed acquired resistance to all tested antimicrobial products. In conclusion, acquired antimicrobial resistance is widespread among Belgian B. hyodysenteriae isolates. The emergence of multi-resistant clonal complexes can pose a threat to swine industry. Copyright © 2017 Elsevier B.V. All rights reserved.

Mouse Liver Mitochondria Isolation, Size Fractionation, and Real-time MOMP Measurement

PubMed Central

Renault, Thibaud T.; Luna-Vargas, Mark P.A.; Chipuk, Jerry E.

2016-01-01

The mitochondrial pathway of apoptosis involves a complex interplay between dozens of proteins and lipids, and is also dependent on the shape and size of mitochondria. The use of cellular models in past studies has not been ideal for investigating how the complex multi-factor interplay regulates the molecular mechanisms of mitochondrial outer membrane permeabilization (MOMP). Isolated systems have proven to be a paradigm to deconstruct MOMP into individual steps and to study the behavior of each subset of MOMP regulators. In particular, isolated mitochondria are key to in vitro studies of the BCL-2 family proteins, a complex family of pro-survival and pro-apoptotic proteins that directly control the mitochondrial pathway of apoptosis (Renault et al., 2013). In this protocol, we describe three complementary procedures for investigating in real-time the effects of MOMP regulators using isolated mitochondria. The first procedure is “Liver mitochondria isolation” in which the liver is dissected from mice to obtain mitochondria. “Mitochondria labeling with JC-1 and size fractionation” is the second procedure that describes a method to label, fractionate by size and standardize subpopulations of mitochondria. Finally, the “Real-time MOMP measurements” protocol allows to follow MOMP in real-time on isolated mitochondria. The aforementioned procedures were used to determine in vitro the role of mitochondrial membrane shape at the level of isolated cells and isolated mitochondria (Renault et al., 2015). PMID:28093578

Staphylococcus aureus isolated from wastewater treatment plants in Tunisia: occurrence of human and animal associated lineages.

PubMed

Ben Said, Meriam; Abbassi, Mohamed Salah; Gómez, Paula; Ruiz-Ripa, Laura; Sghaier, Senda; Ibrahim, Chourouk; Torres, Carmen; Hassen, Abdennaceur

2017-08-01

The objective was to characterize Staphylococcus aureus isolated from two wastewater treatment plants (WWTPs) located in Tunis City (Tunisia), during the period 2014-2015. Genetic lineages, antibiotic resistance mechanisms and virulence factors were determined for the recovered isolates. S. aureus isolates were recovered from 12 of the 62 wastewater samples tested (19.35%), and one isolate/sample was characterized, all of them being methicillin-susceptible (MSSA). Six spa types (t587, t674, t224, t127, t701 and t1534) were found among the 12 isolates, and the spa-t587, associated with the new sequence type ST3245, was the most predominant one (7 isolates). The remaining isolates were assigned to five clonal complexes (CC5, CC97, CC1, CC6 and CC522) according to the sequence-type determined and/or the spa-type detected. S. aureus isolates were ascribed to agrI (n = 3), agrII (n = 7) and agrIII (n = 1); however, one isolate was non-typeable. S. aureus showed resistance to (number of isolates): penicillin (12), erythromycin (7), tetracycline (one) and clindamycin (one). Among the virulence factors investigated, only one isolate harboured the tst gene, encoding the TSST-1 (toxic shock syndrome toxin 1). Despite the low number of studied isolates, the present study reports the occurrence of both human- and animal-associated S. aureus clonal complexes in WWTPs in Tunisia.

Salen complexes with dianionic counterions

DOEpatents

Job, Gabriel E.; Farmer, Jay J.; Cherian, Anna E.

2016-08-02

The present invention describes metal salen complexes having dianionic counterions. Such complexes can be readily precipitated and provide an economical method for the purification and isolation of the complexes, and are useful to prepare novel polymer compositions.

Characterisation of pks15/1 in clinical isolates of Mycobacterium tuberculosis from Mexico

PubMed Central

Zenteno-Cuevas, Roberto; Silva-Hernández, Francisco X; Mendoza-Damián, Fabiola; Ramírez-Hernández, Maria Dolores; Vázquez-Medina, Karen; Widrobo-García, Lorena; Cuellar-Sanchez, Aremy; Muñíz-Salazar, Raquel; Enciso-Moreno, Leonor; Pérez-Navarro, Lucia Monserrat; Enciso-Moreno, José Antonio

2013-01-01

Tuberculosis (TB) is an infectocontagious respiratory disease caused by members of the Mycobacterium tuberculosis complex. A 7 base pair (bp) deletion in the locus polyketide synthase (pks)15/1 is described as polymorphic among members of the M. tuberculosis complex, enabling the identification of Euro-American, Indo-Oceanic and Asian lineages. The aim of this study was to characterise this locus in TB isolates from Mexico. One hundred twenty clinical isolates were recovered from the states of Veracruz and Estado de Mexico. We determined the nucleotide sequence of a ± 400 bp fragment of the locus pks15/1, while genotypic characterisation was performed by spoligotyping. One hundred and fifty isolates contained the 7 bp deletion, while five had the wild type locus. Lineages X (22%), LAM (18%) and T (17%) were the most frequent; only three (2%) of the isolates were identified as Beijing and two (1%) EAI-Manila. The wild type pks15/1 locus was observed in all Asian lineage isolates tested. Our results confirm the utility of locus pks15/1 as a molecular marker for identifying Asian lineages of the M. tuberculosis complex. This marker could be of great value in the epidemiological surveillance of TB, especially in countries like Mexico, where the prevalence of such lineages is unknown. PMID:24037193

Activation of Latent Dihydroorotase from Aquifex aeolicus by Pressure*

PubMed Central

Hervé, Guy; Evans, Hedeel Guy; Fernado, Roshini; Patel, Chandni; Hachem, Fatme; Evans, David R.

2017-01-01

Elevated hydrostatic pressure was used to probe conformational changes of Aquifex aeolicus dihydroorotase (DHO), which catalyzes the third step in de novo pyrimidine biosynthesis. The isolated protein, a 45-kDa monomer, lacks catalytic activity but becomes active upon formation of a dodecameric complex with aspartate transcarbamoylase (ATC). X-ray crystallographic studies of the isolated DHO and of the complex showed that association induces several major conformational changes in the DHO structure. In the isolated DHO, a flexible loop occludes the active site blocking the access of substrates. The loop is mostly disordered but is tethered to the active site region by several electrostatic and hydrogen bonds. This loop becomes ordered and is displaced from the active site upon formation of DHO-ATC complex. The application of pressure to the complex causes its time-dependent dissociation and the loss of both DHO and ATC activities. Pressure induced irreversible dissociation of the obligate ATC trimer, and as a consequence the DHO is also inactivated. However, moderate hydrostatic pressure applied to the isolated DHO subunit mimics the complex formation and reversibly activates the isolated subunit in the absence of ATC, suggesting that the loop has been displaced from the active site. This effect of pressure is explained by the negative volume change associated with the disruption of ionic interactions and exposure of ionized amino acids to the solvent (electrostriction). The interpretation that the loop is relocated by pressure was validated by site-directed mutagenesis and by inhibition by small peptides that mimic the loop residues. PMID:27746403

Methicillin-susceptible Staphylococcus aureus endocarditis isolates are associated with clonal complex 30 genotype and a distinct repertoire of enterotoxins and adhesins.

PubMed

Nienaber, Juhsien J C; Sharma Kuinkel, Batu K; Clarke-Pearson, Michael; Lamlertthon, Supaporn; Park, Lawrence; Rude, Thomas H; Barriere, Steve; Woods, Christopher W; Chu, Vivian H; Marín, Mercedes; Bukovski, Suzana; Garcia, Patricia; Corey, G Ralph; Korman, Tony; Doco-Lecompte, Thanh; Murdoch, David R; Reller, L Barth; Fowler, Vance G

2011-09-01

Using multinational collections of methicillin-susceptible Staphylococcus aureus (MSSA) isolates from infective endocarditis (IE) and soft tissue infections (STIs), we sought to (1) validate the finding that S. aureus in clonal complex (CC) 30 is associated with hematogenous complications and (2) test the hypothesis that specific genetic characteristics in S. aureus are associated with infection severity. IE and STI isolates from 2 cohorts were frequency matched by geographic origin. Isolates underwent spa typing to infer CC and multiplex polymerase chain reaction for presence of virulence genes. 114 isolate pairs were genotyped. IE isolates were more likely to be CC30 (19.5% vs 6.2%; P = .005) and to contain 3 adhesins (clfB, cna, map/eap; P < .0001 for all) and 5 enterotoxins (tst, sea, sed, see, and sei; P ≤ .005 for all). CC30 isolates were more likely to contain cna, tst, sea, see, seg, and chp (P < .05 for all). MSSA IE isolates were significantly more likely to be CC30 and to possess a distinct repertoire of virulence genes than MSSA STI isolates from the same region. The genetic basis of this association requires further study.

Closed Genome Sequences of Seven Histophilus somni Isolates from Beef Calves with Bovine Respiratory Disease Complex

PubMed Central

Harhay, Dayna M.; Bono, James L.; Smith, Timothy P. L.; Capik, Sarah F.; DeDonder, Keith D.; Apley, Michael D.; Lubbers, Brian V.; White, Bradley J.; Larson, Robert L.

2017-01-01

ABSTRACT Histophilus somni is a fastidious Gram-negative opportunistic pathogenic Pasteurellaceae that affects multiple organ systems and is one of the principal bacterial species contributing to bovine respiratory disease complex (BRDC) in feed yard cattle. Here, we present seven closed genome sequences isolated from three beef calves showing sign of BRDC. PMID:28983006

Non-Tuberculous Mycobacteria. An Emerging Threat?

PubMed

Martínez González, Susana; Cano Cortés, Arantxa; Sota Yoldi, Luis Alfonso; García García, José María; Alba Álvarez, Luz María; Palacios Gutiérrez, Juan José

2017-10-01

Non-tuberculous mycobacteria (NTM) isolates are becoming more common. The main objective of our study was to establish the number and diversity of NTM species in our region and their distribution according to the source sample, age and gender of the patients, and to analyse clinically significant isolates. Prospective study of all NTM isolated in Asturias from 2005 to 2012. Samples were processed following internationally accepted guidelines. Statistical analysis was based on Fisher's exact test for 2×2 contingency tables. A total of 3,284 mycobacteria were isolated: 1,499 Mycobacterium tuberculosis complex (MTB) and 1,785 NTM.During the study, NTM isolation rates increased while MTB isolation decreased. NTM were more frequent in men (P<.001). M.gordonae was the most frequently isolated species but did not cause disease in any case. NTM isolates from 212 patients were associated with clinically significant disease (17.1%). M.kansasii and M.avium were most commonly associated with disease. The number of M.kansasii isolates from men was statistically significant (P<.01). In our study, NTM isolates increased by 35%, compared with a 21% decline in cases of MTB. Both isolation of NTM and clinically significant cases were more common in men. Only 17.1% of NTM isolates were associated with disease, most commonly M.avium complex and M.kansasii. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Increased frequency of self-fertile isolates in Phytophthora infestans may attribute to their higher fitness relative to the A1 isolates

PubMed Central

Zhu, Wen; Shen, Lin-Lin; Fang, Zhi-Guo; Yang, Li-Na; Zhang, Jia-Feng; Sun, Dan-Li; Zhan, Jiasui

2016-01-01

Knowledge of population dynamics of mating types is important for better understanding pathogen’s evolutionary potential and sustainable management of natural and chemical resources such as host resistances and fungicides. In this study, 2250 Phytophthora infestans isolates sampled from 61 fields across China were assayed for spatiotemporal dynamics of mating type frequency. Self-fertile isolates dominated in ~50% of populations and all but one cropping region with an average frequency of 0.64 while no A2 isolates were detected. Analyses of 140 genotypes consisting of 82 self-fertile and 58 A1 isolates indicated that on average self-fertile isolates grew faster, demonstrated higher aggressiveness and were more tolerant to fungicides than A1 isolates; Furthermore, pattern of association between virulence complexity (defined as the number of differential cultivars on which an isolate can induce disease) and frequency was different in the two mating types. In A1 isolates, virulence complexity was negatively correlated (r = −0.515, p = 0.043) with frequency but this correlation was positive (r = 0.532, p = 0.037) in self-fertile isolates. Our results indicate a quick increase of self-fertile isolates possibly attributable to their higher fitness relative to A1 mating type counterpart in the field populations of P. infestans in China. PMID:27384813

Approaches to catheter ablation for persistent atrial fibrillation.

PubMed

Verma, Atul; Jiang, Chen-yang; Betts, Timothy R; Chen, Jian; Deisenhofer, Isabel; Mantovan, Roberto; Macle, Laurent; Morillo, Carlos A; Haverkamp, Wilhelm; Weerasooriya, Rukshen; Albenque, Jean-Paul; Nardi, Stefano; Menardi, Endrj; Novak, Paul; Sanders, Prashanthan

2015-05-07

Catheter ablation is less successful for persistent atrial fibrillation than for paroxysmal atrial fibrillation. Guidelines suggest that adjuvant substrate modification in addition to pulmonary-vein isolation is required in persistent atrial fibrillation. We randomly assigned 589 patients with persistent atrial fibrillation in a 1:4:4 ratio to ablation with pulmonary-vein isolation alone (67 patients), pulmonary-vein isolation plus ablation of electrograms showing complex fractionated activity (263 patients), or pulmonary-vein isolation plus additional linear ablation across the left atrial roof and mitral valve isthmus (259 patients). The duration of follow-up was 18 months. The primary end point was freedom from any documented recurrence of atrial fibrillation lasting longer than 30 seconds after a single ablation procedure. Procedure time was significantly shorter for pulmonary-vein isolation alone than for the other two procedures (P<0.001). After 18 months, 59% of patients assigned to pulmonary-vein isolation alone were free from recurrent atrial fibrillation, as compared with 49% of patients assigned to pulmonary-vein isolation plus complex electrogram ablation and 46% of patients assigned to pulmonary-vein isolation plus linear ablation (P=0.15). There were also no significant differences among the three groups for the secondary end points, including freedom from atrial fibrillation after two ablation procedures and freedom from any atrial arrhythmia. Complications included tamponade (three patients), stroke or transient ischemic attack (three patients), and atrioesophageal fistula (one patient). Among patients with persistent atrial fibrillation, we found no reduction in the rate of recurrent atrial fibrillation when either linear ablation or ablation of complex fractionated electrograms was performed in addition to pulmonary-vein isolation. (Funded by St. Jude Medical; ClinicalTrials.gov number, NCT01203748.).

A Dicobalt Complex with an Unsymmetrical Quinonoid Bridge Isolated in Three Units of Charge: A Combined Structural, (Spectro)electrochemical, Magnetic and Spectroscopic Study.

PubMed

van der Meer, Margarethe; Rechkemmer, Yvonne; Frank, Uta; Breitgoff, Frauke D; Hohloch, Stephan; Su, Cheng-Yong; Neugebauer, Petr; Marx, Raphael; Dörfel, María; van Slageren, Joris; Sarkar, Biprajit

2016-09-19

Quinonoid ligands are excellent bridges for generating redox-rich dinuclear assemblies. A large majority of these bridges are symmetrically substituted, with examples of unsymmetrically substituted quinonoid bridges being extremely rare. We present here a dicobalt complex in its various redox states with an unsymmetrically substituted quinonoid bridging ligand. Two homovalent forms and one mixed-valent form have been isolated and characterized by single crystal X-ray diffraction. The complex displays a large comproportionation constant for the mixed-valent state which is three orders of magnitude higher than that observed for the analogous complex with a symmetrically substituted bridge. Results from electrochemistry, UV/Vis/NIR spectroelectrochemistry, SQUID magnetometry, multi-frequency EPR spectroscopy and FIR spectroscopy are used to probe the electronic structures of these complexes. FIR provides direct evidence of exchange coupling. The results presented here display the advantages of using an unsymmetrically substituted bridge: site specific redox chemistry, high thermodynamic stabilization of the mixed-valent form, isolation and crystallization of various redox forms of the complex. This work represents an important step on the way to generating heterodinuclear complexes for use in cooperative catalysis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Major globally disseminated clonal complexes of antimicrobial resistant enterococci associated with infections in cancer patients in Brazil.

PubMed

Santos, Barbara A; Oliveira, Jéssica S; Cardoso, Nayara T; Barbosa, André V; Superti, Silvana V; Teixeira, Lúcia M; Neves, Felipe P G

2017-11-01

Cancer and hematological malignancies constitute major comorbidities in enterococcal infections, but little is known about the characteristics of enterococci affecting cancer patients. The aim of this study was to characterize 132 enterococcal clinical isolates obtained from cancer patients attending a Cancer Reference Center in Brazil between April 2013 and March 2014. Susceptibility to 17 antimicrobial agents was assessed by disk diffusion method. Resistance and virulence genes were investigated by PCR. Multilocus sequence typing (MLST) was performed for selected Enterococcus faecalis and Enterococcus faecium isolates. The predominant species was E. faecalis (108 isolates), followed by E. faecium (18), Enterococcus gallinarum (3), Enterococcus avium (2) and Enterococcus durans (1). Multidrug-resistant (MDR) isolates made up 44.7%, but all isolates were susceptible to fosfomycin, linezolid and glycopeptides. The most prevalent genes associated with erythromycin- and tetracycline-non susceptible isolates were erm(B) (47/71; 66.2%) and tet(M) (24/68; 35.3%), respectively. High-level resistance (HLR) to gentamicin was found in 22 (16.7%) isolates and 13 (59.1%) of them carried the aac(6')-Ie-aph(2″)-Ia gene. HLR to streptomycin was detected in 34 (25.8%) isolates, of which 15 (44.1%) isolates had the ant(6')-Ia gene. The most common virulence genes were gelE (48.9%), esp (30.5%) and asa1 (29.8%). MLST performed for 26 E. faecalis isolates revealed 18 different sequence-types (STs), with seven corresponding to novel STs (625, 626, 627, 628, 629, 630, and 635). On the other hand, nine of 10 E. faecium isolates analyzed by MLST belonged to a single clonal complex, comprised of mostly ST412, which emerged worldwide after mid-2000s, but also two novel STs (963 and 964). We detected major globally disseminated E. faecalis and E. faecium clonal complexes along with novel closely related STs, indicating the fitness and continuous evolution of these hospital-adapted lineages. Copyright © 2017 Elsevier B.V. All rights reserved.

Semi-automated repetitive sequence-based PCR amplification for species of the Scedosporium apiospermum complex.

PubMed

Matray, Olivier; Mouhajir, Abdelmounaim; Giraud, Sandrine; Godon, Charlotte; Gargala, Gilles; Labbé, Franck; Rougeron, Amandine; Ballet, Jean-Jacques; Zouhair, Rachid; Bouchara, Jean-Philippe; Favennec, Loïc

2016-05-01

The Scedosporium apiospermum species complex usually ranks second among the filamentous fungi colonizing the airways of patients with cystic fibrosis (CF), but little is known about the molecular epidemiology of the airway colonization. Polymerase chain reaction (PCR) amplification of repetitive sequences (rep-PCR) was applied to the retrospective analysis of a panel of isolates already studied by random amplification of polymorphic DNA (RAPD) and comprising 63 isolates recovered from sputa from 9 CF patients. Results were compared to those obtained previously by RAPD, and herein by beta-tubulin (TUB) gene sequencing and Multilocus Sequence Typing (MLST). Within the panel of isolates studied,S. apiospermum sensu stricto and Scedosporium boydii, as expected, were the predominant species with 21 and 36 isolates, respectively. Four isolates from one patient were identified as Scedosporium aurantiacum, whereas two isolates belonged to the Pseudallescheria ellipsoidea subgroup of S. boydii rep-PCR analysis of these isolates clearly differentiated the three species and P. ellipsoidea isolates, whatever the rep-PCR kit used, and also permitted strain differentiation. When using the mold primer kit, results from rep-PCR were in close agreement with those obtained by MLST. For both S. apiospermum and S. boydii, 8 genotypes were differentiated by rep-PCR and MLST compared to 10 by RAPD. All S. aurantiacum isolates shared the same RAPD genotype and exhibited the same rep-PCR profile and sequence type. These results illustrate the efficacy of rep-PCR for both species identification within the S. apiospermum complex and genotyping for the two major species of this complex.Abstract presentation: Part of this work was presented during the 18th Congress of the International Society for Human and Animal Mycology, Berlin (Germany), June 2012.S. Giraud, C. Godon, A. Rougeron, J.P. Bouchara and L. Favennec are members of the ECMM/ISHAM working group on Fungal respiratory infections in Cystic Fibrosis(Fri-CF). © The Author 2015. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Post-synthetic modifications of cadmium-based knots and links.

PubMed

Prakasam, Thirumurugan; Bilbeisi, Rana A; Lusi, Matteo; Olsen, John-Carl; Platas-Iglesias, Carlos; Trabolsi, Ali

2016-05-31

Three topologically non-trivial cadmium(ii)-based complexes-Cd-[2]C, Cd-TK and Cd-SL-were simultaneously self-assembled in a dynamic library, individually isolated and fully characterized using solid-state, gas-phase and solution-phase techniques. Post-synthetic modifications, including reduction and transmetalation, were subsequently achieved. Imine bond reduction followed by demetallation led to the isolation of the corresponding organic molecules [2]C, TK and SL. Transmetalation of Cd-TK and Cd-SL with the zinc(ii) cation resulted in isolation of the corresponding zinc(ii)-containing complexes Zn-TK and Zn-SL.

Novel type of red-shifted chlorophyll a antenna complex from Chromera velia: II. Biochemistry and spectroscopy.

PubMed

Bína, David; Gardian, Zdenko; Herbstová, Miroslava; Kotabová, Eva; Koník, Peter; Litvín, Radek; Prášil, Ondřej; Tichý, Josef; Vácha, František

2014-06-01

A novel chlorophyll a containing pigment-protein complex expressed by cells of Chromera velia adapted to growth under red/far-red illumination [1]. Purification of the complex was achieved by means of anion-exchange chromatography and gel-filtration. The antenna is shown to be an aggregate of ~20kDa proteins of the light-harvesting complex (LHC) family, unstable in the isolated form. The complex possesses an absorption maximum at 705nm at room temperature in addition to the main chlorophyll a maximum at 677nm producing the major emission band at 714nm at room temperature. The far-red absorption is shown to be the property of the isolated aggregate in the intact form and lost upon dissociation. The purified complex was further characterized by circular dichroism spectroscopy and fluorescence spectroscopy. This work thus identified the third different class of antenna complex in C. velia after the recently described FCP-like and LHCr-like antennas. Possible candidates for red antennas are identified in other taxonomic groups, such as eustigmatophytes and the relevance of the present results to other known examples of red-shifted antenna from other organisms is discussed. This work appears to be the first successful isolation of a chlorophyll a-based far-red antenna complex absorbing above 700nm unrelated to LHCI. Copyright © 2014 Elsevier B.V. All rights reserved.

Modified multiplex PCR for identification of Bacillus Calmette-Guérin substrain Tokyo among clinical isolates.

PubMed

Seki, Masaaki; Sato, Akimasa; Honda, Ikuro; Yamazaki, Toshio; Yano, Ikuya; Koyama, Akira; Toida, Ichiro

2005-05-02

When an adverse reaction occurs and a mycobacterial species is isolated from a person vaccinated with Bacillus Calmette-Guérin (BCG) or a patient receiving BCG immunotherapy, it is essential to identify whether the isolate is BCG or another mycobacterial species. However, differentiation of BCG from other members of Mycobacterium tuberculosis complex has been very difficult. Using several specific primer-pairs, Bedwell et al. [Bedwell J, Kairo SK, Behr MA, Bygraves JA. Identification of substrains of BCG vaccine using multiplex PCR. Vaccine 2001; 19: 2146-51] recently reported that they could distinguish BCG substrains. We modified their method to improve differentiation of Tokyo 172 from other members of the M. tuberculosis complex, and examined whether this modified method could be applied to clinical isolates. Our method clearly identified BCG substrain (BCG Tokyo 172) among clinical isolates and easily distinguished between M. tuberculosis and wild-type Mycobacterium bovis.

Pinus pinaster Knot: A Source of Polyphenols against Plasmopara viticola.

PubMed

Gabaston, Julien; Richard, Tristan; Cluzet, Stéphanie; Palos Pinto, Antonio; Dufour, Marie-Cécile; Corio-Costet, Marie-France; Mérillon, Jean-Michel

2017-10-11

Pine knot extract from Pinus pinaster byproducts was characterized by UHPLC-DAD-MS and NMR. Fourteen polyphenols divided into four classes were identified as follows: lignans (nortrachelogenin, pinoresinol, matairesinol, isolariciresinol, secoisolariciresinol), flavonoids (pinocembrin, pinobanksin, dihydrokaempferol, taxifolin), stilbenes (pinosylvin, pinosylvin monomethyl ether, pterostilbene), and phenolic acids (caffeic acid, ferulic acid). The antifungal potential of pine knot extract, as well as the main compounds, was tested in vitro against Plasmopara viticola. The ethanolic extract showed a strong antimildew activity. In addition, pinosylvins and pinocembrin demonstrated significant inhibition of zoospore mobility and mildew development. These findings strongly suggest that pine knot is a potential biomass that could be used as a natural antifungal product.

High prevalence of mec complex C and ccrC is independent of SCCmec type V in Staphylococcus haemolyticus.

PubMed

Bouchami, O; Ben Hassen, A; de Lencastre, H; Miragaia, M

2012-04-01

Staphylococcus haemolyticus is one of the most clinically relevant coagulase-negative staphylococci (CoNS), particularly in immunocompromised patients; however, little is known regarding its molecular epidemiology. In this work, we characterized the genetic background and the SCCmec region of 36 methicillin-resistant S. haemolyticus (MRSHae) and 10 methicillin-susceptible S. haemolyticus (MSSHae) collected from neutropenic patients in Tunisia between 2002 and 2004. The molecular characterization of MRSHae by pulsed-field gel electrophoresis (PFGE) showed that the great majority of the isolates (77.8%) belonged to only four types. SCCmec typing by polymerase chain reaction (PCR) and Southern hybridization showed that isolates belonging to each PFGE type could carry either one or two SCCmec types. SCCmec V was the most common, but mec complex C was frequently associated to ccr allotypes other than ccrC. The mec complex class C was predominant in MRSHae (47%) and ccrC was predominant among both methicillin-resistant and -susceptible isolates (31 and 50%, respectively). Interestingly, one half (50%) of the MRSHae isolates analyzed lacked the known ccr complexes (ccrAB and ccrC), although they carried the mecA. Conversely, all MSSHae carrying a ccrC complex were multidrug-resistant, although they lack the mecA. The results suggest that ccrC and mec complex C are frequent and may exist autonomously and independently of SCCmec type V in S. haemolyticus. Moreover, the data obtained suggest that small chromosomal rearrangements promoting the loss or structural variation of mec and ccr complex appear to occur frequently, which probably provide S. haemolyticus with a specialized means for SCCmec trapping and/or diversification.

Staphylococcus aureus Complex in the Straw-Colored Fruit Bat (Eidolon helvum) in Nigeria.

PubMed

Olatimehin, Ayodele; Shittu, Adebayo O; Onwugamba, Francis C; Mellmann, Alexander; Becker, Karsten; Schaumburg, Frieder

2018-01-01

Bats are economically important animals and serve as food sources in some African regions. They can be colonized with the Staphylococcus aureus complex, which includes Staphylococcus schweitzeri and Staphylococcus argenteus . Fecal carriage of S. aureus complex in the straw-colored fruit bat ( Eidolon helvum ) has been described. However, data on their transmission and adaptation in animals and humans are limited. The aim of this study was to investigate the population structure of the S. aureus complex in E. helvum and to assess the geographical spread of S. aureus complex among other animals and humans. Fecal samples were collected from E. helvum in Obafemi Awolowo University, Ile-Ife, Nigeria. The isolates were characterized by antimicrobial susceptibility testing, spa typing and multilocus sequence typing (MLST). Isolates were screened for the presence of lukS / lukF -PV and the immune evasion cluster ( scn, sak, chp ) which is frequently found in isolates adapted to the human host. A Neighbor-Joining tree was constructed using the concatenated sequences of the seven MLST genes. A total of 250 fecal samples were collected and 53 isolates were included in the final analysis. They were identified as S. aureus ( n = 28), S. schweitzeri ( n = 11) and S. argenteus ( n = 14). Only one S. aureus was resistant to penicillin and another isolate was intermediately susceptible to tetracycline. The scn, sak , and chp gene were not detected. Species-specific MLST clonal complexes (CC) were detected for S. aureus (CC1725), S. argenteus (CC3960, CC3961), and S. schweitzeri (CC2463). STs of S. schweitzeri from this study were similar to STs from bats in Nigeria (ST2464) and Gabon (ST1700) or from monkey in Côte d'Ivoire (ST2058, ST2072). This suggests host adaptation of certain clones to wildlife mammals with a wide geographical spread in Africa. In conclusion, there is evidence of fecal carriage of members of S. aureus complex in E. helvum . S. schweitzeri from bats in Nigeria are closely related to those from bats and monkeys in West and Central Africa suggesting a cross-species transmission and wide geographical distribution. The low antimicrobial resistance rates and the absence of the immune evasion cluster suggests a limited exposure of these isolates to humans.

Susceptibility of Acinetobacter Strains Isolated from Deployed U.S. Military Personnel▿

PubMed Central

Hawley, Joshua S.; Murray, Clinton K.; Griffith, Matthew E.; McElmeel, M. Leticia; Fulcher, Letitia C.; Hospenthal, Duane R.; Jorgensen, James H.

2007-01-01

The susceptibilities of 142 Acinetobacter baumannii-calcoaceticus complex isolates (95 from wounded U.S. soldiers deployed overseas) to 13 antimicrobial agents were determined by broth microdilution. The most active antimicrobial agents (≥95% of isolates susceptible) were colistin, polymyxin B, and minocycline. PMID:17043112

Evaluation of the Vitek MS v3.0 Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry System for Identification of Mycobacterium and Nocardia Species.

PubMed

Body, Barbara A; Beard, Melodie A; Slechta, E Susan; Hanson, Kimberly E; Barker, Adam P; Babady, N Esther; McMillen, Tracy; Tang, Yi-Wei; Brown-Elliott, Barbara A; Iakhiaeva, Elena; Vasireddy, Ravikiran; Vasireddy, Sruthi; Smith, Terry; Wallace, Richard J; Turner, S; Curtis, L; Butler-Wu, Susan; Rychert, Jenna

2018-06-01

This multicenter study was designed to assess the accuracy and reproducibility of the Vitek MS v3.0 matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry system for identification of Mycobacterium and Nocardia species compared to DNA sequencing. A total of 963 clinical isolates representing 51 taxa were evaluated. In all, 663 isolates were correctly identified to the species level (69%), with another 231 (24%) correctly identified to the complex or group level. Fifty-five isolates (6%) could not be identified despite repeat testing. All of the tuberculous mycobacteria (45/45; 100%) and most of the nontuberculous mycobacteria (569/606; 94%) were correctly identified at least to the group or complex level. However, not all species or subspecies within the M. tuberculosis , M. abscessus , and M. avium complexes and within the M. fortuitum and M. mucogenicum groups could be differentiated. Among the 312 Nocardia isolates tested, 236 (76%) were correctly identified to the species level, with an additional 44 (14%) correctly identified to the complex level. Species within the N. nova and N. transvalensis complexes could not always be differentiated. Eleven percent of the isolates (103/963) underwent repeat testing in order to get a final result. Identification of a representative set of Mycobacterium and Nocardia species was highly reproducible, with 297 of 300 (99%) replicates correctly identified using multiple kit lots, instruments, analysts, and sites. These findings demonstrate that the system is robust and has utility for the routine identification of mycobacteria and Nocardia in clinical practice. Copyright © 2018 American Society for Microbiology.

Simple low cost differentiation of Candida auris from Candida haemulonii complex using CHROMagar Candida medium supplemented with Pal's medium.

PubMed

Kumar, Anil; Sachu, Arun; Mohan, Karthika; Vinod, Vivek; Dinesh, Kavitha; Karim, Shamsul

Candida auris is unique due to its multidrug resistance and misidentification as Candida haemulonii by commercial systems. Its correct identification is important to avoid inappropriate treatments. To develop a cheap method for differentiating C. auris from isolates identified as C. haemulonii by VITEK2. Fifteen C. auris isolates, six isolates each of C. haemulonii and Candida duobushaemulonii, and one isolate of Candida haemulonii var. vulnera were tested using CHROMagar Candida medium supplemented with Pal's agar for better differentiation. On CHROMagar Candida medium supplemented with Pal's agar all C. auris strains showed confluent growth of white to cream colored smooth colonies at 37°C and 42°C after 24 and 48h incubation and did not produce pseudohyphae. The isolates of the C. haemulonii complex, on the contrary, showed poor growth of smooth, light-pink colonies at 24h while at 48h the growth was semiconfluent with the production of pseudohyphae. C. haemulonii complex failed to grow at 42°C. We report a rapid and cheap method using CHROMagar Candida medium supplemented with Pal's agar for differentiating C. auris from isolates identified as C. haemulonii by VITEK2. Copyright © 2017 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.

First Molecular Characterization of Leishmania Species Causing Visceral Leishmaniasis among Children in Yemen

PubMed Central

Mahdy, Mohammed A. K.; Al-Mekhlafi, Abdulsalam M.; Abdul-Ghani, Rashad; Saif-Ali, Reyadh; Al-Mekhlafi, Hesham M.; Al-Eryani, Samira M.; Lim, Yvonne A. L.; Mahmud, Rohela

2016-01-01

Visceral leishmaniasis (VL) is a debilitating, often fatal disease caused by Leishmania donovani complex; however, it is a neglected tropical disease. L. donovani complex comprises two closely related species, L. donovani that is mostly anthroponotic and L. infantum that is zoonotic. Differentiation between these two species is critical due to the differences in their epidemiology and pathology. However, they cannot be differentiated morphologically, and their speciation using isoenzyme-based methods poses a difficult task and may be unreliable. Molecular characterization is now the most reliable method to differentiate between them and to determine their phylogenetic relationships. The present study aims to characterize Leishmania species isolated from bone marrows of Yemeni pediatric patients using sequence analysis of the ribosomal internal transcribed spacer-1 (ITS1) gene. Out of 41 isolates from Giemsa-stained bone marrow smears, 25 isolates were successfully amplified by nested polymerase chain reaction and sequenced in both directions. Phylogenetic analysis using neighbor joining method placed all study isolates in one cluster with L. donovani complex (99% bootstrap). The analysis of ITS1 for microsatellite repeat numbers identified L. infantum in 11 isolates and L. donovani in 14 isolates. These data suggest the possibility of both anthroponotic and zoonotic transmission of VL-causing Leishmania species in Yemen. Exploring the possible animal reservoir hosts is therefore needed for effective control to be achieved. PMID:26966902

Serogroup and Clonal Characterization of Czech Invasive Neisseria meningitidis Strains Isolated from 1971 to 2015

PubMed Central

Jandova, Zuzana; Musilek, Martin; Vackova, Zuzana; Kozakova, Jana; Krizova, Pavla

2016-01-01

Background This study presents antigenic and genetic characteristics of Neisseria meningitidis strains recovered from invasive meningococcal disease (IMD) in the Czech Republic in 1971–2015. Material and Methods A total of 1970 isolates from IMD, referred to the National Reference Laboratory for Meningococcal Infections in 1971–2015, were studied. All isolates were identified and characterized by conventional biochemical and serological tests. Most isolates (82.5%) were characterized by multilocus sequence typing method. Results In the study period 1971–2015, the leading serogroup was B (52.4%), most often assigned to clonal complexes cc32, cc41/44, cc18, and cc269. A significant percentage of strains were of serogroup C (41.4%), with high clonal homogeneity due to hyperinvasive complex cc11, which played an important role in IMD in the Czech Republic in the mid-1990s. Serogroup Y isolates, mostly assigned to cc23, and isolates of clonally homogeneous serogroup W have also been recovered more often over the last years. Conclusion The incidence of IMD and distribution of serogroups and clonal complexes of N. meningitidis in the Czech Republic varied over time, as can be seen from the long-term monitoring, including molecular surveillance data. Data from the conventional and molecular IMD surveillance are helpful in refining the antimeningococcal vaccination strategy in the Czech Republic. PMID:27936105

The Tom Core Complex

PubMed Central

Ahting, Uwe; Thun, Clemens; Hegerl, Reiner; Typke, Dieter; Nargang, Frank E.; Neupert, Walter; Nussberger, Stephan

1999-01-01

Translocation of nuclear-encoded preproteins across the outer membrane of mitochondria is mediated by the multicomponent transmembrane TOM complex. We have isolated the TOM core complex of Neurospora crassa by removing the receptors Tom70 and Tom20 from the isolated TOM holo complex by treatment with the detergent dodecyl maltoside. It consists of Tom40, Tom22, and the small Tom components, Tom6 and Tom7. This core complex was also purified directly from mitochondria after solubilization with dodecyl maltoside. The TOM core complex has the characteristics of the general insertion pore; it contains high-conductance channels and binds preprotein in a targeting sequence-dependent manner. It forms a double ring structure that, in contrast to the holo complex, lacks the third density seen in the latter particles. Three-dimensional reconstruction by electron tomography exhibits two open pores traversing the complex with a diameter of ∼2.1 nm and a height of ∼7 nm. Tom40 is the key structural element of the TOM core complex. PMID:10579717

Observation of Electronic Excitation Transfer Through Light Harvesting Complex II Using Two-Dimensional Electronic-Vibrational Spectroscopy

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

Lewis, Nicholas H. C.; Gruenke, Natalie L.; Oliver, Thomas A. A.

Light-harvesting complex II (LHCII) serves a central role in light harvesting for oxygenic photosynthesis and is arguably the most important photosynthetic antenna complex. In this article, we present two-dimensional electronic–vibrational (2DEV) spectra of LHCII isolated from spinach, demonstrating the possibility of using this technique to track the transfer of electronic excitation energy between specific pigments within the complex. We assign the spectral bands via comparison with the 2DEV spectra of the isolated chromophores, chlorophyll a and b, and present evidence that excitation energy between the pigments of the complex are observed in these spectra. Lastly, we analyze the essential componentsmore » of the 2DEV spectra using singular value decomposition, which makes it possible to reveal the relaxation pathways within this complex.« less

Advanced instrumental methods for analyzing organics in solid waste: The use of gas chromatography/matrix isolation infrared spectroscopy (GC/MIIR) and supercritical fluid chromatography (SFC) for waste characterization

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

Raphaelian, L.A.; Boparai, A.S.; Schneider, J.F.

1987-01-01

Objectives of this research project were: (1) to enhance the capabilities of analyzing the complex mixtures found in coal wastes by using gas chromatography/matrix isolation infrared spectroscopy (GC/MIIR); (2) to separate, by supercritical fluid chromatography (SFC), the complex mixtures found in coal wastes into a few, less-complex mixtures so that analysis by gas chromatography (GC/MS) and GC/MIIR would be simplified. Preliminary results are presented for the mass spectra and infrared spectra of xylene isomers, gas chromatogram of 12 C/sub 2/-Napthalenes, averaged IR spectrum and a comparison of matrix isolation with light-pipe infrared spectra. A SFC chromatogram of polynuclear aromatic hydrocarbonsmore » is also presented. 2 refs., 5 figs.« less

Methicillin-Susceptible Staphylococcus aureus Endocarditis Isolates Are Associated With Clonal Complex 30 Genotype and a Distinct Repertoire of Enterotoxins and Adhesins

PubMed Central

Nienaber, Juhsien J.C.; Sharma Kuinkel, Batu K.; Clarke-Pearson, Michael; Lamlertthon, Supaporn; Park, Lawrence; Rude, Thomas H.; Barriere, Steve; Woods, Christopher W.; Chu, Vivian H.; Marín, Mercedes; Bukovski, Suzana; Garcia, Patricia; Corey, G.Ralph; Korman, Tony; Doco-Lecompte, Thanh; Murdoch, David R.; Reller, L. Barth

2011-01-01

Background. Using multinational collections of methicillin-susceptible Staphylococcus aureus (MSSA) isolates from infective endocarditis (IE) and soft tissue infections (STIs), we sought to (1) validate the finding that S. aureus in clonal complex (CC) 30 is associated with hematogenous complications and (2) test the hypothesis that specific genetic characteristics in S. aureus are associated with infection severity. Methods. IE and STI isolates from 2 cohorts were frequency matched by geographic origin. Isolates underwent spa typing to infer CC and multiplex polymerase chain reaction for presence of virulence genes. Results. 114 isolate pairs were genotyped. IE isolates were more likely to be CC30 (19.5% vs 6.2%; P = .005) and to contain 3 adhesins (clfB, cna, map/eap; P < .0001 for all) and 5 enterotoxins (tst, sea, sed, see, and sei; P ≤ .005 for all). CC30 isolates were more likely to contain cna, tst, sea, see, seg, and chp (P < .05 for all). Conclusions. MSSA IE isolates were significantly more likely to be CC30 and to possess a distinct repertoire of virulence genes than MSSA STI isolates from the same region. The genetic basis of this association requires further study. PMID:21844296

Identification and molecular epidemiology of dermatophyte isolates by repetitive-sequence-PCR-based DNA fingerprinting using the DiversiLab system in Turkey.

PubMed

Koc, A Nedret; Atalay, Mustafa A; Inci, Melek; Sariguzel, Fatma M; Sav, Hafize

2017-05-01

Dermatophyte species, isolation and identification in clinical samples are still difficult and take a long time. The identification and molecular epidemiology of dermatophytes commonly isolated in a clinical laboratory in Turkey by repetitive sequence-based PCR (rep-PCR) were assessed by comparing the results with those of reference identification. A total of 44 dermatophytes isolated from various clinical specimens of 20 patients with superficial mycoses in Kayseri and 24 patients in Hatay were studied. The identification of dermatophyte isolates was based on the reference identification and rep-PCR using the DiversiLab System (BioMerieux). The genotyping of dermatophyte isolates from different patients was determined by rep-PCR. In the identification of dermatophyte isolates, agreement between rep-PCR and conventional methods was 87.8 % ( 36 of 41). The dermatophyte strains belonged to four clones (A -D) which were determined by the use of rep-PCR. The dermatophyte strains in Clone B, D showed identical patterns with respect to the region. In conclusion, rep-PCR appears to be useful for evaluation of the identification and clonal relationships between Trichophyton rubrum species complex and Trichophyton mentagrophytes species complex isolates. The similarity and diversity of these isolates may be assessed according to different regions by rep-PCR. © 2017 Blackwell Verlag GmbH.

Efficacy of species-specific recA PCR tests in the identification of Burkholderia cepacia complex environmental isolates.

PubMed

Dalmastri, Claudia; Pirone, Luisa; Tabacchioni, Silvia; Bevivino, Annamaria; Chiarini, Luigi

2005-05-01

In this study, we evaluated if recA species-specific PCR assays could be successfully applied to identify environmental isolates of the widespread Burkholderia cepacia complex (Bcc) species. A total of 729 Bcc rhizosphere isolates collected in different samplings were assigned to the species B. cepacia genomovar I (61), B. cenocepacia recA lineage IIIB (514), B. ambifaria (124) and B. pyrrocinia (30), by means of recA (RFLP) analysis, and PCR tests were performed to assess sensitivity and specificity of recA species-specific primers pairs. B. cepacia genomovar I specific primers produced the expected amplicon with all isolates of the corresponding species (sensitivity, 100%), and cross-reacted with all B. pyrrocinia isolates. On the contrary, B. cenocepacia IIIB primers did not give the expected amplicon in 164 B. cenocepacia IIIB isolates (sensitivity, 68.1%), and isolates of distinct populations showed different sensitivity. B. ambifaria primers failed to amplify a recA-specific fragment only in a few isolates of this species (sensitivity, 93.5%). The absence of specific amplification in a high number of B. cenocepacia rhizosphere isolates indicates that recA specific PCR assays can lead to an underestimation of environmental microorganisms belonging to this bacterial species.

Reliable differentiation of Meyerozyma guilliermondii from Meyerozyma caribbica by internal transcribed spacer restriction fingerprinting.

PubMed

Romi, Wahengbam; Keisam, Santosh; Ahmed, Giasuddin; Jeyaram, Kumaraswamy

2014-02-28

Meyerozyma guilliermondii (anamorph Candida guilliermondii) and Meyerozyma caribbica (anamorph Candida fermentati) are closely related species of the genetically heterogenous M. guilliermondii complex. Conventional phenotypic methods frequently misidentify the species within this complex and also with other species of the Saccharomycotina CTG clade. Even the long-established sequencing of large subunit (LSU) rRNA gene remains ambiguous. We also faced similar problem during identification of yeast isolates of M. guilliermondii complex from indigenous bamboo shoot fermentation in North East India. There is a need for development of reliable and accurate identification methods for these closely related species because of their increasing importance as emerging infectious yeasts and associated biotechnological attributes. We targeted the highly variable internal transcribed spacer (ITS) region (ITS1-5.8S-ITS2) and identified seven restriction enzymes through in silico analysis for differentiating M. guilliermondii from M. caribbica. Fifty five isolates of M. guilliermondii complex which could not be delineated into species-specific taxonomic ranks by API 20 C AUX and LSU rRNA gene D1/D2 sequencing were subjected to ITS-restriction fragment length polymorphism (ITS-RFLP) analysis. TaqI ITS-RFLP distinctly differentiated the isolates into M. guilliermondii (47 isolates) and M. caribbica (08 isolates) with reproducible species-specific patterns similar to the in silico prediction. The reliability of this method was validated by ITS1-5.8S-ITS2 sequencing, mitochondrial DNA RFLP and electrophoretic karyotyping. We herein described a reliable ITS-RFLP method for distinct differentiation of frequently misidentified M. guilliermondii from M. caribbica. Even though in silico analysis differentiated other closely related species of M. guilliermondii complex from the above two species, it is yet to be confirmed by in vitro analysis using reference strains. This method can be used as a reliable tool for rapid and accurate identification of closely related species of M. guilliermondii complex and for differentiating emerging infectious yeasts of the Saccharomycotina CTG clade.

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

Kang, Kyungsu; Lee, Kyung-Mi; Yoo, Ji-Hye

Graphical abstract: Schematic diagram of the possible molecular mechanism underlying the inhibition of the Wnt/{beta}-catenin signaling pathway and the induction of G0/G1-phase arrest by gomisins J and N, derived from the fruits of S. chinensis, in HCT116 human colon cancer cells. Highlights: Black-Right-Pointing-Pointer Gomisins J and N inhibited Wnt/{beta}-catenin signaling pathway in HCT116 cells. Black-Right-Pointing-Pointer Gomisins J and N disrupted the binding of {beta}-catenin to specific DNA sequences, TBE. Black-Right-Pointing-Pointer Gomisins J and N inhibited the HCT116 cell proliferation through G0/G1 phase arrest. Black-Right-Pointing-Pointer Gomisins J and N inhibited the expression of Cyc D1, a Wnt/{beta}-catenin target gene. -- Abstract:more » Here, we report that gomisin J and gomisin N, dibenzocyclooctadiene type lignans isolated from Schisandra chinensis, inhibit Wnt/{beta}-catenin signaling in HCT116 cells. Gomisins J and N appear to inhibit Wnt/{beta}-catenin signaling by disrupting the interaction between {beta}-catenin and its specific target DNA sequences (TCF binding elements, TBE) rather than by altering the expression of the {beta}-catenin protein. Gomisins J and N inhibit HCT116 cell proliferation by arresting the cell cycle at the G0/G1 phase. The G0/G1 phase arrest induced by gomisins J and N appears to be caused by a decrease in the expression of Cyclin D1, a representative target gene of the Wnt/{beta}-catenin signaling pathway, as well as Cdk2, Cdk4, and E2F-1. Therefore, gomisins J and N, the novel Wnt/{beta}-catenin inhibitors discovered in this study, may serve as potential agents for the prevention and treatment of human colorectal cancers.« less

The anti-cancer charm of flavonoids: a cup-of-tea will do!

PubMed

Amin, Amr; Buratovich, Michael

2007-06-01

Hormone-dependent cancers of the breast, prostate and colon have, in the past decade, become the leading causes of morbidity and mortality. Billions of dollars have been, and still are being spent to study cancers like these, and, in the past three decades, thanks to work by thousands of dedicated scientists, tremendous advancements in the understanding and treatment of cancer have been made. Nevertheless, as there is no sure-fire cure for a variety of cancers to date, natural protection against cancer has been receiving a great deal of attention lately not only from cancer patients but, surprisingly, from physicians as well. Phytoestrogens, plant-derived secondary metabolites, are diphenolic substances with structural similarity to naturally-occurring human steroid hormones. Phytoestrogens are normally divided into three main classes: flavonoids, coumestans and lignans. Flavonoids are found in almost all plant families in the leaves, stems, roots, flowers and seeds of plants and are among the most popular anti-cancer candidates. Flavonoidic derivatives have a wide range of biological actions such as antibacterial, antiviral, anti-inflammatory, anticancer, and antiallergic activities. Some of these benefits are explained by the potent antioxidant effects of flavonoids, which include metal chelation and free-radical scavenging activities. Patent applications regarding flavonoids range from protocols for extraction and purification from natural resources and the establishment of various biological activities for these extracts to novel methods for the production and isolation of flavonoids with known biological activities. This review will bring the reader up to date on the current knowledge and research available in the field of flavonoids and hormone-dependent cancers, and many of the submitted patents that exploit flavonoids.

Schisantherin A suppresses osteoclast formation and wear particle-induced osteolysis via modulating RANKL signaling pathways

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

He, Yi; Zhang, Qing; Shen, Yi

Highlights: • Schisantherin A suppresses osteoclasts formation and function in vitro. • Schisantherin A impairs RANKL signaling pathway. • Schisantherin A suppresses osteolysis in vivo. • Schisantherin A may be used for treating osteoclast related diseases. - Abstract: Receptor activator of NF-κB ligand (RANKL) plays critical role in osteoclastogenesis. Targeting RANKL signaling pathways has been a promising strategy for treating osteoclast related bone diseases such as osteoporosis and aseptic prosthetic loosening. Schisantherin A (SA), a dibenzocyclooctadiene lignan isolated from the fruit of Schisandra sphenanthera, has been used as an antitussive, tonic, and sedative agent, but its effect on osteoclasts hasmore » been hitherto unknown. In the present study, SA was found to inhibit RANKL-induced osteoclast formation and bone resorption. The osteoclastic specific marker genes induced by RANKL including c-Src, SA inhibited OSCAR, cathepsin K and TRAP in a dose dependent manner. Further signal transduction studies revealed that SA down-regulate RANKL-induced nuclear factor-kappaB (NF-κB) signaling activation by suppressing the phosphorylation and degradation of IκBα, and subsequently preventing the NF-κB transcriptional activity. Moreover, SA also decreased the RANKL-induced MAPKs signaling pathway, including JNK and ERK1/2 posphorylation while had no obvious effects on p38 activation. Finally, SA suppressed the NF-κB and MAPKs subsequent gene expression of NFATc1 and c-Fos. In vivo studies, SA inhibited osteoclast function and exhibited bone protection effect in wear-particle-induced bone erosion model. Taken together, SA could attenuate osteoclast formation and wear particle-induced osteolysis by mediating RANKL signaling pathways. These data indicated that SA is a promising therapeutic natural compound for the treatment of osteoclast-related prosthesis loosening.« less

Arctigenin enhances chemosensitivity of cancer cells to cisplatin through inhibition of the STAT3 signaling pathway.

PubMed

Yao, Xiangyang; Zhu, Fenfen; Zhao, Zhihui; Liu, Chang; Luo, Lan; Yin, Zhimin

2011-10-01

Arctigenin is a dibenzylbutyrolactone lignan isolated from Bardanae fructus, Arctium lappa L, Saussureamedusa, Torreya nucifera, and Ipomea cairica. It has been reported to exhibit anti-inflammatory activities, which is mainly mediated through its inhibitory effect on nuclear transcription factor-kappaB (NF-κB). But the role of arctigenin in JAK-STAT3 signaling pathways is still unclear. In present study, we investigated the effect of arctigenin on signal transducer and activator of transcription 3 (STAT3) pathway and evaluated whether suppression of STAT3 activity by arctigenin could sensitize cancer cells to a chemotherapeutic drug cisplatin. Our results show that arctigenin significantly suppressed both constitutively activated and IL-6-induced STAT3 phosphorylation and subsequent nuclear translocation in cancer cells. Inhibition of STAT3 tyrosine phosphorylation was found to be achieved through suppression of Src, JAK1, and JAK2, while suppression of STAT3 serine phosphorylation was mediated by inhibition of ERK activation. Pervanadate reversed the arctigenin-induced downregulation of STAT3 activation, suggesting the involvement of a protein tyrosine phosphatase. Indeed, arctigenin can obviously induce the expression of the PTP SHP-2. Furthermore, the constitutive activation level of STAT3 was found to be correlated to the resistance of cancer cells to cisplatin-induced apoptosis. Arctigenin dramatically promoted cisplatin-induced cell death in cancer cells, indicating that arctigenin enhanced the sensitivity of cancer cells to cisplatin mainly via STAT3 suppression. These observations suggest a novel anticancer function of arctigenin and a potential therapeutic strategy of using arctigenin in combination with chemotherapeutic agents for cancer treatment. Copyright © 2011 Wiley-Liss, Inc.

The Effects of Non-Redox Active Metal Ions on the Activation of Dioxygen: Isolation and Characterization of a Heterobimetallic Complex Containing a MnIII–(μ-OH)–CaII core

PubMed Central

Park, Young Jun; Ziller, Joseph W.; Borovik, A. S.

2011-01-01

Rate enhancements for the reduction of dioxygen by a MnII complex were observed in the presence of redox inactive Group 2 metal ions. The rate changes correlated with an increase in the Lewis acidity of the Group 2 metal ions. These studies led to the isolation of heterobimetallic complexes that contain MnIII-(μ-OH)-MII cores (MII = CaII, BaII), in which the hydroxo oxygen atom is derived from O2. This type of core structure has relevance to the oxygen evolving complexes within photosystem II. PMID:21595481

Races of the celery pathogen Fusarium oxysporum f. sp. apii are polyphyletic

USDA-ARS?s Scientific Manuscript database

Fusarium oxysporum species complex (FOSC) isolates were obtained from celery with symptoms of Fusarium yellows between 1993 and 2013 primarily in California. Virulence tests and a two-gene dataset from 174 isolates indicated that virulent isolates collected before 2013 were a highly clonal populatio...

Isolation by ion-exchange methods. In Sarker S.D. (ed) Natural Products Isolation, 3rd edition

USDA-ARS?s Scientific Manuscript database

The primary goal of many natural products chemists is to extract, isolate, and characterize specific analytes from complex plant, animal, microbial, and food matrices. To achieve this goal, they rely considerably on highly sophisticated and highly hyphenated modern instrumentation. Yet, the vast maj...

Conformation Control of a Conjugated Polymer through Complexation with Bile Acids Generates Its Novel Spectral and Morphological Properties.

PubMed

Tsuchiya, Youichi; Noguchi, Takao; Yoshihara, Daisuke; Roy, Bappaditya; Yamamoto, Tatsuhiro; Shinkai, Seiji

2016-11-29

Control of higher-order polymer structures attracts a great deal of interest for many researchers when they lead to the development of materials having various advanced functions. Among them, conjugated polymers that are useful as starting materials in the design of molecular wires are particularly attractive. However, an equilibrium existing between isolated chains and bundled aggregates is inevitable and has made their physical properties very complicated. As an attempt to simplify this situation, we previously reported that a polymer chain of a water-soluble polythiophene could be isolated through complexation with a helix-forming polysaccharide. More recently, a covalently self-threading polythiophene was reported, the main chain of which was physically protected from self-folding and chain-chain π-stacking. In this report, we wish to report a new strategy to isolate a water-soluble polythiophene and to control its higher-order structure by a supramolecular approach: that is, among a few bile acids, lithocholate can form stoichiometric complexes with cationic polythiophene to isolate the polymer chain, and the higher-order structure is changeable by the molar ratio. The optical and morphological studies have been thoroughly performed, and the resultant complex has been applied to the selective recognition of two AMP structural isomers.

Accurate and Practical Identification of 20 Fusarium Species by Seven-Locus Sequence Analysis and Reverse Line Blot Hybridization, and an In Vitro Antifungal Susceptibility Study▿†

PubMed Central

Wang, He; Xiao, Meng; Kong, Fanrong; Chen, Sharon; Dou, Hong-Tao; Sorrell, Tania; Li, Ruo-Yu; Xu, Ying-Chun

2011-01-01

Eleven reference and 25 clinical isolates of Fusarium were subject to multilocus DNA sequence analysis to determine the species and haplotypes of the fusarial isolates from Beijing and Shandong, China. Seven loci were analyzed: the translation elongation factor 1 alpha gene (EF-1α); the nuclear rRNA internal transcribed spacer (ITS), large subunit (LSU), and intergenic spacer (IGS) regions; the second largest subunit of the RNA polymerase gene (RPB2); the calmodulin gene (CAM); and the mitochondrial small subunit (mtSSU) rRNA gene. We also evaluated an IGS-targeted PCR/reverse line blot (RLB) assay for species/haplotype identification of Fusarium. Twenty Fusarium species and seven species complexes were identified. Of 25 clinical isolates (10 species), the Gibberella (Fusarium) fujikuroi species complex was the commonest (40%) and was followed by the Fusarium solani species complex (FSSC) (36%) and the F. incarnatum-F. equiseti species complex (12%). Six FSSC isolates were identified to the species level as FSSC-3+4, and three as FSSC-5. Twenty-nine IGS, 27 EF-1α, 26 RPB2, 24 CAM, 18 ITS, 19 LSU, and 18 mtSSU haplotypes were identified; 29 were unique, and haplotypes for 24 clinical strains were novel. By parsimony informative character analysis, the IGS locus was the most phylogenetically informative, and the rRNA gene regions were the least. Results by RLB were concordant with multilocus sequence analysis for all isolates. Amphotericin B was the most active drug against all species. Voriconazole MICs were high (>8 μg/ml) for 15 (42%) isolates, including FSSC. Analysis of larger numbers of isolates is required to determine the clinical utility of the seven-locus sequence analysis and RLB assay in species classification of fusaria. PMID:21389150

Adaptation of Fusarium oxysporum and Fusarium dimerum to the specific aquatic environment provided by the water systems of hospitals.

PubMed

Steinberg, Christian; Laurent, Julie; Edel-Hermann, Véronique; Barbezant, Marie; Sixt, Nathalie; Dalle, Frédéric; Aho, Serge; Bonnin, Alain; Hartemann, Philippe; Sautour, Marc

2015-06-01

Members of the Fusarium group were recently detected in water distribution systems of several hospitals in the world. An epidemiological investigation was conducted over 2 years in hospital buildings in Dijon and Nancy (France) and in non-hospital buildings in Dijon. The fungi were detected only within the water distribution systems of the hospital buildings and also, but at very low concentrations, in the urban water network of Nancy. All fungi were identified as Fusarium oxysporum species complex (FOSC) and Fusarium dimerum species complex (FDSC) by sequencing part of the translation elongation factor 1-alpha (TEF-1α) gene. Very low diversity was found in each complex, suggesting the existence of a clonal population for each. Density and heterogeneous distributions according to buildings and variability over time were explained by episodic detachments of parts of the colony from biofilms in the pipes. Isolates of these waterborne populations as well as soilborne isolates were tested for their ability to grow in liquid medium in the presence of increasing concentrations of sodium hypochlorite, copper sulfate, anti-corrosion pipe coating, at various temperatures (4°-42 °C) and on agar medium with amphotericin B and voriconazole. The waterborne isolates tolerated higher sodium hypochlorite and copper sulfate concentrations and temperatures than did soilborne isolates but did not show any specific resistance to fungicides. In addition, unlike waterborne isolates, soilborne isolates did not survive in water even supplemented with glucose, while the former developed in the soil as well as soilborne isolates. We concluded the existence of homogeneous populations of FOSC and FDSC common to all contaminated hospital sites. These populations are present at very low densities in natural waters, making them difficult to detect, but they are adapted to the specific conditions offered by the complex water systems of public hospitals in Dijon and Nancy and probably other localities in the world. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sky island bird populations isolated by ancient genetic barriers are characterized by different song traits than those isolated by recent deforestation.

PubMed

Purushotham, Chetana B; Robin, V V

2016-10-01

Various mechanisms of isolation can structure populations and result in cultural and genetic differentiation. Similar to genetic markers, for songbirds, culturally transmitted sexual signals such as breeding song can be used as a measure of differentiation as songs can also be impacted by geographic isolation resulting in population-level differences in song structure. Several studies have found differences in song structure either across ancient geographic barriers or across contemporary habitat barriers owing to deforestation. However, very few studies have examined the effect of both ancient barriers and recent deforestation in the same system. In this study, we examined the geographic variation in song structure across six populations of the White-bellied Shortwing, a threatened and endemic songbird species complex found on isolated mountaintops or "sky islands" of the Western Ghats. While some sky islands in the system are isolated by ancient valleys, others are separated by deforestation. We examined 14 frequency and temporal spectral traits and two syntax traits from 835 songs of 38 individuals across the six populations. We identified three major song clusters based on a discriminant model of spectral traits, degree of similarity of syntax features, as well as responses of birds to opportunistic playback. However, some traits like complex vocal mechanisms (CVM), relating to the use of syrinxes, clearly differentiated both ancient and recently fragmented populations. We suggest that CVMs may have a cultural basis and can be used to identify culturally isolated populations that cannot be differentiated using genetic markers or commonly used frequency-based song traits. Our results demonstrate the use of bird songs to reconstruct phylogenetic groups and impacts of habitat fragmentation even in complex scenarios of historic and contemporary isolation.

Translation and Assembly of Radiolabeled Mitochondrial DNA-Encoded Protein Subunits from Cultured Cells and Isolated Mitochondria.

PubMed

Formosa, Luke E; Hofer, Annette; Tischner, Christin; Wenz, Tina; Ryan, Michael T

2016-01-01

In higher eukaryotes, the mitochondrial electron transport chain consists of five multi-subunit membrane complexes responsible for the generation of cellular ATP. Of these, four complexes are under dual genetic control as they contain subunits encoded by both the mitochondrial and nuclear genomes, thereby adding another layer of complexity to the puzzle of respiratory complex biogenesis. These subunits must be synthesized and assembled in a coordinated manner in order to ensure correct biogenesis of different respiratory complexes. Here, we describe techniques to (1) specifically radiolabel proteins encoded by mtDNA to monitor the rate of synthesis using pulse labeling methods, and (2) analyze the stability, assembly, and turnover of subunits using pulse-chase methods in cultured cells and isolated mitochondria.

Isolation of a Mycobacterium microti-like organism from a rock hyrax (Procavia capensis) in a Canadian zoo

PubMed Central

Lutze-Wallace, Cyril; Turcotte, Claude; Glover, Gordon; Cousins, Debby; Bell, John; Berlie-Surujballi, Gloria; Barbeau, Yvon; Randall, Geoff

2006-01-01

A Mycobacterium tuberculosis complex organism was isolated from a zoo resident rock hyrax (Procavia capensis) imported into Canada from South Africa. The strain was identified biochemically as Mycobacterium microti. The spoligotype pattern obtained for this isolate was found to be rare. This represents the first report of isolation and spoligotyping of M. microti in North America. PMID:17078252

NACE-ESI-TOF MS to reveal phenolic compounds from olive oil: introducing enriched olive oil directly inside capillary.

PubMed

Gómez-Caravaca, Ana María; Carrasco-Pancorbo, Alegría; Segura-Carretero, Antonio; Fernández-Gutiérrez, Alberto

2009-09-01

Most CE methods for the analysis of phenols from olive oil use an aqueous electrolyte separation medium, although the importance of NACE is obvious, as this kind of CE seems to be more compatible with the hydrophobic olive oil matrix and could facilitate its direct injection. In the current work we develop a method involving SPE and NACE coupled to ESI-TOF MS. All the CE and ESI-TOF MS parameters were optimized in order to maximize the number of phenolic compounds detected and the sensitivity in their determination. Electrophoretic separation was carried out using a CE buffer system consisting of 25 mM NH(4)OAc/AcH in methanol/ACN (1/1 v/v) at an apparent pH value of 5.0. We studied in depth the effect of the nature and concentration of different electrolytes dissolved in different organic solvents and other experimental and instrumental CE variables. The results were compared with those obtained by CZE (with aqueous buffers) coupled to ESI-TOF MS; both methods offered to the analyst the chance to study phenolic compounds of different families (such as phenolic alcohols, lignans, complex phenols, flavonoids, etc.) from virgin olive oil by injecting methanolic extracts with efficient and fast CE separations. In the case of NACE method, we also studied the direct injection of the investigated matrix introducing a plug of olive oil directly into the capillary.

Capillary electrophoresis-electrospray ionization-mass spectrometry method to determine the phenolic fraction of extra-virgin olive oil.

PubMed

Carrasco-Pancorbo, Alegría; Arráez-Román, David; Segura-Carretero, Antonio; Fernández-Gutiérrez, Alberto

2006-06-01

We describe the first analytical method involving SPE and CZE coupled to ESI-IT MS (CZE-ESI-MS) used to identify and characterize phenolic compounds in olive oil samples. The SPE, CZE and ESI-MS parameters were optimized in order to maximize the number of phenolic compounds detected and the sensitivity of their determination. To this end we have devised a detailed method to find the best conditions for CE separation and the detection by MS of the phenolic compounds present in olive oil using a methanol-water extract of Picual extra-virgin olive oil (VOO). Electrophoretic separation was carried out using an aqueous CE buffer system consisting of 60 mM NH(4)OAc at pH 9.5 with 5% of 2-propanol, a sheath liquid containing 2-propanol/water 60:40 v/v and 0.1% v/v triethylamine. This method offers to the analyst the chance to study important phenolic compounds such as phenolic alcohols (tyrosol (TY), hydroxytyrosol (HYTY) and 2-(4-hydroxyphenyl)ethyl acetate), lignans ((+)-pinoresinol and (+)-1-acetoxypinoresinol), complex phenols (ligstroside aglycon (Lig Agl), oleuropein aglycon, their respective decarboxylated derivatives and several isomeric forms of these (dialdehydic form of oleuropein aglycon, dialdehydic form of ligstroside aglycon, dialdehydic form of decarboxymethyl elenolic acid linked to HYTY, dialdehydic form of decarboxymethyl elenolic acid linked to TY) and 10-hydroxy-oleuropein aglycon) and one other phenolic compound (elenolic acid) in extra-VOO by using a simple SPE before CE-ESI-MS analysis.

Sequential Test Strategies for Multiple Fault Isolation

NASA Technical Reports Server (NTRS)

Shakeri, M.; Pattipati, Krishna R.; Raghavan, V.; Patterson-Hine, Ann; Kell, T.

1997-01-01

In this paper, we consider the problem of constructing near optimal test sequencing algorithms for diagnosing multiple faults in redundant (fault-tolerant) systems. The computational complexity of solving the optimal multiple-fault isolation problem is super-exponential, that is, it is much more difficult than the single-fault isolation problem, which, by itself, is NP-hard. By employing concepts from information theory and Lagrangian relaxation, we present several static and dynamic (on-line or interactive) test sequencing algorithms for the multiple fault isolation problem that provide a trade-off between the degree of suboptimality and computational complexity. Furthermore, we present novel diagnostic strategies that generate a static diagnostic directed graph (digraph), instead of a static diagnostic tree, for multiple fault diagnosis. Using this approach, the storage complexity of the overall diagnostic strategy reduces substantially. Computational results based on real-world systems indicate that the size of a static multiple fault strategy is strictly related to the structure of the system, and that the use of an on-line multiple fault strategy can diagnose faults in systems with as many as 10,000 failure sources.

Expedient preparative isolation and tandem mass spectrometric characterization of C-seco triterpenoids from Neem oil.

PubMed

Haldar, Saikat; Mulani, Fayaj A; Aarthy, Thiagarayaselvam; Dandekar, Devdutta S; Thulasiram, Hirekodathakallu V

2014-10-31

C-seco triterpenoids are widely bioactive class of natural products with high structural complexity and diversity. The preparative isolation of these molecules with high purity is greatly desirable, although restricted due to the complexity of natural extracts. In this article we have demonstrated a Medium Pressure Liquid Chromatography (MPLC) based protocol for the isolation of eight major C-seco triterpenoids of salannin skeleton from Neem (Azadirachta indica) oil. Successive application of normal phase pre-packed silica-gel columns for the fractionation followed by reverse phase in automated MPLC system expedited the process and furnished highly pure metabolites. Furthermore, eight isolated triterpenoids along with five semi-synthesized derivatives were characterized using ultra performance liquid chromatography-electrospray ionization-quadrupole/orbitrap-MS/MS spectrometry as a rapid and sensitive identification technique. The structure-fragment relationships were established on the basis of plausible mechanistic pathway for the generation of daughter ions. The MS/MS spectral information of the triterpenoids was further utilized for the identification of studied molecules in the complex extract of stem and bark tissues from Neem. Copyright © 2014 Elsevier B.V. All rights reserved.

Plasmodium vivax Isolates from Cambodia and Thailand Show High Genetic Complexity and Distinct Patterns of P. vivax Multidrug Resistance Gene 1 (pvmdr1) Polymorphisms

PubMed Central

Lin, Jessica T.; Patel, Jaymin C.; Kharabora, Oksana; Sattabongkot, Jetsumon; Muth, Sinuon; Ubalee, Ratawan; Schuster, Anthony L.; Rogers, William O.; Wongsrichanalai, Chansuda; Juliano, Jonathan J.

2013-01-01

Plasmodium vivax accounts for an increasing fraction of malaria infections in Thailand and Cambodia. We compared P. vivax genetic complexity and antimalarial resistance patterns in the two countries. Use of a heteroduplex tracking assay targeting the merozoite surface protein 1 gene revealed that vivax infections in both countries are frequently polyclonal (84%), with parasites that are highly diverse (HE = 0.86) but closely related (GST = 0.18). Following a history of different drug policies in Thailand and Cambodia, distinct patterns of antimalarial resistance have emerged: most Cambodian isolates harbor the P. vivax multidrug resistance gene 1 (pvmdr1) 976F mutation associated with chloroquine resistance (89% versus 8%, P < 0.001), whereas Thai isolates more often display increased pvmdr1 copy number (39% versus 4%, P < 0.001). Finally, genotyping of paired isolates from individuals suspected of suffering relapse supports a complex scheme of relapse whereby recurrence of multiple identical variants is sometimes accompanied by the appearance of novel variants. PMID:23509126

A distinct alleles and genetic recombination of pmrCAB operon in species of Acinetobacter baumannii complex isolates.

PubMed

Kim, Dae Hun; Ko, Kwan Soo

2015-07-01

To investigate pmrCAB sequence divergence in 5 species of Acinetobacter baumannii complex, a total of 80 isolates from a Korean hospital were explored. We evaluated nucleotide and amino acid polymorphisms of pmrCAB operon, and phylogenetic trees were constructed for each gene of prmCAB operon. Colistin and polymyxin B susceptibility was determined for all isolates, and multilocus sequence typing was also performed for A. baumannii isolates. Our results showed that each species of A. baumannii complex has divergent pmrCAB operon sequences. We identified a distinct pmrCAB allele allied with Acinetobacter nosocomialis in gene trees. Different grouping in each gene tree suggests sporadic recombination or emergence of pmrCAB genes among Acinetobacter species. Sequence polymorphisms among Acinetobacter species might not be associated with colistin resistance. We revealed that a distinct pmrCAB allele may be widespread across the continents such as North America and Asia and that sporadic genetic recombination or emergence of pmrCAB genes might occur. Copyright © 2015 Elsevier Inc. All rights reserved.

mer and fac isomerism in tris chelate diimine metal complexes.

PubMed

Dabb, Serin L; Fletcher, Nicholas C

2015-03-14

In this perspective, we highlight the issue of meridional (mer) and facial (fac) orientation of asymmetrical diimines in tris-chelate transition metal complexes. Diimine ligands have long been the workhorse of coordination chemistry, and whilst there are now good strategies to isolate materials where the inherent metal centered chirality is under almost complete control, and systematic methodologies to isolate heteroleptic complexes, the conceptually simple geometrical isomerism has not been widely investigated. In systems where the two donor atoms are significantly different in terms of the σ-donor and π-accepting ability, the fac isomer is likely to be the thermodynamic product. For the diimine complexes with two trigonal planar nitrogen atoms there is much more subtlety to the system, and external factors such as the solvent, lattice packing and the various steric considerations play a delicate role in determining the observed and isolable product. In this article we discuss the possibilities to control the isomeric ratio in labile systems, consider the opportunities to separate inert complexes and discuss the observed differences in their spectroscopic properties. Finally we report on the ligand orientation in supramolecular systems where facial coordination leads to simple regular structures such as helicates and tetrahedra, but the ability of the ligand system to adopt a mer orientation enables self-assembled structures of considerable beauty and complexity.

Isolation and preliminary characterization of circulating immune complexes from rabbits with experimental syphilis.

PubMed Central

Baughn, R E; Musher, D M

1983-01-01

Immune complexes isolated from sera of rabbits with experimental, disseminated syphilis were found to have sedimentation coefficients greater than 19s. By radioimmunoblot assays, materials precipitated with 2.5% polyethylene glycol or chromatographed on DEAE-Affi-Gel Blue were found to contain albumin, C3, immunoglobulin M (IgM), IgG, and treponemal antigen(s), whereas control materials contained only albumin and IgG. When polyethylene glycol precipitation of immune complexes from syphilitic rabbits was followed by immobilization on protein A and acid elution, radioimmunoblots detected only IgG and treponemal antigen(s). Images PMID:6358025

Update on the Spoligotypes of Mycobacterium tuberculosis complex isolates from the Fernando Fonseca Hospital (Amadora-Sintra, Portugal).

PubMed

David, Suzana; Barros, Vanessa; Portugal, Clara; Antunes, Abílio; Cardoso, Angela; Calado, Ana; Sancho, Luísa; de Sousa, José Germano

2005-01-01

The present population study, from 1999 to 2003, has been based on the use of Spoligotyping in the genotyping of 452 isolates of the Mycobacterium tuberculosis complex from tuberculosis patients of the Fernando Fonseca Hospital. Spoligotypes were identified as "shared types" (STs) with the aid of an international database. Eleven rarely found STs, not identified in the database, grouped 8.4% of the isolates. Moreover, particular to Portugal, may be the predominance of STs identified in the database but not previously classified as genotypic families, such as ST244, ST150 and ST389, representing 13.3 % of the total. The identification of clinical isolates of M. africanum genotype Afri1 and of M. tuberculosis genotype CAS1 may confirm import of isolates of African and Asian origin. M. tuberculosis of the Beijing family was first reported by us as of 1999. Since then, the number of isolates at the Hospital has passed from one to five annually, representing 2.2% of the total and the tenth most predominant family in the present study. M. tuberculosis Beijing may correspond to an emerging problem in Portugal due to recent immigration from Eastern Europe and Asia. Other genotypes, ST150 and ST389, have shown increase, the significance of which is not clear. However, the relative frequencies of the predominant families LAM, T1 and Haarlem remained relatively stable. The present study confirms the genetic variability in Portugal of M. tuberculosis complex isolates. These studies may contribute to the definition of priorities in the national tuberculosis control programs.

Improved stability and oral bioavailability of Ganneng dropping pills following transforming lignans of herpetospermum caudigerum into nanosuspensions.

PubMed

Li, Juan-Juan; Cheng, Ling; Shen, Gang; Qiu, Ling; Shen, Cheng-Ying; Zheng, Juan; Xu, Rong; Yuan, Hai-Long

2018-01-01

The present study was designed to improve storage stability and oral bioavailability of Ganneng dropping pills (GNDP) by transforming lignans of Herpetospermum caudigerum (HL) composed of herpetrione (HPE) and herpetin (HPN) into nanosuspension (HL-NS), the main active ingredient of GNDP, HL-NS was prepared by high pressure homogenization and lyophilized to transform into solid nanoparticles (HL nanoparticles), and then the formulated HL nanoparticles were perfused into matrix to obtain NS-GNDP by melting method. For a period of 3 months, the content uniformity, storage stability and pharmacokinetics test in vivo of NS-GNDP were evaluated and compared with regular GNDP at room temperature. The results demonstrated that uniformity of dosage units of NS-GNDP was acceptable according to the criteria of Chinese Pharmacopoeia 2015J. Physical stability of NS-GNDP was investigated systemically using photon correlation spectroscopy (PCS), zeta potential measurement, and scanning electron microscopy (SEM). There was a slight increase in particles and PI of HL-NS re-dispersed from NS-GNDP after storage for 3 months, compared with new formulated NS-GNDP, which indicated a good redispersibility of the NS-GNDP containing HL-NS after storage. Besides, chemical stability of NS-GNDP was studied and the results revealed that HPE and HPN degradation was less when compared with that of GNDP, providing more than 99% of drug residue after storage for 3 months. In the dissolution test in vitro, NS-GNDP remarkably exhibited an increased dissolution velocity compared with GNDP and no distinct dissolution difference existed within 3 months. The pharmacokinetic study showed that HPE and HPN in NS-GNDP exhibited a significant increase in AUC 0-t , C max and decrease in T max when compared with regular GNDP. These results indicated that NS-GNDP possessed superiority with improved storage stability and increased dissolution rate and oral bioavailability. Copyright © 2018 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Plasma Enterolactone and Breast Cancer Risk in the Nurses’ Health Study II

PubMed Central

Xie, Jing; Tworoger, Shelley S.; Franke, Adrian A.; Terry, Kathryn L.; Rice, Megan S.; Rosner, Bernard A.; Willett, Walter C.; Hankinson, Susan E.; Eliassen, A. Heather

2013-01-01

Background Lignans are plant-based phytoestrogens with both estrogenic and anti-estrogenic properties that may be important for breast carcinogenesis. Retrospective studies have observed decreased breast cancer risk associated with high circulating enterolactone concentrations, a biomarker of lignan intake, but results from prospective studies are conflicting. Methods To prospectively examine this association, we measured plasma enterolactone levels in 802 breast cancer cases and 802 matched controls nested among predominantly premenopausal women in the Nurses’ Health Study II (NHSII) cohort. We used conditional logistic regression and polytomous logistic regression models, adjusting for known breast cancer risk factors, to calculate relative risks (RR) and 95% confidence intervals (CI). Results Compared to women with enterolactone concentrations ≤ 4nmol/L, the multivariate adjusted RRs for breast cancer were 1.18 (95% CI: 0.86–1.62), 0.91 (95% CI: 0.66–1.25), and 0.96 (95% CI: 0.70–1.33) for women with enterolactone levels in the 2nd to the 4th quartiles, respectively; Ptrend=0.60. Results were similar across tumors defined by estrogen and progesterone receptor status. Among premenopausal women with follicular estradiol levels below the median (<47 pg/mL), women in the highest category of enterolactone levels had a 51% lower breast cancer risk compared to those in the lowest category (95% CI: 0.27–0.91); Ptrend=0.02. No association was observed among women with high follicular estradiol levels (≥47 pg/mL), (comparable RR=1.39, 95% CI: 0.73–2.65; Pinteraction=0.02). Conclusions We did not observe an overall association between plasma enterolactone and breast cancer risk in a large nested case-control study of US women. However, a significant inverse association was observed among premenopausal women with low follicular estradiol levels, suggesting that enterolactone may be important in a low estrogen environment. This should be confirmed in future studies. PMID:23760859

Enterolactone glucuronide and β-glucuronidase in antibody directed enzyme prodrug therapy for targeted prostate cancer cell treatment.

PubMed

Di, Yunyun; Ji, Shaoping; Wolf, Philipp; Krol, Ed S; Alcorn, Jane

2017-08-01

Evidence from preclinical and animal studies demonstrated an anticancer effect of flaxseed lignans, particularly enterolactone (ENL), against prostate cancer. However, extensive first-pass metabolism following oral lignan consumption results in their systemic availability primarily as glucuronic acid conjugates (ENL-Gluc) and their modest in vivo effects. To overcome the unfavorable pharmacokinetics and improve their effectiveness in prostate cancer, antibody-directed enzyme prodrug therapy (ADEPT) might offer a novel strategy to allow for restricted activation of ENL from circulating ENL-Gluc within the tumor environment. The anti-prostate-specific membrane antigen (PSMA) antibody D7 was fused with human β-glucuronidase (hβG) via a flexible linker. The binding property of the fusion construct, D7-hβG, against purified or cell surface PSMA was determined by flow cytometry and Octet Red 384 system, respectively, with a binding rate constant, K d, of 2.5 nM. The enzymatic activity of D7-hβG was first tested using the probe, 4-methylumbelliferone glucuronide. A 3.8-fold greater fluorescence intensity was observed at pH 4.5 at 2 h compared with pH 7.4. The ability of D7-hβG to activate ENL from ENL-Gluc was tested and detected using LC-MS/MS. Enhanced generation of ENL was observed with increasing ENL-Gluc concentrations and reached 3613.2 ng/mL following incubation with 100 μM ENL-Gluc at pH 4.5 for 0.5 h. D7-hβG also decreased docetaxel IC 50 value from 23 nM to 14.9 nM in C4-2 cells. These results confirmed the binding and activity of D7-hβG and additional in vitro investigation is needed to support the future possibility of introducing this ADEPT system to animal models.