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Sample records for enhanced anti-proliferative anti-inflammatory

  1. Anti-oxidant, anti-inflammatory and anti-proliferative activities of Moroccan commercial essential oils.

    PubMed

    Aazza, Smail; Lyoussi, Badiaa; Megías, Cristina; Cortés-Giraldo, Isabel; Vioque, Javier; Figueiredo, A Cristina; Miguel, Maria G

    2014-04-01

    Essential oils (EO) possess antimicrobial, anti-inflammatory, insect repellent, anti-cancer, and antioxidant properties, among others. In the present work, the antioxidant, anti-inflammatory and anti-proliferative activities of Moroccan commercial EOs (Citrus aurantium, C. limon, Cupressus sempervirens, Eucalyptus globulus, Foeniculum vulgare and Thymus vulgaris) were evaluated and compared with their main constituents. T. vulgaris EO showed the best free radicals scavenging capacity. This EO was also the most effective against lipid peroxidation along with C. limon and F. vulgare EOs. C. sempervirens EO was the most effective in scavenging NO free radicals, whereas C. limon EO showed the best chelating power. Not all of the major compounds of the EO were responsible for the whole activity of the EOs. T. vulgaris EO showed the best anti-proliferative activity against THP-1 cells in contrast to that of F. vulgare. The antioxidant and anti-inflammatory activities of the EOs were plant species dependent and not always attributable to the EOs main components. Nevertheless, the EOs anti-proliferative activities were more related to their main components, as with T. vulgaris, C. limon, E. globulus and C. sempervirens. PMID:24868891

  2. Anti-inflammatory and anti-proliferative activities of the wild edible cruciferous: Diplotaxis simplex.

    PubMed

    Jdir, Hamida; Khemakham, Bassem; Najjaa, Hanen; Chakroun, Mouna; Jridi, Mourad; Ben Arfa, Abdelkarim; Ben Ali, Yassine; Zouari, Nacim

    2016-10-01

    Context The present study deals with new biological properties of the wild edible Diplotaxis simplex (Viv.) Spreng (Brassicaceae). Objectives The current study evaluates the antioxidant, the anti-inflammatory and the anti-cancer properties of ethyl acetate and ethanol extracts from D. simplex flowers. Materials and methods The anti-proliferative activity of the extracts (10-70 μg/mL) was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) against human colon cancer cell line Caco-2. The anti-inflammatory potential was evaluated by the inhibitory effect of the extracts (1.5-7.5 mg/mL) on phospholipase A2 activity as well as on carrageenan-induced paw oedema in mice. Extracts (200 mg/kg) or indomethacin (50 mg/kg) as positive control were injected intraperitoneally for albino mice prior to the induction of the oedema by carrageenan. Antioxidant activities were investigated using various complementary methods. Results Flower extracts contained a high level of polyphenolics (17.10-52.70 mg GAE/g) and flavonoids (74.20-100.60 mg QE/g), which correlate with its appreciable antioxidant potential in β-carotene peroxidation (IC50 value: 12.50-27.10 μg/mL), DPPH(•) radical-scavenging (IC50 value: 0.20-0.40 mg/mL), Fe(3+ )reducing (EC50 value: 0.10-0.14 mg/mL) and Fe(2+ )chelating (IC50 value: 0.20-0.60 mg/mL) assays. These extracts were effective in inhibiting cancer cell growth (IC50 value: 62.0-63.25 μg/mL). Besides, the ethyl acetate extract inhibited phospholipase A2 activity (IC50 value: 2.97 mg/mL) and reduced the paw oedema in mice (from 0.38 ± 0.01 to 0.24 ± 0.01 cm), 4 h post-carrageenan challenge. Conclusion These data suggest that D. simplex may be useful as a candidate in the treatment of inflammation and the colon cancer. PMID:26916801

  3. Chinese herbal medicine (Tuhuai extract) exhibits topical anti-proliferative and anti-inflammatory activity in murine disease models

    PubMed Central

    Man, Mao-Qiang; Shi, Yuejun; Man, Mona; Lee, Seung Hun; Demerjian, Marianne; Chang, Sandra; Feingold, Kenneth R.; Elias, Peter M.

    2010-01-01

    While psoriasis is one of the most common skin disorders in humans, effective, safe and inexpensive treatments are still largely unavailable. Chinese herbal medicine (CHM) has been used for centuries for treating psoriasis and several reports claim that systemic administration of one such CHM, Tuhuai, mainly composed of flos sophorae, smilax glabra roxb and licorice, is effective in psoriasis. However, the mechanisms by which this CHM improves psoriasis are not yet clear. Two universal features of psoriasis are epidermal hyperplasia and inflammation. Moreover, drugs that specifically inhibit epidermal hyperplasia and/or inflammation are widely used to treat psoriasis. Here, we investigated whether topical applications of Tuhuai extract exhibit anti-proliferative and anti-inflammatory activities in two murine models of inflammatory dermatoses. To assess Tuhuai's potential anti-proliferative effect, we disrupted epidermal barrier function twice-daily for 4 days in normal hairless mice followed by topical applications of either 1% Tuhuai extract or Vehicle to both flanks immediately after each barrier perturbation. Changes in epidermal proliferation and apoptosis were evaluated by immunohistochemistry and TUNEL staining. To assess the anti-inflammatory effects of Tuhuai, both irritant (phorbol ester) and acute allergic contact dermatitis (oxazolone) models were used. Whereas topical Tuhuai extract did not alter epidermal proliferation or induce irritation in normal skin, it both reduced epidermal hyperplasia in the epidermal hyperproliferative model, and reduced inflammation in both irritant and allergic contact dermatitis models. As topical Tuhuai extract exhibits anti-proliferative and anti-inflammatory properties in a variety of human models of inflammatory dermatoses, Tuhuai could provide an effective, relatively safe and inexpensive therapeutic alternative for the treatment of inflammatory dermatoses, including psoriasis. PMID:18341576

  4. Chemical composition, antioxidant, anti-inflammatory and anti-proliferative activities of essential oils of plants from Burkina Faso.

    PubMed

    Bayala, Bagora; Bassole, Imaël Henri Nestor; Gnoula, Charlemagne; Nebie, Roger; Yonli, Albert; Morel, Laurent; Figueredo, Gilles; Nikiema, Jean-Baptiste; Lobaccaro, Jean-Marc A; Simpore, Jacques

    2014-01-01

    This research highlights the chemical composition, antioxidant, anti-inflammatory and anti-proliferative activities of essential oils from leaves of Ocimum basilicum, Ocimum americanum, Hyptis spicigera, Lippia multiflora, Ageratum conyzoides, Eucalyptus camaldulensis and Zingiber officinale. Essential oils were analyzed by gas chromatography-mass spectrometry and gas chromatography-flame ionization detector. Major constituents were α-terpineol (59.78%) and β-caryophyllene (10.54%) for Ocimum basilicum; 1, 8-cineol (31.22%), camphor (12.730%), α-pinene (6.87%) and trans α-bergamotene (5.32%) for Ocimum americanum; β-caryophyllene (21%), α-pinene (20.11%), sabinene (10.26%), β-pinene (9.22%) and α-phellandrene (7.03%) for Hyptis spicigera; p-cymene (25.27%), β-caryophyllene (12.70%), thymol (11.88), γ-terpinene (9.17%) and thymyle acetate (7.64%) for Lippia multiflora; precocene (82.10%)for Ageratum conyzoides; eucalyptol (59.55%), α-pinene (9.17%) and limonene (8.76%) for Eucalyptus camaldulensis; arcurcumene (16.67%), camphene (12.70%), zingiberene (8.40%), β-bisabolene (7.83%) and β-sesquiphellandrène (5.34%) for Zingiber officinale. Antioxidant activities were examined using 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) methods. O. basilicum and L. multiflora exhibited the highest antioxidant activity in DPPH and ABTS tests, respectively. Anti-inflammatory properties were evaluated by measuring the inhibition of lipoxygenase activity and essential oil of Z. officinale was the most active. Anti-proliferative effect was assayed by the measurement of MTT on LNCaP and PC-3 prostate cancer cell lines, and SF-763 and SF-767 glioblastoma cell lines. Essential oils from A. conyzoides and L. multiflora were the most active on LNCaP and PC-3 cell lines, respectively. The SF-767 glioblastoma cell line was the most sensitive to O. basilicum and L. multiflora EOs while essential oil of A. conyzoides

  5. Chemical Composition, Antioxidant, Anti-Inflammatory and Anti-Proliferative Activities of Essential Oils of Plants from Burkina Faso

    PubMed Central

    Bayala, Bagora; Bassole, Imaël Henri Nestor; Gnoula, Charlemagne; Nebie, Roger; Yonli, Albert; Morel, Laurent; Figueredo, Gilles; Nikiema, Jean-Baptiste; Lobaccaro, Jean-Marc A.; Simpore, Jacques

    2014-01-01

    This research highlights the chemical composition, antioxidant, anti-inflammatory and anti-proliferative activities of essential oils from leaves of Ocimum basilicum, Ocimum americanum, Hyptis spicigera, Lippia multiflora, Ageratum conyzoides, Eucalyptus camaldulensis and Zingiber officinale. Essential oils were analyzed by gas chromatography–mass spectrometry and gas chromatography–flame ionization detector. Major constituents were α-terpineol (59.78%) and β-caryophyllene (10.54%) for Ocimum basilicum; 1, 8-cineol (31.22%), camphor (12.730%), α-pinene (6.87%) and trans α-bergamotene (5.32%) for Ocimum americanum; β-caryophyllene (21%), α-pinene (20.11%), sabinene (10.26%), β-pinene (9.22%) and α-phellandrene (7.03%) for Hyptis spicigera; p-cymene (25.27%), β-caryophyllene (12.70%), thymol (11.88), γ-terpinene (9.17%) and thymyle acetate (7.64%) for Lippia multiflora; precocene (82.10%)for Ageratum conyzoides; eucalyptol (59.55%), α-pinene (9.17%) and limonene (8.76%) for Eucalyptus camaldulensis; arcurcumene (16.67%), camphene (12.70%), zingiberene (8.40%), β-bisabolene (7.83%) and β-sesquiphellandrène (5.34%) for Zingiber officinale. Antioxidant activities were examined using 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) methods. O. basilicum and L. multiflora exhibited the highest antioxidant activity in DPPH and ABTS tests, respectively. Anti-inflammatory properties were evaluated by measuring the inhibition of lipoxygenase activity and essential oil of Z. officinale was the most active. Anti-proliferative effect was assayed by the measurement of MTT on LNCaP and PC-3 prostate cancer cell lines, and SF-763 and SF-767 glioblastoma cell lines. Essential oils from A. conyzoides and L. multiflora were the most active on LNCaP and PC-3 cell lines, respectively. The SF-767 glioblastoma cell line was the most sensitive to O. basilicum and L. multiflora EOs while essential oil of A. conyzoides

  6. Chemical composition, antioxidant, anti-inflammatory and anti-proliferative activities of essential oils of plants from Burkina Faso.

    PubMed

    Bayala, Bagora; Bassole, Imaël Henri Nestor; Gnoula, Charlemagne; Nebie, Roger; Yonli, Albert; Morel, Laurent; Figueredo, Gilles; Nikiema, Jean-Baptiste; Lobaccaro, Jean-Marc A; Simpore, Jacques

    2014-01-01

    This research highlights the chemical composition, antioxidant, anti-inflammatory and anti-proliferative activities of essential oils from leaves of Ocimum basilicum, Ocimum americanum, Hyptis spicigera, Lippia multiflora, Ageratum conyzoides, Eucalyptus camaldulensis and Zingiber officinale. Essential oils were analyzed by gas chromatography-mass spectrometry and gas chromatography-flame ionization detector. Major constituents were α-terpineol (59.78%) and β-caryophyllene (10.54%) for Ocimum basilicum; 1, 8-cineol (31.22%), camphor (12.730%), α-pinene (6.87%) and trans α-bergamotene (5.32%) for Ocimum americanum; β-caryophyllene (21%), α-pinene (20.11%), sabinene (10.26%), β-pinene (9.22%) and α-phellandrene (7.03%) for Hyptis spicigera; p-cymene (25.27%), β-caryophyllene (12.70%), thymol (11.88), γ-terpinene (9.17%) and thymyle acetate (7.64%) for Lippia multiflora; precocene (82.10%)for Ageratum conyzoides; eucalyptol (59.55%), α-pinene (9.17%) and limonene (8.76%) for Eucalyptus camaldulensis; arcurcumene (16.67%), camphene (12.70%), zingiberene (8.40%), β-bisabolene (7.83%) and β-sesquiphellandrène (5.34%) for Zingiber officinale. Antioxidant activities were examined using 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) methods. O. basilicum and L. multiflora exhibited the highest antioxidant activity in DPPH and ABTS tests, respectively. Anti-inflammatory properties were evaluated by measuring the inhibition of lipoxygenase activity and essential oil of Z. officinale was the most active. Anti-proliferative effect was assayed by the measurement of MTT on LNCaP and PC-3 prostate cancer cell lines, and SF-763 and SF-767 glioblastoma cell lines. Essential oils from A. conyzoides and L. multiflora were the most active on LNCaP and PC-3 cell lines, respectively. The SF-767 glioblastoma cell line was the most sensitive to O. basilicum and L. multiflora EOs while essential oil of A. conyzoides

  7. In vitro screening of probiotics and synbiotics according to anti-inflammatory and anti-proliferative effects.

    PubMed

    Grimoud, Julien; Durand, Henri; de Souza, Sarah; Monsan, Pierre; Ouarné, Françoise; Theodorou, Vassilia; Roques, Christine

    2010-11-15

    There is emerging evidence of the efficiency of probiotic, prebiotic and synbiotic treatments in inflammatory bowel diseases (IBDs) and one of their long-term complications, colorectal cancer (CRC). In this study, various strains of probiotic lactic acid bacteria, prebiotic glucooligosaccharides (GOS) or a synbiotic combination of the two were screened for anti-inflammatory and anti-proliferative effects in different in vitro models in the context of such diseases. To mimic IBD response to Gram negative bacteria, HT-29 cells were sensitised to inflammatory response to lipopolysaccharide (LPS) by IFNγ which increased expression of TLR4, the LPS biosensor, and were then treated by probiotics, prebiotics and synbiotics. Secreted IL-8 and activated NF-κB were monitored as inflammation biomarkers. A selection of active strains were then subjected to a second inflammatory cell culture model consisting of inflammatory activated transgenic Caco-2 cells transfected by a reporter gene under the control of NF-κB inducible promoter. Quantification of reporter gene expression allowed us to demonstrate some probiotic inhibitory properties or to confirm such characteristics in two different models. Proliferation of cancerous HT-29 cells was monitored by XTT assay. Only three probiotic strains induced a proliferation decrease, but with a lack of reproducibility. Binary or ternary probiotic associations, complemented or not by prebiotic GOS, significantly decreased proliferation, especially with a synbiotic association of Bifidobacterium breve, Lactococcus lactis and oligoalternan, a GOS. This combination was selected for the following experiments. We showed the involvement of both bacterial and carbohydrate compounds of this synbiotic in the observed effect by dose range tests. We demonstrated that this decrease in proliferation may be due to an induction of a differentiated phenotype, as shown by the up-regulation of intestinal alkaline phosphatase, a biomarker of

  8. N-Acyl-N-phenyl ureas of piperidine and substituted piperidines endowed with anti-inflammatory and anti-proliferative activities.

    PubMed

    Ranise, A; Schenone, S; Bruno, O; Bondavalli, F; Filippelli, W; Falcone, G; Rivaldi, B

    2001-09-01

    Six series of N-acyl-N-phenyl ureas 1-6 of piperidine (1), and 2-ethyl- (2), 3-methyl- (3), 4-methyl- (4), 4-phenyl- (5), cis-2,6-dimethyl- (6) piperidine were synthesised and evaluated for their anti-inflammatory, anaesthetic, anti-pyretic properties. Some derivatives of series 1 and 5 were also assayed for anti-proliferative activity. Several compounds showed an anti-inflammatory activity comparable or slighty inferior to that of indomethacin in rats (1c,d, 2a,b,g,h, 3b, 4h, 5d,e). Moreover, an appreciable anti-inflammatory activity was also found in 2c,e, 3e,f,g, 4g, 5a,b,c,f,h, and 6a,b,d. All the compounds were devoid of anti-pyretic activity and only a few of them exhibited a low level of infiltration anaesthesia in mice. Compound 5a showed a broad spectrum anti-cancer activity (at low micromolar concentrations), particulary significant against leukemia subpanel. PMID:11680808

  9. In vitro anti-inflammatory and anti-proliferative activity of sulfolipids from the red alga Porphyridium cruentum.

    PubMed

    Bergé, J P; Debiton, E; Dumay, J; Durand, P; Barthomeuf, C

    2002-10-01

    A sulfoglycolipidic fraction (SF) isolated from the red microalga Porphyridium cruentum was analyzed for fatty acid composition and assayed for ability to inhibit, in vitro, the generation of superoxide anion in primed leucocytes and the proliferation of a panel of human cancer cell-lines. Results demonstrated that SF contained large amounts of palmitic acid (26.1%), arachidonic acid (C20: 4 omega-6, 36.8%), and eicopentaenoic (C20:5 omega-3, 16.6%) acids, and noticeable amounts of 16:1n-9 fatty acid (10.5%). It strongly inhibited both the production of superoxide anion generated by peritoneal leukocytes primed with phorbol myristate acetate (IC(50): 29.5 microg/mL), and the growth of human colon adenocarcinoma DLD-1 and to a lesser extent of human breast adenocarcinoma MCF-7, human prostate adenocarcinoma PC-3, and human malignant melanoma M4 Beu cell-lines, and therefore might have a chemopreventive or chemotherapeutic potential, or both. It was found markedly more cytotoxic than sulfoquinovosyldiacylglycerols from plant used as a standard (STD), due to a stronger ability to inhibit DNA alpha-polymerase (IC(50): 378 microg/mL, vs 1784 microg/mL for STD). After a 48-h continuous treatment, IC(50) values for growth inhibition were in the range of 20-46 microg/mL instead of 94 to >250 microg/mL for STD, and those for inhibition of metabolic activity were in the range of 34-87 microg/mL instead of >250 microg/mL for STD. The higher anti-proliferative effect was observed on colon adenocarcinoma DLD-1 cells, and the weaker effect was observed on breast adenocarcinoma MCF-7.

  10. Arctigenin in combination with quercetin synergistically enhances the anti-proliferative effect in prostate cancer cells

    PubMed Central

    Wang, Piwen; Phan, Tien; Gordon, David; Chung, Seyung; Henning, Susanne M.; Vadgama, Jaydutt V.

    2014-01-01

    Scope We investigated whether a combination of two promising chemopreventive agents arctigenin and quercetin increases the anti-carcinogenic potency at lower concentrations than necessary when used individually in prostate cancer. Methods and results Androgen-dependent LAPC-4 and LNCaP prostate cancer cells were treated with low doses of arctigenin and quercetin alone or in combination for 48h. The anti-proliferative activity of arctigenin was 10-20 fold stronger than quercetin in both cell lines. Their combination synergistically enhanced the anti-proliferative effect, with a stronger effect in androgen receptor (AR) wild-type LAPC-4 cells than in AR mutated LNCaP cells. Arctigenin demonstrated a strong ability to inhibit AR protein expression in LAPC-4 cells. The combination treatment significantly inhibited both AR and PI3K/Akt pathways compared to control. A protein array analysis revealed that the mixture targets multiple pathways particularly in LAPC-4 cells including Stat3 pathway. The mixture significantly inhibited the expression of several oncogenic microRNAs including miR-21, miR-19b, and miR-148a compared to control. The mixture also enhanced the inhibition of cell migration in both cell lines compared to individual compounds tested. Conclusion The combination of arctigenin and quercetin, that target similar pathways, at low physiological doses, provides a novel regimen with enhanced chemoprevention in prostate cancer. PMID:25380086

  11. Enhancement of anti-proliferative activities of Metformin, when combined with Celecoxib, without increasing DNA damage.

    PubMed

    Ullah, Asad; Ashraf, Muhammad; Javeed, Aqeel; Anjum, Aftab Ahmad; Attiq, Ali; Ali, Sarwat

    2016-07-01

    Pathophysiological changes in diabetes like hyperglycemia, oxidative stress, insulin resistance and compensatory hyperinsulinemia predispose cells to malignant transformation and damage DNA repair mechanism. This study was designed to explore the potential synergistic toxic effects of anti-diabetic drug (Metformin), and an analgesic drug (Celecoxib) at cellular level. MTT assay run on Vero cell line revealed that the combinations of Metformin and Celecoxib augment the anti-proliferative effects, whereas Single cell gel electrophoresis spotlighted that Metformin produce non-significant DNA damage with the threshold concentration of 400μg/ml in peripheral blood mononuclear cells (lymphocytes and monocytes), while Celecoxib produced significant (P<0.05) DNA damage (class III comets) above the concentration of 75μg/ml, however the DNA damage or DNA tail protrusions by combinations of both drugs were less than what was observed with Celecoxib alone. Metformin or Celecoxib did not appear mutagenic against any mutant strains (TA 100 and TA 98) but their combination exhibited slight mutagenicity at much higher concentration. The results obtained at concentrations higher than the therapeutic level of drugs and reflect that Metformin in combination with Celecoxib synergistically inhibits the cell proliferation in a concentration dependent pattern. Since, this increase in cytotoxicity did not confer an increase in DNA damage; this combination could be adopted to inhibit the growth of malignant cell without producing any genotoxic or mutagenic effects at cellular level. PMID:27327526

  12. ESR1 mutations affect anti-proliferative responses to tamoxifen through enhanced cross-talk with IGF signaling.

    PubMed

    Gelsomino, Luca; Gu, Guowei; Rechoum, Yassine; Beyer, Amanda R; Pejerrey, Sasha M; Tsimelzon, Anna; Wang, Tao; Huffman, Kenneth; Ludlow, Andrew; Andò, Sebastiano; Fuqua, Suzanne A W

    2016-06-01

    The purpose of this study was to address the role of ESR1 hormone-binding mutations in breast cancer. Soft agar anchorage-independent growth assay, Western blot, ERE reporter transactivation assay, proximity ligation assay (PLA), coimmunoprecipitation assay, silencing assay, digital droplet PCR (ddPCR), Kaplan-Meier analysis, and statistical analysis. It is now generally accepted that estrogen receptor (ESR1) mutations occur frequently in metastatic breast cancers; however, we do not yet know how to best treat these patients. We have modeled the three most frequent hormone-binding ESR1 (HBD-ESR1) mutations (Y537N, Y537S, and D538G) using stable lentiviral transduction in human breast cancer cell lines. Effects on growth were examined in response to hormonal and targeted agents, and mutation-specific changes were studied using microarray and Western blot analysis. We determined that the HBD-ESR1 mutations alter anti-proliferative effects to tamoxifen (Tam), due to cell-intrinsic changes in activation of the insulin-like growth factor receptor (IGF1R) signaling pathway and levels of PIK3R1/PIK3R3. The selective estrogen receptor degrader, fulvestrant, significantly reduced the anchorage-independent growth of ESR1 mutant-expressing cells, while combination treatments with the mTOR inhibitor everolimus, or an inhibitor blocking IGF1R, and the insulin receptor significantly enhanced anti-proliferative responses. Using digital drop (dd) PCR, we identified mutations at high frequencies ranging from 12 % for Y537N, 5 % for Y537S, and 2 % for D538G in archived primary breast tumors from women treated with adjuvant mono-tamoxifen therapy. The HBD-ESR1 mutations were not associated with recurrence-free or overall survival in response in this patient cohort and suggest that knowledge of other cell-intrinsic factors in combination with ESR1 mutation status will be needed determine anti-proliferative responses to Tam. PMID:27178332

  13. Enhancement of anti-inflammatory activity of bromelain by its encapsulation in katira gum nanoparticles.

    PubMed

    Bernela, Manju; Ahuja, Munish; Thakur, Rajesh

    2016-06-01

    Bromelain-loaded katira gum nanoparticles were synthesized using 3 level optimization process and desirability approach. Nanoparticles of the optimized batch were characterized using particle size analysis, zeta potential, transmission electron microscopy and Fourier-transform infrared spectroscopy. Investigation of their in vivo anti-inflammatory activity by employing carrageenan induced rat-paw oedema method showed that encapsulation of bromelain in katira gum nanoparticles substantially enhanced its anti-inflammatory potential. This may be attributed to enhanced absorption owing to reduced particle size or to protection of bromelain from acid proteases.

  14. Genetically Engineered Immunomodulatory Streptococcus thermophilus Strains Producing Antioxidant Enzymes Exhibit Enhanced Anti-Inflammatory Activities

    PubMed Central

    del Carmen, Silvina; de Moreno de LeBlanc, Alejandra; Martin, Rebeca; Chain, Florian; Langella, Philippe; Bermúdez-Humarán, Luis G.

    2014-01-01

    The aims of this study were to develop strains of lactic acid bacteria (LAB) having both immunomodulatory and antioxidant properties and to evaluate their anti-inflammatory effects both in vitro, in different cellular models, and in vivo, in a mouse model of colitis. Different Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus strains were cocultured with primary cultures of mononuclear cells. Analysis of the pro- and anti-inflammatory cytokines secreted by these cells after coincubation with candidate bacteria revealed that L. delbrueckii subsp. bulgaricus CRL 864 and S. thermophilus CRL 807 display the highest anti-inflammatory profiles in vitro. Moreover, these results were confirmed in vivo by the determination of the cytokine profiles in large intestine samples of mice fed with these strains. S. thermophilus CRL 807 was then transformed with two different plasmids harboring the genes encoding catalase (CAT) or superoxide dismutase (SOD) antioxidant enzymes, and the anti-inflammatory effects of recombinant streptococci were evaluated in a mouse model of colitis induced by trinitrobenzenesulfonic acid (TNBS). Our results showed a decrease in weight loss, lower liver microbial translocation, lower macroscopic and microscopic damage scores, and modulation of the cytokine production in the large intestines of mice treated with either CAT- or SOD-producing streptococci compared to those in mice treated with the wild-type strain or control mice without any treatment. Furthermore, the greatest anti-inflammatory activity was observed in mice receiving a mixture of both CAT- and SOD-producing streptococci. The addition of L. delbrueckii subsp. bulgaricus CRL 864 to this mixture did not improve their beneficial effects. These findings show that genetically engineering a candidate bacterium (e.g., S. thermophilus CRL 807) with intrinsic immunomodulatory properties by introducing a gene expressing an antioxidant enzyme enhances its anti-inflammatory

  15. The combination of vitamins and omega-3 fatty acids has an enhanced anti-inflammatory effect on microglia.

    PubMed

    Kurtys, E; Eisel, U L M; Verkuyl, J M; Broersen, L M; Dierckx, R A J O; de Vries, E F J

    2016-10-01

    Neuroinflammation is a common phenomenon in the pathology of many brain diseases. In this paper we explore whether selected vitamins and fatty acids known to modulate inflammation exert an effect on microglia, the key cell type involved in neuroinflammation. Previously these nutrients have been shown to exert anti-inflammatory properties acting on specific inflammatory pathways. We hypothesized that combining nutrients acting on converging anti-inflammatory pathways may lead to enhanced anti-inflammatory properties as compared to the action of a single nutrient. In this study, we investigated the anti-inflammatory effect of combinations of nutrients based on the ability to inhibit the LPS-induced release of nitric oxide and interleukin-6 from BV-2 cells. Results show that omega-3 fatty acids, vitamins A and D can individually reduce the LPS-induced secretion of the pro-inflammatory cytokines by BV-2 cells. Moreover, we show that vitamins A, D and omega-3 fatty acids (docosahexaenoic and eicosapentaenoic) at concentrations where they individually had little effect, significantly reduced the secretion of the inflammatory mediator, nitric oxide, when they were combined. The conclusion of this study is that combining different nutrients acting on convergent anti-inflammatory pathways may result in an increased anti-inflammatory efficacy. PMID:27465516

  16. The combination of vitamins and omega-3 fatty acids has an enhanced anti-inflammatory effect on microglia.

    PubMed

    Kurtys, E; Eisel, U L M; Verkuyl, J M; Broersen, L M; Dierckx, R A J O; de Vries, E F J

    2016-10-01

    Neuroinflammation is a common phenomenon in the pathology of many brain diseases. In this paper we explore whether selected vitamins and fatty acids known to modulate inflammation exert an effect on microglia, the key cell type involved in neuroinflammation. Previously these nutrients have been shown to exert anti-inflammatory properties acting on specific inflammatory pathways. We hypothesized that combining nutrients acting on converging anti-inflammatory pathways may lead to enhanced anti-inflammatory properties as compared to the action of a single nutrient. In this study, we investigated the anti-inflammatory effect of combinations of nutrients based on the ability to inhibit the LPS-induced release of nitric oxide and interleukin-6 from BV-2 cells. Results show that omega-3 fatty acids, vitamins A and D can individually reduce the LPS-induced secretion of the pro-inflammatory cytokines by BV-2 cells. Moreover, we show that vitamins A, D and omega-3 fatty acids (docosahexaenoic and eicosapentaenoic) at concentrations where they individually had little effect, significantly reduced the secretion of the inflammatory mediator, nitric oxide, when they were combined. The conclusion of this study is that combining different nutrients acting on convergent anti-inflammatory pathways may result in an increased anti-inflammatory efficacy.

  17. Morinda citrifolia leaf enhanced performance by improving angiogenesis, mitochondrial biogenesis, antioxidant, anti-inflammatory & stress responses.

    PubMed

    Mohamad Shalan, Nor Aijratul Asikin; Mustapha, Noordin M; Mohamed, Suhaila

    2016-12-01

    Morinda citrifolia fruit, (noni), enhanced performances in athletes and post-menopausal women in clinical studies. This report shows the edible noni leaves water extract enhances performance in a weight-loaded swimming animal model better than the fruit or standardized green tea extract. The 4weeks study showed the extract (containing scopoletin and epicatechin) progressively prolonged the time to exhaustion by threefold longer than the control, fruit or tea extract. The extract improved (i) the mammalian antioxidant responses (MDA, GSH and SOD2 levels), (ii) tissue nutrient (glucose) and metabolite (lactate) management, (iii) stress hormone (cortisol) regulation; (iv) neurotransmitter (dopamine, noradrenaline, serotonin) expressions, transporter or receptor levels, (v) anti-inflammatory (IL4 & IL10) responses; (v) skeletal muscle angiogenesis (VEGFA) and (v) energy and mitochondrial biogenesis (via PGC, UCP3, NRF2, AMPK, MAPK1, and CAMK4). The ergogenic extract helped delay fatigue by enhancing energy production, regulation and efficiency, which suggests benefits for physical activities and disease recovery.

  18. Novel combination of sorafenib and biochanin-A synergistically enhances the anti-proliferative and pro-apoptotic effects on hepatocellular carcinoma cells

    PubMed Central

    Youssef , Mohieldin M.; Tolba, Mai F.; Badawy, Noha N.; Liu, Andrew W.; El-Ahwany, Eman; Khalifa, Amani E.; Zada, Suher; Abdel-Naim, Ashraf B.

    2016-01-01

    Sorafenib (SOR) is the first-line treatment for hepatocellular carcinoma (HCC). However, its use is hindered by the recently expressed safety concerns. One approach for reducing SOR toxicity is to use lower doses in combination with other less toxic agents. Biochanin-A (Bio-A), a promising isoflavone, showed selective toxicity to liver cancer cells. We postulated that combining SOR and Bio-A could be synergistically toxic towards HCC cells. We further evaluated the underlying mechanism. Cytotoxicity assay was performed to determine the IC50 of Bio-A and SOR in HepG2, SNU-449 and Huh-7 cells. Then, combination index in HepG2 was evaluated using Calcusyn showing that the concurrent treatment with lower concentrations of SOR and Bio-A synergistically inhibited cell growth. Our combination induced significant arrest in pre-G and G0/G1 cell cycle phases and decrease in cyclin D1 protein level. Concomitantly, SOR/Bio-A reduced Bcl-2/Bax ratio. Furthermore, this co-treatment significantly increased caspase-3 & -9 apoptotic markers, while decreased anti-apoptotic and proliferative markers; survivin and Ki-67, respectively. Active caspase-3 in HepG2, SNU-449 and Huh-7 confirmed our synergism hypothesis. This study introduces a novel combination, where Bio-A synergistically enhanced the anti-proliferative and apoptotic effects of SOR in HCC cells, which could serve as a potential effective regimen for treatment. PMID:27470322

  19. Morinda citrifolia leaf enhanced performance by improving angiogenesis, mitochondrial biogenesis, antioxidant, anti-inflammatory & stress responses.

    PubMed

    Mohamad Shalan, Nor Aijratul Asikin; Mustapha, Noordin M; Mohamed, Suhaila

    2016-12-01

    Morinda citrifolia fruit, (noni), enhanced performances in athletes and post-menopausal women in clinical studies. This report shows the edible noni leaves water extract enhances performance in a weight-loaded swimming animal model better than the fruit or standardized green tea extract. The 4weeks study showed the extract (containing scopoletin and epicatechin) progressively prolonged the time to exhaustion by threefold longer than the control, fruit or tea extract. The extract improved (i) the mammalian antioxidant responses (MDA, GSH and SOD2 levels), (ii) tissue nutrient (glucose) and metabolite (lactate) management, (iii) stress hormone (cortisol) regulation; (iv) neurotransmitter (dopamine, noradrenaline, serotonin) expressions, transporter or receptor levels, (v) anti-inflammatory (IL4 & IL10) responses; (v) skeletal muscle angiogenesis (VEGFA) and (v) energy and mitochondrial biogenesis (via PGC, UCP3, NRF2, AMPK, MAPK1, and CAMK4). The ergogenic extract helped delay fatigue by enhancing energy production, regulation and efficiency, which suggests benefits for physical activities and disease recovery. PMID:27374554

  20. Investigation of heat treating conditions for enhancing the anti-inflammatory activity of citrus fruit (Citrus reticulata) peels.

    PubMed

    Ho, Su-Chen; Lin, Chih-Cheng

    2008-09-10

    In traditional Chinese medicine, dried citrus fruit peels are widely used as remedies to alleviate coughs and reduce phlegm in the respiratory tract. Induction of inducible nitric oxide synthase (iNOS) in inflammatory cells and increased airway production of nitric oxide (NO) are well recognized as key events in inflammation-related respiratory tract diseases. Despite the fact that the enhancing effect of heat treatment on the antioxidant activity of citrus fruit peels has been well documented, the impact of heat treatment on citrus peel beneficial activities regarding anti-inflammation is unclear. To address this issue, we determined the anti-inflammatory activities of heat-treated citrus peel extracts by measuring their inhibitory effect upon NO production by lipopolysaccharide-activated RAW 264.7 macrophages. Results showed that the anti-inflammatory activity of citrus peel was significantly elevated after 100 degrees C heat treatment in a time-dependent fashion during a period from 0 to 120 min. Inhibition of iNOS gene expression was the major NO-suppressing mechanism of the citrus peel extract. Additionally, the anti-inflammatory activity of citrus peel extract highly correlated with the content of nobiletin and tangeretin. Conclusively, proper and reasonable heat treatment helped to release nobiletin and tangeretin, which were responsible for the increased anti-inflammatory activity of heat-treated citrus peels. PMID:18683945

  1. Enhanced anti-inflammatory activity of carbopol loaded meloxicam nanoethosomes gel.

    PubMed

    Ahad, Abdul; Raish, Mohammad; Al-Mohizea, Abdullah M; Al-Jenoobi, Fahad I; Alam, Mohd Aftab

    2014-06-01

    The aim of the current investigation is to develop nanoethosomes for transdermal meloxicam delivery. The ethosomes were prepared by varying the variables such as concentrations of phospholipids 90G, ethanol, and sonication time while entrapment efficiency, vesicle size and transdermal flux were the chosen responses. Results indicate that the nanoethosomes of meloxicam provides lesser vesicles size, better entrapment efficiency and improved flux for transdermal delivery as compared to rigid liposomes. The optimized formulation (MCEF-OPT) obtained was further evaluated for an in vivo anti-inflammatory activity in rats. Optimized nanoethosomal formulation with vesicles size of 142.3nm showed 78.25% entrapment efficiency and achieved transdermal flux of 10.42μg/cm(2)/h. Nanoethosomes proved to be significantly superior in terms of, amount of drug permeated into the skin, with an enhancement ratio of 3.77 when compared to rigid liposomes. In vivo pharmacodynamic study of carbopol(®) loaded nanoethosomal gel showed significant higher percent inhibition of rat paw edema compared with oral administration of meloxicam. Our results suggest that nanoethosomes are an efficient carrier for transdermal delivery of meloxicam. PMID:24657163

  2. Enhancement of Anti-Inflammatory Activity of Curcumin Using Phosphatidylserine-Containing Nanoparticles in Cultured Macrophages

    PubMed Central

    Wang, Ji; Kang, Yu-Xia; Pan, Wen; Lei, Wan; Feng, Bin; Wang, Xiao-Juan

    2016-01-01

    Macrophages are one kind of innate immune cells, and produce a variety of inflammatory cytokines in response to various stimuli, such as oxidized low density lipoprotein found in the pathogenesis of atherosclerosis. In this study, the effect of phosphatidylserine on anti-inflammatory activity of curcumin-loaded nanostructured lipid carriers was investigated using macrophage cultures. Different amounts of phosphatidylserine were used in the preparation of curcumin nanoparticles, their physicochemical properties and biocompatibilities were then compared. Cellular uptake of the nanoparticles was investigated using a confocal laser scanning microscope and flow cytometry analysis in order to determine the optimal phosphatidylserine concentration. In vitro anti-inflammatory activities were evaluated in macrophages to test whether curcumin and phosphatidylserine have interactive effects on macrophage lipid uptake behavior and anti-inflammatory responses. Here, we showed that macrophage uptake of phosphatidylserine-containing nanostructured lipid carriers increased with increasing amount of phosphatidylserine in the range of 0%–8%, and decreased when the phosphatidylserine molar ratio reached over 12%. curcumin-loaded nanostructured lipid carriers significantly inhibited lipid accumulation and pro-inflammatory factor production in cultured macrophages, and evidently promoted release of anti-inflammatory cytokines, when compared with curcumin or phosphatidylserine alone. These results suggest that the delivery system using PS-based nanoparticles has great potential for efficient delivery of drugs such as curcumin, specifically targeting macrophages and modulation of their anti-inflammatory functions. PMID:27331813

  3. Anti-proliferative effect of horehound leaf and wild cherry bark extracts on human colorectal cancer cells.

    PubMed

    Yamaguchi, Kiyoshi; Liggett, Jason L; Kim, Nam-Cheol; Baek, Seung Joon

    2006-01-01

    Marubium vulgare (horehound) and Prunus serotina (wild cherry) have been traditionally used for the treatment of inflammatory-related symptoms such as cold, fever, and sore throat. In this report, we show that extracts of anti-inflammatory horehound leaves and wild cherry bark exhibit anti-proliferative activity in human colorectal cancer cells. Both horehound and wild cherry extracts cause suppression of cell growth as well as induction of apoptosis. We found that horehound extract up-regulates pro-apoptotic non-steroidal anti-inflammatory drug-activated gene (NAG-1) through transactivation of the NAG-1 promoter. In contrast, wild cherry extract decreased cyclin D1 expression and increased NAG-1 expression in HCT-116 and SW480 cell lines. Treatment with wild cherry extract resulted in the suppression of beta-catenin/T cell factor transcription, as assessed by TOP/FOP reporter constructs, suggesting that suppressed beta-catenin signaling by wild cherry extract leads to the reduction of cyclin D1 expression. Our data suggest the mechanisms by which these extracts suppress cell growth and induce apoptosis involve enhanced NAG-1 expression and/or down-regulation of beta-catenin signaling, followed by reduced cyclin D1 expression in human colorectal cancer cells. These findings may provide mechanisms for traditional anti-inflammatory products as cancer chemopreventive agents. PMID:16328068

  4. Enhanced Anti-inflammatory Effects of γ-irradiated Pig Placenta Extracts

    PubMed Central

    Kim, Youn Kyu; Kim, Chang-Kyu; Oh, Yu-Kyung

    2015-01-01

    Porcine placenta extract (PPE) is known to possess anti-inflammatory properties owing to its high concentration of bioactive substances. However, the need to eliminate blood-borne infectious agents while maintaining biological efficacy raises concerns about the optimal method for sterilizing PPE. Therefore, the objective of this study was to compare the effects of the standard pressurized heat (autoclaving) method of sterilization with γ-irradiation on the anti-inflammatory effects of PPE. The anti-inflammatory actions of these two preparations of PPE were evaluated by measuring their inhibitory effects on the production of NO, the expression of iNOS protein, and the expression of iNOS, COX2, TNF-α, IL-1β, and IL-6 mRNA in lipopolysaccharide-stimulated RAW 264.7 cells. Compared with autoclaved PPE, γ-irradiated PPE showed significantly greater inhibition of NO production and iNOS protein expression, and produced a greater reduction in the expression of iNOS, COX2, TNF-α, IL-1β, and IL-6 mRNA. These results provide evidence that the sterilization process is crucial in determining the biological activity of PPE, especially its anti-inflammatory activity. Collectively, our data suggest that γ-irradiated PPE acts at the transcriptional level to effectively and potently suppresses the production of NO and the expression of pro-inflammatory cytokines. PMID:26761842

  5. Esters of some non-steroidal anti-inflammatory drugs with cinnamyl alcohol are potent lipoxygenase inhibitors with enhanced anti-inflammatory activity.

    PubMed

    Theodosis-Nobelos, Panagiotis; Kourti, Malamati; Tziona, Paraskevi; Kourounakis, Panos N; Rekka, Eleni A

    2015-11-15

    Novel esters of non steroidal anti-inflammatory drugs, α-lipoic acid and indol-3-acetic acid with cinnamyl alcohol were synthesised by a straightforward method and at high yields (60-98%). They reduced acute inflammation more than the parent acids and are potent inhibitors of soybean lipoxygenase. Selected structures decreased plasma lipidemic indices in Triton-induced hyperlipidemia to rats. Therefore, the synthesised compounds may add to the current knowledge about agents acting against various inflammatory disorders.

  6. Esters of some non-steroidal anti-inflammatory drugs with cinnamyl alcohol are potent lipoxygenase inhibitors with enhanced anti-inflammatory activity.

    PubMed

    Theodosis-Nobelos, Panagiotis; Kourti, Malamati; Tziona, Paraskevi; Kourounakis, Panos N; Rekka, Eleni A

    2015-11-15

    Novel esters of non steroidal anti-inflammatory drugs, α-lipoic acid and indol-3-acetic acid with cinnamyl alcohol were synthesised by a straightforward method and at high yields (60-98%). They reduced acute inflammation more than the parent acids and are potent inhibitors of soybean lipoxygenase. Selected structures decreased plasma lipidemic indices in Triton-induced hyperlipidemia to rats. Therefore, the synthesised compounds may add to the current knowledge about agents acting against various inflammatory disorders. PMID:26494261

  7. Enzymatically-Processed Wheat Bran Enhances Macrophage Activity and Has in Vivo Anti-Inflammatory Effects in Mice

    PubMed Central

    Kang, Hee; Lee, Mi-Gi; Lee, Jae-Kang; Choi, Yong-Hyun; Choi, Yong-Seok

    2016-01-01

    Wheat bran is a rich source of dietary fiber, of which arabinoxylan is the most abundant non-starch polysaccharide. Arabinoxylan has been known to exert in vivo immunological activities. Based on prior findings, we pretreated wheat bran with enzymatic hydrolysis to increase the release of soluble arabinoxylan and investigated whether oral administration of wheat bran altered macrophage activity in a mouse model. After four weeks of treatment, we isolated peritoneal macrophages for phagocytic receptor analysis and lipopolysaccharide (LPS)-induced inflammatory changes. In the second experiment, mice given wheat bran were intraperitoneally stimulated with LPS and serum levels of pro- and anti-inflammatory cytokines were determined. The expression of SRA and CD36, and phagocytic activity increased (p < 0.05, respectively). Ex vivo stimulation of macrophages by LPS resulted in reduced surface expression of CD40 (p < 0.05) and decreased production of nitric oxide (p < 0.005), tumor necrosis factor (TNF)-α (p < 0.005), interleukin (IL)-6 (p < 0.01), and IL-12 (p < 0.05). Mice treated with wheat bran showed decreased levels of serum TNF-α and IL-6 (p < 0.05, respectively) and an increased level of serum anti-inflammatory IL-10 (p < 0.05) in response to intraperitoneal LPS. Enzymatically-processed wheat bran boosts macrophage phagocytic capacity possibly through up-regulation of scavenger receptors and confers anti-inflammatory effects, indicating its potential as an immuno-enhancing functional food. PMID:27043618

  8. Cytoprotective and enhanced anti-inflammatory activities of liposomal piroxicam formulation in lipopolysaccharide-stimulated RAW 264.7 macrophages

    PubMed Central

    Chiong, Hoe Siong; Yong, Yoke Keong; Ahmad, Zuraini; Sulaiman, Mohd Roslan; Zakaria, Zainul Amiruddin; Yuen, Kah Hay; Hakim, Muhammad Nazrul

    2013-01-01

    Background Liposomal drug delivery systems, a promising lipid-based nanoparticle technology, have been known to play significant roles in improving the safety and efficacy of an encapsulated drug. Methods Liposomes, prepared using an optimized proliposome method, were used in the present work to encapsulate piroxicam, a widely prescribed nonsteroidal anti-inflammatory drug. The cytotoxic effects as well as the in vitro efficacy in regulation of inflammatory responses by free-form piroxicam and liposome-encapsulated piroxicam were evaluated using a lipopolysaccharide-sensitive macrophage cell line, RAW 264.7. Results Cells treated with liposome-encapsulated piroxicam demonstrated higher cell viabilities than those treated with free-form piroxicam. In addition, the liposomal piroxicam formulation resulted in statistically stronger inhibition of pro-inflammatory mediators (ie, nitric oxide, tumor necrosis factor-α, interleukin-1β, and prostaglandin E2) than piroxicam at an equivalent dose. The liposome-encapsulated piroxicam also caused statistically significant production of interleukin-10, an anti-inflammatory cytokine. Conclusion This study affirms the potential of a liposomal piroxicam formulation in reducing cytotoxicity and enhancing anti-inflammatory responses in vitro. PMID:23569374

  9. Multitargeting of selected prostanoid receptors provides agents with enhanced anti-inflammatory activity in macrophages.

    PubMed

    Wang, Jenny W; Woodward, David F; Martos, Jose L; Cornell, Clive L; Carling, Robert W; Kingsley, Philip J; Marnett, Lawrence J

    2016-01-01

    A polypharmacologic approach to prostanoid based anti-inflammatory therapeutics was undertaken in order to exploit both the anti- and proinflammatory properties attributed to the various prostanoid receptors. Multitargeting of selected prostanoid receptors yielded a prototype compound, compound 1 (AGN 211377), that antagonizes prostaglandin D2 receptors (DPs) DP1 (49) and DP2 (558), prostaglandin E2 receptors (EPs) EP1 (266) and EP4 (117), prostaglandin F2α receptor (FP) (61), and thromboxane A2 receptor (TP) (11) while sparing EP2, EP3, and prostaglandin I2 receptors (IPs); Kb values (in nanomoles) are given in parentheses. Compound 1 evoked a pronounced inhibition of cytokine/chemokine secretion from lipopolysaccharide or TNF-α stimulated primary human macrophages. These cytokine/chemokines included cluster of designation 40 receptor (CD40), epithelial-derived neutrophil-activating protein 78 (ENA-78), granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), IL-8, IL-18, monocyte chemotactic protein-1 (CCL2) (MCP-1), tissue plasminogen activator inhibitor (PAI-1), and regulated on activation, normal T cell expressed and secreted (RANTES). In contrast, the inhibitory effects of most antagonists selective for a single receptor were modest or absent, and selective EP2 receptor blockade increased cytokine release in some instances. Compound 1 also showed clear superiority to the cyclooxygenase inhibitors diclofenac and rofecoxib. These findings reveal that blockade of multiple prostanoid receptors, with absent antagonism of EP2 and IP, may provide more effective anti-inflammatory activity than global suppression of prostanoid synthesis or highly selective prostanoid receptor blockade. These investigations demonstrate the first working example of prostanoid receptor polypharmacology for potentially safer and more effective anti-inflammatory therapeutics by blocking multiple proinflammatory receptors while sparing

  10. Curcumin Conjugated with PLGA Potentiates Sustainability, Anti-Proliferative Activity and Apoptosis in Human Colon Carcinoma Cells

    PubMed Central

    Waghela, Bhargav N.; Sharma, Anupama; Dhumale, Suhashini; Pandey, Shashibahl M.; Pathak, Chandramani

    2015-01-01

    Curcumin, an ingredient of turmeric, exhibits a variety of biological activities such as anti-inflammatory, anti-atherosclerotic, anti-proliferative, anti-oxidant, anti-cancer and anti-metastatic. It is a highly pleiotropic molecule that inhibits cell proliferation and induces apoptosis in cancer cells. Despite its imperative biological activities, chemical instability, photo-instability and poor bioavailability limits its utilization as an effective therapeutic agent. Therefore, enhancing the bioavailability of curcumin may improve its therapeutic index for clinical setting. In the present study, we have conjugated curcumin with a biodegradable polymer Poly (D, L-lactic-co-glycolic acid) and evaluated its apoptotic potential in human colon carcinoma cells (HCT 116). The results show that curcumin-PLGA conjugate efficiently inhibits cell proliferation and cell survival in human colon carcinoma cells as compared to native curcumin. Additionally, curcumin conjugated with PLGA shows improved cellular uptake and exhibits controlled release at physiological pH as compared to native curcumin. The curcumin-PLGA conjugate efficiently activates the cascade of caspases and promotes intrinsic apoptotic signaling. Thus, the results suggest that conjugation potentiates the sustainability, anti-proliferative and apoptotic activity of curcumin. This approach could be a promising strategy to improve the therapeutic index of cancer therapy. PMID:25692854

  11. Ulinastatin attenuates experimental autoimmune encephalomyelitis by enhancing anti-inflammatory responses.

    PubMed

    Feng, Ming; Shu, Yaqing; Yang, Yu; Zheng, Xueping; Li, Rui; Wang, Yuge; Dai, Yongqiang; Qiu, Wei; Lu, Zhengqi; Hu, Xueqiang

    2014-01-01

    Multiple sclerosis (MS) is a common inflammatory and demyelinating neurological disease. Experimental autoimmune encephalomyelitis (EAE), an animal model of MS, has been widely used to test MS treatment methods. Ulinastatin (UTI), a drug used to treat acute inflammatory disorders, has been tested in animal models of autoimmune inflammatory diseases, such as ulcerative colitis and crescentic glomerulonephritis. We recently found that UTI has a neuroprotective effect on EAE by reducing oligodendrocyte apoptosis and demyelination. The anti-inflammatory effects of UTI on EAE/MS, however, have never been investigated. We have therefore evaluated the anti-inflammatory effects of UTI in EAE and explored the mechanisms underlying this effect. EAE was induced in mice with and without UTI treatment. Inflammation and demyelination of spinal cords were evaluated by staining with hematoxylin and eosin and with Luxol fast blue, respectively. Inflammatory markers in serum were analyzed by the Luminex method, and spinal cords were evaluated by immunofluorescence and Western blotting. UTI significantly lowered the clinical and pathological scores and the serum concentrations of the inflammatory cytokines interleukin (IL)-1β, IL-6, and matrix metal protease-9 (MMP-9). UTI also reduced the expression of tumor necrosis factor-alpha (TNF-α)/nuclear factor kappaB (NF-κB)/inducible nitric oxide synthase (iNOS) proteins and decreased CD11b(+) cells in spinal cord lesions. UTI may protect against EAE in mice by suppressing inflammatory responses. We think that UTI might be a potential therapeutic agent for MS.

  12. Enhancement of antioxidant and anti-inflammatory activities of bioflavonoid rutin by complexation with transition metals.

    PubMed

    Afanas'eva, I B; Ostrakhovitch, E A; Mikhal'chik, E V; Ibragimova, G A; Korkina, L G

    2001-03-15

    The antioxidant and anti-inflammatory activities of two transition metal complexes of bioflavonoid rutin, Fe(rut)Cl(3) and Cu(rut)Cl(2), were studied. It was found that Cu(rut)Cl(2) was a highly efficient in vitro and ex vivo free radical scavenger that sharply decreased (by 2-30 times compared to the parent rutin): oxygen radical production by xanthine oxidase, rat liver microsomes, and rat peritoneal macrophages; the formation of thiobarbituric acid-reactive products in microsomal lipid peroxidation; and the generation of oxygen radicals by broncho-alveolar cells from bleomycin-treated rats. The copper-rutin complex was also a superior inhibitor of inflammatory and fibrotic processes (characterized by such parameters as macrophage/neutrophil ratio, wet lung weight, total protein content, and hydroxyproline concentration) in the bleomycin-treated rats. The antioxidant activity of Fe(rut)Cl(3) was much lower and in some cases approached that of rutin. Fe(rut)Cl(3) also stimulated to some degree spontaneous oxygen radical production by macrophages. We suggested that the superior antioxidant and anti-inflammatory activity of the copper-rutin complex is a consequence of its acquiring the additional superoxide-dismuting copper center. The inhibitory activity of Fe(rut)Cl(3) was lower, probably due to the partial reduction into Fe(rut)Cl(2) in the presence of biological reductants; however, similarly to the copper-rutin complex, this complex efficiently suppressed lung edema. PMID:11266652

  13. Identification of a novel dehydroergosterol enhancing microglial anti-inflammatory activity in a dairy product fermented with Penicillium candidum.

    PubMed

    Ano, Yasuhisa; Kutsukake, Toshiko; Hoshi, Ayaka; Yoshida, Aruto; Nakayama, Hiroyuki

    2015-01-01

    Despite the ever-increasing number of dementia patients worldwide, fundamental therapeutic approaches to treat this disease remain to be established. Preventive approaches such as diet, exercise and learning attract attention. Several epidemiological studies suggest that ingestion of fermented dairy products prevents cognitive decline in the elderly. These reports indicate that specific ingredients in the fermented dairy products elicit an anti-inflammatory or anti-oxidative activity that facilitates neuroprotection. The responsible components remain to be investigated. A number of studies have shown that inflammation caused by microglia is closely related to exaggeration of the pathology and cognitive decline seen in the elderly. Many researchers have proposed that controlling microglial activities could be effective in preventing and possibly curing dementia. In the present study, to elucidate specific compounds that regulate microglial activity from dairy products, repeated purification by HPLC, combined with evaluation using primary microglia, facilitated the identification of dehydroergosterol (DHE) as a novel component of the extract that enhances microglial anti-inflammatory activity. DHE contains three conjugated double bonds in a steroid ring system and is an analogue of ergosterol. Despite their related chemical structures, the anti-inflammatory activity of DHE is markedly stronger than that of ergosterol. P. candidum for camembert cheese produces DHE, but P. Roqueforti for blue cheese and Aspergillus do not. DHE also induces CD11b-positive microglia cells into CD206-positive M2 type microglia. Neurotoxicity and neuronal cell death induced by excessively activated microglia is suppressed by treatment with DHE. Thus, this is the first report to demonstrate that DHE, identified as a responsible compound in dairy products, can induce microglia into a preferable phenotype for our brain environment and can be safely introduced into the body by consumption of

  14. Self-assembling polymeric nanoparticles for enhanced intra-articular anti-inflammatory protein delivery

    NASA Astrophysics Data System (ADS)

    Whitmire, Rachel Elisabeth

    Osteoarthritis (OA) affects 26 million Americans, or approximately 14% of the adult population. The incidence of OA is predicted to dramatically increase in the next 20 years as the US grows older and the rate of obesity continues to increase. There are currently no clinical interventions that cure OA. Current biomaterial delivery systems exhibit several limitations. First, most drug-delivery particles are hydrophobic, which is not optimal for hydrophilic protein encapsulation. Second, hydrophobic particles, such as PLGA, could cause wear damage to the already-fragile OA cartilage structure. Additionally, these particles usually suffer from non-specific protein adsorption, which causes increased phagocytosis and can lead to increased inflammation. New therapies that increase the effectiveness of OA treatments or reverse OA disease progression will greatly decrease the economic costs and individual pain associated with this disease. The goal of this thesis was to develop a new drug-delivering material to deliver anti-inflammatory protein for treating OA. Our central hypothesis for this work is that a controlled release/presentation system will more effectively deliver anti-inflammatory protein therapies to the OA joint. The primary goal of this work was to synthesize a block copolymer that could self-assemble into injectable, sub-micron-scale particles and would allow an anti-inflammatory protein, IL-1ra, to be tethered to its surface for efficient protein delivery. The block copolymer incorporated an oligo-ethylene monomer for tissue compatibility and non-fouling behavior, a 4-nitrophenol group for efficient protein tethering, and cyclohexyl methacrylate, a hydrophobic monomer, for particle stability. We engineered the copolymer and tested it in both in vitro culture experiments and an in vivo model to evaluate protein retention in the knee joint. The rationale for this project was that the rational design and synthesis of a new drug- and protein

  15. Retention of Endogenous Viable Cells Enhances the Anti-Inflammatory Activity of Cryopreserved Amnion

    PubMed Central

    Duan-Arnold, Yi; Gyurdieva, Alexandra; Johnson, Amy; Uveges, Thomas E.; Jacobstein, Douglas A.; Danilkovitch, Alla

    2015-01-01

    Objective: Human amniotic membrane (hAM) has been used to treat wounds for more than 100 years. However, widespread use of fresh hAM has been limited due to its short shelf life and safety concerns. To overcome these concerns, different preservation methods have been introduced. The majority of these methods result in devitalized hAM (dev-hAM). Recently, we developed a cryopreservation method that retains all hAM components intact (int-hAM), including viable endogenous cells. To understand the advantages of retaining viable cells in preserved hAM, we compared the anti-inflammatory properties of int-hAM and dev-hAM. Approach: The tissue composition of int-hAM and dev-hAM was compared with fresh hAM through histology and cell viability analysis. We also evaluated the ability of int-hAM and dev-hAM to regulate tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), and IL-10 release when co-cultured with immune cells; to produce prostaglandin E2 (PGE2) on TNF-α stimulation; and to inhibit proteases. Results: Int-hAM maintained the structural and cellular integrity of fresh hAM. Int-hAM had >80% cell viability post-thaw and remained viable for at least a week in culture. Viable cells were not detected in dev-hAM. Compared with dev-hAM, int-hAM showed significantly greater downregulation of TNF-α and IL-1α, upregulation of PGE2 and IL-10, and stronger inhibition of collagenase. Innovation and Conclusion: A new cryopreservation method has been developed to retain all native components of hAM. For the first time, we show that viable endogenous cells significantly augment the anti-inflammatory activity of cryopreserved hAM. PMID:26401419

  16. Myeloperoxidase-Oxidized LDLs Enhance an Anti-Inflammatory M2 and Antioxidant Phenotype in Murine Macrophages

    PubMed Central

    Sauvage, Aude; Van Steenbrugge, Martine

    2016-01-01

    Macrophages and oxidized LDLs play a key role in atherogenesis but their heterogeneity has been neglected up to now. Macrophages are prone to polarization and subsets of polarized macrophages have been described in atheromas. LDLs can be oxidized not only chemically by copper (Ox-LDLs) but also enzymatically by myeloperoxidase (MpOx-LDLs) resulting in oxidized LDLs poor in lipid peroxides. The effects of physiologically relevant myeloperoxidase-oxidized LDLs on macrophage polarization or on polarized macrophages remain largely unknown. In this study, the effects of LDLs on macrophage polarization were investigated by monitoring the expression of M1 and M2 genes following stimulation with native LDLs, Ox-LDLs, or MpOx-LDLs in RAW 264.7 cells. Except for MRC1, which is induced only by Ox-LDLs, MpOx-LDLs induced an overexpression of most of the selected marker genes at the mRNA level. MpOx-LDLs also modulate marker gene expression in polarized macrophages favoring notably anti-inflammatory Arg1 expression in M2 cells and also in the other phenotypes. Noteworthy, MpOx-LDLs were the most efficient to accumulate lipids intracellularly in (un)polarized macrophages whatever the phenotype. These data were largely confirmed in murine bone marrow-derived macrophages. Our data suggest that MpOx-LDLs were the most efficient to accumulate within cells and to enhance an anti-inflammatory and antioxidant phenotype in M2 cells and also in the other macrophage phenotypes.

  17. Release-active dilutions of diclofenac enhance anti-inflammatory effect of diclofenac in carrageenan-induced rat paw edema model.

    PubMed

    Sakat, Sachin S; Mani, Kamaraj; Demidchenko, Yulia O; Gorbunov, Evgeniy A; Tarasov, Sergey A; Mathur, Archna; Epstein, Oleg I

    2014-02-01

    The study was aimed to investigate the effect of technologically treated diclofenac (release-active dilutions of diclofenac (RAD of diclofenac)) on anti-inflammatory activity of diclofenac in carrageenan-induced rat paw edema model. Ninety male Wistar albino rats (6-8 weeks) divided into nine groups (n = 10) were used. Anti-inflammatory activity was assessed at 1, 2, 3, 4, and 6 h after subplantar injection of carrageenan (0.1 ml of a 1 % solution in normal saline). Diclofenac alone was studied at 5 and 20 mg/kg, RAD of diclofenac alone at 7.5 ml/kg and their combination at 5 and 7.5 ml/kg, respectively. Diclofenac reduced (p < 0.05 at least) paw edema at all time points. RAD of diclofenac enhanced (p < 0.05) anti-inflammatory effect of diclofenac (5 mg/kg) at 2, 4, and 6 h on concurrent and at 2 and 4 h on sequential administration. Moreover at 2 h, anti-inflammatory effect of combination treatment reached values comparable to those of diclofenac (20 mg/kg). In conclusion, RAD of diclofenac enhanced anti-inflammatory effect of diclofenac.

  18. Myeloperoxidase-Oxidized LDLs Enhance an Anti-Inflammatory M2 and Antioxidant Phenotype in Murine Macrophages

    PubMed Central

    Sauvage, Aude; Van Steenbrugge, Martine

    2016-01-01

    Macrophages and oxidized LDLs play a key role in atherogenesis but their heterogeneity has been neglected up to now. Macrophages are prone to polarization and subsets of polarized macrophages have been described in atheromas. LDLs can be oxidized not only chemically by copper (Ox-LDLs) but also enzymatically by myeloperoxidase (MpOx-LDLs) resulting in oxidized LDLs poor in lipid peroxides. The effects of physiologically relevant myeloperoxidase-oxidized LDLs on macrophage polarization or on polarized macrophages remain largely unknown. In this study, the effects of LDLs on macrophage polarization were investigated by monitoring the expression of M1 and M2 genes following stimulation with native LDLs, Ox-LDLs, or MpOx-LDLs in RAW 264.7 cells. Except for MRC1, which is induced only by Ox-LDLs, MpOx-LDLs induced an overexpression of most of the selected marker genes at the mRNA level. MpOx-LDLs also modulate marker gene expression in polarized macrophages favoring notably anti-inflammatory Arg1 expression in M2 cells and also in the other phenotypes. Noteworthy, MpOx-LDLs were the most efficient to accumulate lipids intracellularly in (un)polarized macrophages whatever the phenotype. These data were largely confirmed in murine bone marrow-derived macrophages. Our data suggest that MpOx-LDLs were the most efficient to accumulate within cells and to enhance an anti-inflammatory and antioxidant phenotype in M2 cells and also in the other macrophage phenotypes. PMID:27656049

  19. Cognitive-enhancing effects of Rhus verniciflua bark extract and its active flavonoids with neuroprotective and anti-inflammatory activities.

    PubMed

    Cho, Namki; Lee, Ki Yong; Huh, Jungmoo; Choi, Ji Hoon; Yang, Heejung; Jeong, Eun Ju; Kim, Hong Pyo; Sung, Sang Hyun

    2013-08-01

    The neuroprotective potential of flavonoids within the brain comprises anti-apoptosis of neuronal cells, anti-neuroinflammation and enhancement of cognitive function. We reported that Rhus vernciflua inhibits glutamate-induced neurotoxicity in primary cultured rat cortical cells. Here we narrowed it down to get neuroprotective fractions from the plant yielding flavonoid-rich ethyl acetate fraction (PREF). Among its active flavonoids, fisetin exhibited not only inhibitory effect against lipopolysaccharide (LPS)-induced neuroinflammation by suppressing inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 but also memory enhancing effects via reactivation of cAMP responsive element binding protein (CREB)-brain derived neurotrophic factor (BDNF) pathway in memory-impaired mice by scopolamine. Butein also showed a similar activity to fisetin even though to a lesser extent. The neuroprotection by PREF and selected flavonoids may involve maintenance of antioxidant defense mechanism including glutathione peroxidase (GSH-Px), glutathione reductase (GR) and superoxide dismutase (SOD). Conclusively, we demonstrate the R. vernciflua bark extract and its active flavonoids with potent neuroprotective and anti-inflammatory effects might be good therapeutic candidates as cognitive-enhancers.

  20. The anti-inflammatory glycoprotein, CD200, restores neurogenesis and enhances amyloid phagocytosis in a mouse model of Alzheimer's disease.

    PubMed

    Varnum, Megan M; Kiyota, Tomomi; Ingraham, Kaitlin L; Ikezu, Seiko; Ikezu, Tsuneya

    2015-11-01

    Cluster of Differentiation-200 (CD200) is an anti-inflammatory glycoprotein expressed in neurons, T cells, and B cells, and its receptor is expressed on glia. Both Alzheimer's disease patients and mouse models display age-related or amyloid-β peptide (Aβ)-induced reductions in CD200. The goal of this study was to determine if neuronal CD200 expression restores hippocampal neurogenesis and reduces Aβ in the amyloid precursor protein mouse model. Amyloid precursor protein and wild-type mice were injected at 6 months of age with an adeno-associated virus expressing CD200 into the hippocampus and sacrificed at 12 months. CD200 expression restored neural progenitor cell proliferation and differentiation in the subgranular and granular cell layers of the dentate gyrus and reduced diffuse but not thioflavin-S(+) plaques in the hippocampus. In vitro studies demonstrated that CD200-stimulated microglia increased neural differentiation of neural stem cells and enhanced axon elongation and dendrite number. CD200 also enhanced Aβ uptake by microglia. These data indicate that CD200 is capable of enhancing microglia-mediated Aβ clearance and neural differentiation and has potential as a therapeutic for Alzheimer's disease.

  1. Physical activity, by enhancing parasympathetic tone and activating the cholinergic anti-inflammatory pathway, is a therapeutic strategy to restrain chronic inflammation and prevent many chronic diseases.

    PubMed

    Lujan, Heidi L; DiCarlo, Stephen E

    2013-05-01

    Chronic diseases are the leading cause of death in the world and chronic inflammation is a key contributor to many chronic diseases. Accordingly, interventions that reduce inflammation may be effective in treating multiple adverse chronic conditions. In this context, physical activity is documented to reduce systemic low-grade inflammation and is acknowledged as an anti-inflammatory intervention. Furthermore, physically active individuals are at a lower risk of developing chronic diseases. However the mechanisms mediating this anti-inflammatory phenotype and range of health benefits are unknown. We hypothesize that the "cholinergic anti-inflammatory pathway" (CAP) mediates the anti-inflammatory phenotype and range of health benefits associated with physical activity. The CAP is an endogenous, physiological mechanism by which acetylcholine from the vagus nerve, interacts with the innate immune system to modulate and restrain the inflammatory cascade. Importantly, higher levels of physical activity are associated with enhanced parasympathetic (vagal) tone and lower levels of C-reactive protein, a marker of low-grade inflammation. Accordingly, physical activity, by enhancing parasympathetic tone and activating the CAP, may be a therapeutic strategy to restrain chronic inflammation and prevent many chronic diseases.

  2. Eugenol enhances the chemotherapeutic potential of gemcitabine and induces anticarcinogenic and anti-inflammatory activity in human cervical cancer cells.

    PubMed

    Hussain, Arif; Brahmbhatt, Kruti; Priyani, Anita; Ahmed, Musthaq; Rizvi, Tahir A; Sharma, Chhavi

    2011-10-01

    Administration of natural or synthetic agents to inhibit, delay, block, or reverse the initiation and promotional events associated with carcinogenesis opens a new avenue for cancer prevention and treatment to reduce cancer morbidity and mortality. Eugenol, a potential chemopreventive agent, is a component of clove and several other spices such as basil, cinnamon, and bay leaves. A number of reports have shown that eugenol possesses antiseptic, analgesic, antibacterial, and anticancer properties. The present study was undertaken to evaluate the chemopreventive potential of eugenol alone and in combination with a chemotherapeutic agent such as gemcitabine. Eugenol showed dose-dependent selective cytotoxicity toward HeLa cells in comparison to normal cells, pointing to its safe cytotoxicity profile. A combination of eugenol and gemcitabine induced growth inhibition and apoptosis at lower concentrations, compared with the individual drugs. The analysis of the data using a combination index showed combination index values of <1 indicating strong synergistic interaction. The combination thus may enhance the efficacy of gemcitabine at lower doses and minimize the toxicity on normal cells. In addition, the expression analysis of genes involved in apoptosis and inflammation revealed significant downregulation of Bcl-2, COX-2, and IL-1β on treatment with eugenol. Thus, the results suggest that eugenol exerts its anticancer activities via apoptosis induction and anti-inflammatory properties and also provide the first evidence demonstrating synergism between eugenol and gemcitabine, which may enhance the therapeutic index of prevention and/or treatment of cervical cancer.

  3. Suppression of PRKAR1A expression enhances anti-proliferative and apoptotic effects of protein kinase inhibitors and chemotherapeutic drugs on cholangiocarcinoma cells.

    PubMed

    Loilome, Watcharin; Juntana, Sirinun; Pinitsoontorn, Chadamas; Namwat, Nisana; Tassaneeyakul, Wichittra; Yongvanit, Puangrat

    2012-01-01

    Suppression of protein kinase A regulatory subunit 1 alpha (PRKAR1A) has been proven to inhibit cholangiocarcinoma (CCA) cell growth and enhance apoptosis. In the present study, we aimed to determine synergistic and/or additive effects of chemotherapeutic agents, including protein kinase inhibitors (i.e. sorafenib, sunitinib, gefitinib, Met inhibitor) and conventional chemotherapeutic drugs (i.e. 5-fluorouracil, doxorubicin, paclitaxel, gemcitabine), in PRKARIA knockdown CCA cell lines. The results revealed that PRKAR1A suppressed CCA cell lines demonstrated enhanced sensitivity to some chemotherapeutic drugs when compared to control cells. Moreover, PRKAR1A knockdown in combination with either sorafenib or 5-fluorouracil increased apoptotic effects on CCA cell lines. Therefore, selective inhibition of PRKAR1A appears to enhance the growth inhibitory effects of chemotherapeutic drugs as well as induce apoptotic cell death. Our findings suggest that additional suppression of PRKAR1A expression may increase the efficacy of conventional CCA chemotherapeutic treatment. Clinical studies in CCA patients now need to be conducted. PMID:23480756

  4. Anti-proliferative activity of oral anti-hyperglycemic agents on human vascular smooth muscle cells: thiazolidinediones (glitazones) have enhanced activity under high glucose conditions

    PubMed Central

    Little, Peter J; Osman, Narin; de Dios, Stephanie T; Cemerlang, Nelly; Ballinger, Mandy; Nigro, Julie

    2007-01-01

    Background Inhibition of vascular smooth muscle cell (vSMC) proliferation by oral anti-hyperglycemic agents may have a role to play in the amelioration of vascular disease in diabetes. Thiazolidinediones (TZDs) inhibit vSMC proliferation but it has been reported that they anomalously stimulate [3H]-thymidine incorporation. We investigated three TZDs, two biguanides and two sulfonylureas for their ability of inhibit vSMC proliferation. People with diabetes obviously have fluctuating blood glucose levels thus we determined the effect of media glucose concentration on the inhibitory activity of TZDs in a vSMC preparation that grew considerably more rapidly under high glucose conditions. We further explored the mechanisms by which TZDs increase [3H]-thymidine incorporation. Methods VSMC proliferation was investigated by [3H]-thymidine incorporation into DNA and cell counting. Activation and inhibition of thymidine kinase utilized short term [3H]-thymidine uptake. Cell cycle events were analyzed by FACS. Results VSMC cells grown for 3 days in DMEM with 5% fetal calf serum under low (5 mM glucose) and high (25 mM glucose) increased in number by 2.5 and 4.7 fold, respectively. Rosiglitazone and pioglitazone showed modest but statistically significantly greater inhibitory activity under high versus low glucose conditions (P < 0.05 and P < 0.001, respectively). We confirmed an earlier report that troglitazone (at low concentrations) causes enhanced incorporation of [3H]-thymidine into DNA but did not increase cell numbers. Troglitazone inhibited serum mediated thymidine kinase induction in a concentration dependent manner. FACS analysis showed that troglitazone and rosiglitazone but not pioglitazone placed a slightly higher percentage of cells in the S phase of a growing culture. Of the biguanides, metformin had no effect on proliferation assessed as [3H]-thymidine incorporation or cell numbers whereas phenformin was inhibitory in both assays albeit at high concentrations

  5. Anti-inflammatory Diets.

    PubMed

    Sears, Barry

    2015-01-01

    Chronic disease is driven by inflammation. This article will provide an overview on how the balance of macronutrients and omega-6 and omega-3 fatty acids in the diet can alter the expression of inflammatory genes. In particular, how the balance of the protein to glycemic load of a meal can alter the generation of insulin and glucagon and the how the balance of omega-6 and omega-3 fatty acids can effect eicosanoid formation. Clinical results on the reduction of inflammation following anti-inflammatory diets are discussed as well as the molecular targets of anti-inflammatory nutrition. To overcome silent inflammation requires an anti-inflammatory diet (with omega-3s and polyphenols, in particular those of Maqui). The most important aspect of such an anti-inflammatory diet is the stabilization of insulin and reduced intake of omega-6 fatty acids. The ultimate treatment lies in reestablishing hormonal and genetic balance to generate satiety instead of constant hunger. Anti-inflammatory nutrition, balanced 40:30:30 with caloric restriction, should be considered as a form of gene silencing technology, in particular the silencing of the genes involved in the generation of silent inflammation. To this anti-inflammatory diet foundation supplemental omega-3 fatty acids at the level of 2-3 g of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) per day should be added. Finally, a diet rich in colorful, nonstarchy vegetables would contribute adequate amounts of polyphenols to help not only to inhibit nuclear factor (NF)-κB (primary molecular target of inflammation) but also activate AMP kinase. Understanding the impact of an anti-inflammatory diet on silent inflammation can elevate the diet from simply a source of calories to being on the cutting edge of gene-silencing technology. PMID:26400429

  6. Mutually enhancing anti-inflammatory activities of dimethyl fumarate and NF-κB inhibitors--implications for dose-sparing combination therapies.

    PubMed

    Hund, Anna-Carina; Lockmann, Anike; Schön, Michael P

    2016-02-01

    Fumaric acid esters, dimethyl fumarate (DMF) in particular, have been established for the therapy of psoriasis and, more recently, multiple sclerosis. In the light of therapy-limiting dose-dependent side effects, such as gastrointestinal irritation, reducing the effective doses of FAE is a worthwhile goal. In search of strategies to maintain the anti-inflammatory activity of DMF at reduced concentrations, we found that NF-κB inhibition augmented key anti-inflammatory effects of DMF in two complementary experimental settings in vitro. At non-toxic concentrations, both proteasome inhibition with bortezomib as well as blocking NF-κB activation through KINK-1, a small molecule inhibitor of IKKβ-profoundly enhanced DMF-dependent inhibition of nuclear NF-κB translocation in TNFα-stimulated human endothelial cells. This resulted in significant and selective co-operative down-regulation of endothelial adhesion molecules crucial for leucocyte extravasation, namely E-selectin (CD62E), VCAM-1 (CD106) and ICAM-1 (CD54), on both mRNA and protein levels. Functionally, these molecular changes led to synergistically decreased rolling and firm adhesion of human lymphocytes on TNF-activated endothelial cells, as demonstrated in a dynamic flow chamber system. If our in vitro findings can be translated into clinical settings, it is conceivable that anti-inflammatory effects of DMF can be achieved with lower doses than currently used, thus potentially reducing unwanted side effects. PMID:26513635

  7. Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug

    PubMed Central

    Dang, Tram T.; Thai, Anh V.; Cohen, Joshua; Slosberg, Jeremy E.; Siniakowicz, Karolina; Doloff, Joshua C.; Ma, Minglin; Hollister-Lock, Jennifer; Tang, Katherine; Gu, Zhen; Cheng, Hao; Weir, Gordon C.; Langer, Robert; Anderson, Daniel G.

    2013-01-01

    Immuno-isolation of islets has the potential to enable the replacement of pancreatic function in diabetic patients. However, host response to the encapsulated islets frequently leads to fibrotic overgrowth with subsequent impairment of the transplanted grafts. Here, we identified and incorporated anti-inflammatory agents into islet-containing microcapsules to address this challenge. In vivo subcutaneous screening of 16 small molecule anti-inflammatory drugs was performed to identify promising compounds that could minimize the formation of fibrotic cell layers. Using parallel non-invasive fluorescent and bioluminescent imaging, we identified dexamethasone and curcumin as the most effective drugs in inhibiting the activities of inflammatory proteases and reactive oxygen species in the host response to subcutaneously injected biomaterials. Next, we demonstrated that co-encapsulating curcumin with pancreatic rat islets in alginate microcapsules reduced fibrotic overgrowth and improved glycemic control in a mouse model of chemically-induced type I diabetes. These results showed that localized administration of anti-inflammatory drug can improve the longevity of encapsulated islets and may facilitate the translation of this technology towards a long-term cure for type I diabetes. PMID:23660251

  8. Inhibition of soluble epoxide hydrolase enhances the anti-inflammatory effects of aspirin and 5-lipoxygenase activation protein inhibitor in a murine model.

    PubMed

    Liu, Jun-Yan; Yang, Jun; Inceoglu, Bora; Qiu, Hong; Ulu, Arzu; Hwang, Sung-Hee; Chiamvimonvat, Nipavan; Hammock, Bruce D

    2010-03-15

    Inflammation is a multi-staged process whose expansive phase is thought to be driven by acutely released arachidonic acid (AA) and its metabolites. Inhibition of cyclooxygenase (COX), lipoxygenase (LOX), or soluble epoxide hydrolase (sEH) is known to be anti-inflammatory. Inhibition of sEH stabilizes the cytochrome P450 (CYP450) products epoxyeicosatrienoic acids (EETs). Here we used a non-selective COX inhibitor aspirin, a 5-lipoxygenase activation protein (FLAP) inhibitor MK886, and a sEH inhibitor t-AUCB to selectively modulate the branches of AA metabolism in a lipopolysaccharide (LPS)-challenged murine model. We used metabolomic profiling to simultaneously monitor representative AA metabolites of each branch. In addition to the significant crosstalk among branches of the AA cascade during selective modulation of COX, LOX, or sEH, we demonstrated that co-administration of t-AUCB enhanced the anti-inflammatory effects of aspirin or MK886, which was evidenced by the observations that co-administration resulted in favorable eicosanoid profiles and better control of LPS-mediated hypotension as well as hepatic protein expression of COX-2 and 5-LOX. Targeted disruption of the sEH gene displayed a parallel profile to that produced by t-AUCB. These observations demonstrate a significant level of crosstalk among the three major branches of the AA cascade and that they are not simply parallel pathways. These data illustrate that inhibition of sEH by both pharmacological intervention and gene knockout enhances the anti-inflammatory effects of aspirin and MK886, suggesting the possibility of modulating multiple branches to achieve better therapeutic effects. PMID:19896470

  9. A peroxisome proliferator-activated receptor ligand MCC-555 imparts anti-proliferative response in pancreatic cancer cells by PPARgamma-independent up-regulation of KLF4

    SciTech Connect

    Min, Kyung-Won; Zhang, Xiaobo; Imchen, Temjenmongla; Baek, Seung Joon

    2012-09-01

    MCC-555 is a novel PPARα/γ dual ligand of the thiazolidinedione class and was recently developed as an anti-diabetic drug with unique properties. MCC-555 also has anti-proliferative activity through growth inhibition and apoptosis induction in several cancer cell types. Our group has shown that MCC-555 targets several proteins in colorectal tumorigenesis including nonsteroidal anti-inflammatory drug (NSAID)-activated gene (NAG-1) which plays an important role in chemoprevention responsible for chemopreventive compounds. NAG-1 is a member of the TGF-β superfamily and is involved in tumor progression and development; however, NAG-1's roles in pancreatic cancer have not been studied. In this report, we found that MCC-555 alters not only NAG-1 expression, but also p21 and cyclin D1 expression. NAG-1 and p21 expression was not blocked by PPARγ-specific antagonist GW9662, suggesting that MCC-555-induced NAG-1 and p21 expression is independent of PPARγ activation. However, decreasing cyclin D1 by MCC-555 seems to be affected by PPARγ activation. Further, we found that the GC box located in the NAG-1 promoter play an important role in NAG-1 transactivation by MCC-555. Subsequently, we screened several transcription factors that may bind to the GC box region in the NAG-1 promoter and found that KLF4 potentially binds to this region. Expression of KLF4 precedes NAG-1 and p21 expression in the presence of MCC-555, whereas blocking KLF4 expression using specific KLF4 siRNA showed that both NAG-1 and p21 expression by MCC-555 was blocked. In conclusion, MCC-555's actions on anti-proliferation involve both PPARγ-dependent and -independent pathways, thereby enhancing anti-tumorigenesis in pancreatic cancer cells. -- Highlights: ► PPARα/γ ligand MCC-555 exhibits anti-proliferative activity in pancreatic cancer cells. ► MCC-555 affects KLF4 expression following by NAG-1 and p21 expression in a PPARγ independent manner. ► MCC-555 also affects cyclin D1 down

  10. The Anti-Inflammatory Compound Curcumin Enhances Locomotor and Sensory Recovery after Spinal Cord Injury in Rats by Immunomodulation.

    PubMed

    Machova Urdzikova, Lucia; Karova, Kristyna; Ruzicka, Jiri; Kloudova, Anna; Shannon, Craig; Dubisova, Jana; Murali, Raj; Kubinova, Sarka; Sykova, Eva; Jhanwar-Uniyal, Meena; Jendelova, Pavla

    2015-12-31

    Well known for its anti-oxidative and anti-inflammation properties, curcumin is a polyphenol found in the rhizome of Curcuma longa. In this study, we evaluated the effects of curcumin on behavioral recovery, glial scar formation, tissue preservation, axonal sprouting, and inflammation after spinal cord injury (SCI) in male Wistar rats. The rats were randomized into two groups following a balloon compression injury at the level of T9-T10 of the spinal cord, namely vehicle- or curcumin-treated. Curcumin was applied locally on the surface of the injured spinal cord immediately following injury and then given intraperitoneally daily; the control rats were treated with vehicle in the same manner. Curcumin treatment improved behavioral recovery within the first week following SCI as evidenced by improved Basso, Beattie, and Bresnahan (BBB) test and plantar scores, representing locomotor and sensory performance, respectively. Furthermore, curcumin treatment decreased glial scar formation by decreasing the levels of MIP1α, IL-2, and RANTES production and by decreasing NF-κB activity. These results, therefore, demonstrate that curcumin has a profound anti-inflammatory therapeutic potential in the treatment of spinal cord injury, especially when given immediately after the injury.

  11. The Anti-Inflammatory Compound Curcumin Enhances Locomotor and Sensory Recovery after Spinal Cord Injury in Rats by Immunomodulation.

    PubMed

    Machova Urdzikova, Lucia; Karova, Kristyna; Ruzicka, Jiri; Kloudova, Anna; Shannon, Craig; Dubisova, Jana; Murali, Raj; Kubinova, Sarka; Sykova, Eva; Jhanwar-Uniyal, Meena; Jendelova, Pavla

    2016-01-01

    Well known for its anti-oxidative and anti-inflammation properties, curcumin is a polyphenol found in the rhizome of Curcuma longa. In this study, we evaluated the effects of curcumin on behavioral recovery, glial scar formation, tissue preservation, axonal sprouting, and inflammation after spinal cord injury (SCI) in male Wistar rats. The rats were randomized into two groups following a balloon compression injury at the level of T9-T10 of the spinal cord, namely vehicle- or curcumin-treated. Curcumin was applied locally on the surface of the injured spinal cord immediately following injury and then given intraperitoneally daily; the control rats were treated with vehicle in the same manner. Curcumin treatment improved behavioral recovery within the first week following SCI as evidenced by improved Basso, Beattie, and Bresnahan (BBB) test and plantar scores, representing locomotor and sensory performance, respectively. Furthermore, curcumin treatment decreased glial scar formation by decreasing the levels of MIP1α, IL-2, and RANTES production and by decreasing NF-κB activity. These results, therefore, demonstrate that curcumin has a profound anti-inflammatory therapeutic potential in the treatment of spinal cord injury, especially when given immediately after the injury. PMID:26729105

  12. The Anti-Inflammatory Compound Curcumin Enhances Locomotor and Sensory Recovery after Spinal Cord Injury in Rats by Immunomodulation

    PubMed Central

    Machova Urdzikova, Lucia; Karova, Kristyna; Ruzicka, Jiri; Kloudova, Anna; Shannon, Craig; Dubisova, Jana; Murali, Raj; Kubinova, Sarka; Sykova, Eva; Jhanwar-Uniyal, Meena; Jendelova, Pavla

    2015-01-01

    Well known for its anti-oxidative and anti-inflammation properties, curcumin is a polyphenol found in the rhizome of Curcuma longa. In this study, we evaluated the effects of curcumin on behavioral recovery, glial scar formation, tissue preservation, axonal sprouting, and inflammation after spinal cord injury (SCI) in male Wistar rats. The rats were randomized into two groups following a balloon compression injury at the level of T9–T10 of the spinal cord, namely vehicle- or curcumin-treated. Curcumin was applied locally on the surface of the injured spinal cord immediately following injury and then given intraperitoneally daily; the control rats were treated with vehicle in the same manner. Curcumin treatment improved behavioral recovery within the first week following SCI as evidenced by improved Basso, Beattie, and Bresnahan (BBB) test and plantar scores, representing locomotor and sensory performance, respectively. Furthermore, curcumin treatment decreased glial scar formation by decreasing the levels of MIP1α, IL-2, and RANTES production and by decreasing NF-κB activity. These results, therefore, demonstrate that curcumin has a profound anti-inflammatory therapeutic potential in the treatment of spinal cord injury, especially when given immediately after the injury. PMID:26729105

  13. Enhanced osteogenic activity and anti-inflammatory properties of Lenti-BMP-2-loaded TiO₂ nanotube layers fabricated by lyophilization following trehalose addition.

    PubMed

    Zhang, Xiaochen; Zhang, Zhiyuan; Shen, Gang; Zhao, Jun

    2016-01-01

    To enhance biocompatibility and osseointegration between titanium implants and surrounding bone tissue, numerous efforts have been made to modify the surface topography and composition of Ti implants. In this paper, Lenti-BMP-2-loaded TiO2 nanotube coatings were fabricated by lyophilization in the presence of trehalose to functionalize the surface. We characterized TiO2 nanotube layers in terms of the following: surface morphology; Lenti-BMP-2 and trehalose release; their ability to induce osteogenesis, proliferation, and anti-inflammation in vitro; and osseointegration in vivo. The anodized TiO2 nanotube surfaces exhibited an amorphous glassy matrix perpendicular to the Ti surface. Both Lenti-BMP-2 and trehalose showed sustained release over the course of 8 days. Results from real-time quantitative polymerase chain reaction studies demonstrated that lyophilized Lenti-BMP-2/TiO2 nanotubes constructed with trehalose (Lyo-Tre-Lenti-BMP-2) significantly promoted osteogenic differentiation of bone marrow stromal cells but not their proliferation. In addition, Lyo-Tre-Lenti-BMP-2 nanotubes effectively inhibited lipopolysaccharide-induced interleukin-1β and tumor necrosis factor-α production. In vivo, the formulation also promoted osseointegration. This study presents a promising new method for surface-modifying biomedical Ti-based implants to simultaneously enhance their osteogenic potential and anti-inflammatory properties, which can better satisfy clinical needs.

  14. Enhanced osteogenic activity and anti-inflammatory properties of Lenti-BMP-2-loaded TiO₂ nanotube layers fabricated by lyophilization following trehalose addition.

    PubMed

    Zhang, Xiaochen; Zhang, Zhiyuan; Shen, Gang; Zhao, Jun

    2016-01-01

    To enhance biocompatibility and osseointegration between titanium implants and surrounding bone tissue, numerous efforts have been made to modify the surface topography and composition of Ti implants. In this paper, Lenti-BMP-2-loaded TiO2 nanotube coatings were fabricated by lyophilization in the presence of trehalose to functionalize the surface. We characterized TiO2 nanotube layers in terms of the following: surface morphology; Lenti-BMP-2 and trehalose release; their ability to induce osteogenesis, proliferation, and anti-inflammation in vitro; and osseointegration in vivo. The anodized TiO2 nanotube surfaces exhibited an amorphous glassy matrix perpendicular to the Ti surface. Both Lenti-BMP-2 and trehalose showed sustained release over the course of 8 days. Results from real-time quantitative polymerase chain reaction studies demonstrated that lyophilized Lenti-BMP-2/TiO2 nanotubes constructed with trehalose (Lyo-Tre-Lenti-BMP-2) significantly promoted osteogenic differentiation of bone marrow stromal cells but not their proliferation. In addition, Lyo-Tre-Lenti-BMP-2 nanotubes effectively inhibited lipopolysaccharide-induced interleukin-1β and tumor necrosis factor-α production. In vivo, the formulation also promoted osseointegration. This study presents a promising new method for surface-modifying biomedical Ti-based implants to simultaneously enhance their osteogenic potential and anti-inflammatory properties, which can better satisfy clinical needs. PMID:26869786

  15. Enhanced osteogenic activity and anti-inflammatory properties of Lenti-BMP-2-loaded TiO2 nanotube layers fabricated by lyophilization following trehalose addition

    PubMed Central

    Zhang, Xiaochen; Zhang, Zhiyuan; Shen, Gang; Zhao, Jun

    2016-01-01

    To enhance biocompatibility and osseointegration between titanium implants and surrounding bone tissue, numerous efforts have been made to modify the surface topography and composition of Ti implants. In this paper, Lenti-BMP-2-loaded TiO2 nanotube coatings were fabricated by lyophilization in the presence of trehalose to functionalize the surface. We characterized TiO2 nanotube layers in terms of the following: surface morphology; Lenti-BMP-2 and trehalose release; their ability to induce osteogenesis, proliferation, and anti-inflammation in vitro; and osseointegration in vivo. The anodized TiO2 nanotube surfaces exhibited an amorphous glassy matrix perpendicular to the Ti surface. Both Lenti-BMP-2 and trehalose showed sustained release over the course of 8 days. Results from real-time quantitative polymerase chain reaction studies demonstrated that lyophilized Lenti-BMP-2/TiO2 nanotubes constructed with trehalose (Lyo-Tre-Lenti-BMP-2) significantly promoted osteogenic differentiation of bone marrow stromal cells but not their proliferation. In addition, Lyo-Tre-Lenti-BMP-2 nanotubes effectively inhibited lipopolysaccharide-induced interleukin-1β and tumor necrosis factor-α production. In vivo, the formulation also promoted osseointegration. This study presents a promising new method for surface-modifying biomedical Ti-based implants to simultaneously enhance their osteogenic potential and anti-inflammatory properties, which can better satisfy clinical needs. PMID:26869786

  16. Peptoid-Substituted Hybrid Antimicrobial Peptide Derived from Papiliocin and Magainin 2 with Enhanced Bacterial Selectivity and Anti-inflammatory Activity.

    PubMed

    Shin, Areum; Lee, Eunjung; Jeon, Dasom; Park, Young-Guen; Bang, Jeong Kyu; Park, Yong-Sun; Shin, Song Yub; Kim, Yangmee

    2015-06-30

    Antimicrobial peptides (AMPs) are important components of the host innate immune system. Papiliocin is a 37-residue AMP purified from larvae of the swallowtail butterfly Papilio xuthus. Magainin 2 is a 23-residue AMP purified from the skin of the African clawed frog Xenopus laevis. We designed an 18-residue hybrid peptide (PapMA) incorporating N-terminal residues 1-8 of papiliocin and N-terminal residues 4-12 of magainin 2, joined by a proline (Pro) hinge. PapMA showed high antimicrobial activity but was cytotoxic to mammalian cells. To decrease PapMA cytotoxicity, we designed a lysine (Lys) peptoid analogue, PapMA-k, which retained high antimicrobial activity but displayed cytotoxicity lower than that of PapMA. Fluorescent dye leakage experiments and confocal microscopy showed that PapMA targeted bacterial cell membranes whereas PapMA-k penetrated bacterial cell membranes. Nuclear magnetic resonance experiments revealed that PapMA contained an N-terminal α-helix from Lys(3) to Lys(7) and a C-terminal α-helix from Lys(10) to Lys(17), with a Pro(9) hinge between them. PapMA-k also had two α-helical structures in the same region connected with a flexible hinge residue at Nlys(9), which existed in a dynamic equilibrium of cis and trans conformers. Using lipopolysaccharide-stimulated RAW264.7 macrophages, the anti-inflammatory activity of PapMA and PapMA-k was confirmed by inhibition of nitric oxide and inflammatory cytokine production. In addition, treatment with PapMA and PapMA-k decreased the level of ultraviolet irradiation-induced expression of genes encoding matrix metalloproteinase-1 (MMP-1), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in human keratinocyte HaCaT cells. Thus, PapMA and PapMA-k are potent peptide antibiotics with antimicrobial and anti-inflammatory activity, with PapMA-k displaying enhanced bacterial selectivity.

  17. Anti-Proliferative Effect of Rosmarinus officinalis L. Extract on Human Melanoma A375 Cells

    PubMed Central

    Cattaneo, Lucia; Cicconi, Rosella; Mignogna, Giuseppina; Giorgi, Alessandra; Mattei, Maurizio; Graziani, Giulia; Ferracane, Rosalia; Grosso, Alessandro; Aducci, Patrizia; Schininà, M. Eugenia; Marra, Mauro

    2015-01-01

    Rosemary (Rosmarinus officinalis L.) has been used since ancient times in traditional medicine, while nowadays various rosemary formulations are increasingly exploited by alternative medicine to cure or prevent a wide range of health disorders. Rosemary’s bioproperties have prompted scientific investigation, which allowed us to ascertain antioxidant, anti-inflammatory, cytostatic, and cytotoxic activities of crude extracts or of pure components. Although there is a growing body of experimental work, information about rosemary’s anticancer properties, such as chemoprotective or anti-proliferative effects on cancer cells, is very poor, especially concerning the mechanism of action. Melanoma is a skin tumor whose diffusion is rapidly increasing in the world and whose malignancy is reinforced by its high resistance to cytotoxic agents; hence the availability of new cytotoxic drugs would be very helpful to improve melanoma prognosis. Here we report on the effect of a rosemary hydroalcoholic extract on the viability of the human melanoma A375 cell line. Main components of rosemary extract were identified by liquid chromatography coupled to tandem mass spectrometry (LC/ESI-MS/MS) and the effect of the crude extract or of pure components on the proliferation of cancer cells was tested by MTT and Trypan blue assays. The effect on cell cycle was investigated by using flow cytometry, and the alteration of the cellular redox state was evaluated by intracellular ROS levels and protein carbonylation analysis. Furthermore, in order to get information about the molecular mechanisms of cytotoxicity, a comparative proteomic investigation was performed. PMID:26176704

  18. DLBS1425, a Phaleria macrocarpa (Scheff.) Boerl. extract confers anti proliferative and proapoptosis effects via eicosanoid pathway.

    PubMed

    Tjandrawinata, Raymond R; Arifin, Poppy Firzani; Tandrasasmita, Olivia M; Rahmi, Dina; Aripin, Asep

    2010-01-01

    Phaleria macrocarpa (Scheff.) Boerl. (Thymelaeaceae), an Indonesian native plant, has been used to treat various diseases in Indonesia. DLBS1425, a standardized extract of flesh fruit of Phaleria macrocarpa, is hypothesized to have anti-cancer activities. Anti-proliferative and induction of apoptosis conferred by DLBS1425 on breast cancer cells, MDA-MB-231 and MCF-7 cells were investigated. DLBS1425 showed an inhibition of proliferation in both cell lines. Induction of apoptosis was shown by DNA fragmentation, activation of caspase 9, and regulation of Bax and Bcl-2 at the mRNA level. DLBS1425 downregulated COX-2, cPLA2, and VEGF-C mRNA expressions. DLBS1425 also down-regulated c-fos and HER-2/neu mRNA expression in TPA- or fatty acid-induced MDA-MB-231 cells. These findings demonstrate that DLBS1425 has anti-proliferative, anti-inflammatory, and anti-angiogenic properties, which make it pharmacologically ideal for the prevention and/or treatment of breast cancer. PMID:20734918

  19. Enhanced Neuroprotection of Acetyl-11-Keto-β-Boswellic Acid (AKBA)-Loaded O-Carboxymethyl Chitosan Nanoparticles Through Antioxidant and Anti-Inflammatory Pathways.

    PubMed

    Ding, Yi; Qiao, Youbei; Wang, Min; Zhang, Huinan; Li, Liang; Zhang, Yikai; Ge, Jie; Song, Ying; Li, Yuwen; Wen, Aidong

    2016-08-01

    Acetyl-11-keto-β-boswellic acid (AKBA), a main active constituent from Boswellia serrata resin, is a novel candidate for therapy of cerebral ischemia-reperfusion (I/R) injury. Nevertheless, its poor solubility in aqueous solvent, bioavailability, and rapid clearance limit its curative efficacy. To enhance its potency, in our study, AKBA-loaded o-carboxymethyl chitosan nanoparticle (AKBA-NP) delivery system was synthesized. The transmission electron microscopy and transmission electron microscope images of AKBA-NPs suggested that particle size was 132 ± 18 nm, and particles were spherical in shape with smooth morphology. In pharmacokinetics study, AKBA-NPs apparently increases the area under the curve of plasma concentration-time and prolonged half-life compared with AKBA. The tissue distribution study confirmed that AKBA-NPs had a better brain delivery efficacy in comparison with AKBA. The results from our pharmacodynamic studies showed that AKBA-NPs possess better neuroprotection compared with AKBA in primary neurons with oxygen-glucose deprivation (OGD) model and in animals with middle cerebral artery occlusion (MCAO) model. Additionally, AKBA-NPs modulate antioxidant and anti-inflammatory pathways more effectively than AKBA by increasing nuclear erythroid 2-related factor 2 and heme oxygenase-1 expression, and by decreasing nuclear factor-kappa B and 5-lipoxygenase expression. Collectively, our results suggest that AKBA-NPs serve as a potent delivery vehicle for AKBA in cerebral ischemic therapy. PMID:26162321

  20. Anti-inflammatory and anti-proliferative effect of herbal medicines (APR) in RAW264.7 cells

    PubMed Central

    CHOI, HAN-SEOK; SEO, HYE SOOK; KIM, SOON RE; CHOI, YOUN KYUNG; SHIN, YONG-CHEOL; KO, SEONG-GYU

    2014-01-01

    The objective of the present study was to analyze the effect of a mixture of medicinal plants [Angelica gigas Nakai, Panax ginseng and Rhus verniciflua Stokes (APR)] on lipopolysaccharide (LPS)-induced inflammatory responses in the murine macrophage cell line RAW264.7. Cells were treated with APR and LPS at various concentrations and indicated times. WST assay, trypan blue assay and quantification of activated cells demonstrated that APR suppressed cell proliferation in a dose-dependent manner. APR induced G1 cell cycle arrest and inhibited the LPS-induced phosphorylation of protein kinase B (AKT), extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (p38) and necrosis factor κB (NF-κB). APR also suppressed nitric oxide synthase isoform (iNOS) and prostaglandin endoperoxide synthase 2 (Cox-2) messenger ribonucleic acid (mRNA) expression induced by LPS. Furthermore, APR decreased LPS-induced intracellular reactive oxygen species (ROS) levels, mitochondrial membrane potential, as well as induced PARP and caspase-3 cleavage, suggesting that APR causes apoptosis. In conclusion, the present study indicated that APR may be advantageous in treating inflammatory disease. PMID:24626965

  1. Preventive effects of a fermented dairy product against Alzheimer's disease and identification of a novel oleamide with enhanced microglial phagocytosis and anti-inflammatory activity.

    PubMed

    Ano, Yasuhisa; Ozawa, Makiko; Kutsukake, Toshiko; Sugiyama, Shinya; Uchida, Kazuyuki; Yoshida, Aruto; Nakayama, Hiroyuki

    2015-01-01

    Despite the ever-increasing number of patients with dementia worldwide, fundamental therapeutic approaches to this condition have not been established. Epidemiological studies suggest that intake of fermented dairy products prevents cognitive decline in the elderly. However, the active compounds responsible for the effect remain to be elucidated. The present study aims to elucidate the preventive effects of dairy products on Alzheimer's disease and to identify the responsible component. Here, in a mouse model of Alzheimer's disease (5xFAD), intake of a dairy product fermented with Penicillium candidum had preventive effects on the disease by reducing the accumulation of amyloid β (Aβ) and hippocampal inflammation (TNF-α and MIP-1α production), and enhancing hippocampal neurotrophic factors (BDNF and GDNF). A search for preventive substances in the fermented dairy product identified oleamide as a novel dual-active component that enhanced microglial Aβ phagocytosis and anti-inflammatory activity towards LPS stimulation in vitro and in vivo. During the fermentation, oleamide was synthesized from oleic acid, which is an abundant component of general dairy products owing to lipase enzymatic amidation. The present study has demonstrated the preventive effect of dairy products on Alzheimer's disease, which was previously reported only epidemiologically. Moreover, oleamide has been identified as an active component of dairy products that is considered to reduce Aβ accumulation via enhanced microglial phagocytosis, and to suppress microglial inflammation after Aβ deposition. Because fermented dairy products such as camembert cheese are easy to ingest safely as a daily meal, their consumption might represent a preventive strategy for dementia.

  2. Effect of new hybrids based on 5,16-pregnadiene scaffold linked to an anti-inflammatory drug on the growth of a human astrocytoma cell line (U373).

    PubMed

    Garrido, Mariana; González-Arenas, Aliesha; Camacho-Arroyo, Ignacio; Cabeza, Marisa; Alcaraz, Belén; Bratoeff, Eugene

    2015-03-26

    In spite of the fact that anaplastic astrocytoma is an uncommon disease, very often the pathology of this disease is associated with lethal effects due to the late diagnosis and unspecific treatments. This paper reports the synthesis and the biological effect on the growth of U373 cell line (human anaplastic astrocytoma) of new hybrid compounds based on 5,16-pregnadiene scaffold linked to an anti-inflammatory drug (6a-e). Moreover, we also determined the cell growth effect of five non-steroidal anti-inflammatory drugs (naproxen, ibuprofen, ketoprofen, indomethacin and sulindac) as well as the free steroidal alcohol 5. The results from this study indicated that sulindac as well as compound 5 decreased the number of U373 cells at different concentrations. However, when an anti-inflammatory drug was bound to the steroidal structure (5), the resulting compounds (6a-e) showed an enhanced biological effect with exception of hybrid 6c. Furthermore, derivative 6e (sulindac hybrid) did not allow cell growth during six days of experiment at a concentration of 10 μM. The overall data indicated that these molecules showed an anti-proliferative activity on anaplastic astrocytoma cell line. PMID:25666913

  3. Enhancement of Anti-Inflammatory Activity of Aloe vera Adventitious Root Extracts through the Alteration of Primary and Secondary Metabolites via Salicylic Acid Elicitation

    PubMed Central

    Lee, Yun Sun; Ju, Hyun Kyoung; Kim, Yeon Jeong; Lim, Tae-Gyu; Uddin, Md Romij; Kim, Yeon Bok; Baek, Jin Hong; Kwon, Sung Won; Lee, Ki Won; Seo, Hak Soo; Park, Sang Un; Yang, Tae-Jin

    2013-01-01

    Aloe vera (Asphodeloideae) is a medicinal plant in which useful secondary metabolites are plentiful. Among the representative secondary metabolites of Aloe vera are the anthraquinones including aloe emodin and chrysophanol, which are tricyclic aromatic quinones synthesized via a plant-specific type III polyketide biosynthesis pathway. However, it is not yet clear which cellular responses can induce the pathway, leading to production of tricyclic aromatic quinones. In this study, we examined the effect of endogenous elicitors on the type III polyketide biosynthesis pathway and identified the metabolic changes induced in elicitor-treated Aloe vera adventitious roots. Salicylic acid, methyl jasmonate, and ethephon were used to treat Aloe vera adventitious roots cultured on MS liquid media with 0.3 mg/L IBA for 35 days. Aloe emodin and chrysophanol were remarkably increased by the SA treatment, more than 10–11 and 5–13 fold as compared with untreated control, respectively. Ultra-performance liquid chromatography-electrospray ionization mass spectrometry analysis identified a total of 37 SA-induced compounds, including aloe emodin and chrysophanol, and 3 of the compounds were tentatively identified as tricyclic aromatic quinones. Transcript accumulation analysis of polyketide synthase genes and gas chromatography mass spectrometry showed that these secondary metabolic changes resulted from increased expression of octaketide synthase genes and decreases in malonyl-CoA, which is the precursor for the tricyclic aromatic quinone biosynthesis pathway. In addition, anti-inflammatory activity was enhanced in extracts of SA-treated adventitious roots. Our results suggest that SA has an important role in activation of the plant specific-type III polyketide biosynthetic pathway, and therefore that the efficacy of Aloe vera as medicinal agent can be improved through SA treatment. PMID:24358188

  4. Enhancement of anti-inflammatory activity of Aloe vera adventitious root extracts through the alteration of primary and secondary metabolites via salicylic acid elicitation.

    PubMed

    Lee, Yun Sun; Ju, Hyun Kyoung; Kim, Yeon Jeong; Lim, Tae-Gyu; Uddin, Md Romij; Kim, Yeon Bok; Baek, Jin Hong; Kwon, Sung Won; Lee, Ki Won; Seo, Hak Soo; Park, Sang Un; Yang, Tae-Jin

    2013-01-01

    Aloe vera (Asphodeloideae) is a medicinal plant in which useful secondary metabolites are plentiful. Among the representative secondary metabolites of Aloe vera are the anthraquinones including aloe emodin and chrysophanol, which are tricyclic aromatic quinones synthesized via a plant-specific type III polyketide biosynthesis pathway. However, it is not yet clear which cellular responses can induce the pathway, leading to production of tricyclic aromatic quinones. In this study, we examined the effect of endogenous elicitors on the type III polyketide biosynthesis pathway and identified the metabolic changes induced in elicitor-treated Aloe vera adventitious roots. Salicylic acid, methyl jasmonate, and ethephon were used to treat Aloe vera adventitious roots cultured on MS liquid media with 0.3 mg/L IBA for 35 days. Aloe emodin and chrysophanol were remarkably increased by the SA treatment, more than 10-11 and 5-13 fold as compared with untreated control, respectively. Ultra-performance liquid chromatography-electrospray ionization mass spectrometry analysis identified a total of 37 SA-induced compounds, including aloe emodin and chrysophanol, and 3 of the compounds were tentatively identified as tricyclic aromatic quinones. Transcript accumulation analysis of polyketide synthase genes and gas chromatography mass spectrometry showed that these secondary metabolic changes resulted from increased expression of octaketide synthase genes and decreases in malonyl-CoA, which is the precursor for the tricyclic aromatic quinone biosynthesis pathway. In addition, anti-inflammatory activity was enhanced in extracts of SA-treated adventitious roots. Our results suggest that SA has an important role in activation of the plant specific-type III polyketide biosynthetic pathway, and therefore that the efficacy of Aloe vera as medicinal agent can be improved through SA treatment.

  5. Oleoylethanolamide exerts anti-inflammatory effects on LPS-induced THP-1 cells by enhancing PPARα signaling and inhibiting the NF-κB and ERK1/2/AP-1/STAT3 pathways

    PubMed Central

    Yang, Lichao; Guo, Han; Li, Ying; Meng, Xianglan; Yan, Lu; Dan Zhang; Wu, Sangang; Zhou, Hao; Peng, Lu; Xie, Qiang; Jin, Xin

    2016-01-01

    The present study aimed to examine the anti-inflammatory actions of oleoylethanolamide (OEA) in lipopolysaccharide (LPS)-induced THP-1 cells. The cells were stimulated with LPS (1 μg/ml) in the presence or absence of OEA (10, 20 and 40 μM). The pro-inflammatory cytokines were evaluated by qRT-PCR and ELISA. The THP-1 cells were transiently transfected with PPARα small-interfering RNA, and TLR4 activity was determined with a blocking test using anti-TLR4 antibody. Additionally, a special inhibitor was used to analyse the intracellular signaling pathway. OEA exerted a potent anti-inflammatory effect by reducing the production of pro-inflammatory cytokines and TLR4 expression, and by enhancing PPARα expression. The modulatory effects of OEA on LPS-induced inflammation depended on PPARα and TLR4. Importantly, OEA inhibited LPS-induced NF-κB activation, IκBα degradation, expression of AP-1, and the phosphorylation of ERK1/2 and STAT3. In summary, our results demonstrated that OEA exerts anti-inflammatory effects by enhancing PPARα signaling, inhibiting the TLR4-mediated NF-κB signaling pathway, and interfering with the ERK1/2-dependent signaling cascade (TLR4/ERK1/2/AP-1/STAT3), which suggests that OEA may be a therapeutic agent for inflammatory diseases. PMID:27721381

  6. Polish Natural Bee Honeys Are Anti-Proliferative and Anti-Metastatic Agents in Human Glioblastoma multiforme U87MG Cell Line

    PubMed Central

    Moskwa, Justyna; Borawska, Maria H.; Markiewicz-Zukowska, Renata; Puscion-Jakubik, Anna; Naliwajko, Sylwia K.; Socha, Katarzyna; Soroczynska, Jolanta

    2014-01-01

    Honey has been used as food and a traditional medicament since ancient times. However, recently many scientists have been concentrating on the anti-oxidant, anti-proliferative, anti-inflammatory and other properties of honey. In this study, we investigated for the first time an anticancer effect of different honeys from Poland on tumor cell line - glioblastoma multiforme U87MG. Anti-proliferative activity of honeys and its interferences with temozolomide were determined by a cytotoxicity test and DNA binding by [H3]-thymidine incorporation. A gelatin zymography was used to conduct an evaluation of metalloproteinases (MMP-2 and MMP-9) expression in U87MG treatment with honey samples. The honeys were previously tested qualitatively (diastase activity, total phenolic content, lead and cadmium content). The data demonstrated that the examined honeys have a potent anti-proliferative effect on U87MG cell line in a time- and dose-dependent manner, being effective at concentrations as low as 0.5% (multifloral light honey - viability 53% after 72 h of incubation). We observed that after 48 h, combining honey with temozolomide showed a significantly higher inhibitory effect than the samples of honey alone. We observed a strong inhibition of MMP-2 and MMP-9 for the tested honeys (from 20 to 56% and from 5 to 58% compared to control, respectively). Our results suggest that Polish honeys have an anti-proliferative and anti-metastatic effect on U87MG cell line. Therefore, natural bee honey can be considered as a promising adjuvant treatment for brain tumors. PMID:24594866

  7. Polish natural bee honeys are anti-proliferative and anti-metastatic agents in human glioblastoma multiforme U87MG cell line.

    PubMed

    Moskwa, Justyna; Borawska, Maria H; Markiewicz-Zukowska, Renata; Puscion-Jakubik, Anna; Naliwajko, Sylwia K; Socha, Katarzyna; Soroczynska, Jolanta

    2014-01-01

    Honey has been used as food and a traditional medicament since ancient times. However, recently many scientists have been concentrating on the anti-oxidant, anti-proliferative, anti-inflammatory and other properties of honey. In this study, we investigated for the first time an anticancer effect of different honeys from Poland on tumor cell line - glioblastoma multiforme U87MG. Anti-proliferative activity of honeys and its interferences with temozolomide were determined by a cytotoxicity test and DNA binding by [H3]-thymidine incorporation. A gelatin zymography was used to conduct an evaluation of metalloproteinases (MMP-2 and MMP-9) expression in U87MG treatment with honey samples. The honeys were previously tested qualitatively (diastase activity, total phenolic content, lead and cadmium content). The data demonstrated that the examined honeys have a potent anti-proliferative effect on U87MG cell line in a time- and dose-dependent manner, being effective at concentrations as low as 0.5% (multifloral light honey - viability 53% after 72 h of incubation). We observed that after 48 h, combining honey with temozolomide showed a significantly higher inhibitory effect than the samples of honey alone. We observed a strong inhibition of MMP-2 and MMP-9 for the tested honeys (from 20 to 56% and from 5 to 58% compared to control, respectively). Our results suggest that Polish honeys have an anti-proliferative and anti-metastatic effect on U87MG cell line. Therefore, natural bee honey can be considered as a promising adjuvant treatment for brain tumors.

  8. Plumbagin exhibits an anti-proliferative effect in human osteosarcoma cells by downregulating FHL2 and interfering with Wnt/β-catenin signalling

    PubMed Central

    Xue, Yuan-Liang; Meng, Xiang-Qi; Ma, Long-Jun; Yuan, Zhen

    2016-01-01

    Plumbagin, a naphthoquinone constituent of Plumbago zeylanica L. (Plumbaginaceae) is widely used in traditional Chinese medicine as an antifungal, antibacterial and anti-inflammatory agent. Plumbagin is known to exhibit proapoptotic, antiangiogenic and antimetastatic effects in cancer cells. The transcriptional co-factor four and a half LIM domains 2 (FHL2) is a multifunctional adaptor protein that is involved in the regulation of gene expression, signal transduction and cell proliferation and differentiation, and also acts as a tumor suppressor or oncoprotein depending on the tissue microenvironment. The present study investigated the effect of plumbagin on FHL2 expression, Wnt/β-catenin signalling and its anti-proliferative activity in various human osteosarcoma cell lines, including SaOS2, MG63, HOS and U2OS. The cells were exposed to plumbagin and the expression of FHL2 was evaluated using western blot analysis. Furthermore, the anti-proliferative effect of plumbagin was evaluated using a 3-(4,5 dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. In addition, since FHL2 is involved in Wnt/β-catenin signaling, the effect of plumbagin on β-catenin and its primary target genes, including v-myc avian myelocytomatosis viral oncogene homolog (c-Myc) and WNT1 inducible signaling pathway protein-1 (WISP-1), was evaluated using western blot analysis. It was observed that plumbagin suppressed the expression of FHL2 and exhibited significant anti-proliferative activity in osteosarcoma cells. It also attenuated Wnt/β-catenin signalling by downregulating β-catenin and its target genes, including c-Myc and WISP-1. In conclusion, plumbagin demonstrated anti-proliferative activity in osteosarcoma cells by downregulating FHL2 and interfering with Wnt/β-catenin signalling. PMID:27446400

  9. An Autologous Protein Solution prepared from the blood of osteoarthritic patients contains an enhanced profile of anti-inflammatory cytokines and anabolic growth factors

    PubMed Central

    O'Shaughnessey, Krista; Matuska, Andrea; Hoeppner, Jacy; Farr, Jack; Klaassen, Mark; Kaeding, Christopher; Lattermann, Christian; King, William; Woodell-May, Jennifer

    2014-01-01

    The objective of this clinical study was to test if blood from osteoarthritis (OA) patients (n = 105) could be processed by a device system to form an autologous protein solution (APS) with preferentially increased concentrations of anti-inflammatory cytokines compared to inflammatory cytokines. To address this objective, APS was prepared from patients exhibiting radiographic evidence of knee OA. Patient metrics were collected including: demographic information, medical history, medication records, and Knee Injury and Osteoarthritis Outcome Score (KOOS) surveys. Cytokine and growth factor concentrations in whole blood and APS were measured using enzyme-linked immunosorbent assays. Statistical analyses were used to identify relationships between OA patient metrics and cytokines. The results of this study indicated that anti-inflammatory cytokines were preferentially increased compared to inflammatory cytokines in APS from 98% of OA patients. APS contained high concentrations of anti-inflammatory proteins including 39,000 ± 20,000 pg/ml IL-1ra, 21,000 ± 5,000 pg/ml sIL-1RII, 2,100 ± 570 pg/ml sTNF-RI, and 4,200 ± 1,500 pg/ml sTNF-RII. Analysis of the 82 patient metrics indicated that no single patient metric was strongly correlated (R2 > .7) with the key cytokine concentrations in APS. Therefore, APS can be prepared from a broad range of OA patients. PMID:24981198

  10. Potentiated clinoptilolite: artificially enhanced aluminosilicate reduces symptoms associated with endoscopically negative gastroesophageal reflux disease and nonsteroidal anti-inflammatory drug induced gastritis

    PubMed Central

    Potgieter, Wilna; Samuels, Caroline Selma; Snyman, Jacques Renè

    2014-01-01

    Purpose The cation exchanger, a potentiated clinoptilolite (Absorbatox™ 2.4D), is a synthetically enhanced aluminosilicate. The aim of this study was to evaluate the possible benefits of a potentiated clinoptilolite as a gastroprotective agent in reducing the severity of clinical symptoms and signs associated with 1) endoscopically negative gastroesophageal reflux disease (ENGORD) and 2) nonsteroidal anti-inflammatory drug (NSAID) medication. Methods and patients Two randomized, double-blind, placebo-controlled, pilot studies, the ENGORD and NSAID studies, were conducted. After initial negative gastroscopy, a total of 25 patients suffering from ENGORD were randomized to receive either placebo capsules or 750 mg Absorbatox twice daily for 14 days. The NSAID study recruited 23 healthy patients who received orally either 1,500 mg Absorbatox or placebo three times daily, plus 500 mg naproxen twice daily. Patients underwent gastroscopic evaluation of their stomach linings prior to and on day 14 of the study. Gastric biopsies were obtained and evaluated via the upgraded Sydney system, whereas visible gastric events and status of the gastric mucosa were evaluated via a 0–3 rating scale. During both studies, patients recorded gastric symptoms in a daily symptom diary. Results In the ENGORD study, patients who received the potentiated clinoptilolite reported a significant reduction (P≤0.05) in severity of symptoms including reduction in heartburn (44%), discomfort (54%), and pain (56%). Symptom-free days improved by 41% compared to the group who received placebo (not significant). This was over and above the benefits seen with the proton pump inhibitor. In the NSAID study, the reduction in gastric symptom severity was echoed in the group who received the potentiated clinoptilolite. Treatment with the potentiated clinoptilolite resulted in significant prevention (P≤0.05) of mucosal erosion severity as graded by the gastroenterologist. Conclusion Absorbatox is a

  11. Bioassay-guided chemical study of the anti-inflammatory effect of Senna villosa (Miller) H.S. Irwin & Barneby (Leguminosae) in TPA-induced ear edema.

    PubMed

    Susunaga-Notario, Ana del Carmen; Pérez-Gutiérrez, Salud; Zavala-Sánchez, Miguel Angel; Almanza-Pérez, Julio Cesar; Gutiérrez-Carrillo, Atilano; Arrieta-Báez, Daniel; López-López, Ana Laura; Román-Ramos, Rubén; Flores-Sáenz, José Luis Eduardo; Alarcón-Aguilar, Francisco Javier

    2014-07-15

    Senna villosa (Miller) is a plant that grows in México. In traditional Mexican medicine, it is used topically to treat skin infections, pustules and eruptions and to heal wounds by scar formation. However, studies of its potential anti-inflammatory effects have not been performed. The aim of the present study was to determine the anti-inflammatory effect of extracts from the leaves of Senna villosa and to perform a bioassay-guided chemical study of the extract with major activity in a model of ear edema induced by 12-O-tetradecanoylphorbol 13-acetate (TPA). The results reveal that the chloroform extract from Senna villosa leaves has anti-inflammatory and anti-proliferative properties. Nine fractions were obtained from the bioassay-guided chemical study, including a white precipitate from fractions 2 and 3. Although none of the nine fractions presented anti-inflammatory activity, the white precipitate exhibited pharmacological activity. It was chemically characterized using mass spectrometry and infrared and nuclear magnetic resonance spectroscopy, resulting in a mixture of three aliphatic esters, which were identified as the principal constituents: hexyl tetradecanoate (C20H40O2), heptyl tetradecanoate (C21H42O2) and octyl tetradecanoate (C22H44O2). This research provides, for the first time, evidence of the anti-inflammatory and anti-proliferative properties of compounds isolated from Senna villosa.

  12. Bioassay-guided chemical study of the anti-inflammatory effect of Senna villosa (Miller) H.S. Irwin & Barneby (Leguminosae) in TPA-induced ear edema.

    PubMed

    Susunaga-Notario, Ana del Carmen; Pérez-Gutiérrez, Salud; Zavala-Sánchez, Miguel Angel; Almanza-Pérez, Julio Cesar; Gutiérrez-Carrillo, Atilano; Arrieta-Báez, Daniel; López-López, Ana Laura; Román-Ramos, Rubén; Flores-Sáenz, José Luis Eduardo; Alarcón-Aguilar, Francisco Javier

    2014-01-01

    Senna villosa (Miller) is a plant that grows in México. In traditional Mexican medicine, it is used topically to treat skin infections, pustules and eruptions and to heal wounds by scar formation. However, studies of its potential anti-inflammatory effects have not been performed. The aim of the present study was to determine the anti-inflammatory effect of extracts from the leaves of Senna villosa and to perform a bioassay-guided chemical study of the extract with major activity in a model of ear edema induced by 12-O-tetradecanoylphorbol 13-acetate (TPA). The results reveal that the chloroform extract from Senna villosa leaves has anti-inflammatory and anti-proliferative properties. Nine fractions were obtained from the bioassay-guided chemical study, including a white precipitate from fractions 2 and 3. Although none of the nine fractions presented anti-inflammatory activity, the white precipitate exhibited pharmacological activity. It was chemically characterized using mass spectrometry and infrared and nuclear magnetic resonance spectroscopy, resulting in a mixture of three aliphatic esters, which were identified as the principal constituents: hexyl tetradecanoate (C20H40O2), heptyl tetradecanoate (C21H42O2) and octyl tetradecanoate (C22H44O2). This research provides, for the first time, evidence of the anti-inflammatory and anti-proliferative properties of compounds isolated from Senna villosa. PMID:25029073

  13. Synthesis and biological evaluation of substituted 2-benzoylpyridine thiosemicarbazones: novel structure-activity relationships underpinning their anti-proliferative and chelation efficacy.

    PubMed

    Lukmantara, Adeline Y; Kalinowski, Danuta S; Kumar, Naresh; Richardson, Des R

    2013-02-15

    The 2-benzoylpyridine thiosemicarbazone (BpT) chelators demonstrate potent anti-proliferative effects against tumor cells. To understand their structure-activity relationships, BpT analogues incorporating electron-donating substituents on the pyridine and phenyl rings of the BpT scaffold were designed and represent the first attempts to modify the pyridine ring of these thiosemicarbazones. Eight analogues showed significantly (p <0.001) greater anti-proliferative activity than the 'gold-standard' chelator, desferrioxamine. Structure-activity analysis revealed that mono- or di-methoxy substitution at the phenyl ring resulted in lower anti-proliferative activity, while methoxy substitutions at the phenyl ring enhanced iron chelation efficacy. These important findings facilitate the design of thiosemicarbazones with greater anti-tumor activity.

  14. Erdosteine: antitussive and anti-inflammatory effects.

    PubMed

    Dal Negro, Roberto W

    2008-01-01

    Erdosteine is a multifactorial drug currently used in COPD for its rheologic activity on bronchial secretions and its positive effects on bacterial adhesiveness. Erdosteine produces an active metabolite (Met 1) which was shown to produce antioxidant effects during the respiratory burst of human PMNs, due to the presence of an SH group. The substantial antitussive effects of erdosteine were first documented in clinical trials even though mucolytic agents are regarded as not consistently effective in ameliorating cough in patients with bronchitis, although they may be of benefit to this population in other ways. Actually, a mucolytic drug could exert antitussive effects if it also affects mucus consistency and enhances ciliary function. In the last decade, data from several studies on animal models pointed to the possible antitussive and anti-inflammatory properties of erdosteine and an indirect anti-inflammatory mechanism of action was suggested. Recently, data from some controlled versus placebo studies documented the antioxidant properties of erdosteine in humans and in current smokers with COPD. The mechanism of action was described as related to erdosteine's ability to inhibit some inflammatory mediators and some pro-inflammatory cytokines that are specifically involved in oxidative stress. As oxidative stress is also presumed to impair beta-adrenoceptor function and contribute to airway obstruction, specific controlled studies recently investigated the effect of antioxidant intervention on short-term airway response to salbutamol in nonreversible COPD, according to a double-blind design versus placebo and NAC. Only erdosteine consistently restored a significant short-term reversibility in COPD subjects, previously unresponsive to beta(2) adrenergics. This peculiar activity of erdosteine (to our knowledge never previously assessed) proved related to the ROS scavenging activity (which actually proved equal to that of N), and its significant inhibiting effect on

  15. Erdosteine: antitussive and anti-inflammatory effects.

    PubMed

    Dal Negro, Roberto W

    2008-01-01

    Erdosteine is a multifactorial drug currently used in COPD for its rheologic activity on bronchial secretions and its positive effects on bacterial adhesiveness. Erdosteine produces an active metabolite (Met 1) which was shown to produce antioxidant effects during the respiratory burst of human PMNs, due to the presence of an SH group. The substantial antitussive effects of erdosteine were first documented in clinical trials even though mucolytic agents are regarded as not consistently effective in ameliorating cough in patients with bronchitis, although they may be of benefit to this population in other ways. Actually, a mucolytic drug could exert antitussive effects if it also affects mucus consistency and enhances ciliary function. In the last decade, data from several studies on animal models pointed to the possible antitussive and anti-inflammatory properties of erdosteine and an indirect anti-inflammatory mechanism of action was suggested. Recently, data from some controlled versus placebo studies documented the antioxidant properties of erdosteine in humans and in current smokers with COPD. The mechanism of action was described as related to erdosteine's ability to inhibit some inflammatory mediators and some pro-inflammatory cytokines that are specifically involved in oxidative stress. As oxidative stress is also presumed to impair beta-adrenoceptor function and contribute to airway obstruction, specific controlled studies recently investigated the effect of antioxidant intervention on short-term airway response to salbutamol in nonreversible COPD, according to a double-blind design versus placebo and NAC. Only erdosteine consistently restored a significant short-term reversibility in COPD subjects, previously unresponsive to beta(2) adrenergics. This peculiar activity of erdosteine (to our knowledge never previously assessed) proved related to the ROS scavenging activity (which actually proved equal to that of N), and its significant inhibiting effect on

  16. High Spinal Anesthesia Enhances Anti-Inflammatory Responses in Patients Undergoing Coronary Artery Bypass Graft Surgery and Aortic Valve Replacement: Randomized Pilot Study

    PubMed Central

    Lee, Trevor W. R.; Kowalski, Stephen; Falk, Kelsey; Maguire, Doug; Freed, Darren H.; HayGlass, Kent T.

    2016-01-01

    Background Cardiac surgery induces many physiologic changes including major inflammatory and sympathetic nervous system responses. Here, we conducted a single-centre pilot study to generate hypotheses on the potential immune impact of adding high spinal anaesthesia to general anaesthesia during cardiac surgery in adults. We hypothesized that this strategy, previously shown to blunt the sympathetic response and improve pain management, could reduce the undesirable systemic inflammatory responses caused by cardiac surgery. Methods This prospective randomized unblinded pilot study was conducted on 14 patients undergoing cardiac surgery for coronary artery bypass grafting and/or aortic valve replacement secondary to severe aortic stenosis. The primary outcome measures examined longitudinally were serum pro-inflammatory (IL-6, IL-1b, CCL2), anti-inflammatory (IL-10, TNF-RII, IL-1Ra), acute phase protein (CRP, PTX3) and cardiovascular risk (sST2) biomarkers. Results The kinetics of pro- and anti-inflammatory biomarker was determined following surgery. All pro-inflammatory and acute phase reactant biomarker responses induced by surgical stress were indistinguishable in intensity and duration between control groups and those who also received high spinal anaesthesia. Conversely, IL-10 levels were markedly elevated in both intensity and duration in the group receiving high spinal anesthesia (p = 0.005). Conclusions This hypothesis generating pilot study suggests that high spinal anesthesia can alter the net inflammatory response that results from cardiac surgery. In appropriately selected populations, this may add incremental benefit by dampening the net systemic inflammatory response during the week following surgery. Larger population studies, powered to assess immune, physiologic and clinical outcomes in both acute and longer term settings, will be required to better assess potential benefits of incorporating high spinal anesthesia. Trial Registration Clinical

  17. Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells.

    PubMed

    Tiptiri-Kourpeti, Angeliki; Spyridopoulou, Katerina; Santarmaki, Valentina; Aindelis, Georgios; Tompoulidou, Evgenia; Lamprianidou, Eleftheria E; Saxami, Georgia; Ypsilantis, Petros; Lampri, Evangeli S; Simopoulos, Constantinos; Kotsianidis, Ioannis; Galanis, Alex; Kourkoutas, Yiannis; Dimitrellou, Dimitra; Chlichlia, Katerina

    2016-01-01

    Probiotic microorganisms such as lactic acid bacteria (LAB) exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof) on murine (CT26) and human (HT29) colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 10(9) CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells). In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 10(9) CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain. PMID:26849051

  18. Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells

    PubMed Central

    Santarmaki, Valentina; Aindelis, Georgios; Tompoulidou, Evgenia; Lamprianidou, Eleftheria E.; Saxami, Georgia; Ypsilantis, Petros; Lampri, Evangeli S.; Simopoulos, Constantinos; Kotsianidis, Ioannis; Galanis, Alex; Kourkoutas, Yiannis; Dimitrellou, Dimitra; Chlichlia, Katerina

    2016-01-01

    Probiotic microorganisms such as lactic acid bacteria (LAB) exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof) on murine (CT26) and human (HT29) colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 109 CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells). In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 109 CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain. PMID:26849051

  19. Enhanced therapeutic anti-inflammatory effect of betamethasone upon topical administration with low frequency, low intensity (20 kHz, 100 mW/cm2) ultrasound exposure on carrageenan-induced arthritis in mice model

    PubMed Central

    Cohen, Gadi; Natsheh, Hiba; Sunny, Youhan; Bawiec, Christopher R.; Touitou, Elka; Lerman, Melissa A.; Lazarovici, Philip; Lewin, Peter A.

    2015-01-01

    The purpose of this work was to investigate whether low frequency, low intensity (LFLI, 20 kHz, <100 mW/cm2, spatial-peak, temporal-peak) ultrasound (US), delivered by a light-weight (<100g), tether-free, fully wearable, battery powered applicator is capable of reducing inflammation in a mouse model of Rheumatoid Arthritis (RA). The therapeutic, acute, anti-inflammatory effect was estimated by the relative swelling induced in mice hind limb paws. In an independent, indirect approach, the inflammation was bio-imaged by measuring glycolytic activity with near infrared labeled 2-deoxy-glucose (2DG). The outcome of the experiments indicated that the combination of US exposure with topical application of 0.1% w/w betamethasone gel, exhibited statistically significant (p<0.05) enhanced anti-inflammatory properties in comparison with the drug or US treatment alone. The present study underscores the potential benefits of LFLI US assisted drug delivery. However, the proof of concept presented indicates the need for additional experiments to systematically evaluate and optimize the potential of, and the conditions for, safe, LFLI ultrasound promoted non-invasive drug delivery. PMID:26003010

  20. Enhancement of the 1-Octanol/Water Partition Coefficient of the Anti-Inflammatory Indomethacin in the Presence of Lidocaine and Other Local Anesthetics.

    PubMed

    Tateuchi, Ryo; Sagawa, Naoki; Shimada, Yohsuke; Goto, Satoru

    2015-07-30

    Side effects and excessive potentiation of drug efficacy caused by polypharmacy are becoming important social issues. The apparent partition coefficient of indomethacin (log P'IND) increases in the presence of lidocaine, and this is used as a physicochemical model for investigating polypharmacy. We examined the changes in log P'IND caused by clinically used local anesthetics-lidocaine, tetracaine, mepivacaine, bupivacaine, and dibucaine-and by structurally similar basic drugs-procainamide, imipramine, and diltiazem. The quantitative structure-activity relationship study of log P'IND showed that the partition coefficient values (log PLA) and the structural entropic terms (ΔSobs, log f) of the additives affect log P'IND. These results indicate that the local anesthetics and structurally similar drugs function as phase-transfer catalysts, increasing the membrane permeability of indomethacin via heterogeneous intermolecular association. Therefore, we expect that the potency of indomethacin, an acidic nonsteroidal anti-inflammatory drug, will be increased by concurrent administration of the other drugs.

  1. Anti-proliferative activity of Monensin and its tertiary amide derivatives.

    PubMed

    Huczyński, Adam; Klejborowska, Greta; Antoszczak, Michał; Maj, Ewa; Wietrzyk, Joanna

    2015-10-15

    New tertiary amide derivatives of polyether ionophore Monensin A (MON) were synthesised and their anti-proliferative activity against cancer cell lines was studied. Very high activity (IC50=0.09 μM) and selectivity (SI=232) of MON against human biphenotypic myelomonocytic leukemia cell line (MV4-11) was demonstrated. The MON derivatives obtained exhibit interesting anti-proliferative activity, high selectivity index and also are able to break the drug-resistance of cancer cell line.

  2. A Mixed Flavonoid-Fish Oil Supplement Induces Immune-Enhancing and Anti-Inflammatory Transcriptomic Changes in Adult Obese and Overweight Women—A Randomized Controlled Trial

    PubMed Central

    Cialdella-Kam, Lynn; Nieman, David C.; Knab, Amy M.; Shanely, R. Andrew; Meaney, Mary Pat; Jin, Fuxia; Sha, Wei; Ghosh, Sujoy

    2016-01-01

    Flavonoids and fish oils have anti-inflammatory and immune-modulating influences. The purpose of this study was to determine if a mixed flavonoid-fish oil supplement (Q-Mix; 1000 mg quercetin, 400 mg isoquercetin, 120 mg epigallocatechin (EGCG) from green tea extract, 400 mg n3-PUFAs (omega-3 polyunsaturated fatty acid) (220 mg eicosapentaenoic acid (EPA) and 180 mg docosahexaenoic acid (DHA)) from fish oil, 1000 mg vitamin C, 40 mg niacinamide, and 800 µg folic acid) would reduce complications associated with obesity; that is, reduce inflammatory and oxidative stress markers and alter genomic profiles in overweight women. Overweight and obese women (n = 48; age = 40–70 years) were assigned to Q-Mix or placebo groups using randomized double-blinded placebo-controlled procedures. Overnight fasted blood samples were collected at 0 and 10 weeks and analyzed for cytokines, C-reactive protein (CRP), F2-isoprostanes, and whole-blood-derived mRNA, which was assessed using Affymetrix HuGene-1_1 ST arrays. Statistical analysis included two-way ANOVA models for blood analytes and gene expression and pathway and network enrichment methods for gene expression. Plasma levels increased with Q-Mix supplementation by 388% for quercetin, 95% for EPA, 18% for DHA, and 20% for docosapentaenoic acid (DPA). Q-Mix did not alter plasma levels for CRP (p = 0.268), F2-isoprostanes (p = 0.273), and cytokines (p > 0.05). Gene set enrichment analysis revealed upregulation of pathways in Q-Mix vs. placebo related to interferon-induced antiviral mechanism (false discovery rate, FDR < 0.001). Overrepresentation analysis further disclosed an inhibition of phagocytosis-related inflammatory pathways in Q-Mix vs. placebo. Thus, a 10-week Q-Mix supplementation elicited a significant rise in plasma quercetin, EPA, DHA, and DPA, as well as stimulated an antiviral and inflammation whole-blood transcriptomic response in overweight women. PMID:27187447

  3. A Mixed Flavonoid-Fish Oil Supplement Induces Immune-Enhancing and Anti-Inflammatory Transcriptomic Changes in Adult Obese and Overweight Women-A Randomized Controlled Trial.

    PubMed

    Cialdella-Kam, Lynn; Nieman, David C; Knab, Amy M; Shanely, R Andrew; Meaney, Mary Pat; Jin, Fuxia; Sha, Wei; Ghosh, Sujoy

    2016-01-01

    Flavonoids and fish oils have anti-inflammatory and immune-modulating influences. The purpose of this study was to determine if a mixed flavonoid-fish oil supplement (Q-Mix; 1000 mg quercetin, 400 mg isoquercetin, 120 mg epigallocatechin (EGCG) from green tea extract, 400 mg n3-PUFAs (omega-3 polyunsaturated fatty acid) (220 mg eicosapentaenoic acid (EPA) and 180 mg docosahexaenoic acid (DHA)) from fish oil, 1000 mg vitamin C, 40 mg niacinamide, and 800 µg folic acid) would reduce complications associated with obesity; that is, reduce inflammatory and oxidative stress markers and alter genomic profiles in overweight women. Overweight and obese women (n = 48; age = 40-70 years) were assigned to Q-Mix or placebo groups using randomized double-blinded placebo-controlled procedures. Overnight fasted blood samples were collected at 0 and 10 weeks and analyzed for cytokines, C-reactive protein (CRP), F₂-isoprostanes, and whole-blood-derived mRNA, which was assessed using Affymetrix HuGene-1_1 ST arrays. Statistical analysis included two-way ANOVA models for blood analytes and gene expression and pathway and network enrichment methods for gene expression. Plasma levels increased with Q-Mix supplementation by 388% for quercetin, 95% for EPA, 18% for DHA, and 20% for docosapentaenoic acid (DPA). Q-Mix did not alter plasma levels for CRP (p = 0.268), F2-isoprostanes (p = 0.273), and cytokines (p > 0.05). Gene set enrichment analysis revealed upregulation of pathways in Q-Mix vs. placebo related to interferon-induced antiviral mechanism (false discovery rate, FDR < 0.001). Overrepresentation analysis further disclosed an inhibition of phagocytosis-related inflammatory pathways in Q-Mix vs. placebo. Thus, a 10-week Q-Mix supplementation elicited a significant rise in plasma quercetin, EPA, DHA, and DPA, as well as stimulated an antiviral and inflammation whole-blood transcriptomic response in overweight women. PMID:27187447

  4. Anti-Inflammatory Agents for Cancer Therapy

    PubMed Central

    Rayburn, Elizabeth R.; Ezell, Scharri J.; Zhang, Ruiwen

    2010-01-01

    Inflammation is closely linked to cancer, and many anti-cancer agents are also used to treat inflammatory diseases, such as rheumatoid arthritis. Moreover, chronic inflammation increases the risk for various cancers, indicating that eliminating inflammation may represent a valid strategy for cancer prevention and therapy. This article explores the relationship between inflammation and cancer with an emphasis on epidemiological evidence, summarizes the current use of anti-inflammatory agents for cancer prevention and therapy, and describes the mechanisms underlying the anti-cancer effects of anti-inflammatory agents. Since monotherapy is generally insufficient for treating cancer, the combined use of anti-inflammatory agents and conventional cancer therapy is also a focal point in discussion. In addition, we also briefly describe future directions that should be explored for anti-cancer anti-inflammatory agents. PMID:20333321

  5. Boswellia carterii liquisolid systems with promoted anti-inflammatory activity.

    PubMed

    Mostafa, Dina Mahmoud; Ammar, Nagwa Mohammed; Abd El-Alim, Sameh Hosam; Kassem, Ahmed Alaa; Hussein, Rehab Ali; Awad, Gamal; El-Awdan, Sally Abdul-Wanees

    2015-01-01

    Boswellia carterii (BC) Birdwood oleogum resin is an ancient remedy of inflammation processes known since Ancient Egyptian time. Of boswellic acids, 3-acetyl-11-keto-β-boswellic acid (AKBA) is the most potent anti-inflammatory active principle. Liquisolid systems of the biologically active fraction of BC oleogum resin were prepared for improving dissolution properties using low dose oral delivery to achieve enhanced anti-inflammatory activity, in comparison with the standard oral anti-inflammatory; Indomethacin. AKBA was assayed, employing an accurate and sensitive HPLC method. Detection was carried out at 210 nm using UV/Vis detector. A solubility study for the bioactive fraction was conducted. Microcrystalline cellulose and Aeroperl®300 Pharma were used as carrier and coating materials. Angle of slide, liquid load factor and Carr's flow index were estimated. Six systems were prepared using polyethylene glycol 400, solvent and two drug loading concentrations; 20 and 40 %. For each concentration, three carrier: coat ratios were dispensed; 20:1, 10:1, and 5:1. Dissolution study was performed and two systems were selected for characterization and in vivo evaluation by investigating upper GIT ulcerogenic effect and anti-inflammatory efficacy in rats. Results indicate absence of ulcers and significantly higher and prolonged anti-inflammatory efficacy for formulations F1 and F2, with carrier: coat ratio, 5:1 and drug loads of 20 and 40 %, respectively, compared with standard oral indomethacin. We conclude higher efficacy of BC bioactive fraction liquisolids compared with Indomethacin with greater safety on GIT, longer duration of action and hence better patient compliance. PMID:25895614

  6. Enhancing of Women Functional Status with Metabolic Syndrome by Cardioprotective and Anti-Inflammatory Effects of Combined Aerobic and Resistance Training

    PubMed Central

    Alsamir Tibana, Ramires; da Cunha Nascimento, Dahan; Frade de Sousa, Nuno Manuel; de Souza, Vinicius Carolino; Durigan, João; Vieira, Amilton; Bottaro, Martim; de Toledo Nóbrega, Otávio; de Almeida, Jeeser Alves; Navalta, James Wilfred; Franco, Octavio Luiz; Prestes, Jonato

    2014-01-01

    These data describe the effects of combined aerobic plus resistance training (CT) with regards to risk factors of metabolic syndrome (MetS), quality of life, functional capacity, and pro- and anti-inflammatory cytokines in women with MetS. In this context, thirteen women (35.4±6.2 yr) completed 10 weeks of CT consisting of three weekly sessions of ∼60 min aerobic training (treadmill at 65–70% of reserve heart rate, 30 min) and resistance training (3 sets of 8–12 repetitions maximum for main muscle groups). Dependent variables were maximum chest press strength; isometric hand-grip strength; 30 s chair stand test; six minute walk test; body mass; body mass index; body adiposity index; waist circumference; systolic (SBP), diastolic and mean blood pressure (MBP); blood glucose; HDL-C; triglycerides; interleukins (IL) 6, 10 and 12, osteoprotegerin (OPG) and serum nitric oxide metabolite (NOx); quality of life (SF-36) and Z-Score of MetS. There was an improvement in muscle strength on chest press (p = 0.009), isometric hand-grip strength (p = 0.03) and 30 s chair stand (p = 0.007). There was a decrease in SBP (p = 0.049), MBP (p = 0.041), Z-Score of MetS (p = 0.046), OPG (0.42±0.26 to 0.38±0.19 ng/mL, p<0.05) and NOx (13.3±2.3 µmol/L to 9.1±2.3 µmol/L; p<0.0005). IL-10 displayed an increase (13.6±7.5 to 17.2±12.3 pg/mL, p<0.05) after 10 weeks of training. Combined training also increased the perception of physical capacity (p = 0.011). This study endorses CT as an efficient tool to improve blood pressure, functional capacity, quality of life and reduce blood markers of inflammation, which has a clinical relevance in the prevention and treatment of MetS. Trial Registration Brazilian Clinical Trials Registry (ReBec) - RBR-6gdyvz - http://www.ensaiosclinicos.gov.br/rg/?q=RBR-6gdyvz PMID:25379699

  7. Bioconverted Jeju Hallabong tangor (Citrus kiyomi × ponkan) peel extracts by cytolase enhance antioxidant and anti-inflammatory capacity in RAW 264.7 cells

    PubMed Central

    Chang, Yun-Hee; Seo, Jieun; Song, Eunju; Choi, Hyuk-Joon; Shim, Eugene; Lee, Okhee

    2016-01-01

    BACKGROUND/OBJECTIVES Citrus and its peels have been used in Asian folk medicine due to abundant flavonoids and usage of citrus peels, which are byproducts from juice and/or jam processing, may be a good strategy. Therefore, the aim of this study was to examine antioxidant and anti-inflammatory effects of bioconversion of Jeju Hallabong tangor (Citrus kiyomi × ponkan; CKP) peels with cytolase (CKP-C) in RAW 264.7 cells. MATERIALS/METHODS Glycosides of CKP were converted into aglycosides with cytolase treatment. RAW 264.7 cells were pre-treated with 0, 100, or 200 µg/ml of citrus peel extracts for 4 h, followed by stimulation with 1 µg/ml lipopolysaccharide (LPS) for 8 h. Cell viability, DPPH radical scavenging activity, nitric oxide (NO), and prostagladin E2 (PGE2) production were examined. Real time-PCR and western immunoblotting assay were performed for detection of mRNA and/or protein expression of pro-inflammatory mediators and cytokines, respectively. RESULTS HPLC analysis showed that treatment of CKP with cytolase resulted in decreased flavanone rutinoside forms (narirutin and hesperidin) and increased flavanone aglycoside forms (naringenin and hesperetin). DPPH scavenging activities were observed in a dose-dependent manner for all of the citrus peel extracts and CKP-C was more potent than intact CKP. All of the citrus peel extracts decreased NO production by inducible nitric oxide synthase (iNOS) activity and PGE2 production by COX-2. Higher dose of CKP and all CKP-C groups significantly decreased mRNA and protein expression of LPS-stimulated iNOS. Only 200 µg/ml of CKP-C markedly decreased mRNA and protein expression of cyclooxygenase-2 in LPS-stimulated RAW 264.7 cells. Both 100 and 200 µg/ml of CKP-C notably inhibited mRNA levels of interleukin-1β (IL-1β) and IL-6, whereas 200 µg/ml CKP-C significantly inhibited mRNA levels of TNF-α. CONCLUSIONS This result suggests that bioconversion of citrus peels with cytolase may enrich aglycoside flavanones

  8. In vitro evaluation of the cytotoxic and anti-proliferative properties of resveratrol and several of its analogs.

    PubMed

    Billack, Blase; Radkar, Vijayalaxmi; Adiabouah, Christelle

    2008-01-01

    Resveratrol (RES), a component of red wine, possesses anti-inflammatory properties. The studies described in the present work were aimed at evaluating the potential for RES and related stilbene analogs (piceatannol, PIC; pterostilbene, TPS; trans-stilbene, TS; and trans-stilbene oxide, TSO) to exhibit toxicity towards RAW 264.7 mouse macrophages. The effect of TS, TSO, RES and TPS on RAW 264.7 macrophage viability was determined by two standard methods: (a) the MTT assay and (b) the trypan blue dye exclusion test. Whereas macrophages were more sensitive to PIC (LC(50 trypan) approximately 1.3 muM) and to TPS (LC(50 trypan) approximately 4.0 microM and LC(50 MTT) approximately 8.3 microM) than to RES (LC(50 trypan) approximately 8.9 microM and LC(50 MTT) approximately 29.0 microM), they were relatively resistant to TSO (LC(50 trypan) approximately 61.0 microM and LC(50 MTT) > 100 microM) and to TS (LC(50 trypan) > or = 5.0 microM and LC(50 MTT) > or = 5.0 microM). The ability of selected stilbenes (RES, TPS and PIC) to exhibit growth inhibitory effects was also examined. Although RES and TPS were observed to inhibit cell proliferation in macrophages (IC(50) < or = 25 microM), these cells were resistant to growth inhibition by PIC (IC(50) > or = 50 microM). The data obtained in the present analysis demonstrate that substituted stilbene compounds such as RES have the capacity to exhibit cytotoxic and anti-proliferative activities in macrophages.

  9. Nitric oxide-releasing NSAIDs: a novel class of GI-sparing anti-inflammatory drugs.

    PubMed

    Wallace, J L; Pittman, Q J; Cirino, G

    1995-01-01

    The addition of a nitric oxide-releasing moiety to a number of common nonsteroidal anti-inflammatory drugs markedly reduces their toxicity in the gastrointestinal tract without interfering with their ability to inhibit prostaglandin synthesis. Moreover, the anti-inflammatory and anti-pyretic activities of the nitric-oxide releasing NSAID were comparable to the parent compound, while the anti-thrombotic activity in vivo was significantly enhanced. Nitric oxide-releasing NSAIDs may represent an alternative to existing anti-inflammatory, anti-pyretic and anti-thrombotic agents with greatly reduced toxicity in the gastrointestinal tract. PMID:7610982

  10. Anti-Inflammatory Iridoids of Botanical Origin

    PubMed Central

    Viljoen, A; Mncwangi, N; Vermaak, I

    2012-01-01

    Inflammation is a manifestation of a wide range of disorders which include; arthritis, atherosclerosis, Alzheimer’s disease, inflammatory bowel syndrome, physical injury and infection amongst many others. Common treatment modalities are usually non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, paracetamol, indomethacin and ibuprofen as well as corticosteroids such as prednisone. These however, may be associated with a host of side effects due to non-selectivity for cyclooxygenase (COX) enzymes involved in inflammation and those with selectivity may be highly priced. Thus, there is a continuing search for safe and effective anti-inflammatory molecules from natural sources. Research has confirmed that iridoids exhibit promising anti-inflammatory activity which may be beneficial in the treatment of inflammation. Iridoids are secondary metabolites present in various plants, especially in species belonging to the Apocynaceae, Lamiaceae, Loganiaceae, Rubiaceae, Scrophulariaceae and Verbenaceae families. Many of these ethnobotanicals have an illustrious history of traditional use alluding to their use to treat inflammation. Although iridoids exhibit a wide range of pharmacological activities such as cardiovascular, hepatoprotection, hypoglycaemic, antimutagenic, antispasmodic, anti-tumour, antiviral, immunomodulation and purgative effects this review will acutely focus on their anti-inflammatory properties. The paper aims to present a summary for the most prominent iridoid-containing plants for which anti-inflammatory activity has been demonstrated in vitro and / or in vivo. PMID:22414102

  11. [The anti-inflammatory effect of auranofin].

    PubMed

    Hiroi, J; Ohara, K; Fujitsu, T; Hirai, O; Satoh, S; Ochi, T; Senoh, H; Mori, J; Kikuchi, H

    1985-12-01

    The anti-inflammatory effects of auranofin were studied and compared with those of indomethacin, gold sodium thiomalate (GST) and D-penicillamine. Auranofin was active as indomethacin in inhibiting carrageenan induced paw edema in rats, but was less potent than indomethacin in inhibiting UV-induced erythema in guinea pigs. Auranofin inhibited Arthus type paw edema and reverse PCA reaction in rats, on which indomethacin was ineffective. The inhibitory activity of auranofin on adjuvant arthritis was weaker than that of indomethacin. In in vitro experiments, auranofin did not show any suppression of cyclooxygenase activity, but was capable of suppression of lysosomal enzyme release and chemotaxis of neutrophils and macrophages. In addition to these anti-inflammatory activities, auranofin had almost equal anti-analgesic and anti-pyretic activity to that of indomethacin. The above results indicated that the anti-inflammatory profiles of auranofin and indomethacin differ, so we can expect new therapeutic activities of auranofin. GST had similar anti-inflammatory and anti-analgesic profiles to those of auranofin; however, the activities were less potent than auranofin and devoid of anti-pyretic activity. D-penicillamine did not show any anti-inflammatory, anti-analgesic or anti-pyretic activity. PMID:3937805

  12. Pharmacology in rehabilitation: nonsteroidal anti-inflammatory agents.

    PubMed

    Biederman, Ross E

    2005-06-01

    Nonsteroidal anti-inflammatory agents (NSAIDs) are the most commonly encountered over-the-counter (OTC) and prescription medications in physical therapy practice. Worldwide, over 73000000 prescriptions for nonsteroidal agents are written yearly. NSAIDs produce a wide range of beneficial effects to the physical therapy patient, enhancing the outcome of treatment. Helpful effects of NSAIDs include analgesia, antipyretic, anti-inflammatory, and antithrombotic properties. However, NSAIDs are also associated with frequent and significant side effects that are deleterious to treatment outcome, including delay in soft tissue and bone healing, renal and liver toxicity, hemorrhagic events, gastric irritation and ulceration, and central nervous system effects. Understanding of the pharmacological properties of these drugs, exemplified by aspirin, and the individual pharmacokinetics of specific preparations will help the therapist to screen patients for potential side effects, develop more effective plans of care, and, where allowed, effectively and safely prescribe NSAIDs. PMID:16001907

  13. Pharmacology in rehabilitation: nonsteroidal anti-inflammatory agents.

    PubMed

    Biederman, Ross E

    2005-06-01

    Nonsteroidal anti-inflammatory agents (NSAIDs) are the most commonly encountered over-the-counter (OTC) and prescription medications in physical therapy practice. Worldwide, over 73000000 prescriptions for nonsteroidal agents are written yearly. NSAIDs produce a wide range of beneficial effects to the physical therapy patient, enhancing the outcome of treatment. Helpful effects of NSAIDs include analgesia, antipyretic, anti-inflammatory, and antithrombotic properties. However, NSAIDs are also associated with frequent and significant side effects that are deleterious to treatment outcome, including delay in soft tissue and bone healing, renal and liver toxicity, hemorrhagic events, gastric irritation and ulceration, and central nervous system effects. Understanding of the pharmacological properties of these drugs, exemplified by aspirin, and the individual pharmacokinetics of specific preparations will help the therapist to screen patients for potential side effects, develop more effective plans of care, and, where allowed, effectively and safely prescribe NSAIDs.

  14. Acetylsalicylic acid enhances the anti-inflammatory effect of fluoxetine through inhibition of NF-κB, p38-MAPK and ERK1/2 activation in lipopolysaccharide-induced BV-2 microglia cells.

    PubMed

    Yang, J M; Rui, B B; Chen, C; Chen, H; Xu, T J; Xu, W P; Wei, W

    2014-09-01

    The latest advancements in neurobiological research provide increasing evidence that inflammatory and neurodegenerative pathways play an important role in depression. According to the cytokine hypothesis, depression could be due to the increased production of pro-inflammatory cytokines by microglia activation. Thus, using the BV-2 microglial cell line, the aim of the present study was to investigate whether fluoxetine (FLX) or acetylsalicylic acid (ASA) could inhibit this microglia activation and could achieve better results in combination. Our results showed that FLX could attenuate lipopolysaccharide (LPS)-induced production of interleukin-1β (IL-1β), the expression of the indoleamine 2,3 dioxygenase (IDO) enzyme and the depletion of 5-HT. Moreover, FLX could inhibit phosphorylation of nuclear factor-κB (NF-κB) and phosphorylation of p38 mitogen-activated protein kinase (MAPK), and the combined use with ASA could enhance these effects. Notably, the adjunctive agent ASA could also inhibit phosphorylation of extracellular-regulated kinase 1/2 (ERK1/2). Taken together, our results suggest that FLX may have some anti-inflammatory effects by modulating microglia activation and that ASA served as an effective adjunctive agent by enhancing these therapeutic effects.

  15. The anti-inflammatory effect of opioids.

    PubMed

    Gavalas, A; Victoratos, P; Yiangou, M; Hadjipetrou-Kourounakis, L; Rekka, E; Kourounakis, P

    1994-01-01

    The anti-inflammatory activity of two novel opioids PM and PO as well as of pethidine was studied. The mouse paw edema, induced by various phlogistic agents, was significantly inhibited after the administration of opioids, fact that was independent of their antioxidant properties. The anti-inflammatory action of the above opioids was not reversed by naloxone. These results suggest that a variety of complex regulatory activities may be performed by opioid agonists via naloxone-sensitive or naloxone insensitive receptors on inflammatory cells, directly or indirectly by the inhibition of cytokines and mediators involved in inflammation.

  16. Anti-inflammatory glucocorticoids: changing concepts.

    PubMed

    Newton, Robert

    2014-02-01

    Despite being the most effective anti-inflammatory treatment for chronic inflammatory diseases, the mechanisms by which glucocorticoids (corticosteroids) effect repression of inflammatory gene expression remain incompletely understood. Direct interaction of the glucocorticoid receptor (NR3C1) with inflammatory transcription factors to repress transcriptional activity, i.e. transrepression, represents one mechanism of action. However, transcriptional activation, or transactivation, by NR3C1 also represents an important mechanism of glucocorticoid action. Glucocorticoids rapidly and profoundly increase expression of multiple genes, many with properties consistent with the repression of inflammatory gene expression. For example: the dual specificity phosphatase, DUSP1, reduces activation of mitogen-activated protein kinases; glucocorticoid-induced leucine zipper (TSC22D3) represses nuclear factor-κB (NF-κB) and activator protein 1 (AP-1) transcriptional responses; inhibitor of κBα (NFKBIA) inhibits NF-κB; tristraprolin (ZFP36) destabilises and translationally represses inflammatory mRNAs; CDKN1C, a cell cycle regulator, may attenuate JUN N-terminal kinase signalling; and regulator of G-protein signalling 2 (RGS2), by reducing signalling from Gαq-linked G protein-coupled receptors (GPCRs), is bronchoprotective. While glucocorticoid-dependent transrepression can co-exist with transactivation, transactivation may account for the greatest level and most potent repression of inflammatory genes. Equally, NR3C1 transactivation is enhanced by β2-adrenoceptor agonists and may explain the enhanced clinical efficacy of β2-adrenoceptor/glucocorticoid combination therapies in asthma and chronic obstructive pulmonary disease. Finally, NR3C1 transactivation is reduced by inflammatory stimuli, including respiratory syncytial virus and human rhinovirus. This provides an explanation for glucocorticoid resistance. Continuing efforts to understand roles for glucocorticoid

  17. Anti-inflammatory guaiane-type sesquiterpenes from the fruits of Pittosporum undulatum.

    PubMed

    Mendes, Sofia A C; Mansoor, Tayyab A; Rodrigues, Ana; Armas, Jácome Bruges; Ferreira, Maria-José U

    2013-11-01

    Two unprecedented guaiane-type sesquiterpene glycosides (undulatumosides A and B) were isolated by bioassay-guided fractionation from the MeOH extract of Pittosporum undulatum fruits, along with six known compounds, including the guaiane isomers 5-guaien-11-ol and 4-guaien-11-ol. The structures of the compounds were established as 4-guaiene-11-O-β-d-(3'-angeloxy-6'-deoxy)-glucopyranoside and 1(5)-guaiene-11-O-β-d-(3'-angeloxy-6'-deoxy)-glucopyranoside by spectroscopic methods, including 1D and 2D homo- and heteronuclear NMR experiments (COSY, HSQC, HMBC and NOESY), and HR-mass spectrometry. P. undulatum is a highly invasive weed that often outcompetes other plants, yet its fruits have become a traditional anti-inflammatory medicine in Azores. Therefore, aiming to investigate the claimed properties, the in vitro anti-inflammatory activity of guaiane-type sesquiterpenes was evaluated by analyzing their inhibitory effects on chemical mediators released by the LPS activated RAW 264.7 murine macrophages cell line. In addition, the cytotoxicity of these compounds was also evaluated in this cell line. Undulatumoside A, 5-guaien-11-ol and 4-guaien-11-ol displayed anti-inflammatory activity with IC50 values of 16.4, 8.1 and 7.2μM, respectively, comparable to that of the positive control, indomethacin (IC50=18.2 μM), with no cytotoxic effects (IC50 ≥ 198 μM). Furthermore, the same set of compounds was also assessed for anti-proliferative activity in lung large cell carcinoma COR-L23 and amelanotic melanoma C32 cells. PMID:23899690

  18. [Active ingredients in rhubarb with anti-proliferative effects on scar fibroblasts].

    PubMed

    Wang, Qian; Zhang, Nan-Nan; Li, Hong-Yan; Jiang, Min; Gao, Jie; Bai, Gang

    2012-12-01

    This study is to explore the active ingredients of traditional Chinese medicine rhubarb with antiproliferative activity on hypertrophic scar fibroblasts (HSF). Rhubarb was extracted with Soxhlet extraction method by different polar solvents. MTS method was used to screen rhubarb solvent extracts (25 microg x mL(-1)) with anti-proliferative activity on HSF, and flow cytometry was used to detect their influences on cell cycle. Then, the active ingredients were analyzed by HPLC. The components with high activity were identified by UPLC-Q/TOF and verified by HE staining. The results showed that the ethyl acetate extract of rhubarb had higher anti-proliferative activity (P < 0.01), increased significantly the proportion of cells in G0/G1 phase (P < 0.01), and reduced the proliferation index (PI) (P < 0.01). The main active ingredients were anthraquinones. The results of confirming experiment showed that emodin, rhein and gallic acid could inhibit cell proliferation in a dose-dependent manner. In conclusion, the ethyl acetate extract of rhubarb showed anti-proliferative activity on HSF, and the anti-proliferative ingredients might be anthraquinones.

  19. Sulforaphane enhances protection and repair of gastric mucosa against oxidative stress in vitro, and demonstrates anti-inflammatory effects on Helicobacter pylori-infected gastric mucosae in mice and human subjects.

    PubMed

    Yanaka, Akinori

    2011-01-01

    Helicobacter pylori infection induces oxidative stress on gastric mucosa, thereby causing mucosal damage, retarding mucosal repair, and eventually inducing gastric cancer. Cells can survive against chronic oxidative stress by enhancing activities of antioxidant enzymes, thereby protecting cells from DNA damage. Recent studies have clearly shown that the genes encoding nrf2 (NF-E2 p45-related factor-2) and keap1 (Kelch-like ECH-associated protein 1) play an important role in the induction of antioxidant enzymes against oxidative stress. In this paper, we will first describe the cellular mechanisms by which the nrf2-keap1 system contributes to induction of a variety of antioxidant enzymes during exposure to oxidative stress. Secondly, we will also mention beneficial effects of a natural compound sulforaphane, an isothiocyanate family, rich in broccoli sprouts, on gastric mucosa. Sulforaphane stimulates nrf2 gene-dependent antioxidant enzyme activities, thereby protecting cells from oxidative injury. Finally, we will show our data on the effect of sulforaphane, a natural chemical compound rich in broccoli sprouts, on protection and repair of gastric mucosa against oxidative stress, and anti-inflammatory effects on gastric mucosa during H. pylori infection, which appears to be closely related to chemoprotection against gastric cancer induced by .H. pylori-infection.

  20. Anti-inflammatory iridoids of botanical origin.

    PubMed

    Viljoen, A; Mncwangi, N; Vermaak, I

    2012-01-01

    Inflammation is a manifestation of a wide range of disorders which include; arthritis, atherosclerosis, Alzheimer's disease, inflammatory bowel syndrome, physical injury and infection amongst many others. Common treatment modalities are usually nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, paracetamol, indomethacin and ibuprofen as well as corticosteroids such as prednisone. These however, may be associated with a host of side effects due to non-selectivity for cyclooxygenase (COX) enzymes involved in inflammation and those with selectivity may be highly priced. Thus, there is a continuing search for safe and effective antiinflammatory molecules from natural sources. Research has confirmed that iridoids exhibit promising anti-inflammatory activity which may be beneficial in the treatment of inflammation. Iridoids are secondary metabolites present in various plants, especially in species belonging to the Apocynaceae, Lamiaceae, Loganiaceae, Rubiaceae, Scrophulariaceae and Verbenaceae families. Many of these ethnobotanicals have an illustrious history of traditional use alluding to their use to treat inflammation. Although iridoids exhibit a wide range of pharmacological activities such as cardiovascular, hepatoprotection, hypoglycaemic, antimutagenic, antispasmodic, anti-tumour, antiviral, immunomodulation and purgative effects this review will acutely focus on their anti-inflammatory properties. The paper aims to present a summary for the most prominent iridoid-containing plants for which anti-inflammatory activity has been demonstrated in vitro and / or in vivo.

  1. Anti-inflammatory iridoids of botanical origin.

    PubMed

    Viljoen, A; Mncwangi, N; Vermaak, I

    2012-01-01

    Inflammation is a manifestation of a wide range of disorders which include; arthritis, atherosclerosis, Alzheimer's disease, inflammatory bowel syndrome, physical injury and infection amongst many others. Common treatment modalities are usually nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, paracetamol, indomethacin and ibuprofen as well as corticosteroids such as prednisone. These however, may be associated with a host of side effects due to non-selectivity for cyclooxygenase (COX) enzymes involved in inflammation and those with selectivity may be highly priced. Thus, there is a continuing search for safe and effective antiinflammatory molecules from natural sources. Research has confirmed that iridoids exhibit promising anti-inflammatory activity which may be beneficial in the treatment of inflammation. Iridoids are secondary metabolites present in various plants, especially in species belonging to the Apocynaceae, Lamiaceae, Loganiaceae, Rubiaceae, Scrophulariaceae and Verbenaceae families. Many of these ethnobotanicals have an illustrious history of traditional use alluding to their use to treat inflammation. Although iridoids exhibit a wide range of pharmacological activities such as cardiovascular, hepatoprotection, hypoglycaemic, antimutagenic, antispasmodic, anti-tumour, antiviral, immunomodulation and purgative effects this review will acutely focus on their anti-inflammatory properties. The paper aims to present a summary for the most prominent iridoid-containing plants for which anti-inflammatory activity has been demonstrated in vitro and / or in vivo. PMID:22414102

  2. LPS induces mediators of neuroinflammation, cell proliferation, and GFAP expression in human astrocytoma cells U373MG: the anti-inflammatory and anti-proliferative effect of guggulipid.

    PubMed

    Niranjan, Rituraj; Nagarajan, Rajasekar; Hanif, Kashif; Nath, Chandishwar; Shukla, Rakesh

    2014-03-01

    Neuroinflammation has been considered to be an integrated part of human neurodegenerative diseases. In this study, we examined the effect of guggulipid on cell proliferation, nitrite release, interleukin IL-6 and IL-1 beta release, and expression of COX-2 and glial fibrillary acidic protein (GFAP) in LPS-stimulated U373MG cells. LPS significantly stimulated human astrocytoma cells U373MG by up-regulating these neuroinflammatory mediators. Guggulipid alone had no effect on the cell proliferation of U373MG cells. The up regulation in nitrite release, cell proliferation, and release of IL-6 and IL-1 beta in LPS stimulated human astrocytoma cells were dose-dependently inhibited by co-treatment with guggulipid. The expression level of COX-2 and GFAP proteins was up regulated by LPS but the increased level of COX-2 and GFAP was significantly down regulated by treatment with guggulipid. These data indicate that guggulipid has a modulatory effect on all these parameters, which might explain its beneficial effect in the treatment of neuroinflammation-associated disorders directly relating to human aspects.

  3. Insulin-sensitizing and anti-proliferative effects of Argania spinosa seed extracts.

    PubMed

    Samane, Samira; Noël, Josette; Charrouf, Zoubida; Amarouch, Hamid; Haddad, Pierre Selim

    2006-09-01

    Argania spinosa is an evergreen tree endemic of southwestern Morocco. Many preparations have been used in traditional Moroccan medicine for centuries to treat several illnesses including diabetes. However, scientific evidence supporting these actions is lacking. Therefore, we prepared various extracts of the argan fruit, namely keel, cake and argan oil extracts, which we tested in the HTC hepatoma cell line for their potential to affect cellular insulin responses. Cell viability was measured by Trypan Blue exclusion and the response to insulin evaluated by the activation of the extracellular regulated kinase (ERK1/2), ERK kinase (MEK1/2) and protein kinase B (PKB/Akt) signaling components. None of the extracts demonstrated significant cytotoxic activity. Certain extracts demonstrated a bi-phasic effect on ERK1/2 activation; low doses of the extract slightly increased ERK1/2 activation in response to insulin, whereas higher doses completely abolished the response. In contrast, none of the extracts had any significant effect on MEK whereas only a cake saponin subfraction enhanced insulin-induced PKB/Akt activation. The specific action of argan oil extracts on ERK1/2 activation made us consider an anti-proliferative action. We have thus tested other transformed cell lines (HT-1080 and MSV-MDCK-INV cells) and found similar results. Inhibition of ERK1/2 activation was also associated with decreased DNA synthesis as evidenced by [(3)H]thymidine incorporation experiments. These results suggest that the products of Argania spinosa may provide a new therapeutic avenue against proliferative diseases. PMID:16951716

  4. Insulin-sensitizing and Anti-proliferative Effects of Argania spinosa Seed Extracts

    PubMed Central

    Samane, Samira; Noël, Josette; Charrouf, Zoubida; Amarouch, Hamid; Haddad, Pierre Selim

    2006-01-01

    Argania spinosa is an evergreen tree endemic of southwestern Morocco. Many preparations have been used in traditional Moroccan medicine for centuries to treat several illnesses including diabetes. However, scientific evidence supporting these actions is lacking. Therefore, we prepared various extracts of the argan fruit, namely keel, cake and argan oil extracts, which we tested in the HTC hepatoma cell line for their potential to affect cellular insulin responses. Cell viability was measured by Trypan Blue exclusion and the response to insulin evaluated by the activation of the extracellular regulated kinase (ERK1/2), ERK kinase (MEK1/2) and protein kinase B (PKB/Akt) signaling components. None of the extracts demonstrated significant cytotoxic activity. Certain extracts demonstrated a bi-phasic effect on ERK1/2 activation; low doses of the extract slightly increased ERK1/2 activation in response to insulin, whereas higher doses completely abolished the response. In contrast, none of the extracts had any significant effect on MEK whereas only a cake saponin subfraction enhanced insulin-induced PKB/Akt activation. The specific action of argan oil extracts on ERK1/2 activation made us consider an anti-proliferative action. We have thus tested other transformed cell lines (HT-1080 and MSV-MDCK-INV cells) and found similar results. Inhibition of ERK1/2 activation was also associated with decreased DNA synthesis as evidenced by [3H]thymidine incorporation experiments. These results suggest that the products of Argania spinosa may provide a new therapeutic avenue against proliferative diseases. PMID:16951716

  5. Insulin-sensitizing and anti-proliferative effects of Argania spinosa seed extracts.

    PubMed

    Samane, Samira; Noël, Josette; Charrouf, Zoubida; Amarouch, Hamid; Haddad, Pierre Selim

    2006-09-01

    Argania spinosa is an evergreen tree endemic of southwestern Morocco. Many preparations have been used in traditional Moroccan medicine for centuries to treat several illnesses including diabetes. However, scientific evidence supporting these actions is lacking. Therefore, we prepared various extracts of the argan fruit, namely keel, cake and argan oil extracts, which we tested in the HTC hepatoma cell line for their potential to affect cellular insulin responses. Cell viability was measured by Trypan Blue exclusion and the response to insulin evaluated by the activation of the extracellular regulated kinase (ERK1/2), ERK kinase (MEK1/2) and protein kinase B (PKB/Akt) signaling components. None of the extracts demonstrated significant cytotoxic activity. Certain extracts demonstrated a bi-phasic effect on ERK1/2 activation; low doses of the extract slightly increased ERK1/2 activation in response to insulin, whereas higher doses completely abolished the response. In contrast, none of the extracts had any significant effect on MEK whereas only a cake saponin subfraction enhanced insulin-induced PKB/Akt activation. The specific action of argan oil extracts on ERK1/2 activation made us consider an anti-proliferative action. We have thus tested other transformed cell lines (HT-1080 and MSV-MDCK-INV cells) and found similar results. Inhibition of ERK1/2 activation was also associated with decreased DNA synthesis as evidenced by [(3)H]thymidine incorporation experiments. These results suggest that the products of Argania spinosa may provide a new therapeutic avenue against proliferative diseases.

  6. Anti-inflammatory properties of diclofenac transition metalloelement complexes.

    PubMed

    Konstandinidou, M; Kourounakis, A; Yiangou, M; Hadjipetrou, L; Kovala-Demertzi, D; Hadjikakou, S; Demertzis, M

    1998-04-01

    As part of our research into understanding drug-metalloelement interactions, we have prepared complexes of Cu(II), Co(II), Ni(II), Mn(II), Fe(II), Fe(III), and Pd(II) with Diclofenac, in order to investigate their anti-inflammatory activity. Their inhibitory effects on rat or mouse paw edema induced by Carrageenan, Con-A, Nystatin, and Baker's yeast were compared with those of Diclofenac. Furthermore, the action of Diclofenac's metalloelement complexes on phagocytosis of yeast by rat peritoneal cells, as well as the capacity of some of the metalloelement complexes to inhibit lipid peroxidation of liver microsomal membranes was also investigated. These complexes exhibited a strong inhibitory effect on Carrageenan-, ConA-, and Nystatin-induced edemas (35-80% inhibition) comparable to the inhibition caused by Diclofenac (61-76% inhibition). Furthermore, complexes with Co(II), Ni(II), Pd(II), and Mn(II) were found to have an anti-inflammatory profile (35-50% inhibition) superior to diclofenac (17% inhibition) when inhibiting inflammations due to Baker's yeast, the mechanism of which involves mainly the activation of lipoxygenase and/or complement system. Complexes of Ni(II) and Pd(II), which showed significant inhibition of induced-edemas in rats, were also tested in mice at lower and higher doses and showed a significant dose-dependent inhibition of edemas in mice. Some of these complexes also interfere with in vitro phagocytosis. The most active anti-inflammatory complexes Co(II), Pd(II), and Ni(II), also offered significant protection against lipid peroxidation in vitro, acting as antioxidant compounds, properties that are not demonstrated by Diclofenac. Finally, it is noted that almost all metalloelement complexes of Diclofenac showed high anti-inflammatory activity at molecular concentrations much lower than that of Diclofenac. From the present study it is suggested that the anti-inflammatory activity of Diclofenac is enhanced by the formation of coordination

  7. Nonsteroidal anti-inflammatory drugs.

    PubMed

    Kallings, P

    1993-12-01

    NSAIDs' mechanism of action by inhibiting the synthesis of prostanoids accounts for both their therapeutic and toxic effects. They are commonly used in acute and chronic musculoskeletal and soft-tissue conditions. Adverse reactions include gastrointestinal disturbances and hypoproteinemia. Their pharmacologic effect seems to have a longer duration than their plasma concentrations indicate. This gives implications on current regulations for competing horses and the relevance of permitted levels has been questioned. The NSAIDs do not appear to enhance performance, but rather allow the horse to run up to its potential by reducing pain and lameness. There is concern over the possible hazards to the horse by this kind of therapeutic use. In conclusion, NSAIDs have well justifiable therapeutic uses in equine practice. They should, however, be used when there is a clear clinical indication, in safe dose rates and without jeopardizing the welfare of the performance horse.

  8. Reactive oxygen species induced by non-steroidal anti-inflammatory drugs enhance the effects of photodynamic therapy in gastric cancer cells.

    PubMed

    Ito, Hiromu; Matsui, Hirofumi; Hirayama, Aki; Indo, Hiroko P; Majima, Hideyuki J; Hyodo, Ichinosuke

    2016-05-01

    Photodynamic therapy is useful for the treatment of cancer because it is minimally invasive for patients. Certain porphyrin compounds and their derivatives have been used as the photosensitizer because they accumulate specifically in cancerous tissues. However, the detailed mechanism of this phenomenon has not been clarified. We previously reported that a proton-coupled folate transporter, HCP1, transported porphyrins and that regulation of the protein was associated with cancer-specific reactive oxygen species from mitochondria (mitROS). Therefore, over-generation of mitROS could increase HCP1 expression and the effect of photodynamic therapy. We investigated whether pretreatment with indomethacin influenced photodynamic therapy by using a rat normal gastric mucosal cell line, RGM1, its cancer-like mutated cell line, RGK1, and a manganese superoxide dismutase (MnSOD)-overexpressing RGK cell line, RGK-MnSOD. Indomethacin promotes the generation of cellular mitROS by inhibiting the electron transport chain, and MnSOD scavenges the mitROS. We elucidated that indomethacin enhanced cancer-specific mitROS generation and increased HCP1 expression. Furthermore, RGK1 cells showed higher cellular incorporation of hematoporphyrin and better therapeutic effect with indomethacin treatment whereas RGK-MnSOD cells did not show a difference. Thus, we concluded that indomethacin improved the effect of photodynamic therapy by inducing increased mitROS generation in cancer cells.

  9. Medicinal plants with anti-inflammatory activities.

    PubMed

    Maione, Francesco; Russo, Rosa; Khan, Haroon; Mascolo, Nicola

    2016-06-01

    Medicinal plants have been the main remedy to treat various ailments for a long time and nowadays, many drugs have been developed from traditional medicine. This paper reviews some medicinal plants and their main constituents which possess anti-inflammatory activities useful for curing joint inflammation, inflammatory skin disorders, cardiovascular inflammation and other inflammatory diseases. Here, we provide a brief overview of quick and easy reading on the role of medicinal plants and their main constituents in these inflammatory diseases. We hope that this overview will shed some light on the function of these natural anti-inflammatory compounds and attract the interest of investigators aiming at the design of novel therapeutic approaches for the treatment of various inflammatory conditions.

  10. Medicinal plants with anti-inflammatory activities.

    PubMed

    Maione, Francesco; Russo, Rosa; Khan, Haroon; Mascolo, Nicola

    2016-06-01

    Medicinal plants have been the main remedy to treat various ailments for a long time and nowadays, many drugs have been developed from traditional medicine. This paper reviews some medicinal plants and their main constituents which possess anti-inflammatory activities useful for curing joint inflammation, inflammatory skin disorders, cardiovascular inflammation and other inflammatory diseases. Here, we provide a brief overview of quick and easy reading on the role of medicinal plants and their main constituents in these inflammatory diseases. We hope that this overview will shed some light on the function of these natural anti-inflammatory compounds and attract the interest of investigators aiming at the design of novel therapeutic approaches for the treatment of various inflammatory conditions. PMID:26221780

  11. Anti-inflammatory actions of acupuncture.

    PubMed Central

    Zijlstra, Freek J; van den Berg-de Lange, Ineke; Huygen, Frank J P M; Klein, Jan

    2003-01-01

    Acupuncture has a beneficial effect when treating many diseases and painful conditions, and therefore is thought to be useful as a complementary therapy or to replace generally accepted pharmacological intervention. The attributive effect of acupuncture has been investigated in inflammatory diseases, including asthma, rhinitis, inflammatory bowel disease, rheumatoid arthritis, epicondylitis, complex regional pain syndrome type 1 and vasculitis. Large randomised trials demonstrating the immediate and sustained effect of acupuncture are missing. Mechanisms underlying the ascribed immunosuppressive actions of acupuncture are reviewed in this communication. The acupuncture-controlled release of neuropeptides from nerve endings and subsequent vasodilative and anti-inflammatory effects through calcitonine gene-related peptide is hypothesised. The complex interactions with substance P, the analgesic contribution of beta-endorphin and the balance between cell-specific pro-inflammatory and anti-inflammatory cytokines tumour necrosis factor-alpha and interleukin-10 are discussed. PMID:12775355

  12. Anti-Inflammatory Effect of Selected Dihydroxyflavones

    PubMed Central

    Sangeetha, K.S.Sridevi

    2015-01-01

    Background The mechanism of inflammation is attributed, to release of reactive oxygen species from activated neutrophils and macrophages. Over production of reactive oxygen species may result in tissue injury by damaging macromolecules. Flavones are the polyphenolic compounds with antioxidant property. This antioxidant property of flavones may have beneficial effect against inflammation. Aim To study the anti-inflammatory effect of selected dihydroxyflavones (DHF) in albino rats. The prime objective of the present study is to identify safe and effective agents to treat inflammation from among the selected DHF group of compounds. Materials and Methods The present study was designed to investigate the anti-inflammatory action of four selected dihydroxyflavone derivatives; 2’,3’- dihydroxyflavone and 2’, 4’ -dihydroxyflavones, 5, 3’- dihydroxyflavone and 7, 3’ dihydroxyflavone. The anti-inflammatory activity of selected DHF was studied in rats by carrageenan induced hind paw oedema method. Results All the selected dihydroxyflavone derivatives showed dose and time dependent inhibition of carrageenan induced paw oedema. PMID:26155493

  13. Comparison of ultrasound-enhanced air-assisted liquid-liquid microextraction and low-density solvent-based dispersive liquid-liquid microextraction methods for determination of nonsteroidal anti-inflammatory drugs in human urine samples.

    PubMed

    Barfi, Behruz; Asghari, Alireza; Rajabi, Maryam; Goochani Moghadam, Ahmad; Mirkhani, Nasim; Ahmadi, Farhad

    2015-01-01

    Two dispersive-based liquid-liquid microextraction methods including ultrasound-enhanced air-assisted liquid-liquid microextraction (USE-AALLME) and low-density solvent-based dispersive liquid-liquid microextraction (LDS-DLLME) were compared for the extraction of salicylic acid (the hydrolysis product of acetylsalicylic acid), diclofenac and ibuprofen, as instances of the most commonly used nonsteroidal anti-inflammatory drugs (NSAIDs), in human urine prior to their determination by gas chromatography with flame ionization detection (GC-FID). The influence of different parameters affecting the USE-AALLME (including type and volume of the extraction solvent, sample pH, ionic strength, and simultaneous sonication and number of extraction cycles) and the LDS-DLLME (including type and volume of the extraction and disperser solvents, sample pH, and ionic strength) were investigated to optimize their extraction efficiencies. Both methods are fast, simple and convenient with organic solvent consumption at μL level. However, the best results were obtained using the USE-AALLME method, applying 30 μL of 1-octanol as extraction solvent, 5.0 mL of sample at pH 3.0, without salt addition, and 5 extraction cycles during 20s of sonication. This method was validated based on linearities (r(2) >0 .971), limits of detection (0.1-1.0 μg L(-1)), linear dynamic ranges (0.4-1000.0 μg L(-1)), enrichment factors (115 ± 3-135 ± 3), consumptive indices (0.043-0.037), inter- and intra-day precisions (4.3-4.8 and 5.6-6.1, respectively), and relative recoveries (94-103%). The USE-AALLME in combination with GC-FID, and with no need to derivatization step, was demonstrated to be a simple, inexpensive, sensitive and efficient method to determine NSAIDs in human urine samples.

  14. Synthesis and anti-proliferative activity of fluoro-substituted chalcones.

    PubMed

    Burmaoglu, Serdar; Algul, Oztekin; Anıl, Derya Aktas; Gobek, Arzu; Duran, Gulay Gulbol; Ersan, Ronak Haj; Duran, Nizami

    2016-07-01

    A series of novel fluoro-substituted chalcone derivatives have been synthesized. All synthesized compounds were characterized by (1)H nuclear magnetic resonance (NMR), (13)C NMR, and elemental analysis. Their anti-proliferative activities were evaluated against five cancer cells lines, namely, A549, A498, HeLa, A375, and HepG2 using the MTT method. Most of the compounds showed moderate to high activity with IC50 values in the range of 0.029-0.729μM. Of all the synthesized compounds, 10 and 19 exhibited the most potent anti-proliferative activities against cancer cells, and 10 was identified as the most promising compound. PMID:27217001

  15. Evaluation of the anti-proliferative and cytostatic effect of Citrus sinensis (orange) fruit juice

    PubMed Central

    Chinedu, Enegide; Arome, David; Ameh, Solomon F; Ameh, Gift E

    2014-01-01

    Aim: This work has been designed to evaluate the anti-proliferative and cytostatic effects of Citrus sinensis (orange) fruit juice on rapidly proliferating cells. Materials and Methods: The study was carried out on the seeds of Sorghum bicolor for 72 h. The mean radicle length (mm) of the seeds was taken at 48 and 72 h. Result: The result showed that when compared with the control, methotrexate, the standard drug showed a significant (P < 0.001) anti-proliferative effect throughout the experiment. The inhibition of the radicle growth was more after 72 h (87.42%). At a dose of 5% (v/v), the juice showed a slightly significant (P < 0.05) effect affect after 72 h; however, there was no significant effect at 48 h. The juice at doses of 10% and 20% (v/v) showed a highly significant (P < 0.001) anti-proliferative effect throughout the experiment; however, the percentage inhibitions were higher at 72 h. At 72 h, the percentage inhibition for juice at 10% (v/v) was 72.37% and at 20% (v/v) was 91.96%. The concentrations of 40% and 60% (v/v) showed cytostatic effects as no appreciable growth of the radicles of the seeds was observed throughout the experiment. The percentage inhibition for 40% (v/v) was 100% and 99.72% for 48 and 72 h, respectively, while that for the juice concentration of 60% (v/v) was 100% throughout the study. Conclusion: The experiment has shown that C. sinensis fruit juice has a potential for causing both anti-proliferative and cytostatic effects on fast proliferating cells and hence cancerous cells. PMID:25298937

  16. Anti-proliferative activity and chemoprotective effects towards DNA oxidative damage of fresh and cooked Brassicaceae.

    PubMed

    Ferrarini, Lisa; Pellegrini, Nicoletta; Mazzeo, Teresa; Miglio, Cristiana; Galati, Serena; Milano, Francesco; Rossi, Carlo; Buschini, Annamaria

    2012-05-01

    Epidemiological evidence shows that regular consumption of Brassicaceae is associated with a reduced risk of cancer and heart disease. Cruciferous species are usually processed before eating and the real impact of cooking practices on their bioactive properties is not fully understood. We have evaluated the effect of common cooking practices (boiling, microwaving, and steaming) on the biological activities of broccoli, cauliflower and Brussels sprouts. Anti-proliferative and chemoprotective effects towards DNA oxidative damage of fresh and cooked vegetable extracts were evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium and Comet assays on HT-29 human colon carcinoma cells. The fresh vegetable extracts showed the highest anti-proliferative and antioxidant activities on HT-29 cells (broccoli>cauliflower = Brussels sprouts). No genotoxic activity was detected in any of the samples tested. The cooking methods that were applied influenced the anti-proliferative activity of Brassica extracts but did not alter considerably the antioxidant activity presented by the raw vegetables. Raw, microwaved, boiled (except broccoli) and steamed vegetable extracts, at different concentrations, presented a protective antioxidative action comparable with vitamin C (1 mm). These data provide new insight into the influence of domestic treatment on the quality of food, which could support the recent epidemiological studies suggesting that consumption of cruciferous vegetables, mainly cooked, may be related to a reduced risk of developing cancer.

  17. Tristetraprolin mediates the anti-proliferative effects of metformin in breast cancer cells.

    PubMed

    Pandiri, Indira; Chen, Yingqing; Joe, Yeonsoo; Kim, Hyo Jeong; Park, Jeongmin; Chung, Hun Taeg; Park, Jeong Woo

    2016-02-01

    Metformin, which is a drug commonly prescribed to treat type 2 diabetes, has anti-proliferative effects in cancer cells; however, the molecular mechanisms underlying this effect remain largely unknown. The aim is to investigate the role of tristetraprolin (TTP), an AU-rich element-binding protein, in anti-proliferative effects of metformin in cancer cells. p53 wild-type and p53 mutant breast cancer cells were treated with metformin, and expression of TTP and c-Myc was analyzed by semi-quantitative RT-PCR, Western blots, and promoter activity assay. Breast cancer cells were transfected with siRNA against TTP to inhibit TTP expression or c-Myc and, after metformin treatment, analyzed for cell proliferation by MTS assay. Metformin induces the expression of tristetraprolin (TTP) in breast cancer cells in a p53-independent manner. Importantly, inhibition of TTP abrogated the anti-proliferation effect of metformin. We observed that metformin decreased c-Myc levels, and ectopic expression of c-Myc blocked the effect of metformin on TTP expression and cell proliferation. Our data indicate that metformin induces TTP expression by reducing the expression of c-Myc, suggesting a new model whereby TTP acts as a mediator of metformin's anti-proliferative activity in cancer cells. PMID:26956973

  18. In vitro anti-proliferative and anti-angiogenic activities of thalidomide dithiocarbamate analogs.

    PubMed

    El-Aarag, Bishoy Y A; Kasai, Tomonari; Zahran, Magdy A H; Zakhary, Nadia I; Shigehiro, Tsukasa; Sekhar, Sreeja C; Agwa, Hussein S; Mizutani, Akifumi; Murakami, Hiroshi; Kakuta, Hiroki; Seno, Masaharu

    2014-08-01

    Inhibition of angiogenesis is currently perceived as a promising strategy in the treatment of cancer. The anti-angiogenicity of thalidomide has inspired a second wave of research on this teratogenic drug. The present study aimed to investigate the anti-proliferative and anti-angiogenic activities of two thalidomide dithiocarbamate analogs by studying their anti-proliferative effects on human umbilical vein endothelial cells (HUVECs) and MDA-MB-231 human breast cancer cell lines. Their action on the expression levels of IL-6, IL-8, TNF-α, VEGF165, and MMP-2 was also assessed. Furthermore, their effect on angiogenesis was evaluated through wound healing, migration, tube formation, and nitric oxide (NO) assays. Results illustrated that the proliferation of HUVECs and MDA-MB-231 cells was not significantly affected by thalidomide at 6.25-100μM. Thalidomide failed to block angiogenesis at similar concentrations. By contrast, thalidomide dithiocarbamate analogs exhibited significant anti-proliferative action on HUVECs and MDA-MB-231 cells without causing cytotoxicity and also showed powerful anti-angiogenicity in wound healing, migration, tube formation, and NO assays. Thalidomide analogs 1 and 2 demonstrated more potent activity to suppress expression levels of IL-6, IL-8, TNF-α, VEGF165, and MMP-2 than thalidomide. Analog 1 consistently, showed the highest potency and efficacy in all the assays. Taken together, our results support further development and evaluation of novel thalidomide analogs as anti-tumor and anti-angiogenic agents.

  19. Quinazolinones-Phenylquinoxaline hybrids with unsaturation/saturation linkers as novel anti-proliferative agents.

    PubMed

    Palem, Jyothsna Devi; Alugubelli, Gopi Reddy; Bantu, Rajashaker; Nagarapu, Lingaiah; Polepalli, Sowjanya; Jain, S Nishanth; Bathini, Raju; Manga, Vijjulatha

    2016-07-01

    A new series of novel quinazolinones with allylphenyl quinoxaline hybrids 9a-n were efficiently synthesized in good yields by the reaction of 3-allyl-2-methylquinazolin-4(3H)-one (5a-n) with bromophenyl)quinoxaline (8) utilizing Pd catalyzed Heck-cross coupling and evaluated for anti-proliferative activity against four cancer cell lines such as HeLa (cervical), MIAPACA (pancreatic), MDA-MB-231 (breast) and IMR32 (neuroblastoma). Compounds 9a, 9e, 9g and 9h exhibited promising anti-proliferative activity with GI50 values ranging from 0.06 to 0.2μM against four cell lines, while compounds 9e and 9k showed significant activity against HeLa and MIAPACA cell lines and compounds 9b, 9d, 9h and 9j showed selective potency against IMR32 and MDA-MB-231 cell lines. This is the first report on the synthesis and in vitro anti-proliferative evaluation of E-2-(4-substituted)-3-(3-(4-(quinoxalin-2-yl)phenyl)allyl)quinazolin-4(3H)-ones (9a-n). Docking results indicate a sign of good correlation between experimental activity and calculated binding affinity (dock score), suggesting that these compounds could act as promising DNA intercalates. PMID:27209232

  20. Quinazolinones-Phenylquinoxaline hybrids with unsaturation/saturation linkers as novel anti-proliferative agents.

    PubMed

    Palem, Jyothsna Devi; Alugubelli, Gopi Reddy; Bantu, Rajashaker; Nagarapu, Lingaiah; Polepalli, Sowjanya; Jain, S Nishanth; Bathini, Raju; Manga, Vijjulatha

    2016-07-01

    A new series of novel quinazolinones with allylphenyl quinoxaline hybrids 9a-n were efficiently synthesized in good yields by the reaction of 3-allyl-2-methylquinazolin-4(3H)-one (5a-n) with bromophenyl)quinoxaline (8) utilizing Pd catalyzed Heck-cross coupling and evaluated for anti-proliferative activity against four cancer cell lines such as HeLa (cervical), MIAPACA (pancreatic), MDA-MB-231 (breast) and IMR32 (neuroblastoma). Compounds 9a, 9e, 9g and 9h exhibited promising anti-proliferative activity with GI50 values ranging from 0.06 to 0.2μM against four cell lines, while compounds 9e and 9k showed significant activity against HeLa and MIAPACA cell lines and compounds 9b, 9d, 9h and 9j showed selective potency against IMR32 and MDA-MB-231 cell lines. This is the first report on the synthesis and in vitro anti-proliferative evaluation of E-2-(4-substituted)-3-(3-(4-(quinoxalin-2-yl)phenyl)allyl)quinazolin-4(3H)-ones (9a-n). Docking results indicate a sign of good correlation between experimental activity and calculated binding affinity (dock score), suggesting that these compounds could act as promising DNA intercalates.

  1. In vitro anti-proliferative and anti-angiogenic activities of thalidomide dithiocarbamate analogs.

    PubMed

    El-Aarag, Bishoy Y A; Kasai, Tomonari; Zahran, Magdy A H; Zakhary, Nadia I; Shigehiro, Tsukasa; Sekhar, Sreeja C; Agwa, Hussein S; Mizutani, Akifumi; Murakami, Hiroshi; Kakuta, Hiroki; Seno, Masaharu

    2014-08-01

    Inhibition of angiogenesis is currently perceived as a promising strategy in the treatment of cancer. The anti-angiogenicity of thalidomide has inspired a second wave of research on this teratogenic drug. The present study aimed to investigate the anti-proliferative and anti-angiogenic activities of two thalidomide dithiocarbamate analogs by studying their anti-proliferative effects on human umbilical vein endothelial cells (HUVECs) and MDA-MB-231 human breast cancer cell lines. Their action on the expression levels of IL-6, IL-8, TNF-α, VEGF165, and MMP-2 was also assessed. Furthermore, their effect on angiogenesis was evaluated through wound healing, migration, tube formation, and nitric oxide (NO) assays. Results illustrated that the proliferation of HUVECs and MDA-MB-231 cells was not significantly affected by thalidomide at 6.25-100μM. Thalidomide failed to block angiogenesis at similar concentrations. By contrast, thalidomide dithiocarbamate analogs exhibited significant anti-proliferative action on HUVECs and MDA-MB-231 cells without causing cytotoxicity and also showed powerful anti-angiogenicity in wound healing, migration, tube formation, and NO assays. Thalidomide analogs 1 and 2 demonstrated more potent activity to suppress expression levels of IL-6, IL-8, TNF-α, VEGF165, and MMP-2 than thalidomide. Analog 1 consistently, showed the highest potency and efficacy in all the assays. Taken together, our results support further development and evaluation of novel thalidomide analogs as anti-tumor and anti-angiogenic agents. PMID:24859059

  2. Anti-proliferative and apoptotic effects of Ziziphus Jujube on cervical and breast cancer cells

    PubMed Central

    Abedini, Mohammad Reza; Erfanian, Nafiseh; Nazem, Habibollah; Jamali, Sara; Hoshyar, Reyhane

    2016-01-01

    Objective: Ziziphus Jujube (Jujube) plant has exhibited numerous medicinal and pharmacological properties including antioxidant and anti-inflammatory effects. This study was carried out to investigate its anti-cancer and pro-apoptotic abilities in human cervical and breast cancer cells in vitro. Materials and Methods: The cervical OV2008 and breast MCF-7 cancer cells were incubated with different concentrations of Jujube aqueous extraction (0-3 mg/ml) for various times (0-72 h). Cell viability was assessed by Trypan Blue and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of two apoptosis-related genes in treated cells evaluated by quantitative Real Time -PCR analysis. Results: Jujube significantly inhibited cancer cell viability in a dose- and time- dependent manner. Herb-induced apoptosis was associated with enhanced expression of Bax and decreased Bcl2 gene leading eventually to a time-dependent six fold increase in the Bax/Bcl-2 ratio. Conclusion: These results indicated that Jujube may be a natural potential and promising agent to prevent or treat human cancers. PMID:27222827

  3. Sperm Binding to Oviduct Epithelial Cells Enhances TGFB1 and IL10 Expressions in Epithelial Cells as Well as Neutrophils In Vitro: Prostaglandin E2 As a Main Regulator of Anti-Inflammatory Response in the Bovine Oviduct

    PubMed Central

    Yousef, Mohamed Samy; Marey, Mohamed Ali; Hambruch, Nina; Hayakawa, Hiroyuki; Shimizu, Takashi; Hussien, Hassan Ali; Abdel-Razek, Abdel-Razek Khalifa; Pfarrer, Christiane; Miyamoto, Akio

    2016-01-01

    Sperm are allogenic to the female genital tract; however, oviducts provide optimal conditions for survival and capacitation of these non-self cells until fertilization. Recently, we showed that oviduct-conditioned media and prostaglandin E2 (PGE2) suppress sperm phagocytosis by polymorphonuclear neutrophils (PMNs) under physiological conditions. We hypothesized that sperm binding to bovine oviduct epithelial cells (BOECs) could change the local innate immunity via PGE2. As the first step to obtain basic information, sub-confluent BOEC monolayers were co-cultured with swim-up sperm for 2 h. BOECs with viable bound sperm were cultured for an additional 3, 6, 12, or 24 h. Then, we confirmed the impact of the sperm-BOEC binding on both BOECs and PMN gene expression. Immunohistochemistry revealed that BOECs strongly express TGFB1 and IL10 in the oviduct. Sperm binding to BOECs in culture induced the anti-inflammatory cytokines (TGFB1 and IL10) and PGE2 production by BOECs. Exogenous PGE2 in vitro suppressed pro-inflammatory cytokine expression (TNF and IL1B) in BOECs. Moreover, pre-exposure of PMNs to BOEC-conditioned media suppressed the TNF expression, but the BOEC media co-cultured with sperm stimulated PMNs to express TGFB1 and IL10, with increasing PGE2 secretion. Of note, exogenous PGE2 led PMNs in vitro to decrease their TNF expression and increase anti-inflammatory cytokines expression. Our findings strongly suggest that BOECs provide an anti-inflammatory environment under physiological conditions and the sperm-BOEC binding further strengthens this milieu thus suppresses PMNs in the bovine oviduct. PGE2 is likely to drive this stable anti-inflammatory environment in the oviduct. PMID:27662642

  4. Nanoliposomal Nitroglycerin Exerts Potent Anti-Inflammatory Effects

    NASA Astrophysics Data System (ADS)

    Ardekani, Soroush; Scott, Harry A.; Gupta, Sharad; Eum, Shane; Yang, Xiao; Brunelle, Alexander R.; Wilson, Sean M.; Mohideen, Umar; Ghosh, Kaustabh

    2015-11-01

    Nitroglycerin (NTG) markedly enhances nitric oxide (NO) bioavailability. However, its ability to mimic the anti-inflammatory properties of NO remains unknown. Here, we examined whether NTG can suppress endothelial cell (EC) activation during inflammation and developed NTG nanoformulation to simultaneously amplify its anti-inflammatory effects and ameliorate adverse effects associated with high-dose NTG administration. Our findings reveal that NTG significantly inhibits human U937 cell adhesion to NO-deficient human microvascular ECs in vitro through an increase in endothelial NO and decrease in endothelial ICAM-1 clustering, as determined by NO analyzer, microfluorimetry, and immunofluorescence staining. Nanoliposomal NTG (NTG-NL) was formulated by encapsulating NTG within unilamellar lipid vesicles (DPhPC, POPC, Cholesterol, DHPE-Texas Red at molar ratio of 6:2:2:0.2) that were ~155 nm in diameter and readily uptaken by ECs, as determined by dynamic light scattering and quantitative fluorescence microscopy, respectively. More importantly, NTG-NL produced a 70-fold increase in NTG therapeutic efficacy when compared with free NTG while preventing excessive mitochondrial superoxide production associated with high NTG doses. Thus, these findings, which are the first to reveal the superior therapeutic effects of an NTG nanoformulation, provide the rationale for their detailed investigation for potentially superior vascular normalization therapies.

  5. Synthesis and biological evaluation of quinic acid derivatives as anti-inflammatory agents.

    PubMed

    Zeng, Kui; Thompson, Karin Emmons; Yates, Charles R; Miller, Duane D

    2009-09-15

    Quinic acid (QA) esters found in hot water extracts of Uncaria tomentosa (a.k.a. cat's claw) exert anti-inflammatory activity through mechanisms involving inhibition of the pro-inflammatory transcription factor nuclear factor kappa B (NF-kappaB). Herein, we describe the synthesis and biological testing of novel QA derivatives. Inhibition of NF-kappaB was assessed using A549 (Type II alveolar epithelial-like) cells that stably express a secreted alkaline phosphatase (SEAP) reporter driven by an NF-kappaB response element. A549-NF-kappaB cells were stimulated with TNF-alpha (10 ng/mL) in the presence or absence of QA derivative for 18 hours followed by measurement of SEAP activity. Amide substitution at the carboxylic acid position yielded potent inhibitors of NF-kappaB. A variety of modifications to the amide substitution were tolerated with the N-propyl amide derivative being the most potent. Further examination of the SAR demonstrated that acetylation of the hydroxyl groups reduced NF-kappaB inhibitory activity. QA amide derivatives lacked anti-oxidant activity and were found to be neither anti-proliferative nor cytotoxic at concentrations up to 100 microM. In conclusion, we have discovered a novel series of non-toxic QA amides that potently inhibit NF-kappaB, despite their lack of anti-oxidant activity. Mechanistic studies and pre-clinical efficacy studies in various inflammatory animal models are on-going.

  6. In vitro anti-inflammatory and anticancer activities of extracts of Acalypha alopecuroidea (Euphorbiaceae).

    PubMed

    Madlener, Sibylle; Svacinová, Jana; Kitner, Miloslav; Kopecky, Jirí; Eytner, Ruth; Lackner, Andreas; Vo, Than Phuong Nha; Frisch, Richard; Grusch, Michael; De Martin, Rainer; Dolezal, Karel; Strnad, Miroslav; Krupitza, Georg

    2009-10-01

    More than 60% of conventional drugs are derived from natural compounds, some of the most effective pharmaceuticals (e.g. aspirin, quinine and various antibiotics) originate from plants or microbes, and large numbers of potentially valuable natural substances remain to be discovered. Plants with considerable medicinal potential include members of the genus Acalypha. Notably, extracts of A. platyphilla, A. fruticosa, A. siamensis, A. guatemalensis and A. wilkesiana have been recently shown to have antioxidant, antimicrobial and cytotoxic effects. In the study presented here we investigated the anti-inflammatory, anti-proliferative and pro-apoptotic activities of A. alopecuroidea, which is endemic in parts of Central America and is traditionally used by the Mopan- and Itza-Maya in the form of decoctions to treat skin conditions, and as a tea to treat stomach and urinary complaints. We demonstrate here that extracts of A. alopecuroidea can inhibit TNFalpha-induced E-selectin production, providing a mechanistic validation of its traditional use against inflammatory diseases. Furthermore, a fraction of A. alopecuroidea root extracts purified by solid phase extraction and separated by HPLC displayed strong cell cycle inhibitory activity by down-regulating and inactivating two proto-oncogenes (cyclin D1 and Cdc25A), and simultaneously inducing cyclin A, thereby disturbing orchestrated cell cycle arrest, and thus (presumably) triggering caspase 3-dependent apoptosis. The results of this study indicate that there are high prospects for purifying an active principle from A. alopecuroidea for further in vivo and preclinical studies.

  7. Monoterpene derivatives from the roots of Paeonia lactiflora and their anti-proliferative activity.

    PubMed

    Li, Pan; Zhang, Ze-Ming; Li, Tao; Zhang, Yan-Bo; Sze, Stephen Cho Wing; Wang, Guo-Cai; Li, Yao-Lan; Ye, Wen-Cai

    2014-10-01

    An unusual nor-monoterpene with only nine carbons, nor-paeonilactone (1), two new monoterpenes, paeonisuffrone C (2), paeonilactone D (9), and a new monoterpene glucoside, paeonin D (3), along with ten known compounds were isolated from the dried roots of Paeonia lactiflora. Their structures were elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR, and computational data. Compounds 4-14 were evaluated for their anti-proliferative activities against BT 483 human breast cancer cells and OVCA 429 human ovarian cancer cells by MTT assay. PMID:25068201

  8. Gaseous mediator-based anti-inflammatory drugs.

    PubMed

    Sulaieva, Oksana; Wallace, John L

    2015-12-01

    Among the most commonly used drugs, nonsteroidal anti-inflammatory drugs (NSAIDs) remain problematic because of their propensity to cause serious adverse events, principally affecting the gastrointestinal tract. In recent years, the discovery of potent anti-inflammatory and cytoprotective effects of endogenous gaseous mediators (nitric oxide, hydrogen sulfide, carbon monoxide) stimulated efforts to develop novel, combination NSAIDs that suppress prostaglandin synthesis (producing anti-inflammatory and analgesic effects) and release one or more of the cytoprotective gaseous mediators. Gaseous mediator-based anti-inflammatory drugs have reached the human clinical trial stage and show considerable promise as a safer option for treating chronic inflammatory diseases.

  9. Inhibition of lipid peroxidation and enhancement of GST activity by cardamom and cinnamon during chemically induced colon carcinogenesis in Swiss albino mice.

    PubMed

    Bhattacharjee, Shamee; Rana, Tapasi; Sengupta, Archana

    2007-01-01

    Globally, colorectal cancer is the third commonest cancer in men since 1975.The present study focuses on the preventive strategies aimed at reducing the incidences and mortality of large bowel cancer. Chemoprevention of colon cancer appears to be a very realistic possibility because various intermediate stages have been identified preceding the development of malignant colonic tumors. Several studies have demonstrated that generous consumption of vegetables reduces the risk of colon cancer. This idea has prompted the present investigation to search for some novel plant products, which may have possible anticarcinogenic activity. It has already been proved from various experiments that chemopreventive agents, by virtue of their anti-oxidant, anti-inflammatory, anti-proliferative, apoptosis-inducing activity, act at various levels including molecular, cellular, tissue and organ levels to interfere with carcinogens. Previous studies from our laboratory have already reported the inhibitory effect of cinnamon and cardamom on azoxymethane induced colon carcinogenesis by virtue of their anti-inflammatory, anti-proliferative and pro-apoptotic activity. This particular experiment was carried out to assess the anti-oxidative potential of these spices. Aqueous suspensions of cinnamon and cardamom have been shown to enhance the level of detoxifying enzyme (GST activity) with simultaneous decrease in lipid peroxidation levels in the treatment groups when compared to that of the carcinogen control group.

  10. Review of Anti-Inflammatory Herbal Medicines.

    PubMed

    Ghasemian, Mona; Owlia, Sina; Owlia, Mohammad Bagher

    2016-01-01

    Medicinal plants and their secondary metabolites are progressively used in the treatment of diseases as a complementary medicine. Inflammation is a pathologic condition that includes a wide range of diseases such as rheumatic and immune-mediated conditions, diabetes, cardiovascular accident, and etcetera. We introduce some herbs which their anti-inflammatory effects have been evaluated in clinical and experimental studies. Curcuma longa, Zingiber officinale, Rosmarinus officinalis, Borago officinalis, evening primrose, and Devil's claw are some of the introduced medicinal herbs in this review. Since the treatment of inflammation is not a one-dimensional remedy, this review tries to reach a multidimensional therapeutic approach to inflammation with the help of herbal medicine and modification in lifestyle. PMID:27247570

  11. Review of Anti-Inflammatory Herbal Medicines

    PubMed Central

    Ghasemian, Mona; Owlia, Sina; Owlia, Mohammad Bagher

    2016-01-01

    Medicinal plants and their secondary metabolites are progressively used in the treatment of diseases as a complementary medicine. Inflammation is a pathologic condition that includes a wide range of diseases such as rheumatic and immune-mediated conditions, diabetes, cardiovascular accident, and etcetera. We introduce some herbs which their anti-inflammatory effects have been evaluated in clinical and experimental studies. Curcuma longa, Zingiber officinale, Rosmarinus officinalis, Borago officinalis, evening primrose, and Devil's claw are some of the introduced medicinal herbs in this review. Since the treatment of inflammation is not a one-dimensional remedy, this review tries to reach a multidimensional therapeutic approach to inflammation with the help of herbal medicine and modification in lifestyle. PMID:27247570

  12. Anti-proliferative activity of Fumaria vaillantii extracts on different cancer cell lines

    PubMed Central

    Tabrizi, Fatemeh Haji Abbas; Irian, Saeed; Amanzadeh, Amir; Heidarnejad, Fatemeh; Gudarzi, Hoda; Salimi, Mona

    2016-01-01

    Plant-derived natural products are known to have cancer chemo-preventive and chemo-therapeutic properties. Plant extracts or their active constituents are used as folk medicine in traditional therapies by 80% of the world population. The aim of the present study was to determine the anti-proliferative potential of Fumaria vaillantii extracts on three different cancer cell lines including malignant melanoma SKMEL-3, human breast adenocarcinoma MCF-7 and human myelogenous leukemia K562 as well as human gingival fibroblast (HGF) as normal cell line. Anti-proliferative activity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flowcytometry and annexin methods. Total phenolics and flavonoids were determined by Folin-Ciocalteu and aluminum chloride methods. Chloroform fraction had the lowest IC50 value at 72 h (0.1 μg/ml) in MCF-7 cells. Flowcytometry and annexin-V analysis indicated that the chloroform fraction induced necrosis in MCF-7 cells. In addition, the colorimetric methods showed that the methanolic fraction possessed the highest amount of total phenolics (33.03 ± 0.75 mg/g of dry powder) and flavonoids (10.5 ± 2.0 mg/g of dry powder). The collective data demonstrated that F. vaillantii chloroform fraction may contain effective compounds with chemo-therapeutic potential act through an apoptotic independent pathway. PMID:27168755

  13. [Synthesis and anti-proliferative activity of fluoroquinolone (rhodanine unsaturated ketone) amide derivatives].

    PubMed

    Gao, Liu-zhou; Xie, Yu-suo; Yan, Qiang; Wu, Shu-min; Ni, Li-li; Zhao, Hui; Huang, Wen-long; Hu, Guo-qiang

    2015-08-01

    To discover novel antitumor rhodanine unsaturated ketones, a series of fluoroquinolone (rhodanine α, β-unsaturated ketone) amine derivatives (5a-5r) were designed and synthesized with fluoroquinolone amide scaffold as a carrier. The structures of eighteen title compounds were characterized by elemental analysis, 1H NMR and MS. The in vitro anti-proliferative activity against Hep-3B, Capan-1 and HL60 cells was evaluated by MTT assay. The results showed that the title compounds not only had more significant anti-proliferative activity against three tested cancer cell lines than that of the parent ciprofloxacin 1, but also exhibited the highest activity against Capan-1 cells. The SAR revealed that some compounds carrying aromatic heterocyclic rings or phenyl attached to an electron-withdrawing carboxyl or sulfonamide substituent were comparable to or better than comparison doxorubicin against Capan-1 cells. As such, it suggests that fluoroquinolone (rhodanine α, β-unsaturated ketone) amines are promising leads for the development of novel antitumor fluoroquinolones or rhodanine analogues. PMID:26669001

  14. Apoptotic and anti-proliferative effects of all-trans retinoic acid

    SciTech Connect

    Zamora, Monica; Ortega, Juan Alberto; Alana, Lide; Vinas, Octavi; Mampel, Teresa . E-mail: tmampel@ub.edu

    2006-06-10

    We examined the apoptotic and anti-proliferative effects of all-trans retinoic acid (atRA) in HeLa cells. Our results demonstrated that HeLa cells were more sensitive to the anti-proliferative effects of atRA than to its apoptotic effects. Furthermore, we demonstrated that caspase inhibition attenuates cell death but does not alter the atRA-dependent reduction in cell proliferation, which suggests that atRA-induced apoptosis is independent of the arrest in cell proliferation. To check whether ANT proteins mediated these atRA effects, we transiently transfected cells with expression vectors encoding for individual ANT (adenine nucleotide translocase 1-3). Our results revealed that ANT1 and ANT3 over-expressing HeLa cells increased their atRA sensitivity. Thus, our results not only demonstrate the different functional activities of ANT isoforms, but also contribute to a better understanding of the properties of atRA as an anti-tumoral agent used in cancer therapy.

  15. Anti-proliferative activity of Fumaria vaillantii extracts on different cancer cell lines.

    PubMed

    Tabrizi, Fatemeh Haji Abbas; Irian, Saeed; Amanzadeh, Amir; Heidarnejad, Fatemeh; Gudarzi, Hoda; Salimi, Mona

    2016-01-01

    Plant-derived natural products are known to have cancer chemo-preventive and chemo-therapeutic properties. Plant extracts or their active constituents are used as folk medicine in traditional therapies by 80% of the world population. The aim of the present study was to determine the anti-proliferative potential of Fumaria vaillantii extracts on three different cancer cell lines including malignant melanoma SKMEL-3, human breast adenocarcinoma MCF-7 and human myelogenous leukemia K562 as well as human gingival fibroblast (HGF) as normal cell line. Anti-proliferative activity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flowcytometry and annexin methods. Total phenolics and flavonoids were determined by Folin-Ciocalteu and aluminum chloride methods. Chloroform fraction had the lowest IC50 value at 72 h (0.1 μg/ml) in MCF-7 cells. Flowcytometry and annexin-V analysis indicated that the chloroform fraction induced necrosis in MCF-7 cells. In addition, the colorimetric methods showed that the methanolic fraction possessed the highest amount of total phenolics (33.03 ± 0.75 mg/g of dry powder) and flavonoids (10.5 ± 2.0 mg/g of dry powder). The collective data demonstrated that F. vaillantii chloroform fraction may contain effective compounds with chemo-therapeutic potential act through an apoptotic independent pathway. PMID:27168755

  16. Anti-proliferative activities of sinigrin on carcinogen-induced hepatotoxicity in rats.

    PubMed

    Jie, Meng; Cheung, Wan Man; Yu, Vivian; Zhou, Yanling; Tong, Pak Ho; Ho, John W S

    2014-01-01

    Liver cancer is one of the leading causes of cancer death worldwide. A very high incidence of new liver cancer cases is diagnosed every year, and metastasis has been found to correlate to poor prognoses in humans. Better treatments for liver cancer are thus clearly needed. Sinigrin is one of the major ingredients present in Brassica nigra, which has been used in combination with other herbs for treatment of various diseases. The anti-proliferative activities of sinigrin were studied in a model of carcinogen-induced hepatotoxicity in rats. Rats were orally administered with sinigrin on a daily basis for three months before sacrifice. Sinigrin was found to significantly inhibit the proliferation of liver tumor cells; the number of surface tumors in the rat liver was dramatically reduced. Sinigrin induced apoptosis of liver cancer cells through up-regulation of p53 and down-regulation of Bcl-2 family members and caspases. Our findings indicated that the liver functions were gradually restored after treatment with sinigrin and that the agent did not cause liver toxicity. Cell cycle analysis indicated that sinigrin caused cell cycle arrest in G0/G1 phase. The results suggest that sinigrin exerts important anti-proliferative activities in carcinogen-induced hepatocarcinogenesis in rats, and highlight the potential of sinigrin as an anti-cancer agent for liver cancer. PMID:25329483

  17. Phytochemical profile of Rosmarinus officinalis and Salvia officinalis extracts and correlation to their antioxidant and anti-proliferative activity.

    PubMed

    Kontogianni, Vassiliki G; Tomic, Goran; Nikolic, Ivana; Nerantzaki, Alexandra A; Sayyad, Nisar; Stosic-Grujicic, Stanislava; Stojanovic, Ivana; Gerothanassis, Ioannis P; Tzakos, Andreas G

    2013-01-01

    The goal of this study was to monitor the anti-proliferative activity of Rosmarinus officinalis and Salvia officinalis extracts against cancer cells and to correlate this activity with their phytochemical profiles using liquid chromatography/diode array detection/electrospray ion trap tandem mass spectrometry (LC/DAD/ESI-MS(n)). For the quantitative estimation of triterpenic acids in the crude extracts an NMR based methodology was used and compared with the HPLC measurements, both applied for the first time, for the case of betulinic acid. Both extracts exerted cytotoxic activity through dose-dependent impairment of viability and mitochondrial activity of rat insulinoma m5F (RINm5F) cells. Decrease of RINm5F viability was mediated by nitric oxide (NO)-induced apoptosis. Importantly, these extracts potentiated NO and TNF-α release from macrophages therefore enhancing their cytocidal action. The rosemary extract developed more pronounced antioxidant, cytotoxic and immunomodifying activities, probably due to the presence of betulinic acid and a higher concentration of carnosic acid in its phytochemical profile.

  18. Anti-inflammatory and immunomodulatory properties of Carica papaya.

    PubMed

    Pandey, Saurabh; Cabot, Peter J; Shaw, P Nicholas; Hewavitharana, Amitha K

    2016-07-01

    Chronic inflammation is linked with the generation and progression of various diseases such as cancer, diabetes and atherosclerosis, and anti-inflammatory drugs therefore have the potential to assist in the treatment of these conditions. Carica papaya is a tropical plant that is traditionally used in the treatment of various ailments including inflammatory conditions. A literature search was conducted by using the keywords "papaya", "anti-inflammatory and inflammation" and "immunomodulation and immune" along with cross-referencing. Both in vitro and in vivo investigation studies were included. This is a review of all studies published since 2000 on the anti-inflammatory activity of papaya extracts and their effects on various immune-inflammatory mediators. Studies on the anti-inflammatory activities of recognized phytochemicals present in papaya are also included. Although in vitro and in vivo studies have shown that papaya extracts and papaya-associated phytochemicals possess anti-inflammatory and immunomodulatory properties, clinical studies are lacking.

  19. Anti-inflammatory and immunomodulatory properties of Carica papaya.

    PubMed

    Pandey, Saurabh; Cabot, Peter J; Shaw, P Nicholas; Hewavitharana, Amitha K

    2016-07-01

    Chronic inflammation is linked with the generation and progression of various diseases such as cancer, diabetes and atherosclerosis, and anti-inflammatory drugs therefore have the potential to assist in the treatment of these conditions. Carica papaya is a tropical plant that is traditionally used in the treatment of various ailments including inflammatory conditions. A literature search was conducted by using the keywords "papaya", "anti-inflammatory and inflammation" and "immunomodulation and immune" along with cross-referencing. Both in vitro and in vivo investigation studies were included. This is a review of all studies published since 2000 on the anti-inflammatory activity of papaya extracts and their effects on various immune-inflammatory mediators. Studies on the anti-inflammatory activities of recognized phytochemicals present in papaya are also included. Although in vitro and in vivo studies have shown that papaya extracts and papaya-associated phytochemicals possess anti-inflammatory and immunomodulatory properties, clinical studies are lacking. PMID:27416522

  20. Improvement of bioavailability and anti-inflammatory potential of curcumin in combination with emu oil.

    PubMed

    Jeengar, Manish Kumar; Shrivastava, Shweta; Nair, Kala; Singareddy, Sreenivasa Reddy; Putcha, Uday Kumar; Talluri, M V N Kumar; Naidu, V G M; Sistla, Ramakrishna

    2014-12-01

    The purpose of the present study is to evaluate the effect of emu oil on bioavailability of curcumin when co-administered and to evaluate the property that enhances the anti-inflammatory potential of curcumin. Oral bioavailability of curcumin in combination with emu oil was determined by measuring the plasma concentration of curcumin by HPLC. The anti-inflammatory potential was evaluated in carrageenan-induced paw edema model (acute model) and in Freund's complete adjuvant (FCA)-induced arthritis model (chronic model) in male SD rats. The anti-inflammatory potential of curcumin in combination with emu oil has been significantly increased in both acute and chronic inflammatory models as evident from inhibition of increase in paw volume, arthritic score, and expression of pro-inflammatory cytokines. The increased anti-inflammatory activity in combination therapy is due to enhanced bioavailability (5.2-fold compared to aqueous suspension) of curcumin by emu oil. Finally, it is concluded that the combination of emu oil with curcumin will be a promising approach for the treatment of arthritis. PMID:25028100

  1. Antidepressant augmentation with anti-inflammatory agents.

    PubMed

    Andrade, Chittaranjan

    2014-09-01

    Antidepressant augmentation strategies are commonly employed to treat depressed patients who do not respond to antidepressant monotherapy. Neuroinflammatory mechanisms have been implicated in depression, and nonsteroidal anti-inflammatory drugs (NSAIDs) have been found effective in animal models of depression both in monotherapy and when used to augment antidepressant drugs. However, results with NSAIDs have been mixed in human observational studies, with both better and worse depression outcomes reported. Four small (pooled N = 160) randomized controlled trials suggest that celecoxib (200-400 mg/d) augmentation of antidepressant medication improves 4-6 week outcomes in major depressive disorder. There are no data, however, to support the use of celecoxib or other NSAIDs in antidepressant-resistant depression. There are also concerns about adverse events associated with NSAID treatment, and about pharmacodynamic drug interactions between these drugs and serotonin reuptake inhibitors. A reasonable conclusion for the present is that NSAID augmentation of antidepressants is, at best, a tentative approach in nonrefractory major depression.

  2. Synthesis, characterization, in vitro anti-proliferative and hemolytic activity of hydroxyapatite

    NASA Astrophysics Data System (ADS)

    Palanivelu, R.; Ruban Kumar, A.

    2014-06-01

    Hydroxyapatite (Ca10(PO4)6(OH)2, HAP) nanoparticles are widely used in several biomedical applications due to its compositional similarities to bone mineral, excellent biocompatibility and bioactivity, osteoconductivity. In this present investigation, HAP nanoparticles synthesized by precipitation technique using calcium nitrate and di-ammonium phosphate. The crystalline nature and the functional group analysis are confirmed using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and Fourier transform Raman spectroscopy (FT-Raman) respectively. The morphological observations are ascertained from field emission electron scanning electron microscope (FE-SEM) and transmission electron microscope (TEM). In vitro anti-proliferative and hemolytic activities are carried out on the synthesized HAP samples and the studies reveals that HAP have mild activity against erythrocytes.

  3. Buformin exhibits anti-proliferative and anti-invasive effects in endometrial cancer cells

    PubMed Central

    Kilgore, Joshua; Jackson, Amanda L; Clark, Leslie H; Guo, Hui; Zhang, Lu; Jones, Hannah M; Gilliam, Timothy P; Gehrig, Paola A; Zhou, Chunxiao; Bae-Jump, Victoria L

    2016-01-01

    Objective: Biguanides are anti-diabetic drugs that are thought to have anti-tumorigenic effects. Most pre-clinical studies have focused on metformin for cancer treatment and prevention; however, buformin may be potentially more potent than metformin. Given this, our goal was to evaluate the effects of buformin on cell growth, adhesion and invasion in endometrial cancer cell lines. Methods: The ECC-1 and Ishikawa endometrial cancer cell lines were used. Cell proliferation was assessed by MTT assay. Apoptosis and cell cycle analysis was performed by FITC Annexin V assay and propidium iodide staining, respectively. Adhesion was analyzed using the laminin adhesion assay. Invasion was assessed using the transwell invasion assay. The effects of buformin on the AMPK/mTOR pathway were determined by Western immunoblotting. Results: Buformin and metformin inhibited cell proliferation in a dose-dependent manner in both endometrial cancer cell lines. IC50s were 1.4-1.6 mM for metformin and 8-150 μM for buformin. Buformin induced cell cycle G1 phase arrest in the ECC-1 cells and G2 phase arrest in the Ishikawa cells. For both ECC-1 and Ishikawa cells, treatment with buformin resulted in induction of apoptosis, reduction in adhesion and invasion, activation of AMPK and inhibition of phosphorylated-S6. Buformin potentiated the anti-proliferative effects of paclitaxel in both cell lines. Conclusion: Buformin has significant anti-proliferative and anti-metastatic effects in endometrial cancer cells through modulation of the AMPK/mTOR pathway. IC50 values were lower for buformin than metformin, suggesting that buformin may be more potent for endometrial cancer treatment and worthy of further investigation. PMID:27398153

  4. Anti-proliferative activity and protection against oxidative DNA damage by punicalagin isolated from pomegranate husk

    PubMed Central

    Aqil, Farrukh; Munagala, Radha; Vadhanam, Manicka V.; Kausar, Hina; Jeyabalan, Jeyaprakash; Schultz, David J.; Gupta, Ramesh C.

    2012-01-01

    Ellagitannins are the most abundant polyphenols in pomegranate (Punica granatum) husk and contribute greatly towards its biological properties. A pre-enriched pomegranate husk powder was extracted with water and then further purified by an Amberlite XAD-16 column. Punicalagin (PC) anomers were eluted using a gradient of methanol and water. Fractions eluted with 20% and 25% methanol yielded 1.08 g of light brown powder (purity > 97%) from a total of 40 g of extract. This fraction was identified as PC by HPLC-UV using reference compounds and confirmed by FTICR-MS analysis. PC (10–40 µM) was found to significantly inhibit oxidative DNA products, about 70% inhibition at 40 µM (p=0.0017), resulting from Cu2+-catalyzed redox cycling of 4-hydroxy-17β-estradiol as analyzed by 32P-postlabeling. Evidence of high antioxidant activity of PC was also obtained based on ORAC assay (1556±79 µmol of TE/g), as well as by 2,2′-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS)-, 2,2-diphenyl-1-picrylhydrazyl (DPPH)-, hydrogen peroxide (H2O2) scavenging and ferrous ion-chelating activities (IC50=1.1, 17.1, 24 and 45.4 µg/ml, respectively). Further, PC exhibited strong anti-proliferative activity against the human lung, breast and cervical cancer cell lines. Together, these data suggest that PC can be isolated in its purified form by simple column chromatography, inhibits oxidative DNA damage and possesses high anti-proliferative activity. PMID:23493479

  5. Anti-proliferative effects of qianliening capsules on prostatic hyperplasia in vitro and in vivo

    PubMed Central

    ZHONG, XIAOYONG; LIN, JIUMAO; ZHOU, JIANHENG; XU, WEI; HONG, ZHENFENG

    2015-01-01

    Previous studies by our group showed that Qianliening capsules (QC), a clinically proven effective traditional Chinese formulation that has long been used in the treatment of benign prostatic hyperplasia (BPH), is capable of inhibiting BPH in vivo and in vitro via the promotion of apoptosis, suppression of the EGFR/STAT3 signaling pathway and regulating the expression of sex hormones as well as their receptors. However, the mechanism of its anti-BPH activity has remained to be fully elucidated. The present study aimed to investigate the mechanism underlying the anti-proliferative effect of QC in vivo and in vitro. Castrated male Sprage-Dawley (SD) rats where subcutaneously injected with testosterone propionate and the WPMY-1 cell line was stimulated with basic fibroblast growth factor in order to generate BPH in vivo and in vitro separately, both of which were then subjected to QC treatment. Finasteride was used as a positive control drug for the in vivo study. In the present study, it was found that treatment with QC or finasteride significantly reduced the prostatic index (PI=prostate wet weight/body weight × 100) in a rat model of BPH (P<0.05). In addition, reverse transcription quantitative polymerase chain reaction (RT-PCR) and western blot analyses showed that QC or finasteride treatment significantly inhibited model construction-induced upregulation of expression of proliferating cell nuclear antigen, cyclin D1 and cyclin-dependent kinase 4 in prostatic tissues of rats with BPH (P<0.05). The in vitro study further proved that QC exhibited anti-proliferative properties via G1/S cell cycle arrest in the WPMY-1 cell line, as evidenced by colony formation, flow cytometric cell cycle, immunoblot and RT-PCR analyses. In conclusion, the present study demonstrated that inhibition of cell proliferation via G1/S cell cycle arrest may be one of the underlying mechanisms of the effect of QC on BPH. PMID:25825141

  6. The anti-proliferative and anti-angiogenic effect of the methanol extract from brittle star

    PubMed Central

    Baharara, Javad; Amini, Elaheh; Mousavi, Marzieh

    2015-01-01

    Background: Anti-angiogenic therapy is a crucial step in cancer treatment. The discovery of new anti-angiogenic compounds from marine organisms has become an attractive concept in anti-cancer therapy. Because little data correlated to the pro- and anti-angiogenic efficacies of Ophiuroidea, which include brittle star, the current study was designed to explore the anti-angiogenic potential of brittle star methanol extract in vitro and in vivo. Methods: The anti-proliferative effect of brittle star extract on A2780cp cells was examined by MTT assays, and transcriptional expression of VEGF and b-FGF was evaluated by RT-PCR. In an in vivo model, 40 fertilized Ross eggs were divided into control and three experimental groups. The experimental groups were incubated with brittle star extract at concentrations of 25, 50 and 100 µg/ml, and photographed by photo-stereomicroscopy. Ultimately, numbers and lengths of vessels were measured by Image J software. Data were analyzed with SPSS software (p<0.05). Results: Results illustrated that the brittle star extract exerted a dose- and time-dependent anti-proliferative effect on A2780cp cancer cells. In addition, VEGF and b-FGF expression decreased with brittle star methanol extract treatment. Macroscopic evaluations revealed significant changes in the second and third experimental group compared to controls (p<0.05). Conclusion: These finding revealed the anti-angiogenic effects of brittle star methanol extract in vitro and in vivo confer novel insight into the application of natural marine products in angiogenesis-related pathologies. PMID:26989740

  7. Anti-inflammatory activity of Bacopa monniera in rodents.

    PubMed

    Channa, Shabana; Dar, Ahsana; Anjum, Shazia; Yaqoob, Muhammad; Atta-Ur-Rahman

    2006-03-01

    The ethanol extract of Bacopa monniera (Scrophulariaceae) exhibited marked anti-inflammatory activity against carrageenan-induced paw edema in mice and rats, an acute inflammatory model. To assess the possible mechanism of anti-inflammatory action against carrageenan, the ethanol extract was treated with chemical mediators (histamine, serotonin, bradykinin, prostaglandin E(2) and arachidonic acid)-induced edema in rats. The extract selectively inhibited prostaglandin E(2)-induced inflammation. Thus, it may be inferred that B. monniera possesses significant anti-inflammatory activity that may well be relevant for its effectiveness in the healing of various inflammatory conditions in traditional medicine.

  8. The anti-inflammatory action of nepitrin, a flavonoid.

    PubMed

    Agarwal, O P

    1982-07-01

    The anti-inflammatory efficacy of nepitrin (5,3',4'-trihydroxy-6-methoxy flavone), a flavonoid, was investigated in both acute and chronic models of inflammation in rats. Nepitrin was found to possess significant anti-inflammatory activity in the exudative and proliferative phases of inflammation. This action of nepitrin could be due to its anti-bradykinin and anti-angiotensin action. Nepitrin also possessed anti-pyretic and weak analgesic activity. The study reveals that nepitrin may be useful as an anti-inflammatory and anti-arthritic agent. PMID:6982607

  9. Immuno-modulation and anti-inflammatory benefits of antibiotics: the example of tilmicosin.

    PubMed

    Buret, André G

    2010-01-01

    Exaggerated immune responses, such as those implicated in severe inflammatory reactions, are costly to the metabolism. Inflammation and pro-inflammatory mediators negatively affect production in the food animal industry by reducing growth, feed intake, reproduction, milk production, and metabolic health. An ever-increasing number of findings have established that antibiotics, macrolides in particular, may generate anti-inflammatory effects, including the modulation of pro-inflammatory cytokines and the alteration of neutrophil function. The effects are time- and dose-dependent, and the mechanisms responsible for these phenomena remain incompletely understood. Recent studies, mostly using the veterinary macrolide tilmicosin, may have shed new light on the mode of action of some macrolides and their anti-inflammatory properties. Indeed, research findings demonstrate that this compound, amongst others, induces neutrophil apoptosis, which in turn provides anti-inflammatory benefits. Studies using tilmicosin model systems in vitro and in vivo demonstrate that this antibiotic has potent immunomodulatory effects that may explain why at least parts of its clinical benefits are independent of anti-microbial effects. More research is needed, using this antibiotic and others that may have similar properties, to clarify the biological mechanisms responsible for antibiotic-induced neutrophil apoptosis, and how this, in turn, may provide enhanced clinical benefits. Such studies may help establish a rational basis for the development of novel, efficacious, anti-microbial compounds that generate anti-inflammatory properties in addition to their antibacterial effects.

  10. Anti-inflammatory therapies for cardiovascular disease

    PubMed Central

    Ridker, Paul M.; Lüscher, Thomas F.

    2014-01-01

    Atherothrombosis is no longer considered solely a disorder of lipoprotein accumulation in the arterial wall. Rather, the initiation and progression of atherosclerotic lesions is currently understood to have major inflammatory influences that encompass components of both the innate and acquired immune systems. Promising clinical data for ‘upstream’ biomarkers of inflammation such as interleukin-6 (IL-6) as well as ‘downstream’ biomarkers such as C-reactive protein, observations regarding cholesterol crystals as an activator of the IL-1β generating inflammasome, and recent Mendelian randomization data for the IL-6 receptor support the hypothesis that inflammatory mediators of atherosclerosis may converge on the central IL-1, tumour necrosis factor (TNF-α), IL-6 signalling pathway. On this basis, emerging anti-inflammatory approaches to vascular protection can be categorized into two broad groups, those that target the central IL-6 inflammatory signalling pathway and those that do not. Large-scale Phase III trials are now underway with agents that lead to marked reductions in IL-6 and C-reactive protein (such as canakinumab and methotrexate) as well as with agents that impact on diverse non-IL-6-dependent pathways (such as varespladib and darapladib). Both approaches have the potential to benefit patients and reduce vascular events. However, care should be taken when interpreting these trials as outcomes for agents that target IL-6 signalling are unlikely to be informative for therapies that target alternative pathways, and vice versa. As the inflammatory system is redundant, compensatory, and crucial for survival, evaluation of risks as well as benefits must drive the development of agents in this class. PMID:24864079

  11. Cannabinoids as novel anti-inflammatory drugs

    PubMed Central

    Nagarkatti, Prakash; Pandey, Rupal; Rieder, Sadiye Amcaoglu; Hegde, Venkatesh L; Nagarkatti, Mitzi

    2009-01-01

    Cannabinoids are a group of compounds that mediate their effects through cannabinoid receptors. The discovery of Δ9-tetrahydrocannabinol (THC) as the major psychoactive principle in marijuana, as well as the identification of cannabinoid receptors and their endogenous ligands, has led to a significant growth in research aimed at understanding the physiological functions of cannabinoids. Cannabinoid receptors include CB1, which is predominantly expressed in the brain, and CB2, which is primarily found on the cells of the immune system. The fact that both CB1 and CB2 receptors have been found on immune cells suggests that cannabinoids play an important role in the regulation of the immune system. Recent studies demonstrated that administration of THC into mice triggered marked apoptosis in T cells and dendritic cells, resulting in immunosuppression. In addition, several studies showed that cannabinoids downregulate cytokine and chemokine production and, in some models, upregulate T-regulatory cells (Tregs) as a mechanism to suppress inflammatory responses. The endocannabinoid system is also involved in immunoregulation. For example, administration of endocannabinoids or use of inhibitors of enzymes that break down the endocannabinoids, led to immunosuppression and recovery from immune-mediated injury to organs such as the liver. Manipulation of endocannabinoids and/or use of exogenous cannabinoids in vivo can constitute a potent treatment modality against inflammatory disorders. This review will focus on the potential use of cannabinoids as a new class of anti-inflammatory agents against a number of inflammatory and autoimmune diseases that are primarily triggered by activated T cells or other cellular immune components. PMID:20191092

  12. Cell-based microfluidic device for screening anti-proliferative activity of drugs in vascular smooth muscle cells.

    PubMed

    Rodriguez-Rodriguez, R; Muñoz-Berbel, X; Demming, S; Büttgenbach, S; Herrera, M D; Llobera, A

    2012-12-01

    This paper presents a microfluidic device consisting of five parallel microchambers with integrated readout-grid for the screening of anti-proliferative activity of drugs in vascular smooth muscle cells (VSMC). A two-level SU-8 master was fabricated and replicated with poly(dimethylsiloxane), PDMS, using standard soft-lithographic methods. The relative small height (4-10 μm) of the integrated grid allowed the identification of single-cells or cell groups and the monitoring of their motility, morphology and size with time, without disturbing their proliferation pattern. This is of particular interest when considering VSMC which, apart of being crucial in the atherosclerotic process, do not proliferate in a single layer but in a non-homogenous hill and valley phenotype. The performance of the microfluidic device has been validated by comparison with conventional culturing methods, proving that the cell proliferation remains unaffected by the microchamber structure (with the integrated grid) and the experimental conditions. Finally, the microfluidic device was also used to evaluate the anti-proliferative activity of curcumin and colchicine in VSMC. With this cellular type, the anti-proliferative activity of curcumin (IC(50) =35 ± 5 μM) was found to be much lower than colchicine (IC(50) =3.2 ± 1.2 μM). These results demonstrate the good performance of the microfluidic device in the evaluation of the anti-proliferative activity (or cytotoxicity) of drugs.

  13. Anti-Proliferative Activities and Apoptosis Induction by Triterpenes Derived from Eriobotrya japonica in Human Leukemia Cell Lines

    PubMed Central

    Uto, Takuhiro; Sakamoto, Ayana; Tung, Nguyen Huu; Fujiki, Tsukasa; Kishihara, Kenji; Oiso, Shigeru; Kariyazono, Hiroko; Morinaga, Osamu; Shoyama, Yukihiro

    2013-01-01

    Eriobotrya japonica leaf is a traditional herbal medicine that contains numerous triterpenes, which have various pharmacological properties. In this study, we investigated the anti-proliferative activity of four triterpenes derived from E. japonica, including corosolic acid (CA), ursolic acid (UA), maslinic acid (MA) and oleanolic acid (OA), in human leukemia cell lines. CA showed the strongest anti-proliferative activity in all of the leukemia cell lines tested, but not in normal human skin fibroblast cell lines. To determine the mechanism underlying the anti-proliferative effect of CA, we examined the effect of CA on molecular events known as apoptosis induction. CA induced chromatin condensation, DNA fragmentation, sub-G1 phase DNA, activation of caspase-3, -8 and -9 and the cleavage of PARP in HL-60. CA also activated Bid and Bax, leading to the loss of mitochondrial membrane potential (Δψm) and cytochrome c release into the cytosol, whereas Bcl-2 and Bcl-xL were unaffected by CA. These results suggest that CA has an anti-proliferative effect on leukemia cells via the induction of apoptosis mediated by mitochondrial dysfunction and caspase activation. CA may be a potential chemotherapeutic agent for the treatment of human leukemia. PMID:23429195

  14. Anti-Proliferative Activities and Apoptosis Induction by Triterpenes Derived from Eriobotrya japonica in Human Leukemia Cell Lines.

    PubMed

    Uto, Takuhiro; Sakamoto, Ayana; Tung, Nguyen Huu; Fujiki, Tsukasa; Kishihara, Kenji; Oiso, Shigeru; Kariyazono, Hiroko; Morinaga, Osamu; Shoyama, Yukihiro

    2013-02-18

    Eriobotrya japonica leaf is a traditional herbal medicine that contains numerous triterpenes, which have various pharmacological properties. In this study, we investigated the anti-proliferative activity of four triterpenes derived from E. japonica, including corosolic acid (CA), ursolic acid (UA), maslinic acid (MA) and oleanolic acid (OA), in human leukemia cell lines. CA showed the strongest anti-proliferative activity in all of the leukemia cell lines tested, but not in normal human skin fibroblast cell lines. To determine the mechanism underlying the anti-proliferative effect of CA, we examined the effect of CA on molecular events known as apoptosis induction. CA induced chromatin condensation, DNA fragmentation, sub-G(1) phase DNA, activation of caspase-3, -8 and -9 and the cleavage of PARP in HL-60. CA also activated Bid and Bax, leading to the loss of mitochondrial membrane potential (∆ψ(m)) and cytochrome c release into the cytosol, whereas Bcl-2 and Bcl-xL were unaffected by CA. These results suggest that CA has an anti-proliferative effect on leukemia cells via the induction of apoptosis mediated by mitochondrial dysfunction and caspase activation. CA may be a potential chemotherapeutic agent for the treatment of human leukemia.

  15. Anti-inflammatory properties of bioactive titanium metals.

    PubMed

    Yang, Bangcheng; Gan, Lu; Qu, Yang; Yue, Chongxia

    2010-09-01

    Anti-inflammatory properties of bioactive titanium metals prepared by anodic oxidation (AO-Ti) and alkali-heat (AH-Ti) treatments were studied by bacterial adhesion test and myeloperoxidase (MPO) activity assay methods. The bioactivities of the metals were also evaluated by apatite formation ability and osteoblasts culture experiments. Both metals could induce apatite formation and support osteoblasts proliferation. At the condition with normal incandescent light shine, both bioactive titanium metals had antibacterial adhesion properties compared with the titanium metal without treatment. The MPO activity assay proved that they both showed anti-inflammatory properties in vivo. The bioactive AO-Ti had better anti-inflammatory properties than the AH-Ti. It indicated that it is possible to optimize the anti-inflammatory properties of the bioactive titanium metals by different preparation methods.

  16. Biochemical pharmacology of biflavonoids: implications for anti-inflammatory action.

    PubMed

    Kim, Hyun Pyo; Park, Haeil; Son, Kun Ho; Chang, Hyeun Wook; Kang, Sam Sik

    2008-03-01

    Biflavonoids belong to a subclass of the plant flavonoid family. Distribution of biflavonoids in the plant kingdom is limited to several species. Previously, some pharmacological activities of biflavonoids were described such as inhibition of histamine release from mast cells and inhibition of lymphocyte proliferation, suggesting the anti-inflammatory/antiallergic potential of the biflavonoids. Furthermore, several natural biflavonoids including ochnaflavone and ginkgetin inhibit phospholipase A2. Most importantly, certain biflavonoids exhibit anti-inflammatory activity through the regulation of proinflammatory gene expression in vitro and in vivo. Recently, several synthetic approaches yielded new biflavonoid molecules with anti-inflammatory potential. These molecules also exhibit phospholipase A2 and cyclooxygenase-2 inhibitory activity. Although the bioavailability needs be improved, certain biflavonoids may have potential as new anti-inflammatory agents. This is the first review of biflavonoid pharmacology to date.

  17. Anti-inflammatory therapy in sports injury. The role of nonsteroidal drugs and corticosteroid injection.

    PubMed

    Leadbetter, W B

    1995-04-01

    Strong statements regarding the efficacy of anti-inflammatory medication are based primarily on experience with rheumatic disease. Such experience, over 32 years, involving more than 400,000 injections in more than 12,000 patients, has led Hollander and associates to conclude that "no other form of treatment for arthritis has given such consistent local symptomatic relief in so many for so long with so few harmful effects." Such endorsement has not been clearly transferrable to sports medicine experience. Anti-inflammatory medications can unquestionably affect excessive inflammation. Whether this tissue effect is significant with regard to enhancing sports performance has been difficult to prove. To quote Oriole baseball pitcher Jim Palmer, "cortisone is a miracle drug ... for a week!" Perhaps this is because in rheumatologic disease, inflammation is the problem, whereas in sports injury, performance recovery depends on restoration of both the injured tissue and its kinetic environment. The tendency to place an inflammatory label (i.e., "itis") on sports-induced pain has promoted the value of anti-inflammatory treatment while risking a de-emphasis of the role of physical rehabilitation and even well-timed surgical repair. If pain and signs of inflammation are persistent, repeated efforts to turn off the body's alarm is not a substitute for finding the cause of the fire. Indeed, to remove the "fire alarm" of pain from the onset of an injury can clearly place the athlete in great jeopardy with respect to tissue overload and failure. Perhaps the greatest criticism that can be raised regarding anti-inflammatory treatment as a sole solution in sports injury is that it tends, in its worst application, to be too passive and dependent a modality and does not challenge the athlete's sense of responsibility to properly train, condition, and develop correct technique. Thus, anti-inflammatory therapy may succeed only if the patient has been instilled with the proper

  18. Synthesis and anti-inflammatory activity of chalcone derivatives.

    PubMed

    Herencia, F; Ferrándiz, M L; Ubeda, A; Domínguez, J N; Charris, J E; Lobo, G M; Alcaraz, M J

    1998-05-19

    Chalcones and their derivatives were synthesized and evaluated for their anti-inflammatory activity. In vitro, chalcones 2, 4, 8, 10 and 13 inhibited degranulation and 5-lipoxygenase in human neutrophils, whereas 11 behaved as scavenger of superoxide. Only four compounds (4-7) inhibited cyclo-oxygenase-2 activity. The majority of these samples showed anti-inflammatory effects in the mouse air pouch model.

  19. Synthesis and anti-inflammatory activity of aromatic glucosinolates.

    PubMed

    Vo, Quan V; Trenerry, Craige; Rochfort, Simone; Wadeson, Jenny; Leyton, Carolina; Hughes, Andrew B

    2013-10-01

    Aromatic GLs are important members of the glucosinolate family of compounds because of their potential biological activity and medicinal properties. This study has shown success in the high yielding synthesis of some important aromatic GLs as well as the results of testing for anti-inflammatory properties of the synthetic GLs. 3,4-Dimethoxyphenylglucosinolate was found to be the most active anti-inflammatory of the seven glucosinolates assayed. PMID:23978357

  20. Hypoglycemic agents and potential anti-inflammatory activity

    PubMed Central

    Kothari, Vishal; Galdo, John A; Mathews, Suresh T

    2016-01-01

    Current literature shows an association of diabetes and secondary complications with chronic inflammation. Evidence of these immunological changes include altered levels of cytokines and chemokines, changes in the numbers and activation states of various leukocyte populations, apoptosis, and fibrosis during diabetes. Therefore, treatment of diabetes and its complications may include pharmacological strategies to reduce inflammation. Apart from anti-inflammatory drugs, various hypoglycemic agents have also been found to reduce inflammation that could contribute to improved outcomes. Extensive studies have been carried out with thiazolidinediones (peroxisome proliferator-activated receptor-γ agonist), dipeptidyl peptidase-4 inhibitors, and metformin (AMP-activated protein kinase activator) with each of these classes of compounds showing moderate-to-strong anti-inflammatory action. Sulfonylureas and alpha glucosidase inhibitors appeared to exert modest effects, while the injectable agents, insulin and glucagon-like peptide-1 receptor agonists, may improve secondary complications due to their anti-inflammatory potential. Currently, there is a lack of clinical data on anti-inflammatory effects of sodium–glucose cotransporter type 2 inhibitors. Nevertheless, for all these glucose-lowering agents, it is essential to distinguish between anti-inflammatory effects resulting from better glucose control and effects related to intrinsic anti-inflammatory actions of the pharmacological class of compounds. PMID:27114714

  1. [Anti-inflammatory effects of methylprednisolone aceponate in animals].

    PubMed

    Ikoma, Y; Yamashita, M; Kamitani, K; Nakagawa, H

    1991-11-01

    In the case of dermal application of the drugs to croton oil-induced ear edema in rats and picryl chloride-induced delayed type hypersensitivity in mice, the anti-inflammatory effect of methylprednisolone aceponate (MPA) was slightly weaker than those of clobetasol 17-propionate and diflucortolone 21-valerate, but stronger than those of hydrocortisone 17-butyrate and hydrocortisone 17-butyrate 21-propionate. Betamethasone 17-valerate applied dermally was less and more effective than MPA to ear edema in rats and delayed type hypersensitivity in mice, respectively. The anti-inflammatory effect of MPA was weaker in subcutaneous administration than in topical application to the two inflammatory models. It was suggested that MPA has strong anti-inflammatory effects and weak systemic effects by topical application. Methylprednisolone 17-propionate (MP-17P) and methylprednisolone (MP), unesterified in only the C-21 position and in both the C-17 and 21 positions of MPA, respectively, showed weaker anti-inflammatory activities than MPA by topical application to croton oil-induced ear edema. The ratio of the anti-inflammatory effects by topical application to subcutaneous administration of MPA was higher than those of MP-17P and MP. The excellent characteristics of MPA as a dermal anti-inflammatory drug are suggested to be derived from di-esterification of MP, which has a weak activity intrinsically. PMID:1813371

  2. Nonsteroidal Anti-inflammatory-Organometallic Anticancer Compounds.

    PubMed

    Păunescu, Emilia; McArthur, Sarah; Soudani, Mylène; Scopelliti, Rosario; Dyson, Paul J

    2016-02-15

    Compounds that combine metal-based drugs with covalently linked targeted organic agents have been shown, in some instances, to exhibit superior anticancer properties compared to the individual counterparts. Within this framework, we prepared a series of organometallic ruthenium(II)- and osmium(II)-p-cymene complexes modified with the nonsteroidal anti-inflammatory drugs (NSAIDs) indomethacin and diclofenac. The NSAIDs are attached to the organometallic moieties via monodentate (pyridine/phosphine) or bidentate (bipyridine) ligands, affording piano-stool Ru(II) and Os(II) arene complexes of general formula [M(η(6)-p-cymene)Cl2(N)], where N is a pyridine-based ligand, {2-(2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetoxy)ethyl-3-(pyridin-3-yl)propanoate} or {2-(2-(2-((2,6-dichlorophenyl)amino)phenyl)acetoxy)ethyl-3-(pyridin-3-yl)propanoate}, [M(η(6)-p-cymene)Cl2(P)], where P is a phosphine ligand, {2-(2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetoxy)ethyl-4-(diphenylphosphanyl)benzoate} or {2-(2-(2-((2,6-dichlorophenyl)amino)phenyl)acetoxy)ethyl-4-(diphenylphosphanyl)benzoate, and [M(η(6)-p-cymene)Cl(N,N')][Cl], where N,N' is a bipyridine-based ligand, (4'-methyl-[2,2'-bipyridin]-4-yl)methyl-2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetate), (4'-methyl-[2,2'-bipyridin]-4-yl)methyl-2-(2-((2,6-dichlorophenyl)amino)phenyl)acetate), (bis(2-(2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetoxy)ethyl)[2,2'-bipyridine]-5,5'-dicarboxylate), or (bis(2-(2-(2-((2,6-dichlorophenyl)amino)phenyl)acetoxy)ethyl)[2,2'-bipyridine]-5,5'-dicarboxylate). The antiproliferative properties of the complexes were assessed in human ovarian cancer cells (A2780 and A2780cisR, the latter being resistant to cisplatin) and nontumorigenic human embryonic kidney (HEK-293) cells. Some of the complexes are considerably more cytotoxic than the original drugs and also display significant cancer cell selectivity. PMID:26824462

  3. Consumption of high-dose vitamin C (1250 mg per day) enhances functional and structural properties of serum lipoprotein to improve anti-oxidant, anti-atherosclerotic, and anti-aging effects via regulation of anti-inflammatory microRNA.

    PubMed

    Kim, Seong-Min; Lim, So-Mang; Yoo, Jeong-Ah; Woo, Moon-Jea; Cho, Kyung-Hyun

    2015-11-01

    Background Although the health effects of vitamin C are well known, its physiological effect on serum lipoproteins and microRNA still remain to be investigated, especially daily consumption of a high dosage. Objectives To investigate the physiological effect of vitamin C on serum lipoprotein metabolism in terms of its anti-oxidant and anti-glycation activities, and gene expression via microRNA regulation. Methods We analyzed blood parameters and lipoprotein parameters in young subjects (n = 46, 22 ± 2 years old) including smokers who consumed a high dose of vitamin C (1250 mg) daily for 8 weeks. Results Antioxidant activity of serum was enhanced with the elevation of Vit C content in plasma during 8 weeks consumption. In the LDL fraction, the apo-B48 band disappeared at 8 weeks post-consumption in all subjects. In the HDL fraction, apoA-I expression was enhanced by 20% at 8 weeks, especially in male smokers. In the lipoprotein fraction, all subjects showed significantly reduced contents of advanced glycated end products and reactive oxygen species (ROS). Triglyceride (TG) contents in each LDL and HDL fraction were significantly reduced in all groups following the Vit C consumption, suggesting that the lipoprotein was changed to be more anti-inflammatory and atherogenic properties. Phagocytosis of LDL, which was purified from each individual, into macrophages was significantly reduced at 8-weeks post-consumption of vitamin C. Anti-inflammatory and anti-senescence effects of HDL from all subjects were enhanced after the 8-weeks consumption. The expression level of microRNA 155 in HDL3 was reduced by 49% and 75% in non-smokers and smokers, respectively. Conclusion The daily consumption of a high dose of vitamin C for 8 weeks resulted in enhanced anti-senescence and anti-atherosclerotic effects via an improvement of lipoprotein parameters and microRNA expression through anti-oxidation and anti-glycation, especially in smokers.

  4. White kidney bean lectin exerts anti-proliferative and apoptotic effects on cancer cells.

    PubMed

    Chan, Yau Sang; Xia, Lixin; Ng, Tzi Bun

    2016-04-01

    A 60-kDa glucosamine binding lectin, white kidney bean lectin (WKBL), was purified from Phaseolus vulgaris cv. white kidney beans, by application of anion exchange chromatography on Q-Sepharose, affinity chromatography on Affi-gel blue gel, and FPLC-size exclusion on Superdex 75. The anti-proliferative activity of WKBL on HONE1 cells and HepG2 cells was stronger than the activity on MCF7 cells and WRL68 cells (IC50 values for a 48-h treatment with WKBL on HONE1 cells: 18.8 μM; HepG2 cells: 19.7 μM; MCF7 cells: 26.9 μM; and WRL68 cells: >80 μM). The activity could be reduced by addition of glucosamine, which occupies the binding sites of WKBL, indicating that carbohydrate binding is crucial for the activity. Annexin V-FITC and PI staining, JC-1 staining and Hoechst 33342 staining revealed that apoptosis was induced on WKBL-treated HONE1 cells and HepG2 cells, but not as obviously on MCF7 cells. Cell cycle analysis also showed a slight cell cycle arrest on HONE1 cells after WKBL treatment. Western blotting suggested that WKBL induced apoptosis of HONE1 cells occurred through the extrinsic apoptosis pathway, with detection of increased level of active caspase 3, 8 and 9.

  5. Two new diterpene derivatives from Euphorbia lunulata Bge and their anti-proliferative activities.

    PubMed

    Liu, Chao; Liao, Zhi-xin; Liu, Shi-jun; Qu, Yan-bo; Wang, Heng-shan

    2014-07-01

    A new ent-abietane-type diterpene lactone (1) and a new jatrophane-type diterpenoid (2), together with twelve known compounds including three diterpenes (3-5), five triterpenes (6-10) and four sterides (11-14) were isolated from the ethanol extract of the whole plant of Euphorbia lunulata Bge. The structure of compounds 1 and 2 was elucidated on the basis of 1D and 2D NMR spectra and the HR-ESI-MS data. The structure of compound 2 was further analyzed by an X-ray crystallographic study. The in vitro anti-proliferative activities against MCF-7 and NCI-H460 cell lines for compounds 1-5 (diterpene) were evaluated. The results showed marked activity for compound 1 against the two cell lines with the IC50 values 19.5 (NCI-H460) and 18.6 (MCF-7) μM, while for cis-platinum (a positive cytotoxic control agent) 29.7 (NCI-H460) and 27.7 (MCF-7) μM. Compounds 2-5 exhibited moderate cytotoxic activities for the two cell lines with the IC50 values ranging from 32.1 to 58.2 μM.

  6. White kidney bean lectin exerts anti-proliferative and apoptotic effects on cancer cells.

    PubMed

    Chan, Yau Sang; Xia, Lixin; Ng, Tzi Bun

    2016-04-01

    A 60-kDa glucosamine binding lectin, white kidney bean lectin (WKBL), was purified from Phaseolus vulgaris cv. white kidney beans, by application of anion exchange chromatography on Q-Sepharose, affinity chromatography on Affi-gel blue gel, and FPLC-size exclusion on Superdex 75. The anti-proliferative activity of WKBL on HONE1 cells and HepG2 cells was stronger than the activity on MCF7 cells and WRL68 cells (IC50 values for a 48-h treatment with WKBL on HONE1 cells: 18.8 μM; HepG2 cells: 19.7 μM; MCF7 cells: 26.9 μM; and WRL68 cells: >80 μM). The activity could be reduced by addition of glucosamine, which occupies the binding sites of WKBL, indicating that carbohydrate binding is crucial for the activity. Annexin V-FITC and PI staining, JC-1 staining and Hoechst 33342 staining revealed that apoptosis was induced on WKBL-treated HONE1 cells and HepG2 cells, but not as obviously on MCF7 cells. Cell cycle analysis also showed a slight cell cycle arrest on HONE1 cells after WKBL treatment. Western blotting suggested that WKBL induced apoptosis of HONE1 cells occurred through the extrinsic apoptosis pathway, with detection of increased level of active caspase 3, 8 and 9. PMID:26769089

  7. Anti-proliferative effect of Melissa officinalis on human colon cancer cell line.

    PubMed

    Encalada, Manuel Alejandro; Hoyos, Kelly Melissa; Rehecho, Sheyla; Berasategi, Izaskun; de Ciriano, Mikel García-Íñiguez; Ansorena, Diana; Astiasarán, Iciar; Navarro-Blasco, Iñigo; Cavero, Rita Yolanda; Calvo, María Isabel

    2011-11-01

    Melissa officinalis L. (Lamiaceae) is consumed as a traditional herbal tea in the Mediterranean region. The cytotoxic effect of the 50% ethanolic and aqueous extract, determined by the MTT and NR assays, was evaluated in vitro on Human Colon Cancer Cell Line (HCT-116), using Triton 10% as positive control. The 50% ethanolic extract showed significant differences after 72 h of treatment, reducing cell proliferation to values close to 40%, even the lowest dose tested (5 μg/ml). In the MTT assay, the same extract caused the lowest cell viability with 13% at a concentration of 1,000 μg/ml after 72 h of treatment, being a value lower than Triton 10%. The antioxidant activity was also confirmed evaluating the capacity of the extracts to scavenge ABTS and DPPH radicals, and IC(50) values were highly correlated with the total phenolic and flavonoid content. Bioassay guided fractionation led to the isolation of an anti-proliferative compound, rosmarinic acid. Its structural elucidation was performed by HPLC/DAD/ESI/MS analysis. High dose of rosmarinic acid (1,000 μg/ml) was clearly cytotoxic against HCT-116 cells, with a significant decrease in cell number since the earliest time point (24 h).

  8. Antioxidant, antimicrobial and anti-proliferative activities of Solanum tuberosum L. var. Vitelotte.

    PubMed

    Bontempo, Paola; Carafa, Vincenzo; Grassi, Roberto; Basile, Adriana; Tenore, Gian Carlo; Formisano, Carmen; Rigano, Daniela; Altucci, Lucia

    2013-05-01

    Solanum tuberosum L. var. Vitelotte is a potato variety widely used for human consumption. The pigments responsible for its attractive color belong to the class of anthocyanins. The objectives of this study were to characterize and measure the concentration of anthocyanins in pigmented potatoes and to evaluate their antioxidant and antimicrobial activities and their anti-proliferative effects in solid and hematological cancer cell lines. Anthocyanins exert anti-bacterial activity against different bacterial strains and a slight activity against three fungal strains. The Gram-positive bacterium Staphylococcus aureus and the fungus Rhyzoctonia solani were the most affected microorganisms. Antioxidant activities were evaluated by DPPH and FRAP methods; the extract showed a higher reducing capability than anti-radical activity. Moreover, we found that in different cancer cell models the anthocyanins cause inhibition of proliferation and apoptosis in a dose dependent manner. These biological activities are likely due to the high content of malvidin 3-O-p-coumaroyl-rutinoside-5-O-glucoside and petunidin 3-O-p-coumaroyl-rutinoside-5-O-glucoside. PMID:23313609

  9. Chitin and chitosan from the Norway lobster by-products: Antimicrobial and anti-proliferative activities.

    PubMed

    Sayari, Nadhem; Sila, Assaâd; Abdelmalek, Baha Eddine; Abdallah, Rihab Ben; Ellouz-Chaabouni, Semia; Bougatef, Ali; Balti, Rafik

    2016-06-01

    Chitin was recovered through enzymatic deproteinization of the Norway lobster (Nephrops norvegicus) processing by-products. The obtained chitin was characterized and converted into chitosan by N-deacetylation, the acid-soluble form of chitin. Chitosan samples were then characterized by Fourier transform infrared spectroscopy (FTIR) and 13 Cross polarization magic angle spinning nuclear magnetic resonance (CP/MAS)-NMR spectroscopy. The antimicrobial activity and anti-proliferative capacity of chitosan were evaluated. Antimicrobial activity assays indicated that prepared chitosan exhibited marked inhibitory activity against the bacterial and fungal strains tested. Further, cytotoxic effects of chitosan samples on human colon carcinoma cells HCT116 was evaluated using the MTT assay. Chitosan showed the antiproliferative capacity against the colon-cancer-cell HCT116 in a dose dependent manner with IC50 of 4.6mg/ml. Indeed, HCT116 cell proliferation was significantly inhibited (p<0.05) between 13.5 and 67.5% at 0.5-6mg/mL of chitosan after 24h of cell treatment. The chitosan showed high antitumor activity which seemed to be dependent on its characteristics such as acetylation degree.

  10. Chronic Renal Transplant Rejection and Possible Anti-Proliferative Drug Targets

    PubMed Central

    Usman, Muhammad

    2015-01-01

    The global prevalence of renal transplants is increasing with time, and renal transplantation is the only definite treatment for end-stage renal disease. We have limited the acute and late acute rejection of kidney allografts, but the long-term survival of renal tissues still remains a difficult and unanswered question as most of the renal transplants undergo failure within a decade of their transplantation. Among various histopathological changes that signify chronic allograft nephropathy (CAN), tubular atrophy, fibrous thickening of the arteries, fibrosis of the kidney interstitium, and glomerulosclerosis are the most important. Moreover, these structural changes are followed by a decline in the kidney function as well. The underlying mechanism that triggers the long-term rejection of renal transplants involves both humoral and cell-mediated immunity. T cells, with their related cytokines, cause tissue damage. In addition, CD 20+ B cells and their antibodies play an important role in the long-term graft rejection. Other risk factors that predispose a recipient to long-term graft rejection include HLA-mismatching, acute episodes of graft rejection, mismatch in donor-recipient age, and smoking. The purpose of this review article is the analyze current literature and find different anti-proliferative agents that can suppress the immune system and can thus contribute to the long-term survival of renal transplants. The findings of this review paper can be helpful in understanding the long-term survival of renal transplants and various ways to improve it. PMID:26677426

  11. Euphorbia mauritanica and Kedrostis hirtella extracts can induce anti-proliferative activities in lung cancer cells.

    PubMed

    Thafeni, Makhosazana A; Sayed, Yasien; Motadi, Lesetja R

    2012-12-01

    Cancer is a public health problem in the world accounting for most of the deaths. Currently, common treatment of cancer such as chemotherapy works by killing fast-growing cancer cells. Unfortunately, chemotherapy cannot tell the difference between cancer cells and fast-growing healthy cells, including red and white blood cells. As a result, one of the most serious potential side effects of some types of chemotherapy is a low white blood cell count that makes it unreliable (Parkin et al. [34]; Pauk et al. [3]). Even though intense research has been going on in recent years, successful therapeutic targets against this disease have been elusive. In this study, we evaluate the anti-proliferative activity of Euphorbia mauritanica and Kedrostis hirtella in lung cancer. In our assessment it was observed that E. mauritanica and K. hirtella were able to induce cell death at 5 μg/ml in A549 cells over 22 h and at 10 μg/ml over 24 h in the Lqr1 cell line. Molecular analysis of DNA fragmentation and Annexin V were used to examine the type of cell death induced by E. mauritanica and K. hirtella extracts. These results showed an increase in necrotic and apoptotic characteristics with both nuclear DNA fragmentation and smear. Therefore, these results suggest that E. mauritanica and K. hirtella may play a role in inducing cell death in lung cancer cells. However, further studies need to be conducted to ascertain these results. PMID:23086267

  12. Chitin and chitosan from the Norway lobster by-products: Antimicrobial and anti-proliferative activities.

    PubMed

    Sayari, Nadhem; Sila, Assaâd; Abdelmalek, Baha Eddine; Abdallah, Rihab Ben; Ellouz-Chaabouni, Semia; Bougatef, Ali; Balti, Rafik

    2016-06-01

    Chitin was recovered through enzymatic deproteinization of the Norway lobster (Nephrops norvegicus) processing by-products. The obtained chitin was characterized and converted into chitosan by N-deacetylation, the acid-soluble form of chitin. Chitosan samples were then characterized by Fourier transform infrared spectroscopy (FTIR) and 13 Cross polarization magic angle spinning nuclear magnetic resonance (CP/MAS)-NMR spectroscopy. The antimicrobial activity and anti-proliferative capacity of chitosan were evaluated. Antimicrobial activity assays indicated that prepared chitosan exhibited marked inhibitory activity against the bacterial and fungal strains tested. Further, cytotoxic effects of chitosan samples on human colon carcinoma cells HCT116 was evaluated using the MTT assay. Chitosan showed the antiproliferative capacity against the colon-cancer-cell HCT116 in a dose dependent manner with IC50 of 4.6mg/ml. Indeed, HCT116 cell proliferation was significantly inhibited (p<0.05) between 13.5 and 67.5% at 0.5-6mg/mL of chitosan after 24h of cell treatment. The chitosan showed high antitumor activity which seemed to be dependent on its characteristics such as acetylation degree. PMID:26920243

  13. Colonic anastomoses and non-steroidal anti-inflammatory drugs.

    PubMed

    Slim, K; Joris, J; Beloeil, H

    2016-08-01

    Nonsteroidal anti-inflammatory drugs (NSAID) play an important role in the treatment of post-operative pain, particularly in the context of enhanced recovery after colorectal surgery. Several recent articles have suggested that NSAID may have a deleterious effect on colo-colic or colo-rectal anastomoses. The aim of this review is to analyze the evidence based on meta-analyses and cohort studies in the literature. A systematic review of clinical studies identified twelve studies including two meta-analyses and ten comparative cohort studies that included a large number of patients. The data in these studies are heterogeneous, often biased, and do not permit a formal recommendation based on a high level of evidence. The main conclusion of this review is that the balance of benefit vs. risk (analgesic effect/risk of anastomotic disruption) is acceptable; it appears (with a low level of evidence) that a prescription of NSAID for 48h after surgery may be recommended for elective colon surgery. Nevertheless, it is important to respect the specific contra-indications of NSAID and avoid post-operative NSAID use if there are risk factors for anastomotic leakage: advanced age, malnutrition, severe co-morbidities, intra-operative difficulties. PMID:27480526

  14. Anti-Proliferative and Pro-Apoptotic Activities of 4-Methyl-2,6-bis(1-phenylethyl)phenol in Cancer Cells.

    PubMed

    Sung, Nak Yoon; Kim, Seung Cheol; Kim, Yun Hwan; Kim, Gihyeon; Lee, Yunmi; Sung, Gi-Ho; Kim, Ji Hye; Yang, Woo Seok; Kim, Mi Seon; Baek, Kwang-Soo; Kim, Jong-Hoon; Cho, Jae Youl

    2016-07-01

    It has been found that 4-isopropyl-2,6-bis(1-phenylethyl)phenol (KTH-13), a novel compound isolated from Cordyceps bassiana, is able to suppress tumor cell proliferation by inducing apoptosis. To mass-produce this compound, we established a total synthesis method. Using those conditions, we further synthesized various analogs with structural similarity to KTH-13. In this study, we aimed to test their anti-cancer activity by measuring anti-proliferative and pro-apoptotic activities. Of 8 compounds tested, 4-methyl-2,6-bis(1-phenylethyl)phenol (KTH-13-Me) exhibited the strongest anti-proliferative activity toward MDA-MB 231 cells. KTH-13-Me also similarly suppressed the survival of various cancer cell lines, including C6 glioma, HCT-15, and LoVo cells. Treatment of KTH-13-Me induced several apoptotic signs in C6 glioma cells, such as morphological changes, induction of apoptotic bodies, and nuclear fragmentation and chromatin condensation. Concordantly, early-apoptotic cells were also identified by staining with FITC-Annexin V/PI. Moreover, KTH-13-Me highly enhanced the activation of caspase-3 and caspase-9, and decreased the protein level of Bcl-2. In addition, the phosphorylation levels of Src and STAT3 were diminished in KTH-13-Me-treated C6 cells. Therefore, these results suggest that KTH-13-Me can be developed as a novel anti-cancer drug capable of blocking proliferation, inducing apoptosis, and blocking cell survival signaling in cancer cells. PMID:27068261

  15. Anti-Proliferative and Pro-Apoptotic Activities of 4-Methyl-2,6-bis(1-phenylethyl)phenol in Cancer Cells

    PubMed Central

    Sung, Nak Yoon; Kim, Seung Cheol; Kim, Yun Hwan; Kim, Gihyeon; Lee, Yunmi; Sung, Gi-Ho; Kim, Ji Hye; Yang, Woo Seok; Kim, Mi Seon; Baek, Kwang-Soo; Kim, Jong-Hoon; Cho, Jae Youl

    2016-01-01

    It has been found that 4-isopropyl-2,6-bis(1-phenylethyl)phenol (KTH-13), a novel compound isolated from Cordyceps bassiana, is able to suppress tumor cell proliferation by inducing apoptosis. To mass-produce this compound, we established a total synthesis method. Using those conditions, we further synthesized various analogs with structural similarity to KTH-13. In this study, we aimed to test their anti-cancer activity by measuring anti-proliferative and pro-apoptotic activities. Of 8 compounds tested, 4-methyl-2,6-bis(1-phenylethyl)phenol (KTH-13-Me) exhibited the strongest anti-proliferative activity toward MDA-MB 231 cells. KTH-13-Me also similarly suppressed the survival of various cancer cell lines, including C6 glioma, HCT-15, and LoVo cells. Treatment of KTH-13-Me induced several apoptotic signs in C6 glioma cells, such as morphological changes, induction of apoptotic bodies, and nuclear fragmentation and chromatin condensation. Concordantly, early-apoptotic cells were also identified by staining with FITC-Annexin V/PI. Moreover, KTH-13-Me highly enhanced the activation of caspase-3 and caspase-9, and decreased the protein level of Bcl-2. In addition, the phosphorylation levels of Src and STAT3 were diminished in KTH-13-Me-treated C6 cells. Therefore, these results suggest that KTH-13-Me can be developed as a novel anti-cancer drug capable of blocking proliferation, inducing apoptosis, and blocking cell survival signaling in cancer cells. PMID:27068261

  16. Role of VDR in anti-proliferative effects of calcitriol in tumor-derived endothelial cells and tumor angiogenesis in vivo

    PubMed Central

    Chung, Ivy; Han, Guangzhou; Seshadri, Mukund; Gillard, Bryan M.; Yu, Wei-dong; Foster, Barbara A.; Trump, Donald L.; Johnson, Candace S.

    2008-01-01

    Calcitriol (1, 25-dihydroxycholecalciferol), the major active form of vitamin D, is anti-proliferative in tumor cells and tumor-derived endothelial cells (TDEC). These actions of calcitriol are mediated at least in part by vitamin D receptor (VDR), which is expressed in many tissues including endothelial cells. To investigate the role of VDR in calcitriol effects on tumor vasculature, we established TRAMP-2 tumors subcutaneously into either VDR wild type (WT) or knockout (KO) mice. Within 30 days post inoculation, tumors in KO mice were larger than those in WT (P<0.001). TDEC from WT expressed VDR and were able to transactivate a reporter gene whereas TDEC from KO mice were not. Treatment with calcitriol resulted in growth inhibition in TDEC expressing VDR. However, TDEC from KO mice were relatively resistant, suggesting that calcitriol-mediated growth inhibition on TDEC is VDR-dependent. Further analysis of the TRAMP-C2 tumor sections revealed that the vessels in KO mice were enlarged and had less pericyte coverage compared to WT (P<0.001). Contrast-enhanced MRI demonstrated an increase in vascular volume of TRAMP tumors grown in VDR KO mice compared to WT mice (P<0.001) and FITC-dextran permeability assay suggested a higher extent of vascular leakage in tumors from KO mice. Using ELISA and Western blot analysis, there was an increase of HIF-1 alpha, VEGF, Ang1 and PDGF-BB levels observed in tumors from KO mice. These results indicate that calcitriol-mediated anti-proliferative effects on TDEC are VDR dependent and loss of VDR can lead to abnormal tumor angiogenesis. PMID:19141646

  17. Anti-inflammatory activity of Bromelia hieronymi: comparison with bromelain.

    PubMed

    Errasti, María E; Caffini, Néstor O; Pelzer, Lilian E; Rotelli, Alejandra E

    2013-03-01

    Some plant proteases (e. g., papain, bromelain, ficin) have been used as anti-inflammatory agents for some years, and especially bromelain is still being used as alternative and/or complementary therapy to glucocorticoids, nonsteroidal antirheumatics, and immunomodulators. Bromelain is an extract rich in cysteine endopeptidases obtained from Ananas comosus. In this study the anti-inflammatory action of a partially purified extract of Bromelia hieronymi fruits, whose main components are cysteine endopeptidases, is presented. Different doses of a partially purified extract of B. hieronymi were assayed on carrageenan-induced and serotonine-induced rat paw edema, as well as in cotton pellet granuloma model. Doses with equal proteolytic activity of the partially purified extract and bromelain showed significantly similar anti-inflammatory responses. Treatment of the partially purified extract and bromelain with E-64 provoked loss of anti-inflammatory activity on carrageenan-induced paw edema, a fact which is consistent with the hypothesis that the proteolytic activity would be responsible for the anti-inflammatory action.

  18. Modeling Natural Anti-Inflammatory Compounds by Molecular Topology

    PubMed Central

    Galvez-Llompart, María; Zanni, Riccardo; García-Domenech, Ramón

    2011-01-01

    One of the main pharmacological problems today in the treatment of chronic inflammation diseases consists of the fact that anti-inflammatory drugs usually exhibit side effects. The natural products offer a great hope in the identification of bioactive lead compounds and their development into drugs for treating inflammatory diseases. Computer-aided drug design has proved to be a very useful tool for discovering new drugs and, specifically, Molecular Topology has become a good technique for such a goal. A topological-mathematical model, obtained by linear discriminant analysis, has been developed for the search of new anti-inflammatory natural compounds. An external validation obtained with the remaining compounds (those not used in building up the model), has been carried out. Finally, a virtual screening on natural products was performed and 74 compounds showed actual anti-inflammatory activity. From them, 54 had been previously described as anti-inflammatory in the literature. This can be seen as a plus in the model validation and as a reinforcement of the role of Molecular Topology as an efficient tool for the discovery of new anti-inflammatory natural compounds. PMID:22272145

  19. Analgesic and Anti-Inflammatory Activity of Pinus roxburghii Sarg.

    PubMed Central

    Kaushik, Dhirender; Kumar, Ajay; Kaushik, Pawan; Rana, A. C.

    2012-01-01

    The Chir Pine, Pinus roxburghii, named after William Roxburgh, is a pine native to the Himalaya. Pinus roxburghii Sarg. (Pinaceae) is traditionally used for several medicinal purposes in India. As the oil of the plant is extensively used in number of herbal preparation for curing inflammatory disorders, the present study was undertaken to assess analgesic and anti-inflammatory activities of its bark extract. Dried and crushed leaves of Pinus roxburghii Sarg. were defatted with petroleum ether and then extracted with alcohol. The alcoholic extract at the doses of 100 mg/kg, 300 mg/kg, and 500 mg/kg body weight was subjected to evaluation of analgesic and anti-inflammatory activities in experimental animal models. Analgesic activity was evaluated by acetic acid-induced writhing and tail immersion tests in Swiss albino mice; acute and chronic anti-inflammatory activity was evaluated by carrageenan-induced paw oedema and cotton pellet granuloma in Wistar albino rats. Diclofenac sodium and indomethacin were employed as reference drugs for analgesic and anti-inflammatory studies, respectively. In the present study, the alcoholic bark extract of Pinus roxburghii Sarg. demonstrated significant analgesic and anti-inflammatory activities in the tested models. PMID:22761611

  20. Optimization and Pharmacological Validation of a Leukocyte Migration Assay in Zebrafish Larvae for the Rapid In Vivo Bioactivity Analysis of Anti-Inflammatory Secondary Metabolites

    PubMed Central

    Vicet-Muro, Liliana; Wilches-Arizábala, Isabel María; Esguerra, Camila V.; de Witte, Peter A. M.; Crawford, Alexander D.

    2013-01-01

    Over the past decade, zebrafish (Danio rerio) have emerged as an attractive model for in vivo drug discovery. In this study, we explore the suitability of zebrafish larvae to rapidly evaluate the anti-inflammatory activity of natural products (NPs) and medicinal plants used in traditional medicine for the treatment of inflammatory disorders. First, we optimized a zebrafish assay for leukocyte migration. Inflammation was induced in four days post-fertilization (dpf) zebrafish larvae by tail transection and co-incubation with bacterial lipopolysaccharides (LPS), resulting in a robust recruitment of leukocytes to the zone of injury. Migrating zebrafish leukocytes were detected in situ by myeloperoxidase (MPO) staining, and anti-inflammatory activity was semi-quantitatively scored using a standardized scale of relative leukocyte migration (RLM). Pharmacological validation of this optimized assay was performed with a panel of anti-inflammatory drugs, demonstrating a concentration-responsive inhibition of leukocyte migration for both steroidal and non-steroidal anti-inflammatory drugs (SAIDs and NSAIDs). Subsequently, we evaluated the bioactivity of structurally diverse NPs with well-documented anti-inflammatory properties. Finally, we further used this zebrafish-based assay to quantify the anti-inflammatory activity in the aqueous and methanolic extracts of several medicinal plants. Our results indicate the suitability of this LPS-enhanced leukocyte migration assay in zebrafish larvae as a front-line screening platform in NP discovery, including for the bioassay-guided isolation of anti-inflammatory secondary metabolites from complex NP extracts. PMID:24124487

  1. Isolation and anti-inflammatory activity of Bakuchiol from Ulmus davidiana var. japonica.

    PubMed

    Choi, Sang Yoon; Lee, Sanghyun; Choi, Won-Hee; Lee, Yeonmi; Jo, Youn Ock; Ha, Tae-Youl

    2010-08-01

    The bark of the root and stem of Ulmus davidiana var. japonica has been used as a traditional Korean medicine to treat inflammatory disorders. This plant reportedly exhibits antioxidant, anticancer, and anti-inflammatory effects. A search for biologically active compounds in U. davidiana var. japonica extracts yielded bakuchiol, which we structurally identified on the basis of spectral data, including two-dimensional nuclear magnetic resonance spectroscopy and distortionless enhancement by polarization transfer. In our study, bakuchiol (50 microM) inhibited lipopolysaccharide-induced nitric oxide and prostaglandin E(2) production in RAW 264.7 macrophages by 53.7% and 84.2%, respectively. These results suggested that bakuchiol is one of the potent anti-inflammatory components of U. davidiana var. japonica.

  2. Antitussive, expectorant and anti-inflammatory alkaloids from Bulbus Fritillariae Cirrhosae.

    PubMed

    Wang, Dongdong; Zhu, Jingyi; Wang, Shu; Wang, Xiaoxia; Ou, Yang; Wei, Dandan; Li, Xueping

    2011-12-01

    The primary objective of this study is to evaluate the antitussive, expectorant and anti-inflammatory effects of alkaloids imperialine (I), chuanbeinone (II), verticinone (III), and verticine (IV), which were isolated from the Bulbus Fritillariae Cirrhosae (BFC) using phytochemical method. The results showed that all the alkaloids significantly inhibited cough frequency and increased latent period of cough in mice induced by ammonia. Besides, imperialine(I), verticinone(III) and verticine(IV) markedly enhanced mice's tracheal phenol red output in expectorant evaluation, and imperialine(I), chuanbeinone(II) significantly inhibited the development of ear edema in a dose-dependent manner in anti-inflammatory assessment. Moreover, important differences were found among the structure-activity relationships for the four alkaloids. These results confirmed that the four alkaloids imperialine, chuanbeinone, verticinone and verticine may be the active ingredients of the Bulbus F. Cirrhosae (BFC).

  3. Anti-inflammatory and antioxidant properties of a novel resveratrol-salicylate hybrid analog.

    PubMed

    Aldawsari, Fahad S; Aguiar, Rafael Pazinatto; Wiirzler, Luiz Alexandre Marques; Aguayo-Ortiz, Rodrigo; Aljuhani, Naif; Cuman, Roberto Kenji Nakamura; Medina-Franco, José L; Siraki, Arno G; Velázquez-Martínez, Carlos A

    2016-03-01

    Resveratrol is a natural compound with a plethora of activities as well as limitations. We recently reported a series of resveratrol-salicylate analogs with potential chemopreventive activity. Herein, we report the anti-inflammatory and antioxidant properties of these resveratrol derivatives. Using an in vitro COX inhibition assay, and two in vivo protocols (carrageenan-induced peritonitis and paw edema), we identified a novel compound (C10) as a potent anti-inflammatory agent. The enhanced potency of C10 was associated with the ability of C10 to decrease the activity of myeloperoxidase (MPO) enzyme at 10mg/kg, whereas resveratrol and it's natural analog (TMS) did not exert the same effect. Additionally, C10 significantly reduced the concentration of intracellular reactive oxygen species. Because of the proven association between cancer, inflammation, and oxidative stress, we believe that C10 is a promising chemopreventive molecule.

  4. New insights into insulin: The anti-inflammatory effect and its clinical relevance.

    PubMed

    Sun, Qiang; Li, Jia; Gao, Feng

    2014-04-15

    Hyperglycemia, a commonly exhibited metabolic disorder in critically ill patients, activates the body's inflammatory defense mechanism, causing the waterfall release of numerous inflammatory mediators and cytokines, and eventually leads to organ damage. As the only glucose-lowering hormone in the body, insulin not only alleviates the detrimental effects of hyperglycemia through its metabolic regulation, but also directly modulates inflammatory mediators and acts upon immune cells to enhance immunocompetence. In this sense, hyperglycemia is pro-inflammatory whereas insulin is anti-inflammatory. Therefore, during the past 50 years, insulin has not only been used in the treatment of diabetes, but has also been put into practical use in dealing with cardiovascular diseases and critical illnesses. This review summarizes the recent advances regarding the anti-inflammatory effects of insulin in both basic research and clinical trials, with the hope of aiding in the design of further experimental research and promoting effective insulin administration in clinical practice. PMID:24765237

  5. Anti-proliferative activity of essential oil extracted from Thai medicinal plants on KB and P388 cell lines.

    PubMed

    Manosroi, Jiradej; Dhumtanom, Pongsathorn; Manosroi, Aranya

    2006-04-01

    Anti-proliferative activity of essential oil from 17 Thai medicinal plants on human mouth epidermal carcinoma (KB) and murine leukemia (P388) cell lines using MTT assay were investigated. An amount of 1 x 10(4)cells/well of KB cell line and 1 x 10(5) cells/well of P388 cell line were treated with the oil samples at different concentrations ranging from 0.019 to 4.962 mg/ml. In KB cell line, Guava (Psidium guajava L.) leaf oil showed the highest anti-proliferative activity with the IC(50) value of 0.0379 mg/ml (4.37 times more potent than vincristine) whereas Sweet Basil (Ocimum basilicum L.) oil gave the highest anti-proliferative activity with the IC(50) value of 0.0362 mg/ml (12.7 times less potent than 5-FU) in P388 cell line. The results demonstrated the potential of essential oil from Thai medicinal plants for cancer treatment.

  6. Phytochemical properties and anti-proliferative activity of Olea europaea L. leaf extracts against pancreatic cancer cells.

    PubMed

    Goldsmith, Chloe D; Vuong, Quan V; Sadeqzadeh, Elham; Stathopoulos, Costas E; Roach, Paul D; Scarlett, Christopher J

    2015-01-01

    Olea europaea L. leaves are an agricultural waste product with a high concentration of phenolic compounds; especially oleuropein. Oleuropein has been shown to exhibit anti-proliferative activity against a number of cancer types. However, they have not been tested against pancreatic cancer, the fifth leading cause of cancer related death in Western countries. Therefore, water, 50% ethanol and 50% methanol extracts of Corregiola and Frantoio variety Olea europaea L. leaves were investigated for their total phenolic compounds, total flavonoids and oleuropein content, antioxidant capacity and anti-proliferative activity against MiaPaCa-2 pancreatic cancer cells. The extracts only had slight differences in their phytochemical properties, and at 100 and 200 μg/mL, all decreased the viability of the pancreatic cancer cells relative to controls. At 50 μg/mL, the water extract from the Corregiola leaves exhibited the highest anti-proliferative activity with the effect possibly due to early eluting HPLC peaks. For this reason, olive leaf extracts warrant further investigation into their potential anti-pancreatic cancer benefits.

  7. Hesperetin derivatives: Synthesis and anti-inflammatory activity.

    PubMed

    Wang, Qian-Qian; Shi, Jing-Bo; Chen, Chen; Huang, Cheng; Tang, Wen-Jian; Li, Jun

    2016-03-01

    Sixteen novel hesperetin derivatives containing Mannich base moiety were designed and synthesized and their anti-inflammatory activities were evaluated by inhibiting tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in mouse RAW264.7 macrophages. Compounds 3a-3k showed better hydrophilic, while compounds 3l-3p with aromatic groups was hydrophobic. The anti-inflammatory activity of title compounds was correlated with logP values, among them, compounds 3c, 3e and 3i with minus logP values exhibited best anti-inflammatory activity through decreasing both IL-6 and TNF-α. Furthermore, the expression of LPS-induced notch1 and inos was reduced by compounds 3c, 3e, and 3i, and compound 3e attenuated LPS-induced inos protein levels in a dose-dependent manner.

  8. Hesperetin derivatives: Synthesis and anti-inflammatory activity.

    PubMed

    Wang, Qian-Qian; Shi, Jing-Bo; Chen, Chen; Huang, Cheng; Tang, Wen-Jian; Li, Jun

    2016-03-01

    Sixteen novel hesperetin derivatives containing Mannich base moiety were designed and synthesized and their anti-inflammatory activities were evaluated by inhibiting tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in mouse RAW264.7 macrophages. Compounds 3a-3k showed better hydrophilic, while compounds 3l-3p with aromatic groups was hydrophobic. The anti-inflammatory activity of title compounds was correlated with logP values, among them, compounds 3c, 3e and 3i with minus logP values exhibited best anti-inflammatory activity through decreasing both IL-6 and TNF-α. Furthermore, the expression of LPS-induced notch1 and inos was reduced by compounds 3c, 3e, and 3i, and compound 3e attenuated LPS-induced inos protein levels in a dose-dependent manner. PMID:26848111

  9. Anti-inflammatory Flavonoids Isolated from Passiflora foetida.

    PubMed

    Nguyen, Thi Yen; To, Dao Cuong; Tran, Manh Hung; Lee, Joo Sang; Lee, Jeong Hyung; Kim, Jeong Ah; Woo, Mi Hee; Min, Byung Sun

    2015-06-01

    In this study, we evaluated the anti-inflammatory activity of the soluble ethyl acetate fraction and chemical components of the stem bark of Passiflora foetida (Passifloraceae). Ten flavonoids (1-10) were isolated by various chromatographic techniques, and their structures were determined based on spectroscopic analyses by using nuclear magnetic resonance (NMR). Luteolin (2) and chrysoeriol (3) showed the most potent inhibition of nitric oxide (NO) production in macrophage cell line, RAW264.7, with half maximal inhibitor concentration (IC50) values of 1.2 and 3.1 μM, respectively. These compounds suppressed lipopolysaccharide (LPS)-induced inducible NO synthase (iNOS) expression at the transcription level. Our research indicates that the stem bark of P. foetida has significant anti-inflammatory properties, suggesting that its flavonoids may have anti-inflammatory benefits. PMID:26197519

  10. Modifying anti-inflammatory effect of Diclofenac with Murraya koenigii.

    PubMed

    Kaur, Ginpreet; Daftardar, Saloni; Barve, Kalyani H

    2014-01-01

    Murraya koenigii (Curry leaves) has been widely used in Asian countries for the treatment of some ailments such as diabetes and hypertension. In the present study, leaves of Murraya koenigii were extracted with ethanol and evaluated for anti-inflammatory activity in rats using carrageenan induced paw edema method. Ethanolic extract showed a potent anti-inflammatory activity at third hour after carrageenan administration when compared with the standard drug, Diclofenac. The percent inhibition of paw volume was found to be 84.75% for 50 mg/kg of extract whereas it was found to be 80.86% for 50 mg/kg extract in combination with Diclofenac 10 mg/kg. Thus, the present study suggests that the combination therapy potentiates the anti-inflammatory effect of diclofenac and may help in reducing the dose of the synthetic drug. Some relevant patents are also outlined in this article.

  11. Anti-inflammatory activity of Syzygium cumini bark.

    PubMed

    Muruganandan, S; Srinivasan, K; Chandra, S; Tandan, S K; Lal, J; Raviprakash, V

    2001-05-01

    The ethanolic extract of the bark of Syzygium cumini was investigated for its anti-inflammatory activity in animal models. The extract did not show any sign of toxicity up to a dose of 10.125 g/kg, p.o. in mice. Significant anti-inflammatory activity was observed in carrageenin (acute), kaolin-carrageenin (subacute), formaldehyde (subacute)-induced paw oedema and cotton pellet granuloma (chronic) tests in rats. The extract did not induce any gastric lesion in both acute and chronic ulcerogenic tests in rats. Thus, the present study demonstrated that S. cumini bark extract has a potent anti-inflammatory action against different phases of inflammation without any side effect on gastric mucosa. PMID:11395258

  12. IL-35 is a novel responsive anti-inflammatory cytokine--a new system of categorizing anti-inflammatory cytokines.

    PubMed

    Li, Xinyuan; Mai, Jietang; Virtue, Anthony; Yin, Ying; Gong, Ren; Sha, Xiaojin; Gutchigian, Stefanie; Frisch, Andrew; Hodge, Imani; Jiang, Xiaohua; Wang, Hong; Yang, Xiao-Feng

    2012-01-01

    It remains unknown whether newly identified anti-inflammatory/immunosuppressive cytokine interleukin-35 (IL-35) is different from other anti-inflammatory cytokines such as IL-10 and transforming growth factor (TGF)-β in terms of inhibition of inflammation initiation and suppression of full-blown inflammation. Using experimental database mining and statistical analysis methods we developed, we examined the tissue expression profiles and regulatory mechanisms of IL-35 in comparison to other anti-inflammatory cytokines. Our results suggest that in contrast to TGF-β, IL-35 is not constitutively expressed in human tissues but it is inducible in response to inflammatory stimuli. We also provide structural evidence that AU-rich element (ARE) binding proteins and microRNAs target IL-35 subunit transcripts, by which IL-35 may achieve non-constitutive expression status. Furthermore, we propose a new system to categorize anti-inflammatory cytokines into two groups: (1) the house-keeping cytokines, such as TGF-β, inhibit the initiation of inflammation whereas (2) the responsive cytokines including IL-35 suppress inflammation in full-blown stage. Our in-depth analyses of molecular events that regulate the production of IL-35 as well as the new categorization system of anti-inflammatory cytokines are important for the design of new strategies of immune therapies.

  13. Binding, Antioxidant and Anti-proliferative Properties of Bioactive Compounds of Sweet Paprika (Capsicum annuum L.).

    PubMed

    Kim, Hong-Gi; Bae, Jong-Hyang; Jastrzebski, Zenon; Cherkas, Andriy; Heo, Buk-Gu; Gorinstein, Shela; Ku, Yang-Gyu

    2016-06-01

    The scope of this research was to determine the bioactive composition, antioxidant, binding, and anti-proliferative properties of red sweet paprika growing under artificial light. The amounts of carotenoids, chlorophyll, polyphenols, tannins, and flavonoids in red paprika (RP), cultivated in Korea, before and after light treatments under high pressure sodium (HPS) and lighting emitting plasma (LEP) lamps (RPControl, RPHPS, RPLEP), were analyzed in water (W) and ethanolic extracts (Et). Spectroscopic, radical scavenging assays, fluorescence and cytotoxicity measurements were applied. The results of this study showed that total chlorophyll and carotenes were the highest in RPHPS (10.50 ± 1.02 and 33.90 ± 3.26 μg/g dry weight (DW)). The strongest antioxidant capacity (μM TE/g DW) in a 2, 2'-azino-bis (3-ethyl-benzothiazoline-6-sulfonic acid) diammonium salt (ABTS(•+)) assay was in RPControlEt (24.34 ± 2.36), in a ferric-reducing/antioxidant power (FRAP) assay in RPHPSW (27.08 ± 2.4) and in a cupric reducing antioxidant (CUPRAC) in RPLEPW (70.99 ± 7.11). The paprika ethanolic extracts showed lower values in their bioactivity than the water ones. The binding and cytotoxicity abilities of extracted polyphenols correlated with their amounts. LEP treatment is better for plant growth characteristics than other conventional treatments. The investigated paprika samples can be used as a source of antioxidants.

  14. Anti-proliferative and cytotoxic activity of rosuvastatin against melanoma cells

    PubMed Central

    Czajkowski, Rafal; Zegarska, Barbara; Kowaliszyn, Bogna; Pokrywczynska, Marta; Drewa, Tomasz

    2016-01-01

    Introduction Statins are considered potential candidate agents for melanoma chemoprevention. Statin-induced mevalonate pathway inhibition leads to reduction of cholesterol synthesis and also to decreased cellular levels of non-steroidal isoprenoids, geranylgeranyl pyrophosphate and farnesyl pyrophosphate. This results in the impairment of protein prenylation which affects carcinogenesis. Aim To analyze anti-proliferative and cytotoxic activity of rosuvastatin against melanoma cells. Material and methods Melanoma cell lines (A375 and WM1552C) and normal fibroblasts (BJ) were used as the primary research material. Cells were treated with rosuvastatin at concentrations ranging from 0.01 µM to 10 µM. Cell viability was analyzed with the use of an MTT assay. Expression of proliferation marker Ki67 was assessed on the basis of immunofluorescence staining. Results Rosuvastatin reduced A375 and BJ cell viability in a time- and dose-dependent manner. After 72 h incubation, the IC50, half maximal inhibitory concentration, was 2.3 µM for melanoma cells and 7.4 µM for normal fibroblasts. In turn, rosuvastatin exhibited relatively lower activity against WM1552C cells. A significant reduction of Ki67 expression was also noted for BJ fibroblasts after prolonged incubation with the tested drug. Conclusions The results indicate that the anti-melanoma properties of rosuvastatin are highly dependent on the tumor cell line assessed. However, the concentrations required to decrease melanoma cell viability in vitro exceed the plasma concentrations reached in patients treated with rosuvastatin at well-tolerated doses. What is more disturbing, reduction of proliferation and viability observed in BJ fibroblasts indicated that rosuvastatin at high doses may be toxic for normal cells. PMID:27605895

  15. Anti-proliferative role and prognostic implication of miR-141 in gastric cancer

    PubMed Central

    Huang, Mingwei; Wu, Liucheng; Qin, Yuzhou; Li, Zhao; Luo, Shanshan; Qin, Haiquan; Yang, Yang; Chen, Jiansi

    2016-01-01

    Gastric cancer is a prevalent disease causing a high annual death rate worldwide. Recent studies suggest the pivotal regulatory role of microRNAs in gastric cancer and the aberrant expression of microRNA-141 (miR-141) in gastric cancer cells. This study aims to explore the role and possible mechanism of miR-141 in gastric cancer prognosis and cell proliferation. A total of 30 gastric cancer patients were recruited for miR-141 level detection and a follow up of 115 weeks. Human adenocarcinoma cell line AGS was transfected with miR-141 mimic or inhibitor for cell viability, colony formation and cell cycle assays. A gastric cancer mouse model was constructed by implantation of transfected AGS cells. Insulin-like growth factor 1 receptor (IGF1R) was overexpressed in AGS cells to investigate miR-141 mechanism. Results showed that miR-141 was significantly down-regulated in gastric cancer tissue (P < 0.001). The patients with lower miR-141 levels exhibited poorer prognosis. miR-141 inhibited AGS cell viability (P < 0.01), colony formation (P < 0.01) and cell cycle (P < 0.05), and the mice implanted with miR-141 mimic cells showed an obvious smaller tumor size (P < 0.01), suggesting the anti-proliferative role of miR-141. Both the phosphorylated and total IGF1R protein levels were inhibited by miR-141, while IGF1R overexpression reversed the effects of miR-141 in AGS cell proliferation. These results indicate the potential roles of miR-141 as a prognostic factor and as a therapeutic alternative for gastric cancer. Its mechanism may be associated with IGF1R, and further research is necessary for more detail information. PMID:27648145

  16. Binding, Antioxidant and Anti-proliferative Properties of Bioactive Compounds of Sweet Paprika (Capsicum annuum L.).

    PubMed

    Kim, Hong-Gi; Bae, Jong-Hyang; Jastrzebski, Zenon; Cherkas, Andriy; Heo, Buk-Gu; Gorinstein, Shela; Ku, Yang-Gyu

    2016-06-01

    The scope of this research was to determine the bioactive composition, antioxidant, binding, and anti-proliferative properties of red sweet paprika growing under artificial light. The amounts of carotenoids, chlorophyll, polyphenols, tannins, and flavonoids in red paprika (RP), cultivated in Korea, before and after light treatments under high pressure sodium (HPS) and lighting emitting plasma (LEP) lamps (RPControl, RPHPS, RPLEP), were analyzed in water (W) and ethanolic extracts (Et). Spectroscopic, radical scavenging assays, fluorescence and cytotoxicity measurements were applied. The results of this study showed that total chlorophyll and carotenes were the highest in RPHPS (10.50 ± 1.02 and 33.90 ± 3.26 μg/g dry weight (DW)). The strongest antioxidant capacity (μM TE/g DW) in a 2, 2'-azino-bis (3-ethyl-benzothiazoline-6-sulfonic acid) diammonium salt (ABTS(•+)) assay was in RPControlEt (24.34 ± 2.36), in a ferric-reducing/antioxidant power (FRAP) assay in RPHPSW (27.08 ± 2.4) and in a cupric reducing antioxidant (CUPRAC) in RPLEPW (70.99 ± 7.11). The paprika ethanolic extracts showed lower values in their bioactivity than the water ones. The binding and cytotoxicity abilities of extracted polyphenols correlated with their amounts. LEP treatment is better for plant growth characteristics than other conventional treatments. The investigated paprika samples can be used as a source of antioxidants. PMID:27184000

  17. Anti-proliferative role and prognostic implication of miR-141 in gastric cancer.

    PubMed

    Huang, Mingwei; Wu, Liucheng; Qin, Yuzhou; Li, Zhao; Luo, Shanshan; Qin, Haiquan; Yang, Yang; Chen, Jiansi

    2016-01-01

    Gastric cancer is a prevalent disease causing a high annual death rate worldwide. Recent studies suggest the pivotal regulatory role of microRNAs in gastric cancer and the aberrant expression of microRNA-141 (miR-141) in gastric cancer cells. This study aims to explore the role and possible mechanism of miR-141 in gastric cancer prognosis and cell proliferation. A total of 30 gastric cancer patients were recruited for miR-141 level detection and a follow up of 115 weeks. Human adenocarcinoma cell line AGS was transfected with miR-141 mimic or inhibitor for cell viability, colony formation and cell cycle assays. A gastric cancer mouse model was constructed by implantation of transfected AGS cells. Insulin-like growth factor 1 receptor (IGF1R) was overexpressed in AGS cells to investigate miR-141 mechanism. Results showed that miR-141 was significantly down-regulated in gastric cancer tissue (P < 0.001). The patients with lower miR-141 levels exhibited poorer prognosis. miR-141 inhibited AGS cell viability (P < 0.01), colony formation (P < 0.01) and cell cycle (P < 0.05), and the mice implanted with miR-141 mimic cells showed an obvious smaller tumor size (P < 0.01), suggesting the anti-proliferative role of miR-141. Both the phosphorylated and total IGF1R protein levels were inhibited by miR-141, while IGF1R overexpression reversed the effects of miR-141 in AGS cell proliferation. These results indicate the potential roles of miR-141 as a prognostic factor and as a therapeutic alternative for gastric cancer. Its mechanism may be associated with IGF1R, and further research is necessary for more detail information. PMID:27648145

  18. Anti-proliferative and cytotoxic activity of rosuvastatin against melanoma cells

    PubMed Central

    Czajkowski, Rafal; Zegarska, Barbara; Kowaliszyn, Bogna; Pokrywczynska, Marta; Drewa, Tomasz

    2016-01-01

    Introduction Statins are considered potential candidate agents for melanoma chemoprevention. Statin-induced mevalonate pathway inhibition leads to reduction of cholesterol synthesis and also to decreased cellular levels of non-steroidal isoprenoids, geranylgeranyl pyrophosphate and farnesyl pyrophosphate. This results in the impairment of protein prenylation which affects carcinogenesis. Aim To analyze anti-proliferative and cytotoxic activity of rosuvastatin against melanoma cells. Material and methods Melanoma cell lines (A375 and WM1552C) and normal fibroblasts (BJ) were used as the primary research material. Cells were treated with rosuvastatin at concentrations ranging from 0.01 µM to 10 µM. Cell viability was analyzed with the use of an MTT assay. Expression of proliferation marker Ki67 was assessed on the basis of immunofluorescence staining. Results Rosuvastatin reduced A375 and BJ cell viability in a time- and dose-dependent manner. After 72 h incubation, the IC50, half maximal inhibitory concentration, was 2.3 µM for melanoma cells and 7.4 µM for normal fibroblasts. In turn, rosuvastatin exhibited relatively lower activity against WM1552C cells. A significant reduction of Ki67 expression was also noted for BJ fibroblasts after prolonged incubation with the tested drug. Conclusions The results indicate that the anti-melanoma properties of rosuvastatin are highly dependent on the tumor cell line assessed. However, the concentrations required to decrease melanoma cell viability in vitro exceed the plasma concentrations reached in patients treated with rosuvastatin at well-tolerated doses. What is more disturbing, reduction of proliferation and viability observed in BJ fibroblasts indicated that rosuvastatin at high doses may be toxic for normal cells.

  19. Understanding the mode of action of a pterostilbene derivative as anti-inflammatory agent.

    PubMed

    Nikhil, Kumar; Sharan, Shruti; Palla, Srinivasa Rao; Sondhi, Sham M; Peddinti, Rama Krishna; Roy, Partha

    2015-09-01

    Inflammatory response plays an important role not only in the normal physiology, but also in the pathology of certain diseases such as cancers. In our previous study, we found a novel derivative of pterostilbene (PTER), to be an effective inducer of apoptosis in human breast and prostate cancer cells affecting various cellular targets. Herein, we further attempted to investigate its anti-inflammatory potential followed by its probable mode of action. The newly developed compound was tested for its anti-inflammatory actions in lipopolysaccharide (LPS) stimulated RAW264.7 macrophages and carrageenan induced rat paw edema models. Our data showed that the derivative inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as the downstream products like nitric oxide (NO) and PGE2, at much lower doses as compared to PTER. This effect was found to be associated with the inhibition of phosphorylation/degradation of IκB-α and nuclear translocation of the p-NFκB p65. Moreover, inhibition of mitogen-activated protein kinases (MAPKs) and activator protein-1 (AP-1) was also observed. In addition, the newly developed compound also reduced the paw edema, the tissue content of NO, PGE2 and expression of iNOS and COX-2 proteins within the tissues after λ-carrageenan stimulation. Taken together, our findings provide the possibility that the PTER derivative might have enhanced cancer chemopreventive potential based on its stronger anti-NFκB and anti-inflammatory activities as compared to its natural counterpart, i.e., PTER. Thus, this compound can be used towards the development of an effective anti-inflammatory agent.

  20. Anti-inflammatory drugs for Duchenne muscular dystrophy: focus on skeletal muscle-releasing factors.

    PubMed

    Miyatake, Shouta; Shimizu-Motohashi, Yuko; Takeda, Shin'ichi; Aoki, Yoshitsugu

    2016-01-01

    Duchenne muscular dystrophy (DMD), an incurable and a progressive muscle wasting disease, is caused by the absence of dystrophin protein, leading to recurrent muscle fiber damage during contraction. The inflammatory response to fiber damage is a compelling candidate mechanism for disease exacerbation. The only established pharmacological treatment for DMD is corticosteroids to suppress muscle inflammation, however this treatment is limited by its insufficient therapeutic efficacy and considerable side effects. Recent reports show the therapeutic potential of inhibiting or enhancing pro- or anti-inflammatory factors released from DMD skeletal muscles, resulting in significant recovery from muscle atrophy and dysfunction. We discuss and review the recent findings of DMD inflammation and opportunities for drug development targeting specific releasing factors from skeletal muscles. It has been speculated that nonsteroidal anti-inflammatory drugs targeting specific inflammatory factors are more effective and have less side effects for DMD compared with steroidal drugs. For example, calcium channels, reactive oxygen species, and nuclear factor-κB signaling factors are the most promising targets as master regulators of inflammatory response in DMD skeletal muscles. If they are combined with an oligonucleotide-based exon skipping therapy to restore dystrophin expression, the anti-inflammatory drug therapies may address the present therapeutic limitation of low efficiency for DMD. PMID:27621596

  1. Anti-inflammatory drugs for Duchenne muscular dystrophy: focus on skeletal muscle-releasing factors

    PubMed Central

    Miyatake, Shouta; Shimizu-Motohashi, Yuko; Takeda, Shin’ichi; Aoki, Yoshitsugu

    2016-01-01

    Duchenne muscular dystrophy (DMD), an incurable and a progressive muscle wasting disease, is caused by the absence of dystrophin protein, leading to recurrent muscle fiber damage during contraction. The inflammatory response to fiber damage is a compelling candidate mechanism for disease exacerbation. The only established pharmacological treatment for DMD is corticosteroids to suppress muscle inflammation, however this treatment is limited by its insufficient therapeutic efficacy and considerable side effects. Recent reports show the therapeutic potential of inhibiting or enhancing pro- or anti-inflammatory factors released from DMD skeletal muscles, resulting in significant recovery from muscle atrophy and dysfunction. We discuss and review the recent findings of DMD inflammation and opportunities for drug development targeting specific releasing factors from skeletal muscles. It has been speculated that nonsteroidal anti-inflammatory drugs targeting specific inflammatory factors are more effective and have less side effects for DMD compared with steroidal drugs. For example, calcium channels, reactive oxygen species, and nuclear factor-κB signaling factors are the most promising targets as master regulators of inflammatory response in DMD skeletal muscles. If they are combined with an oligonucleotide-based exon skipping therapy to restore dystrophin expression, the anti-inflammatory drug therapies may address the present therapeutic limitation of low efficiency for DMD.

  2. Anticancer and anti-inflammatory activities of shallot (Allium ascalonicum) extract

    PubMed Central

    Mohammadi-Motlagh, Hamid-Reza; Mostafaie, Ali; Mansouri, Kamran

    2011-01-01

    Introduction Alliumplants are an important part of the diet of many populations and there is a long-held belief in their health-enhancing properties such as cancer prevention. In this study, the anticancer and anti-inflammatory activities of the aqueous extract of the Allium ascalonicum bulbs have been studied. Material and methods The antiproliferative and anti-growth activity of the aqueous extract of A. ascalonicum was examined in vitro on different tumor cell lines. Furthermore, the acetic acid-induced vascular permeability as an in vivo assay was used for studying anti-inflammatory activity of the extract. Results The aqueous extract of A. ascalonicum had the most anti-growth activity on the cancer cell lines; Jurkat and K562 against Wehi 164 with lower cytotoxic preference. The extract also showed much less cytotoxicity against the normal cell (HUVEC) line and significant anti-inflammatory activity in vivo. Conclusions It is of interest that the extract of this plant has shown much less cytotoxicity against the normal cell line, and, if this also occurs in vivo, the use of this plant clinically for the treatment of cancer patients would have some scientific support. The results of these assays indicated that A. ascalonicum can be a candidate for prevention and treatment of many diseases related to inflammation and malignancy. PMID:22291731

  3. Prodrugs of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), More Than Meets the Eye: A Critical Review

    PubMed Central

    Qandil, Amjad M.

    2012-01-01

    The design and the synthesis of prodrugs for nonsteroidal anti-inflammatory drugs (NSAIDs) have been given much attention by medicinal chemists, especially in the last decade. As a therapeutic group, NSAIDs are among the most widely used prescribed and over the counter (OTC) medications. The rich literature about potential NSAID prodrugs clearly shows a shift from alkyl, aryalkyl or aryl esters with the sole role of masking the carboxylic acid group, to more elaborate conjugates that contain carefully chosen groups to serve specific purposes, such as enhancement of water solubility and dissolution, nitric oxide release, hydrogen sulfide release, antioxidant activity, anticholinergic and acetylcholinesterase inhibitory (AChEI) activity and site-specific targeting and delivery. This review will focus on NSAID prodrugs that have been designed or were, later, found to possess intrinsic pharmacological activity as an intact chemical entity. Such intrinsic activity might augment the anti-inflammatory activity of the NSAID, reduce its side effects or transform the potential therapeutic use from classical anti-inflammatory action to something else. Reports discussed in this review will be those of NO-NSAIDs, anticholinergic and AChEI-NSAIDs, Phospho-NSAIDs and some miscellaneous agents. In most cases, this review will cover literature dealing with these NSAID prodrugs from the year 2006 and later. Older literature will be used when necessary, e.g., to explain the chemical and biological mechanisms of action. PMID:23247285

  4. Anti-inflammatory drugs for Duchenne muscular dystrophy: focus on skeletal muscle-releasing factors.

    PubMed

    Miyatake, Shouta; Shimizu-Motohashi, Yuko; Takeda, Shin'ichi; Aoki, Yoshitsugu

    2016-01-01

    Duchenne muscular dystrophy (DMD), an incurable and a progressive muscle wasting disease, is caused by the absence of dystrophin protein, leading to recurrent muscle fiber damage during contraction. The inflammatory response to fiber damage is a compelling candidate mechanism for disease exacerbation. The only established pharmacological treatment for DMD is corticosteroids to suppress muscle inflammation, however this treatment is limited by its insufficient therapeutic efficacy and considerable side effects. Recent reports show the therapeutic potential of inhibiting or enhancing pro- or anti-inflammatory factors released from DMD skeletal muscles, resulting in significant recovery from muscle atrophy and dysfunction. We discuss and review the recent findings of DMD inflammation and opportunities for drug development targeting specific releasing factors from skeletal muscles. It has been speculated that nonsteroidal anti-inflammatory drugs targeting specific inflammatory factors are more effective and have less side effects for DMD compared with steroidal drugs. For example, calcium channels, reactive oxygen species, and nuclear factor-κB signaling factors are the most promising targets as master regulators of inflammatory response in DMD skeletal muscles. If they are combined with an oligonucleotide-based exon skipping therapy to restore dystrophin expression, the anti-inflammatory drug therapies may address the present therapeutic limitation of low efficiency for DMD.

  5. Anti-inflammatory drugs for Duchenne muscular dystrophy: focus on skeletal muscle-releasing factors

    PubMed Central

    Miyatake, Shouta; Shimizu-Motohashi, Yuko; Takeda, Shin’ichi; Aoki, Yoshitsugu

    2016-01-01

    Duchenne muscular dystrophy (DMD), an incurable and a progressive muscle wasting disease, is caused by the absence of dystrophin protein, leading to recurrent muscle fiber damage during contraction. The inflammatory response to fiber damage is a compelling candidate mechanism for disease exacerbation. The only established pharmacological treatment for DMD is corticosteroids to suppress muscle inflammation, however this treatment is limited by its insufficient therapeutic efficacy and considerable side effects. Recent reports show the therapeutic potential of inhibiting or enhancing pro- or anti-inflammatory factors released from DMD skeletal muscles, resulting in significant recovery from muscle atrophy and dysfunction. We discuss and review the recent findings of DMD inflammation and opportunities for drug development targeting specific releasing factors from skeletal muscles. It has been speculated that nonsteroidal anti-inflammatory drugs targeting specific inflammatory factors are more effective and have less side effects for DMD compared with steroidal drugs. For example, calcium channels, reactive oxygen species, and nuclear factor-κB signaling factors are the most promising targets as master regulators of inflammatory response in DMD skeletal muscles. If they are combined with an oligonucleotide-based exon skipping therapy to restore dystrophin expression, the anti-inflammatory drug therapies may address the present therapeutic limitation of low efficiency for DMD. PMID:27621596

  6. Marine Diterpenoids as Potential Anti-Inflammatory Agents.

    PubMed

    González, Yisett; Torres-Mendoza, Daniel; Jones, Gillian E; Fernandez, Patricia L

    2015-01-01

    The inflammatory response is a highly regulated process, and its dysregulation can lead to the establishment of chronic inflammation and, in some cases, to death. Inflammation is the cause of several diseases, including rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, and asthma. The search for agents inhibiting inflammation is a great challenge as the inflammatory response plays an important role in the defense of the host to infections. Marine invertebrates are exceptional sources of new natural products, and among those diterpenoids secondary metabolites exhibit notable anti-inflammatory properties. Novel anti-inflammatory diterpenoids, exclusively produced by marine organisms, have been identified and synthetic molecules based on those structures have been obtained. The anti-inflammatory activity of marine diterpenoids has been attributed to the inhibition of Nuclear Factor-κB activation and to the modulation of arachidonic acid metabolism. However, more research is necessary to describe the mechanisms of action of these secondary metabolites. This review is a compilation of marine diterpenoids, mainly isolated from corals, which have been described as potential anti-inflammatory molecules. PMID:26538822

  7. Anti-inflammatory defense mechanisms of Entamoeba histolytica.

    PubMed

    Silva-García, Raúl; Rico-Rosillo, Guadalupe

    2011-02-01

    The monocyte locomotion inhibitory factor (MLIF), a heat-stable oligopeptide found in the supernatant fluid of Entamoeba histolytica axenic cultures, may contribute to the delayed inflammation observed in amoebic hepatic abscess. This factor was isolated by ultra-filtration and high powered liquid chromatography, obtaining a primary Met-Gln-Cys-Asn-Ser structure, identified afterwards as the carboxyl-terminal (…Cys-Asn-Ser) active site. The selective anti-inflammatory effects of the pentapeptide have been observed in both in vitro and in vivo models, using a synthetic pentapeptide to maintain the same anti-inflammatory conditions during the experimental assays. Anti-inflammatory effects observed include inhibition of human monocyte locomotion and the respiratory burst in monocytes and neutrophils, increasing expression of anti-inflammatory cytokines and inhibiting expression of the adhesion molecules VLA-4 and VCAM, among others. In this review, we will describe the effects of MLIF detected so far and how it might be used as a therapeutical agent against inflammatory diseases.

  8. Marine Diterpenoids as Potential Anti-Inflammatory Agents

    PubMed Central

    González, Yisett; Torres-Mendoza, Daniel; Jones, Gillian E.; Fernandez, Patricia L.

    2015-01-01

    The inflammatory response is a highly regulated process, and its dysregulation can lead to the establishment of chronic inflammation and, in some cases, to death. Inflammation is the cause of several diseases, including rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, and asthma. The search for agents inhibiting inflammation is a great challenge as the inflammatory response plays an important role in the defense of the host to infections. Marine invertebrates are exceptional sources of new natural products, and among those diterpenoids secondary metabolites exhibit notable anti-inflammatory properties. Novel anti-inflammatory diterpenoids, exclusively produced by marine organisms, have been identified and synthetic molecules based on those structures have been obtained. The anti-inflammatory activity of marine diterpenoids has been attributed to the inhibition of Nuclear Factor-κB activation and to the modulation of arachidonic acid metabolism. However, more research is necessary to describe the mechanisms of action of these secondary metabolites. This review is a compilation of marine diterpenoids, mainly isolated from corals, which have been described as potential anti-inflammatory molecules. PMID:26538822

  9. The Use of Nonsteroidal Anti-Inflammatory Drugs in Sports.

    ERIC Educational Resources Information Center

    Calabrese, Leonard H.; Rooney, Theodore W.

    1986-01-01

    Recent advances in the understanding of the mechanism of action and clinical pharmacology of the new nonsteroidal anti-inflammatory drugs (NSAIDs) can help practitioners decide which to use and how to administer them. Indications for and effects of NSAIDs are described. (MT)

  10. Analgesic and anti-inflammatory activity of Leonurus sibiricus.

    PubMed

    Islam, M Amirul; Ahmed, Firoj; Das, A K; Bachar, S C

    2005-06-01

    The methanolic extract of Leonurus sibiricus aerial parts injected intraperitoneally at dose of 250 and 500 mg/kg showed a significant analgesic effect in acetic acid-induced writhing in mice. Moreover, when given orally to rats at dose of 200 and 400 mg/kg, it showed a significant anti-inflammatory activity against carrageenin induced rat paw edema in rats.

  11. Anti-inflammatory activity of some traditional medicinal plants.

    PubMed

    Singh, R K; Joshi, V K; Gambhir, S S

    1998-10-01

    The ethanol extract of roots, fruits and roots of solanum indicum and saccharum munja respectively and water soluble resin of commiphora myrrha were studied for antiinflammatory activity against carrageenin induced oedema in rats, the significant antiinflammatory activity were found in former two plants will slight anti inflammatory activity was observed in latter plant.

  12. Anti-proliferative activity and mechanism of action of titanocene dichloride.

    PubMed Central

    Christodoulou, C. V.; Eliopoulos, A. G.; Young, L. S.; Hodgkins, L.; Ferry, D. R.; Kerr, D. J.

    1998-01-01

    Development of resistance to cytotoxic agents is a major limitation to their clinical use. Novel compounds are synthesized with a view to develop non-cross-resistant, less toxic and more potent activity. The detection of the anti-tumour properties of the inorganic compound cisplatin stimulated a broad search for other metal-containing complexes. Titanocene dichloride was synthesized on this basis and has shown potent anti-neoplastic activity in experimental animals. We have examined the in vitro activity of titanocene dichloride in two pairs of platinum-sensitive and resistant human ovarian carcinoma cell lines, A2780/2780CP and CH1/CH1cisR, and in mutated p53- and bcl-2-transfected clones of A2780 cells. A time- and concentration-dependent anti-proliferative effect was observed in all cell lines treated with titanocene dichloride. The drug was found to significantly overcome platinum resistance in the 2780CP and the CH1 cisR cell lines and in the bcl-2 and the mutant p53 transfectants of A2780 cells. Titanocene dichloride induced a block in late S/early G2 phase of the cell cycle; however apoptotic cell death occurred from any phase of cycle. Titanium-DNA adducts were detected in A2780 cells treated with titanocene dichloride using atomic absorption spectrometry, suggesting that DNA may be a target for this drug. In agreement with this finding, p53 accumulated rapidly in drug-treated A2780 cells, indicative of a role for titanocene dichloride as a DNA-damaging agent. We have also performed studies to determine whether titanocene dichloride could demonstrate synergy with other cytotoxic agents in vitro. Isobologram analysis of cytotoxicity data obtained suggests that the combination of titanocene dichloride and 5-fluorouracil (5-FU) is synergistic. The potent in vivo anti-tumour activity of this compound, supported by the encouraging results from two phase I clinical trials, suggests that titanocene dichloride could be a promising novel chemotherapeutic agent

  13. Bioengineered Colorectal Cancer Drugs: Orally Delivered Anti-Inflammatory Agents.

    PubMed

    Urbanska, Aleksandra Malgorzata; Zhang, Xiaoying; Prakash, Satya

    2015-07-01

    Intestinal inflammation is one of the major factors that increase colorectal cancer (CRC) incidence worldwide. Inflammation in the gastrointestinal tract is directly linked to tumor development at the early stages of the disease, thus a key issue toward the prevention and the treatment of colonic neoplasia. Thus, the use of anti-inflammatory drugs has emerged first as a strategy to reduce chronic inflammation in case of many inflammatory bowel diseases (IBD), but it has proven its efficacy by reducing the risk of colonic neoplasia. This comprehensive review highlights the role of chronic inflammation, mainly in IBD, in the development of CRC including molecular and immune mechanisms that have tumorigenic effects. Multiple lines of evidence indicate that several bioactive and phytochemical compounds used as anti-inflammatory drugs have also antitumoral attributes. The uses of orally delivered cytokines and small molecules, as well as key dietary supplementation as anti-inflammatory therapeutics are discussed. In addition, comprehensive knowledge about CRC and intestinal inflammation, and the importance of the intestinal mucosal wall as a mucosal immunological barrier that comes into play during interactions with gut microbiota (pathogens and commensal), luminal secretions (bile acids, and bacterial and epithelial metabolites), and ingested chemicals (food components, high fat content, heterocyclic amines, and low intake of dietary fiber) are underscored. The multifunctionality of several anti-inflammatory drugs opens a line for their application in the treatment and prevention not only in IBD but also in CRC. Current bioengineering approaches for oral delivery of anti-inflammatory agents including cytokines, genetically modified bacteria, or small molecule inhibitors of inflammation directly contribute to the early management of CRC. Limitations of the current therapeutics, which stem from the lack of complete understanding of the complex molecular interactions

  14. The Role of MKP-1 in the Anti-Proliferative Effects of Glucocorticoids in Primary Rat Pre-Osteoblasts

    PubMed Central

    Sanderson, Micheline; Sadie-Van Gijsen, Hanél; Ferris, William F.

    2015-01-01

    Glucocorticoid (GC)-induced osteoporosis has been attributed to a GC-induced suppression of pre-osteoblast proliferation. Our previous work identified a critical role for mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) in mediating the anti-proliferative effects of GCs in immortalized pre-osteoblasts, but we subsequently found that MKP-1 null mice were not protected against the pathological effects of GCs on bone. In order to reconcile this discrepancy, we have assessed the effects of GCs on proliferation, activation of the MAPK ERK1/2 and MKP-1 expression in primary adipose-derived stromal cells (ADSCs) and ADSC-derived pre-osteoblasts (ADSC-OBs). ADSCs were isolated by means of collagenase digestion from adipose tissue biopsies harvested from adult male Wistar rats. ADSC-OBs were prepared by treating ADSCs with osteoblast differentiation media for 7 days. The effects of increasing concentrations of the GC dexamethasone on basal and mitogen-stimulated cell proliferation were quantified by tritiated thymidine incorporation. ERK1/2 activity was measured by Western blotting, while MKP-1 expression was quantified on both RNA and protein levels, using semi-quantitative real-time PCR and Western blotting, respectively. GCs were strongly anti-proliferative in both naïve ADSCs and ADSC-OBs, but had very little effect on mitogen-induced ERK1/2 activation and did not upregulate MKP-1 protein expression. These findings suggest that the anti-proliferative effects of GCs in primary ADSCs and ADSC-OBs in vitro do not require the inhibition of ERK1/2 activation by MKP-1, which is consistent with our in vivo findings in MKP-1 null mice. PMID:26263165

  15. Anti-inflammatory and cytotoxic activities of Bursera copallifera

    PubMed Central

    Columba-Palomares, M. F. María C.; Villareal, Dra. María L.; Acevedo Quiroz, M. C. Macdiel E.; Marquina Bahena, M. C. Silvia; Álvarez Berber, Dra. Laura P.; Rodríguez-López, Dra. Verónica

    2015-01-01

    Background: The plant species Bursera copallifera (DC) bullock is used in traditional medicine to treat inflammation. The leaves of this plant can be prepared as an infusion to treat migraines, bronchitis, and dental pain Objective: The purpose of this study was to determine the anti-inflammatory and cytotoxic activities of organic extracts from the stems, stem bark, and leaves of B. copallifera, which was selected based on the knowledge of its traditional use. Materials and Methods: We evaluated the ability of extracts to inhibit mouse ear inflammation in response to topical application of 12-O tetradecanoylphorbol-13-acetate. The extracts with anti-inflammatory activity were evaluated for their inhibition of pro-inflammatory enzymes. In addition, the in vitro cytotoxic activities of the organic extracts were evaluated using the sulforhodamine B assay. Results: The hydroalcoholic extract of the stems (HAS) exhibited an anti-inflammatory activity of 54.3% (0.5 mg/ear), whereas the anti-inflammatory activity of the dichloromethane-methanol extract from the leaves (DMeL) was 55.4% at a dose of 0.1 mg/ear. Methanol extract from the leaves (MeL) showed the highest anti-inflammatory activity (IC50 = 4.4 μg/mL), hydroalcoholic extract of leaves, and DMeL also reduce the enzyme activity, (IC50 = 6.5 μg/mL, IC50 = 5.7 μg/mL), respectively, from stems HAS exhibit activity at the evaluated concentrations (IC50 =6.4 μg/mL). The hydroalcoholic extract of the stems exhibited the highest cytotoxic activity against a breast adenocarcinoma cell line (MCF7, IC50 = 0.90 μg/mL), whereas DMeL exhibited an IC50 value of 19.9 μg/mL. Conclusion: In conclusion, extracts from leaves and stems inhibited cyclooxygenase-1, which is the target enzyme for nonsteroidal anti inflammatory drugs, and some of these extracts demonstrated substantial antiproliferative effects against the MCF7 cell line. These results validate the traditional use of B. copallifera. PMID:26664022

  16. Anti-inflammatory and antipyretic effects of boldine.

    PubMed

    Backhouse, N; Delporte, C; Givernau, M; Cassels, B K; Valenzuela, A; Speisky, H

    1994-10-01

    Boldine, an antioxidant alkaloid isolated from Peumus boldus, exhibits a dose-dependent anti-inflammatory activity in the carrageenan-induced guinea pig paw edema test with an oral ED50 of 34 mg/kg. Boldine also reduces bacterial pyrogen-induced hyperthermia in rabbits to an extent which varied between 51% and 98% at a dose of 60 mg/kg p.o. In vitro studies carried out in rat aortal rings revealed that boldine is an effective inhibitor of prostaglandin biosynthesis, promoting 53% inhibition at 75 microM. The latter in vitro effect may be mechanistically linked to the anti-inflammatory and antipyretic effects of boldine exerted in vivo. PMID:7879695

  17. Antibiotic and Anti-Inflammatory Therapies for Cystic Fibrosis

    PubMed Central

    Chmiel, James F.; Konstan, Michael W.; Elborn, J. Stuart

    2013-01-01

    Cystic fibrosis (CF) lung disease is characterized by chronic bacterial infection and an unremitting inflammatory response, which are responsible for most of CF morbidity and mortality. The median expected survival has increased from <6 mo in 1940 to >38 yr now. This dramatic improvement, although not great enough, is due to the development of therapies directed at secondary disease pathologies, especially antibiotics. The importance of developing treatments directed against the vigorous inflammatory response was realized in the 1990s. New therapies directed toward the basic defect are now visible on the horizon. However, the impact of these drugs on downstream pathological consequences is unknown. It is likely that antibiotics and anti-inflammatory drugs will remain an important part of the maintenance regimen for CF in the foreseeable future. Current and future antibiotic and anti-inflammatory therapies for CF are reviewed. PMID:23880054

  18. Isoflavones: Anti-Inflammatory Benefit and Possible Caveats

    PubMed Central

    Yu, Jie; Bi, Xiaojuan; Yu, Bing; Chen, Daiwen

    2016-01-01

    Inflammation, a biological response of body tissues to harmful stimuli, is also known to be involved in a host of diseases, such as obesity, atherosclerosis, rheumatoid arthritis, and even cancer. Isoflavones are a class of flavonoids that exhibit antioxidant, anticancer, antimicrobial, and anti-inflammatory properties. Increasing evidence has highlighted the potential for isoflavones to prevent the chronic diseases in which inflammation plays a key role, though the underlying mechanisms remain unclear. Recently, some studies have raised concerns about isoflavones induced negative effects like carcinogenesis, thymic involution, and immunosuppression. Therefore, this review aims to summarize the anti-inflammatory effects of isoflavones, unravel the underlying mechanisms, and present the potential health risks. PMID:27294954

  19. Anti-inflammatory effects of praseodymium, gadolinium and ytterbium chlorides.

    PubMed

    Basile, A C; Hanada, S; Sertié, J A; Oga, S

    1984-02-01

    Anti-inflammatory effects of chloride salts of praseodymium, gadolinium and ytterbium were investigated, using various experimental inflammatory models in rats. The lanthanide salts administered by oral route showed no significant effect, but when injected intraperitoneally they significantly inhibited the carrageenin-induced oedema, proportional to their doses ranging from 15 to 75 mg/kg. They also reduced nystatin-induced oedema and vascular permeability response to histamine and serotonin. Pronounced inhibitory effect of lanthanide salts at the dose of 50 mg/kg, i.p., was observed in histamine- and serotonin-induced changes in vascular permeability. Repeated administration of lanthanide salts in the dose of 20 mg/kg for 13 d significantly inhibited arthritis development. The same dose of these salts for a 6-d period similarly reduced granuloma formation. However, praseodymium, gadolinium and ytterbium chlorides showed no significant difference among themselves and their anti-inflammatory effects were smaller than those from phenylbutazone.

  20. Novel anti-inflammatory therapies for the treatment of atherosclerosis.

    PubMed

    Khan, Razi; Spagnoli, Vincent; Tardif, Jean-Claude; L'Allier, Philippe L

    2015-06-01

    The underlying role of inflammation in atherosclerosis has been characterized. However, current treatment of coronary artery disease (CAD) predominantly consists of targeted reductions in serum lipoprotein levels rather than combating the deleterious effects of acute and chronic inflammation. Vascular inflammation acts by a number of different molecular and cellular pathways to contribute to atherogenesis. Over the last decades, both basic studies and clinical trials have provided evidence for the potential benefits of treatment of inflammation in CAD. During this period, development of pharmacotherapies directed towards inflammation in atherosclerosis has accelerated quickly. This review will highlight specific therapies targeting interleukin-1β (IL-1β), P-selectin and 5-lipoxygenase (5-LO). It will also aim to examine the anti-inflammatory effects of serpin administration, colchicine and intravenous HDL-directed treatment of CAD. We summarize the mechanistic rationale and evidence for these novel anti-inflammatory treatments at both the experimental and clinical levels.

  1. Anti-inflammatory and Antinociceptive Activity of Ouabain in Mice

    PubMed Central

    de Vasconcelos, Danielle Ingrid Bezerra; Leite, Jacqueline Alves; Carneiro, Luciana Teles; Piuvezam, Márcia Regina; de Lima, Maria Raquel Vitorino; de Morais, Liana Clébia Lima; Rumjanek, Vivian Mary; Rodrigues-Mascarenhas, Sandra

    2011-01-01

    Ouabain, an inhibitor of the Na+/K+-ATPase pump, was identified as an endogenous substance of human plasma. Ouabain has been studied for its ability to interfere with various regulatory mechanisms. Despite the studies portraying the ability of ouabain to modulate the immune response, little is known about the effect of this substance on the inflammatory process. The aim of this work was to study the effects triggered by ouabain on inflammation and nociceptive models. Ouabain produced a reduction in the mouse paw edema induced by carrageenan, compound 48/80 and zymosan. This anti-inflammatory potential might be related to the inhibition of prostaglandin E2, bradykinin, and mast-cell degranulation but not to histamine. Ouabain also modulated the inflammation induced by concanavalin A by inhibiting cell migration. Besides that, ouabain presented antinociceptive activity. Taken these data together, this work demonstrated, for the first time, that ouabain presented in vivo analgesic and anti-inflammatory effects. PMID:21772669

  2. Anti-inflammatory effects of a Houttuynia cordata supercritical extract.

    PubMed

    Shin, Sunhee; Joo, Seong Soo; Jeon, Jeong Hee; Park, Dongsun; Jang, Min Jung; Kim, Tae Ook; Kim, Hyun Kyu; Hwang, Bang Yeon; Kim, Ki Yon; Kim, Yun Bae

    2010-09-01

    Anti-inflammatory effects of Houttuynia cordata supercritical extract (HSE) were investigated in a carrageenan-air pouch model. HSE (200 mg/kg, oral) suppressed exudation and albumin leakage, as well as inflammatory cell infiltration. Dexamethasone (2 mg/kg, i.p.) only decreased exudation and cell infiltration, while indomethacin (2 mg/kg, i.p.) reduced exudate volume and albumin content. HSE lowered tumor-necrosis factor (TNF)-alpha and nitric oxide (NO), as well as prostaglandin E(2) (PGE(2)). Dexamethasone only reduced TNF-alpha and NO, while indomethacin decreased TNF-alpha and PGE(2). The suppressive activity of HSE on NO and PGE(2) production was confirmed in RAW 264.7. These results demonstrate that HSE exerts anti-inflammatory effects by inhibiting both TNF-alpha-NO and cyclooxygenase II-PGE(2) pathways. PMID:20706037

  3. Therapeutic Potential of Hydrazones as Anti-Inflammatory Agents

    PubMed Central

    Bala, Suman; Sharma, Neha; Saini, Vipin

    2014-01-01

    Hydrazones are a special class of organic compounds in the Schiff base family. Hydrazones constitute a versatile compound of organic class having basic structure (R1R2C=NNR3R4). The active centers of hydrazone, that is, carbon and nitrogen, are mainly responsible for the physical and chemical properties of the hydrazones and, due to the reactivity toward electrophiles and nucleophiles, hydrazones are used for the synthesis of organic compound such as heterocyclic compounds with a variety of biological activities. Hydrazones and their derivatives are known to exhibit a wide range of interesting biological activities like antioxidant, anti-inflammatory, anticonvulsant, analgesic, antimicrobial, anticancer, antiprotozoal, antioxidant, antiparasitic, antiplatelet, cardioprotective, anthelmintic, antidiabetic, antitubercular, trypanocidal, anti-HIV, and so forth. The present review summarizes the efficiency of hydrazones as potent anti-inflammatory agents. PMID:25383223

  4. Anti-Inflammatory Drug Design Using a Molecular Hybridization Approach

    PubMed Central

    Bosquesi, Priscila Longhin; Melo, Thais Regina Ferreira; Vizioli, Ednir Oliveira; dos Santos, Jean Leandro; Chung, Man Chin

    2011-01-01

    The design of new drugs with better physiochemical properties, adequate absorption, distribution, metabolism, and excretion, effective pharmacologic potency and lacking toxicity remains is a challenge. Inflammation is the initial trigger of several different diseases, such as Alzheimer's disease, asthma, atherosclerosis, colitis, rheumatoid arthritis, depression, cancer; and disorders such as obesity and sexual dysfunction. Although inflammation is not the direct cause of these disorders, inflammatory processes often increase related pain and suffering. New anti-inflammatory drugs developed using molecular hybridization techniques to obtain multiple-ligand drugs can act at one or multiple targets, allowing for synergic action and minimizing toxicity. This work is a review of new anti-inflammatory drugs developed using the molecular modification approach.

  5. Aminocarbonyl arylvinylbenzamides as gastric sparing anti-inflammatory agents.

    PubMed

    Khadse, Saurabh C; Talele, Gokul S; Agrawal, Surendra S

    2011-05-01

    Some (E/Z)-aminocarbonyl arylvinylbenzamides (B1-B15) were synthesized, evaluated for anti-inflammatory activity and ulcerogenic tendency, and their effect on gastro-intestinal motility in the rats was studied. These benzamides comprising of aliphatic unsaturated region situated between two amide linkages were synthesized by nucleophilic ring opening of appropriate azlactones (AZ1-AZ4) by suitable amines. The characterization of newly synthesized benzamides was performed by IR, (1)H- and (13)C-NMR, mass and elemental analysis. Amongst the tested compounds, benzamide B1, B2, B4, B5, and B13 were able to produce comparable or superior anti-inflammatory activity at 10 and 20 mg/kg p.o. dose with respect to standard diclofenac in carrageenan induced rat paw edema model with lessened propensity to cause gastro-intestinal hypermotility and were found to have nil tendencies to generate gastric ulcers.

  6. Antibiotic and anti-inflammatory therapies for cystic fibrosis.

    PubMed

    Chmiel, James F; Konstan, Michael W; Elborn, J Stuart

    2013-10-01

    Cystic fibrosis (CF) lung disease is characterized by chronic bacterial infection and an unremitting inflammatory response, which are responsible for most of CF morbidity and mortality. The median expected survival has increased from <6 mo in 1940 to >38 yr now. This dramatic improvement, although not great enough, is due to the development of therapies directed at secondary disease pathologies, especially antibiotics. The importance of developing treatments directed against the vigorous inflammatory response was realized in the 1990s. New therapies directed toward the basic defect are now visible on the horizon. However, the impact of these drugs on downstream pathological consequences is unknown. It is likely that antibiotics and anti-inflammatory drugs will remain an important part of the maintenance regimen for CF in the foreseeable future. Current and future antibiotic and anti-inflammatory therapies for CF are reviewed.

  7. Constituents from Vigna vexillata and Their Anti-Inflammatory Activity

    PubMed Central

    Leu, Yann-Lii; Hwang, Tsong-Long; Kuo, Ping-Chung; Liou, Kun-Pei; Huang, Bow-Shin; Chen, Guo-Feng

    2012-01-01

    The seeds of Vigna genus are important food resources and there have already been many reports regarding their bioactivities. In our preliminary bioassay, the chloroform layer of methanol extracts of V. vexillata demonstrated significant anti-inflammatory bioactivity. Therefore, the present research is aimed to purify and identify the anti-inflammatory principles of V. vexillata. One new sterol (1) and two new isoflavones (2,3) were reported from the natural sources for the first time and their chemical structures were determined by the spectroscopic and mass spectrometric analyses. In addition, 37 known compounds were identified by comparison of their physical and spectroscopic data with those reported in the literature. Among the isolates, daidzein (23), abscisic acid (25), and quercetin (40) displayed the most significant inhibition of superoxide anion generation and elastase release. PMID:22949828

  8. Semisynthesis of Derivatives of Oleanolic Acid from Syzygium aromaticum and Their Antinociceptive and Anti-Inflammatory Properties.

    PubMed

    Rali, Sibusiso; Oyedeji, Opeoluwa O; Aremu, Olukayode O; Oyedeji, Adebola O; Nkeh-Chungag, Benedicta N

    2016-01-01

    Oleanolic acid is a pentacyclic triterpenoid compound widely found in plants and well known for its medicinal properties. Oleanolic acid (OA) was isolated from the ethyl acetate extract of Syzygium aromaticum flower buds. Semisynthesis afforded both acetate and ester derivatives. The derived compounds were monitored with thin layer chromatography and confirmed with nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), Fourier infrared (FT-IR) spectroscopy, and melting point (Mp). All these compounds were evaluated for their analgesic and anti-inflammatory properties at a dose of 40 mg/kg. Significant analgesic and anti-inflammatory effects were noted for all OA-derived compounds. In the formalin-induced pain test, the derivatives showed better analgesic effects compared to their precursor, whereas, in the tale flick test, oleanolic acid proved to be superior in analgesic effects compared to all its derivatives with the exception of the acetyl derivative. Acute inflammatory tests showed that acetyl derivatives possessed better anti-inflammatory activity compared to the other compounds. In conclusion, semisynthesis of oleanolic acid yielded several derivatives with improved solubility and enhanced analgesic and anti-inflammatory properties. PMID:27382191

  9. Semisynthesis of Derivatives of Oleanolic Acid from Syzygium aromaticum and Their Antinociceptive and Anti-Inflammatory Properties

    PubMed Central

    Rali, Sibusiso; Aremu, Olukayode O.; Oyedeji, Adebola O.; Nkeh-Chungag, Benedicta N.

    2016-01-01

    Oleanolic acid is a pentacyclic triterpenoid compound widely found in plants and well known for its medicinal properties. Oleanolic acid (OA) was isolated from the ethyl acetate extract of Syzygium aromaticum flower buds. Semisynthesis afforded both acetate and ester derivatives. The derived compounds were monitored with thin layer chromatography and confirmed with nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), Fourier infrared (FT-IR) spectroscopy, and melting point (Mp). All these compounds were evaluated for their analgesic and anti-inflammatory properties at a dose of 40 mg/kg. Significant analgesic and anti-inflammatory effects were noted for all OA-derived compounds. In the formalin-induced pain test, the derivatives showed better analgesic effects compared to their precursor, whereas, in the tale flick test, oleanolic acid proved to be superior in analgesic effects compared to all its derivatives with the exception of the acetyl derivative. Acute inflammatory tests showed that acetyl derivatives possessed better anti-inflammatory activity compared to the other compounds. In conclusion, semisynthesis of oleanolic acid yielded several derivatives with improved solubility and enhanced analgesic and anti-inflammatory properties. PMID:27382191

  10. Anti-inflammatory activity of arctigenin from Forsythiae Fructus.

    PubMed

    Kang, Hyo Sook; Lee, Ji Yun; Kim, Chang Jong

    2008-03-01

    Oleaceae Forsythiae Fructus has been used for anti-inflammatory, diuretics, antidote, and antibacterials in traditional herbal medicine. Our previous screening of medicinal plants showed that methanol (MeOH) extract of Forsythiae Fructus had significant anti-inflammatory activity, but the active ingredients remain unclear. For isolation of active ingredient of MeOH extract of Forsythiae Fructus, it was partitioned with n-hexane and ethylacetate (EtOAc), and arctigenin was isolated from EtOAc fraction by column chromatography with anti-inflammatory activity-guided separation. Its activity was evaluated in the animal models of inflammation including myeloperoxidase (MPO) and eosinophil peroxidase (EPO) activities in the edematous tissues homogenate, and silica-induced reactive oxygen species (ROS) production in the RAW 264.7 cell line. It was shown that arctigenin (100 mg/kg) had significantly decreased not only carrageenan-induced paw edema 3 and 4h after injection of carrageenan, arachidonic acid (AA)-induced ear edema at a painting dose of 0.1-1.0mg/ear, and acetic acid-induced writhing response and acetic acid-induced capillary permeability accentuation at an oral dose of 25-100, and 100 mg/kg, respectively, but also MPO and EPO activities at a painting dose of 0.1-1.0mg/ear in the AA-induced edematous tissues homogenate as indicators of neutrophils and eosinophils recruitment into the inflamed tissue. Further, arctigenin (0.1-10 microM) also significantly inhibited the intracellular ROS production by silica. These results indicate that arctigenin is a bioactive agent of Forsythiae Fructus having significant anti-inflammatory action by inhibition of the exudation, and leukocytes recruitment into the inflamed tissues. The pharmacologic mechanism of action of arctigenin may be due to the inhibition of release/production of inflammatory mediators such as AA metabolites and free radicals.

  11. Anti-inflammatory activity of mycelial extracts from medicinal mushrooms.

    PubMed

    Geng, Yan; Zhu, Shuiling; Lu, Zhenming; Xu, Hongyu; Shi, Jin-Song; Xu, Zheng-Hong

    2014-01-01

    Medicinal mushrooms have been essential components of traditional Chinese herbal medicines for thousands of years, and they protect against diverse health-related conditions. The components responsible for their anti-inflammatory activity have yet to be fully studied. This study investigates the anti-inflammatory activity of n-hexane, chloroform, ethyl acetate, and methanol extracts of mycelia in submerged culture from 5 commercially available medicinal mushrooms, namely Cephalosporium sinensis, Cordyceps mortierella, Hericium erinaceus, Ganoderma lucidum, and Armillaria mellea. MTT colorimetric assay was applied to measure the cytotoxic effects of different extracts. Their anti-inflammatory activities were evaluated via inhibition against production of lipopolysaccharide (LPS)-induced nitric oxide (NO) in murine macrophage-like cell line RAW264.7 cells. Of the 20 extracts, n-hexane, chloroform, ethyl acetate, and methanol extracts from C. sinensis, C. mortierella, and G. lucidum; chloroform extracts from H. erinaceus and A. mellea; and ethyl acetate extracts from A. mellea at nontoxic concentrations (<300 μg/mL) dose-dependently inhibited LPS-induced NO production. Among them, the chloroform extract from G. lucidum was the most effective inhibitor, with the lowest half maximal inhibitory concentration (64.09 ± 6.29 μg/mL) of the LPS-induced NO production. These results indicate that extracts from medicinal mushrooms exhibited anti-inflammatory activity that might be attributable to the inhibition of NO generation and can therefore be considered a useful therapeutic and preventive approach to various inflammation-related diseases.

  12. Mechanisms of nonsteroidal anti-inflammatory drugs in cancer prevention.

    PubMed

    Umar, Asad; Steele, Vernon E; Menter, David G; Hawk, Ernest T

    2016-02-01

    Various clinical and epidemiologic studies show that nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin and cyclooxygenase inhibitors (COXIBs) help prevent cancer. Since eicosanoid metabolism is the main inhibitory targets of these drugs the resulting molecular and biological impact is generally accepted. As our knowledge base and technology progress we are learning that additional targets may be involved. This review attempts to summarize these new developments in the field. PMID:26970125

  13. Hepatoprotective and anti-inflammatory activities of Plantago major L

    PubMed Central

    Türel, Idris; Özbek, Hanefi; Erten, Remzi; Öner, Ahmet Cihat; Cengiz, Nureddin; Yilmaz, Orhan

    2009-01-01

    Objective: The aim of this study was to investigate anti-inflammatory and hepatoprotective activities of Plantago major L. (PM). Materials and Methods: Anti-inflammatory activity: Control and reference groups were administered isotonic saline solution (ISS) and indomethacin, respectively. Plantago major groups were injected PM in doses of 5 mg/kg (PM-I), 10 mg/kg (PM-II), 20 mg/kg (PM-III) and 25 mg/kg (PM-IV). Before and three hours after the injections, the volume of right hind-paw of rats was measured using a plethysmometer. Hepatoprotective Activity: The hepatotoxicity was induced by carbon tetrachloride (CCl4) administration. Control, CCl4 and reference groups received isotonic saline solution, CCl4 and silibinin, respectively. Plantago major groups received CCl4 (0.8 ml/kg) and PM in doses of 10, 20 and 25 mg/kg, respectively for seven days. Blood samples and liver were collected on the 8th day after the animals were killed. Results: Plantago major had an anti-inflammatory effect matching to that of control group at doses of 20 and 25 mg/kg. It was found that reduction in the inflammation was 90.01% with indomethacin, 3.10% with PM-I, 41.56% with PM-II, 45.87% with PM-III and 49.76% with PM-IV. Median effective dose (ED50) value of PM was found to be 7.507 mg/kg. Plantago major (25 mg/kg) significantly reduced the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels when compared to the CCl4 group. The histopathological findings showed a significant difference between the PM (25 mg/kg) and CCl4 groups. Conclusion: The results showed that PM had a considerable anti-inflammatory and hepatoprotective activities. PMID:20442819

  14. Anti-Inflammatory Activity and Composition of Senecio salignus Kunth

    PubMed Central

    Pérez González, Cuauhtemoc; Serrano Vega, Roberto; González-Chávez, Marco; Zavala Sánchez, Miguel Angel; Pérez Gutiérrez, Salud

    2013-01-01

    We investigated the anti-inflammatory activity of Senecio salignus. This medicinal plant is often used in Mexico for the treatment of fever and rheumatism. Chloroform and methanol extracts of the plant were tested on 12-O-tetradecanoylphorbol-13-acetate- (TPA-) induced edema in mice ears. The methanol extract of the plant inhibited edema by 36 ± 4.4% compared with the control, while the chloroform extract exhibited an even greater level of inhibition (64.1%). The chloroform extract was then fractionated, and the composition of the active fraction was determined by GC-MS. The anti-inflammatory activity of this fraction was then tested on TPA-induced ear edema in mice, and we found that the active fraction could inhibit edema by 46.9%. The anti-inflammatory effect of the fraction was also tested on carrageenan-induced paw edema in rats at doses of 100 mg/kg; a 58.9 ± 2.8% reduction of the edema was observed 4 h after administration of carrageenan, and the effect was maintained for 5 h. PMID:23691512

  15. Anti-inflammatory effect of thalidomide dithiocarbamate and dithioate analogs.

    PubMed

    Talaat, Roba; El-Sayed, Waheba; Agwa, Hussein S; Gamal-Eldeen, Amira M; Moawia, Shaden; Zahran, Magdy A H

    2015-08-01

    Thalidomide has anti-inflammatory, immunomodulatory, and anti-angiogenic properties. It has been used to treat a variety of cancers and autoimmune diseases. This study aimed to characterize anti-inflammatory activities of novel thalidomide analogs by exploring their effects on splenocytes proliferation and macrophage functions and their antioxidant activity. MTT assay was used to assess the cytotoxic effect of thalidomide analogs against splenocytes. Tumor necrosis factor (TNF-α) and nuclear factor kappa B (NF-κB-P65) were determined by enzyme-linked immunosorbent assay (ELISA). Nitric oxide (NO) was estimated by colorimetric assay. Antioxidant activity was examined by ORAC assay. Our results demonstrated that thalidomide dithioate analog 2 and thalidomide dithiocarbamate analog 4 produced a slight increase in splenocyte proliferation compared with thalidomide. Thalidomide dithiocarbamate analog 1 is a potent inhibitor of TNF-α production, whereas thalidomide dithiocarbamate analog 5 is a potent inhibitor of both TNF-α and NO. Analog 2 has a pronounced inhibitory effect on NF-κB-P65 production level. All thalidomide analogs showed prooxidant activity against hydroxyl (OH) radical. Analog 1 and thalidomide dithioate analog 3 have prooxidant activity against peroxyl (ROO) radical in relation to thalidomide. On the other hand, analog 4 has a potent scavenging capacity against peroxyl (ROO) radical compared with thalidomide. Taken together, the results of this study suggest that thalidomide analogs might have valuable anti-inflammatory activities with more pronounced effect than thalidomide itself.

  16. Anti-inflammatory activity of traditional Chinese medicinal herbs

    PubMed Central

    Pan, Min-Hsiung; Chiou, Yi-Shiou; Tsai, Mei-Ling; Ho, Chi-Tang

    2011-01-01

    Accumulating epidemiological and clinical evidence shows that inflammation is an important risk factor for various human diseases. Thus, suppressing chronic inflammation has the potential to delay, prevent, and control various chronic diseases, including cerebrovascular, cardiovascular, joint, skin, pulmonary, blood, lymph, liver, pancreatic, and intestinal diseases. Various natural products from traditional Chinese medicine (TCM) have been shown to safely suppress proinflammatory pathways and control inflammation-associated disease. In vivo and/or in vitro studies have demonstrated that anti-inflammatory effects of TCM occur by inhibition of the expression of master transcription factors (for example, nuclear factor-κB (NF-κB)), pro-inflammatory cytokines (for example, tumor necrosis factor-α (TNF-α), chemokines (for example, chemokine (C-C motif) ligand (CCL)-24), intercellular adhesion molecule expression and pro-inflammatory mediators (for example, inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2)). However, a handful of review articles have focused on the anti-inflammatory activities of TCM and explore their possible mechanisms of action. In this review, we summarize recent research attempting to identify the anti-inflammatory constituents of TCM and their molecular targets that may create new opportunities for innovation in modern pharmacology. PMID:24716101

  17. Anti-inflammatory activity and chemical profile of Galphimia glauca.

    PubMed

    González-Cortazar, Manasés; Herrera-Ruiz, Maribel; Zamilpa, Alejandro; Jiménez-Ferrer, Enrique; Marquina, Silvia; Alvarez, Laura; Tortoriello, Jaime

    2014-01-01

    Galphimia glauca, commonly known as "flor de estrella", is a plant species used in Mexican traditional medicine for the treatment of different diseases that have an acute or chronic inflammatory process in common. Aerial parts of this plant contain nor-seco-triterpenoids with anxiolytic properties, which have been denominated galphimines. Other compounds identified in the plant are tetragalloyl-quinic acid, gallic acid, and quercetin, which are able to inhibit the bronchial obstruction induced by platelet-activating factor. The objective of this work was to evaluate the anti-inflammatory effect of crude extracts from G. glauca and, by means of bioguided chemical separation, to identify the compounds responsible for this pharmacological activity. n-Hexane, ethyl acetate, dichloromethane, and methanol extracts showed an important anti-inflammatory effect. Chemical separation of the active methanol extract allowed us to identify the nor-seco-triterpenes galphimine-A (1) and galphimine-E (3) as the anti-inflammatory principles. Analysis of structure-activity relationships evidenced that the presence of an oxygenated function in C6 is absolutely necessary to show activity. In this work, the isolation and structural elucidation of two new nor-seco-triterpenes denominated as galphimine-K (4) and galphimine-L (5), together with different alkanes, fatty acids, as well as three flavonoids (17-19), are described, to our knowledge for the first time, from Galphimia glauca.

  18. Anti-inflammatory properties of pterocarpanquinone LQB-118 in mice.

    PubMed

    Riça, Ingred G; Netto, Chaquip D; Rennó, Magdalena N; Abreu, Paula A; Costa, Paulo R R; da Silva, Alcides J M; Cavalcante, Moisés C M

    2016-09-15

    Pterocarpanquinone (+/-)-LQB-118 presents antineoplastic and antiparasitic properties and also shows great inhibitory effect on TNF-α release in vitro. Here, its anti-inflammatory activity was evaluated in a lipopolysaccharide (LPS)-induced lung inflammation model in C57BL/6 mice. LPS inhalation induced a marked neutrophil infiltration to the lungs which was reduced by intraperitoneal treatment with (+/-)-LQB-118 in a similar manner to that of dexamethasone and even better than that of acetylsalicylic acid. Moreover, (+/-)-LQB-118 administration resulted in decrease of NF-κB activation and KC level in lungs, with a pronounced inhibitory effect on TNF-α release, measured in bronchoalveolar lavage fluid. Trying to understand the anti-inflammatory mechanism by which (+/-)-LQB-118 acts, we performed a molecular modeling analysis, including docking to estrogen receptors α and β. Results suggested that (+/-)-LQB-118 may bind to both receptors, with a similar orientation to 17-β-estradiol. Together, these results showed that (+/-)-LQB-118 exhibits an anti-inflammatory effect, most likely by inhibiting TNF-α release and NF-κB activation, which may be related to the estrogen receptor binding.

  19. Anti-inflammatory and antimicrobial activities of novel pyrazole analogues.

    PubMed

    Surendra Kumar, R; Arif, Ibrahim A; Ahamed, Anis; Idhayadhulla, Akbar

    2016-09-01

    A new sequence of pyrazole derivatives (1-6) was synthesized from condensation technique under utilizing ultrasound irradiation. Synthesized compounds were characterized from IR, (1)H NMR, (13)C NMR, Mass and elemental analysis. Synthesized compounds (1-6) were screened for antimicrobial activity. Among the compounds 3 (MIC: 0.25 μg/mL) was exceedingly antibacterially active against gram negative bacteria of Escherichia coli and compound 4 (MIC: 0.25 μg/mL) was highly active against gram positive bacteria of Streptococcus epidermidis compared with standard Ciprofloxacin. Compound 2 (MIC: 1 μg/mL) was highly antifungal active against Aspergillus niger proportionate to Clotrimazole. Synthesized compounds (1-6) were screened for anti-inflammatory activity and the compound 2-((5-hydroxy-3-methyl-1H-pyrazol-4-yl)(4-nitrophenyl)methyl)hydrazinecarboxamide (4) was better activity against anti-inflammatory when compared with standard drugs (Diclofenac sodium). Compounds (2, 3 and 4) are the most important molecules and hence the need to develop new drugs of antibacterial, antifungal and anti-inflammatory agents. PMID:27579011

  20. Anti-inflammatory properties of pterocarpanquinone LQB-118 in mice.

    PubMed

    Riça, Ingred G; Netto, Chaquip D; Rennó, Magdalena N; Abreu, Paula A; Costa, Paulo R R; da Silva, Alcides J M; Cavalcante, Moisés C M

    2016-09-15

    Pterocarpanquinone (+/-)-LQB-118 presents antineoplastic and antiparasitic properties and also shows great inhibitory effect on TNF-α release in vitro. Here, its anti-inflammatory activity was evaluated in a lipopolysaccharide (LPS)-induced lung inflammation model in C57BL/6 mice. LPS inhalation induced a marked neutrophil infiltration to the lungs which was reduced by intraperitoneal treatment with (+/-)-LQB-118 in a similar manner to that of dexamethasone and even better than that of acetylsalicylic acid. Moreover, (+/-)-LQB-118 administration resulted in decrease of NF-κB activation and KC level in lungs, with a pronounced inhibitory effect on TNF-α release, measured in bronchoalveolar lavage fluid. Trying to understand the anti-inflammatory mechanism by which (+/-)-LQB-118 acts, we performed a molecular modeling analysis, including docking to estrogen receptors α and β. Results suggested that (+/-)-LQB-118 may bind to both receptors, with a similar orientation to 17-β-estradiol. Together, these results showed that (+/-)-LQB-118 exhibits an anti-inflammatory effect, most likely by inhibiting TNF-α release and NF-κB activation, which may be related to the estrogen receptor binding. PMID:27492193

  1. Preparative Purification of Anti-Proliferative Diarylheptanoids from Betula platyphylla by High-Speed Counter-Current Chromatography.

    PubMed

    Cho, Namki; Kim, Hyun Woo; Kim, Tae Bum; Ransom, Tanya T; Beutler, John A; Sung, Sang Hyun

    2016-01-01

    A simple and rapid method using high-speed counter-current chromatography (HSCCC), along with bioassay-guided fractionation based on the anti-proliferative activity against renal and colon cancer cells, has been developed for the preparative separation of aceroside VIII (1) and platyphylloside (2) from Betula platyphylla. A solvent system composed of ethyl acetate/acetonitrile/water (1:0.1:1, v/v/v) was optimized for the separation. The upper phase was used as the stationary phase, and the lower phase was used as the mobile phase. Among these isolated diarylheptanoids, platyphylloside (2) showed anti-proliferative activity in the COLO205 and KM12 colon cells and renal cancer cell lines A498, U031, as well as in MG63 and MG 63.3 osteosarcoma cells. In addition, it showed dose dependent inhibitory effects in the NCI 60 cell line assay. These results suggest that the diarylheptanoids isolated from B. platyphylla with an efficient HSCCC method could be potential multi-targeted therapeutic agents for cancer.

  2. Proteomics Guided Discovery of Flavopeptins: Anti-Proliferative Aldehydes Synthesized by a Reductase Domain-Containing Nonribosomal Peptide Synthetase

    PubMed Central

    Chen, Yunqiu; McClure, Ryan A.; Zheng, Yupeng; Thomson, Regan J.; Kelleher, Neil L.

    2013-01-01

    Due to the importance of proteases in regulating cellular processes, the development of protease inhibitors has garnered great attention. Peptide-based aldehydes are a class of compounds that exhibit inhibitory activities against various proteases and proteasomes in the context of anti-proliferative treatments for cancer and other diseases. More than a dozen peptide-based natural products containing aldehydes have been discovered such as chymostatin, leupeptin, and fellutamide; however, the biosynthetic origin of the aldehyde functionality has yet to be elucidated. Herein we describe the discovery of a new group of lipopeptide aldehydes, the flavopeptins, and the corresponding biosynthetic pathway arising from an orphan gene cluster in Streptomyces sp. NRRL-F6652, a close relative of Streptomyces flavogriseus ATCC 33331. This research was initiated using a proteomics approach that screens for expressed enzymes involved in secondary metabolism in microorganisms. Flavopeptins are synthesized through a nonribosomal peptide synthetase containing a terminal NAD(P)H dependent reductase domain likely for the reductive release of the peptide with a C-terminal aldehyde. Solid phase peptide synthesis of several flavopeptin species and derivatives enabled structural verification and subsequent screening of biological activity. Flavopeptins exhibited submicromolar inhibition activities against cysteine proteases such as papain and calpain as well as the human 20S proteasome. They also showed anti-proliferative activities against multiple myeloma and lymphoma cell lines. PMID:23763305

  3. Tristetraprolin mediates anti-inflammatory effects of carbon monoxide on lipopolysaccharide-induced acute lung injury.

    PubMed

    Joe, Yeonsoo; Kim, Seul-Ki; Chen, Yingqing; Yang, Jung Wook; Lee, Jeong-Hee; Cho, Gyeong Jae; Park, Jeong Woo; Chung, Hun Taeg

    2015-11-01

    Low-dose inhaled carbon monoxide is reported to suppress inflammatory responses and exhibit a therapeutic effect in models of lipopolysaccharide (LPS)-induced acute lung injury (ALI). However, the precise mechanism by which carbon monoxide confers protection against ALI is not clear. Tristetraprolin (TTP; official name ZFP36) exerts anti-inflammatory effects by enhancing decay of proinflammatory cytokine mRNAs. With the use of TTP knockout mice, we demonstrate here that the protection by carbon monoxide against LPS-induced ALI is mediated by TTP. Inhalation of carbon monoxide substantially increased the pulmonary expression of TTP. carbon monoxide markedly enhanced the decay of mRNA-encoding inflammatory cytokines, blocked the expression of inflammatory cytokines, and decreased tissue damage in LPS-treated lung tissue. Moreover, knockout of TTP abrogated the anti-inflammatory and tissue-protective effects of carbon monoxide in LPS-induced ALI. These results suggest that carbon monoxide-induced TTP mediates the protective effect of carbon monoxide against LPS-induced ALI by enhancing the decay of mRNA encoding proinflammatory cytokines.

  4. Furanodiene presents synergistic anti-proliferative activity with paclitaxel via altering cell cycle and integrin signaling in 95-D lung cancer cells.

    PubMed

    Xu, Wen-Shan; Dang, Yuan-Ye; Chen, Xiu-Ping; Lu, Jin-Jian; Wang, Yi-Tao

    2014-02-01

    Furanodiene (FUR) is a natural terpenoid isolated from Rhizoma Curcumae, a well-known Chinese medicinal herb that presents anti-proliferative activities in several cancer cell lines. Recently, we found that the combined treatment of FUR with paclitaxel (TAX) showed synergetic anti-proliferative activities in 95-D lung cancer cells. Herein, we showed that FUR reduced the cell numbers distributed in mitosis phase induced by TAX while increased those in G1 phase. The protein levels of cyclin D1, cyclin B1, CDK6 and c-Myc were all down-regulated in the group of combined treatment. The dramatically down-regulated expression of integrin β4, focal adhesion kinase and paxillin might partially contribute to the synergic effect. Though FUR alone obviously induced endoplasmic reticulum stress, this signaling pathway may not contribute to the synergetic anti-proliferative effect as the protein expression of CHOP and BIP was similar in FUR alone and combined treatment group.

  5. Synthesis and anti-inflammatory properties of some aromatic and heterocyclic aromatic curcuminoids.

    PubMed

    Khan, M Akram; El-Khatib, Riyad; Rainsford, K D; Whitehouse, M W

    2012-02-01

    A variety of novel aromatic and heterocyclic aromatic curcuminoids were synthesised, characterised and their anti-inflammatory activities (AIA) determined in vivo. Some of these compounds also were tested for inflammatory mediator production. The AIA of the main representatives of these compounds were assessed by oral administration to female Wistar rats using (a) acute carrageenan-induced paw oedema, (b) chronic adjuvant arthritis (therapeutic mode), and (c) anti-pyretic activity assessed in the yeast pyrexia. Gastric ulceration was determined in pre-inflamed rats. Natural curcumin showed modest aspirin-like anti-inflammatory activity which was enhanced when co-administered with the PGE(1) analogue misoprostol as a synergist. In contrast, four novel curcuminoids (RK-97, RK-103, RK-104 and RK-106) in which the bis-methoxy-phenyl group of curcumin was replaced with bis-dimethoxybutenolidyl-(ascorbate), bis-naphthyl, and bis-furanyl derivatives, respectively, had potent activity in the anti-arthritic assay with little gastric or systemic toxicity, compared with the vehicle-treated controls. Of the curcuminoids the furan RK-106 was the only compound to inhibit production of TNFα and IL-1β in a monocytic cell-line THP-1 in vitro. The inactivity of RK-106 on the production of PGE(2) may be related to its absence of gastrotoxicity. None of the curcuminoids exhibited anti-pyretic activity and this may also be related to its insensitivity to PGE(2). Thus, these novel curcuminoids, such as RK-106, may warrant the development of new low gastro-toxic anti-inflammatory agents with selective inhibitory activity of cytokine inflammatory mediators. PMID:22172598

  6. Microparticles Containing Curcumin Solid Dispersion: Stability, Bioavailability and Anti-Inflammatory Activity.

    PubMed

    Teixeira, C C C; Mendonça, L M; Bergamaschi, M M; Queiroz, R H C; Souza, G E P; Antunes, L M G; Freitas, L A P

    2016-04-01

    This work aimed at improving the solubility of curcumin by the preparation of spray-dried ternary solid dispersions containing Gelucire®50/13-Aerosil® and quantifying the resulting in vivo oral bioavailability and anti-inflammatory activity. The solid dispersion containing 40% of curcumin was characterised by calorimetry, infrared spectroscopy and X-ray powder diffraction. The solubility and dissolution rate of curcumin in aqueous HCl or phosphate buffer improved up to 3600- and 7.3-fold, respectively. Accelerated stability test demonstrated that the solid dispersion was stable for 9 months. The pharmacokinetic study showed a 5.5-fold increase in curcumin in rat blood plasma when compared to unprocessed curcumin. The solid dispersion also provided enhanced anti-inflammatory activity in rat paw oedema. Finally, the solid dispersion proposed here is a promising way to enhance curcumin bioavailability at an industrial pharmaceutical perspective, since its preparation applies the spray drying, which is an easy to scale up technique. The findings herein stimulate further in vivo evaluations and clinical tests as a cancer and Alzheimer chemoprevention agent. PMID:26040724

  7. Microparticles Containing Curcumin Solid Dispersion: Stability, Bioavailability and Anti-Inflammatory Activity.

    PubMed

    Teixeira, C C C; Mendonça, L M; Bergamaschi, M M; Queiroz, R H C; Souza, G E P; Antunes, L M G; Freitas, L A P

    2016-04-01

    This work aimed at improving the solubility of curcumin by the preparation of spray-dried ternary solid dispersions containing Gelucire®50/13-Aerosil® and quantifying the resulting in vivo oral bioavailability and anti-inflammatory activity. The solid dispersion containing 40% of curcumin was characterised by calorimetry, infrared spectroscopy and X-ray powder diffraction. The solubility and dissolution rate of curcumin in aqueous HCl or phosphate buffer improved up to 3600- and 7.3-fold, respectively. Accelerated stability test demonstrated that the solid dispersion was stable for 9 months. The pharmacokinetic study showed a 5.5-fold increase in curcumin in rat blood plasma when compared to unprocessed curcumin. The solid dispersion also provided enhanced anti-inflammatory activity in rat paw oedema. Finally, the solid dispersion proposed here is a promising way to enhance curcumin bioavailability at an industrial pharmaceutical perspective, since its preparation applies the spray drying, which is an easy to scale up technique. The findings herein stimulate further in vivo evaluations and clinical tests as a cancer and Alzheimer chemoprevention agent.

  8. Improved dissolution and anti-inflammatory activity of ibuprofen-polyethylene glycol 8000 solid dispersion systems

    PubMed Central

    Ofokansi, Kenneth C.; Kenechukwu, Franklin C.; Ezugwu, Richard O.; Attama, Anthony A.

    2016-01-01

    Background: The purpose of this study was to develop ibuprofen (IB)-polyethylene glycol (PEG) 8000 solid dispersions (SDs) and investigate them for in vitro dissolution and in vivo anti-inflammatory activity. Materials and Methods: IB-PEG 8000 SDs were prepared by fusion method using varying combination ratios of IB and PEG 8000. Characterization based on surface morphology, particle size, absolute drug content, and Fourier transform infrared (FT-IR) spectroscopy was carried out on the SDs. The in vitro release of IB from the SDs was performed in simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.4) without enzymes, whereas the anti-inflammatory activity was evaluated using egg albumin-induced rat paw edema model. Results: Greenish brown, discrete, and irregularly shaped SDs of mean particle size range 113.5 ± 2.5-252.5 ± 1.9 μm, which were stable over 3 months, were obtained. The drug content of the SDs ranged from 73.4 ± 2.9 % to 83.5 ± 2.7%. Although the drug content increased with increased concentration of PEG 8000 in the SDs, the mean particle size decreased with increased concentration of PEG 8000 in the SDs. The FT-IR results indicate no strong chemical interaction of IB and PEG 8000 in the SDs. There was marked increase in the dissolution rate of IB from the SDs (P < 0.05) as compared to pure IB and physical mixture. The dissolution was better in SIF than in SGF. The increased dissolution rate of IB may be due to the formation of microcrystals, increased wettability and dispersibility in PEG 8000. The SDs showed good anti-inflammatory properties achieving up to 90% edema inhibition at 6 h while the pure sample of IB had 77% edema inhibition at 6 h. Conclusion: SDs based on IB-PEG 8000 is a good approach to enhance the dissolution rate and anti-inflammatory activity of IB, thus, encouraging further development of the SDs. PMID:27606257

  9. Improved dissolution and anti-inflammatory activity of ibuprofen-polyethylene glycol 8000 solid dispersion systems

    PubMed Central

    Ofokansi, Kenneth C.; Kenechukwu, Franklin C.; Ezugwu, Richard O.; Attama, Anthony A.

    2016-01-01

    Background: The purpose of this study was to develop ibuprofen (IB)-polyethylene glycol (PEG) 8000 solid dispersions (SDs) and investigate them for in vitro dissolution and in vivo anti-inflammatory activity. Materials and Methods: IB-PEG 8000 SDs were prepared by fusion method using varying combination ratios of IB and PEG 8000. Characterization based on surface morphology, particle size, absolute drug content, and Fourier transform infrared (FT-IR) spectroscopy was carried out on the SDs. The in vitro release of IB from the SDs was performed in simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.4) without enzymes, whereas the anti-inflammatory activity was evaluated using egg albumin-induced rat paw edema model. Results: Greenish brown, discrete, and irregularly shaped SDs of mean particle size range 113.5 ± 2.5-252.5 ± 1.9 μm, which were stable over 3 months, were obtained. The drug content of the SDs ranged from 73.4 ± 2.9 % to 83.5 ± 2.7%. Although the drug content increased with increased concentration of PEG 8000 in the SDs, the mean particle size decreased with increased concentration of PEG 8000 in the SDs. The FT-IR results indicate no strong chemical interaction of IB and PEG 8000 in the SDs. There was marked increase in the dissolution rate of IB from the SDs (P < 0.05) as compared to pure IB and physical mixture. The dissolution was better in SIF than in SGF. The increased dissolution rate of IB may be due to the formation of microcrystals, increased wettability and dispersibility in PEG 8000. The SDs showed good anti-inflammatory properties achieving up to 90% edema inhibition at 6 h while the pure sample of IB had 77% edema inhibition at 6 h. Conclusion: SDs based on IB-PEG 8000 is a good approach to enhance the dissolution rate and anti-inflammatory activity of IB, thus, encouraging further development of the SDs.

  10. Anti-inflammatory ligustilides from Ligusticum chuanxiong Hort.

    PubMed

    Huang, Jian; Lu, Xiao-Qing; Zhang, Cui; Lu, Jin; Li, Guo-Yu; Lin, Rui-Chao; Wang, Jin-Hui

    2013-12-01

    Four new ligustilides chuanxiongnolide R1 (1), chuanxiongnolide R2 (2), chuanxiongdiolide R1 (3) and chuanxiongdiolide R2 (4) together with eight known derivatives (5-12) were isolated from the root of Ligusticum chuanxiong Hort. Their structures were elucidated by HR-ESI-MS, UV, IR, 1D and 2D NMR (HSQC, HMBC, (1)H-(1)H COSY, NOESY) methods. The absolute configurations were confirmed via the circular dichroism (CD) spectrum. The anti-inflammatory assay in LPS-triggered RAW 264.7 macrophages was carried out on the twelve compounds. 1, 3, 5 and 6 showed significant inhibitory effects against LPS-induced NO production. PMID:23973655

  11. Anti-inflammatory sesquiterpene lactones from Lourteigia ballotaefolia.

    PubMed

    Rosas-Romero, Alfredo; Manchado, Carlos Martinez; Crescente, Oscar; Acosta, Mercedes; Curini, Massimo; Epifano, Francesco; Marcotullio, Maria Carla; Rosati, Ornelio; Tubaro, Aurelia; Sosa, Silvio

    2002-09-01

    Three sesquiterpene lactones were isolated from Lourteigia ballotaefolia (H. B. K.). 9beta-hydroxy-atripliciolide-8- O-tiglate ( 1) was isolated for the first time from this plant and was previously reported in Conocliniopsis prasiifolia (DC) K. et R., 9beta-hydroxy-atripliciolide-8- O-(5'-acetoxytiglate) ( 2) had been already reported in this species. The minor component, 9beta-(tigloyloxy)-atripliciolide, is a new compound. The anti-inflammatory activity of compounds 1 and 2 was evaluated using the croton oil ear test in mice.

  12. Anti-inflammatory and immunosuppressive drugs and reproduction

    PubMed Central

    Østensen, Monika; Khamashta, Munther; Lockshin, Michael; Parke, Ann; Brucato, Antonio; Carp, Howard; Doria, Andrea; Rai, Raj; Meroni, Pierluigi; Cetin, Irene; Derksen, Ronald; Branch, Ware; Motta, Mario; Gordon, Caroline; Ruiz-Irastorza, Guillermo; Spinillo, Arsenio; Friedman, Deborah; Cimaz, Rolando; Czeizel, Andrew; Piette, Jean Charles; Cervera, Ricard; Levy, Roger A; Clementi, Maurizio; De Carolis, Sara; Petri, Michelle; Shoenfeld, Yehuda; Faden, David; Valesini, Guido; Tincani, Angela

    2006-01-01

    Rheumatic diseases in women of childbearing years may necessitate drug treatment during a pregnancy, to control maternal disease activity and to ensure a successful pregnancy outcome. This survey is based on a consensus workshop of international experts discussing effects of anti-inflammatory, immunosuppressive and biological drugs during pregnancy and lactation. In addition, effects of these drugs on male and female fertility and possible long-term effects on infants exposed to drugs antenatally are discussed where data were available. Recommendations for drug treatment during pregnancy and lactation are given. PMID:16712713

  13. Aerosolized Surfactants, Anti-Inflammatory Drugs, and Analgesics.

    PubMed

    Willson, Douglas F

    2015-06-01

    Drug delivery by aerosol may have several advantages over other modes, particularly if the lung is the target organ. Aerosol delivery may allow achievement of higher concentrations while minimizing systemic effects and offers convenience, rapid onset of action, and avoidance of the needles and sterile technique necessary with intravenous drug administration. Aerosol delivery may change the pharmacokinetics of many drugs, however, and an awareness of the caveats of aerosolized drug delivery is mandatory to ensure both safety and adequate drug delivery. This paper discusses the administration of surfactants, anti-inflammatory agents, and analgesics by the aerosol route.

  14. Nitro-fatty acids: novel anti-inflammatory lipid mediators

    PubMed Central

    Rubbo, H.

    2013-01-01

    Nitro-fatty acids are formed and detected in human plasma, cell membranes, and tissue, modulating metabolic as well as inflammatory signaling pathways. Here we discuss the mechanisms of nitro-fatty acid formation as well as their key chemical and biochemical properties. The electrophilic properties of nitro-fatty acids to activate anti-inflammatory signaling pathways are discussed in detail. A critical issue is the influence of nitroarachidonic acid on prostaglandin endoperoxide H synthases, redirecting arachidonic acid metabolism and signaling. We also analyze in vivo data supporting nitro-fatty acids as promising pharmacological tools to prevent inflammatory diseases. PMID:24068188

  15. Anti-inflammatory activity of Abutilon indicum extract.

    PubMed

    Tripathi, Priyanka; Chauhan, N S; Patel, J R

    2012-01-01

    Abutilon indicum Linn. had been broadly used for its reported biological activities in indigenous system of medicine. The ethanolic extract of the whole plant of A. indicum Linn. was evaluated for its anti-inflammatory activity at doses 250, 500 and 750 mg kg⁻¹ using the carrageenan-induced paw oedema in healthy Wistar albino rats. Results of in vivo activity led to the conclusion that the ethanolic extract of A. indicum showed predominantly significant activity in a dose-dependent manner, which is comparable to the reference standard ibuprofen. The results prove the traditional use of plant in the treatment of inflammation. PMID:21999427

  16. Synthesis and anti-inflammatory activity of indole glucosinolates.

    PubMed

    Vo, Quan V; Trenerry, Craige; Rochfort, Simone; Wadeson, Jenny; Leyton, Carolina; Hughes, Andrew B

    2014-01-15

    The nitronate and nitrovinyl methods to synthesize indole glucosinolates (GLs) have been investigated. The results were applied to generally the most prevalent natural indole glucosinolates to synthesize 4-methoxyglucobrassicin (MGB) and neo-glucobrassicin (NGB) in moderate overall yield for the first time. The anti-inflammatory activity of the synthetic indole GLs was determined by inhibition of TNF-α secretion in LPS-stimulated THP-1 cells. The data showed that glucobrassicin (GB) exhibited higher activity than other synthetic indolyl GLs. PMID:24360830

  17. Topical Nonsteroidal Anti-Inflammatory Drugs for Macular Edema

    PubMed Central

    Parmeggiani, Francesco; Romano, Mario R.; dell'Omo, Roberto

    2013-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are nowadays widely used in ophthalmology to reduce eye inflammation, pain, and cystoid macular edema associated with cataract surgery. Recently, new topical NSAIDs have been approved for topical ophthalmic use, allowing for greater drug penetration into the vitreous. Hence, new therapeutic effects can be achieved, such as reduction of exudation secondary to age-related macular degeneration or diabetic maculopathy. We provide an updated review on the clinical use of NSAIDs for retinal diseases, with a focus on the potential future applications. PMID:24227908

  18. Nonsteroidal Anti-Inflammatory Drugs for Retinal Disease

    PubMed Central

    Schoenberger, Scott D.; Kim, Stephen J.

    2013-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are used extensively in ophthalmology for pain and photophobia after photorefractive surgery and to reduce miosis, inflammation, and cystoid macular edema following cataract surgery. In recent years, the US Food and Drug Administration has approved new topical NSAIDs and previously approved NSAIDs have been reformulated. These changes may allow for greater drug penetration into the retina and thereby offer additional therapeutic advantages. For example, therapeutic effects on diabetic retinopathy and age-related macular degeneration may now be achievable. We provide an updated review on the scientific rationale and clinical use of NSAIDs for retinal disease. PMID:23365785

  19. Natural anti-inflammatory agents for pain relief

    PubMed Central

    Maroon, Joseph C.; Bost, Jeffrey W.; Maroon, Adara

    2010-01-01

    The use of both over-the-counter and prescription nonsteroidal medications is frequently recommended in a typical neurosurgical practice. But persistent long-term use safety concerns must be considered when prescribing these medications for chronic and degenerative pain conditions. This article is a literature review of the biochemical pathways of inflammatory pain, the potentially serious side effects of nonsteroidal drugs and commonly used and clinically studied natural alternative anti-inflammatory supplements. Although nonsteroidal medications can be effective, herbs and dietary supplements may offer a safer, and often an effective, alternative treatment for pain relief, especially for long-term use. PMID:21206541

  20. The Design, Synthesis and Evaluation of Coumarin Ring Derivatives of the Novobiocin Scaffold that Exhibit Anti-proliferative Activity

    PubMed Central

    Donnelly, Alison C.; Mays, Jared R.; Burlison, Joseph A.; Nelson, John T.; Vielhauer, George; Holzbeierlein, Jeffrey; Blagg, Brian S. J.

    2009-01-01

    Novobiocin, a known DNA gyrase inhibitor, binds to a nucleotide-binding site located on the C-terminus of Hsp90 and induces degradation of Hsp90-dependent client proteins at ~700 μM in breast cancer cells (SkBr3). Although many analogues of novobiocin have been synthesized, it was only recently demonstrated that monomeric species can exhibit anti-proliferative activity against various cancer cell lines. To further refine the essential elements of the coumarin core, a series of modified coumarin derivatives was synthesized and evaluated for elucidation of structure–activity relationships for novobiocin as an anti-cancer agent. Results obtained from these studies have produced novobiocin analogues that manifest low micromolar activity against several cancer cell lines. PMID:18939877

  1. Acyl sulfonamide anti-proliferatives: benzene substituent structure-activity relationships for a novel class of antitumor agents.

    PubMed

    Lobb, Karen L; Hipskind, Philip A; Aikins, James A; Alvarez, Enrique; Cheung, Yiu-Yin; Considine, Eileen L; De Dios, Alfonso; Durst, Gregory L; Ferritto, Rafael; Grossman, Cora Sue; Giera, Deborah D; Hollister, Beth A; Huang, Zhongping; Iversen, Philip W; Law, Kevin L; Li, Tiechao; Lin, Ho-Shen; Lopez, Beatriz; Lopez, Jose E; Cabrejas, Luisa M Martin; McCann, Denis J; Molero, Victoriano; Reilly, John E; Richett, Michael E; Shih, Chuan; Teicher, Beverly; Wikel, James H; White, Wesley T; Mader, Mary M

    2004-10-21

    Two closely related diaryl acylsulfonamides were recently reported as potent antitumor agents against a broad spectrum of human tumor xenografts (colon, lung, breast, ovary, and prostate) in nude mice. Especially intriguing was their activity against colorectal cancer xenografts. In this paper, rapid parallel synthesis along with traditional medicinal chemistry techniques were used to quickly delineate the structure-activity relationships of the substitution patterns in both phenyl rings of the acylsufonamide anti-proliferative scaffold. Although the molecular target of the compounds remains unclear, we determined that the vascular endothelial growth factor-dependent human umbilical vein endothelial cells assay in combination with a soft agar disk diffusion assay allowed for optimization of potency in the series. The pharmacokinetic properties and in vivo activity in an HCT116 xenograft model are reported for representative compounds. PMID:15481975

  2. Synthesis and anti-inflammatory activity evaluation of novel triazolyl-isatin hybrids.

    PubMed

    Sharma, Pramod K; Balwani, Sakshi; Mathur, Divya; Malhotra, Shashwat; Singh, Brajendra K; Prasad, Ashok K; Len, Christophe; Van der Eycken, Erik V; Ghosh, Balaram; Richards, Nigel G J; Parmar, Virinder S

    2016-12-01

    New isatin-triazole based hybrids have been synthesized and evaluated for their inhibitory activity of TNF-α induced expression of Intercellular Adhesion Molecule-1 (ICAM-1) on the surface of human endothelial cells. Structure-activity relationship (SAR) studies revealed that the presence of the electron-attracting bromo substituent at position-5 of the isatin moiety played an important role in enhancing the anti-inflammatory potential of the synthesized compounds. Z-1-[3-(1H-1,2,4-Triazol-1-yl)propyl]-5-bromo-3-[2-(4-methoxyphenyl)hydrazono]indolin-2-one (19) with an IC50 = 20 μM and 89% ICAM-1 inhibition with MTD at 200 μM was found to be the most potent of all the synthesized derivatives. Introduction of 1,2,4-triazole ring and electron-donating methoxy group on the phenylhydrazone moiety resulted in four-fold increase of the anti-inflammatory activity.

  3. Hugan Qingzhi Exerts Anti-Inflammatory Effects in a Rat Model of Nonalcoholic Fatty Liver Disease

    PubMed Central

    Tang, WaiJiao; Zeng, Lu; Yin, JinJin; Yao, YuFa; Feng, LiJuan; Yao, XiaoRui; Sun, XiaoMin; Zhou, BenJie

    2015-01-01

    Ethnopharmacological Relevance. The Hugan Qingzhi tablet (HQT) is a traditional Chinese medicine used for treating NAFLD (nonalcoholic fatty liver disease). The present study evaluated the anti-inflammatory effects of HQT in rats with NAFLD. Materials and Methods. HQT was administered daily to the NAFLD experimental groups. Biochemical markers, histopathological data, and oxidative stress/antioxidant biomarkers were determined. Proinflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6) were detected by enzyme-linked immunoassay. Expressions of silent information regulator 1 (SIRT1) and acetylated-nuclear-factor kappaB-p65 (Ac-NF-κB-p65) were performed by western blotting. Results. At high and moderate doses, HQT was highly effective in decreasing serum alanine aminotransferase (P < 0.01), aspartate aminotransferase (P < 0.01), hepatic total cholesterol (P < 0.01), triglycerides (P < 0.01), and free fatty acid levels (P < 0.01). Moreover, high and moderate doses of HQT reduced hepatic levels of the proinflammatory cytokines TNF-α (P < 0.01), IL-1β (P < 0.01), and IL-6 (P < 0.01), enhanced SIRT1 expression, and depressed Ac-NF-κB-p65 expression at protein level. Conclusions. In our NAFLD rat model, HQT exerted substantial anti-inflammatory and antioxidant activities, possibly involving the regulation of SIRT1 and Ac-NF-κB-p65 expression. PMID:26146507

  4. The Immunomodulation and Anti-Inflammatory Effects of Garlic Organosulfur Compounds in Cancer Chemoprevention

    PubMed Central

    Schäfer, Georgia; Kaschula, Catherine H.

    2014-01-01

    Garlic (Allium sativum) has been used for centuries as a prophylactic and therapeutic medicinal agent. Importantly, garlic has been suggested to have both cancer-preventive potential as well as significant enhancing effects on the immune system. While these observations are supported experimentally both in vitro and in vivo, the impact of garlic in assisting the immune system in the prevention of cancer still lacks experimental confirmation. Studies addressing the immunomodulatory effects of garlic reveal conflicting data as to pro- or anti-inflammatory responses depending on the particular experimental set-ups and the garlic preparation used (i.e. garlic extract versus chemically pure garlic compounds). Here we provide an overview of the chemistry of the major garlic organosulfur compounds, summarize the current understanding and propose a link between the immunomodulating activity of garlic and the prevention of cancer. We hypothesize that garlic rather elicits anti-inflammatory and anti-oxidative responses that aid in priming the organism towards eradication of an emerging tumor. PMID:24237225

  5. [Appropriate prescription, adherence and safety of non-steroidal anti-inflammatory drugs].

    PubMed

    Sostres, Carlos; Lanas, Ángel

    2016-03-18

    Non-steroidal anti-inflammatory drugs (NSAIDs) are the most numerous category of drugs sharing the same mechanism of action and therapeutic activities (anti-inflammatory, analgesic and anti-pyretic). Despite having similar efficacy for pain relieve, the different available NSAIDs show variability in its safety profile. The risk of gastrointestinal and cardiovascular complications varies depending on the dose of NSAID and also the presence of different risk factors. It is necessary, therefore, an individualized case assessment before establishing the indication of the best NSAID for each patient, taking account of the best gastroprotection strategy. Improved prescription and enhanced treatment adherence are central objectives to reduce NSAID-related complications. A recent consensus of the Spanish Association of Gastroenterology and the Spanish societies of Cardiology and Rheumatology intends to promote the rational use of NSAIDs according to new recent studies. This review provides additional aspects to facilitate the optimal decision-making process in the routine use of these drugs in clinical practice. PMID:26724872

  6. A Functional Variant of Elafin With Improved Anti-inflammatory Activity for Pulmonary Inflammation

    PubMed Central

    Small, Donna M; Zani, Marie-Louise; Quinn, Derek J; Dallet-Choisy, Sandrine; Glasgow, Arlene MA; O'Kane, Cecilia; McAuley, Danny F; McNally, Paul; Weldon, Sinéad; Moreau, Thierry; Taggart, Clifford C

    2015-01-01

    Elafin is a serine protease inhibitor produced by epithelial and immune cells with anti-inflammatory properties. Research has shown that dysregulated protease activity may elicit proteolytic cleavage of elafin, thereby impairing the innate immune function of the protein. The aim of this study was to generate variants of elafin (GG- and QQ-elafin) that exhibit increased protease resistance while retaining the biological properties of wild-type (WT) elafin. Similar to WT-elafin, GG- and QQ-elafin variants retained antiprotease activity and susceptibility to transglutaminase-mediated fibronectin cross-linking. However, in contrast to WT-elafin, GG- and QQ-elafin displayed significantly enhanced resistance to degradation when incubated with bronchoalveolar lavage fluid from patients with cystic fibrosis. Intriguingly, both variants, particularly GG-elafin, demonstrated improved lipopolysaccharide (LPS) neutralization properties in vitro. In addition, GG-elafin showed improved anti-inflammatory activity in a mouse model of LPS-induced acute lung inflammation. Inflammatory cell infiltration into the lung was reduced in lungs of mice treated with GG-elafin, predominantly neutrophilic infiltration. A reduction in MCP-1 levels in GG-elafin treated mice compared to the LPS alone treatment group was also demonstrated. GG-elafin showed increased functionality when compared to WT-elafin and may be of future therapeutic relevance in the treatment of lung diseases characterized by a protease burden. PMID:25189740

  7. The immunomodulation and anti-inflammatory effects of garlic organosulfur compounds in cancer chemoprevention.

    PubMed

    Schäfer, Georgia; Kaschula, Catherine H

    2014-02-01

    Garlic (Allium sativum) has been used for centuries as a prophylactic and therapeutic medicinal agent. Importantly, garlic has been suggested to have both cancer-preventive potential as well as significant enhancing effects on the immune system. While these observations are supported experimentally both in vitro and in vivo, the impact of garlic in assisting the immune system in the prevention of cancer still lacks experimental confirmation. Studies addressing the immunomodulatory effects of garlic reveal conflicting data as to pro- or anti-inflammatory responses depending on the particular experimental set-ups and the garlic preparation used (i.e. garlic extract versus chemically pure garlic compounds). Here we provide an overview of the chemistry of the major garlic organosulfur compounds, summarize the current understanding and propose a link between the immunomodulating activity of garlic and the prevention of cancer. We hypothesize that garlic rather elicits anti-inflammatory and anti-oxidative responses that aid in priming the organism towards eradication of an emerging tumor.

  8. Anti-inflammatory effects of fangchinoline and tetrandrine.

    PubMed

    Choi, H S; Kim, H S; Min, K R; Kim, Y; Lim, H K; Chang, Y K; Chung, M W

    2000-02-01

    Fangchinoline and tetrandrine are the major alkaloids from Stephania tetrandrae S. Moore which has been used traditionally for the treatment of inflammatory diseases in oriental countries including Korea. Both fangchinoline and tetrandrine showed anti-inflammatory effects on mouse ear edema induced by croton oil. In addition, the effects of fangchinoline and tetrandrine on cyclooxygenase, murine interleukin-5 (mIL-5) and human interleukin-6 (hIL-6) were examined in vitro to investigate the anti-inflammatory action mechanisms. One hundred micromolar of fangchinoline showed 35% of inhibition on cyclooxygenase, but the same concentration of tetrandrine did not show any inhibition. On the other hand, 12.5 microM of tetrandrine exhibited 95% of inhibition on mIL-5 activity, while fangchinoline did not show any effects. However, 4 microM of fangchinoline and 6 microM of tetrandrine showed 63 and 86% of inhibitions on hIL-6 activity, respectively. These results suggest that biochemical mechanisms of fangchinoline and tetrandrine on anti-inflammation are significantly different even though they are similar in chemical structure. PMID:10687873

  9. Oncostatin M in the anti-inflammatory response

    PubMed Central

    Wahl, A; Wallace, P

    2001-01-01

    Oncostatin M (OM) is a pleiotropic cytokine of the interleukin 6 family, whose in vivo properties and physiological function remain in dispute and poorly defined. These in vivo studies strongly suggest that OM is anabolic, promoting wound healing and bone formation, and anti-inflammatory. In models of inflammation OM is produced late in the cytokine response and protects from lipopolysaccharide (LPS)-induced toxicities, promoting the re-establishment of homoeostasis by cooperating with proinflammatory cytokines and acute phase molecules to alter and attenuate the inflammatory response. Administration of OM inhibited bacterial LPS-induced production of tumour necrosis factor α and septic lethality in a dose dependent manner. Consistent with these findings, in animal models of chronic inflammatory disease OM potently suppressed inflammation and tissue destruction in murine models of rheumatoid arthritis and multiple sclerosis. T cell function and antibody production were not impaired by OM treatment. Taken together, these data indicate that the activities of this cytokine in vivo are anti-inflammatory without concordant immunosuppression.

 PMID:11890661

  10. Anti-inflammatory Cerebrosides from Cultivated Cordyceps militaris.

    PubMed

    Chiu, Ching-Peng; Liu, Shan-Chi; Tang, Chih-Hsin; Chan, You; El-Shazly, Mohamed; Lee, Chia-Lin; Du, Ying-Chi; Wu, Tung-Ying; Chang, Fang-Rong; Wu, Yang-Chang

    2016-02-24

    Cordyceps militaris (bei-chong-chaw, northern worm grass) is a precious and edible entomopathogenic fungus, which is widely used in traditional Chinese medicine (TCM) as a general booster for the nervous system, metabolism, and immunity. Saccharides, nucleosides, mannitol, and sterols were isolated from this fungus. The biological activity of C. militaris was attributed to the saccharide and nucleoside contents. In this study, the aqueous methanolic fraction of C. militaris fruiting bodies exhibited a significant anti-inflammatory activity. Bioactivity-guided fractionation of the active fraction led to the isolation of eight compounds, including one new and two known cerebrosides (ceramide derivatives), two nucleosides, and three sterols. Cordycerebroside A (1), the new cerebroside, along with soyacerebroside I (2) and glucocerebroside (3) inhibited the accumulation of pro-inflammatory iNOS protein and reduced the expression of COX-2 protein in LPS-stimulated RAW264.7 macrophages. This is the first study on the isolation of cerebrosides with anti-inflammatory activity from this TCM. PMID:26853111

  11. A Novel Anti-Inflammatory Effect for High Density Lipoprotein

    PubMed Central

    Cameron, Scott J.; Morrell, Craig N.; Bao, Clare; Swaim, AnneMarie F.; Rodriguez, Annabelle; Lowenstein, Charles J.

    2015-01-01

    High density lipoprotein has anti-inflammatory effects in addition to mediating reverse cholesterol transport. While many of the chronic anti-inflammatory effects of high density lipoprotein (HDL) are attributed to changes in cell adhesion molecules, little is known about acute signal transduction events elicited by HDL in endothelial cells. We now show that high density lipoprotein decreases endothelial cell exocytosis, the first step in leukocyte trafficking. ApoA-I, a major apolipoprotein of HDL, mediates inhibition of endothelial cell exocytosis by interacting with endothelial scavenger receptor-BI which triggers an intracellular protective signaling cascade involving protein kinase C (PKC). Other apolipoproteins within the HDL particle have only modest effects upon endothelial exocytosis. Using a human primary culture of endothelial cells and murine apo-AI knockout mice, we show that apo-AI prevents endothelial cell exocytosis which limits leukocyte recruitment. These data suggest that high density lipoprotein may inhibit diseases associated with vascular inflammation in part by blocking endothelial exocytosis. PMID:26680360

  12. Immunosuppressive and anti-inflammatory properties of engineered nanomaterials

    PubMed Central

    Ilinskaya, A N; Dobrovolskaia, M A

    2014-01-01

    Nanoparticle interactions with various components of the immune system are determined by their physicochemical properties such as size, charge, hydrophobicity and shape. Nanoparticles can be engineered to either specifically target the immune system or to avoid immune recognition. Nevertheless, identifying their unintended impacts on the immune system and understanding the mechanisms of such accidental effects are essential for establishing a nanoparticle's safety profile. While immunostimulatory properties have been reviewed before, little attention in the literature has been given to immunosuppressive and anti-inflammatory properties. The purpose of this review is to fill this gap. We will discuss intended immunosuppression achieved by either nanoparticle engineering, or the use of nanoparticles to carry immunosuppressive or anti-inflammatory drugs. We will also review unintended immunosuppressive properties of nanoparticles per se and consider how such properties could be either beneficial or adverse. Linked Articles This article is part of a themed section on Nanomedicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-17 PMID:24724793

  13. Anti-inflammatory strategies in the treatment of schizophrenia.

    PubMed

    Andrade, Chittaranjan

    2016-01-01

    Schizophrenia is a major mental illness with a lifetime prevalence of about 1%. Antipsychotic drugs, with a primary mechanism of action that involves dopamine receptor blockade, are the mainstay in the treatment of the disorder. However, despite optimum antipsychotic treatment, few patients return to pre-morbid levels; the treatment deficit includes refractory positive symptoms, negative symptoms, mood impairments, cognitive impairments, social impairments, and/or a variety of medication-related adverse effects, including extrapyramidal symptoms, metabolic disturbances, hyperprolactinemia, and others. To address these, antipsychotic treatment has been augmented with psychosocial interventions, cognitive rehabilitation, different kinds of electrical and magnetic brain stimulation, and a large range of drugs from the neuropsychiatric as well as, surprise, the general medical pharmacopeia. The pleomorphic pathophysiology of schizophrenia includes abnormalities in immunological and inflammatory pathways, and so it is not surprising that anti-inflammatory drugs have also been trialed as augmentation agents in schizophrenia. This article critically examines the outcomes after augmentation with conventional anti-inflammatory interventions; results from randomized controlled trials do not encourage the use of either aspirin (1000 mg/day) or celecoxib (400 mg/day), both of which have been studied for this indication during the past decade and a half.

  14. Develop Anti-Inflammatory Nanotherapies to Treat Cardiovascular Disease

    NASA Astrophysics Data System (ADS)

    Tang, Jun

    Cardiovascular disease (CVD) is the leading cause of disease-related death in the world, accounting for 30 % global mortality. The majority of CVD is caused by atherosclerosis, a chronic inflammatory disease of major arteries featured by the deposition of lipids and cholesterol. Inflammation of atherosclerosis is mainly promoted by the pathological macrophages and monocytes, and modulating their functions has been proposed as a promising therapeutic target. This dissertation first presents the development of a novel simvastatin-loaded high-density lipoprotein (HDL) based nanoparticle ([S]-rHDL), which was able to deliver anti-inflammatory simvastatin preferentially to inflammatory monocytes in the blood and to macrophages in advanced atherosclerotic plaques, leading to the reduced inflammation in the tissue. Second, extensive in vivo characterization of [S]-rHDL in a mouse atherosclerosis model revealed that the anti-inflammatory capability of [S]-rHDL derived from its effects on blood monocytes, endothelial layer, monocyte recruitment, and plaque macrophage function. Third, a translational study that integrated the use of [S]-rHDL into oral statin treatment demonstrated a great potential for this nanomedicine as an attractive addition to the current high-dose oral statin standard-of-care for acute coronary syndrome. Finally, preliminary results suggested potential applications of the rHDL platform to other macrophage-implicated diseases.

  15. Anti-inflammatory triterpenoids from the stems of Microtropis fokienensis.

    PubMed

    Chen, I-Hsiao; Du, Ying-Chi; Hwang, Tsong-Long; Chen, I-Fen; Lan, Yu-Hsuan; Yen, Hsin-Fu; Chang, Fang-Rong; Wu, Yang-Chang

    2014-01-01

    Three new ursane- and four new oleanane- type triterpenoids 1-7 were isolated, along with six known compounds 8-13, from the methanolic extract of Microtropis fokienensis. All structures were elucidated by mass and NMR spectroscopic methods. The isolates 4-10 and known compounds 14-17 that were previously isolated from this material were evaluated for anti-inflammatory activity based on effects against superoxide anion generation and elastase release by neutrophils in response to fMLP/CB. 11α,30-Dihydroxy-2,3-seco-olean-12-en-2,3-dioic anhydride (7) was the first triterpene anhydride from the genus of Microtropis to have the ring A expanded to a seven-membered ring; it showed significant anti-inflammatory activity against superoxide anion generation and elastase release. Unexpectedly, 30-hydroxy-2,3-seco-lup-20(29)-ene-2,3-dioic acid (17) showed the best effect against superoxide anion generation and elastase release with IC50 values of 0.06±0.01 and 1.03±0.35 µg/mL, respectively. Compound 17 had a dioic acid function, and compound 7 had an anhydride function modification in ring A; both showed promising activity in the target assays.

  16. AHR-5850: a potent anti-inflammatory compound.

    PubMed

    Sancilio, L F; Reese, D L; Cheung, S; Alphin, R S

    1977-03-01

    AHR-5850 is a non-steroidal anti-inflammatory compound possessing antipyretic and analgesic properties. AHR-5850 was 16.4 and 22.8 times more potent than phenylbutazone in suppressing acute (Evans blue-carrageenan pleural effusion) and chronic (adjuvant-induced arthritis) inflammation, respectively. The analgesic activity of AHR 5850 was 43 times that of acetylsalicylic acid in the Randall-Selitto assay, and 156 and 56.3 times more potent than phenylbutazone in the acetylcholine-induced abdominal constriction in mice and in the bradykinin-induced nociceptive response in dogs, respectively. Single-dose studies showed that AHR-5850 produced less gastric irritation than acetylsalicylic acid when applied topically to the exposed gastric mucosa of cats or when administered orally to rats and dogs. Upon subchronic oral administration to rats, the therapeutic ratio of AHR-5850 was twice that of phenylbutazone. This was based on the ratio of its potency relative to phenylbutazone in producing intestinal lesions to its anti-inflammatory potency relative to phenylbutazone in the adjuvant-induced arthritis.

  17. Potential anti-inflammatory actions of the elmiric (lipoamino) acids

    PubMed Central

    Burstein, Sumner H.; Adams, Jeffrey K.; Bradshaw, Heather B.; Fraioli, Cristian; Rossetti, Ronald G.; Salmonsen, Rebecca A.; Shaw, John W.; Walker, J. Michael; Zipkin, Robert E.; Zurier, Robert B.

    2007-01-01

    A library of amino acid-fatty acid conjugates (elmiric acids) was synthesized and evaluated for activity as potential anti-inflammatory agents. The compounds were tested in vitro for their effects on cell proliferation and prostaglandin production and compared with their effects on in vivo models of inflammation. LPS stimulated RAW 267.4 mouse macrophage cells was the in vitro model and phorbol ester-induced mouse ear edema served as the principal in vivo model. The prostaglandin responses were found to be strongly dependent on the nature of the fatty acid part of the molecule. Polyunsaturated acid conjugates produced a marked increase in media levels of i15-deoxy-PGJ2 with minimal effects on PGE production. It is reported in the literature that prostaglandin ratios in which the J series predominates over the E series promote the resolution of inflammatory conditions. Several of the elmiric acids tested here produced such favorable ratios suggesting that their potential anti-inflammatory activity occurs via a novel mechanism of action. The ear edema assay results were generally in agreement with the prostaglandin assay findings indicating a connection between them. PMID:17383881

  18. Anti-inflammatory and redox-protective activities of citronellal.

    PubMed

    Melo, Mônica S; Guimarães, Adriana G; Santana, Michele F; Siqueira, Rosana S; De Lima, Amanda Do Carmo B; Dias, Antonio S; Santos, Márcio Roberto V; Onofre, Alexandre S C; Quintans, Jullyana S S; De Sousa, Damião P; Almeida, Jackson R G S; Estevam, Charles S; Araujo, Brancilene S; Quintans-Júnior, Lucindo J

    2011-01-01

    The anti-inflammatory and redox protective effects of the citronellal (CT) were evaluated using in vivo and in vitro tests. Intraperitoneal (i.p.) administration of CT (50, 100, and 200 mg/kg) inhibited (p < 0.05) the carrageenan-induced leukocyte migration to the peritoneal cavity. Additionally, the carrageenan- and arachidonic acid-induced rat hind paw edema was significantly inhibited (p < 0.05) by i.p. administration of 100 and 200 mg/kg of the compound. When the redox activity was evaluated, CT (200 mg/kg) significantly reduced hepatic lipoperoxidation (p < 0.001), as well as oxidation of plasmatic (p < 0.05) and hepatic (p < 0.01) proteins. The results of the present study support the hypothesis that CT possesses anti-inflammatory and redox protective activities. It is suggested that its effects are associated with the inhibition of the enzymes in the arachidonic acid pathway, which prevent cell migration by inhibiting leukotriene production, edema formation and the increase of reactive oxygen species in tissues. Therefore, CT is of potential benefit to manage inflammatory disorders and correlated damages caused by oxidant agents.

  19. Anti-inflammatory, antiapoptotic, and antioxidant activity of fluoxetine.

    PubMed

    Caiaffo, Vitor; Oliveira, Belisa D R; de Sá, Fabrício B; Evêncio Neto, Joaquim

    2016-06-01

    Fluoxetine is a selective serotonin uptake inhibitor that has been widely used to determine the neurotransmission of serotonin in the central nervous system. This substance has emerged as the drug of choice for the treatment of depression due to is safer profile, fewer side effects, and greater tolerability. Studies have found the following important functions of fluoxetine related to the central nervous system: neuroprotection; anti-inflammatory properties similar to standard drugs for the treatment of inflammatory conditions; antioxidant properties, contributing to its therapeutic action and an important intracellular mechanism underlying the protective pharmacological effects seen in clinical practice in the treatment of different stress-related adverse health conditions; and antiapoptotic properties, with greater neuron survival and a reduction in apoptosis mediators as well as oxidative substances, such as superoxide dismutase and hydrogen peroxide. The aim of this study was to perform a review of the literature on the important role of fluoxetine in anti-inflammatory, cell survival, and neuron trophicity mechanisms (antiapoptotic properties) as well as its role regarding enzymes of the antioxidant defense system. PMID:27433341

  20. Anti-Inflammatory Activity Comparison among Scropoliosides-Catalpol Derivatives with 6-O-Substituted Cinnamyl Moieties.

    PubMed

    Zhu, Tiantian; Zhang, Liuqiang; Ling, Shuang; Qian, Fei; Li, Yiming; Xu, Jin-Wen

    2015-11-03

    We have previously shown that scropolioside B has higher anti-inflammatory activity than catalpol does after the inhibition of nuclear factor (NF)-κB activity and IL-1β expression, maturation, and secretion. Various scropoliosides were extracted, isolated, and purified from Scrophularia dentata Royle ex Benth. We then compared their anti-inflammatory activities against LPS-induced NF-κB activity, cytokines mRNA expression, IL-1β secretion, and cyclooxygenase-2 activity. The inhibitory effects of the scropoliosides varied depending on whether the 6-O-substituted cinnamyl moiety was linked to C'' 2-OH, C''3-OH, or C''4-OH, and on the number of moieties linked, which is closely related to the enhancement of antiinflammatory activity. Among these compounds, scropolioside B had the strongest antiinflammatory effects.

  1. Strong and Long-Lasting Antinociceptive and Anti-inflammatory Conjugate of Naturally Occurring Oleanolic Acid and Aspirin

    PubMed Central

    Bednarczyk-Cwynar, Barbara; Wachowiak, Natalia; Szulc, Michal; Kamińska, Ewa; Bogacz, Anna; Bartkowiak-Wieczorek, Joanna; Zaprutko, Lucjusz; Mikolajczak, Przemyslaw L.

    2016-01-01

    The conjugate 8 was obtained as a result of condensation of 3-hydroxyiminooleanolic acid morfolide (7) and aspirin in dioxane. Analgesic effect of OAO-ASA (8) for the range of doses 0.3–300.0 mg/kg (p.o.) was performed in mice using a hot-plate test. Anti-inflammatory activity was assessed on carrageenan-induced paw edema in rats for the same range of doses. The conjugate OAO-ASA (8) did not significantly change locomotor activity of mice, therefore sedative properties of the compound should be excluded. The compound 8 proved a simple, proportional, dose-dependent analgesic action and expressed strong anti-inflammatory activity showing a reversed U-shaped, dose-dependent relation with its maximum at 30.0 mg/kg. After its combined administration with morphine (MF, 5.0 mg/kg, s.c.) the lowering of antinociceptive activity was found; however, the interaction with naloxone (NL, 3.0 mg/kg, s.c.) did not affect the antinociceptive effect of OAO-ASA (8), therefore its opioid mechanism of action should be rather excluded. After combined administration with acetylsalicylic acid (ASA, 300.0 mg/kg, p.o.) in hot-plate test, the examined compound 8 enhanced the antinociceptive activity in significant way. It also shows that rather the whole molecule is responsible for the antinociceptive and anti-inflammatory effect of the tested compound 8, however, it cannot be excluded that the summarizing effect is produced by ASA released from the compound 8 and the rest of triterpene derivative. The occurrence of tolerance for triterpenic derivative 8 was not observed, since the analgesic and anti-inflammatory effects after chronic administration of the conjugate OAO-ASA (8) was on the same level as after its single treatment. It seemed that the anti-inflammatory mechanism of action of OAO-ASA (8) is not simple, even its chronic administration lowered both blood concentration of IL-6 and mRNA IL-6 expression. However, the effects of the conjugate OAO-ASA (8) on TNF-α level and m

  2. Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: Identification of novel components of turmeric.

    PubMed

    Aggarwal, Bharat B; Yuan, Wei; Li, Shiyou; Gupta, Subash C

    2013-09-01

    Turmeric, a dried powder derived from the rhizome of Curcuma longa, has been used for centuries in certain parts of the world and has been linked to numerous biological activities including antioxidant, anti-inflammatory, anticancer, antigrowth, anti-arthritic, anti-atherosclerotic, antidepressant, anti-aging, antidiabetic, antimicrobial, wound healing, and memory-enhancing activities. One component of turmeric is curcumin, which has been extensively studied, as indicated by more than 5600 citations, most of which have appeared within the past decade. Recent research has identified numerous chemical entities from turmeric other than curcumin. It is unclear whether all of the activities ascribed to turmeric are due to curcumin or whether other compounds in turmeric can manifest these activities uniquely, additively, or synergistically with curcumin. However, studies have indicated that turmeric oil, present in turmeric, can enhance the bioavailability of curcumin. Studies over the past decade have indicated that curcumin-free turmeric (CFT) components possess numerous biological activities including anti-inflammatory, anticancer, and antidiabetic activities. Elemene derived from turmeric is approved in China for the treatment of cancer. The current review focuses on the anticancer and anti-inflammatory activities exhibited by CFT and by some individual components of turmeric, including turmerin, turmerone, elemene, furanodiene, curdione, bisacurone, cyclocurcumin, calebin A, and germacrone.

  3. Anti-inflammatory and antifibrotic effects of methyl palmitate

    SciTech Connect

    El-Demerdash, Ebtehal

    2011-08-01

    Methyl palmitate (MP) has been shown earlier to inhibit Kupffer cells and rat peritoneal macrophages. To evaluate the potential of MP to inhibit the activation of other macrophages, RAW cells (macrophages of alveolar origin) were treated with varying concentrations of MP (0.25, 0.5, 1 mM). Assessment of cytotoxicity using MTT assay revealed that 0.25 and 0.5 mM are not toxic to RAW cells. MP was able to inhibit the phagocytic function of RAW cells. Treatment of cells with MP 24 hours prior to LPS stimulation significantly decreased nitric oxide release and altered the pattern of cytokines release; there was a significant decrease in TNF-{alpha} and a significant increase in IL-10 compared to the controls. However, there is a non-significant change in IL-6 level. Furthermore, phosphorylation of inhibitory kappa B (I{kappa}B{alpha}) protein was significantly decreased in RAW cells treated with 0.5 mM MP after LPS stimulation. Based upon the in-vitro results, it was examined whether MP treatment will be effective in preventing bleomycin-induced lung inflammation and fibrosis in-vivo. Bleomycin given by itself caused destruction of the lung architecture characterized by pulmonary fibrosis with collapse of air alveoli and emphysematous. Bleomycin induced a significant increase in hydroxyproline level and activated NF-{kappa}B, p65 expression in the lung. MP co-treatment significantly ameliorated bleomycin effects. These results suggest that MP has a potential of inhibiting macrophages in general. The present study demonstrated for the first time that MP has anti-inflammatory and antifibrotic effect that could be through NF-kB inhibition. Thus MP like molecule could be a promising anti-inflammatory and antifibrotic drug. - Research Highlights: >Methyl palmitate is a universal macrophage inhibitor. >It could be a promising nucleus of anti-inflammatory and antifibrotic drugs. >The underlying mechanism of these effects could be through NF-kB inhibition.

  4. New Anti-Inflammatory Metabolites by Microbial Transformation of Medrysone

    PubMed Central

    Bano, Saira; Wahab, Atia-tul-; Yousuf, Sammer; Jabeen, Almas; Mesaik, Mohammad Ahmed; Rahman, Atta-ur-; Choudhary, M. Iqbal

    2016-01-01

    Microbial transformation of the anti-inflammatory steroid medrysone (1) was carried out for the first time with the filamentous fungi Cunninghamella blakesleeana (ATCC 8688a), Neurospora crassa (ATCC 18419), and Rhizopus stolonifer (TSY 0471). The objective was to evaluate the anti-inflammatory potential of the substrate (1) and its metabolites. This yielded seven new metabolites, 14α-hydroxy-6α-methylpregn-4-ene-3,11,20-trione (2), 6β-hydroxy-6α-methylpregn-4-ene-3,11,20-trione (3), 15β-hydroxy-6α-methylpregn-4-ene-3,11,20-trione (4), 6β,17α-dihydroxy-6α-methylpregn-4-ene-3,11,20-trione (5), 6β,20S-dihydroxy-6α-methylpregn-4-ene-3,11-dione (6), 11β,16β-dihydroxy-6α-methylpregn-4-ene-3,11-dione (7), and 15β,20R-dihydroxy-6α-methylpregn-4-ene-3,11-dione (8). Single-crystal X-ray diffraction technique unambiguously established the structures of the metabolites 2, 4, 6, and 8. Fungal transformation of 1 yielded oxidation at the C-6β, -11β, -14α, -15β, -16β positions. Various cellular anti-inflammatory assays, including inhibition of phagocyte oxidative burst, T-cell proliferation, and cytokine were performed. Among all the tested compounds, metabolite 6 (IC50 = 30.3 μg/mL) moderately inhibited the reactive oxygen species (ROS) produced from zymosan-induced human whole blood cells. Compounds 1, 4, 5, 7, and 8 strongly inhibited the proliferation of T-cells with IC50 values between <0.2–10.4 μg/mL. Compound 7 was found to be the most potent inhibitor (IC50 < 0.2 μg/mL), whereas compounds 2, 3, and 6 showed moderate levels of inhibition (IC50 = 14.6–20.0 μg/mL). Compounds 1, and 7 also inhibited the production of pro-inflammatory cytokine TNF-α. All these compounds were found to be non-toxic to 3T3 cells (mouse fibroblast), and also showed no activity when tested against HeLa (human epithelial carcinoma), or against PC3 (prostate cancer) cancer cell lines. PMID:27104348

  5. Anti-Inflammatory Effects of Metformin Irrespective of Diabetes Status

    PubMed Central

    Cameron, Amy R.; Morrison, Vicky L.; Levin, Daniel; Mohan, Mohapradeep; Forteath, Calum; Beall, Craig; McNeilly, Alison D.; Balfour, David J.K.; Savinko, Terhi; Wong, Aaron K.F.; Viollet, Benoit; Sakamoto, Kei; Fagerholm, Susanna C.; Foretz, Marc

    2016-01-01

    Rationale: The diabetes mellitus drug metformin is under investigation in cardiovascular disease, but the molecular mechanisms underlying possible benefits are poorly understood. Objective: Here, we have studied anti-inflammatory effects of the drug and their relationship to antihyperglycemic properties. Methods and Results: In primary hepatocytes from healthy animals, metformin and the IKKβ (inhibitor of kappa B kinase) inhibitor BI605906 both inhibited tumor necrosis factor-α–dependent IκB degradation and expression of proinflammatory mediators interleukin-6, interleukin-1β, and CXCL1/2 (C-X-C motif ligand 1/2). Metformin suppressed IKKα/β activation, an effect that could be separated from some metabolic actions, in that BI605906 did not mimic effects of metformin on lipogenic gene expression, glucose production, and AMP-activated protein kinase activation. Equally AMP-activated protein kinase was not required either for mitochondrial suppression of IκB degradation. Consistent with discrete anti-inflammatory actions, in macrophages, metformin specifically blunted secretion of proinflammatory cytokines, without inhibiting M1/M2 differentiation or activation. In a large treatment naive diabetes mellitus population cohort, we observed differences in the systemic inflammation marker, neutrophil to lymphocyte ratio, after incident treatment with either metformin or sulfonylurea monotherapy. Compared with sulfonylurea exposure, metformin reduced the mean log-transformed neutrophil to lymphocyte ratio after 8 to 16 months by 0.09 U (95% confidence interval, 0.02–0.17; P=0.013) and increased the likelihood that neutrophil to lymphocyte ratio would be lower than baseline after 8 to 16 months (odds ratio, 1.83; 95% confidence interval, 1.22–2.75; P=0.00364). Following up these findings in a double-blind placebo controlled trial in nondiabetic heart failure (trial registration: NCT00473876), metformin suppressed plasma cytokines including the aging

  6. The spice for joint inflammation: anti-inflammatory role of curcumin in treating osteoarthritis

    PubMed Central

    Chin, Kok-Yong

    2016-01-01

    Osteoarthritis is a degenerative disease of the joint affecting aging populations worldwide. It has an underlying inflammatory cause, which contributes to the loss of chondrocytes, leading to diminished cartilage layer at the affected joints. Compounds with anti-inflammatory properties are potential treatment agents for osteoarthritis. Curcumin derived from Curcuma species is an anti-inflammatory compound as such. This review aims to summarize the antiosteoarthritic effects of curcumin derived from clinical and preclinical studies. Many clinical trials have been conducted to determine the effectiveness of curcumin in osteoarthritic patients. Extracts of Curcuma species, curcuminoids and enhanced curcumin, were used in these studies. Patients with osteoarthritis showed improvement in pain, physical function, and quality of life after taking curcumin. They also reported reduced concomitant usage of analgesics and side effects during treatment. In vitro studies demonstrated that curcumin could prevent the apoptosis of chondrocytes, suppress the release of proteoglycans and metal metalloproteases and expression of cyclooxygenase, prostaglandin E-2, and inflammatory cytokines in chondrocytes. These were achieved by blocking the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) system in the chondrocytes, by preventing the activation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha, phosphorylation, and translocation of the p65 subunit of NF-κB complexes into the nucleus. In conclusion, curcumin is a potential candidate for the treatment of osteoarthritis. More well-planned randomized control trials and enhanced curcumin formulation are required to justify the use of curcumin in treating osteoarthritis. PMID:27703331

  7. Anti-inflammatory effect of three iridoids in human neutrophils.

    PubMed

    Wei, Shihu; Chi, Haidong; Kodama, Hiroyuki; Chen, Guang

    2013-01-01

    To verify the anti-inflammatory potency of iridoids, three iridoids (two natural, loganic acid: LA; geniposide: GE; and an artefact, 7(S)-n-butyl morroniside: BM) were investigated in vitro on the inhibition of superoxide generation in human neutrophils. All compounds showed inhibitory effect on fMLP-induced superoxide generation in a concentration-dependent manner with the following order: BM>LA>GE. BM exhibits potent inhibitory activity on superoxide anion induced by PMA, while LA and GE showed weak effect. When AA was used as stimulus, the generation of superoxide anion was suppressed by BM in a concentration-dependent manner. LA and GE exhibit both sides effect on superoxide generation.

  8. Nonsteroidal Anti-Inflammatory Drugs and the Kidney

    PubMed Central

    Hörl, Walter H.

    2010-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the isoenzymes COX-1 and COX-2 of cyclooxygenase (COX). Renal side effects (e.g., kidney function, fluid and urinary electrolyte excretion) vary with the extent of COX-2-COX-1 selectivity and the administered dose of these compounds. While young healthy subjects will rarely experience adverse renal effects with the use of NSAIDs, elderly patients and those with co-morbibity (e.g., congestive heart failure, liver cirrhosis or chronic kidney disease) and drug combinations (e.g., renin-angiotensin blockers, diuretics plus NSAIDs) may develop acute renal failure. This review summarizes our present knowledge how traditional NSAIDs and selective COX-2 inhibitors may affect the kidney under various experimental and clinical conditions, and how these drugs may influence renal inflammation, water transport, sodium and potassium balance and how renal dysfunction or hypertension may result. PMID:27713354

  9. A Review of Nonsteroidal Anti-inflammatory Drugs.

    PubMed

    Bozimowski, Gregory

    2015-12-01

    It is essential that nurse anesthetists are aware of the potential side effects and interaction of drugs that patients are taking before administering an anesthetic. Among the most commonly taken medications are nonsteroidal anti-inflammatory drugs (NSAIDs). Because these drugs have become almost ubiquitous, there is a risk underestimating potential effects, which may be harmful for the patient undergoing anesthesia and surgery. These effects can range from mild to severe and can be exacerbated by drug interactions with many commonly administered medications. This review of NSAID pharmacology a d interactions is intended to serve as an update and refresher for nurse anesthetists to increase their awareness of the potential untoward effects of postoperative bleeding, gastrointestinal bleeding, asthma, hepatic and renal toxicity and cardiovascular events. PMID:26742337

  10. Anti-inflammatory agents from plants: progress and potential.

    PubMed

    Recio, M C; Andujar, I; Rios, J L

    2012-01-01

    The identification of substances that can promote the resolution of inflammation in a way that is homeostatic, modulatory, efficient, and well-tolerated by the body is of fundamental importance. Traditional medicines have long provided front-line pharmacotherapy for many millions of people worldwide. Medicinal extracts are a rich source of therapeutic leads for the pharmaceutical industry. The use of medicinal plant therapies to treat chronic illness, including rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), is thus widespread and on the rise.The aim of this review is to present recent progress in clinical anti-inflammatory studies of plant extracts and compound leads such as green tea polyphenols, curcumin, resveratrol, boswellic acid, and cucurbitacins, among others, against chronic inflammatory diseases, mainly RA and IBD. In this context, the present paper also highlights the most promising experimental data on those plant extracts and pure compounds active in animal models of the aforementioned diseases.

  11. [Anti-inflammatory and anti-allergic oral vaccines?].

    PubMed

    Lomholt, H B; Kilian, M

    1996-09-16

    Recent data suggest clinical efficacy of specific antigens delivered at mucosal sites in the treatment of certain organ specific autoimmune diseases. This approach appears non-toxic and has no side effects. Phase I/II human trials on multiple sclerosis and rheumatoid arthritis show positive outcomes. Furthermore, animal studies point to beneficial effects on uveitis, diabetes mellitus, transplantation reactions and allergic diseases. The immunological mechanism is oral tolerance, a well known principle for induction of a systemic hyporesponse to specific antigens. The tolerance is most pronounced on delayed type hypersensibility and IgE-mediated reactions. At least three different mechanisms mediate the tolerance. Low doses of antigen induce active suppression, intermediate doses induce clonal T-cell anergy, and high doses induce clonal T-cell deletion. The recent improvements in the understanding of the mechanisms of oral tolerance have fueled an interest in manipulating this principle to develop anti-inflammatory vaccines. PMID:8966773

  12. Anti-inflammatory polyphenol constituents derived from Cissus pteroclada Hayata.

    PubMed

    Li, Yi-Jie; Xu, Cheng-Ting; Lin, Dan-Dan; Qin, Jiang-Ke; Ye, Gao-Jie; Deng, Qing-Hua

    2016-08-01

    A new bergenin derivative, bergenin-11-O-α-d-galactopyranoside (compound 1), together with seven known polyphenolic compounds, were isolated from the stem of Cissus pteroclada Hayata. The structures of the 8 compounds were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Moreover, the in vitro anti-inflammatory effects of compounds (1-8) in LPS-stimulated murine macrophage RAW 264.7 cells were also investigated. Our results revealed that compound 1 inhibited the production of pro-inflammatory mediators NO and PGE2 and the expression of NF-κB, TNF-α, IL-1β, iNOS and COX-2. PMID:27374242

  13. Peptidoglycan diversity and anti-inflammatory capacity in Lactobacillus strains.

    PubMed

    Wu, Zhen; Pan, Daodong; Guo, Yuxing; Sun, Yangying; Zeng, Xiaoqun

    2015-09-01

    Lactobacillus species are potential probiotic bacteria for humans because of their capacity to improve certain biological functions in the host's immune system. In this study, we focused on three peptidoglycans (PGNs) derived from different Lactobacillus strains and investigated each PGN's anti-inflammatory capacity. Each PGN was analyzed using HPLC, MALDI-TOF/TOF MS and FTIR. All three PGNs displayed a β-1,4-linked N-acetylmuramic acid (MurNAc) and N-acetylglucosamine (GlcNAc) structure with some modifications in the polypeptides at the end of the MurNAc residue. In a new insight, we found that PGNs inhibit the release of inflammatory cytokines in LPS-induced RAW 264.7 cells; a capacity that may be related to the TLR-4 pathway. The goal for exploring PGN diversity in Lactobacillus strains is to better understand the potential use of Lactobacillus PGNs in food and pharmaceutical applications.

  14. Anti-inflammatory agents from plants: progress and potential.

    PubMed

    Recio, M C; Andujar, I; Rios, J L

    2012-01-01

    The identification of substances that can promote the resolution of inflammation in a way that is homeostatic, modulatory, efficient, and well-tolerated by the body is of fundamental importance. Traditional medicines have long provided front-line pharmacotherapy for many millions of people worldwide. Medicinal extracts are a rich source of therapeutic leads for the pharmaceutical industry. The use of medicinal plant therapies to treat chronic illness, including rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), is thus widespread and on the rise.The aim of this review is to present recent progress in clinical anti-inflammatory studies of plant extracts and compound leads such as green tea polyphenols, curcumin, resveratrol, boswellic acid, and cucurbitacins, among others, against chronic inflammatory diseases, mainly RA and IBD. In this context, the present paper also highlights the most promising experimental data on those plant extracts and pure compounds active in animal models of the aforementioned diseases. PMID:22414101

  15. [Anti-inflammatory modulators in traumatic brain injury].

    PubMed

    Lescot, T; Marchand-Verrecchia, C; Puybasset, L

    2006-07-01

    Traumatic brain injury leads to primary and secondary brain injuries. Primary brain injury results from mechanical forces applied to the head at the time of impact. Secondary brain injury occurs at some time after the primary impact. Numerous pathophysiological mechanisms have been postulated to explain the progressive tissue damage produced by secondary injuries. The endogenous neuroinflammatory response after traumatic brain injury contributes to the development of blood-brain barrier breakdown, cerebral oedema and neuronal cell death and this has led to various pharmacological therapies to try to limit this type of damage. Studies employing glutamate receptor antagonist for cerebral protection have yielded promising results in laboratory animals but failed to produce clinically significant improvements. The present review will summarize the mechanisms of post traumatic cerebral inflammation with a special focus on the anti-inflammatory drug targets.

  16. A Review of Nonsteroidal Anti-inflammatory Drugs.

    PubMed

    Bozimowski, Gregory

    2015-12-01

    It is essential that nurse anesthetists are aware of the potential side effects and interaction of drugs that patients are taking before administering an anesthetic. Among the most commonly taken medications are nonsteroidal anti-inflammatory drugs (NSAIDs). Because these drugs have become almost ubiquitous, there is a risk underestimating potential effects, which may be harmful for the patient undergoing anesthesia and surgery. These effects can range from mild to severe and can be exacerbated by drug interactions with many commonly administered medications. This review of NSAID pharmacology a d interactions is intended to serve as an update and refresher for nurse anesthetists to increase their awareness of the potential untoward effects of postoperative bleeding, gastrointestinal bleeding, asthma, hepatic and renal toxicity and cardiovascular events.

  17. Anti-inflammatory and antinociceptive activities of azadirachtin in mice.

    PubMed

    Soares, Darly G; Godin, Adriana M; Menezes, Raquel R; Nogueira, Rafaela D; Brito, Ana Mercy S; Melo, Ivo S F; Coura, Giovanna Maria E; Souza, Danielle G; Amaral, Flávio A; Paulino, Tony P; Coelho, Márcio M; Machado, Renes R

    2014-06-01

    Azadirachta indica (Meliaceae) extracts have been reported to exhibit anti-inflammatory and antinociceptive properties. However, the activities of azadirachtin, a limonoid and the major bioactive compound found in the extracts, have been poorly investigated in animal models. In the present study, we investigated the effects induced by azadirachtin in experimental models of pain and inflammation in mice. Carrageenan-induced paw edema and fibrovascular tissue growth induced by subcutaneous cotton pellet implantation were used to investigate the anti-inflammatory activity of azadirachtin in mice. Zymosan-induced writhing and hot plate tests were employed to evaluate the antinociceptive activity. To explore putative mechanisms of action, the level of tumor necrosis factor-α in inflammatory tissue was measured and the effect induced by opioidergic and serotonergic antagonists was evaluated. Previous per os (p. o.) administration of azadirachtin (120 mg/kg) significantly reduced the acute paw edema induced by carrageenan. However, the concomitant increase of the paw concentration of tumor necrosis factor-α induced by this inflammatory stimulus was not reduced by azadirachtin. In addition to inhibiting the acute paw edema induced by carrageenan, azadirachtin (6, 60, and 120 mg/kg) inhibited the proliferative phase of the inflammatory response, as demonstrated by the reduced formation of fibrovascular tissue growth. Azadirachtin (120 mg/kg) also inhibited the nociceptive response in models of nociceptive (hot plate) and inflammatory (writhing induced by zymosan) pain. The activity of azadirachtin (120 mg/kg) in the model of nociceptive pain was attenuated by a nonselective opioid antagonist, naltrexone (10 mg/kg, i. p.), but not by a nonselective serotonergic antagonist, cyproheptadine. In conclusion, this study demonstrates the activity of azadirachtin in experimental models of nociceptive and inflammatory pain, and also in models of acute and chronic inflammation

  18. Atypical Activin A and IL-10 Production Impairs Human CD16+ Monocyte Differentiation into Anti-Inflammatory Macrophages.

    PubMed

    González-Domínguez, Érika; Domínguez-Soto, Ángeles; Nieto, Concha; Flores-Sevilla, José Luis; Pacheco-Blanco, Mariana; Campos-Peña, Victoria; Meraz-Ríos, Marco A; Vega, Miguel A; Corbí, Ángel L; Sánchez-Torres, Carmen

    2016-02-01

    Human CD14(++)CD16(-) and CD14(+/lo)CD16(+) monocyte subsets comprise 85 and 15% of blood monocytes, respectively, and are thought to represent distinct stages in the monocyte differentiation pathway. However, the differentiation fates of both monocyte subsets along the macrophage (Mϕ) lineage have not yet been elucidated. We have now evaluated the potential of CD14(++) CD16(-) and CD16(+) monocytes to differentiate and to be primed toward pro- or anti-inflammatory Mϕs upon culture with GM-CSF or M-CSF, respectively (subsequently referred to as GM14, M14, GM16, or M16). Whereas GM16 and GM14 were phenotypic and functionally analogous, M16 displayed a more proinflammatory profile than did M14. Transcriptomic analyses evidenced that genes associated with M-CSF-driven Mϕ differentiation (including FOLR2, IL10, IGF1, and SERPINB2) are underrepresented in M16 with respect to M14. The preferential proinflammatory skewing of M16 relative to M14 was found to be mediated by the secretion of activin A and the low levels of IL-10 produced by M16. In fact, activin A receptor blockade during the M-CSF-driven differentiation of CD16(+) monocytes, or addition of IL-10-containing M14-conditioned medium, significantly enhanced their expression of anti-inflammatory-associated molecules while impairing their acquisition of proinflammatory-related markers. Thus, we propose that M-CSF drives CD14(++)CD16- monocyte differentiation into bona fide anti-inflammatory Mϕs in a self-autonomous manner, whereas M-CSF-treated CD16(+) monocytes generate Mϕs with a skewed proinflammatory profile by virtue of their high activin A expression unless additional anti-inflammatory stimuli such as IL-10 are provided. PMID:26729812

  19. Comparative study on anti-oxidant and anti-inflammatory activities of Caesalpinia crista and Centella asiatica leaf extracts

    PubMed Central

    Ramesh, B. N.; Girish, T. K.; Raghavendra, R. H.; Naidu, K. Akhilender; Rao, U. J. S. Prasada; Rao, K. S.

    2014-01-01

    Background: Amyloidosis, oxidative stress and inflammation have been strongly implicated in neurodegenerative disorders like Alzheimer's disease. Traditionally, Caesalpinia crista and Centella asiatica leaf extracts are used to treat brain related diseases in India. C. crista is used as a mental relaxant drink as well as to treat inflammatory diseases, whereas C. asiatica is reported to be used to enhance memory and to treat dementia. Objective: The present study is aimed to understand the anti-oxidant and anti-inflammatory potential of C. asiatica and C. crista leaf extracts. Materials and Methods: Phenolic acid composition of the aqueous extracts of C. crista and C. asiatica were separated on a reverse phase C18 column (4.6 x 250 mm) using HPLC system. Antioxidant properties of the leaf extracts were determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay and the reducing potential assay. The anti-inflammatory activities of aqueous extracts of C. crista and C. asiatica were studied using 5-lipoxygenase assay. Polymorphonuclear leukocytes (PMNLs) were isolated from blood by Ficoll-Histopaque density gradient followed by hypotonic lysis of erythrocytes. Results: Gallic, protocatechuic, gentisic, chlorogenic, caffeic, p-coumaric and ferulic acids were the phenolic acids identified in C. crista and C. asiatica leaf aqueous extracts. However, gallic acid and ferulic acid contents were much higher in C. crista compared to C. asiatica. Leaf extracts of C. asiatica and C. crista exhibited antioxidant properties and inhibited 5-lipoxygenase (anti-inflammatory) in a dose dependent manner. However, leaf extracts of C. crista had better antioxidant and anti-inflammatory activity compared to that of C. asiatica. The better activity of C. crista is attributed to high gallic acid and ferulic acid compared to C. asiatica. Conclusions: Thus, the leaf extract of C. crista can be a potential therapeutic role for Alzheimer's disease. PMID:24741275

  20. Evaluation of the wound-healing activity and anti-inflammatory activity of aqueous extracts from Acorus calamus L.

    PubMed

    Shi, Guo-bing; Wang, Bing; Wu, Qiong; Wang, Tong-chao; Wang, Chang-li; Sun, Xue-hui; Zong, Wen-tao; Yan, Ming; Zhao, Qing-chun; Chen, Yu-feng; Zhang, Wei

    2014-01-01

    In folklore medicine, Acorus calamus has been used as a wound-healing agent for thousands of years; however, there have been few scientific reports on this activity so far. Now, we explored deeply the wound-healing effect of aqueous extracts from the fresh roots and rhizomes of A. calamus in vivo, as well as anti-inflammatory activity in vitro, so as to provide scientific evidence for the traditional application. The wound-healing effect was determined by the image analysis techniques and the histological analysis in the excisional wounding test, and the anti-inflammatory activity was evaluated by the real-time RT-PCR techniques in the lipopolysaccharide-induced RAW 264.7 cells test. Aqueous extracts, administered topically at the dose range from twice to thrice in a day, could enhance significantly the rate of skin wound-healing. Moreover, the extracts could effectively inhibit the mRNA expressions of inflammatory mediators induced by lipopolysaccharide in RAW 264.7 cells. These results showed significantly the wound-healing activity of aqueous extracts in the animal model of excise wound healing, and anti-inflammatory activity in vitro.

  1. Anti-inflammatory effect of aqueous extracts of spent Pleurotus ostreatus substrates in mouse ears treated with 12-O-tetradecanoylphorbol-13-acetate

    PubMed Central

    Rivero-Pérez, Nallely; Ayala-Martínez, Maricela; Zepeda-Bastida, Armando; Meneses-Mayo, Marcos; Ojeda-Ramírez, Deyanira

    2016-01-01

    Aims: To evaluate the application of spent Pleurotus ostreatus substrates, enriched or not with medicinal herbs, as a source of anti-inflammatory compounds. Subjects and Methods: P. ostreatus was cultivated on five different substrates: Barley straw (BS) and BS combined 80:20 with medicinal herbs (Chenopodium ambrosioides L. [BS/CA], Rosmarinus officinalis L. [BS/RO], Litsea glaucescens Kunth [BS/LG], and Tagetes lucida Cav. [BS/TL]). The anti-inflammatory activity of aqueous extracts of spent mushroom substrates (SMSs) (4 mg/ear) was studied using an acute inflammation model in the mouse ear induced with 2.5 μg/ear 12-O-tetradecanoylphorbol13-acetate (TPA). Results: Groups treated with BS/CA, BS/RO, and BS/LG aqueous extracts exhibited the best anti-inflammatory activity (94.0% ± 5.5%, 92.9% ± 0.6%, and 90.4% ± 5.0% inhibition of auricular edema [IAO], respectively), and these effects were significantly different (P < 0.05) from that of the positive control indomethacin (0.5 mg/ear). BS/TL and BS were also able to reduce TPA-induced inflammation but to a lesser extent (70.0% ± 6.7% and 43.5% ± 6.6% IAO, respectively). Conclusions: Spent P. ostreatus substrate of BS possesses a slight anti-inflammatory effect. The addition of CA L. to mushroom substrate showed a slightly synergistic effect while RO L. had an additive effect. In addition, LG Kunth and TL Cav. enhanced the anti-inflammatory effect of SMS. However, to determine whether there is a synergistic or additive effect, it is necessary to determine the anti-inflammatory effect of each medicinal herb. PMID:27127316

  2. Biosynthesis of Anti-Proliferative Gold Nanoparticles Using Endophytic Fusarium oxysporum Strain Isolated from Neem (A. indica) Leaves.

    PubMed

    Siddiqui, Ejaz Ahmad; Ahmad, Absar; Julius, Anju; Syed, Asad; Khan, Shadab; Kharat, Mahesh; Pai, Kalpana; Kadoo, Narendra; Gupta, Vidya

    2016-01-01

    Here we report a simple, rapid, environment friendly approach for the synthesis of gold nanoparticles using neem (Azadirachta indica A. Juss.) fungal endophyte, which based upon morphological and cultural characteristics was eventually identified as Fusarium oxysporum. The aqueous precursor (HAuCl4) solution when reacted with endophytic fungus resulted in the biosynthesis of abundant amounts of well dispersed gold nanoparticles of 10-40 nm with an average size of 22nm. These biosynthesized gold nanoparticles were then characterized by standard analytical techniques such as UV-Visible spectroscopy, X-ray diffraction, Transmission Electron Microscopy and Fourier Transform Infrared Spectroscopy. Cytotoxic activity of these nanoparticles was checked against three different cell types including breast cancer (ZR-75-1), Daudi (Human Burkitt's lymphoma cancer) and normal human peripheral blood mononuclear cells (PBMC), where it was found that our gold nanoparticles are anti-proliferative against cancer cells but completely safe toward normal cells. In addition to this, assessment of toxicity toward human RBC revealed less than 0.1 % hemolysis as compared to Triton X-100 suggesting safe nature of our biosynthesized gold nanoparticles on human cells. Also, our nanoparticles exhibited no anti-fungal (against Aspergillus niger) or anti-bacterial [against Gram positive (Bacillus subtilis & Staphylococcus aureus) and Gram negative (Escherichia coli & Pseudomonas aeruginosa) bacteria] activity thus suggesting their non-toxic, biocompatible nature. The present investigation opens up avenues for ecofriendly, biocompatible nanomaterials to be used in a wide variety of application such as drug delivery, therapeutics, theranostics and so on.

  3. Anti-Proliferative and Apoptotic Effects of Methanolic Extracts from Different Cladonia Species on Human Breast Cancer Cells.

    PubMed

    Coskun, Z M; Ersoz, M; Acikgoz, B; Karalti, I; Cobanoglu, G; Sesal, C

    2015-01-01

    This study tries to elucidate the anti-proliferative and apoptotic effects of methanolic lichen extracts from Cladonia rangiformis and Cladonia convolute in MCF-7 human breast cancer cells. Lichen extracts (0-2 mg/ml) were added to MCF-7 cells for 24 h. Cell viability was tested using 3-(4,5-dimethylthiazol- 2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. Cell proliferation was observed using bromodeoxyuridine (BrdU) labelling and proliferating cell nuclear antigen (PCNA) by immunocytochemistry. The TUNEL method was used for cell death detection. The effective dose (ED50) values of methanolic extracts from C. rangiformis and C. convolute were found to be 0.905 and 0.977 mg/ml, respectively. Treatment with C. rangiformis methanolic extract (0.2-0.8 mg/ml) dose-dependently inhibited proliferation of MCF-7 cells as detected by BrdU incorporation. The inhibition was started in 0.2 mg/ml concentration of C. convoluta methanolic extract. The percent of PCNA immunopositive cells showed a decrease in MCF-7 cells treated with two lichen extracts compared to control MCF-7. Both methanolic extracts showed a significant increase in percentage of apoptosis-positive cells. These results indicate that methanolic lichen extracts from C. rangiformis and C. convolute inhibited proliferation of MCF-7 cells and caused apoptosis in MCF-7 cells. The lichens may be novel natural agents for treating breast cancer disease. PMID:26213854

  4. Design, synthesis and in vitro anti-proliferative activity of 4,6-quinazolinediamines as potent EGFR-TK inhibitors.

    PubMed

    Mowafy, Samar; Farag, Nahla A; Abouzid, Khaled A M

    2013-03-01

    4-Anilino-6-substituted-quinazolines were designed, synthesized and evaluated for EGFR-TK and tumor growth inhibitory activities. The target compounds were designed with enamine ester or urea moieties appended at the C-6 of quinazoline as additional hydrogen bond acceptor functions. Most of the synthesized compounds displayed potent EGFR-TK inhibitory activity at 10 μM and the 6-ureido-anilinoquinazoline derivative 7a showed IC50 value of 0.061 μM. Moreover, six compounds were tested by National Cancer Institute (NCI), USA for their anti-proliferative activity at 10 μM in full NCI 60 cell panel. Compound 7a was further assayed for five dose molar ranges in full NCI 60 cell panel and exhibited remarkable growth inhibitory activity pattern against Non-Small Cell Lung Cancer EKVX (GI50 = 0.37 μM), NCI-H322M (GI50 = 0.36 μM), Renal Cancer A498 (GI50 = 0.46 μM), TK-10 (GI50 = 0.99 μM) and Breast Cancer MDA-MB-468 (GI50 = 1.096 μM) which are of high EGFR expression. Docking study was performed for the active compounds into ATP binding site of EGFR-TK which showed similar binding mode to gefitinib and additional binding with Cys-773 at the gatekeeper of EGFR-TK enzyme.

  5. Anti-proliferative and apoptotic effects of S1, a tetrandrine derivative, in human gastric cancer BGC-823 cells.

    PubMed

    Lei, Rong-Rong; Hu, Hai-Feng; Bai, Fan; Liu, Ying; Wu, Chun-Zhen; Huang, Xiao-Xing; Xie, Li-Ping; Hu, You-Jia

    2016-07-01

    The aim of the study was to investigate the anti-proliferation and apoptosis-inducing effects of S1, a novel tetrandrine derivative, in human gastric cancer BGC-823 cells and explore the possible mechanism of action. The anti-proliferative activity was determined by MTT assay; the induction of cell cycle arrest and apoptosis were detected by flow cytometry. Quantitative real time RT-PCR and Western blotting were used to evaluate the mRNA and protein expression levels in mitochondrial pathway. S1 significantly reduced cell viability and induced a G2/M phase arrest and apoptosis in dose- and time-dependent manner. Further studies showed that S1 increased mRNA and protein expression of Bax and the Bax/Bcl-2 ratio. Moreover, S1 decreased the protein expression of procaspase-9 and procaspase-3, suggesting that the induction of apoptosis may be related to the alteration of the ratio of Bax/Bcl-2 and the activation of caspases. These findings suggested that S1 merits further investigation as a novel therapeutic agent for the treatment of human gastric cancer.

  6. Inhibition of p38/CREB phosphorylation and COX-2 expression by olive oil polyphenols underlies their anti-proliferative effects

    SciTech Connect

    Corona, Giulia; Deiana, Monica; Incani, Alessandra; Vauzour, David; Assunta Dessi, M.; Spencer, Jeremy P.E.

    2007-10-26

    We investigated the anti-proliferative effects of an olive oil polyphenolic extract on human colon adenocarcinoma cells. Analysis indicated that the extract contained hydroxytyrosol, tyrosol and the various secoiridoid derivatives, including oleuropein. This extract exerted a strong inhibitory effect on cancer cell proliferation, which was linked to the induction of a G2/M phase cell cycle block. Following treatment with the extract (50 {mu}g/ml) the number of cells in the G2/M phase increased to 51.82 {+-} 2.69% relative to control cells (15.1 {+-} 2.5%). This G2/M block was mediated by the ability of olive oil polyphenols (50 {mu}g/ml) to exert rapid inhibition of p38 (38.7 {+-} 4.7%) and CREB (28.6 {+-} 5.5%) phosphorylation which led to a downstream reduction in COX-2 expression (56.9 {+-} 9.3%). Our data suggest that olive oil polyphenols may exert chemopreventative effects in the large intestine by interacting with signalling pathways responsible for colorectal cancer development.

  7. Conformational study reveals amino acid residues essential for hemagglutinating and anti-proliferative activities of Clematis montana lectin.

    PubMed

    Lu, Bangmin; Zhang, Bin; Qi, Wei; Zhu, Yanan; Zhao, Yan; Zhou, Nan; Sun, Rong; Bao, Jinku; Wu, Chuanfang

    2014-11-01

    Clematis montana lectin (CML), a novel mannose-binding lectin purified from C. montana Buch.-Ham stem (Ranunculaceae), has been proved to have hemagglutinating activity in rabbit erythrocytes and apoptosis-inducing activity in tumor cells. However, the biochemical properties of CML have not revealed and its structural information still needs to be elucidated. In this study, it was found that CML possessed quite good thermostability and alkaline resistance, and its hemagglutinating activity was bivalent metal cation dependent. In addition, hemagglutination test and fluorescence spectroscopy proved that GuHCl, urea, and sodium dodecyl sulfate could change the conformation of CML and further caused the loss of hemagglutination activity. Moreover, the changes of fluorescence spectrum indicated that the tryptophan (Trp) microenvironment conversion might be related to the conformation and bioactivities of CML. In addition, it was also found that Trp residues, arginine (Arg) residues, and sulfhydryl were important for the hemagglutinating activity of CML, but only Trp was proved to be crucial for the CML conformation. Furthermore, the Trp, Arg, and sulfhydryl-modified CML exhibited 97.17%, 76.99%, and 49.64% loss of its anti-proliferative activity, respectively, which was consistent with the alterations of its hemagglutinating activity. Given these findings, Trp residues on the surface of CML are essential for the active center to form substrate-accessible conformation and suitable environment for carbohydrate binding. PMID:25239139

  8. Anti-proliferative and apoptotic effects of S1, a tetrandrine derivative, in human gastric cancer BGC-823 cells.

    PubMed

    Lei, Rong-Rong; Hu, Hai-Feng; Bai, Fan; Liu, Ying; Wu, Chun-Zhen; Huang, Xiao-Xing; Xie, Li-Ping; Hu, You-Jia

    2016-07-01

    The aim of the study was to investigate the anti-proliferation and apoptosis-inducing effects of S1, a novel tetrandrine derivative, in human gastric cancer BGC-823 cells and explore the possible mechanism of action. The anti-proliferative activity was determined by MTT assay; the induction of cell cycle arrest and apoptosis were detected by flow cytometry. Quantitative real time RT-PCR and Western blotting were used to evaluate the mRNA and protein expression levels in mitochondrial pathway. S1 significantly reduced cell viability and induced a G2/M phase arrest and apoptosis in dose- and time-dependent manner. Further studies showed that S1 increased mRNA and protein expression of Bax and the Bax/Bcl-2 ratio. Moreover, S1 decreased the protein expression of procaspase-9 and procaspase-3, suggesting that the induction of apoptosis may be related to the alteration of the ratio of Bax/Bcl-2 and the activation of caspases. These findings suggested that S1 merits further investigation as a novel therapeutic agent for the treatment of human gastric cancer. PMID:27507203

  9. Design, Synthesis and Structure-Activity Relationship Studies of Novel Survivin Inhibitors with Potent Anti-Proliferative Properties

    PubMed Central

    Xiao, Min; Wang, Jin; Lin, Zongtao; Lu, Yan; Li, Zhenmei; White, Stephen W.; Miller, Duane D.; Li, Wei

    2015-01-01

    The anti-apoptotic protein survivin is highly expressed in most human cancer cells, but has very low expression in normal differentiated cells. Thus survivin is considered as an attractive cancer drug target. Herein we report the design and synthesis of a series of novel survivin inhibitors based on the oxyquinoline scaffold from our recently identified hit compound UC-112. These new analogs were tested against a panel of cancer cell lines including one with multidrug-resistant phenotype. Eight of these new UC-112 analogs showed IC50 values in the nanomole range in anti-proliferative assays. The best three compounds among them along with UC-112 were submitted for NCI-60 cancer cell line screening. The results indicated that structural modification from UC-112 to our best compound 4g has improved activity by four folds (2.2 μM for UC-112 vs. 0.5 μM for 4g, average GI50 values over all cancer cell lines in the NCI-60 panel).Western blot analyses demonstrated the new compounds maintained high selectivity for survivin inhibition over other members in the inhibition of apoptosis protein family. When tested in an A375 human melanoma xenograft model, the most active compound 4g effectively suppressed tumor growth and strongly induced cancer cell apoptosis in tumor tissues. This novel scaffold is promising for the development of selective survivin inhibitors as potential anticancer agents. PMID:26070194

  10. In-vitro anti- inflammatory activity of aqueous extract of leaves of Plectranthus amboinicus (Lour.) Spreng.

    PubMed

    Ravikumar, V R; Dhanamani, M; Sudhamani, T

    2009-04-01

    Aqueous extract of leaves of Plectranthus amboinicus (lour.) Spreng, which is traditionally used in the treatment of cough and cold was screened for its anti- inflammatory activity by HRBC membrane stabilisation model. Aqueous extract (500 mcg/ml) showed significant anti-inflammatory activity as compared to that of hydrocortisone sodium. PMID:22557324

  11. In-vitro anti- inflammatory activity of aqueous extract of leaves of Plectranthus amboinicus (Lour.) Spreng

    PubMed Central

    Ravikumar, V.R.; Dhanamani, M.; Sudhamani, T.

    2009-01-01

    Aqueous extract of leaves of Plectranthus amboinicus (lour.) Spreng, which is traditionally used in the treatment of cough and cold was screened for its anti- inflammatory activity by HRBC membrane stabilisation model. Aqueous extract (500 mcg/ml) showed significant anti-inflammatory activity as compared to that of hydrocortisone sodium. PMID:22557324

  12. Preventative oral methylthioadenosine is anti-inflammatory and reduces DSS-induced colitis in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Methylthioadenosine (MTA) is a precursor of the methionine salvage pathway and has been shown to have anti-inflammatory properties in various models of acute and chronic inflammation. However, the anti-inflammatory properties of MTA in models of intestinal inflammation are not defined. We hypothesiz...

  13. Heart rate reduction with ivabradine promotes shear stress-dependent anti-inflammatory mechanisms in arteries.

    PubMed

    Luong, Le; Duckles, Hayley; Schenkel, Torsten; Mahmoud, Marwa; Tremoleda, Jordi L; Wylezinska-Arridge, Marzena; Ali, Majid; Bowden, Neil P; Villa-Uriol, Mari-Cruz; van der Heiden, Kim; Xing, Ruoyu; Gijsen, Frank J; Wentzel, Jolanda; Lawrie, Allan; Feng, Shuang; Arnold, Nadine; Gsell, Willy; Lungu, Angela; Hose, Rodney; Spencer, Tim; Halliday, Ian; Ridger, Victoria; Evans, Paul C

    2016-07-01

    Blood flow generates wall shear stress (WSS) which alters endothelial cell (EC) function. Low WSS promotes vascular inflammation and atherosclerosis whereas high uniform WSS is protective. Ivabradine decreases heart rate leading to altered haemodynamics. Besides its cardio-protective effects, ivabradine protects arteries from inflammation and atherosclerosis via unknown mechanisms. We hypothesised that ivabradine protects arteries by increasing WSS to reduce vascular inflammation. Hypercholesterolaemic mice were treated with ivabradine for seven weeks in drinking water or remained untreated as a control. En face immunostaining demonstrated that treatment with ivabradine reduced the expression of pro-inflammatory VCAM-1 (p<0.01) and enhanced the expression of anti-inflammatory eNOS (p<0.01) at the inner curvature of the aorta. We concluded that ivabradine alters EC physiology indirectly via modulation of flow because treatment with ivabradine had no effect in ligated carotid arteries in vivo, and did not influence the basal or TNFα-induced expression of inflammatory (VCAM-1, MCP-1) or protective (eNOS, HMOX1, KLF2, KLF4) genes in cultured EC. We therefore considered whether ivabradine can alter WSS which is a regulator of EC inflammatory activation. Computational fluid dynamics demonstrated that ivabradine treatment reduced heart rate by 20 % and enhanced WSS in the aorta. In conclusion, ivabradine treatment altered haemodynamics in the murine aorta by increasing the magnitude of shear stress. This was accompanied by induction of eNOS and suppression of VCAM-1, whereas ivabradine did not alter EC that could not respond to flow. Thus ivabradine protects arteries by altering local mechanical conditions to trigger an anti-inflammatory response.

  14. Heart rate reduction with ivabradine promotes shear stress-dependent anti-inflammatory mechanisms in arteries.

    PubMed

    Luong, Le; Duckles, Hayley; Schenkel, Torsten; Mahmoud, Marwa; Tremoleda, Jordi L; Wylezinska-Arridge, Marzena; Ali, Majid; Bowden, Neil P; Villa-Uriol, Mari-Cruz; van der Heiden, Kim; Xing, Ruoyu; Gijsen, Frank J; Wentzel, Jolanda; Lawrie, Allan; Feng, Shuang; Arnold, Nadine; Gsell, Willy; Lungu, Angela; Hose, Rodney; Spencer, Tim; Halliday, Ian; Ridger, Victoria; Evans, Paul C

    2016-07-01

    Blood flow generates wall shear stress (WSS) which alters endothelial cell (EC) function. Low WSS promotes vascular inflammation and atherosclerosis whereas high uniform WSS is protective. Ivabradine decreases heart rate leading to altered haemodynamics. Besides its cardio-protective effects, ivabradine protects arteries from inflammation and atherosclerosis via unknown mechanisms. We hypothesised that ivabradine protects arteries by increasing WSS to reduce vascular inflammation. Hypercholesterolaemic mice were treated with ivabradine for seven weeks in drinking water or remained untreated as a control. En face immunostaining demonstrated that treatment with ivabradine reduced the expression of pro-inflammatory VCAM-1 (p<0.01) and enhanced the expression of anti-inflammatory eNOS (p<0.01) at the inner curvature of the aorta. We concluded that ivabradine alters EC physiology indirectly via modulation of flow because treatment with ivabradine had no effect in ligated carotid arteries in vivo, and did not influence the basal or TNFα-induced expression of inflammatory (VCAM-1, MCP-1) or protective (eNOS, HMOX1, KLF2, KLF4) genes in cultured EC. We therefore considered whether ivabradine can alter WSS which is a regulator of EC inflammatory activation. Computational fluid dynamics demonstrated that ivabradine treatment reduced heart rate by 20 % and enhanced WSS in the aorta. In conclusion, ivabradine treatment altered haemodynamics in the murine aorta by increasing the magnitude of shear stress. This was accompanied by induction of eNOS and suppression of VCAM-1, whereas ivabradine did not alter EC that could not respond to flow. Thus ivabradine protects arteries by altering local mechanical conditions to trigger an anti-inflammatory response. PMID:27075869

  15. Anti-inflammatory activity of gel containing novel elastic niosomes entrapped with diclofenac diethylammonium.

    PubMed

    Manosroi, A; Jantrawut, P; Manosroi, J

    2008-08-01

    enhancement of transdermal absorption through rat skin, but also the in vivo anti-inflammatory effect of DCFD when entrapped in the developed novel elastic Tween 61 niosomes, as well. PMID:18539416

  16. Lipoxins exert antiangiogenic and anti-inflammatory effects on Kaposi's sarcoma cells.

    PubMed

    Marginean, Alexandru; Sharma-Walia, Neelam

    2015-08-01

    Lipoxin A4 (LXA4) is an endogenously produced host molecule with anti-inflammatory resolution effects. Previous studies demonstrated it to be involved in anti-vascular endothelial growth factor (VEGF)-mediated angiogenesis and in a possible anticancer role via interaction with its receptor, lipoxin A 4 receptor (ALXR). Here, we examined the effects of LXA4 and its epimer 15-epi-LXA4 in inhibiting proinflammatory and angiogenic functions in a human Kaposi's sarcoma tumor-derived cell line (KS-IMM). KS-IMM cells expressed increased levels of inflammatory cyclooxygenase 2 (COX-2) and 5-lipoxygenase (5-LO) pathway enzymes when compared with human microvascular dermal endothelial cells (HMVEC-d). KS-IMM cells secreted high levels of prostaglandin E2 (PGE2) and chemotactic leukotriene B4 (LTB4). Treatment with LXA4 or 15-epi-LXA4 effectively reduced the levels of COX-2, 5-LO proteins, and secretion of PGE2 and LTB4 in KS-IMM cells. LXA4 or 15-epi-LXA4 treatment also decreased secretion of proinflammatory interleukin 6 (IL-6) and IL-8 cytokines but induced the secretion of anti-inflammatory IL-10. LXA4 treatment reduced the phosphorylation of VEGF receptor (VEGFR) and ephrin family receptor tyrosine kinases. LXA4 treatment effectively induced dephosphorylation of multiple cellular kinases such as Focal Adhesion Kinase, Protein kinase B, nuclear factor kappa-light-chain-enhancer of activated B cells, and Extracellular signal-regulated kinases (ERK)1/2, and reduced angiogenic factor VEGF-C secretion in KS cells. LX treatment drastically induced the Src-homology 2 domain-containing phosphatase tyrosine (Y542) phosphatase and reduced VEGFR-2 phosphorylation at sites Y1059, Y1175, and Y1212. Treatment of KS-IMM cells with LXA4 resulted in selective localization of VEGFR-2 in nonlipid raft (non-LR) and ALXR to LR fractions. These results demonstrated that LXA4 or 15-epi-LXA4 induce anti-inflammatory and antiangiogenic effects in KS cells and suggest that treatment with LXs is

  17. Anti-inflammatory drugs in the 21st century.

    PubMed

    Rainsford, K D

    2007-01-01

    Historically, anti-inflammatory drugs had their origins in the serendipitous discovery of certain plants and their extracts being applied for the relief of pain, fever and inflammation. When salicylates were discovered in the mid-19th century to be the active components of Willow Spp., this enabled these compounds to be synthesized and from this, acetyl-salicylic acid or Aspirin was developed. Likewise, the chemical advances of the 19th-20th centuries lead to development of the non-steroidal anti-inflammatory drugs (NSAIDs), most of which were initially organic acids, but later non-acidic compounds were discovered. There were two periods of NSAID drug discovery post-World War 2, the period up to the 1970's which was the pre-prostaglandin period and thereafter up to the latter part of the last century in which their effects on prostaglandin production formed part of the screening in the drug-discovery process. Those drugs developed up to the 1980-late 90's were largely discovered empirically following screening for anti-inflammatory, analgesic and antipyretic activities in laboratory animal models. Some were successfully developed that showed low incidence of gastro-intestinal (GI) side effects (the principal adverse reaction seen with NSAIDs) than seen with their predecessors (e.g. aspirin, indomethacin, phenylbutazone); the GI reactions being detected and screened out in animal assays. In the 1990's an important discovery was made from elegant molecular and cellular biological studies that there are two cyclo-oxygenase (COX) enzyme systems controlling the production of prostanoids [prostaglandins (PGs) and thromboxane (TxA2)]; COX-1 that produces PGs and TxA2 that regulate gastrointestinal, renal, vascular and other physiological functions, and COX-2 that regulates production of PGs involved in inflammation, pain and fever. The stage was set in the 1990's for the discovery and development of drugs to selectively control COX-2 and spare the COX-1 that is central to

  18. Therapeutic potential of caffeic acid phenethyl ester and its anti-inflammatory and immunomodulatory effects (Review)

    PubMed Central

    ARMUTCU, FERAH; AKYOL, SUMEYYA; USTUNSOY, SEYFETTIN; TURAN, FATIME FILIZ

    2015-01-01

    Caffeic acid phenethyl ester (CAPE), a naturally occurring compound isolated from propolis extract, has been reported to have a number of biological and pharmacological properties, exerting antioxidant, anti-inflammatory, anticarcinogenic, antibacterial and immunomodulatory effects. Recent in vivo and in vitro study findings have provided novel insights into the molecular mechanisms involved in the anti-inflammatory and immunomodulatory activities of this natural compound. CAPE has been reported to have anti-inflammatory properties involving the inhibition of certain enzyme activities, such as xanthine oxidase, cyclooxygenase and nuclear factor-κB (NF-κB) activation. Since inflammation and immune mechanisms play a crucial role in the onset of several inflammatory diseases, the inhibition of NF-κB represents a rationale for the development of novel and safe anti-inflammatory agents. The primary goal of the present review is to highlight the anti-inflammatory and immunomodulatory activities of CAPE, and critically evaluate its potential therapeutic effects. PMID:26136862

  19. Anti-incretin, Anti-proliferative Action of Dopamine on β-Cells.

    PubMed

    Maffei, Antonella; Segal, Ann Marie; Alvarez-Perez, Juan Carlos; Garcia-Ocaña, Adolfo; Harris, Paul E

    2015-04-01

    Human islet β-cells exploit an autocrine dopamine (DA)-mediated inhibitory circuit to regulate insulin secretion. β-Cells also express the DA active transporter and the large neutral amino acid transporter heterodimer enabling them to import circulating DA or its biosynthetic precursor, L-3,4-dihydroxyphenylalanine (L-DOPA). The capacity to import DA or L-DOPA from the extracellular space possibly indicates that DA may be an endocrine signal as well. In humans, a mixed meal stimulus is accompanied by contemporary serum excursions of incretins, DA and L-DOPA, suggesting that DA may act as an anti-incretin as postulated by the foregut hypothesis proposed to explain the early effects of bariatric surgery on type 2 diabetes. In this report, we take a translational step backwards and characterize the kinetics of plasma DA and incretin production after a mixed meal challenge in a rat model and study the integration of incretin and DA signaling at the biochemical level in a rodent β-cell line and islets. We found that there are similar excursions of incretins and DA in rats, as those reported in humans, after a mixed meal challenge and that DA counters incretin enhanced glucose-stimulated insulin secretion and intracellular signaling at multiple points from dampening calcium fluxes to inhibiting proliferation as well as apoptosis. Our data suggest that DA is an important regulator of insulin secretion and may represent 1 axis of a gut level circuit of glucose and β-cell mass homeostasis.

  20. Hybrid surfactants decorated with copper ions: aggregation behavior, antimicrobial activity and anti-proliferative effect.

    PubMed

    Kaur, Gurpreet; Kumar, Sandeep; Dilbaghi, Neeraj; Bhanjana, Gaurav; Guru, Santosh Kumar; Bhushan, Shashi; Jaglan, Sundeep; Hassan, P A; Aswal, V K

    2016-09-14

    In the present study, the emphasis is laid on the self aggregation behavior of copper based inorganic-organic hybrids in aqueous media. The two complexes, cationic hexadecyl pyridinium trichloro cuprate (1 : 1), [Cp](+)[CuCl3](-), and bishexadecylpyridinium tetrachloro cuprate (2 : 1), [Cp2](2+)[CuCl4](2-), were synthesized using the ligand insertion method. The complexes were characterized using elemental analysis, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), nuclear magnetic resonance (NMR) and thermogravimetric analysis. The copper complexes were found to be thermally stable, and in the solid state, they possessed the perovskite arrangement with [Cp2](2+)[CuCl4](2-) exhibiting superior stability and crystallinity. The self aggregation behavior of the prepared complexes was analyzed in solution phase (in aqueous medium) using surface tension, conductivity, XRD and small angle neutron scattering (SANS). The results show that the presence of copper as a co-ion in both the stoichiometries results in lower critical micellization concentrations than their precursor. Micellization was thermodynamically spontaneous and micelles formed were ellipsoidal in shape and underwent a prolate ellipsoidal growth with an increase in the concentration of metallosurfactant, as estimated from the SANS. Furthermore, these metallosurfactants were investigated for biocompatibility (using hemolytic assay), antimicrobial activity (fungus and bacteria) and cytotoxicity using human cancerous cells. The hemolysis activity was found to depend on the aggregated state of the metallosurfactants, displaying the highest activity in the monomeric state, and the minimum for post micellar concentrations. The surfactants were found to enhance the antibacterial activity by twofold or more, with the addition of metal in both the stoichiometries. On the contrary, for anticancer and antifungal activities, barely any regular trend or generalization could be obtained

  1. Hybrid surfactants decorated with copper ions: aggregation behavior, antimicrobial activity and anti-proliferative effect.

    PubMed

    Kaur, Gurpreet; Kumar, Sandeep; Dilbaghi, Neeraj; Bhanjana, Gaurav; Guru, Santosh Kumar; Bhushan, Shashi; Jaglan, Sundeep; Hassan, P A; Aswal, V K

    2016-09-14

    In the present study, the emphasis is laid on the self aggregation behavior of copper based inorganic-organic hybrids in aqueous media. The two complexes, cationic hexadecyl pyridinium trichloro cuprate (1 : 1), [Cp](+)[CuCl3](-), and bishexadecylpyridinium tetrachloro cuprate (2 : 1), [Cp2](2+)[CuCl4](2-), were synthesized using the ligand insertion method. The complexes were characterized using elemental analysis, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), nuclear magnetic resonance (NMR) and thermogravimetric analysis. The copper complexes were found to be thermally stable, and in the solid state, they possessed the perovskite arrangement with [Cp2](2+)[CuCl4](2-) exhibiting superior stability and crystallinity. The self aggregation behavior of the prepared complexes was analyzed in solution phase (in aqueous medium) using surface tension, conductivity, XRD and small angle neutron scattering (SANS). The results show that the presence of copper as a co-ion in both the stoichiometries results in lower critical micellization concentrations than their precursor. Micellization was thermodynamically spontaneous and micelles formed were ellipsoidal in shape and underwent a prolate ellipsoidal growth with an increase in the concentration of metallosurfactant, as estimated from the SANS. Furthermore, these metallosurfactants were investigated for biocompatibility (using hemolytic assay), antimicrobial activity (fungus and bacteria) and cytotoxicity using human cancerous cells. The hemolysis activity was found to depend on the aggregated state of the metallosurfactants, displaying the highest activity in the monomeric state, and the minimum for post micellar concentrations. The surfactants were found to enhance the antibacterial activity by twofold or more, with the addition of metal in both the stoichiometries. On the contrary, for anticancer and antifungal activities, barely any regular trend or generalization could be obtained

  2. Anti-incretin, Anti-proliferative Action of Dopamine on β-Cells

    PubMed Central

    Segal, Ann Marie; Alvarez-Perez, Juan Carlos; Garcia-Ocaña, Adolfo; Harris, Paul E.

    2015-01-01

    Human islet β-cells exploit an autocrine dopamine (DA)-mediated inhibitory circuit to regulate insulin secretion. β-Cells also express the DA active transporter and the large neutral amino acid transporter heterodimer enabling them to import circulating DA or its biosynthetic precursor, L-3,4-dihydroxyphenylalanine (L-DOPA). The capacity to import DA or L-DOPA from the extracellular space possibly indicates that DA may be an endocrine signal as well. In humans, a mixed meal stimulus is accompanied by contemporary serum excursions of incretins, DA and L-DOPA, suggesting that DA may act as an anti-incretin as postulated by the foregut hypothesis proposed to explain the early effects of bariatric surgery on type 2 diabetes. In this report, we take a translational step backwards and characterize the kinetics of plasma DA and incretin production after a mixed meal challenge in a rat model and study the integration of incretin and DA signaling at the biochemical level in a rodent β-cell line and islets. We found that there are similar excursions of incretins and DA in rats, as those reported in humans, after a mixed meal challenge and that DA counters incretin enhanced glucose-stimulated insulin secretion and intracellular signaling at multiple points from dampening calcium fluxes to inhibiting proliferation as well as apoptosis. Our data suggest that DA is an important regulator of insulin secretion and may represent 1 axis of a gut level circuit of glucose and β-cell mass homeostasis. PMID:25751312

  3. Synthesis and biological evaluation of 2-benzoylpyridine thiosemicarbazones in a dimeric system: structure-activity relationship studies on their anti-proliferative and iron chelation efficacy.

    PubMed

    Lukmantara, Adeline Y; Kalinowski, Danuta S; Kumar, Naresh; Richardson, Des R

    2014-12-01

    Thiosemicarbazone chelators represent an exciting class of biologically active compounds that show great potential as anti-tumor agents. Our previous studies demonstrated the potent anti-tumor activity of the 2'-benzoylpyridine thiosemicarbazone series. While extensive studies have been performed on monomeric thiosemicarbazone compounds, dimeric thiosemicarbazone chelators have received comparatively less attention. Thus, it was of interest to investigate the anti-proliferative activity and iron chelation efficacy of dimeric thiosemicarbazones. Two classes of dimeric thiosemicarbazones were designed and synthesized. The first class consisted of two benzoylpyridine-based thiosemicarbazone units connected via a hexane or dodecane alkyl bridge, while the second class of dimer consisted of two thiosemicarbazones attached to a 2,6-dibenzoylpyridine core. These dimeric ligands demonstrated greater anti-proliferative activity than the clinically used iron chelator, desferrioxamine. This study highlights the importance of optimal lipophilicity as a factor influencing the cytotoxicity and iron chelation efficacy of these chelators.

  4. Separation and purification and in vitro anti-proliferative activity of leukemia cell K562 of Galium aparine L. petroleum ether phase.

    PubMed

    Shi, Guoqing; Liu, Jiang; Zhao, Wen'en; Liu, Yanqi; Tian, Xinfeng

    2016-05-01

    To explore material basis of in vitro anti-proliferative activity of leukemia cell K562 of petroleum ether phase of product resulting from Galium aparine L. 60% ethanol extraction, the experiment adopts column chromatography combined with thin layer preparation, isolates and purifies petroleum ether, conducts structural identification of obtained single compound and applies MTT method for viability assay of in vitro anti-proliferative activity of leukemia cell K562. Experimental results show that G. aparine L. petroleum ether contains mainly β-sitosterol, daucosterol and dibutyl phthalate and other substances. Under experimental conditions, the three could inhibit the proliferation of leukemia cell K562 with dose-effect and time-effect relationship, of which dibutyl phthalate has strongest activity. Dibutyl phthalate with excellent activity, β-sitosterol with rich content and moderate effect should be the main contributor to its biological activity. PMID:27275108

  5. Pro- and anti-inflammatory cytokines in human immunodeficiency virus infection and acquired immunodeficiency syndrome.

    PubMed

    Breen, Elizabeth Crabb

    2002-09-01

    In persons with human immunodeficiency virus (HIV) infection and/or acquired immunodeficiency syndrome (AIDS), the immune system becomes dysfunctional in many ways. There is both immunodeficiency due to the loss of CD4-positive T helper cells and hyperactivity as a result of B-cell activation. Likewise, both decreases and increases are seen in the production and/or activity of cytokines. Cytokine changes in HIV infection have been assessed by a variety of techniques, ranging from determination of cytokine gene expression at the mRNA level to secretion of cytokine proteins in vivo and in vitro. Changes in cytokine levels in HIV-infected persons can affect the function of the immune system, and have the potential to directly impact the course of HIV disease by enhancing or suppressing HIV replication. In particular, the balance between the pro-inflammatory cytokines interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha, which up-regulate HIV expression, and IL-10, which can act both as an anti-inflammatory cytokine and a B-cell stimulatory factor, may play an important role in the progression to AIDS. In light of its ability to suppress the production of pro-inflammatory cytokines and, under some conditions, suppress HIV replication, increased IL-10 may be viewed as beneficial in slowing HIV disease progression. However, an association between increased IL-10 and the development of AIDS-associated B-cell lymphoma highlights the bifunctional nature of IL-10 as both an anti-inflammatory and B-cell-stimulatory cytokine that could have beneficial and detrimental effects on the course of HIV infection and AIDS.

  6. Human TLR10 is an anti-inflammatory pattern-recognition receptor.

    PubMed

    Oosting, Marije; Cheng, Shih-Chin; Bolscher, Judith M; Vestering-Stenger, Rachel; Plantinga, Theo S; Verschueren, Ineke C; Arts, Peer; Garritsen, Anja; van Eenennaam, Hans; Sturm, Patrick; Kullberg, Bart-Jan; Hoischen, Alexander; Adema, Gosse J; van der Meer, Jos W M; Netea, Mihai G; Joosten, Leo A B

    2014-10-21

    Toll-like receptor (TLR)10 is the only pattern-recognition receptor without known ligand specificity and biological function. We demonstrate that TLR10 is a modulatory receptor with mainly inhibitory effects. Blocking TLR10 by antagonistic antibodies enhanced proinflammatory cytokine production, including IL-1β, specifically after exposure to TLR2 ligands. Blocking TLR10 after stimulation of peripheral blood mononuclear cells with pam3CSK4 (Pam3Cys) led to production of 2,065 ± 106 pg/mL IL-1β (mean ± SEM) in comparison with 1,043 ± 51 pg/mL IL-1β after addition of nonspecific IgG antibodies. Several mechanisms mediate the modulatory effects of TLR10: on the one hand, cotransfection in human cell lines showed that TLR10 acts as an inhibitory receptor when forming heterodimers with TLR2; on the other hand, cross-linking experiments showed specific induction of the anti-inflammatory cytokine IL-1 receptor antagonist (IL-1Ra, 16 ± 1.7 ng/mL, mean ± SEM). After cross-linking anti-TLR10 antibody, no production of IL-1β and other proinflammatory cytokines could be found. Furthermore, individuals bearing TLR10 polymorphisms displayed an increased capacity to produce IL-1β, TNF-α, and IL-6 upon ligation of TLR2, in a gene-dose-dependent manner. The modulatory effects of TLR10 are complex, involving at least several mechanisms: there is competition for ligands or for the formation of heterodimer receptors with TLR2, as well as PI3K/Akt-mediated induction of the anti-inflammatory cytokine IL-1Ra. Finally, transgenic mice expressing human TLR10 produced fewer cytokines when challenged with a TLR2 agonist. In conclusion, to our knowledge we demonstrate for the first time that TLR10 is a modulatory pattern-recognition receptor with mainly inhibitory properties.

  7. Anti-inflammatory Actions of Adjunctive Tetracyclines and Other Agents in Periodontitis and Associated Comorbidities

    PubMed Central

    Tilakaratne, Aruni; Soory, Mena

    2014-01-01

    The non-antimicrobial properties of tetracyclines such as anti-inflammatory, proanabolic and anti-catabolic actions make them effective pharmaceuticals for the adjunctive management of chronic inflammatory diseases. An over-exuberant inflammatory response to an antigenic trigger in periodontitis and other chronic inflammatory diseases could contribute to an autoimmune element in disease progression. Their adjunctive use in managing periodontitis could have beneficial effects in curbing excessive inflammatory loading from commonly associated comorbidities such as CHD, DM and arthritis. Actions of tetracyclines and their derivatives include interactions with MMPs, tissue inhibitors of MMPs, growth factors and cytokines. They affect the sequence of inflammation with implications on immunomodulation, cell proliferation and angiogenesis; these actions enhance their scope, in treating a range of disease entities. Non-antimicrobial chemically modified tetracyclines (CMTs) sustain their diverse actions in organ systems which include anti-inflammatory, anti-apoptotic, anti-proteolytic actions, inhibition of angiogenesis and tumor metastasis. A spectrum of biological actions in dermatitis, periodontitis, atherosclerosis, diabetes, arthritis, inflammatory bowel disease, malignancy and prevention of bone resorption is particularly relevant to minocycline. Experimental models of ischemia indicate their specific beneficial effects. Parallel molecules with similar functions, improved Zn binding and solubility have been developed for reducing excessive MMP activity. Curbing excessive MMP activity is particularly relevant to periodontitis, and comorbidities addressed here, where specificity is paramount. Unique actions of tetracyclines in a milieu of excessive inflammatory stimuli make them effective therapeutic adjuncts in the management of chronic inflammatory disorders. These beneficial actions of tetracyclines are relevant to the adjunctive management of periodontitis subjects

  8. Electrospun Microfiber Scaffolds with Anti-Inflammatory Tributanoylated N-Acetyl-d-Glucosamine Promote Cartilage Regeneration.

    PubMed

    Kim, Chaekyu; Shores, Lucas; Guo, Qiongyu; Aly, Ahmed; Jeon, Ok Hee; Kim, Do Hun; Bernstein, Nicholas; Bhattacharya, Rahul; Chae, Jemin Jeremy; Yarema, Kevin J; Elisseeff, Jennifer H

    2016-04-01

    Tissue-engineering strategies offer promising tools for repairing cartilage damage; however, these strategies suffer from limitations under pathological conditions. As a model disease for these types of nonideal systems, the inflammatory environment in an osteoarthritic (OA) joint limits the efficacy of engineered therapeutics by disrupting joint homeostasis and reducing its capacity for regeneration. In this work, we investigated a sugar-based drug candidate, a tributanoylated N-acetyl-d-glucosamine analogue, called 3,4,6-O-Bu3GlcNAc, that is known to reduce nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling in osteoarthritis. 3,4,6-O-Bu3GlcNAc not only inhibited NFκB signaling but also exerted chondrogenic and anti-inflammatory effects on chondrocytes isolated from patients with osteoarthritis. 3,4,6-O-Bu3GlcNAc also increased the expression of extracellular matrix proteins and induced cartilage tissue production in three-dimensional in vitro hydrogel culture systems. To translate these chondrogenic and anti-inflammatory properties to tissue regeneration in osteoarthritis, we implanted 3,4,6-O-Bu3GlcNAc-loaded poly(lactic-co-glycolic acid) microfiber scaffolds into rats. The drug-laden scaffolds were biocompatible, and when seeded with human OA chondrocytes, similarly promoted cartilage tissue formation. 3,4,6-O-Bu3GlcNAc combined with the appropriate structural environment could be a promising therapeutic approach for osteoarthritis. PMID:27019285

  9. Combined Antibacterial and Anti-Inflammatory Activity of a Cationic Disubstituted Dexamethasone-Spermine Conjugate▿

    PubMed Central

    Bucki, Robert; Leszczyńska, Katarzyna; Byfield, Fitzroy J.; Fein, David E.; Won, Esther; Cruz, Katrina; Namiot, Andrzej; Kułakowska, Alina; Namiot, Zbigniew; Savage, Paul B.; Diamond, Scott L.; Janmey, Paul A.

    2010-01-01

    The rising number of antibiotic-resistant bacterial strains represents an emerging health problem that has motivated efforts to develop new antibacterial agents. Endogenous cationic antibacterial peptides (CAPs) that are produced in tissues exposed to the external environment are one model for the design of novel antibacterial compounds. Here, we report evidence that disubstituted dexamethasone-spermine (D2S), a cationic corticosteroid derivative initially identified as a by-product of synthesis of dexamethasone-spermine (DS) for the purpose of improving cellular gene delivery, functions as an antibacterial peptide-mimicking molecule. This moiety exhibits bacterial killing activity against clinical isolates of Staphylococcus aureus, Pseudomonas aeruginosa present in cystic fibrosis (CF) sputa, and Pseudomonas aeruginosa biofilm. Although compromised in the presence of plasma, D2S antibacterial activity resists the proteolytic activity of pepsin and is maintained in ascites, cerebrospinal fluid, saliva, and bronchoalveolar lavage (BAL) fluid. D2S also enhances S. aureus susceptibility to antibiotics, such as amoxicillin (AMC), tetracycline (T), and amikacin (AN). Inhibition of interleukin-6 (IL-6) and IL-8 release from lipopolysaccharide (LPS)- or lipoteichoic acid (LTA)-treated neutrophils in the presence of D2S suggests that this molecule might also prevent systemic inflammation caused by bacterial wall products. D2S-mediated translocation of green fluorescent protein (GFP)-labeled glucocorticoid receptor (GR) in bovine aorta endothelial cells (BAECs) suggests that some of its anti-inflammatory activities involve engagement of glucocorticoid receptors. The combined antibacterial and anti-inflammatory activities of D2S suggest its potential as an alternative to natural CAPs in the prevention and treatment of some bacterial infections. PMID:20308375

  10. Experimental and theoretical study of possible correlation between the electrochemistry of canthin-6-one and the anti-proliferative activity against human cancer stem cells

    NASA Astrophysics Data System (ADS)

    Cebrián-Torrejón, G.; Doménech-Carbó, A.; Scotti, M. T.; Fournet, A.; Figadère, B.; Poupon, E.

    2015-12-01

    This work presents an approach to study the performance of novel targets able to overcome cancer stem cell chemoresistance, based on the voltammetric data for microparticulate films of natural or synthetic alkaloids from the canthin-6-one series. A comparison of this voltammetric technique with conventional solution phase electrochemistry suggests the differences in the anti-proliferative activity of canthin-6-ones could be tentatively correlated to their different capacity to generate semiquinone radical anions. These data also match theoretical calculations.

  11. Anti-proliferative properties of commercial Pelargonium sidoides tincture, with cell-cycle G0/G1 arrest and apoptosis in Jurkat leukaemia cells.

    PubMed

    Pereira, Andreia; Bester, Megan; Soundy, Puffy; Apostolides, Zeno

    2016-09-01

    Context Pelargonium sidoides DC (Geraniaceae) is an important medicinal plant indigenous to South Africa and Lesotho. Previous studies have shown that root extracts are rich in polyphenolic compounds with antibacterial, antiviral and immunomodulatory activities. Little is known regarding the anticancer properties of Pelargonium sidoides extracts. Objective This study evaluates the anti-proliferative effects of a Pelargonium sidoides radix mother tincture (PST). Materials and methods The PST was characterized by LC-MS/MS. Anti-proliferative activity was evaluated in the pre-screen panel of the National Cancer Institute (NCI-H460, MCF-7 and SF-268) and the Jurkat leukaemia cell line at concentrations of 0-150 μg/mL. The effect on cell growth was determined with sulphorhodamine B and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays after 72 h. The effect on cell cycle and apoptosis induction in Jurkat cells was determined by flow cytometry with propidium iodide and Annexin V: fluorescein isothiocyanate staining. Results Dihydroxycoumarin sulphates, gallic acid as well as gallocatechin dimers and trimers were characterized in PST by mass spectrometry. Moderate anti-proliferative effects with GI50 values between 40 and 80 μg/mL were observed in the NCI-pre-screen panel. Strong activity observed with Jurkat cells with a GI50 value of 6.2 μg/mL, significantly better than positive control 5-fluorouracil (GI50 value of 9.7 μg/mL). The PST arrested Jurkat cells at the G0/G1 phase of the cell cycle and increased the apoptotic cells from 9% to 21%, while the dead cells increased from 4% to 17%. Conclusion We present evidence that P. sidoides has cancer cell type-specific anti-proliferative effects and may be a source of novel anticancer molecules. PMID:26794080

  12. A novel anti-inflammatory oligopeptide produced by Entamoeba histolytica.

    PubMed

    Kretschmer, R R; Rico, G; Giménez, J A

    2001-02-01

    The monocyte locomotion inhibitory factor (MLIF), a heat-stable oligopeptide found in the supernatant fluid of Entamoeba histolytica axenic cultures was isolated by ultra-filtration, gel-sieve chromatography and high powered liquid chromatography (HPLC), and its primary structure (Met-Gln-Cys-Asn-Ser) established by Edman sequencing and mass-spectrometry (MS). A synthetic peptide had the same selective anti-inflammatory features as the native material in comparable concentrations: in vitro inhibition of the locomotion in human peripheral blood monocytes, and of the respiratory burst in the same cells and in human neutrophil polymorphonuclear leucocytes; and in vivo depression of delayed hypersensitivity skin reactions to dinitrochlorobenzene in guinea pigs. This oligopeptide is apparently synthesized by the ameba as suggested by [(35)S]-Cys and Met incorporation, probably as part of a larger molecule, from which it is cleaved by proteolysis. The full sequence was not found in the 431 available E. histolytica protein sequences. The factor may contribute to the unexpected paucity of the late inflammatory reaction found in advanced invasive amebiasis and, perhaps in consequence, to the regeneration without scarring (restitutio ad integrum) of the affected organs that is observed following successful treatment of this disease

  13. Incorporation of anti-inflammatory agent into mesoporous silica

    NASA Astrophysics Data System (ADS)

    Rodrigues Braz, Wilson; Lamec Rocha, Natállia; de Faria, Emerson H.; Silva, Márcio L. A. e.; Ciuffi, Katia J.; Tavares, Denise C.; Furtado, Ricardo Andrade; Rocha, Lucas A.; Nassar, Eduardo J.

    2016-09-01

    The unique properties of macroporous, mesoporous, and microporous systems, including their ability to accommodate molecules of different sizes inside their pores and to act as drug delivery systems, have been the object of extensive studies. In this work, mesoporous silica with hexagonal structure was obtained by template synthesis via the sol-gel process. The resulting material was used as support to accommodate the anti-inflammatory agent indomethacin. The alkaline route was used to prepare the mesoporous silica; cetyltrimethylammonium bromide was employed as porogenic agent. The silica particles were functionalized with 3-aminopropyltriethoxysilane alkoxide (APTES) by the sol-gel post-synthesis method. Indomethacin was incorporated into the silica functionalized with APTES and into non-functionalized silica. The resulting systems were characterized by x-ray diffraction (XRD), specific area, infrared spectroscopy, and thermal analyses (TGA). XRD attested to formation of mesoporous silica with hexagonal structure. This structure remained after silica functionalization with APTES and incorporation of indomethacin. Typical infrared spectroscopy vibrations and organic material decomposition during TGA confirmed silica functionalization and drug incorporation. The specific surface area and pore volume of the functionalized material incorporated with indomethacin decreased as compared with the specific surface area and pore volume of the non-functionalized silica containing no drug, suggesting both the functionalizing agent and the drug were present in the silica. Cytotoxicity tests conducted on normal fibroblasts (GM0479A) cells attested that the silica matrix containing indomethacin was less toxic than the free drug.

  14. Anti-inflammatory phenanthrene derivatives from stems of Dendrobium denneanum.

    PubMed

    Lin, Yuan; Wang, Fei; Yang, Li-Juan; Chun, Ze; Bao, Jin-Ku; Zhang, Guo-Lin

    2013-11-01

    Cultivated Dendrobium denneanum has been substituted for other endangered Dendrobium species in recent years, but there have been few studies regarding either its chemical constituents or pharmacological effects. In this study, three phenanthrene glycosides, three 9,10-dihydrophenanthrenes, two 9,10-dihydrophenanthrenes glycosides, and four known phenanthrene derivatives, were isolated from the stems of D. denneanum. Their structures were elucidated on the basis of MS and NMR spectroscopic data. Ten compounds were found to inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-activated mouse macrophage RAW264.7 cells with IC50 values of 0.7-41.5 μM, and exhibited no cytotoxicity in RAW264.7, HeLa, or HepG2 cells. Additionally, it was found that 2,5-dihydroxy-4-methoxy-phenanthrene 2-O-β-d-glucopyranoside, and 5-methoxy-2,4,7,9S-tetrahydroxy-9,10-dihydrophenanthrene suppressed LPS-induced expression of inducible NO synthase (iNOS) inhibited phosphorylation of p38, JNK as well as mitogen-activated protein kinase (MAPK), and inhibitory kappa B-α (IκBα). This indicated that both compounds exert anti-inflammatory effects by inhibiting MAPKs and nuclear factor κB (NF-κB) pathways. PMID:24042064

  15. Anti-inflammatory, Analgesic and Antiulcer properties of Porphyra vietnamensis

    PubMed Central

    Bhatia, Saurabh; Sharma, Kiran; Sharma, Ajay; Nagpal, Kalpana; Bera, Tanmoy

    2015-01-01

    Objectives: Aim of the present work was to investigate the anti-inflammatory, analgesic and antiulcer effects of red seaweed Porphyra vietnamensis (P. vietnamenis). Materials and Methods: Aqueous (POR) and alcoholic (PE) fractions were successfully isolated from P. vietnamenis. Further biological investigations were performed using a classic test of paw edema induced by carrageenan, writhing induced by acetic acid, hot plate method and naproxen induced gastro-duodenal ulcer. Results: Among the fractions POR showed better activity. POR and PE significantly (p < 0.05) reduced carrageenan induced paw edema in a dose dependent manner. In the writhing test POR significantly (p < 0.05) reduced abdominal writhes than PE. In hot plate method POR showed better analgesic activity than PE. POR showed comparable ulcers reducing potential (p<0.01) to that of omeprazole, and has more ulcer reducing potential then PE. Conclusions: The results of this study demonstrated that P. vietnamenis aqueous fraction possesses biological activity that is close to the standards taken for the treatment of peripheral painful or/and inflammatory and ulcer conditions. PMID:25767759

  16. Incorporation of anti-inflammatory agent into mesoporous silica

    NASA Astrophysics Data System (ADS)

    Rodrigues Braz, Wilson; Lamec Rocha, Natállia; de Faria, Emerson H.; Silva, Márcio L. A. e.; Ciuffi, Katia J.; Tavares, Denise C.; Furtado, Ricardo Andrade; Rocha, Lucas A.; Nassar, Eduardo J.

    2016-09-01

    The unique properties of macroporous, mesoporous, and microporous systems, including their ability to accommodate molecules of different sizes inside their pores and to act as drug delivery systems, have been the object of extensive studies. In this work, mesoporous silica with hexagonal structure was obtained by template synthesis via the sol–gel process. The resulting material was used as support to accommodate the anti-inflammatory agent indomethacin. The alkaline route was used to prepare the mesoporous silica; cetyltrimethylammonium bromide was employed as porogenic agent. The silica particles were functionalized with 3-aminopropyltriethoxysilane alkoxide (APTES) by the sol–gel post-synthesis method. Indomethacin was incorporated into the silica functionalized with APTES and into non-functionalized silica. The resulting systems were characterized by x-ray diffraction (XRD), specific area, infrared spectroscopy, and thermal analyses (TGA). XRD attested to formation of mesoporous silica with hexagonal structure. This structure remained after silica functionalization with APTES and incorporation of indomethacin. Typical infrared spectroscopy vibrations and organic material decomposition during TGA confirmed silica functionalization and drug incorporation. The specific surface area and pore volume of the functionalized material incorporated with indomethacin decreased as compared with the specific surface area and pore volume of the non-functionalized silica containing no drug, suggesting both the functionalizing agent and the drug were present in the silica. Cytotoxicity tests conducted on normal fibroblasts (GM0479A) cells attested that the silica matrix containing indomethacin was less toxic than the free drug.

  17. The neuroimmune basis of anti-inflammatory acupuncture.

    PubMed

    Kavoussi, Ben; Ross, B Evan

    2007-09-01

    This review article presents the evidence that the antiinflammatory actions of acupuncture are mediated via the reflexive central inhibition of the innate immune system. Both laboratory and clinical evidence have recently shown the existence of a negative feedback loop between the autonomic nervous system and the innate immunity. There is also experimental evidence that the electrical stimulation of the vagus nerve inhibits macrophage activation and the production of TNF, IL-1beta , IL-6, IL-18, and other proinflammatory cytokines. It is therefore conceivable that along with hypnosis, meditation, prayer, guided imagery, biofeedback, and the placebo effect, the systemic anti-inflammatory actions of traditional and electro-acupuncture are directly or indirectly mediated by the efferent vagus nerve activation and inflammatory macrophage deactivation. In view of this common physiological mediation, assessing the clinical efficacy of a specific acupuncture regimen using conventional double-blind placebo-controlled trials inherently lacks objectivity due to (1) the uncertainty of ancient rules for needle placement, (2) the diffuse noxious inhibitory control triggered by control-needling at irrelevant points, (3) the possibility of a dose-response relationship between stimulation and effects, and (4) the possibility of inadequate blinding using an inert sham procedure. A more objective assessment of its efficacy could perhaps consist of measuring its effects on the surrogate markers of autonomic tone and inflammation. The use of acupuncture as an adjunct therapy to conventional medical treatment for a number of chronic inflammatory and autoimmune diseases seems plausible and should be validated by confirming its cholinergicity.

  18. Cerebral analgesic response to nonsteroidal anti-inflammatory drug ibuprofen.

    PubMed

    Hodkinson, Duncan J; Khawaja, Nadine; OʼDaly, Owen; Thacker, Michael A; Zelaya, Fernando O; Wooldridge, Caroline L; Renton, Tara F; Williams, Steven C R; Howard, Matthew A

    2015-07-01

    Nonopioid agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs), are the most commonly used class of analgesics. Increasing evidence suggests that cyclooxygenase (COX) inhibition at both peripheral and central sites can contribute to the antihyperalgesic effects of NSAIDs, with the predominant clinical effect being mediated centrally. In this study, we examined the cerebral response to ibuprofen in presurgical and postsurgical states and looked at the analgesic interaction between surgical state and treatment. We used an established clinical pain model involving third molar extraction, and quantitative arterial spin labelling (ASL) imaging to measure changes in tonic/ongoing neural activity. Concurrent to the ASL scans, we presented visual analogue scales inside the scanner to evaluate the subjective experience of pain. This novel methodology was incorporated into a randomized double-blind placebo-controlled design, with an open method of drug administration. We found that independent of its antinociceptive action, ibuprofen has no effect on regional cerebral blood flow under pain-free conditions (presurgery). However, in the postsurgical state, we observed increased activation of top-down modulatory circuits, which was accompanied by decreases in the areas engaged because of ongoing pain. Our findings demonstrate that ibuprofen has a measurable analgesic response in the human brain, with the subjective effects of pain relief reflected in two distinct brain networks. The observed activation of descending modulatory circuits warrants further investigation, as this may provide new insights into the inhibitory mechanisms of analgesia that might be exploited to improve safety and efficacy in pain management.

  19. Immunomodulatory and anti-inflammatory effects of chondroitin sulphate

    PubMed Central

    du Souich, Patrick; García, Antonio G; Vergés, Josep; Montell, Eulàlia

    2009-01-01

    Chondroitin sulphate (CS) is a natural glycosaminoglycan present in the extracellular matrix and is formed by the 1–3 linkage of D-glucuronic acid to N-acetylgalactosamine. In chondrocytes, CS diminishes interleukin-1 p (IL-1p)-induced increases in p38 mitogen-activated protein kinase (p38MAPK) and signal-regulated kinase 1/2 (Erk1/2) phosphorylation, and decreases nuclear factor-KB (NF-kB) nuclear translocation and as a consequence, reduces the formation of pro-inflammatory cytokines, IL-1 p and TNF-a, and pro-inflammatory enzymes, such as phospholipase A2 (PLA2), cyclooxygenase 2 (COX-2) and nitric oxide synthase-2 (NOS-2). The mechanism of action of CS explains its beneficial effect on the cartilage, synovial membrane and subchondral bone. On the other hand, in vivo, CS given orally prevents hepatic NF-κB nuclear translocation, suggesting that systemic CS may elicit an anti-inflammatory effect in many tissues besides the articulation. There is preliminary evidence showing that in human beings, CS may be of benefit in other diseases where inflammation is an essential marker, such as psoriasis and atherosclerosis. The review of the literature suggest that CS might also be of interest for the treatment of other diseases with an inflammatory and/or autoimmune character, such as inflammatory bowel disease, degenerative diseases of the central nervous system and stroke, multiple sclerosis and other autoimmune diseases. PMID:19522843

  20. Nonsteroidal anti-inflammatory drug gastropathy: new avenues for safety

    PubMed Central

    Roth, Sanford H

    2011-01-01

    Chronic oral or systemic nonselective nonsteroidal anti-inflammatory drug (NSAID) therapy, ubiquitously used by physicians to treat osteoarthritis-associated pain, is associated with a wide range of symptomatic adverse events, the most frequent and serious of which is gastropathy. Although cardiovascular and renal problems are a very real concern, they are significantly less frequent. These complications can be life-threatening in at-risk populations such as older adults, who are common users of long-term oral systemic NSAID therapy. Topical NSAID formulations deliver effective doses of analgesics directly to the affected joints, thereby limiting systemic exposure and potentially the risk of systemic adverse events, such as gastropathy and serious cardiovascular events. There are currently two topical NSAIDs approved by the US Food and Drug Administration for osteoarthritis-associated pain, as well as for the signs and symptoms of osteoarthritis. This review discusses the relative safety, and the gastrointestinal, cardiovascular, and renal risks of chronic oral or systemic NSAID therapy and topical NSAID formulations in patients with osteoarthritis. PMID:21753867

  1. Non-steroidal Anti-inflammatory Drugs in Raptors

    USGS Publications Warehouse

    Oaks, J. Lindsay; Meteyer, Carol U.; Miller, R. Eric; Fowler, Murray E.

    2012-01-01

    The use of analgesia has become standard, and appropriate, practice in avian medicine. As in mammals, pain control in avian patients is usually accomplished with opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) used singly or in combination for a multimodal approach. Despite their usefulness, widespread use, and relative safety in clinical use, few controlled studies in birds have been conducted on efficacy, safety, and dosing. The guidelines for the use of NSAIDs in raptors and other birds have mainly been empirical. More recently, NSAIDs in free-living raptors have emerged as a major conservation issue with the discovery that diclofenac sodium was responsible for the population crash of three species of Gyps vultures in southern Asia. In this context, residues of veterinary NSAIDs in domestic animals are now considered environmental contaminants that can be significantly toxic to vultures and possibly other avian scavengers. Ironically, the disaster with Asian vultures has led to a considerable body of research on NSAIDs in raptors to the benefit of clinicians who now have scientific information available to help assess dosing, safety, toxicity, and pharmacokinetics of NSAIDs in their raptor patients.

  2. Anti-Inflammatory Dimethylfumarate: A Potential New Therapy for Asthma?

    PubMed Central

    Roth, Michael

    2013-01-01

    Asthma is a chronic inflammatory disease of the airways, which results from the deregulated interaction of inflammatory cells and tissue forming cells. Beside the derangement of the epithelial cell layer, the most prominent tissue pathology of the asthmatic lung is the hypertrophy and hyperplasia of the airway smooth muscle cell (ASMC) bundles, which actively contributes to airway inflammation and remodeling. ASMCs of asthma patients secrete proinflammatory chemokines CXCL10, CCL11, and RANTES which attract immune cells into the airways and may thereby initiate inflammation. None of the available asthma drugs cures the disease—only symptoms are controlled. Dimethylfumarate (DMF) is used as an anti-inflammatory drug in psoriasis and showed promising results in phase III clinical studies in multiple sclerosis patients. In regard to asthma therapy, DMF has been anecdotally reported to reduce asthma symptoms in patients with psoriasis and asthma. Here we discuss the potential use of DMF as a novel therapy in asthma on the basis of in vitro studies of its inhibitory effect on ASMC proliferation and cytokine secretion in ASMCs. PMID:23606796

  3. Anti-inflammatory tirucallane saponins from Paramignya scandens.

    PubMed

    Phan, Nguyen Huu Toan; Thuan, Nguyen Thi Dieu; Ngoc, Ninh Thi; Thao, Nguyen Phuong; Kim, Sohyun; Koh, Young Sang; Thanh, Nguyen Van; Cuong, Nguyen Xuan; Nam, Nguyen Hoai; Kiem, Phan Van; Kim, Young Ho; Minh, Chau Van

    2015-01-01

    Five new tirucallane saponins, paramignyosides A-E (1-5), were isolated from the water fraction of the Paramignya scandens stem and leaves. Their structures were elucidated on the basis of spectroscopic evidence including high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and one dimensional (1D)- and 2D-NMR. The effects of isolated compounds on pro-inflammatory cytokines were evaluated by measuring the production of interleukin (IL)-12 p40, IL-6, and tumor necrosis factor-α (TNF-α) in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs). Paramignyoside C (3) exhibited selective and potent inhibitory effect (IC50=5.03±0.19 µM) on the production of IL-12 p40 comparable to that of the positive control, SB203580 (IC50=5.00±0.16 µM). Further studies are required to confirm efficacy in vivo and the mechanism of anti-inflammatory effects. PMID:26133071

  4. Anti-inflammatory effects of glaucocalyxin B in microglia cells.

    PubMed

    Gan, Ping; Zhang, Li; Chen, Yanke; Zhang, Yu; Zhang, Fali; Zhou, Xiang; Zhang, Xiaohu; Gao, Bo; Zhen, Xuechu; Zhang, Jian; Zheng, Long Tai

    2015-05-01

    Over-activated microglia is involved in various kinds of neurodegenerative process including Parkinson, Alzheimer and HIV dementia. Suppression of microglial over activation has emerged as a novel strategy for treatment of neuroinflammation-based neurodegeneration. In the current study, anti-inflammatory and neuroprotective effects of the ent-kauranoid diterpenoids, which were isolated from the aerial parts of Rabdosia japonica (Burm. f.) var. glaucocalyx (Maxim.) Hara, were investigated in cultured microglia cells. Glaucocalyxin B (GLB), one of five ent-kauranoid diterpenoids, significantly decreased the generation of nitric oxide (NO), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) in the lipopolysaccharide (LPS)-activated microglia cells. In addition, GLB inhibited activation of nuclear factor-κB (NF-κB), p38 mitogen-activated protein kinase (MAPK) and generation of reactive oxygen species (ROS) in LPS-activated microglia cells. Furthermore, GLB strongly induced the expression of heme oxygenase (HO)-1 in BV-2 microglia cells. Finally, GLB exhibited neuroprotective effect by preventing over-activated microglia induced neurotoxicity in a microglia/neuron co-culture model. Taken together, the present study demonstrated that the GLB possesses anti-nueroinflammatory activity, and might serve as a potential therapeutic agent for treating neuroinflammatory diseases. PMID:26003084

  5. Anti-inflammatory properties of drugs from saffron crocus.

    PubMed

    Poma, Anna; Fontecchio, Gabriella; Carlucci, Giuseppe; Chichiriccò, Giuseppe

    2012-01-01

    The medicinal uses of saffron (Crocus sativus Linnaeus) have a long history beginning in Asian countries since the Late Bronze Age. Recent studies have validated its potential to lower the risk of several diseases. Some metabolites derived from saffron stigmas exert numerous therapeutic effects due to hypolipidemic, antitussive, antioxidant, antidiabetic activities and many others. Water and ethanol extracts of Crocus sativus L. are cardioprotective and counteract neurodegenerative disorders. Many of these medicinal properties of saffron can be attributed to a number of its compounds such as crocetin, crocins and other substances having strong antioxidant and radical scavenger properties against a variety of radical oxygen species and pro-inflammatory cytokines. Botany, worldwide spreading of cultivars, biochemical pathways, active constituents and chemical detection methods are reviewed. Therapeutic uses of saffron principles with particular regard to those exhibiting antioxidant and thus anti-inflammatory features are discussed. To date, very few adverse health effects of saffron have been demonstrated. At high doses (more than 5 g/die day), it should be avoided in pregnancy owing to its uterine stimulation activity.

  6. Anti-inflammatory Hydrolyzable Tannins from Myricaria bracteata.

    PubMed

    Liu, Jia-Bao; Ding, Ya-Si; Zhang, Ying; Chen, Jia-Bao; Cui, Bao-Song; Bai, Jin-Ye; Lin, Ming-Bao; Hou, Qi; Zhang, Pei-Cheng; Li, Shuai

    2015-05-22

    Twelve hydrolyzable tannins were obtained from the twigs of Myricaria bracteata, including two new hellinoyl-type dimers, bracteatinins D1 (1) and D2 (2); a new hellinoyl-type trimer, bracteatinin T1 (3); two known monomers, nilotinin M4 (4) and 1,3-di-O-galloyl-4,6-O-(aS)-hexahydroxydiphenoyl-β-d-glucose (5); six known dimers, tamarixinin A (6), nilotinin D8 (7), hirtellins A (10), B (9), and E (8), and isohirtellin C (11); and a known trimer, hirtellin T3 (12). The structures of the tannins were elucidated by spectroscopic data analysis and comparisons to known tannins. All compounds were evaluated as free radical scavengers using 1,1-diphenyl-2-picrylhydrazyl and hydroxy radicals and compared to the activity of BHT and Trolox. Compound 6 showed a significant anti-inflammatory effect on croton oil-induced ear edema in mice (200 mg/kg, inhibition rate 69.8%) and on collagen-induced arthritis in DBA/1 mice (20 mg/kg, inhibition rate 46.0% at day 57).

  7. Anti-inflammatory and side effects of cyclooxygenase inhibitors.

    PubMed

    Süleyman, Halis; Demircan, Berna; Karagöz, Yalçin

    2007-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used drugs in inflammatory diseases, since they are effective in management of pain, fever, redness, edema arising as a consequence of inflammatory mediator release. Studies have shown that both therapeutic and side effects of NSAIDs are dependent on cyclooxygenase (COX) inhibition. COX isoforms have been named constitutive (COX-1) and inducible (COX-2). COX-1 catalyzes formation of cytoprotective prostaglandins in thrombocytes, vascular endothelium, stomach mucosa, kidneys, pancreas, Langerhans islets, seminal vesicles, and brain. Induction of COX-2 by various growth factors, proinflammatory agents, endotoxins, mitogens, and tumor agents indicates that this isoform may have a role in induction of pathological processes, such as inflammation. It is well known that therapy with COX inhibitors is associated with a number of side effects including gastrointestinal erosions, and renal and hepatic insufficiency. Such critical adverse reactions are mostly dependent on COX-1 inhibition. As a result of research focused on reduction of the adverse effects of NSAIDs, selective COX-2 inhibitors, such as celecoxib and rofecoxib have been developed. However, many data demonstrate that mechanisms of action of these drugs are multidirectional and complex. These drugs or their derivatives, which belong to the same group, have distinct pharmacological effects, side effects and potencies which implies that there may be more than two, five or even tens of COX isoforms.

  8. Anti-proliferative and pro-apoptotic effects of lichen-derived compound protolichesterinic acid are not mediated by its lipoxygenase-inhibitory activity.

    PubMed

    Bessadóttir, M; Eiríksson, F F; Becker, S; Ögmundsdóttir, M H; Ómarsdóttir, S; Thorsteinsdóttir, M; Ögmundsdóttir, H M

    2015-07-01

    Lipoxygenases (LOXs) and their products are involved in several biological functions and have been associated with carcinogenesis. Protolichesterinic acid (PA), a lichen metabolite, inhibits 5- and 12-LOX and has anti-proliferative effects on various cancer cell lines. Here, PA was shown to inhibit proliferation of multiple myeloma cells, RPMI 8226 and U266, and pancreatic cancer cells AsPC-1. Apoptosis was induced only in multiple myeloma cells. Cell-cycle associated changes in expression and sub-cellular localization of 5- and 12-LOX were not affected by PA but increased cytoplasmic localisation was found to accompany morphological changes at later stages. Assessment by mass spectrometry showed that PA entered the pancreatic cancer cells. However, effects on LOX metabolites were only evident after treatment with concentrations exceeding those having anti-proliferative effects and no effects were measurable in the myeloma cells. We conclude that the anti-proliferative and pro-apoptotic effects of PA are not mediated directly through inhibition of LOX activity. PMID:25964147

  9. Biocatalytic polymer thin films: optimization of the multilayered architecture towards in situ synthesis of anti-proliferative drugs

    NASA Astrophysics Data System (ADS)

    Andreasen, Sidsel Ø.; Fejerskov, Betina; Zelikin, Alexander N.

    2014-03-01

    We report on the assembly of multi-layered polyelectrolyte thin films containing an immobilized enzyme to perform conversion of externally administered prodrugs and achieve delivery of the resulting therapeutics to adhering cells. Towards this goal, multi-layered coatings were assembled using poly(sodium styrene sulfonate) and poly(allylamine hydrochloride). Activity of the incorporated enzyme was quantified as a function of the assembly conditions, position of the enzyme within the multi-layered architecture, concentration of the enzyme in the adsorption solution, and concentration of the administered prodrug. Biocatalytic coatings exhibited sustained levels of enzymatic activity over at least one week of incubation in physiological buffers without signs of loss of activity of the enzyme. Developed enzyme-containing polymer films afforded zero-order release of the in situ synthesized cargo with kinetics of synthesis (nM per hour) covering at least 3 orders of magnitude. Internalization of the synthesized product by adhering cells was visualized using a fluorogenic enzyme substrate. Therapeutic utility of biocatalytic coatings was demonstrated using a myoblast cell line and a prodrug for the anti-proliferative agent, 5-fluorouridine. Taken together, this work presents a novel approach to delivery of small molecule drugs using multi-layered polymer thin films with utility in surface-mediated drug delivery, assembly of therapeutic implantable devices, and tissue engineering.We report on the assembly of multi-layered polyelectrolyte thin films containing an immobilized enzyme to perform conversion of externally administered prodrugs and achieve delivery of the resulting therapeutics to adhering cells. Towards this goal, multi-layered coatings were assembled using poly(sodium styrene sulfonate) and poly(allylamine hydrochloride). Activity of the incorporated enzyme was quantified as a function of the assembly conditions, position of the enzyme within the multi

  10. Involvement of proton-sensing receptor TDAG8 in the anti-inflammatory actions of dexamethasone in peritoneal macrophages

    SciTech Connect

    He, Xiao-dong; Tobo, Masayuki; Mogi, Chihiro; Nakakura, Takashi; Komachi, Mayumi; Murata, Naoya; Takano, Mutsumi; Tomura, Hideaki; Sato, Koichi; Okajima, Fumikazu

    2011-12-02

    Highlights: Black-Right-Pointing-Pointer Glucocorticoid (GC) induced the expression of proton-sensing TDAG8 in macrophages. Black-Right-Pointing-Pointer GC enhanced acidic pH-induced cAMP accumulation and inhibition of TNF-{alpha} production. Black-Right-Pointing-Pointer The enhancement of the GC-induced actions was lost by TDAG8 deficiency. Black-Right-Pointing-Pointer GC-induced anti-inflammatory actions are partly mediated by TDAG8 expression. -- Abstract: Dexamethasone (DEX), a potent glucocorticoid, increased the expression of T-cell death associated gene 8 (TDAG8), a proton-sensing G protein-coupled receptor, which is associated with the enhancement of acidic pH-induced cAMP accumulation, in peritoneal macrophages. We explored the role of increased TDAG8 expression in the anti-inflammatory actions of DEX. The treatment of macrophages with either DEX or acidic pH induced the cell death of macrophages; however, the cell death was not affected by TDAG8 deficiency. While DEX inhibited lipopolysaccharide-induced production of tumor necrosis factor-{alpha}, an inflammatory cytokine, which was independent of TDAG8, at neutral pH, the glucocorticoid enhanced the acidic pH-induced inhibition of tumor necrosis factor-{alpha} production in a manner dependent on TDAG8. In conclusion, the DEX-induced increase in TDAG8 expression is in part involved in the glucocorticoid-induced anti-inflammatory actions through the inhibition of inflammatory cytokine production under the acidic pH environment. On the other hand, the role of TDAG8 in the DEX-induced cell death is questionable.

  11. UP1306, a Botanical Composition with Analgesic and Anti-inflammatory Effect

    PubMed Central

    Yimam, Mesfin; Lee, Young-Chul; Jiao, Ping; Hong, Mei; Nam, Jeong-Bum; Brownell, Lidia; Hyun, Eujin; Jia, Qi

    2016-01-01

    and abdominal constriction (writhing's) assays in mouse are among the widely used models to evaluate the anti-inflammatory and analgesic effects of nutraceuticalsCyclooxygenase and lipoxygenase (LO) inhibition assays were carried out to determine the IC50 of Acacia and Morus extracts.Efficacy of UP1306, a composition containing a blend of two standardized extracts from the heartwood of Acacia catechu and root bark of Morus alba, was evaluated in the above models.UP1306 demonstrated its enhanced significance by improving the major cardinal signs of arthritis in vivo and inflammation markers in vitro.UP1306 could potentially be considered as a dietary supplement product for the management of arthritis. PMID:27365987

  12. Pomegranate Ellagitannin-Derived Compounds Exhibit Anti-proliferative and Anti-aromatase Activity in Breast Cancer Cells In Vitro

    PubMed Central

    Adams, Lynn S.; Zhang, Yanjun; Seeram, Navindra P.; Heber, David; Chen, Shiuan

    2009-01-01

    Estrogen stimulates the proliferation of breast cancer cells and the growth of estrogen-responsive tumors. The aromatase enzyme, which converts androgen to estrogen, plays a key role in breast carcinogenesis. The pomegranate fruit, a rich source of ellagitannins (ETs), has attracted recent attention due to its anti-cancer and anti-atherosclerotic properties. On consumption, pomegranate ETs hydrolyze, releasing ellagic acid (EA) which is then converted to 3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one (‘urolithin’) derivatives by gut microflora. The purpose of this study was to investigate the anti-aromatase activity and inhibition of testosterone-induced breast cancer cell proliferation by ellagitannin (ET)-derived compounds isolated from pomegranates. A panel of ten ET-derived compounds including EA, gallagic acid (GA), and urolithins A and B (and their acetylated, methylated and sulfated analogs prepared in our laboratory) were examined for ability to inhibit aromatase activity and testosterone-induced breast cancer cell proliferation. Using a microsomal aromatase assay, we screened the panel of ET-derived compounds and identified six with anti-aromatase activity. Among these, urolithin B (UB) was shown to most effectively inhibit aromatase activity in a live-cell assay. Kinetic analysis of UB demonstrated mixed inhibition, suggesting more than one inhibitory mechanism. Proliferation assays also determined that UB significantly inhibited testosterone-induced MCF-7aro cell proliferation. The remaining test compounds also exhibited anti-proliferative activity, but to a lesser degree than UB. These studies suggest that pomegranate ET-derived compounds have potential for the prevention of estrogen-responsive breast cancers. PMID:20051378

  13. MicroRNA mir-16 is anti-proliferative in enterocytes and exhibits diurnal rhythmicity in intestinal crypts

    SciTech Connect

    Balakrishnan, Anita; Stearns, Adam T.; Park, Peter J.; Dreyfuss, Jonathan M.; Ashley, Stanley W.; Rhoads, David B.; Tavakkolizadeh, Ali

    2010-12-10

    Background and aims: The intestine exhibits profound diurnal rhythms in function and morphology, in part due to changes in enterocyte proliferation. The regulatory mechanisms behind these rhythms remain largely unknown. We hypothesized that microRNAs are involved in mediating these rhythms, and studied the role of microRNAs specifically in modulating intestinal proliferation. Methods: Diurnal rhythmicity of microRNAs in rat jejunum was analyzed by microarrays and validated by qPCR. Temporal expression of diurnally rhythmic mir-16 was further quantified in intestinal crypts, villi, and smooth muscle using laser capture microdissection and qPCR. Morphological changes in rat jejunum were assessed by histology and proliferation by immunostaining for bromodeoxyuridine. In IEC-6 cells stably overexpressing mir-16, proliferation was assessed by cell counting and MTS assay, cell cycle progression and apoptosis by flow cytometry, and cell cycle gene expression by qPCR and immunoblotting. Results: mir-16 peaked 6 hours after light onset (HALO 6) with diurnal changes restricted to crypts. Crypt depth and villus height peaked at HALO 13-14 in antiphase to mir-16. Overexpression of mir-16 in IEC-6 cells suppressed specific G1/S regulators (cyclins D1-3, cyclin E1 and cyclin-dependent kinase 6) and produced G1 arrest. Protein expression of these genes exhibited diurnal rhythmicity in rat jejunum, peaking between HALO 11 and 17 in antiphase to mir-16. Conclusions: This is the first report of circadian rhythmicity of specific microRNAs in rat jejunum. Our data provide a link between anti-proliferative mir-16 and the intestinal proliferation rhythm and point to mir-16 as an important regulator of proliferation in jejunal crypts. This function may be essential to match proliferation and absorptive capacity with nutrient availability.

  14. Imatinib Mesylate Exerts Anti-Proliferative Effects on Osteosarcoma Cells and Inhibits the Tumour Growth in Immunocompetent Murine Models

    PubMed Central

    Ory, Benjamin; Charrier, Céline; Brion, Régis; Blanchard, Frederic; Redini, Françoise; Heymann, Dominique

    2014-01-01

    Osteosarcoma is the most common primary malignant bone tumour characterized by osteoid production and/or osteolytic lesions of bone. A lack of response to chemotherapeutic treatments shows the importance of exploring new therapeutic methods. Imatinib mesylate (Gleevec, Novartis Pharma), a tyrosine kinase inhibitor, was originally developed for the treatment of chronic myeloid leukemia. Several studies revealed that imatinib mesylate inhibits osteoclast differentiation through the M-CSFR pathway and activates osteoblast differentiation through PDGFR pathway, two key cells involved in the vicious cycle controlling the tumour development. The present study investigated the in vitro effects of imatinib mesylate on the proliferation, apoptosis, cell cycle, and migration ability of five osteosarcoma cell lines (human: MG-63, HOS; rat: OSRGA; mice: MOS-J, POS-1). Imatinib mesylate was also assessed as a curative and preventive treatment in two syngenic osteosarcoma models: MOS-J (mixed osteoblastic/osteolytic osteosarcoma) and POS-1 (undifferentiated osteosarcoma). Imatinib mesylate exhibited a dose-dependent anti-proliferative effect in all cell lines studied. The drug induced a G0/G1 cell cycle arrest in most cell lines, except for POS-1 and HOS cells that were blocked in the S phase. In addition, imatinib mesylate induced cell death and strongly inhibited osteosarcoma cell migration. In the MOS-J osteosarcoma model, oral administration of imatinib mesylate significantly inhibited the tumour development in both preventive and curative approaches. A phospho-receptor tyrosine kinase array kit revealed that PDGFRα, among 7 other receptors (PDFGFRβ, Axl, RYK, EGFR, EphA2 and 10, IGF1R), appears as one of the main molecular targets for imatinib mesylate. In the light of the present study and the literature, it would be particularly interesting to revisit therapeutic evaluation of imatinib mesylate in osteosarcoma according to the tyrosine-kinase receptor status of patients

  15. Evaluation of the Anti-proliferative Effects of Ophiocoma erinaceus Methanol Extract Against Human Cervical Cancer Cells

    PubMed Central

    Baharara, Javad; Amini, Elaheh; Namvar, Farideh

    2016-01-01

    Background: Marine organisms provide appreciable source of novel bioactive compounds with pharmacological potential. There is little information in correlation with anti-cancer activities of brittle star. In the present study, anti-neoplastic efficacy of Ophiocoma erinaceus methanol extract against human cervical cancer cells was investigated. Methods: The HeLa cells were cultured and exposed to brittle star methanol extract for 24 and 48 hr. The anti-proliferative properties were examined by MTT assay and the type of cell death induced was evaluated through morphological changes, flow cytometry, Annexin kit and caspase assay. To assess the anti-metastatic activity, wound healing assay was conducted and photographs were taken from the scratched areas. Further, to understand molecular mechanism of cell apoptosis, the expression of Bax was evaluated. Results: The morphological analysis and MTT assay exhibited that the brittle star methanol extract can exert dose dependent inhibitory effect on cells viability (IC50, 50 μg/ml). Flow cytometry and fluorescence microscopy demonstrated increment of sub-G1 peak, early and late apoptosis in HeLa treated cells. Wound healing migration assay showed that brittle star extract has anti-neoplastic efficacy by inhibiting cell migration. Caspase assay and RT-PCR analysis revealed that brittle star methanol extract induced caspase dependent apoptosis in HeLa cells through up-regulation of caspase-3 followed by up-regulation of Bax gene which is a hallmark of intrinsic pathway recruitment. Conclusion: These results represented further insights into the chemopreventive potential of brittle star as a valuable source of unknown therapeutic agents against human cervical cancer. PMID:26855733

  16. Quinoline-Based Compound BPIQ Exerts Anti-Proliferative Effects on Human Retinoblastoma Cells via Modulating Intracellular Reactive Oxygen Species.

    PubMed

    Cheng, Kai-Chun; Hung, Chun-Tzu; Chen, Kuo-Jen; Wu, Wen-Chuan; Suen, Jau-Ling; Chang, Cheng-Hsien; Lu, Chi-Yu; Tseng, Chih-Hua; Chen, Yeh-Long; Chiu, Chien-Chih

    2016-04-01

    Retinoblastoma (Rb) is the most common primary intraocular malignant tumor of childhood. It is important to develop the strategy for Rb treatment. We have tested a quinolone derivative 2,9-bis[2-(pyrrolidin-1-yl)ethoxy]-6-{4-[2-(pyrrolidin-1-yl)ethoxy]phenyl}-11H-indeno[1,2-c]quinolin-11-one (BPIQ) for its anti-cancer effects against Rb via cultured human Rb cell line Y79. Our results showed that BPIQ significantly inhibits cell growth of Y79. Furthermore, the flow cytometer-based assays and Western blotting showed that BPIQ induces the apoptosis of Y79 via increasing the level of reactive oxygen species (ROS). Besides, the activation of γH2AX, a DNA damage sensor in human Y79 cells was also observed, indicating the potential of BPIQ for causing DNA damage of Rb cells. On the contrary, BPIQ-induced apoptosis of Y79 cells was attenuated significantly by N-acetyl-L-cysteine (NAC), an ROS scavenger. The results of Western blot showed that BPIQ down-regulates the levels of anti-apoptotic proteins Bcl-2, survivin and XIAP while up-regulates the pro-apoptotic proteins Bad, Bax and Bid. Our present study demonstrated the anti-proliferative effect of BPIQ in human Y79 cells. The inhibitory effect of BPIQ on the proliferation of Y79 cells is, at least, partly mediated by the regulation of ROS and DNA damage pathway. In conclusion, BPIQ may provide an alternative option in the chemotherapeutics or chemoprevention on the Rb therapy in the future. PMID:26564153

  17. Anti-proliferative and angio-suppressive effect of Stoechospermum marginatum (C. Agardh) Kutzing extract using various experimental models

    PubMed Central

    Puttananjaiah, Shilpa; Chatterji, Anil; Salimath, Bharati

    2014-01-01

    BACKGROUND/OBJECTIVES Abundant consumption of seaweeds in the diet is epidemiologically linked to the reduction in risk of developing cancer. In larger cases, however, identification of particular seaweeds that are accountable for these effects is still lacking, hindering the recognition of competent dietary-based chemo preventive approaches. The aim of this research was to establish the antiproliferative potency and angiosuppressive mode of action of Stoechospermum marginatum seaweed methanolic extract using various experimental models. MATERIALS/METHODS Among the 15 seaweeds screened for antiproliferative activity against Ehrlich ascites tumor (EAT) cell line, Stoechospermum marginatum extract (SME) was found to be the most promising. Therefore, it was further investigated for its anti-proliferative activity in-vitro against choriocarcinoma (BeWo) and non-transformed Human embryonic kidney (HEK 293) cells, and for its anti-migratory/tube formation activity against HUVEC cells in-vitro. Subsequently, the angiosuppressive activity of S. marginatum was established by inhibition of angiogenesis in in-vivo (peritoneal angiogenesis and chorioallantoic membrane assay) and ex-vivo (rat cornea assay) models. RESULTS Most brown seaweed extracts inhibited the proliferation of EAT cells, while green and red seaweed extracts were much less effective. According to the results, SME selectively inhibited proliferation of BeWo cells in-vitro in a dose-dependent manner, but had a lesser effect on HEK 293 cells. SME also suppressed the migration and tube formation of HUVEC cells in-vitro. In addition, SME was able to suppress VEGF-induced angiogenesis in the chorio allantoic membrane, rat cornea, and tumor induced angiogenesis in the peritoneum of EAT bearing mice. A decrease in the microvessel density count and CD31 antigen staining of treated mice peritoneum provided further evidence of its angiosuppressive activity. CONCLUSIONS Altogether, the data underline that VEGF mediated

  18. Low-molecular-weight fractions of Alcalase hydrolyzed egg ovomucin extract exert anti-inflammatory activity in human dermal fibroblasts through the inhibition of tumor necrosis factor-mediated nuclear factor κB pathway.

    PubMed

    Sun, Xiaohong; Chakrabarti, Subhadeep; Fang, Jun; Yin, Yulong; Wu, Jianping

    2016-07-01

    Ovomucin is a mucin-like protein from egg white with a variety of biological functions. We hypothesized that ovomucin-derived peptides might exert anti-inflammatory activity. The specific objectives were to test the anti-inflammatory activities of different ovomucin hydrolysates and its various fractions in human dermal fibroblasts, and to understand the possible molecular mechanisms. Three ovomucin hydrolysates were prepared and desalted; only the desalted Alcalase hydrolysate showed anti-inflammatory activity. Desalting of ovomucin hydrolysate enriched the proportion of low-molecular-weight (MW) peptides. Indeed, ultrafiltration of this hydrolysate displayed comparable anti-inflammatory activity in dermal fibroblasts, indicating the responsible role of low-MW bioactive peptides in exerting the beneficial biological function. The anti-inflammatory activity of low-MW peptides was regulated through the inhibition of tumor necrosis factor-mediated nuclear factor κ-light-chain-enhancer of activated B cells activity. Our study demonstrated that both peptide composition and MW distribution play important roles in anti-inflammatory activity. The low-MW fractions prepared from ovomucin Alcalase hydrolysate may have potential applications for maintenance of dermal health and treatment of skin diseases. PMID:27333955

  19. Polysaccharide Constituents of Three Types of Sea Urchin Shells and Their Anti-Inflammatory Activities.

    PubMed

    Jiao, Heng; Shang, Xiaohui; Dong, Qi; Wang, Shuang; Liu, Xiaoyu; Zheng, Heng; Lu, Xiaoling

    2015-09-16

    As a source of potent anti-inflammatory traditional medicines, the quantitative chromatographic fingerprints of sea urchin shell polysaccharides were well established via pre-column derivatization high performance liquid chromatography (HPLC) analysis. Based on the quantitative results, the content of fucose and glucose could be used as preliminary distinguishing indicators among three sea urchin shell species. Besides, the anti-inflammatory activities of the polysaccharides from sea urchin shells and their gonads were also determined. The gonad polysaccharide of Anthocidaris crassispina showed the most potent anti-inflammatory activity among all samples tested.

  20. Polysaccharide Constituents of Three Types of Sea Urchin Shells and Their Anti-Inflammatory Activities

    PubMed Central

    Jiao, Heng; Shang, Xiaohui; Dong, Qi; Wang, Shuang; Liu, Xiaoyu; Zheng, Heng; Lu, Xiaoling

    2015-01-01

    As a source of potent anti-inflammatory traditional medicines, the quantitative chromatographic fingerprints of sea urchin shell polysaccharides were well established via pre-column derivatization high performance liquid chromatography (HPLC) analysis. Based on the quantitative results, the content of fucose and glucose could be used as preliminary distinguishing indicators among three sea urchin shell species. Besides, the anti-inflammatory activities of the polysaccharides from sea urchin shells and their gonads were also determined. The gonad polysaccharide of Anthocidaris crassispina showed the most potent anti-inflammatory activity among all samples tested. PMID:26389925

  1. Anti-inflammatory activity of root bark and stem bark of Shyonaka

    PubMed Central

    Doshi, Krunal; Ilanchezhian, R; Acharya, Rabinarayan; Patel, B. R.; Ravishankar, B.

    2012-01-01

    Background: Shyonaka (Oroxylum indicum Vent.; Bignoniaceae) root bark is one of the ingredients of dashamoola (a group of 10 roots), and is used for its anti-inflammatory and analgesic action in a number of compound formulations in Ayurveda. Aim: Ayurvedic Pharmacopoeia of India (API) recommends using the stem bark instead of root bark. Material and Methods: An attempt has been made to study the anti-inflammatory activity of both root bark and stem bark kashaya (decoction) experimentally. Conclusion Results showed significant anti-inflammatory activity of root bark and stem bark decoction. PMID:23326090

  2. ANTI-INFLAMMATORY AND MAST CELL PROTECTIVE EFFECT OF FICUS RELIGIOSA

    PubMed Central

    Viswanathan, S.; Thirugnanasambantham, P.; Reddy, M. Kannappa; Narasimhan, S.; Subramaniam, G. Anantha

    1990-01-01

    The aqueous extract of bark of Ficus religiosa was prepared and investigated for its anti-inflammatory effect and for its protective effect on mast cells against degranulation. A significant anti-inflammatory effect was observed in both acute and chronic models of inflammation. The extract also protected mast cells from degranulation induced by various degranulatiors. The observed anti-inflammatory and mast cell protective effect may be responsible for the beneficial effect of Ficus religiosa in kumkum dermatitis and other inflammatory conditions. PMID:22556521

  3. Anti-inflammatory and mast cell protective effect of ficus religiosa.

    PubMed

    Viswanathan, S; Thirugnanasambantham, P; Reddy, M K; Narasimhan, S; Subramaniam, G A

    1990-10-01

    The aqueous extract of bark of Ficus religiosa was prepared and investigated for its anti-inflammatory effect and for its protective effect on mast cells against degranulation. A significant anti-inflammatory effect was observed in both acute and chronic models of inflammation. The extract also protected mast cells from degranulation induced by various degranulatiors. The observed anti-inflammatory and mast cell protective effect may be responsible for the beneficial effect of Ficus religiosa in kumkum dermatitis and other inflammatory conditions. PMID:22556521

  4. Anti-inflammatory activity of lupeol and lupeol linoleate in rats.

    PubMed

    Geetha, T; Varalakshmi, P

    2001-06-01

    Two pentacyclic triterpenes, namely lupeol and lupeol linoleate, were investigated for their anti-inflammatory, antinociceptive, anti-pyretic and ulcerogenic properties in comparison with the commonly used non-steroidal anti-inflammatory drug, indomethacin in rats. Lupeol, lupeol linoleate and indomethacin showed a reduction in paw swelling by 39, 58 and 35%, respectively, in adjuvant arthritis. Triterpenes were devoid of any antinociceptive, anti-pyretic and ulcerogenic actions. However, indomethacin exhibited a positive response to these properties. These results suggest that the mechanism of action of triterpenes is different from the non-steroidal anti-inflammatory drug. PMID:11378285

  5. Accelerated wound healing and anti-inflammatory effects of physically cross linked polyvinyl alcohol-chitosan hydrogel containing honey bee venom in diabetic rats.

    PubMed

    Amin, Mohamed A; Abdel-Raheem, Ihab T

    2014-08-01

    Diabetes is one of the leading causes of impaired wound healing. The objective of this study was to develop a bee venom-loaded wound dressing with an enhanced healing and anti-inflammatory effects to be examined in diabetic rats. Different preparations of polyvinyl alcohol (PVA), chitosan (Chit) hydrogel matrix-based wound dressing containing bee venom (BV) were developed using freeze-thawing method. The mechanical properties such as gel fraction, swelling ratio, tensile strength, percentage of elongation and surface pH were determined. The pharmacological activities including wound healing and anti-inflammatory effects in addition to primary skin irritation and microbial penetration tests were evaluated. Moreover, hydroxyproline, glutathione and IL-6 levels were measured in the wound tissues of diabetic rats. The bee venom-loaded wound dressing composed of 10 % PVA, 0.6 % Chit and 4 % BV was more swellable, flexible and elastic than other formulations. Pharmacologically, the bee venom-loaded wound dressing that has the same previous composition showed accelerated healing of wounds made in diabetic rats compared to the control. Moreover, this bee venom-loaded wound dressing exhibited anti-inflammatory effect that is comparable to that of diclofenac gel, the standard anti-inflammatory drug. Simultaneously, wound tissues covered with this preparation displayed higher hydroxyproline and glutathione levels and lower IL-6 levels compared to control. Thus, the bee venom-loaded hydrogel composed of 10 % PVA, 0.6 % Chit and 4 % BV is a promising wound dressing with excellent forming and enhanced wound healing as well as anti-inflammatory activities. PMID:24293065

  6. The neurotrophin receptor p75NTR mediates early anti-inflammatory effects of estrogen in the forebrain of young adult rats

    PubMed Central

    Nordell, Vanessa L; Lewis, Danielle K; Bake, Shameena; Sohrabji, Farida

    2005-01-01

    Background Estrogen suppresses microglial activation and extravasation of circulating monocytes in young animals, supporting an anti-inflammatory role for this hormone. However, the mechanisms underlying estrogen's anti-inflammatory effects, especially in vivo, are not well understood. The present study tests the hypothesis that anti-inflammatory effects of estrogen are mediated by the pan-neurotrophin receptor p75NTR. Previously, we reported that estrogen attenuated local increases of interleukin(IL)-1β in the NMDA-lesioned olfactory bulb, while further increasing NGF expression. Results The present studies show that this lesion enhances expression of the neurotrophin receptor p75NTR at the lesion site, and p75NTR expression is further enhanced by estrogen treatment to lesioned animals. Specifically, estrogen stimulates p75NTR expression in cells of microvessels adjacent to the lesion site. To determine the role of this receptor in mediating estrogen's anti-inflammatory effects, a p75NTR neutralizing antibody was administered at the same time the lesion was created (by stereotaxic injections of NMDA) and specific markers of the inflammatory cascade were measured. Olfactory bulb injections of NMDA+vehicle (preimmune serum) increased IL-1β and activated the signaling molecule c-jun terminal kinase (JNK)-2 at 6 h. At 24 h, the lesion significantly increased matrix metalloproteinase (MMP)-9 and prostaglandin (PG)E2, a COX-2 mediated metabolite of arachadonic acid. All of these markers were significantly attenuated by estrogen in a time-dependent manner. However, estrogen's effects on all these markers were abolished in animals that received anti-p75NTR. Conclusion These data support the hypothesis that estrogen's anti-inflammatory effects may be, in part, mediated by this neurotrophin receptor. In view of the novel estrogen-dependent expression of p75NTR in cells associated with microvessels, these data also suggest that the blood brain barrier is a critical locus

  7. Anti-inflammatory effect of Momordica charantia in sepsis mice.

    PubMed

    Chao, Che-Yi; Sung, Ping-Jyun; Wang, Wei-Hsien; Kuo, Yueh-Hsiung

    2014-01-01

    Wild bitter gourd (Momordica charantia L. var. abbreviate Seringe), a common vegetable in Asia, is used in traditional medicine to treat various diseases, including inflammation. Extant literature indicates that wild bitter gourds have components that activate PPARα and PPARγ. This research probed the influence of adding wild bitter gourd to diets on inflammation responses in mice with sepsis induced by intraperitoneal injection of LPS. Male BALB/c mice were divided normal, sepsis, positive control, and three experimental groups. The latter ate diets with low (1%), moderate (2%), and high (10%) ratios of wild bitter gourd lyophilized powder. Before mice were sacrificed, with the exception of the normal group, intraperitoneal injection of LPS induced sepsis in each group; positive control group was injected with LPS after PDTC. This experiment revealed starkly lower weights in groups with added wild bitter gourd than those of the remaining groups. Blood lipids (TG, cholesterol, and NEFA) were also lower in comparison to the sepsis group, and blood glucose concentrations recovered and approached normal levels. Blood biochemistry values related to inflammation reactions indicated GOT, GPT, C-RP, and NO concentrations of groups with added wild bitter gourd were all lower than those of the sepsis group. Secretion levels of the spleen pro-inflammatory cytokines IL-1, IL-6, and TNF-α tallied significantly lower in comparison to the sepsis group, whereas secretion levels of IL-10 anti-inflammatory cytokine increased. Expression level of proteins NF-κB, iNOS, and COX-2 were significantly inhibited. Results indicate wild bitter gourd in diets promoted lipid metabolism, reducing fat accumulation, and improving low blood glucose in sepsis. Addition of wild bitter gourd can reduce inflammation biochemical markers or indicators and pro-inflammatory cytokines in the body, hence improving the inflammation responses in mice with sepsis. PMID:25153878

  8. Determination of Teloschistes flavicans (sw) norm anti-inflammatory activity

    PubMed Central

    Pereira, Eugênia C.; da Silva, Nicácio H.; Santos, Renata Almeida; Sudário, Ana Patrícia Paiva; Rodrigues e Silva, Antonio Alfredo; de Sousa Maia, Maria Bernadete

    2010-01-01

    Background: Lichens produce a variety of substances that possesses pharmacological actions. However, rare products are submitted to rigorous scientific tests or have the risk potential or side effects evaluated. The lack of medical and sanitary control, absence of accurate botanical identification or purity certification, founded in diverse natural products, may represent great danger to population health. This work aimed to evaluate toxic effects and anti-inflammatory action in vivo of Teloschistes flavicans (Sw.) Norm. (TFN) unrefined extracts, as well as determinate its main constituents. Methods: The carrageenan induced paw edema and cotton pellet implant induced granuloma methods were utilized, besides a classic acute toxicity test. TFN acetone extract inhibited carrageenan paw edema on 60, 120, and 180 min (inhibition percentiles of 45.03%, 60.59% and 41.72%). Results: TFN ethereal (inhibition percentiles of 23.95% and 29.01%) and chloroform (inhibition percentiles of 28.8% and 22.04%) extracts inhibited edema on 120 and 180 min. None of the extract inhibited the granuloma development. None of the extract caused death or other acute toxicity signs. Vicanicine (60.26% in ethereal extract and 51.17% in acetone extract), parietine (9.60% in ethereal extract and 15.38% on second), falacinol (0.78% in ether and 14.95% in acetone) and very low concentration of falacinal (0.15% in ethereal extract and 3.32% in acetone extract) were detected in the medicine. Conclusions: The tested extracts have antiedematogenic activity, but are not effective on subchronic inflammation. The extracts do not present toxic effects in administered doses. PMID:21808568

  9. Anti-Inflammatory Effect of Taurine in Burned Patients

    PubMed Central

    Lak, Sima; Ostadrahimi, Alireza; Nagili, Behrooz; Asghari-Jafarabadi, Mohammad; Beigzali, Sanaz; Salehi, Feridoon; Djafarzadeh, Roxana

    2015-01-01

    Purpose: Burn induced inflammatory response can be mediated by reactive oxygen metabolites and accompanied by multiple organ dysfunction. Taurine has protective effects against various inflammatory conditions. The aim of this study was to determine the effect of Taurine supplement in thermal burn victims. Methods: Thirty patients with severe thermal burns were enrolled in this randomized double-blinded clinical trial. These patients were randomly divided into two equal groups (namely Control and Taurine groups), where both received isocaloric and isonitrogenous formula. One group was supplemented with 50 mg/kg of Taurine per day for a duration of 10 days. Blood samples were obtained to measure Interleukin-10 (IL-10), high-sensitivity C-reactive protein (hs-CRP), and Tumor Necrosis Factor alpha (TNF-α) levels at the beginning and the end of the study. Results: Change in serum level of IL-10 in Taurine group was more than Control group [-13.60(-31.40, -10.40) compared to -4.00(-20.00, -0.20) respectively; P = 0.030]. This change was significant in patients with more than 30% TBSA of burn [-14.20(-31.40, -10.40) compared to -2.40(-9.60, 0.40) respectively; P = 0.013]. As for the hs-CRP and TNF-α levels, the difference between the two groups were not significant. Conclusion: Based on the results obtained, Taurine supplement showed a positive outcome on anti-inflammatory cytokine IL-10 in all burn patients. This effect was even more significant in patients with higher percentage of burn area. Taurine had no significant effect on the inflammatory marker hs-CRP and the pro-inflammatory cytokine TNF-α level. For a more thorough verification, measurement of a wider range of inflammatory cytokines in more frequent time intervals are suggested. PMID:26819926

  10. Anti-inflammatory and antiviral effects of Glossogyne tenuifolia.

    PubMed

    Wu, Ming-Jiuan; Weng, Ching-Yi; Ding, Hsiou-Yu; Wu, Pei-Jong

    2005-01-21

    Glossogyne tenuifolia (Hsiang-Ju) is a traditional antipyretic and hepatoprotective herb used in Chinese medicine. The aim of this research is to investigate the pharmacological activities and potent components of the ethanol extract of Glossogyne tenuifolia (GT) in human primary cells and cell line. We found that GT (0.1 approximately 0.25 mg/ml) exerted dose-dependent inhibitions on the release of TNF-alpha and IL-6 in LPS-activated human whole blood and peripheral blood mononuclear cells (PBMC), and IFN-gamma in PHA-stimulated human whole blood. The lack of cytotoxicity indicated that the inhibitory effects of GT on cytokine production were not due to cell death. Luteolin, the deglycosylated derivative of one of the major compositions, luteolin-7-glucoside, exerted inhibitory effects on TNF-alpha, IL-6 and IFN-gamma production in activated human whole blood with estimated IC(50)s of 42.73 microM, 44.86 microM and 3.34 microM, respectively. Furthermore, GT had potent anti-hepatitis B virus (HBV) effects on the human hepatocellular carcinoma cell line, PLC/PRF/5. GT exhibited a dose-dependent inhibition on the release of hepatitis B surface antigen (HBsAg) by repressing the expression of HBsAg with IC(50) of 0.093 mg/ml. We concluded that GT exerted combinatorial anti-inflammatory and antiviral effects, and the multiple actions may underlie its traditional hepatoprotective function. PMID:15620577

  11. Phenolic composition, anitproliferative and anti-inflammatory properties of conventional and organic cinnamon and peppermint

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Conventional and organic cinnamon and peppermint were investigated for their phenolic profile, antiproliferative, anti-inflammatory, and antioxidant properties. Accelerated solvent extraction (ASE) with 75% acetone was a better method than Soxhlet and overnight extraction for phenolic content and a...

  12. Anti-inflammatory and gastroprotective properties of Hypericum richeri oil extracts.

    PubMed

    Zdunić, Gordana; Godevac, Dejan; Milenković, Marina; Savikin, Katarina; Menković, Nebojsa; Petrović, Silvana

    2010-08-01

    Oil extracts of flowering tops of Hypericum richeri Vill. prepared in three different ways were evaluated for chemical composition, and anti-inflammatory and gastroprotective activities. An HPLC method was developed for determination of two dominant flavonoids, quercetin and I3,II8-biapigenin. The carrageenan-induced rat paw edema test was used for screening the anti-inflammatory activity, while indomethacin-induced rat gastric mucosa damage test was used for evaluation of gastroprotective activity. The oil extract prepared by maceration with 96% ethanol, followed by extraction with sunflower oil by heating on a water bath, exhibited the highest anti-inflammatory (38.4%) and gastroprotective activities (gastric damage score of 0.9). The same oil extract had the highest content of quercetin (49 microg/mL) and I3,II8-biapigenin (60 microg/mL). These results approve the usage of oil extracts of H. richeri as an anti-inflammatory and gastroprotective agent.

  13. Evaluation of anti-inflammatory activity of Calotropis gigantea (AKANDA) in various biological system.

    PubMed

    Adak, Manoranjan; Gupta, Joyanta Kumar

    2006-09-01

    To evaluate the effect of Calotropis G in various experimental animal models. The anti-inflammatory activity was evaluated using carrageenin-induced kaolin -induced rat paw oedema for acute and cotton-pellet granuloma, adjuvant-induced arthritis model for chronic inflammation. Antipyretic activity was carried out using yeast induced pyresis method. Phenylquinone--induced writhing method in mice was used for analgesic activity. Test compounds exhibited variable anti-inflammatory activity and peak activity of the test compounds were reached at 2 h. Alkaloid fraction possesses comparatively high initial anti-inflammatory activity. The residual anti-inflammatory activity of alkaloid fraction of Calotropis G suggest either a greater protein binding nature of the compound there by providing a slow released pool of active drug molecule in the system or non available of possible bioactive metabolites to retain the activity profile relation.

  14. Experimental evaluation of analgesic and anti-inflammatory potential of Oyster mushroom Pleurotus florida

    PubMed Central

    Ganeshpurkar, Aditya; Rai, Gopal

    2013-01-01

    Background: Edible mushrooms have been used as flavorful foods and as health nutritional supplements for several centuries. A number of bioactive molecules have been identified in numerous mushroom species Objective: To evaluate the analgesic and anti-inflammatory potential of Oyster Mushroom Pleurotus florida using various experimental models in Wistar rats. Materials and Methods: Acute toxicity studies were performed whereby dose of 250 mg/ kg and 500 mg/kg was selected for present study, Analgesic activity was determined using hot plate method, tail flick method, acetic acid induced writhing and formalin induced pain in rats, while carrageenan was used to induce inflammation and anti-inflammatory studies were performed. Results: HEE showed significant (P < 0.01) analgesic and anti-inflammatory response against all experimental models. Conclusion: These studies conclude that Pleurotus florida possesses analgesic and anti- inflammatory potential which might be due to presence of myochemicals like flavonoids, phenolics and polysaccharides. PMID:23543896

  15. Rhododendrin, an analgesic/anti-inflammatory arylbutanoid glycoside, from the leaves of Rhododendron aureum.

    PubMed

    Kim, Myung-Hoe; Nugroho, Agung; Choi, Jongwon; Park, Jong Hee; Park, Hee-Juhn

    2011-06-01

    To identify an analgesic/anti-inflammatory component from the leaves of Rhododendron aureum (Ericaceae), phytochemical isolation and pharmacological assays (writhing assays and vascular permeability assay for analgesic action in mice; carrageenan-induced paw edemaand TPA-induced ear edema assays of anti-inflammatory action in rats) were performed. Four compounds were isolated from the active fraction (BuOH fraction) by silica gel column chromatography and identified as (-)-rhododendrol, (-)-rhododendrin, avicularin and hyperoside by spectroscopic methods. Rhododendrin, the main compound of the BuOH fraction, exhibited significant analgesic actions in mice and anti-inflammatory actions in rats. This compound accounted for 3.1% of the MeOH extract and 0.48% of dried leaves, respectively, on HPLC analysis. These results suggest that rhododendrin is the major biologically active substance in the leaves of R. aureum with analgesic/anti-inflammatory activity.

  16. Anti-inflammatory and related properties of 2-(2,4-dichlorophenoxy)phenylacetic acid (fenclofenac).

    PubMed

    Atkinson, D C; Leach, E C

    1976-09-01

    Fenclofenac was shown to possess anti-inflammatory, antinociceptive and antipyretic properties as measured by tests in rats that detect clinically active compounds. In a chronic test for assessing anti-inflammatory activity (established adjuvant arthritis), it was approximately equipotent to alclofenac, fenoprofen calcium and phenylbutazone, more potent than acetylsalicylic acid and ibuprofen, but was less potent than diclofenac sodium, indomethacin, ketoprofen and naproxen. In contrast, the potency of fenclofenac in acute tests for anti-inflammatory, antinociceptive and anti-pyretic activity was generally lower, the drug being approximately equipotent to acetylsalicylic acid in such tests. The anti-inflammatory activity of fenclofenac was not mediated via the pituitary-adrenal axis or a counter-irritant action. Fenclofenac was shown to have remarkably low gastric ulcerogenic potential, both acutely and chronically. PMID:970297

  17. Medium Renewal Blocks Anti-Proliferative Effects of Metformin in Cultured MDA-MB-231 Breast Cancer Cells.

    PubMed

    Rajh, Maruša; Dolinar, Klemen; Miš, Katarina; Pavlin, Mojca; Pirkmajer, Sergej

    2016-01-01

    Epidemiological studies indicate that metformin, a widely used type 2 diabetes drug, might reduce breast cancer risk and mortality in patients with type 2 diabetes. Metformin might protect against breast cancer indirectly by ameliorating systemic glucose homeostasis. Alternatively, it might target breast cancer cells directly. However, experiments using MDA-MB-231 cells, a standard in vitro breast cancer model, produced inconsistent results regarding effectiveness of metformin as a direct anti-cancer agent. Metformin treatments in cultured MDA-MB-231 cells are usually performed for 48-96 hours, but protocols describing renewal of cell culture medium during these prolonged treatments are rarely reported. We determined whether medium renewal protocol might alter sensitivity of MDA-MB-231 cells treated with metformin. Using the MTS assay, BrdU incorporation and Hoechst staining we found that treatment with metformin for 48-72 hours failed to suppress viability and proliferation of MDA-MB-231 cells if low-glucose (1 g/L) medium was renewed every 24 hours. Conversely, metformin suppressed their viability and proliferation if medium was not renewed. Without renewal glucose concentration in the medium was reduced to 0.1 g/L in 72 hours, which likely explains increased sensitivity to metformin under these conditions. We also examined whether 2-deoxy-D-glucose (2-DG) reduces resistance to metformin. In the presence of 2-DG metformin reduced viability and proliferation of MDA-MB-231 cells with or without medium renewal, thus demonstrating that 2-DG reduces their resistance to metformin. In sum, we show that medium renewal blocks anti-proliferative effects of metformin during prolonged treatments in low-glucose medium. Differences in medium renewal protocols during prolonged treatments might therefore lead to apparently inconsistent results as regards effectiveness of metformin as a direct anti-cancer agent. Finally, our results indicate that co-therapy with 2-DG and

  18. The Anti-inflammatory Drug Indomethacin Alters Nanoclustering in Synthetic and Cell Plasma Membranes*

    PubMed Central

    Zhou, Yong; Plowman, Sarah J.; Lichtenberger, Lenard M.; Hancock, John F.

    2010-01-01

    The nonsteroidal anti-inflammatory drug indomethacin exhibits diverse biological effects, many of which have no clear molecular mechanism. Membrane-bound receptors and enzymes are sensitive to their phospholipid microenvironment. Amphipathic indomethacin could therefore potentially modulate cell signaling by changing membrane properties. Here we examined the effect of indomethacin on membrane lateral heterogeneity. Fluorescence lifetime imaging of cells expressing lipid-anchored probes revealed that treatment of BHK cells with therapeutic levels of indomethacin enhances cholesterol-dependent nanoclustering, but not cholesterol-independent nanoclustering. Immuno-electron microscopy and quantitative spatial mapping of intact plasma membrane sheets similarly showed a selective effect of indomethacin on promoting cholesterol-dependent, but not cholesterol-independent, nanoclustering. To further evaluate the biophysical effects of indomethacin, we measured fluorescence polarization of the phase-sensitive probe Laurdan and FRET between phase-partitioning probes in model bilayers. Therapeutic levels of indomethacin enhanced phase seperation in DPPC/DOPC/Chol (1:1:1) and DPPC/Chol membranes in a temperature-dependent manner, but had minimal effect on the phase behavior of pure DOPC at any temperature. Taken together, the imaging results on intact epithelial cells and the biophysical assays of model membranes suggest that indomethacin can enhance phase separation and stabilize cholesterol-dependent nanoclusters in biological membranes. These effects on membrane lateral heterogeneity may have significant consequences for cell signaling cascades that are assembled on the plasma membrane. PMID:20826816

  19. [Anti-Inflammatory Activity of the Polypeptide of the Sea Anemone, Heteractis crispa].

    PubMed

    Sintsova, O V; Monastyrnaya, M M; Pislyagin, E A; Menchinskaya, E S; Leychenko, E V; Aminin, D L; Kozlovskaya, E P

    2015-01-01

    The anti-inflammatory effect of the recombinant polypeptide HCGS 1.20, a Kunitz-type serine protease inhibitor of the sea anemone Heteractis crispa, was investigated. It was shown that the polypeptide inhibits the increase of the concentration of calcium ions in mouse bone marrow derived macrophages elicited by histamine, and reduces the content of NO in lipopolysaccharide stimulated macrophages. A presumable mechanism of anti-inflammatory action of the polypeptide was being discussed. PMID:27125018

  20. Anti-inflammatory and Immunomodulatory Effects of Antibiotics and Their Use in Dermatology

    PubMed Central

    Pradhan, Swetalina; Madke, Bhushan; Kabra, Poonam; Singh, Adarsh Lata

    2016-01-01

    Antibiotics (antibacterial, antiviral, and antiparasitic) are class of drugs which result in either killing or inhibiting growth and multiplication of infectious organisms. Antibiotics are commonly prescribed by all specialties for treatment of infections. However, antibiotics have hitherto immunomodulatory and anti-inflammatory properties and can be exploited for various noninfectious dermatoses. Dermatologists routinely prescribe antibiotics in treatment of various noninfectious disorders. This study will review anti-inflammatory and immunomodulatory effects of antibiotics and their use in dermatology.

  1. Anti-inflammatory and Immunomodulatory Effects of Antibiotics and Their Use in Dermatology.

    PubMed

    Pradhan, Swetalina; Madke, Bhushan; Kabra, Poonam; Singh, Adarsh Lata

    2016-01-01

    Antibiotics (antibacterial, antiviral, and antiparasitic) are class of drugs which result in either killing or inhibiting growth and multiplication of infectious organisms. Antibiotics are commonly prescribed by all specialties for treatment of infections. However, antibiotics have hitherto immunomodulatory and anti-inflammatory properties and can be exploited for various noninfectious dermatoses. Dermatologists routinely prescribe antibiotics in treatment of various noninfectious disorders. This study will review anti-inflammatory and immunomodulatory effects of antibiotics and their use in dermatology. PMID:27688434

  2. Anti-inflammatory and Immunomodulatory Effects of Antibiotics and Their Use in Dermatology

    PubMed Central

    Pradhan, Swetalina; Madke, Bhushan; Kabra, Poonam; Singh, Adarsh Lata

    2016-01-01

    Antibiotics (antibacterial, antiviral, and antiparasitic) are class of drugs which result in either killing or inhibiting growth and multiplication of infectious organisms. Antibiotics are commonly prescribed by all specialties for treatment of infections. However, antibiotics have hitherto immunomodulatory and anti-inflammatory properties and can be exploited for various noninfectious dermatoses. Dermatologists routinely prescribe antibiotics in treatment of various noninfectious disorders. This study will review anti-inflammatory and immunomodulatory effects of antibiotics and their use in dermatology. PMID:27688434

  3. Quercinol, an anti-inflammatory chromene from the wood-rotting fungus Daedalea quercina (Oak Mazegill).

    PubMed

    Gebhardt, P; Dornberger, K; Gollmick, F A; Gräfe, U; Härtl, A; Görls, H; Schlegel, B; Hertweck, C

    2007-05-01

    The fungus Daedalea quercina (oak mazegill) was examined for its capability of producing antioxidative and anti-inflammatory compounds. Bioactivity guided fractionation of the extract from a mycelial culture led to the isolation of quercinol, which was identified as (-)-(2S)-2-hydroxymethyl-2-methyl-6-hydroxychromene 1 by NMR and X-ray analyses. The cryptic hydroquinone 1 shows a broad anti-inflammatory activity against cyclooxygenase 2 (COX-2), xanthine oxidase (XO), and horseradish peroxidase (HRP) at micromolar concentrations.

  4. Chemical Constituents from the Fruiting Bodies of Hexagonia apiaria and Their Anti-inflammatory Activity.

    PubMed

    Thang, Tran Dinh; Kuo, Ping-Chung; Ngoc, Nguyen Thi Bich; Hwang, Tsong-Long; Yang, Mei-Lin; Ta, Shih-Huang; Lee, E-Jian; Kuo, Dai-Huang; Hung, Nguyen Huy; Tuan, Nguyen Ngoc; Wu, Tian-Shung

    2015-11-25

    A chemical investigation of the fruiting bodies of Hexagonia apiaria resulted in the identification of nine compounds including five new triterpenoids, hexagonins A-E (1-5), along with four known compounds. The purified constituents were examined for their anti-inflammatory activity. Among the tested compounds, hexatenuin A displayed the most significant inhibition of superoxide anion generation and elastase release. These triterpenoids may have potentials as anti-inflammatory agents. PMID:26575215

  5. Paraoxonase 2 Induces a Phenotypic Switch in Macrophage Polarization Favoring an M2 Anti-Inflammatory State

    PubMed Central

    Koren-Gluzer, Marie; Rosenblat, Mira; Hayek, Tony

    2015-01-01

    Inflammatory processes are involved in atherosclerosis development. Macrophages play a major role in the early atherogenesis, and they are present in the atherosclerotic lesion in two phenotypes: proinflammatory (M1) or anti-inflammatory (M2). Paraoxonase 2 (PON2) is expressed in macrophages, and it was shown to protect against atherosclerosis. Thus, the aim of our study was to analyze the direct effect of PON2 on macrophage inflammatory phenotypes. Ex vivo studies were performed with murine peritoneal macrophages (MPM) harvested from control C57BL/6 and PON2-deficient (PON2KO) mice. PON2KO MPM showed an enhanced proinflammatory phenotype compared to the control, both in the basal state and following M1 activation by IFNγ and lipopolysaccharide (LPS). In parallel, PON2KO MPM also showed reduced anti-inflammatory responses in the basal state and also following M2 activation by IL-4. Moreover, the PON2-null MPM demonstrated enhanced phagocytosis and reactive oxygen species (ROS) production in the basal state and following M1 activation. The direct effect of PON2 was shown by transfecting human PON2 (hPON2) into PON2KO MPM. PON2 transfection attenuated the macrophages' response to M1 activation and enhanced M2 response. These PON2 effects were associated with attenuation of macrophages' abilities to phagocyte and to generate ROS. We conclude that PON2 promotes an M1 to M2 switch in macrophage phenotypes. PMID:26779262

  6. In vitro antioxidant capacity and anti-inflammatory activity of seven common oats.

    PubMed

    Chu, Yi-Fang; Wise, Mitchell L; Gulvady, Apeksha A; Chang, Tony; Kendra, David F; Jan-Willem van Klinken, B; Shi, Yuhui; O'Shea, Marianne

    2013-08-15

    Oats are gaining increasing scientific and public interest for their purported antioxidant-associated health benefits. Most reported studies focused on specific oat extracts or particular oat components, such as β-glucans, tocols (vitamin E), or avenanthramides. Studies on whole oats with respect to antioxidant and anti-inflammatory activities are still lacking. Here the antioxidant and anti-inflammatory activities from whole oat groats of seven common varieties were evaluated. All oat varieties had very similar oxygen radical absorption capacity compared with other whole grains. In an anti-inflammatory assay, oat variety CDC Dancer inhibited tumor necrosis factor-α induced nuclear factor-kappa B activation by 27.5% at 2 mg/ml, whereas variety Deiter showed 13.7% inhibition at a comparable dose. Avenanthramide levels did not correlate with the observed antioxidant and anti-inflammatory activities. Further investigations are needed to pinpoint the specific antioxidant and anti-inflammatory compounds, and potential synergistic and/or matrix effects that may help explain the mechanisms of oat's anti-inflammatory actions.

  7. Topical Anti-inflammatory Activity of New Hybrid Molecules of Terpenes and Synthetic Drugs.

    PubMed

    Theoduloz, Cristina; Delporte, Carla; Valenzuela-Barra, Gabriela; Silva, Ximena; Cádiz, Solange; Bustamante, Fernanda; Pertino, Mariano Walter; Schmeda-Hirschmann, Guillermo

    2015-06-18

    The aim of the study was to assess changes in the activity of anti-inflammatory terpenes from Chilean medicinal plants after the formation of derivatives incorporating synthetic anti-inflammatory agents. Ten new hybrid molecules were synthesized combining terpenes (ferruginol (1), imbricatolic acid (2) and oleanolic acid (3)) with ibuprofen (4) or naproxen (5). The topical anti-inflammatory activity of the compounds was assessed in mice by the arachidonic acid (AA) and 12-O-tetradecanoyl phorbol 13-acetate (TPA) induced ear edema assays. Basal cytotoxicity was determined towards human lung fibroblasts, gastric epithelial cells and hepatocytes. At 1.4 µmol/mouse, a strong anti-inflammatory effect in the TPA assay was observed for oleanoyl ibuprofenate 12 (79.9%) and oleanoyl ibuprofenate methyl ester 15 (80.0%). In the AA assay, the best activity was observed for 12 at 3.2 µmol/mouse, with 56.8% reduction of inflammation, in the same range as nimesulide (48.9%). All the terpenyl-synthetic anti-inflammatory hybrids showed better effects in the TPA assay, with best activity for 6, 12 and 15. The cytotoxicity of the compounds 8 and 10 with a free COOH, was higher than that of 2. The derivatives from 3 were less toxic than the triterpene. Several of the new compounds presented better anti-inflammatory effect and lower cytotoxicity than the parent terpenes.

  8. Topical Anti-inflammatory Activity of New Hybrid Molecules of Terpenes and Synthetic Drugs.

    PubMed

    Theoduloz, Cristina; Delporte, Carla; Valenzuela-Barra, Gabriela; Silva, Ximena; Cádiz, Solange; Bustamante, Fernanda; Pertino, Mariano Walter; Schmeda-Hirschmann, Guillermo

    2015-01-01

    The aim of the study was to assess changes in the activity of anti-inflammatory terpenes from Chilean medicinal plants after the formation of derivatives incorporating synthetic anti-inflammatory agents. Ten new hybrid molecules were synthesized combining terpenes (ferruginol (1), imbricatolic acid (2) and oleanolic acid (3)) with ibuprofen (4) or naproxen (5). The topical anti-inflammatory activity of the compounds was assessed in mice by the arachidonic acid (AA) and 12-O-tetradecanoyl phorbol 13-acetate (TPA) induced ear edema assays. Basal cytotoxicity was determined towards human lung fibroblasts, gastric epithelial cells and hepatocytes. At 1.4 µmol/mouse, a strong anti-inflammatory effect in the TPA assay was observed for oleanoyl ibuprofenate 12 (79.9%) and oleanoyl ibuprofenate methyl ester 15 (80.0%). In the AA assay, the best activity was observed for 12 at 3.2 µmol/mouse, with 56.8% reduction of inflammation, in the same range as nimesulide (48.9%). All the terpenyl-synthetic anti-inflammatory hybrids showed better effects in the TPA assay, with best activity for 6, 12 and 15. The cytotoxicity of the compounds 8 and 10 with a free COOH, was higher than that of 2. The derivatives from 3 were less toxic than the triterpene. Several of the new compounds presented better anti-inflammatory effect and lower cytotoxicity than the parent terpenes. PMID:26096431

  9. Rose geranium essential oil as a source of new and safe anti-inflammatory drugs

    PubMed Central

    Boukhatem, Mohamed Nadjib; Kameli, Abdelkrim; Ferhat, Mohamed Amine; Saidi, Fairouz; Mekarnia, Maamar

    2013-01-01

    Background Since the available anti-inflammatory drugs exert an extensive variety of side effects, the search for new anti-inflammatory agents has been a priority of pharmaceutical industries. Aims The aim of the present study was to assess the anti-inflammatory activities of the essential oil of rose geranium (RGEO). Methods The chemical composition of the RGEO was investigated by gas chromatography. The major components were citronellol (29.13%), geraniol (12.62%), and citronellyl formate (8.06%). In the carrageenan-induced paw edema, five different groups were established and RGEO was administered orally in three different doses. Results RGEO (100 mg/kg) was able to significantly reduce the paw edema with a comparable effect to that observed with diclofenac, the positive control. In addition, RGEO showed a potent anti-inflammatory activity by topical treatment in the method of croton oil-induced ear edema. When the dose was 5 or 10 µl of RGEO per ear, the inflammation was reduced by 73 and 88%, respectively. This is the first report to demonstrate a significant anti-inflammatory activity of Algerian RGEO. In addition, histological analysis confirmed that RGEO inhibited the inflammatory responses in the skin. Conclusion Our results indicate that RGEO may have significant potential for the development of novel anti-inflammatory drugs with improved safety profile. PMID:24103319

  10. Antibacterial and Anti-Inflammatory Activities of Physalis Alkekengi var. franchetii and Its Main Constituents

    PubMed Central

    Shu, Zunpeng; Xing, Na; Wang, Qiuhong; Li, Xinli; Xu, Bingqing; Li, Zhenyu; Kuang, Haixue

    2016-01-01

    This study was designed to determine whether the 50% EtOH fraction from AB-8 macroporous resin fractionation of a 70% EtOH extract of P. Alkekengi (50-EFP) has antibacterial and/or anti-inflammatory activity both in vivo and in vitro and to investigate the mechanism of 50-EFP anti-inflammatory activity. Additionally, this study sought to define the chemical composition of 50-EFP. Results indicated that 50-EFP showed significant antibacterial activity in vitro and efficacy in vivo. Moreover, 50-EFP significantly reduced nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), interleukin 1 (IL-1), and interleukin 6 (IL-6) production in lipopolysaccharide- (LPS-) stimulated THP-1 cells. Nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) (examined at the protein level) in THP-1 cells were suppressed by 50-EFP, which inhibited nuclear translocation of p65. Consistent with this anti-inflammatory activity in vitro, 50-EFP reduced inflammation in both animal models. Finally, seventeen compounds (8 physalins and 9 flavones) were isolated as major components of 50-EFP. Our data demonstrate that 50-EFP has antibacterial and anti-inflammatory activities both in vitro and in vivo. The anti-inflammatory effect appears to occur, at least in part, through the inhibition of nuclear translocation of p65. Moreover, physalins and flavones are probably the active components in 50-EFP that exert antibacterial and anti-inflammatory activities. PMID:27057196

  11. Anti-nociceptive and anti-inflammatory activities of the extracts of Stauntonia chinensis.

    PubMed

    Ying, Chen; Ning, Wu; Ying, Liu; Hao, Gao; Hua-Jin, Dong; Rui-Bin, Su; Xin-Sheng, Yao; Jin, Li

    2014-09-01

    The aim of this investigation was to study the anti-nociceptive and anti-inflammatory activities of Stauntonia chinensis (S. chinensis) and the possible action mechanisms of effective fractions. The anti-nociceptive and anti-inflammatory activities of S. chinensis extracts, including the 60% EtOH extract (YMG), the n-BuOH extract (YMGB) and the aqueous residue (YMGW) of YMG, and the fractions from YMGB (YMGB1~YMGB7) were investigated by using the mouse acetic acid-induced writhing test and the rat formalin test. The effect of these extracts on the PGE2 production was tested as well. In the mouse acetic acid-induced writhing test and the rat formalin test, YMGW and YMGB displayed anti-nociceptive and anti-inflammatory activities, suggesting that they were the active ingredients of YMG. Among the fractions isolated from YMGB, YMGB1, YMGB3, YMGB4 and YMGB6 were the main active ingredients producing anti-nociceptive activity and YMGB3, YMGB5, YMGB6 and YMGB7 were the main active ingredients producing anti-inflammatory activity. Additionally, YMGW, YMGB and its separations reduced the production of PGE2, which might be the mechanism of them producing anti-inflammatory activity. These results demonstrated the active ingredients of S. chinensis producing anti-nociceptive and anti-inflammatory activities, which is valuable to validate the substance basis of S. chinensis's pharmacological actions.

  12. Antimicrobial, Antiparasitic, Anti-Inflammatory, and Cytotoxic Activities of Lopezia racemosa

    PubMed Central

    Cruz Paredes, Carla; Bolívar Balbás, Paulina; Juárez, Zaida Nelly; Sánchez Arreola, Eugenio; Hernández, Luis Ricardo

    2013-01-01

    The present study investigates the potential benefits of the Mexican medicinal plant Lopezia racemosa (Onagraceae). Extracts and fractions from aerial parts of this plant were assessed to determine their antibacterial, antifungal, antiparasitic, anti-inflammatory and cytotoxic activities in vitro. Aerial parts of the plant were extracted with various solvents and fractionated accordingly. Extracts and fractions were tested against a panel of nine bacterial and four fungal species. The antiparasitic activity was tested against Leishmania donovani, whereas the anti-inflammatory activity of the compounds was determined by measuring the secretion of interleukin-6 from human-derived macrophages. The same macrophage cell line was used to investigate the cytotoxicity of the compounds. Various extracts and fractions showed antibacterial, antifungal, antiparasitic, and anti-inflammatory activities. The hexanic fraction HF 11-14b was the most interesting fraction with antimicrobial, and anti-inflammatory activities. The benefit of L. racemosa as a traditional medicinal plant was confirmed as shown by its antibacterial, antifungal and anti-inflammatory activities. To the best of our knowledge, this is the first study reporting the biological activities of L. racemosa, including antiparasitic and anti-inflammatory activities. PMID:23843731

  13. Leaching potential of nonsteroidal anti-inflammatory drugs in soils.

    PubMed

    Xu, Jian; Wu, Laosheng; Chen, Weiping; Chang, Andrew C

    2010-04-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) in soils resulting from application of municipal wastewater or biosolids may migrate through soils intact or be transformed and reach groundwater. In the present study, the leaching potential of four NSAIDs (ibuprofen, naproxen, ketoprofen, and diclofenac sodium) in three U.S. cropland soils was evaluated, and the effect of CaCl(2) solution (as an index of salinity), dissolved organic matter (DOM), and polyacrylamide (PAM) amendment was investigated. The soils were spiked with selected NSAIDs, incubated for 24 h followed by 7-d storage in glass flasks, and then packed into stainless steel columns and leached with deionized water (DIW), 10 mM CaCl(2), DOM (DOC 34 mg/L), and PAM solution (1.0 mg/L) by gravity. Initial concentrations of ibuprofen, naproxen, ketoprofen, and diclofenac sodium in the three packed soils were 1.93 to 2.07, 1.74 to 2.27, 1.79 to 2.16, and 1.99 to 2.13 mg/kg, respectively. Maximum concentrations of the above NSAIDs in column effluents were 1.23, 0.92, 0.69, and 1.12 mg/L, respectively, when the soil was leached with 10 pore volumes of water, which occupied 17.4, 11.1, 9.6, and 15.2% of the total chemicals in each soil column. Dissolved organic matter or PAM solution did not facilitate the NSAIDs release from soils. The CaCl(2) solution, however, reduced the amounts of NSAIDs leached from all three soils. Leaching of NSAIDs differed among the three tested soils. The results suggest that the leaching of NSAIDs through soil to water is significant, and the mobility of NSAIDs in soil is related to their chemicals' characteristics (such as pK(a) values) and soil properties (such as soil organic matter and clay content). Amending soil with DOM or PAM does not significantly affect the leaching behavior of NSAIDs in soil, whereas increasing the salinity of the irrigation water may decrease the extent of contamination of groundwater posed by NSAIDs.

  14. The Anti-Inflammatory Effect of Algae-Derived Lipid Extracts on Lipopolysaccharide (LPS)-Stimulated Human THP-1 Macrophages.

    PubMed

    Robertson, Ruairi C; Guihéneuf, Freddy; Bahar, Bojlul; Schmid, Matthias; Stengel, Dagmar B; Fitzgerald, Gerald F; Ross, R Paul; Stanton, Catherine

    2015-08-01

    Algae contain a number of anti-inflammatory bioactive compounds such as omega-3 polyunsaturated fatty acids (n-3 PUFA) and chlorophyll a, hence as dietary ingredients, their extracts may be effective in chronic inflammation-linked metabolic diseases such as cardiovascular disease. In this study, anti-inflammatory potential of lipid extracts from three red seaweeds (Porphyra dioica, Palmaria palmata and Chondrus crispus) and one microalga (Pavlova lutheri) were assessed in lipopolysaccharide (LPS)-stimulated human THP-1 macrophages. Extracts contained 34%-42% total fatty acids as n-3 PUFA and 5%-7% crude extract as pigments, including chlorophyll a, β-carotene and fucoxanthin. Pretreatment of the THP-1 cells with lipid extract from P. palmata inhibited production of the pro-inflammatory cytokines interleukin (IL)-6 (p < 0.05) and IL-8 (p < 0.05) while that of P. lutheri inhibited IL-6 (p < 0.01) production. Quantitative gene expression analysis of a panel of 92 genes linked to inflammatory signaling pathway revealed down-regulation of the expression of 14 pro-inflammatory genes (TLR1, TLR2, TLR4, TLR8, TRAF5, TRAF6, TNFSF18, IL6R, IL23, CCR1, CCR4, CCL17, STAT3, MAP3K1) by the lipid extracts. The lipid extracts effectively inhibited the LPS-induced pro-inflammatory signaling pathways mediated via toll-like receptors, chemokines and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling molecules. These results suggest that lipid extracts from P. lutheri, P. palmata, P. dioica and C. crispus can inhibit LPS-induced inflammatory pathways in human macrophages. Therefore, algal lipid extracts should be further explored as anti-inflammatory ingredients for chronic inflammation-linked metabolic diseases. PMID:26308008

  15. The Anti-Inflammatory Effect of Algae-Derived Lipid Extracts on Lipopolysaccharide (LPS)-Stimulated Human THP-1 Macrophages

    PubMed Central

    Robertson, Ruairi C.; Guihéneuf, Freddy; Bahar, Bojlul; Schmid, Matthias; Stengel, Dagmar B.; Fitzgerald, Gerald F.; Ross, R. Paul; Stanton, Catherine

    2015-01-01

    Algae contain a number of anti-inflammatory bioactive compounds such as omega-3 polyunsaturated fatty acids (n-3 PUFA) and chlorophyll a, hence as dietary ingredients, their extracts may be effective in chronic inflammation-linked metabolic diseases such as cardiovascular disease. In this study, anti-inflammatory potential of lipid extracts from three red seaweeds (Porphyra dioica, Palmaria palmata and Chondrus crispus) and one microalga (Pavlova lutheri) were assessed in lipopolysaccharide (LPS)-stimulated human THP-1 macrophages. Extracts contained 34%–42% total fatty acids as n-3 PUFA and 5%–7% crude extract as pigments, including chlorophyll a, β-carotene and fucoxanthin. Pretreatment of the THP-1 cells with lipid extract from P. palmata inhibited production of the pro-inflammatory cytokines interleukin (IL)-6 (p < 0.05) and IL-8 (p < 0.05) while that of P. lutheri inhibited IL-6 (p < 0.01) production. Quantitative gene expression analysis of a panel of 92 genes linked to inflammatory signaling pathway revealed down-regulation of the expression of 14 pro-inflammatory genes (TLR1, TLR2, TLR4, TLR8, TRAF5, TRAF6, TNFSF18, IL6R, IL23, CCR1, CCR4, CCL17, STAT3, MAP3K1) by the lipid extracts. The lipid extracts effectively inhibited the LPS-induced pro-inflammatory signaling pathways mediated via toll-like receptors, chemokines and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling molecules. These results suggest that lipid extracts from P. lutheri, P. palmata, P. dioica and C. crispus can inhibit LPS-induced inflammatory pathways in human macrophages. Therefore, algal lipid extracts should be further explored as anti-inflammatory ingredients for chronic inflammation-linked metabolic diseases. PMID:26308008

  16. Anti-inflammatory effects of tobramycin and a copper–tobramycin complex with superoxide dismutase-like activity

    PubMed Central

    Gziut, M; MacGregor, HJ; Nevell, TG; Mason, T; Laight, D; Shute, JK

    2013-01-01

    Background and Purpose Airway inflammation in cystic fibrosis (CF) patients is characterized by accumulations of neutrophils in the airway and T cells in bronchial tissue, with activation of platelets in the circulation. CF patients are routinely treated with systemic or inhaled tobramycin for airway infection with Pseudomonas aeruginosa. Clinical trials have indicated an anti-inflammatory effect of tobramycin beyond its bactericidal activity. Here, we investigate the anti-inflammatory properties of tobramycin in vitro and consider if these relate to the ability of tobramycin to bind copper, which is elevated in blood and sputum in CF. Experimental Approach A copper–tobramycin complex was synthesized. The effect of tobramycin and copper–tobramycin on neutrophil activation and migration of T cells and neutrophils across human lung microvascular endothelial cells in response to thrombin-activated platelets were investigated in vitro. Tobramycin uptake was detected by immunocytochemistry. Intracellular reactive oxygen species were detected using the fluorescent indicator, 2′,7′-dichlorofluorescein diacetate (DCFDA). Neutrophil superoxide, hydrogen peroxide and neutrophil elastase activity were measured using specific substrates. Copper was measured using atomic absorption spectroscopy. Key Results Tobramycin and copper–tobramycin were taken up by endothelial cells via a heparan sulphate-dependent mechanism and significantly inhibited T-cell and neutrophil transendothelial migration respectively. Copper–tobramycin has intracellular and extracellular superoxide dismutase-like activity. Neutrophil elastase inhibition by α1-antitrypsin is enhanced in the presence of copper–tobramycin. Tobramycin and copper–tobramycin are equally effective anti-pseudomonal antibiotics. Conclusions and Implications Anti-inflammatory effects of tobramycin in vivo may relate to the spontaneous formation of a copper–tobramycin complex, implying that copper–tobramycin may

  17. Anti-Inflammatory Action of Angiotensin 1-7 in Experimental Colitis

    PubMed Central

    Khajah, Maitham A.; Fateel, Maryam M.; Ananthalakshmi, Kethireddy V.; Luqmani, Yunus A.

    2016-01-01

    Background There is evidence to support a role for angiotensin (Ang) 1–7 in reducing the activity of inflammatory signaling molecules such as MAPK, PKC and SRC. Enhanced angiotensin converting enzyme 2 (ACE2) expression has been observed in patients with inflammatory bowel disease (IBD) suggesting a role in its pathogenesis, prompting this study. Methods The colonic expression/activity profile of ACE2, Ang 1–7, MAS1-receptor (MAS1-R), MAPK family and Akt were determined by western blot and immunofluorescence. The effect of either exogenous administration of Ang 1–7 or pharmacological inhibition of its function (by A779 treatment) was determined using the mouse dextran sulfate sodium model. Results Enhanced colonic expression of ACE2, Ang1-7 and MAS1-R was observed post-colitis induction. Daily Ang 1–7 treatment (0.01–0.06 mg/kg) resulted in significant amelioration of DSS-induced colitis. In contrast, daily administration of A779 significantly worsened features of colitis. Colitis-associated phosphorylation of p38, ERK1/2 and Akt was reduced by Ang 1–7 treatment. Conclusion Our results indicate important anti-inflammatory actions of Ang 1–7 in the pathogenesis of IBD, which may provide a future therapeutic strategy to control the disease progression. PMID:26963721

  18. Assessment of diclofenac permeation with different formulations: anti-inflammatory study of a selected formula.

    PubMed

    Escribano, Elvira; Calpena, Ana Cristina; Queralt, Josep; Obach, Rossend; Doménech, Jose

    2003-07-01

    The aim of this study was to improve the transdermal permeation of sodium diclofenac. Permeation studies were carried out in vitro using human skin (0.4 mm thick) from plastic surgery as a membrane. Four liquid formulations of 1% (w/w) sodium diclofenac were assayed: three ternary solvent systems (M4, M5, M6) and one microemulsion (M3). A 1% (w/w) solution of sodium diclofenac and a commercially available semisolid preparation were tested as reference formulations. The following permeation parameters for diclofenac were assessed: permeability coefficient, flux and drug permeated and retained in the skin at 24 h. The highest values of these parameters were obtained with formula M4, which contains transcutol 59.2%, oleic acid 14.9% and d-limonene 5% (w/w) as permeation enhancers. The anti-inflammatory activity of this formula was compared with that of the semisolid preparation on carrageenan-induced paw edema in rats. As expected from in vitro results, the M4 diclofenac delivery system showed higher activity than the semisolid preparation, both when applied locally (to the inflammation area) and when applied systemically (to the back). Neither treatment irritated the skin when tested on rabbits in a 72-h trial. These results suggest that topical delivery of sodium diclofenac with an absorption enhancer such as a mixture of oleic acid and d-limonene (M4) may be an effective medication for both dermal and subdermal injuries.

  19. Anti-Inflammatory, Antioxidant, Anti-Angiogenic and Skin Whitening Activities of Phryma leptostachya var. asiatica Hara Extract

    PubMed Central

    Jung, Hyun-Joo; Cho, Young-Wook; Lim, Hye-Won; Choi, Hojin; Ji, Dam-Jung; Lim, Chang-Jin

    2013-01-01

    This work aimed to assess some pharmacological activities of P. leptostachya var. asiatica Hara. The dried roots of P. leptostachya var. asiatica Hara were extracted with 70% ethanol to generate the powdered extract, named PLE. Anti-angiogenic activity was detected using chick chorioallantoic membrane (CAM) assay. In vitro anti-inflammatory activity was evaluated via analyzing nitric oxide (NO) content, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Antioxidant activity was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay and reactive oxygen species (ROS) level in the stimulated macrophage cells. Matrix metalloproteinase-9 (MMP-9) and -2 (MMP-2) activities in the culture media were detected using zymography. PLE exhibits an anti-angiogenic activity in the CAM assay, and displays an inhibitory action on the generation of NO in the LPS-stimulated macrophage cells. In the stimulated macrophage cells, it is able to diminish the enhanced ROS level. It can potently scavenge the stable DPPH free radical. It suppresses the induction of iNOS and COX-2 and the enhanced MMP-9 activity in the stimulated macrophage cells. Both monooxygenase and oxidase activities of tyrosinase were strongly inhibited by PLE. Taken together, the dried roots of P. leptostachya var. asiatica Hara possess anti-angiogenic, anti-inflammatory, antioxidant and skin whitening activities, which might partly provide its therapeutic efficacy in traditional medicine. PMID:24009862

  20. Kallistatin Modulates Immune Cells and Confers Anti-Inflammatory Response To Protect Mice from Group A Streptococcal Infection

    PubMed Central

    Lu, Shiou-Ling; Tsai, Chiau-Yuang; Luo, Yueh-Hsia; Kuo, Chih-Feng; Lin, Wei-Chieh; Chang, Yu-Tzu; Wu, Jiunn-Jong; Chuang, Woei-Jer; Liu, Ching-Chuan; Chao, Lee; Chao, Julie

    2013-01-01

    Group A streptococcus (GAS) infection may cause severe life-threatening diseases, including necrotizing fasciitis and streptococcal toxic shock syndrome. Despite the availability of effective antimicrobial agents, there has been a worldwide increase in the incidence of invasive GAS infection. Kallistatin (KS), originally found to be a tissue kallikrein-binding protein, has recently been shown to possess anti-inflammatory properties. However, its efficacy in microbial infection has not been explored. In this study, we transiently expressed the human KS gene by hydrodynamic injection and investigated its anti-inflammatory and protective effects in mice via air pouch inoculation of GAS. The results showed that KS significantly increased the survival rate of GAS-infected mice. KS treatment reduced local skin damage and bacterial counts compared with those in mice infected with GAS and treated with a control plasmid or saline. While there was a decrease in immune cell infiltration of the local infection site, cell viability and antimicrobial factors such as reactive oxygen species actually increased after KS treatment. The efficiency of intracellular bacterial killing in neutrophils was directly enhanced by KS administration. Several inflammatory cytokines, including tumor necrosis factor alpha, interleukin 1β, and interleukin 6, in local infection sites were reduced by KS. In addition, KS treatment reduced vessel leakage, bacteremia, and liver damage after local infection. Therefore, our study demonstrates that KS provides protection in GAS-infected mice by enhancing bacterial clearance, as well as reducing inflammatory responses and organ damage. PMID:23959316

  1. In vitro stimulation of HDL anti-inflammatory activity and inhibition of LDL pro-inflammatory activity in the plasma of patients with end-stage renal disease by an apoA-1 mimetic peptide

    PubMed Central

    Vaziri, Nosratola D; Moradi, Hamid; Pahl, Madeleine V; Fogelman, Alan M; Navab, Mohamad

    2010-01-01

    Features of end-stage renal disease such as oxidative stress, inflammation, hypertension, and dyslipidemia are associated with accelerated atherosclerosis and increased risk of death from cardiovascular disease. By inhibiting the formation and increasing the disposal of oxidized lipids, HDL exerts potent antioxidant and anti-inflammatory actions. Given that apolipoproteinA-1 can limit atherosclerosis, we hypothesized that an apolipoproteinA-1 mimetic peptide, 4F, may reduce the proinflammatory properties of LDL and enhance the anti-inflammatory properties of HDL in uremic plasma. To test this, plasma from each of 12 stable hemodialysis patients and age-matched control subjects was incubated with 4F or vehicle. The isolated HDL and LDL fractions were added to cultured human aortic endothelial cells to quantify monocyte chemotactic activity, thus measuring their pro- or anti-inflammatory index. The LDL from the hemodialysis patients was more pro-inflammatory and their HDL was less anti-inflammatory than those of the control subjects. Pre-incubation of the plasma from the hemodialysis patients with 4F decreased LDL pro-inflammatory activity and enhanced HDL anti-inflammatory activity. Whether 4F or other apolipoproteinA-1 mimetic peptides will have any therapeutic benefit in end-stage renal disease will have to be examined directly in clinical studies. PMID:19471321

  2. Anti-Inflammatory Mechanism of Neural Stem Cell Transplantation in Spinal Cord Injury.

    PubMed

    Cheng, Zhijian; Zhu, Wen; Cao, Kai; Wu, Fei; Li, Jin; Wang, Guoyu; Li, Haopen; Lu, Ming; Ren, Yi; He, Xijing

    2016-01-01

    Neural stem cell (NSC) transplantation has been proposed to promote functional recovery after spinal cord injury. However, a detailed understanding of the mechanisms of how NSCs exert their therapeutic plasticity is lacking. We transplanted mouse NSCs into the injured spinal cord seven days after SCI, and the Basso Mouse Scale (BMS) score was performed to assess locomotor function. The anti-inflammatory effects of NSC transplantation was analyzed by immunofluorescence staining of neutrophil and macrophages and the detection of mRNA levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and interleukin-12 (IL-12). Furthermore, bone marrow-derived macrophages (BMDMs) were co-cultured with NSCs and followed by analyzing the mRNA levels of inducible nitric oxide synthase (iNOS), TNF-α, IL-1β, IL-6 and IL-10 with quantitative real-time PCR. The production of TNF-α and IL-1β by BMDMs was examined using the enzyme-linked immunosorbent assay (ELISA). Transplanted NSCs had significantly increased BMS scores (p < 0.05). Histological results showed that the grafted NSCs migrated from the injection site toward the injured area. NSCs transplantation significantly reduced the number of neutrophils and iNOS+/Mac-2+ cells at the epicenter of the injured area (p < 0.05). Meanwhile, mRNA levels of TNF-α, IL-1β, IL-6 and IL-12 in the NSCs transplantation group were significantly decreased compared to the control group. Furthermore, NSCs inhibited the iNOS expression of BMDMs and the release of inflammatory factors by macrophages in vitro (p < 0.05). These results suggest that NSC transplantation could modulate SCI-induced inflammatory responses and enhance neurological function after SCI via reducing M1 macrophage activation and infiltrating neutrophils. Thus, this study provides a new insight into the mechanisms responsible for the anti-inflammatory effect of NSC transplantation after SCI. PMID:27563878

  3. Antioxidant and anti-inflammatory effects of Marrubium alysson extracts in high cholesterol-fed rabbits

    PubMed Central

    Essawy, Soha S.; Abo-elmatty, Dina M.; Ghazy, Nabila M.; Badr, Jihan M.; Sterner, Olov

    2013-01-01

    The antioxidant and anti-inflammatory effects of hexane (HEXA), chloroform (CHLORO), ethyl acetate (EA) and total alcoholic (T. ALCOH) extracts of Marrubium alysson in hypercholesterolemic-fed rabbits were evaluated. Hypercholesterolemia was induced in male rabbits by high cholesterol diet (HCD) (350 mg/kg) for 8 weeks. Hypercholesterolemic rabbits were allocated into groups, treated with simvastatin (SIM 5 mg/kg), different extracts of M. alysson at two doses of 250, 500 mg/kg. A normal control group and an HCD control one were used for comparison. Lipid profile, as well as oxidized low density lipoprotein-cholesterol (ox-LDL-C), myeloperoxidase activity (MPO) and superoxide anion production (O2•−), C-reactive protein (CRP) and monocyte chemoattractant protein-1 (MCP-1) were also evaluated. In addition, histological examination of ascending aorta was performed. We found dyslipidemia associated with significant increases in ox-LDL-C 123.5 ± 9.8 nmol MDA/mg non-HDL, MPO activity 0.08 ± 0.05 U/100 mg tissue and O2•− production 3.5 ± 0.3 nmol cytochrome C reduced/min/g tissue × 10−4 in hypercholerterolemic rabbits. In addition, there was a significant increase in CRP 6.6 ± 0.49 μmol/L and MCP-1 190.9 ± 6.4 pg/ml and its mRNA expression in HCD. Intima appeared thick with thick plaques surrounding the intima and luminal narrowing. SIM, EA and HEXA extracts of M. alysson had lipid lowering effect, decrease in ox-LDL-C, MPO, O2•−, CRP and MCP-1 mRNA expression with improvement of the pathological picture. M. alysson enhanced the stability of plaque, had lipid lowering, anti-inflammatory and antioxidant activities. PMID:25473336

  4. Anti-Inflammatory Mechanism of Neural Stem Cell Transplantation in Spinal Cord Injury

    PubMed Central

    Cheng, Zhijian; Zhu, Wen; Cao, Kai; Wu, Fei; Li, Jin; Wang, Guoyu; Li, Haopen; Lu, Ming; Ren, Yi; He, Xijing

    2016-01-01

    Neural stem cell (NSC) transplantation has been proposed to promote functional recovery after spinal cord injury. However, a detailed understanding of the mechanisms of how NSCs exert their therapeutic plasticity is lacking. We transplanted mouse NSCs into the injured spinal cord seven days after SCI, and the Basso Mouse Scale (BMS) score was performed to assess locomotor function. The anti-inflammatory effects of NSC transplantation was analyzed by immunofluorescence staining of neutrophil and macrophages and the detection of mRNA levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and interleukin-12 (IL-12). Furthermore, bone marrow-derived macrophages (BMDMs) were co-cultured with NSCs and followed by analyzing the mRNA levels of inducible nitric oxide synthase (iNOS), TNF-α, IL-1β, IL-6 and IL-10 with quantitative real-time PCR. The production of TNF-α and IL-1β by BMDMs was examined using the enzyme-linked immunosorbent assay (ELISA). Transplanted NSCs had significantly increased BMS scores (p < 0.05). Histological results showed that the grafted NSCs migrated from the injection site toward the injured area. NSCs transplantation significantly reduced the number of neutrophils and iNOS+/Mac-2+ cells at the epicenter of the injured area (p < 0.05). Meanwhile, mRNA levels of TNF-α, IL-1β, IL-6 and IL-12 in the NSCs transplantation group were significantly decreased compared to the control group. Furthermore, NSCs inhibited the iNOS expression of BMDMs and the release of inflammatory factors by macrophages in vitro (p < 0.05). These results suggest that NSC transplantation could modulate SCI-induced inflammatory responses and enhance neurological function after SCI via reducing M1 macrophage activation and infiltrating neutrophils. Thus, this study provides a new insight into the mechanisms responsible for the anti-inflammatory effect of NSC transplantation after SCI. PMID:27563878

  5. In vivo and In vitro Anti-Inflammatory Activity of Indazole and Its Derivatives

    PubMed Central

    Muniappan, M.

    2016-01-01

    Introduction The inflammatory response is closely intertwined with the process of repair. However in some diseases the inflammatory response may be exaggerated and sustained without apparent benefit and even with severe adverse complications. For decades, we have been primarily relying upon Nonsteroidal (NSAID) and Steroidal Anti-Inflammatory agents for management of various inflammatory conditions. However, adverse effects of these drugs are severe which often leads to patient’s non-compliance with inadequate relief. Therefore, there has been a constant pursuit to develop newer anti - inflammatory treatment with fewer side effects. Aim The study was designed to investigate the possible anti- inflammatory activity of indazole, its derivatives and to further investigate the possible cellular mechanisms underlying the anti-inflammatory effect. Materials and Methods Carrageenan induced hind paw oedema in rats was employed to study the acute anti-inflammatory activity of indazole and its derivatives. Further, the role of cyclooxygenase – 2, pro-inflammatory cytokines like Tumour Necrosis Factor – α, Interleukin – 1β and free radical scavenging activity (LPO, DPPH and NO) in the action of indazole and its derivatives was investigated using in vitro assays. Results SPSS version 16.0 software was used for analyse the anti-inflamatory data. The IC50 values of indazole and its derivatives obtained in in vitro experiments were calculated by linear regression analysis. Indazole and its derivatives significantly, dose dependently and time dependently inhibited carrageenan induced hind paw oedema. In addition, the test compounds inhibited cyclooxygenase–2, pro-inflammatory cytokines and free radicals in a concentration dependent manner. Conclusion The results of the present study revealed the potential anti-inflammatory action of investigated indazoles. The inhibition of cyclooxygenase -2, cytokines and free radicals may contribute to the anti-inflammatory effect of

  6. In Vitro Effects of Some Botanicals with Anti-Inflammatory and Antitoxic Activity

    PubMed Central

    Guidetti, Gianandrea; Giovazzino, Angela; Rubino, Valentina; Palatucci, Anna Teresa; Centenaro, Sara; Fraccaroli, Elena; Cortese, Laura; Bonomo, Maria Grazia; Ruggiero, Giuseppina; Canello, Sergio; Terrazzano, Giuseppe

    2016-01-01

    Several extrinsic factors, like drugs and chemicals, can foster autoimmunity. Tetracyclines, in particular oxytetracycline (OTC), appear to correlate with the emergence of immune-mediated diseases. Accumulation of OTC, the elective drug for gastrointestinal and respiratory infectious disease treatment in broiler chickens, was reported in chicken edible tissues and could represent a potential risk for pets and humans that could assume this antibiotic as residue in meat or in meat-derived byproducts. We investigated the in vitro anti-inflammatory properties of a pool of thirteen botanicals as a part of a nutraceutical diet, with proven immunomodulatory activity. In addition, we evaluated the effect of such botanicals in contrasting the in vitro proinflammatory toxicity of OTC. Our results showed a significant reduction in interferon- (INF-) γ production by human and canine lymphocytes in presence of botanicals (⁎p < 0.05). Increased INF-γ production, dependent on 24-hour OTC-incubation of T lymphocytes, was significantly reduced by the coincubation with Haematococcus pluvialis, with Glycine max, and with the mix of all botanicals (⁎p < 0.05). In conclusion, the use of these botanicals was shown to be able to contrast OTC-toxicity and could represent a new approach for the development of functional foods useful to enhance the standard pharmacological treatment in infections as well as in preventing or reducing the emergence of inflammatory diseases. PMID:27597982

  7. In Vitro Effects of Some Botanicals with Anti-Inflammatory and Antitoxic Activity

    PubMed Central

    Guidetti, Gianandrea; Giovazzino, Angela; Rubino, Valentina; Palatucci, Anna Teresa; Centenaro, Sara; Fraccaroli, Elena; Cortese, Laura; Bonomo, Maria Grazia; Ruggiero, Giuseppina; Canello, Sergio; Terrazzano, Giuseppe

    2016-01-01

    Several extrinsic factors, like drugs and chemicals, can foster autoimmunity. Tetracyclines, in particular oxytetracycline (OTC), appear to correlate with the emergence of immune-mediated diseases. Accumulation of OTC, the elective drug for gastrointestinal and respiratory infectious disease treatment in broiler chickens, was reported in chicken edible tissues and could represent a potential risk for pets and humans that could assume this antibiotic as residue in meat or in meat-derived byproducts. We investigated the in vitro anti-inflammatory properties of a pool of thirteen botanicals as a part of a nutraceutical diet, with proven immunomodulatory activity. In addition, we evaluated the effect of such botanicals in contrasting the in vitro proinflammatory toxicity of OTC. Our results showed a significant reduction in interferon- (INF-) γ production by human and canine lymphocytes in presence of botanicals (⁎p < 0.05). Increased INF-γ production, dependent on 24-hour OTC-incubation of T lymphocytes, was significantly reduced by the coincubation with Haematococcus pluvialis, with Glycine max, and with the mix of all botanicals (⁎p < 0.05). In conclusion, the use of these botanicals was shown to be able to contrast OTC-toxicity and could represent a new approach for the development of functional foods useful to enhance the standard pharmacological treatment in infections as well as in preventing or reducing the emergence of inflammatory diseases.

  8. Macrophage-assisted inflammation and pharmacological regulation of the cholinergic anti-inflammatory pathway.

    PubMed

    Pohanka, M; Snopkova, S; Havlickova, K; Bostik, P; Sinkorova, Z; Fusek, J; Kuca, K; Pikula, Jiri

    2011-01-01

    Macrophages play an important role in the immune system. They also participate in multiple processes including angiogenesis and triggering of inflammation. The present study summarizes pieces of knowledge on the importance of macrophages in disease, especially the inflammation. Special attention is paid to the cholinergic anti-inflammatory pathway (CAP) associated with the nicotinic acetylcholine receptor (nAChR) and the parasympathetic nervous system. The current pharmacological effectiveness in suppressing the inflammation in general and the septic shock in particular, is limited. CAP was discovered recently and it seems to be a suitable target for the development of new drugs. Moreover, available drugs binding to either nAChR or acetylcholinesterase (AChE) are candidates for either an inhibition or enhancement of CAP. Though the current scientific databases do not include all necessary data on the association of CAP with body functions and the research is quite intensive, the objective of the present review is to introduce the current trends and to critically evaluate CAP and macrophage-associated pathways.

  9. In vitro anti-inflammatory effects of diterpenoids and sesquiterpenoids from traditional Chinese medicine Siegesbeckia pubescens.

    PubMed

    Wang, Rui; Liu, Ying-Qian; Ha, Wei; Shi, Yan-Ping; Hwang, Tsong-Long; Huang, Guan-Jhong; Wu, Tian-Shung; Lee, Kuo-Hsiung

    2014-08-15

    Oxidative stress imposed by reactive oxygen species plays a crucial role in pathophysiology of inflammatory diseases. In the present study, sesquiterpenoids and diterpenoids isolated from Siegesbeckia pubescens, a Chinese traditional medicine used to treat arthritis, were evaluated for inhibition of NO production in activated RAW 264.7 macrophages and FMLP/CB induced O2(·-) generation and elastase release in human neutrophils. In the former assay, sesquiterpenoids were more potent than diterpenoids. The C-4 carbonyl group in the carabrane-type sesquiterpenoid 3 and the C-9 ether linkage in the germacrane sesquiterpene 7 were associated with the enhanced potency. Also, for the active ent-kaurane type diterpenoids, esterification of 17-OH with isobutyric acid and acetylation of 18-OH affected the inhibition of O2(·-) generation and elastase release. This report is the first to describe the inhibitory effects on oxidative stress of secondary metabolites from S. pubescens. Its findings suggest that active terpenoids from the herb could be used as lead anti-inflammatory agents.

  10. In Vitro Effects of Some Botanicals with Anti-Inflammatory and Antitoxic Activity.

    PubMed

    Guidetti, Gianandrea; Di Cerbo, Alessandro; Giovazzino, Angela; Rubino, Valentina; Palatucci, Anna Teresa; Centenaro, Sara; Fraccaroli, Elena; Cortese, Laura; Bonomo, Maria Grazia; Ruggiero, Giuseppina; Canello, Sergio; Terrazzano, Giuseppe

    2016-01-01

    Several extrinsic factors, like drugs and chemicals, can foster autoimmunity. Tetracyclines, in particular oxytetracycline (OTC), appear to correlate with the emergence of immune-mediated diseases. Accumulation of OTC, the elective drug for gastrointestinal and respiratory infectious disease treatment in broiler chickens, was reported in chicken edible tissues and could represent a potential risk for pets and humans that could assume this antibiotic as residue in meat or in meat-derived byproducts. We investigated the in vitro anti-inflammatory properties of a pool of thirteen botanicals as a part of a nutraceutical diet, with proven immunomodulatory activity. In addition, we evaluated the effect of such botanicals in contrasting the in vitro proinflammatory toxicity of OTC. Our results showed a significant reduction in interferon- (INF-) γ production by human and canine lymphocytes in presence of botanicals ((⁎) p < 0.05). Increased INF-γ production, dependent on 24-hour OTC-incubation of T lymphocytes, was significantly reduced by the coincubation with Haematococcus pluvialis, with Glycine max, and with the mix of all botanicals ((⁎) p < 0.05). In conclusion, the use of these botanicals was shown to be able to contrast OTC-toxicity and could represent a new approach for the development of functional foods useful to enhance the standard pharmacological treatment in infections as well as in preventing or reducing the emergence of inflammatory diseases. PMID:27597982

  11. β-Arrestin 2 mediates the anti-inflammatory effects of fluoxetine in lipopolysaccharide-stimulated microglial cells.

    PubMed

    Du, Ren-Wei; Du, Ren-Hong; Bu, Wen-Guang

    2014-09-01

    Recent evidence has suggested that microglial activation plays an important role in the pathogenesis of depression. Activated microglia can secrete various pro-inflammatory cytokines, which may contribute to the development and maintenance of depression. Thus, inhibition of microglial activation may have a therapeutic benefit in the treatment of depression. In the present study, we found that fluoxetine significantly inhibited lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-α), interleukin- 6 (IL-6) and nitric oxide (NO) and reduced the phosphorylation of transforming growth factor-beta-activated kinase 1 (TAK1) and nuclear factor-kappa B (NF-κB) p65 nuclear translocation in microglia. We further found that fluoxetine increased the expression of β-arrestin 2 and enhanced the association of β-arrestin 2 with TAK1-binding protein 1 (TAB1) and disrupted TAK1-TAB1 interaction. Moreover, β-arrestin 2 knock-down abolished the anti-inflammatory effects of fluoxetine in lipopolysaccharide-stimulated microglial cells. Collectively, our findings suggest that β-arrestin 2 is necessary for the anti-inflammatory effects of fluoxetine and offers novel drug targets in the convergent fluoxetine/β-arrestin 2 and inflammatory pathways for treating microglial inflammatory neuropathologies like depression.

  12. Thiobenzothiazole-modified Hydrocortisones Display Anti-inflammatory Activity with Reduced Impact on Islet β-Cell Function*

    PubMed Central

    Burke, Susan J.; May, Amanda L.; Noland, Robert C.; Lu, Danhong; Brissova, Marcela; Powers, Alvin C.; Sherrill, Elizabeth M.; Karlstad, Michael D.; Campagna, Shawn R.; Stephens, Jacqueline M.; Collier, J. Jason

    2015-01-01

    Glucocorticoids signal through the glucocorticoid receptor (GR) and are administered clinically for a variety of situations, including inflammatory disorders, specific cancers, rheumatoid arthritis, and organ/tissue transplantation. However, glucocorticoid therapy is also associated with additional complications, including steroid-induced diabetes. We hypothesized that modification of the steroid backbone is one strategy to enhance the therapeutic potential of GR activation. Toward this goal, two commercially unavailable, thiobenzothiazole-containing derivatives of hydrocortisone (termed MS4 and MS6) were examined using 832/13 rat insulinoma cells as well as rodent and human islets. We found that MS4 had transrepression properties but lacked transactivation ability, whereas MS6 retained both transactivation and transrepression activities. In addition, MS4 and MS6 both displayed anti-inflammatory activity. Furthermore, MS4 displayed reduced impact on islet β-cell function in both rodent and human islets. Similar to dexamethasone, MS6 promoted adipocyte development in vitro, whereas MS4 did not. Moreover, neither MS4 nor MS6 activated the Pck1 (Pepck) gene in primary rat hepatocytes. We conclude that modification of the functional groups attached to the D-ring of the hydrocortisone steroid molecule produces compounds with altered structure-function GR agonist activity with decreased impact on insulin secretion and reduced adipogenic potential but with preservation of anti-inflammatory activity. PMID:25851902

  13. Occurrence and fate of antibiotic, analgesic/anti-inflammatory, and antifungal compounds in five wastewater treatment processes.

    PubMed

    Guerra, P; Kim, M; Shah, A; Alaee, M; Smyth, S A

    2014-03-01

    The presence of pharmaceuticals and personal care products (PPCPs) in the aquatic environment as a result of wastewater effluent discharge is a concern in many countries. In order to expand our understanding on the occurrence and fate of PPCPs during wastewater treatment processes, 62 antibiotic, analgesic/anti-inflammatory, and antifungal compounds were analyzed in 72 liquid and 24 biosolid samples from six wastewater treatment plants (WWTPs) during the summer and winter seasons of 2010-2012. This is the first scientific study to compare five different wastewater treatment processes: facultative and aerated lagoons, chemically-enhanced primary treatment, secondary activated sludge, and advanced biological nutrient removal. PPCPs were detected in all WWTP influents at median concentrations of 1.5 to 92,000 ng/L, with no seasonal differences. PPCPs were also found in all final effluents at median levels ranging from 3.6 to 4,200 ng/L with higher values during winter (p<0.05). Removal efficiencies ranged between -450% and 120%, depending on the compound, WWTP type, and season. Mass balance showed that the fate of analgesic/anti-inflammatory compounds was predominantly biodegradation during biological treatment, while antibiotics and antifungal compounds were more likely to sorb to sludge. However, some PPCPs remained soluble and were detected in effluent samples. Overall, this study highlighted the occurrence and behavior of a large set of PPCPs and determined how their removal is affected by environmental/operational factors in different WWTPs. PMID:24370698

  14. Flavonoid-modified surfaces: multifunctional bioactive biomaterials with osteopromotive, anti-inflammatory, and anti-fibrotic potential.

    PubMed

    Córdoba, Alba; Satué, María; Gómez-Florit, Manuel; Hierro-Oliva, Margarita; Petzold, Christiane; Lyngstadaas, Staale P; González-Martín, María Luisa; Monjo, Marta; Ramis, Joana M

    2015-03-11

    Flavonoids are small polyphenolic molecules of natural origin with antioxidant, anti-inflammatory, and antibacterial properties. Here, a bioactive surface based on the covalent immobilization of flavonoids taxifolin and quercitrin on titanium substrates is presented, using (3-aminopropyl)triethoxysilane (APTES) as coupling agent. FTIR and XPS measurements confirm the grafting of the flavonoids to the surfaces. Using 2-aminoethyl diphenylborinate (DPBA, a flavonoid-specific dye), the modified surfaces are imaged by fluorescence microscopy. The bioactivity of the flavonoid-modified surfaces is evaluated in vitro with human umbilical cord derived mesenchymal stem cells (hUC-MSCs) and human gingival fibroblasts (HGFs) and compared to that of simple flavonoid coatings prepared by drop casting. Flavonoid-modified surfaces show anti-inflammatory and anti-fibrotic potential on HGF. In addition, Ti surfaces covalently functionalized with flavonoids promote the differentiation of hUC-MSCs to osteoblasts--enhancing the expression of osteogenic markers, increasing alkaline phosphatase activity and calcium deposition; while drop-casted surfaces do not. These findings could have a high impact in the development of advanced implantable medical devices like bone implants. Given the broad range of bioactivities of flavonoid compounds, these surfaces are ready to be explored for other biomedical applications, e.g., as stent surface or tumor-targeted functionalized nanoparticles for cardiovascular or cancer therapies.

  15. Synthesis of 17β-N-arylcarbamoylandrost-4-en-3-one derivatives and their anti-proliferative effect on human androgen-sensitive LNCaP cell line.

    PubMed

    Cortés-Benítez, Francisco; Cabeza, Marisa; Ramírez-Apan, María Teresa; Alvarez-Manrique, Berenice; Bratoeff, Eugene

    2016-10-01

    In this study, we report the synthesis and anti-proliferative effect of a set of eight androst-4-ene-3-one derivatives with different arylcarbamoyl groups at C-17. The novel compounds were prepared from commercially available 3β-hydroxy-5-pregnen-20-one and evaluated against the androgen-sensitive human prostate adenocarcinoma LNCaP cell line. The cancerous cells were exposed to 50 μM of each compound and the proliferating agent testosterone (T) or dihydrotestosterone (DHT). The most potent compounds from this assay were further tested against the androgen-insensitive PC3 cell line. We also demonstrate the activity of these compounds on rat peripheral blood mononuclear cells for comparison. Both 17β-N-[3,5-bis(trifluoromethyl)phenylcarbamoyl]androst-4-ene-3-one (6f) and 17β-N-(1,3-thiazol-2-ylcarbamoyl)androst-4-ene-3-one (6g) exhibited a higher growth inhibitory effect than commercially available drugs finasteride, flutamide and ketoconazole on LNCaP cells in the presence and absence of androgens. In addition, 6f and 6g demonstrated high potency on PC3 cells suggesting an androgen-independent anti-proliferative effect. Moreover, the novel compounds showed a small effect on rat mononuclear cells, an indication of low toxicity. PMID:27423983

  16. Synthesis, Crystal Study, and Anti-Proliferative Activity of Some 2-Benzimidazolylthioacetophenones towards Triple-Negative Breast Cancer MDA-MB-468 Cells as Apoptosis-Inducing Agents

    PubMed Central

    Abdel-Aziz, Hatem A.; Eldehna, Wagdy M.; Ghabbour, Hazem; Al-Ansary, Ghada H.; Assaf, Areej M.; Al-Dhfyan, Abdullah

    2016-01-01

    On account of its poor prognosis and deficiency of therapeutic stratifications, triple negative breast cancer continues to form the causative platform of an incommensurate number of breast cancer deaths. Aiming at the development of potent anticancer agents as a continuum of our previous efforts, a novel series of 2-((benzimidazol-2-yl)thio)-1-arylethan-1-ones 5a–w was synthesized and evaluated for its anti-proliferative activity towards triple negative breast cancer (TNBC) MDA-MB-468 cells. Compound 5k was the most active analog against MDA-MB-468 (IC50 = 19.90 ± 1.37 µM), with 2.1-fold increased activity compared to 5-fluorouracil (IC50 = 41.26 ± 3.77 µM). Compound 5k was able to induce apoptosis in MDA-MB-468, as evidenced by the marked boosting in the percentage of florecsein isothiocyanate annexin V (Annexin V–FITC)-positive apoptotic cells (upper right (UR) + lower right (LR)) by 2.8-fold in comparison to control accompanied by significant increase in the proportion of cells at pre-G1 (the first gap phase) by 8.13-fold in the cell-cycle analysis. Moreover, a quantitative structure activity relationship (QSAR) model was established to investigate the structural requirements orchestrating the anti-proliferative activity. Finally, we established a theoretical kinetic study. PMID:27483243

  17. Anti-proliferative activity of 2,6-dichloro-9- or 7-(ethoxycarbonylmethyl)-9H- or 7H-purines against several human solid tumour cell lines.

    PubMed

    Morales, Fátima; Ramírez, Alberto; Conejo-García, Ana; Morata, Cynthia; Marchal, Juan A; Campos, Joaquín M

    2014-04-01

    As leads we took several benzo-fused seven- and six-membered scaffolds linked to the pyrimidine or purine moieties with notable anti-proliferative activity against human breast, colon and melanoma cancerous cell lines. We then decided to maintain the double-ringed nitrogenous bases and change the other components to the ethyl acetate moiety. This way six purine and two 5-fluorouracil derivatives were obtained and evaluated against the MCF-7, HCT-116, A-375 and G-361 cancer cell lines. Two QSARs are obtained between the anti-proliferative IC₅₀ values for compounds 26-33 and the clog P against the melanoma cell lines A-375 and G-361. Our results show that two of the analogues [ethyl 2-(2,6-dichloro-9H- or 7H-purine-9- or 7-yl)acetates (30 and 33, respectively)] are potent cytotoxic agents against all the tumour cell lines assayed, showing single-digit micromolar IC₅₀ values. This exemplifies the potential of our previously reported purine compounds to qualify as lead structures for medicinal chemistry campaigns, affording simplified analogues easy to synthesize and with a noteworthy bioactivity. The selective activity of 30 and 33 against the melanoma cell line A-375, via apoptosis, supposes a great advantage for a future therapeutic use.

  18. Synthesis, Crystal Study, and Anti-Proliferative Activity of Some 2-Benzimidazolylthioacetophenones towards Triple-Negative Breast Cancer MDA-MB-468 Cells as Apoptosis-Inducing Agents.

    PubMed

    Abdel-Aziz, Hatem A; Eldehna, Wagdy M; Ghabbour, Hazem; Al-Ansary, Ghada H; Assaf, Areej M; Al-Dhfyan, Abdullah

    2016-01-01

    On account of its poor prognosis and deficiency of therapeutic stratifications, triple negative breast cancer continues to form the causative platform of an incommensurate number of breast cancer deaths. Aiming at the development of potent anticancer agents as a continuum of our previous efforts, a novel series of 2-((benzimidazol-2-yl)thio)-1-arylethan-1-ones 5a-w was synthesized and evaluated for its anti-proliferative activity towards triple negative breast cancer (TNBC) MDA-MB-468 cells. Compound 5k was the most active analog against MDA-MB-468 (IC50 = 19.90 ± 1.37 µM), with 2.1-fold increased activity compared to 5-fluorouracil (IC50 = 41.26 ± 3.77 µM). Compound 5k was able to induce apoptosis in MDA-MB-468, as evidenced by the marked boosting in the percentage of florecsein isothiocyanate annexin V (Annexin V-FITC)-positive apoptotic cells (upper right (UR) + lower right (LR)) by 2.8-fold in comparison to control accompanied by significant increase in the proportion of cells at pre-G1 (the first gap phase) by 8.13-fold in the cell-cycle analysis. Moreover, a quantitative structure activity relationship (QSAR) model was established to investigate the structural requirements orchestrating the anti-proliferative activity. Finally, we established a theoretical kinetic study. PMID:27483243

  19. Synthesis of 17β-N-arylcarbamoylandrost-4-en-3-one derivatives and their anti-proliferative effect on human androgen-sensitive LNCaP cell line.

    PubMed

    Cortés-Benítez, Francisco; Cabeza, Marisa; Ramírez-Apan, María Teresa; Alvarez-Manrique, Berenice; Bratoeff, Eugene

    2016-10-01

    In this study, we report the synthesis and anti-proliferative effect of a set of eight androst-4-ene-3-one derivatives with different arylcarbamoyl groups at C-17. The novel compounds were prepared from commercially available 3β-hydroxy-5-pregnen-20-one and evaluated against the androgen-sensitive human prostate adenocarcinoma LNCaP cell line. The cancerous cells were exposed to 50 μM of each compound and the proliferating agent testosterone (T) or dihydrotestosterone (DHT). The most potent compounds from this assay were further tested against the androgen-insensitive PC3 cell line. We also demonstrate the activity of these compounds on rat peripheral blood mononuclear cells for comparison. Both 17β-N-[3,5-bis(trifluoromethyl)phenylcarbamoyl]androst-4-ene-3-one (6f) and 17β-N-(1,3-thiazol-2-ylcarbamoyl)androst-4-ene-3-one (6g) exhibited a higher growth inhibitory effect than commercially available drugs finasteride, flutamide and ketoconazole on LNCaP cells in the presence and absence of androgens. In addition, 6f and 6g demonstrated high potency on PC3 cells suggesting an androgen-independent anti-proliferative effect. Moreover, the novel compounds showed a small effect on rat mononuclear cells, an indication of low toxicity.

  20. Korean Ginseng Berry Fermented by Mycotoxin Non-producing Aspergillus niger and Aspergillus oryzae: Ginsenoside Analyses and Anti-proliferative Activities.

    PubMed

    Li, Zhipeng; Ahn, Hyung Jin; Kim, Nam Yeon; Lee, Yu Na; Ji, Geun Eog

    2016-01-01

    To transform ginsenosides, Korean ginseng berry (KGB) was fermented by mycotoxin non-producing Aspergillus niger and Aspergillus oryzae. Changes of ginsenoside profile and anti-proliferative activities were observed. Results showed that A. niger tended to efficiently transform protopanaxadiol (PPD) type ginsenosides such as Rb1, Rb2, Rd to compound K while A. oryzae tended to efficiently transform protopanaxatriol (PPT) type ginsenoside Re to Rh1 via Rg1. Butanol extracts of fermented KGB showed high cytotoxicity on human adenocarcinoma HT-29 cell line and hepatocellular carcinoma HepG2 cell line while that of unfermented KGB showed little. The minimum effective concentration of niger-fermented KGB was less than 2.5 µg/mL while that of oryzae-fermented KGB was about 5 µg/mL. As A. niger is more inclined to transform PPD type ginsenosides, niger-fermented KGB showed stronger anti-proliferative activity than oryzae-fermented KGB. PMID:27582326

  1. In vitro antioxidant, antimicrobial and anti-proliferative activities of purple potato extracts (Solanum tuberosum cv Vitelotte noire) following simulated gastro-intestinal digestion.

    PubMed

    Ombra, Maria Neve; Fratianni, Florinda; Granese, Tiziana; Cardinale, Federica; Cozzolino, Autilia; Nazzaro, Filomena

    2015-01-01

    Analyses of antioxidant and in vitro antimicrobial and anti-proliferative activities of anthocyanin-rich extracts from purple potatoes, Solanum tuberosum L. cv Vitelotte noire (Solanaceae), were performed by simulating both a domestic cooking process and human digestion. Extracts of crude and cooked purple potato did not exhibit antimicrobial activity against the tester strains: Bacillus cereus, Escherichia coli and Pseudomonas aeruginosa. The behaviour changed after the simulated gastrointestinal transit, when an inhibition halo was observed against all tester strains used, ranging from 0.53 cm against B. cereus to 0.82 cm against E. coli. In addition antioxidant activity exhibited, before and after the simulated gastrointestinal digestion (5.96 mg/mL ± 0.92; 28 mg/mL ± 0 .13, respectively) and the persistence of anti-proliferative activity against the colon cancer cells Caco-2, SW48 and MCF7, MDA-MB-231 breast cancer cells, after the simulated digestion, (EC50 = 0.21; 1.13 μg/mL), suggest that vitelotte consumption might bring tangible benefits for human health.

  2. Anti-Inflammatory and Antioxidant Activities of Salvia fruticosa: An HPLC Determination of Phenolic Contents.

    PubMed

    Boukhary, Rima; Raafat, Karim; Ghoneim, Asser I; Aboul-Ela, Maha; El-Lakany, Abdalla

    2016-01-01

    Objectives. Salvia fruticosa Mill. (S. fruticosa) is widely used in folk medicine. Accordingly, the present study was designed to evaluate the antioxidant and anti-inflammatory activities of S. fruticosa, and to determine the phenolic constituents of its extracts. Methods. The antioxidant activity was determined using 2,2-diphenylpicrylhydrazyl assay. Total phenolic contents were estimated using Folin-Ciocalteu reagent, and high-performance liquid chromatography was performed to identify phenolic constituents. To evaluate the anti-inflammatory activity, carrageenan-induced mouse paw edema was determined plethysmographically. Key Findings. Different plant extracts demonstrated strong radical scavenging activity, where the ethyl acetate extract had the highest value in the roots and the lowest in the aerial parts. This antioxidant activity was correlated to the total phenolic content of different extracts, where rutin and luteolin were the most abundant constituents. Interestingly, both the roots and aerial parts revealed a significant anti-inflammatory activity comparable to diclofenac. Conclusions. This study is the first to demonstrate pharmacologic evidence of the potential anti-inflammatory activity of S. fruticosa. This activity may partly be due to the radical scavenging effects of its polyphenolic contents. These findings warrant the popular use of the East Mediterranean sage and highlight the potential of its active constituents in the development of new anti-inflammatory drugs.

  3. Anti-Inflammatory Properties and Chemical Characterization of the Essential Oils of Four Citrus Species.

    PubMed

    Amorim, Jorge Luis; Simas, Daniel Luiz Reis; Pinheiro, Mariana Martins Gomes; Moreno, Daniela Sales Alviano; Alviano, Celuta Sales; da Silva, Antonio Jorge Ribeiro; Fernandes, Patricia Dias

    2016-01-01

    Citrus fruits have potential health-promoting properties and their essential oils have long been used in several applications. Due to biological effects described to some citrus species in this study our objectives were to analyze and compare the phytochemical composition and evaluate the anti-inflammatory effect of essential oils (EO) obtained from four different Citrus species. Mice were treated with EO obtained from C. limon, C. latifolia, C. aurantifolia or C. limonia (10 to 100 mg/kg, p.o.) and their anti-inflammatory effects were evaluated in chemical induced inflammation (formalin-induced licking response) and carrageenan-induced inflammation in the subcutaneous air pouch model. A possible antinociceptive effect was evaluated in the hot plate model. Phytochemical analyses indicated the presence of geranial, limonene, γ-terpinene and others. EOs from C. limon, C. aurantifolia and C. limonia exhibited anti-inflammatory effects by reducing cell migration, cytokine production and protein extravasation induced by carrageenan. These effects were also obtained with similar amounts of pure limonene. It was also observed that C. aurantifolia induced myelotoxicity in mice. Anti-inflammatory effect of C. limon and C. limonia is probably due to their large quantities of limonene, while the myelotoxicity observed with C. aurantifolia is most likely due to the high concentration of citral. Our results indicate that these EOs from C. limon, C. aurantifolia and C. limonia have a significant anti-inflammatory effect; however, care should be taken with C. aurantifolia. PMID:27088973

  4. Anti-Inflammatory Properties and Chemical Characterization of the Essential Oils of Four Citrus Species

    PubMed Central

    Amorim, Jorge Luis; Simas, Daniel Luiz Reis; Pinheiro, Mariana Martins Gomes; Moreno, Daniela Sales Alviano; Alviano, Celuta Sales; da Silva, Antonio Jorge Ribeiro

    2016-01-01

    Citrus fruits have potential health-promoting properties and their essential oils have long been used in several applications. Due to biological effects described to some citrus species in this study our objectives were to analyze and compare the phytochemical composition and evaluate the anti-inflammatory effect of essential oils (EO) obtained from four different Citrus species. Mice were treated with EO obtained from C. limon, C. latifolia, C. aurantifolia or C. limonia (10 to 100 mg/kg, p.o.) and their anti-inflammatory effects were evaluated in chemical induced inflammation (formalin-induced licking response) and carrageenan-induced inflammation in the subcutaneous air pouch model. A possible antinociceptive effect was evaluated in the hot plate model. Phytochemical analyses indicated the presence of geranial, limonene, γ-terpinene and others. EOs from C. limon, C. aurantifolia and C. limonia exhibited anti-inflammatory effects by reducing cell migration, cytokine production and protein extravasation induced by carrageenan. These effects were also obtained with similar amounts of pure limonene. It was also observed that C. aurantifolia induced myelotoxicity in mice. Anti-inflammatory effect of C. limon and C. limonia is probably due to their large quantities of limonene, while the myelotoxicity observed with C. aurantifolia is most likely due to the high concentration of citral. Our results indicate that these EOs from C. limon, C. aurantifolia and C. limonia have a significant anti-inflammatory effect; however, care should be taken with C. aurantifolia. PMID:27088973

  5. Anti-Inflammatory Properties and Chemical Characterization of the Essential Oils of Four Citrus Species.

    PubMed

    Amorim, Jorge Luis; Simas, Daniel Luiz Reis; Pinheiro, Mariana Martins Gomes; Moreno, Daniela Sales Alviano; Alviano, Celuta Sales; da Silva, Antonio Jorge Ribeiro; Fernandes, Patricia Dias

    2016-01-01

    Citrus fruits have potential health-promoting properties and their essential oils have long been used in several applications. Due to biological effects described to some citrus species in this study our objectives were to analyze and compare the phytochemical composition and evaluate the anti-inflammatory effect of essential oils (EO) obtained from four different Citrus species. Mice were treated with EO obtained from C. limon, C. latifolia, C. aurantifolia or C. limonia (10 to 100 mg/kg, p.o.) and their anti-inflammatory effects were evaluated in chemical induced inflammation (formalin-induced licking response) and carrageenan-induced inflammation in the subcutaneous air pouch model. A possible antinociceptive effect was evaluated in the hot plate model. Phytochemical analyses indicated the presence of geranial, limonene, γ-terpinene and others. EOs from C. limon, C. aurantifolia and C. limonia exhibited anti-inflammatory effects by reducing cell migration, cytokine production and protein extravasation induced by carrageenan. These effects were also obtained with similar amounts of pure limonene. It was also observed that C. aurantifolia induced myelotoxicity in mice. Anti-inflammatory effect of C. limon and C. limonia is probably due to their large quantities of limonene, while the myelotoxicity observed with C. aurantifolia is most likely due to the high concentration of citral. Our results indicate that these EOs from C. limon, C. aurantifolia and C. limonia have a significant anti-inflammatory effect; however, care should be taken with C. aurantifolia.

  6. [Non-steroid anti-inflammatory drugs and adverse gastrointestinal effects. An unresolved problem].

    PubMed

    López, A

    1999-01-01

    Non-steroid anti-inflammatory drugs are a class of medicine widely used throughout the world. This is a pharmacological group in continuous growth, to which some new molecules have been added in recent years. The great drawback of non-steroid anti-inflammatory drugs are their adverse effects, outstanding of which due to their frequency and importance being those that occur in the gastrointestinal tract. By means of a search in Medline and other databases, this work reviews the latest data published on the incidence of dyspepsia, gastroduodenal lesions, gastrointestinal complications and mortality associated with consumption of non-steroid anti-inflammatory drugs. Similarly, a brief description is made of the mechanism of lesions to the stomach of the non-steroid anti-inflammatory drugs and the different risk factors that condition the appearance of adverse effects at the gastrointestinal level. Finally, an analysis is made of the preventive strategy and the different medicines that can be used to this end and a contrast is made of the evidence extracted from the different published studies and the reality of the use of the different "gastroprotectors". This review concludes with a series of questions that still remain unresolved concerning treatment with non-steroid anti-inflammatory drugs and their lesions to the stomach.

  7. Systems pharmacology dissection of the anti-inflammatory mechanism for the medicinal herb Folium eriobotryae.

    PubMed

    Zhang, Jingxiao; Li, Yan; Chen, Su-Shing; Zhang, Lilei; Wang, Jinghui; Yang, Yinfeng; Zhang, Shuwei; Pan, Yanqiu; Wang, Yonghua; Yang, Ling

    2015-01-28

    Inflammation is a hallmark of many diseases like diabetes, cancers, atherosclerosis and arthritis. Thus, lots of concerns have been raised toward developing novel anti-inflammatory agents. Many alternative herbal medicines possess excellent anti-inflammatory properties, yet their precise mechanisms of action are yet to be elucidated. Here, a novel systems pharmacology approach based on a large number of chemical, biological and pharmacological data was developed and exemplified by a probe herb Folium Eriobotryae, a widely used clinical anti-inflammatory botanic drug. The results show that 11 ingredients of this herb with favorable pharmacokinetic properties are predicted as active compounds for anti-inflammatory treatment. In addition, via systematic network analyses, their targets are identified to be 43 inflammation-associated proteins including especially COX2, ALOX5, PPARG, TNF and RELA that are mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway, the rheumatoid arthritis pathway and NF-κB signaling pathway. All these demonstrate that the integrated systems pharmacology method provides not only an effective tool to illustrate the anti-inflammatory mechanisms of herbs, but also a new systems-based approach for drug discovery from, but not limited to, herbs, especially when combined with further experimental validations.

  8. Systems Pharmacology Dissection of the Anti-Inflammatory Mechanism for the Medicinal Herb Folium Eriobotryae

    PubMed Central

    Zhang, Jingxiao; Li, Yan; Chen, Su-Shing; Zhang, Lilei; Wang, Jinghui; Yang, Yinfeng; Zhang, Shuwei; Pan, Yanqiu; Wang, Yonghua; Yang, Ling

    2015-01-01

    Inflammation is a hallmark of many diseases like diabetes, cancers, atherosclerosis and arthritis. Thus, lots of concerns have been raised toward developing novel anti-inflammatory agents. Many alternative herbal medicines possess excellent anti-inflammatory properties, yet their precise mechanisms of action are yet to be elucidated. Here, a novel systems pharmacology approach based on a large number of chemical, biological and pharmacological data was developed and exemplified by a probe herb Folium Eriobotryae, a widely used clinical anti-inflammatory botanic drug. The results show that 11 ingredients of this herb with favorable pharmacokinetic properties are predicted as active compounds for anti-inflammatory treatment. In addition, via systematic network analyses, their targets are identified to be 43 inflammation-associated proteins including especially COX2, ALOX5, PPARG, TNF and RELA that are mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway, the rheumatoid arthritis pathway and NF-κB signaling pathway. All these demonstrate that the integrated systems pharmacology method provides not only an effective tool to illustrate the anti-inflammatory mechanisms of herbs, but also a new systems-based approach for drug discovery from, but not limited to, herbs, especially when combined with further experimental validations. PMID:25636035

  9. A Systematic Review for Anti-Inflammatory Property of Clusiaceae Family: A Preclinical Approach

    PubMed Central

    de Melo, Mônica Santos; Quintans, Jullyana de Souza Siqueira; Araújo, Adriano Antunes de Souza; Duarte, Marcelo Cavalcante; Bonjardim, Leonardo Rigoldi; Moraes, Valéria Regina de Souza; de Araújo-Júnior, João Xavier

    2014-01-01

    Background. Clusiaceae family (sensu lato) is extensively used in ethnomedicine for treating a number of disease conditions which include cancer, inflammation, and infection. The aim of this review is to report the pharmacological potential of plants of Clusiaceae family with the anti-inflammatory activity in animal experiments. Methods. A systematic review about experiments investigating anti-inflammatory activity of Clusiaceae family was carried out by searching bibliographic databases such as Medline, Scopus and Embase. In this update, the search terms were “anti-inflammatory agents,” “Clusiaceae,” and “animals, laboratory.” Results. A total of 255 publications with plants this family were identified. From the initial 255 studies, a total of 21 studies were selected for the final analysis. Studies with genera Allanblackia, Clusia, Garcinia or Rheedia, and Hypericum showed significant anti-inflammatory activity. The findings include a decrease of total leukocytes, a number of neutrophils, total protein concentration, granuloma formation, and paw or ear edema formation. Other interesting findings included decreased of the MPO activity, and inflammatory mediators such as NF-κB and iNOS expression, PGE2 and Il-1β levels and a decrease in chronic inflammation. Conclusion. The data reported suggests the anti-inflammatory effect potential of Clusiaceae family in animal experiments. PMID:24976853

  10. Design, synthesis and pharmacological evaluation of omeprazole-like agents with anti-inflammatory activity.

    PubMed

    El-Nezhawy, Ahmed O H; Biuomy, Ayman R; Hassan, Fatma S; Ismaiel, Ayman K; Omar, Hany A

    2013-04-01

    A new series of novel benzimidazole derivatives containing substituted pyrid-2-yl moiety and polyhydroxy sugar conjugated to the N-benzimidazole moiety has been synthesized and evaluated as orally bioavailable anti-inflammatory agents with anti-ulcerogenic activity. The anti-inflammatory and anti-ulcerogenic activities of these compounds were compared to diclofenac and omeprazole, respectively. In carrageenan-induced paw oedema assay, 2-methyl-N-((3,4-dimethoxypyridin-2-yl)methyl)-1H-benzimidazol-5-amine (12d) and 1-(1,2,3,5-tetrahydroxy-α-D-mannofuranose)-5-(((3,4-dimethoxypyridin-2yl)methyl)amino)-2-methyl-1H-benzimidazole (15d) displayed dose-dependent anti-inflammatory activities by decreasing the inflammation by 62% and 72%, respectively which is comparable to that of diclofenac (73%). In contrast to diclofenac, the anti-inflammatory activity of these compounds was not only free from any side effects on the gastric mucosa but also showed significant anti-ulcerogenic activity in rat pyloric ligation and ethanol-induced gastric ulcer models similar to that of omeprazole. Together, these findings suggest that 12d and 15d are potent anti-inflammatory agents with concurrent anti-ulcerogenic activity and support its clinical promise as a component of therapeutic strategies for inflammation, for which the gastric side effects are always a major limitation.

  11. Anti-Inflammatory and Antioxidant Activities of Salvia fruticosa: An HPLC Determination of Phenolic Contents

    PubMed Central

    Boukhary, Rima; Ghoneim, Asser I.; Aboul-Ela, Maha; El-Lakany, Abdalla

    2016-01-01

    Objectives. Salvia fruticosa Mill. (S. fruticosa) is widely used in folk medicine. Accordingly, the present study was designed to evaluate the antioxidant and anti-inflammatory activities of S. fruticosa, and to determine the phenolic constituents of its extracts. Methods. The antioxidant activity was determined using 2,2-diphenylpicrylhydrazyl assay. Total phenolic contents were estimated using Folin-Ciocalteu reagent, and high-performance liquid chromatography was performed to identify phenolic constituents. To evaluate the anti-inflammatory activity, carrageenan-induced mouse paw edema was determined plethysmographically. Key Findings. Different plant extracts demonstrated strong radical scavenging activity, where the ethyl acetate extract had the highest value in the roots and the lowest in the aerial parts. This antioxidant activity was correlated to the total phenolic content of different extracts, where rutin and luteolin were the most abundant constituents. Interestingly, both the roots and aerial parts revealed a significant anti-inflammatory activity comparable to diclofenac. Conclusions. This study is the first to demonstrate pharmacologic evidence of the potential anti-inflammatory activity of S. fruticosa. This activity may partly be due to the radical scavenging effects of its polyphenolic contents. These findings warrant the popular use of the East Mediterranean sage and highlight the potential of its active constituents in the development of new anti-inflammatory drugs. PMID:26881007

  12. Chemical composition and anti-inflammatory activity of the leaves of Byrsonima verbascifolia.

    PubMed

    Saldanha, Aline Aparecida; do Carmo, Lucas Fernandes; do Nascimento, Sara Batista; de Matos, Natália Alves; de Carvalho Veloso, Clarice; Castro, Ana Hortência Fonsêca; De Vos, Ric C H; Klein, André; de Siqueira, João Máximo; Carollo, Carlos Alexandre; do Nascimento, Thalita Vieira; Toffoli-Kadri, Mônica Cristina; Soares, Adriana Cristina

    2016-10-01

    An ethnopharmacological survey indicates that the genus Byrsonima has some medicinal species that are commonly found in the Brazilian Cerrado and has been used as an anti-inflammatory and for gastroduodenal disorders. The aim of this study was to evaluate the anti-inflammatory and antioxidant activity along with qualitative chemical characterization of the methanolic extract of the leaves of Byrsonima verbascifolia (BvME) obtained by exhaustive percolation. The data from the chemical analyses by liquid chromatography-mass spectrometry led to tentative identification of 42 compounds belonging to proanthocyanidins, galloyl quinic acid derivatives, flavonoids, and triterpene glycoside derivatives. BvME contain flavonoids and show an antioxidative activity. The methanolic extract administered intraperitoneally at doses of 50, 100, or 300 mg/kg showed a significant reduction in paw edema and modulated the neutrophil influx in a mouse model. Furthermore, the anti-edematogenic activity of the extract provided in smaller doses (12.5 and 25 mg/kg) was also demonstrated in a mouse paw edema model. The extract inhibited NO production by macrophages induced by lipopolysaccharide. We presume that the anti-inflammatory effects of BvME are due to a combination of compounds present in B. verbascifolia, including catechins (procyanidins), flavonoids, and triterpene glycosides and that these anti-inflammatory actions should be mediated, at least partly, through the inhibition of NO production. This study supports and validates the ethnopharmacological uses of B. verbascifolia as an anti-inflammatory.

  13. Evaluation of anti-inflammatory activity of Pseudananas macrodontes (Morr.) Harms (Bromeliaceae) fruit extract in rats.

    PubMed

    Errasti, María E; Caffini, Néstor O; Pelzer, Lilian E; Rotelli, Alejandra E

    2013-01-01

    Several species of the family Bromeliaceae are characterized by the production of proteases in unusual amounts, especially in fruits. Bromelain, an extract rich in cysteine endopeptidases obtained from Ananas comosus L., and a few other proteases have been used as anti-inflammatory agents for some years, but bromelain is still mainly being used as alternative and/or complementary therapy to the treatment with glucocorticoids, nonsteroidal antirheumatics, and immunomodulators. In this study, the anti-inflammatory action of a partially purified extract from Pseudananas macrodontes (Morr.) Harms fruits (PPE(Pm)) is presented, whose main components are cysteine endopeptidases. The effect of PPE(Pm) was assessed in carrageenan-induced and serotonin-induced rat paw edema, as well as in the cotton pellet granuloma model. Doses with equal proteolytic activity of PPE(Pm) and bromelain produced significantly similar anti-inflammatory responses in the acute inflammatory models assayed, supporting the hypothesis that proteolytic activity could be responsible for the anti-inflammatory action. On the contrary, comparable anti-inflammatory effects of PPE(Pm) and bromelain in the chronic inflammatory assay required a much lower proteolytic activity content of PPE(Pm), which could be due to a differential affinity for the protein target involved in this process. PMID:24601082

  14. Gellan gum nanohydrogel containing anti-inflammatory and anti-cancer drugs: a multi-drug delivery system for a combination therapy in cancer treatment.

    PubMed

    D'Arrigo, Giorgia; Navarro, Gemma; Di Meo, Chiara; Matricardi, Pietro; Torchilin, Vladimir

    2014-05-01

    During the last decades, it has become evident that inflammation plays a critical role in tumorigenesis: tumor microenvironment is largely orchestrated by inflammatory cells. In the present work, a novel gellan gum nanohydrogel system (NH) able to carry and deliver simultaneously anti-cancer and anti-inflammatory drugs was developed. Prednisolone was chemically linked to the carboxylic groups of gellan gum to serve as a hydrophobic moiety promoting nanohydrogel formation, whereas paclitaxel was then physically entrapped in it. NH improved drug performances, acting as paclitaxel and prednisolone solubility enhancer and favoring the drug uptake in the cells. Moreover, NH allowed an increased cytotoxic effect in vitro on several types of cancer cells due to the synergistic effect of the combination of anti-inflammatory and anti-cancer drugs. Thus, NH can be useful in a combination therapy that attacks both, malignant cells and tumor inflammatory components. PMID:24215783

  15. Dual evaluation of some novel 2-amino-substituted coumarinylthiazoles as anti-inflammatory-antimicrobial agents and their docking studies with COX-1/COX-2 active sites.

    PubMed

    Chandak, Navneet; Kumar, Pawan; Kaushik, Pawan; Varshney, Parul; Sharma, Chetan; Kaushik, Dhirender; Jain, Sudha; Aneja, Kamal R; Sharma, Pawan K

    2014-08-01

    Synthesis of total eighteen 2-amino-substituted 4-coumarinylthiazoles including sixteen new compounds (3a-o and 5b) bearing the benzenesulfonamide moiety is described in the present report. All the synthesized target compounds were examined for their in vivo anti-inflammatory (AI) activity and in vitro antimicrobial activity. Results revealed that six compounds (3 d, 3 f, 3 g, 3 h, 3 j and 3 n) exhibited pronounced anti-inflammatory activity comparable to the standard drug indomethacin. AI results were further confirmed by the docking studies of the most active (3n) and the least active compound (3a) with COX-1 and COX-2 active sites. In addition, most of the compounds exhibited moderate antimicrobial activity against Gram-positive bacteria as well as fungal yeast, S. cervisiae. Comparison between 3 and 5 indicated that incorporation of additional substituted pyrazole nucleus into the scaffold significantly enhanced AI activity. PMID:23777557

  16. Low-molecular-weight fucoidan and high-stability fucoxanthin from brown seaweed exert prebiotics and anti-inflammatory activities in Caco-2 cells

    PubMed Central

    Hwang, Pai-An; Phan, Nam Nhut; Lu, Wen-Jung; Ngoc Hieu, Bui Thi; Lin, Yen-Chang

    2016-01-01

    Background The aim of this study is to investigate the anti-inflammatory effects of low-molecular-weight fucoidan (LMF) and high-stability fucoxanthin (HS-Fucox) in a lipopolysaccharide-induced inflammatory Caco-2 cell line co-culture with B. lactis. Methods We used various methods such as transepithelial resistance (TER) assay, cytokine secretion assay, and tight junction protein mRNA expression assay to examine LMF and HS-Fucox anti-inflammatory properties. Results LMF and HS-Fucox activated probiotic growth and reduced the inflammation of the intestinal epithelial cells. Moreover, the combination of LMFHS-Fucox dramatically enhanced the intestinal epithelial barrier and immune function against the lipopolysaccharide effect by inhibiting IL-1β and TNF-α and promoting IL-10 and IFN-γ. Conclusion These findings suggested that LMF and HS-Fucox, alone or in combination, could be the potential natural compounds to enhance the immune system and have an anti-inflammatory effect on the intestinal cells. PMID:27487850

  17. Anti-inflammatory properties of new bioisosteres of indomethacin synthesized from safrole which are sulindac analogues.

    PubMed

    Pereira, E F; Pereira, N A; Lima, M E; Coelho, F A; Barreiro, E J

    1989-01-01

    The anti-inflammatory activities of new compounds (I, II, III and IV) synthesized in 30% overall yield from the abundant natural product safrole, the principal chemical constituent of the oil of sassafras (Ocotea pretiosa, Lauraceae), were determined in mice. The synthesis of these new indenyl-acetic acids (I and II) and indenyl-propionic acids (III and IV) was based on the minimal structural features of non-steroid anti-inflammatory agents of the aryl- or heteroarylcarboxylic acid group. The compounds exhibited potencies 4- to 10-fold less than that of indomethacin in inhibiting carrageenan-induced hindpaw edema. In contrast, like sulindac, all the new compounds were more potent than indomethacin in antagonizing writhing pain and increased vascular permeability caused by acetic acid. The results confirm the anticipated bioisosteric relationship between these synthetic derivatives, designed as sulindac analogues, and the classical non-steroidal anti-inflammatory agent, indomethacin.

  18. Anti-inflammatory, analgesic, and antipyretic activities of virgin coconut oil.

    PubMed

    Intahphuak, S; Khonsung, P; Panthong, A

    2010-02-01

    This study investigated some pharmacological properties of virgin coconut oil (VCO), the natural pure oil from coconut [Cocos nucifera Linn (Palmae)] milk, which was prepared without using chemical or high-heat treatment. The anti-inflammatory, analgesic, and antipyretic effects of VCO were assessed. In acute inflammatory models, VCO showed moderate anti-inflammatory effects on ethyl phenylpropiolate-induced ear edema in rats, and carrageenin- and arachidonic acid-induced paw edema. VCO exhibited an inhibitory effect on chronic inflammation by reducing the transudative weight, granuloma formation, and serum alkaline phosphatase activity. VCO also showed a moderate analgesic effect on the acetic acid-induced writhing response as well as an antipyretic effect in yeast-induced hyperthermia. The results obtained suggest anti-inflammatory, analgesic, and antipyretic properties of VCO.

  19. Synthesis and anti-inflammatory activity of 1-acylaminoalkyl-3,4-dialkoxybenzene derivatives.

    PubMed

    Labanauskas, L; Brukstus, A; Udrenaite, E; Bucinskaite, V; Susvilo, I; Urbelis, G

    2005-03-01

    New 1-acylaminoalkyl-3,4-dialkoxybenzene derivatives 17-31 were synthesized by the acylation of amines 9-16 with acyl chlorides. Amines 9-16 were obtained from aryl ketones 1-8. Aryl ketones 1-8 were synthesized by the acylation of corresponding aromatic compounds. As it was preliminary predicted by PASS (Prediction of Activity Spectra for Substance) program, all 1-acylaminoalkyl-3,4-dimethoxy- and 3,4-diethoxybenzene derivatives possess anti-inflammatory activity. Activity of compounds 18, 19, 21, 24, 26, 27, 28, 29 was similar to that of acetylsalicylic acid or ibuprofen however their acute toxicity was less than that of mentioned anti-inflammatory drugs. A series of 1-acylaminoalkyl-3,4-dimethoxybenzene, 1-acylaminoalkyl-3,4-diethoxybenzene and 6-acylaminoalkyl-2,3-dihydro-1,4-benzodioxine derivatives have been synthesized. These compounds possess moderate or strong anti-inflammatory activity and low toxicity.

  20. Anti-inflammatory, analgesic, and antipyretic activities of virgin coconut oil.

    PubMed

    Intahphuak, S; Khonsung, P; Panthong, A

    2010-02-01

    This study investigated some pharmacological properties of virgin coconut oil (VCO), the natural pure oil from coconut [Cocos nucifera Linn (Palmae)] milk, which was prepared without using chemical or high-heat treatment. The anti-inflammatory, analgesic, and antipyretic effects of VCO were assessed. In acute inflammatory models, VCO showed moderate anti-inflammatory effects on ethyl phenylpropiolate-induced ear edema in rats, and carrageenin- and arachidonic acid-induced paw edema. VCO exhibited an inhibitory effect on chronic inflammation by reducing the transudative weight, granuloma formation, and serum alkaline phosphatase activity. VCO also showed a moderate analgesic effect on the acetic acid-induced writhing response as well as an antipyretic effect in yeast-induced hyperthermia. The results obtained suggest anti-inflammatory, analgesic, and antipyretic properties of VCO. PMID:20645831

  1. Nonsteroidal anti-inflammatory drug administration in children with history of wheeze

    PubMed Central

    Sih, Kendra; Goldman, Ran D.

    2016-01-01

    Question A child in my clinic who recently sprained his ankle is experiencing pain and having trouble bearing weight on the affected leg. His mother has been giving him acetaminophen, as she was told never to use nonsteroidal anti-inflammatory drugs (NSAIDs) because of his pharmacologically controlled asthma. Is asthma in children a contraindication to giving NSAIDs? Is NSAID-exacerbated respiratory disease (NERD) a real entity? Answer Nonsteroidal anti-inflammatory drugs are effective analgesic and antipyretic medications. While described in adults with some predisposing conditions, NERD has not been clearly described in a large number of children. Nonsteroidal anti-inflammatory drugs can be recommended to children with known wheeze who do not have a history of NERD reaction. PMID:27521389

  2. Intravital Microscopic Methods to Evaluate Anti-inflammatory Effects and Signaling Mechanisms Evoked by Hydrogen Sulfide

    PubMed Central

    Zuidema, Mozow Y.; Korthuis, Ronald J.

    2016-01-01

    Hydrogen sulfide (H2S) is an endogenous gaseous signaling molecule with potent anti-inflammatory properties. Exogenous application of H2S donors, administered either acutely during an inflammatory response or as an antecedent preconditioning intervention that invokes the activation of anti-inflammatory cell survival programs, effectively limits leukocyte rolling, adhesion and emigration, generation of reactive oxygen species, chemokine and cell adhesion molecule expression, endothelial barrier disruption,capillary perfusion deficits, and parenchymal cell dysfunction and injury. This chapter focuses on intravital microscopic methods that can be used to assess the anti-inflammatory effects exerted by H2S, as well as to explore the cellular signaling mechanisms by which this gaseous molecule limits the aforementioned inflammatory responses. Recent advances include use of intravital multiphoton microscopy and optical biosensor technology to explore signaling mechanisms in vivo. PMID:25747477

  3. The impact of anti-inflammatory cytokines on the pancreatic β-cell

    PubMed Central

    Russell, M A; Morgan, N G

    2014-01-01

    Considerable efforts have been invested to understand the mechanisms by which pro-inflammatory cytokines mediate the demise of β-cells in type 1 diabetes but much less attention has been paid to the role of anti-inflammatory cytokines as potential cytoprotective agents in these cells. Despite this, there is increasing evidence that anti-inflammatory molecules such as interleukin (IL)-4, IL-10 and IL-13 can exert a direct influence of β-cell function and viability and that the circulating levels of these cytokines may be reduced in type 1 diabetes. Thus, it seems possible that targeting of anti-inflammatory pathways might offer therapeutic potential in this disease. In the present review, we consider the evidence implicating IL-4, IL-10 and IL-13 as cytoprotective agents in the β-cell and discuss the receptor components and downstream signaling pathways that mediate these effects. PMID:25322830

  4. In vitro anti-inflammatory activity of phenolic rich extracts from white and red common beans.

    PubMed

    García-Lafuente, Ana; Moro, Carlos; Manchón, Noelia; Gonzalo-Ruiz, Alicia; Villares, Ana; Guillamón, Eva; Rostagno, Mauricio; Mateo-Vivaracho, Laura

    2014-10-15

    According to epidemiological evidence, diets rich in fruits and vegetables can reduce the incidence of several chronic diseases that share an inflammatory component. These protective effects are attributed, in part, to the occurrence of different antioxidant components, mainly phenolic compounds. Our aim was to characterise phenolic composition, and to determine antioxidant and anti-inflammatory activities of phenolic rich extracts obtained from two kinds of common beans, white kidney beans (WKB) and round purple beans (RPB). Phenolic acids were the predominant component in WKB extracts, whereas RPB extracts presented higher concentrations of phenolic compounds, mainly catechin derivatives, proanthocyanidins and catechin glucoside. In addition, RPB extracts showed higher antioxidant capacity and higher anti-inflammatory activity by the reduction of NO production and cytokine mRNA expression of LPS stimulated macrophages. These results suggest that common bean extracts may be used as a source of anti-inflammatory agents as well as a dietary complement for health promotion. PMID:24837943

  5. Mushrooms: A Potential Natural Source of Anti-Inflammatory Compounds for Medical Applications

    PubMed Central

    Elsayed, Elsayed A.; El Enshasy, Hesham; Wadaan, Mohammad A. M.; Aziz, Ramlan

    2014-01-01

    For centuries, macrofungi have been used as food and medicine in different parts of the world. This is mainly attributed to their nutritional value as a potential source of carbohydrates, proteins, amino acids, and minerals. In addition, they also include many bioactive metabolites which make mushrooms and truffles common components in folk medicine, especially in Africa, the Middle East, China, and Japan. The reported medicinal effects of mushrooms include anti-inflammatory effects, with anti-inflammatory compounds of mushrooms comprising a highly diversified group in terms of their chemical structure. They include polysaccharides, terpenoids, phenolic compounds, and many other low molecular weight molecules. The aims of this review are to report the different types of bioactive metabolites and their relevant producers, as well as the different mechanisms of action of mushroom compounds as potent anti-inflammatory agents. PMID:25505823

  6. Phytochemical analysis, antioxidant and anti-inflammatory activity of calyces from Physalis peruviana.

    PubMed

    Toro, Reina M; Aragón, Diana M; Ospina, Luis F; Ramos, Freddy A; Castellanos, Leonardo

    2014-11-01

    Physalis peruviana calyces are used extensively in folk medicine. The crude ethanolic extract and some fractions of calyces were evaluated in order to explore antioxidant and anti-inflammatory activities. The anti-inflammatory activity was evaluated by the TPA-induced ear edema model. The antioxidant in vitro activity was measured by means of the superoxide and nitric oxide scavenging activity of the extracts and fractions. The butanolic fraction was found to be promising due to its anti-inflammatory and antioxidant activities. Therefore, a bio-assay guided approach was employed to isolate and identify rutin (1) and nicotoflorin (2) from their NMR spectroscopic and MS data. The identification of rutin in calyces of P. peruviana supports the possible use of this waste material for phytotherapeutic, nutraceutical and cosmetic preparations.

  7. Anti-Inflammatory Effects of GLP-1-Based Therapies beyond Glucose Control

    PubMed Central

    Lee, Young-Sun; Jun, Hee-Sook

    2016-01-01

    Glucagon-like peptide-1 (GLP-1) is an incretin hormone mainly secreted from intestinal L cells in response to nutrient ingestion. GLP-1 has beneficial effects for glucose homeostasis by stimulating insulin secretion from pancreatic beta-cells, delaying gastric emptying, decreasing plasma glucagon, reducing food intake, and stimulating glucose disposal. Therefore, GLP-1-based therapies such as GLP-1 receptor agonists and inhibitors of dipeptidyl peptidase-4, which is a GLP-1 inactivating enzyme, have been developed for treatment of type 2 diabetes. In addition to glucose-lowering effects, emerging data suggests that GLP-1-based therapies also show anti-inflammatory effects in chronic inflammatory diseases including type 1 and 2 diabetes, atherosclerosis, neurodegenerative disorders, nonalcoholic steatohepatitis, diabetic nephropathy, asthma, and psoriasis. This review outlines the anti-inflammatory actions of GLP-1-based therapies on diseases associated with chronic inflammation in vivo and in vitro, and their molecular mechanisms of anti-inflammatory action. PMID:27110066

  8. In vitro anti-inflammatory activity of phenolic rich extracts from white and red common beans.

    PubMed

    García-Lafuente, Ana; Moro, Carlos; Manchón, Noelia; Gonzalo-Ruiz, Alicia; Villares, Ana; Guillamón, Eva; Rostagno, Mauricio; Mateo-Vivaracho, Laura

    2014-10-15

    According to epidemiological evidence, diets rich in fruits and vegetables can reduce the incidence of several chronic diseases that share an inflammatory component. These protective effects are attributed, in part, to the occurrence of different antioxidant components, mainly phenolic compounds. Our aim was to characterise phenolic composition, and to determine antioxidant and anti-inflammatory activities of phenolic rich extracts obtained from two kinds of common beans, white kidney beans (WKB) and round purple beans (RPB). Phenolic acids were the predominant component in WKB extracts, whereas RPB extracts presented higher concentrations of phenolic compounds, mainly catechin derivatives, proanthocyanidins and catechin glucoside. In addition, RPB extracts showed higher antioxidant capacity and higher anti-inflammatory activity by the reduction of NO production and cytokine mRNA expression of LPS stimulated macrophages. These results suggest that common bean extracts may be used as a source of anti-inflammatory agents as well as a dietary complement for health promotion.

  9. Simple synthesis of modafinil derivatives and their anti-inflammatory activity.

    PubMed

    Jung, Jae-Chul; Lee, Yeonju; Son, Jee-Young; Lim, Eunyoung; Jung, Mankil; Oh, Seikwan

    2012-09-03

    Simple synthesis of modafinil derivatives and their biological activity are described. The key synthetic strategies involve substitution and coupling reactions. We determined the anti-inflammatory effects of modafinil derivatives in cultured BV2 cells by measuring the inhibition of nitrite production and expression of iNOS and COX-2 after LPS stimulation. It was found that for sulfide analogues introduction of aliphatic groups on the amide part (compounds 11a–d) resulted in lower anti-inflammatory activity compared with cyclic or aromatic moieties (compounds 11e–k). However, for the sulfoxide analogues, introduction of aliphatic moieties (compounds 12a–d) showed higher anti-inflammatory activity than cyclic or aromatic fragments (compounds 12e–k) in BV-2 microglia cells.

  10. Anti-inflammatory, Antioxidant and Antimicrobial Effects of Artemisinin Extracts from Artemisia annua L.

    PubMed Central

    Kim, Wan-Su; Choi, Woo Jin; Lee, Sunwoo; Kim, Woo Joong; Lee, Dong Chae; Sohn, Uy Dong; Shin, Hyoung-Shik

    2015-01-01

    The anti-inflammatory, antioxidant, and antimicrobial properties of artemisinin derived from water, methanol, ethanol, or acetone extracts of Artemisia annua L. were evaluated. All 4 artemisinin-containing extracts had anti-inflammatory effects. Of these, the acetone extract had the greatest inhibitory effect on lipopolysaccharide-induced nitric oxide (NO), prostaglandin E2 (PGE2), and proinflammatory cytokine (IL-1β , IL-6, and IL-10) production. Antioxidant activity evaluations revealed that the ethanol extract had the highest free radical scavenging activity, (91.0±3.2%), similar to α-tocopherol (99.9%). The extracts had antimicrobial activity against the periodontopathic microorganisms Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum subsp. animalis, Fusobacterium nucleatum subsp. polymorphum, and Prevotella intermedia. This study shows that Artemisia annua L. extracts contain anti-inflammatory, antioxidant, and antimicrobial substances and should be considered for use in pharmaceutical products for the treatment of dental diseases. PMID:25605993

  11. Analgesic and Anti-inflammatory action of Opuntia elatior Mill fruits

    PubMed Central

    Chauhan, Sanjay P.; Sheth, Navin R.; Suhagia, Bhanubhai N.

    2015-01-01

    Background: Opuntia elatio Mill is a xerophytic plant with potentially active nutrients. It is traditionally appreciated for its pharmacological properties; however, the scientific information on this plant is insufficient. Objective: The present study evaluates the antinociceptive and anti-inflammatory action of prickly pear. Materials and Methods: Writhing and tail-immersion tests were carried out to evaluate analgesic action, while the carrageenan-induced paw edema and neutrophil adhesion tests were conducted in Albino wistar rats to assess anti-inflammatory action. Results: ED50 values of the fruit juice in writhing, tail immersion, and paw edema test were 0.919, 2.77, and 9.282 ml/kg, respectively. The fruits of Opuntia produced analgesic and anti-inflammatory action in a dose-dependent manner. Conclusion: The results establish the folklore use of prickly pear may be due to the presence of betacyanin and/or other phenolic compounds. PMID:26166996

  12. Renal papillary necrosis following regular consumption of non-steroidal anti-inflammatory drugs.

    PubMed

    Munn, E; Lynn, K L; Bailey, R R

    1982-04-14

    Since phenacetin was removed from the Drug Tariff in New Zealand in 1974 there has been a decrease in the number of patients with analgesic nephropathy entering dialysis-transplant programmes. Since then there has been an increase in the consumption of non-steroidal anti-inflammatory agents. Experimental work in animals has shown that these drugs can cause renal papillary necrosis. We report two men with sever osteoarthritis who regularly ingested anti-inflammatory agents and developed papillary necrosis with renal insufficiency and hypertension. One patient consumed 0.5 kg of indomethacin over 10 years and the other 3.5 kg of ibuprofen, 200 g of naproxen and an uncertain amount of ketoprofen over 13 years. The increased chronic usage of non-steroidal anti-inflammatory drugs could bring about an upsurge in the incidence of papillary necrosis.

  13. Mushrooms: a potential natural source of anti-inflammatory compounds for medical applications.

    PubMed

    Elsayed, Elsayed A; El Enshasy, Hesham; Wadaan, Mohammad A M; Aziz, Ramlan

    2014-01-01

    For centuries, macrofungi have been used as food and medicine in different parts of the world. This is mainly attributed to their nutritional value as a potential source of carbohydrates, proteins, amino acids, and minerals. In addition, they also include many bioactive metabolites which make mushrooms and truffles common components in folk medicine, especially in Africa, the Middle East, China, and Japan. The reported medicinal effects of mushrooms include anti-inflammatory effects, with anti-inflammatory compounds of mushrooms comprising a highly diversified group in terms of their chemical structure. They include polysaccharides, terpenoids, phenolic compounds, and many other low molecular weight molecules. The aims of this review are to report the different types of bioactive metabolites and their relevant producers, as well as the different mechanisms of action of mushroom compounds as potent anti-inflammatory agents.

  14. Anti-inflammatory, antinociceptive, and antipyretic effects of Lantana trifolia Linnaeus in experimental animals.

    PubMed

    Uzcátegui, Bercy; Avila, Dinorah; Suárez-Roca, Heberto; Quintero, Luis; Ortega, José; González, Beatriz

    2004-12-01

    Lantana trifolia L. (Verbenaceae) is traditionally used as an anti-inflammatory medicinal plant in Venezuela. The methanol extract of the aerial parts of L. trifolia were assessed for the anti-inflammatory, anti-nociceptive and anti-pyretic properties. The extract produced an inhibition of carrageenan-induced edema in the rat paw over a dose range of 10-300 mg/kg i.p.; the dose-response curve was bell-shaped with a maximal effect at 100 mg/kg. The extract also produced a small but significant increase in the response latency of rats subjected to the hot plate, a thermal pain test that only detects analgesia by high-efficacy agents. The extract did not exhibit antipyretic activity. Thus, the L. trifolia extract could have therapeutically relevant anti-inflammatory and analgesic properties in humans. PMID:15602898

  15. Anti-inflammatory effect and low ulcerogenic activity of etodolac, a cyclooxygenase-2 selective non-steroidal anti-inflammatory drug, on adjuvant-induced arthritis in rats.

    PubMed

    Tachibana, Masaki; Inoue, Naoki; Yoshida, Eri; Matsui, Masami; Ukai, Yojiro; Yano, Junichi

    2003-06-01

    Adjuvant arthritic rats are known to be more susceptible to gastric damage induced by non-steroidal anti-inflammatory drugs (NSAIDs) than are normal rats. We compared the relative gastric safety profile of etodolac with those of meloxicam, diclofenac sodium and indometacin in adjuvant arthritic rats and normal rats or mice. As a measure of the safety profiles of NSAIDs, we used the safety index, the ratio of the dose that elicits gastric mucosal lesions to the effective dose as an anti-inflammatory or analgesic compound. The anti-inflammatory or analgesic effects of NSAIDs were assessed by paw swelling in adjuvant arthritic rats, and either carrageenin-induced paw edema or brewer's yeast-induced hyperalgesia, as well as acetic acid-induced writhing, in normal rats or mice. In addition, we also investigated the effects of these NSAIDs on human COX-1 and COX-2 activity. Etodolac and other NSAIDs inhibited paw swelling and caused gastric mucosal lesions in adjuvant arthritic rats in a dose-dependent manner. Etodolac showed the highest UD(50) value and safety index among these NSAIDs in arthritic rats. In normal rats, etodolac also showed the highest UD(50) value and safety index, except when its effects were assessed by acetic acid-induced writhing. Etodolac and meloxicam showed selectivity for human COX-2 over COX-1. In contrast, diclofenac sodium and indometacin were selective for COX-1. These results suggest that etodolac, a COX-2 selective NSAID, has anti-inflammatory effects with a better safety profile for the stomach than do non-selective NSAIDs, including diclofenac sodium and indometacin, in adjuvant arthritic as well as normal rats.

  16. QSAR and Docking Studies on Capsazepine Derivatives for Immunomodulatory and Anti-Inflammatory Activity

    PubMed Central

    Shukla, Aparna; Sharma, Pooja; Prakash, Om; Singh, Monika; Kalani, Komal; Khan, Feroz; Bawankule, Dnyaneshwar Umrao; Luqman, Suaib; Srivastava, Santosh Kumar

    2014-01-01

    Capsazepine, an antagonist of capsaicin, is discovered by the structure and activity relationship. In previous studies it has been found that capsazepine has potency for immunomodulation and anti-inflammatory activity and emerging as a favourable target in quest for efficacious and safe anti-inflammatory drug. Thus, a 2D quantitative structural activity relationship (QSAR) model against target tumor necrosis factor-α (TNF-α) was developed using multiple linear regression method (MLR) with good internal prediction (r2 = 0.8779) and external prediction (r2pred = 0.5865) using Discovery Studio v3.5 (Accelrys, USA). The predicted activity was further validated by in vitro experiment. Capsazepine was tested in lipopolysaccharide (LPS) induced inflammation in peritoneal mouse macrophages. Anti-inflammatory profile of capsazepine was assessed by its potency to inhibit the production of inflammatory mediator TNF-α. The in vitro experiment indicated that capsazepine is an efficient anti-inflammatory agent. Since, the developed QSAR model showed significant correlations between chemical structure and anti-inflammatory activity, it was successfully applied in the screening of forty-four virtual derivatives of capsazepine, which finally afforded six potent derivatives, CPZ-29, CPZ-30, CPZ-33, CPZ-34, CPZ-35 and CPZ-36. To gain more insights into the molecular mechanism of action of capsazepine and its derivatives, molecular docking and in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) studies were performed. The results of QSAR, molecular docking, in silico ADMET screening and in vitro experimental studies provide guideline and mechanistic scope for the identification of more potent anti-inflammatory & immunomodulatory drug. PMID:25003344

  17. Analgesic and Anti-Inflammatory Activities of Rosa taiwanensis Nakai in Mice.

    PubMed

    Tsai, Der-Shiang; Huang, Mei-Hsuen; Tsai, Jen-Chieh; Chang, Yuan-Shuang; Chiu, Yung-Jia; Lin, Yen-Chang; Wu, Lung-Yuan; Peng, Wen-Huang

    2015-05-01

    In this study, we evaluated the analgesic and anti-inflammatory activities of a 70% ethanol extract from Rosa taiwanensis Nakai (RTEtOH). The analgesic effect was determined using acetic acid-induced writhing response and formalin test. The anti-inflammatory activity was evaluated by λ-carrageenan-induced paw edema in mice. The anti-inflammatory mechanism of RTEtOH was examined by measuring the levels of cyclooxygenase-2 (COX-2), nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and malondialdehyde (MDA) in the paw edema tissue and the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GRd) in the liver tissue. The betulinic acid and oleanolic acid contents of RTEtOH were assayed by HPLC. The results showed that RTEtOH decreased the acetic acid-induced writhing responses (1.0 g/kg) and the late phase of the formalin-induced licking time (0.5 and 1.0 g/kg). In the anti-inflammatory models, RTEtOH (0.5 and 1.0 g/kg) reduced the paw edema at 3, 4, and 5 h after λ-carrageenan administration. Moreover, the anti-inflammatory mechanisms might be due to the decreased levels of COX-2, TNF-α, IL-1β, and IL-6, as well as the inhibition of NO and MDA levels through increasing the activities of SOD, GPx, and GRd. The contents of two active compounds, betulinic acid and oleanolic acid, were quantitatively determined. This study demonstrated the analgesic and anti-inflammatory activities of RTEtOH and provided evidence to support its therapeutic use in inflammatory diseases.

  18. Analgesic and Anti-Inflammatory Activities of Rosa taiwanensis Nakai in Mice

    PubMed Central

    Tsai, Der-Shiang; Huang, Mei-Hsuen; Tsai, Jen-Chieh; Chang, Yuan-Shuang; Chiu, Yung-Jia; Lin, Yen-Chang

    2015-01-01

    Abstract In this study, we evaluated the analgesic and anti-inflammatory activities of a 70% ethanol extract from Rosa taiwanensis Nakai (RTEtOH). The analgesic effect was determined using acetic acid-induced writhing response and formalin test. The anti-inflammatory activity was evaluated by λ-carrageenan-induced paw edema in mice. The anti-inflammatory mechanism of RTEtOH was examined by measuring the levels of cyclooxygenase-2 (COX-2), nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and malondialdehyde (MDA) in the paw edema tissue and the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GRd) in the liver tissue. The betulinic acid and oleanolic acid contents of RTEtOH were assayed by HPLC. The results showed that RTEtOH decreased the acetic acid-induced writhing responses (1.0 g/kg) and the late phase of the formalin-induced licking time (0.5 and 1.0 g/kg). In the anti-inflammatory models, RTEtOH (0.5 and 1.0 g/kg) reduced the paw edema at 3, 4, and 5 h after λ-carrageenan administration. Moreover, the anti-inflammatory mechanisms might be due to the decreased levels of COX-2, TNF-α, IL-1β, and IL-6, as well as the inhibition of NO and MDA levels through increasing the activities of SOD, GPx, and GRd. The contents of two active compounds, betulinic acid and oleanolic acid, were quantitatively determined. This study demonstrated the analgesic and anti-inflammatory activities of RTEtOH and provided evidence to support its therapeutic use in inflammatory diseases. PMID:25494361

  19. Antimicrobial, Anti-inflammatory and Antioxidant Activities of Jatropha multifida L. (Euphorbiaceae)

    PubMed Central

    Anani, Kokou; Adjrah, Yao; Améyapoh, Yaovi; Karou, Simplice Damintoti; Agbonon, Amegnona; de Souza, Comlan; Gbeassor, Messanvi

    2016-01-01

    Background: Jatropha multifida is used in Togolease folk medicine for the healing of chronic wounds. Objective: This study aims to investigate antibacterial, anti-inflammatory and antioxidant activities of the leaves ethanolic extract. Materials and Methods: The antimicrobial activity was assayed by National Committee for Clinical Laboratory Standards broth microdilution method on strains of Staphylococcus aureus and Pseudomoas aeruginosa isolated from wounds, whereas the anti-inflammatory activity was performed by carrageenan and histamine induced paw edema method in rat modele. The 2, 2-diphenyl-1picrylhydrazyl (DPPH) free radical scavenging and ferric reducing antioxidant power (FRAP) were used for the antioxidant activity. Results: The antibacterial assay showed an in vitro growth inhibition of P. aeruginosa and S. aureus in dose-dependent manner, with minimum inhibitory concentration values ranging from 2.5 to 3.12 mg/mL for S. aureus and from 6.25 to 12.5 mg/mL for P. aeruginosa. The maximum paw anti-inflammatory effect occurred after 3 and 5 h administration of histamine and carrageenan, respectively. The DPPH radical scavenging and the FRAP assays yielded weak antioxidant activity. Conclusion: J. multifida possesses antibacterial and anti-inflammatory activities that could justify the use of the plant for the treatment of wounds in the folk medicine. SUMMARY Antibacterial on germs isolated from wound, anti-inflammatory and antioxidant activities of Jatropha multifida were assayed by NCCLS broth method, carrageenan and histamine, DPPH and FRAP respectively. The results indicated that Jatropha multifida possesses antibacterial and anti-inflammatory and weak antioxidant activities that could justify its use for the treatment of wounds in the folk medicine. PMID:27034606

  20. Variation in antibacterial and anti-inflammatory activity of different growth forms of Malva parviflora and evidence for synergism of the anti-inflammatory compounds.

    PubMed

    Shale, T L; Stirk, W A; van Staden, J

    2005-01-01

    Malva parviflora leaves and roots were collected from five sites within the Qacha's Nek District in Lesotho. These plants had two distinct growth forms--upright and prostrate. Hexane, methanol and water extracts were made from the plant material and tested for antibacterial and anti-inflammatory activity using the disc diffusion and cyclooxygenase-1 (Cox-1) bioassays, respectively. Hexane, methanol and water extracts made from Malva parviflora with a prostrate growth form inhibited the growth of Gram-positive and Gram-negative bacteria, while extracts made from plants with an upright growth form inhibited the growth of Gram-positive bacteria only. Cox-1 anti-inflammatory activity of hexane, methanol and water extracts did not show any variation between the two growth forms. The hexane extracts of both the leaves and roots were the most inhibitory. The water extracts had the least inhibitory activity. Bioassay-guided fractionation of the root dichloromethane extract showed that Cox-1 anti-inflammatory activity was caused by at least two compounds that acted synergistically to produce the biological effect.

  1. Treating tendinopathy: perspective on anti-inflammatory intervention and therapeutic exercise.

    PubMed

    Joseph, Michael F; Denegar, Craig R

    2015-04-01

    Tendinopathy is a common and complex disorder. Once viewed as an inflammatory condition labeled tendinitis, it is now viewed along a continuum that can lead to tissue necrosis and risk of tendon rupture. Anti-inflammatory medications can alter symptoms but may also promote tissue degeneration. Loading of the tendon through exercise, especially exercise involving eccentric muscle contraction, has been shown to promote symptom resolution and functional recovery in many patients. This article reviews the pathoetiology of tendinopathy and the role anti-inflammatory interventions and therapeutic exercise in treatment of active patients.

  2. Synthesis, anti-inflammatory evaluation and docking studies of some new fluorinated fused quinazolines.

    PubMed

    Balakumar, C; Lamba, P; Kishore, D Pran; Narayana, B Lakshmi; Rao, K Venkat; Rajwinder, K; Rao, A Raghuram; Shireesha, B; Narsaiah, B

    2010-11-01

    A series of novel 8/10-trifluoromethyl-substituted-imidazo[1,2-c] quinazolines have been synthesized and evaluated in vivo (rat paw edema) for their anti-inflammatory activity and in silico (docking studies) to recognize the hypothetical binding motif of the title compounds with the cyclooxygenase isoenzymes (COX-1 and COX-2) employing GOLD (CCDC, 4.0.1 version) software. The compounds, 9b and 10b, were found to have good anti-inflammatory activity [around 80% of the standard: indomethacin]. The binding mode of the title compounds has been proposed based on the docking studies.

  3. Dental gel viscosity parameters and pharmaceutical availability of non-steroidal anti-inflammatory drugs.

    PubMed

    Kołodziejska, Justyna; Zgoda, Marian Mikołaj

    2004-01-01

    Model prescription for dental anti-inflammatory gels with carboxymethylcellulose sodium salt and non-ionic surfactants have been worked out. Viscosity parameters of 10 variant gel forms were investigated and an attempt on their interpretation was undertaken in relation to pharmaceutical availability of non-steroidal anti-inflammatory drugs (diclofenac, ibuprofen sodium). Viscosity tests demonstrated higher pharmaceutical availability of ibuprofen sodium than of diclofenac sodium particularly from model gels with surfactants of low number of oxyethylene segments in the structure. The above has been confirmed by in vitro studies on the kinetics of therapeutic agent penetration into external compartment.

  4. Anti-Inflammatory Activity of Aqueous Extract of Beta Vulgaris L.

    PubMed Central

    Jain, Swati; Garg, Vipin Kumar; Sharma, Pramod Kumar

    2011-01-01

    The present study deals with the investigation of phytochemically evaluated aqueous extract of leaves of Beta vulgaris for its anti-inflammatory activity. The anti-inflammatory activity was evaluated by carrageenan induced rat paw oedema method for acute inflammation and cotton pellet granuloma method for chronic inflammation. The standard drug used was indomethacin (10 mg/kg) for both the models. In both methods, aqueous extract at a dose level of 1000 mg/kg has shown significant activity which is comparable to that of the standard PMID:24826006

  5. Synthesis, anti-inflammatory evaluation and docking studies of some new fluorinated fused quinazolines.

    PubMed

    Balakumar, C; Lamba, P; Kishore, D Pran; Narayana, B Lakshmi; Rao, K Venkat; Rajwinder, K; Rao, A Raghuram; Shireesha, B; Narsaiah, B

    2010-11-01

    A series of novel 8/10-trifluoromethyl-substituted-imidazo[1,2-c] quinazolines have been synthesized and evaluated in vivo (rat paw edema) for their anti-inflammatory activity and in silico (docking studies) to recognize the hypothetical binding motif of the title compounds with the cyclooxygenase isoenzymes (COX-1 and COX-2) employing GOLD (CCDC, 4.0.1 version) software. The compounds, 9b and 10b, were found to have good anti-inflammatory activity [around 80% of the standard: indomethacin]. The binding mode of the title compounds has been proposed based on the docking studies. PMID:20800934

  6. Anti-inflammatory activity of thiabendazole and its relation to parasitic disease.

    PubMed

    van Arman, G G; Campbell, W C

    1975-01-01

    In 6 differnet animal assays in the laboratory, thiabendazole had clear anti-inflammatory effect, though it was less potent than aspirin in all assays. These findings add support to clinical suggestions that the drug may have anti-inflammatory properties in man. Such properties may contribute to the clinical response observed following the use of thiabendazole in cases of trichinosis, cutaneous larva migrans, visceral larva migrans, dracunculosis and scabies. In parasitic infections in which corticosteroids are commonly used in clinical management, notably trichinosis, the fact that thiabendazole does not appear to have immunosuppressive activity may confer an added clinical advantage.

  7. The anti-inflammatory effects of dexamethasone and therapeutic ultrasound in oral surgery.

    PubMed

    ElHag, M; Coghlan, K; Christmas, P; Harvey, W; Harris, M

    1985-02-01

    A single blind, controlled trial was carried out to assess the anti-inflammatory effects of 10 mg dexamethasone given pre- and post-operatively and also ultrasound therapy in patients following the removal of impacted lower third molars. Facial swelling and trismus were significantly reduced in both the dexamethasone- and the ultrasound-treated groups compared with an untreated control group. This first report of the anti-inflammatory properties of ultrasound in a controlled clinical trial indicates its potential clinical use in reducing post-operative morbidity in oral surgery.

  8. Reflex control of inflammation by the splanchnic anti-inflammatory pathway is sustained and independent of anesthesia.

    PubMed

    Martelli, Davide; Yao, Song T; Mancera, Julian; McKinley, Michael J; McAllen, Robin M

    2014-11-01

    Following an immune challenge, there is two-way communication between the nervous and immune systems. It is proposed that a neural reflex--the inflammatory reflex--regulates the plasma levels of the key proinflammatory cytokine TNF-α, and that its efferent pathway is in the splanchnic sympathetic nerves. The evidence for this reflex is based on experiments on anesthetized animals, but anesthesia itself suppresses inflammation, confounding interpretation. Here, we show that previous section of the splanchnic nerves strongly enhances the levels of plasma TNF-α in conscious rats 90 min after they received intravenous LPS (60 μg/kg). The same reflex mechanism, therefore, applies in conscious as in anesthetized animals. In anesthetized rats, we then determined the longer-term effects of splanchnic nerve section on responses to LPS (60 μg/kg iv). We confirmed that prior splanchnic nerve section enhanced the early (90 min) peak in plasma TNF-α and found that it reduced the 90-min peak of the anti-inflammatory cytokine IL-10; both subsequently fell to low levels in all animals. Splanchnic nerve section also enhanced the delayed rise in two key proinflammatory cytokines IL-6 and interferon γ. That enhancement was undiminished after 6 h, when other measured cytokines had subsided. Finally, LPS treatment caused hypotensive shock in rats with cut splanchnic nerves but not in sham-operated animals. These findings demonstrate that reflex activation of the splanchnic anti-inflammatory pathway has a powerful and sustained restraining influence on inflammatory processes.

  9. The anti-inflammatory effect of diclofenac is considerably augmented by topical capsaicinoids-containing patch in carrageenan-induced paw oedema of rat.

    PubMed

    Ercan, Nilufer; Uludag, Mecit Orhan; Agis, Erol Rauf; Demirel-Yilmaz, Emine

    2013-12-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most used drugs in musculoskeletal disorders, but their systemic adverse effects limit their therapeutic benefit in local inflammation. On the other hand, topical preparations of capsaicinoids are widely used for musculoskeletal disorders as a complementary therapy. In this study, the effects of both topical capsaicinoids-containing patch and local subcutaneous capsaicin application on the anti-inflammatory action of NSAID were examined. Carrageenan-induced paw oedema of rats was used as the inflammation model. The volume and weight of the paw oedema and plasma extravasation in the paw were determined after carrageenan injection. The systemic application of diclofenac (3 mg/kg), which is an NSAID, significantly decreased the volume and weight of the paw oedema. Topical capsaicinoids-containing patch application or local capsaicin injection (2, 10, 20 μg/paw) alone did not cause any effect on oedema volume and weight. However, the combination of diclofenac with topical capsaicinoids-containing patch significantly increased the effectiveness of diclofenac on inflammation. Evans blue content of the paws that represents plasma extravasation was decreased by capsaicinoids-containing patch with and without diclofenac and diclofenac combination with the lowest dose of capsaicin injection. The results of this study indicate that topical application of capsaicinoids-containing patch enhances the anti-inflammatory effect of diclofenac and its beneficial effect may not purely relate to its capsaicin content. In the treatment of local inflammatory disorders, the combination of NSAID with topical capsaicinoids-containing patch could increase the anti-inflammatory efficiency of drug without systemic side effects.

  10. Anti-Inflammatory Effects of Concentrated Ethanol Extracts of Edelweiss (Leontopodium alpinum Cass.) Callus Cultures towards Human Keratinocytes and Endothelial Cells

    PubMed Central

    Daniela, Lulli; Alla, Potapovich; Maurelli, Riccardo; Elena, Dellambra; Giovanna, Pressi; Vladimir, Kostyuk; Roberto, Dal Toso; Chiara, De Luca; Saveria, Pastore; Liudmila, Korkina

    2012-01-01

    Edelweiss (Leontopodium alpinum Cass.) is traditionally employed in folk medicine as an anti-inflammatory remedy. In nature, the plant is sparsely available and protected; therefore production of callus cultures was established. A concentrated ethanolic extract of culture homogenate, with leontopodic acid representing 55 ± 2% of the total phenolic fraction (ECC55), was characterized for anti-inflammatory properties in primary human keratinocytes (PHKs) and endotheliocytes (HUVECs). Inflammatory responses were induced by UVA+UVB, lipopolysaccharide (LPS), oxidized low-density lipoprotein (oxLDL), and a mixture of proinflammatory cytokines. Trichostatin A, a sirtuin inhibitor, was used to induce keratinocyte inflammatory senescence. ECC55 (10–50 μg/mL) protected PHK from solar UV-driven damage, by enhancing early intracellular levels of nitric oxide, although not affecting UV-induced expression of inflammatory genes. Comparison of the dose-dependent inhibition of chemokine (IL-8, IP-10, MCP-1) and growth factor (GM-CSF) release from PHK activated by TNFα + IFNγ showed that leontopodic acid was mainly responsible for the inhibitory effects of ECC55. Sirtuin-inhibited cell cycle, proliferation, and apoptosis markers were restored by ECC55. The extract inhibited LPS-induced IL-6 and VCAM1 genes in HUVEC, as well as oxLDL-induced selective VCAM1 overexpression. Conclusion. Edelweiss cell cultures could be a valuable source of anti-inflammatory substances potentially applicable for chronic inflammatory skin diseases and bacterial and atherogenic inflammation. PMID:23093820

  11. Anti-inflammatory effects of concentrated ethanol extracts of Edelweiss (Leontopodium alpinum Cass.) callus cultures towards human keratinocytes and endothelial cells.

    PubMed

    Daniela, Lulli; Alla, Potapovich; Maurelli, Riccardo; Elena, Dellambra; Giovanna, Pressi; Vladimir, Kostyuk; Roberto, Dal Toso; Chiara, De Luca; Saveria, Pastore; Liudmila, Korkina

    2012-01-01

    Edelweiss (Leontopodium alpinum Cass.) is traditionally employed in folk medicine as an anti-inflammatory remedy. In nature, the plant is sparsely available and protected; therefore production of callus cultures was established. A concentrated ethanolic extract of culture homogenate, with leontopodic acid representing 55 ± 2% of the total phenolic fraction (ECC55), was characterized for anti-inflammatory properties in primary human keratinocytes (PHKs) and endotheliocytes (HUVECs). Inflammatory responses were induced by UVA+UVB, lipopolysaccharide (LPS), oxidized low-density lipoprotein (oxLDL), and a mixture of proinflammatory cytokines. Trichostatin A, a sirtuin inhibitor, was used to induce keratinocyte inflammatory senescence. ECC55 (10-50 μg/mL) protected PHK from solar UV-driven damage, by enhancing early intracellular levels of nitric oxide, although not affecting UV-induced expression of inflammatory genes. Comparison of the dose-dependent inhibition of chemokine (IL-8, IP-10, MCP-1) and growth factor (GM-CSF) release from PHK activated by TNFα + IFNγ showed that leontopodic acid was mainly responsible for the inhibitory effects of ECC55. Sirtuin-inhibited cell cycle, proliferation, and apoptosis markers were restored by ECC55. The extract inhibited LPS-induced IL-6 and VCAM1 genes in HUVEC, as well as oxLDL-induced selective VCAM1 overexpression. Conclusion. Edelweiss cell cultures could be a valuable source of anti-inflammatory substances potentially applicable for chronic inflammatory skin diseases and bacterial and atherogenic inflammation.

  12. Ultrasonic promoted synthesis of novel s-triazine-Schiff base derivatives; molecular structure, spectroscopic studies and their preliminary anti-proliferative activities

    NASA Astrophysics Data System (ADS)

    El-Faham, Ayman; Soliman, Saied M.; Ghabbour, Hazem A.; Elnakady, Yasser A.; Mohaya, Talal A.; Siddiqui, Mohammed R. H.; Albericio, Fernando

    2016-12-01

    Novel series of s-triazine-Schiff base derivatives were synthesized employing ultrasonic irradiation and characterized by NMR (1H and 13C), FT-IR, and elemental analysis. The use of ultrasonic irradiation has allowed the preparation of the target products with better yields in shorter reaction time and excellent purities compared to the conventional heating. X-ray single crystal diffraction experiments verified the molecular structure of four from the new prepared s-triaizne-Schiff base derivatives. The molecular structures of the studied compounds are computerized using DFT/B3LYP method. The effects of substituent at the triazine and phenyl ring on the electronic and spectroscopic properties of the studied compounds were also investigated. The natural atomic charges showed that pipridino-s-triazine derivatives are richer in electrons than those having morpholino derivatives. The anti-proliferative effects for the prepared compounds were tested against three different cancer cell lines.

  13. Acylated oleanane-type triterpene saponins from the flowers of Bellis perennis show anti-proliferative activities against human digestive tract carcinoma cell lines.

    PubMed

    Ninomiya, Kiyofumi; Motai, Chiaki; Nishida, Eriko; Kitagawa, Niichiro; Yoshihara, Kazuya; Hayakawa, Takao; Muraoka, Osamu; Li, Xuezheng; Nakamura, Seikou; Yoshikawa, Masayuki; Matsuda, Hisashi; Morikawa, Toshio

    2016-07-01

    Seven oleanane-type triterpene saponin bisdesmosides, perennisaponins N-T (1-7), were newly isolated from a methanol extract of daisy, the flowers of Bellis perennis L. (Asteraceae). The structures were determined based on chemical and physicochemical data and confirmed using previously isolated related compounds as references. The isolates, including 13 previously reported perennisaponins A-M (8-20), exhibited anti-proliferative activities against human digestive tract carcinoma HSC-2, HSC-4, and MKN-45 cells. Among them, perennisaponin O (2, IC50 = 11.2, 14.3, and 6.9 μM, respectively) showed relatively strong activities. The mechanism of action of 2 against HSC-2 was found to involve apoptotic cell death. PMID:27178360

  14. Effect of ring substitution on the metabolic fate and anti-inflammatory activity of some prodolic acid analogs.

    PubMed

    Robinson, W T; Martel, R R; Ferdinandi, E; Kraml, M

    1977-12-01

    Prodolic acid, 1-n-propyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid, exhibits potent anti-inflammatory activity in adjuvant arthritic rats. The potency of prodolic acid is enhanced by indole ring substitution. This increase correlated well with higher and sustained drug concentrations in the serum of normal animals. Pharmacokinetic studies demonstrated that ring substitution prolonged the serum half-life without affecting the absorption or volume of distribution. Because, in the rat, indole ring hydroxylation is a major pathway for the disposition of prodolic acid, we ascribe the increased pharmacological activity of ring substituted derivatives to the interference of substituents with the hydroxylation reaction. PMID:925966

  15. Grapefruit juice potentiates the anti-inflammatory effects of diclofenac on the carrageenan-induced rat's paw oedema.

    PubMed

    Mahgoub, Afaf A

    2002-01-01

    The anti-inflammatory effect of diclofenac alone or in combination with double strength grapefruit juice was investigated on carrageenan-induced rat's paw oedema. Paw was measured by using a plethysmometer 3 h after injecting the phlogestic agent. There was significant inhibition (P< 0.05) of the oedematous response after oral administration of diclofenac alone (1, 2.5, 5 mg kg(-1)p.o.) in a dose-dependent manner. Coadministration of grapefruit juice (10 ml kg(-1)p.o.) orally with all doses of diclofenac, enhanced the inhibitory effect of diclofenac on rat's paw oedema. Double-strength grapefruit juice has synergistic inhibitory effect on rat's paw oedema when administered in combination with diclofenac.

  16. Bioassay-guided evaluation of anti-inflammatory and antinociceptive activities of pistachio, Pistacia vera L.

    PubMed

    Orhan, I; Küpeli, E; Aslan, M; Kartal, M; Yesilada, E

    2006-04-21

    The ethanolic and aqueous extracts prepared from different parts of Pistacia vera L. (Anacardiaceae) as well as its oleoresin were evaluated for their in vivo anti-inflammatory and antinociceptive activities. Among the extracts screened, only the oleoresin was shown to possess a marked anti-inflammatory activity against carrageenan-induced hind paw edema model in mice without inducing any gastric damage at both 250 and 500 mg/kg doses whereas the rest of the extracts were totally inactive. While the oleoresin was found to display significant antinociceptive activity at 500 mg/kg dose, the ethanolic and aqueous extracts belonging to fruit, leaf, branch and peduncle of Pistacia vera did not exhibit any noticeable antinociception in p-benzoquinone-induced abdominal contractions in mice. Fractionation of the oleoresin indicated the n-hexane fraction to be active, which further led to recognition of some monoterpenes, mainly alpha-pinene (77.5%) by capillary gas chromatography-mass spectrometry (GC-MS) as well as the oleoresin itself. alpha-Pinene was also assessed for its antinociceptive and anti-inflammatory activities in the same manner and exerted a moderate anti-inflammatory effect at 500 mg/kg dose.

  17. Design and In Vivo Anti-Inflammatory Effect of Ketoprofen Delayed Delivery Systems.

    PubMed

    Cerciello, Andrea; Auriemma, Giulia; Morello, Silvana; Pinto, Aldo; Del Gaudio, Pasquale; Russo, Paola; Aquino, Rita P

    2015-10-01

    For the treatment of inflammatory-based diseases affected by circadian rhythms, the development of once-daily dosage forms is required to target early morning symptoms. In this study, Zn-alginate beads containing ketoprofen (K) were developed by a tandem technique prilling/ionotropic gelation. The effect of main critical variables on particles micromeritics, inner structure as well as on drug loading and in vitro drug release was studied. The in vivo anti-inflammatory efficacy was evaluated using a modified protocol of carrageenan-induced edema in rat paw administering beads to rats by oral gavage at 0, 3, or 5 h before edema induction. Good drug loading and desired particle size and morphology were obtained for the optimized formulation F20. In vitro dissolution studies showed that F20 had a gastroresistant behavior and delayed release of the drug in simulated intestinal fluid. The in vitro delayed release pattern was clearly reflected in the prolonged anti-inflammatory effect in vivo of F20, compared to pure ketoprofen; F20, administered 3 h before edema induction, showed a significant anti-inflammatory activity, reducing maximum paw volume in response to carrageenan injection, whereas no response was observed for ketoprofen. The designed beads appear a promising platform suitable for a delayed release of anti-inflammatory drugs. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3451-3458, 2015. PMID:26088065

  18. Analgesic, Anti-Inflammatory and Anticancer Activities of Extra Virgin Olive Oil

    PubMed Central

    Senovilla, Laura; Jemaà, Mohamed; Ben-Attia, Mossadok

    2013-01-01

    Background. In folk medicine, extra virgin olive oil (EVOO) is used as a remedy for a variety of diseases. This study investigates the in vivo antinociceptive, anti-inflammatory, and anti-cancer effects of EVOO on mice and rats. Materials and Methods. In this experimental study, using the acetic acid-induced writhing and formalin tests in mice, the analgesic effect of EVOO was evaluated. Acetylsalicylic acid and morphine were used as standard drugs, respectively. The anti-inflammatory activity was investigated by means of the carrageenan-induced paw edema model in rats using acetylsalicylic acid and dexamethasone as standard drugs. Last, the xenograft model in athymic mice was used to evaluate the anticancer effect in vivo. Results. EVOO significantly decreased acetic acid-induced abdominal writhes and reduces acute and inflammatory pain in the two phases of the formalin test. It has also a better effect than Dexamethasone in the anti-inflammatory test. Finally, the intraperitoneal administration of EVOO affects the growth of HCT 116 tumours xenografted in athymic mice. Conclusion. EVOO has a significant analgesic, anti-inflammatory, and anticancer properties. However, further detailed studies are required to determine the active component responsible for these effects and mechanism pathway. PMID:24455277

  19. Flavonoids as anti-inflammatory agents: implications in cancer and cardiovascular disease.

    PubMed

    García-Lafuente, Ana; Guillamón, Eva; Villares, Ana; Rostagno, Mauricio A; Martínez, José Alfredo

    2009-09-01

    Chronic inflammation is being shown to be increasingly involved in the onset and development of several pathological disturbances such as arteriosclerosis, obesity, diabetes, neurodegenerative diseases and even cancer. Treatment for chronic inflammatory disorders has not been solved, and there is an urgent need to find new and safe anti-inflammatory compounds. Flavonoids belong to a group of natural substances occurring normally in the diet that exhibit a variety of beneficial effects on health. The anti-inflammatory properties of flavonoids have been studied recently, in order to establish and characterize their potential utility as therapeutic agents in the treatment of inflammatory diseases. Several mechanisms of action have been proposed to explain in vivo flavonoid anti-inflammatory actions, such as antioxidant activity, inhibition of eicosanoid generating enzymes or the modulation of the production of proinflammatory molecules. Recent studies have also shown that some flavonoids are modulators of proinflammatory gene expression, thus leading to the attenuation of the inflammatory response. However, much work remains to be done in order to achieve definitive conclusions about their potential usefulness. This review summarizes the known mechanisms involved in the anti-inflammatory activity of flavonoids and the implications of these effects on the protection against cancer and cardiovascular disease.

  20. A Review on the Anti-Inflammatory Activity of Pomegranate in the Gastrointestinal Tract

    PubMed Central

    Colombo, Elisa; Sangiovanni, Enrico; Dell'Agli, Mario

    2013-01-01

    Several biological activities of pomegranate have been widely described in the literature, but the anti-inflammatory effect in the gastrointestinal tract has not been reviewed till now. The aim of the present paper is to summarize the evidence for or against the efficacy of pomegranate for coping with inflammatory conditions of the gastro-intestinal tract. The paper has been organized in three parts: (1) the first one is devoted to the modifications of pomegranate active compounds in the gastro-intestinal tract; (2) the second one considering the literature regarding the anti-inflammatory effect of pomegranate at gastric level; (3) the third part considers the anti-inflammatory effect of pomegranate in the gut. In vivo studies performed on the whole fruit or juice, peel, and flowers demonstrate antiulcer effect in a variety of animal models. Ellagic acid was the main responsible for this effect, although other individual ellagitannins could contribute to the biological activity of the mixture. Different preparations of pomegranate, including extracts from peels, flowers, seeds, and juice, show a significant anti-inflammatory activity in the gut. No clinical studies have been found, thus suggesting that future clinical studies are necessary to clarify the beneficial effects of pomegranate in the gastrointestinal tract. PMID:23573120

  1. An investigation of antioxidant and anti-inflammatory activities from blood components of Crocodile (Crocodylus siamensis).

    PubMed

    Phosri, Santi; Mahakunakorn, Pramote; Lueangsakulthai, Jiraporn; Jangpromma, Nisachon; Swatsitang, Prasan; Daduang, Sakda; Dhiravisit, Apisak; Thammasirirak, Sompong

    2014-10-01

    Antioxidant and anti-inflammatory activities were found from Crocodylus siamensis (C. siamensis) blood. The 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging, nitric oxide scavenging, hydroxyl radical scavenging and linoleic peroxidation assays were used to investigate the antioxidant activities of the crocodile blood. Results show that crocodile blood components had antioxidant activity, especially hemoglobin (40.58 % nitric oxide radical inhibition), crude leukocyte extract (78 % linoleic peroxidation inhibition) and plasma (57.27 % hydroxyl radical inhibition). Additionally, the anti-inflammatory activity of the crocodile blood was studied using murine macrophage (RAW 264.7) as a model. The results show that hemoglobin, crude leukocyte extract and plasma were not toxic to RAW 264.7 cells. Also they showed anti-inflammatory activity by reduced nitric oxide (NO) and interleukin 6 (IL-6) productions from lipopolysaccharide (LPS)-stimulated cells. The NO inhibition percentages of hemoglobin, crude leukocyte extract and plasma were 31.9, 48.24 and 44.27 %, respectively. However, only crude leukocyte extract could inhibit IL-6 production. So, the results of this research directly indicate that hemoglobin, crude leukocyte extract and plasma of C. siamensis blood provide both antioxidant and anti-inflammatory activities, which could be used as a supplementary agent in pharmaceutical products.

  2. AMP-activated protein kinase is activated by non-steroidal anti-inflammatory drugs.

    PubMed

    King, Tanya S; Russe, Otto Quintus; Möser, Christine V; Ferreirós, Nerea; Kynast, Katharina L; Knothe, Claudia; Olbrich, Katrin; Geisslinger, Gerd; Niederberger, Ellen

    2015-09-01

    AMP-activated kinase (AMPK) is a cellular energy sensor, which is activated in stages of increased adenosine triphosphate (ATP) consumption. Its activation has been associated with a number of beneficial effects such as decrease of inflammatory processes and inhibition of disease progression of diabetes and obesity. A recent study suggested that salicylate, the active metabolite of the non-steroidal anti-inflammatory drug (NSAID) acetyl-salicylic acid (aspirin), is able to activate AMPK pharmacologically. This observation raised the question whether or not other NSAIDs might also act as AMPK activators and whether this action might contribute to their cyclooxygenase (COX)-independent anti-inflammatory properties. In this study, we investigated mouse and human neuronal cells and liver tissue of mice after treatment with various NSAIDs. Our results showed that the non-selective acidic NSAIDs ibuprofen and diclofenac induced AMPK activation similar to aspirin while the COX-2 selective drug etoricoxib and the non-opioid analgesic paracetamol, both drugs have no acidic structure, failed to activate AMPK. In conclusion, our results revealed that AMPK can be activated by specific non-steroidal anti-inflammatory drugs such as salicylic acid, ibuprofen or diclofenac possibly depending on the acidic structure of the drugs. AMPK might therefore contribute to their antinociceptive and anti-inflammatory properties. PMID:26049010

  3. Drug Targets for Cardiovascular-Safe Anti-Inflammatory: In Silico Rational Drug Studies

    PubMed Central

    Shahbazi, Sajad; Sahrawat, Tammanna R.; Ray, Monalisa; Dash, Swagatika; Kar, Dattatreya; Singh, Shikha

    2016-01-01

    Cyclooxygenase-2 (COX-2) plays an important role in memory consolidation and synaptic activity, the most fundamental functions of the brain. It converts arachidonic acid to prostaglandin endoperoxide H2. In contrast, if over-expressed, it causes inflammation in response to cytokine, pro-inflammatory molecule, and growth factor. Anti-inflammatory agents, by allosteric or competitive inhibition of COX-2, alleviate the symptoms of inflammation. Coxib family drugs, particularly celecoxib, are the most famous anti-inflammatory agents available in the market showing significant inhibitory effect on COX-2 activity. Due to high cardiovascular risk of this drug group, recent researches are focused on the investigation of new safer drugs for anti-inflammatory diseases. Natural compounds, particularly, phytochemicals are found to be good candidates for drug designing and discovery. In the present study, we performed in silico studies to quantitatively scrutinize the molecular interaction of curcumin and its structural analogs with COX-2, COX-1, FXa and integrin αIIbβIII to investigate their therapeutic potential as a cardiovascular-safe anti-inflammatory medicine (CVSAIM). The results of both ADMET and docking study indicated that out of all the 39 compounds studied, caffeic acid had remarkable interaction with proteins involved in inflammatory response. It was also found to inhibit the proteins that are involved in thrombosis, thereby, having the potential to be developed as therapeutic agent. PMID:27258084

  4. Anti-inflammatory activity of polysaccharide from Schizophyllum commune as affected by ultrasonication.

    PubMed

    Du, Bin; Zeng, Huansong; Yang, Yuedong; Bian, Zhaoxiang; Xu, Baojun

    2016-10-01

    Ultrasound treatment was applied to modify the physicochemical properties of an exopolysaccharide from mycelial culture of Schizophyllum commune. Molecular weight (MW) degradation, viscosity and anti-inflammatory property of ultrasonic treated polysaccharide were optimized with response surface methodology. The best ultrasonic parameters were obtained with a three-variable-three-level Box-Behnken design. The optimized conditions for efficient anti-inflammatory activity are initial concentration at 0.4%, ultrasonic power at 600W, and duration of ultrasonic irradiation for 9min. Under these conditions, the nitric oxide inhibition rate was 95±0.03% which agreed closely with the predicted value (96%). Average MW of polysaccharide decreased after ultrasonic treatments. The viscosity of degraded polysaccharide dropped compared with native polysaccharide. The anti-inflammatory activity was improved by ultrasound treatment. The results suggested that ultrasound treatment is an effective approach to decrease the MW of polysaccharide with high anti-inflammatory activity. Ultrasonic treatment is a viable modification technology for high MW polymer materials. PMID:27189700

  5. Anti-inflammatory effects of apo-9′-fucoxanthinone from the brown alga, Sargassum muticum

    PubMed Central

    2013-01-01

    Background The marine environment is a unique source of bioactive natural products, of which Sargassum muticum (Yendo) Fensholt is an important brown algae distributed in Jeju Island, Korea. S. muticum is a traditional Korean food stuff and has pharmacological functions including anti-inflammatory effects. However, the active ingredients from S. muticum have not been characterized. Methods Bioguided fractionation of the ethanolic extract of S. muticum, collected from Jeju island, led to the isolation of a norisoprenoid. Its structure was determined by analysis of the spectroscopic data. In vitro anti-inflammatory activity and mechanisms of action of this compound were examined using lipopolysaccharide (LPS)-stimulated RAW 264.7 cells through ELISA assays and Western blot analysis. Results Apo-9′-fucoxanthinone, belonging to the norisoprenoid family were identified. Apo-9′-fucoxanthinone effectively suppressed LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production. This compound also exerted their anti-inflammatory actions by down-regulating of NF-κB activation via suppression of IκB-α in macrophages. Conclusions This is the first report describing effective anti-inflammatory activity for apo-9’-fucoxanthinone′-fucoxanthnone isolated from S. muticum. Apo-9′-fucoxanthinone may be a good candidate for delaying the progression of human inflammatory diseases and warrants further studies. PMID:23889890

  6. Anti-inflammatory activity of constituents isolated from Terminalia chebula ***waiting for publication date

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was aimed at the evaluation of the anti-inflammatory activity of twelve compounds isolated from the methanolic extract of fruits of Terminalia chebula. The activity was determined in terms of their ability to inhibit inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in L...

  7. Non-steroidal anti-inflammatory drug gastropathy: clinical results with antacids and sucralfate.

    PubMed

    Lazzaroni, M; Sainaghi, M; Bianchi Porro, G

    1999-01-01

    The efficacy of antacids in the short- and long-term treatment of peptic ulcers, has suggested a possible use in the prevention and in the treatment of non-steroidal anti-inflammatory drug related gastroduodenal lesions. In short-term prevention studies, significant protection against ASA-related lesions was observed when antacids at high-dose were given before the administration of the offending drug. To the contrary, antacids at low dose did not prevent ASA-induced lesions of gastric and duodenal mucosa. As for long-term prophylaxis, no clinical effect was observed. In the treatment of non-steroidal anti-inflammatory drug-related mucosal lesions in patients who were able to discontinue the offending drugs, antacids proved of some use, when compared with placebo, but were significantly less effective than H2 blockers, as cimetidine. Sucralfate is an effective antiulcer drug thought to provide cytoprotective action. Although initial studies utilizing sucralfate for protection against short-term aspirin administration were encouraging, longer term studies (more than 7 days) were generally disappointing. A comparative study with misoprostol demonstrated that the PGE1 analogue was far superior for the prevention of non-steroidal anti-inflammatory drugs ulcers, and that ulceration rates in the sucralfate group were equivalent to rates in the placebo group. As far as the treatment of non-steroidal anti-inflammatory drug-related mucosal lesions is concerned, sucralfate proved superior to placebo, similar to ranitidine, but significantly less effective than omeprazole.

  8. Analgesic and anti-inflammatory activity of root bark of Grewia asiatica Linn. in rodents

    PubMed Central

    Paviaya, Udaybhan Singh; Kumar, Parveen; Wanjari, Manish M.; Thenmozhi, S.; Balakrishnan, B. R.

    2013-01-01

    Background: Grewia asiatica Linn. (Family: Tiliaceae), called Phalsa in Hindi is an Indian medicinal plant used for a variety of therapeutic and nutritional uses. The root bark of the plant is traditionally used in rheumatism (painful chronic inflammatory condition). Aims: The present study demonstrates the analgesic and anti-inflammatory activity of root bark of G. asiatica in rodents. Settings and Design: The methanolic extract of Grewia asiatica (MEGA) and aqueous extract of Grewia asiatica (AEGA) of the bark were prepared and subjected to phytochemical tests and pharmacological screening for analgesic and anti-inflammatory effect in rodents. Materials and Methods: Analgesic effect was studied using acetic acid-induced writhing in mice and hot plate analgesia in rats while anti-inflammatory activity was investigated using carrageenan-induced paw oedema in rats. The MEGA or AEGA was administered orally in doses of 200 and 400 mg/kg/day of body weight. Statistical Analysis: Data were analysed by one-way analysis of variance followed by Dunnett's test. Results: The extracts showed a significant inhibition of writhing response and increase in hot plate reaction time and also caused a decrease in paw oedema. The effects were comparable with the standard drugs used. Conclusions: The present study indicates that root bark of G. asiatica exhibits peripheral and central analgesic effect and anti-inflammatory activity, which may be attributed to the various phytochemicals present in root bark of G. asiatica. PMID:24501443

  9. In Vivo Potential Anti-Inflammatory Activity of Melissa officinalis L. Essential Oil.

    PubMed

    Bounihi, Amina; Hajjaj, Ghizlane; Alnamer, Rachad; Cherrah, Yahia; Zellou, Amina

    2013-01-01

    Melissa officinalis L. (Lamiaceae) had been reported in traditional Moroccan medicine to exhibit calming, antispasmodic, and strengthening heart effects. Therefore, this study is aimed at determining the anti-inflammatory activities of M. officinalis L. leaves. The effect of the essential oil of the leaves of this plant was investigated for anti-inflammatory properties by using carrageenan and experimental trauma-induced hind paw edema in rats. The essential oil extracted from leaves by hydrodistillation was characterized by means of gas chromatography-mass spectrometry (GC-MS). M. officinalis contained Nerol (30.44%), Citral (27.03%), Isopulegol (22.02%), Caryophyllene (2.29%), Caryophyllene oxide (1.24%), and Citronella (1.06%). Anti-inflammatory properties of oral administration of essential oil at the doses of 200, 400 mg/kg p.o., respectively, showed significant reduction and inhibition of edema with 61.76% and 70.58%, respectively, (P < 0.001) induced by carrageenan at 6 h when compared with control and standard drug (Indomethacin). On experimental trauma, M. officinalis L. essential oil showed pronounced reduction and inhibition of edema induced by carrageenan at 6 h at 200 and 400 mg/kg with 91.66% and 94.44%, respectively (P < 0.001). We can conclude that the essential oil of M. officinalis L. possesses potential anti-inflammatory activities, supporting the traditional application of this plant in treating various diseases associated with inflammation and pain.

  10. Guava pomace: a new source of anti-inflammatory and analgesic bioactives

    PubMed Central

    2013-01-01

    Background Guava pomace is an example of the processing waste generated after the manufacturing process from the juice industry that could be a source of bioactives. Thus, the present investigation was carried out in order to evaluate the anti-inflammatory and antinociceptive potential and determinate the main phenolic compounds of a guava pomace extract (GPE). Methods The anti-inflammatory activity was evaluated by carrageenan, dextran, serotonin, histamine-induced paw edema and neutrophils migration in the peritoneal cavity models. Acetic acid-induced abdominal writhing and formalin test were performed to investigate the antinociceptive effects. In addition, the content of total phenolic and of individual phenolic compounds was determined by GC/MS. Results GPE showed anti-inflammatory activity by carrageenan, dextran, serotonin, histamine-induced paw edema and neutrophils migration in the peritoneal cavity models (p < 0.05). GPE also demo