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Gymnema montanum improves endothelial function via inhibition of endoplasmic reticulum stress by activating Nrf2 signaling

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Asian Pacific Journal of Tropical Biomedicine 2020年第8期10卷 379-386页

作者： Dornadula Sireesh Natarajan Suganya Suvro Chatterjee kunka mohanram ramkumar SRM Research Institute SRM Institute of Science and TechnologyKattankulathur-603203Tamil NaduIndia Department of Biotechnology School of BioengineeringSRM Institute of Science and TechnologyKattankulathur-603203Tamil NaduIndia Vascular Biology Lab AU-KBC Research CentreAnna UniversityChromepetChennai-600044Tamil NaduIndia

Objective:To investigate the effects of Gymnema montanum leaf extract against endoplasmic reticulum(ER)stress-induced toxicity in endothelial cells.Methods:The immortalized endothelial hybrid cell,EA.hy926 was treated with different concentrations of Gymnema montanum leaf extract(0–100μg/mL)and the ER stress inducer,tunicamycin.The cytotoxicity was assessed by MTT as well as lactate dehydrogenase and malondialdehyde levels were determined.The levels of ER stress markers,GRP78 and CHOP were analysed by Western blot assay.The Gymnema montanum leaf extract-mediated activation of nuclear factor erythroid 2-related factor 2(Nrf2)was assessed by cell-based luciferase enzyme fragment complementation assay and antioxidant responsive element driven luciferase reporter assay.The levels of phosphoproteins of the MAPK pathway were analyzed using the Bioplex system.Results:A dose-dependent cytoprotective effect of Gymnema montanum leaf extract was observed in tunicamycin-induced toxicity.Gymnema montanum leaf extract significantly reduced lactate dehydrogenase activity and malondialdehyde levels in ER stress-induced endothelial cells.It also suppressed ER stress markers dose dependently and inhibited the phosphorylation of JNK,ERK,MEK and p38 MAPK in tunicamycin-induced endothelial cells.Moreover,Gymnema montanum leaf extract increased the expression of Nrf2 and its downstream targets in endothelial cells.Conclusions:Gymnema montanum leaf extract attenuates ER stress by increasing the expression of Nrf2 and its downstream genes.

关键词： ER stress Gymnema montanum Nrf2 Endothelial cells

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Caffeic acid and protocatechuic acid modulate Nrf2 and inhibit Ehrlich ascites carcinomas in mice

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Asian Pacific Journal of Tropical Biomedicine 2021年第6期11卷 244-253页

作者： Venugopal R.Bovilla Preethi G.Anantharaju Sireesh Dornadula Prashanthkumar M.Veeresh Mahadevaswamy G.Kuruburu Vidya G.Bettada kunka mohanram ramkumar SubbaRao V.Madhunapantula Center of Excellence in Molecular Biology and Regenerative Medicine Department of BiochemistryJSS Medical CollegeJSS Academy of Higher Education&ResearchMysore-570015KarnatakaIndia SRM Research Institute Department of BiotechnologySchool of BioengineeringSRM Institute of Science and TechnologyKattankulathur-603203Tamil NaduIndia

Objective:To assess the nuclear factor-erythroid 2-related factor-2(Nrf2)modulatory effect of caffeic acid and protocatechuic acid and determine the anti-tumor activity of these phenolic compounds against Ehrlich ascites carcinoma growth in mice.Methods:Antioxidant activity of protocatechuic acid and caffeic acid was assessed using ferric reducing antioxidant power(FRAP)and 2,2-diphenyl-1-picrylhydrazyl(DPPH).Nrf2 activation potential of phenolic compounds was tested by quantitative realtime polymerase chain reaction,and luciferase complementation reporter assays.In vivo efficacy was tested using the Ehrlich ascites carcinoma model.Results:FRAP and DPPH radical scavenging assays showed that caffeic acid and protocatechuic acid were more potent compared with cinnamic acid and benzoic acid.Luciferase complementation reporter assays identified caffeic acid and protocatechuic acid as the activators of Nrf2.Both caffeic acid and protocatechuic acid upregulated the expression of Nrf2 target genes heme oxygenase-1(HO-1),glutamate-cysteine ligase catalytic subunit(GCLC),and glutamate-cysteine ligase modifier subunit(GCLM)and the activity of NAD(P)H:quinone oxidoreductase 1(NQO1)when tested on HCT-116 cells using a cell-based assay system at 9 h.In addition,intraperitoneal administration of caffeic acid and protocatechuic acid to Ehrlich ascites carcinoma bearing mice suppressed tumor growth and angiogenesis.Conclusions:Caffeic acid and protocatechuic acid can modulate Nrf2 and inhibit Ehrlich ascites carcinoma cells.

关键词： Ehrlich ascites carcinomas Nrf2 Protocatechuic acid Caffeic acid NQO1 activity

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