title: Gypenosides attenuate cholesterol-induced DNA damage by inhibiting the production of reactive oxygen species in human umbilical vein endothelial cells.
abstract: Previous studies have demonstrated that DNA damage induces atherosclerosis and that oxidative stress has an important role in DNA damage. Gypenosides (Gps), the main ingredient of Gynostemma Pentaphylla (Thunb.) Makino, have been recognized as specific antioxidants and have previously been reported to inhibit high‑fat diet‑induced atherosclerosis in rats. However, whether or not Gps attenuate DNA damage through their antioxidant effects remains to be elucidated. The current study was performed to clarify whether or not Gps can inhibit cholesterol‑induced DNA damage through antioxidation. The present study provided new insights into the pharmacological effects of Gps on atherosclerosis. HUVECs were treated with Gps at various concentrations (1, 10 and 100 µg/ml) for 1 h. The protective effects of Gps on cholesterol‑induced DNA damage were determined using immunofluorescence, western blotting, reverse‑transcription quantitative polymerase chain reaction and flow cytometry. Pretreatment with Gps (1, 10 and 100 µg/ml) effectively attenuated cholesterol‑induced DNA damage in HUVECs by inhibiting phosphorylation of H2AX, a member of the histone family. Furthermore, Gps (100 µg/ml) pretreatment inhibited cholesterol‑induced transcription and activity of nicotinamide adenine dinucleotide phosphate‑oxidase 4 and reduced intracellular ROS levels. In conclusion, Gps attenuated cholesterol‑induced DNA damage by inhibiting ROS production in HUVECs, suggesting that the inhibitory effect of Gps on atherogenesis is correlated with the alleviation of DNA damage.
authors.affiliation: Department of Biochemistry, Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Quan
authors.affiliation: Department of Biochemistry, Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Biochemistry, Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China.
authors.forename: Huixing
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Shu
authors.affiliation: Department of Pharmacology, Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China.
authors.forename: Qi-Hai
authors.initials: QH
authors.lastname: Gong
authors.affiliation: Department of Biochemistry, Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China.
authors.forename: Minzhang
authors.initials: M
authors.lastname: Qian
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D002784:Cholesterol / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D029774:Gynostemma / Q000737:chemistry; D006657:Histones / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D006657:Histones; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C474918:gypenoside; D002784:Cholesterol; D019001:Nitric Oxide Synthase; D014969:Xanthine Oxidase; D019255:NADPH Oxidases