PMID- 25515035 OWN - NLM STAT- MEDLINE DCOM- 20150928 LR - 20171116 IS - 1791-3004 (Electronic) IS - 1791-2997 (Linking) VI - 11 IP - 4 DP - 2015 Apr TI - Gypenosides attenuate cholesterol-induced DNA damage by inhibiting the production of reactive oxygen species in human umbilical vein endothelial cells. PG - 2845-51 LID - 10.3892/mmr.2014.3095 [doi] AB - 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 microg/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 microg/ml) effectively attenuated cholesterol‑induced DNA damage in HUVECs by inhibiting phosphorylation of H2AX, a member of the histone family. Furthermore, Gps (100 microg/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. FAU - Quan, Yuan AU - Quan Y AD - Department of Biochemistry, Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China. FAU - Yang, Yijun AU - Yang Y AD - Department of Biochemistry, Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China. FAU - Wang, Huixing AU - Wang H AD - Department of Biochemistry, Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China. FAU - Shu, Bo AU - Shu B AD - Department of Biochemistry, Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China. FAU - Gong, Qi-Hai AU - Gong QH AD - Department of Pharmacology, Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China. FAU - Qian, Minzhang AU - Qian M AD - Department of Biochemistry, Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141216 PL - Greece TA - Mol Med Rep JT - Molecular medicine reports JID - 101475259 RN - 0 (Antioxidants) RN - 0 (Histones) RN - 0 (Plant Extracts) RN - 0 (Reactive Oxygen Species) RN - 0 (gypenoside) RN - 97C5T2UQ7J (Cholesterol) RN - EC 1.14.13.39 (Nitric Oxide Synthase) RN - EC 1.17.3.2 (Xanthine Oxidase) RN - EC 1.6.3.- (NADPH Oxidases) SB - IM MH - Antioxidants/chemistry/pharmacology MH - Cholesterol/*pharmacology MH - DNA Damage/*drug effects MH - Gene Expression Regulation, Enzymologic/drug effects MH - Gynostemma/chemistry MH - Histones/metabolism MH - Human Umbilical Vein Endothelial Cells/*drug effects/*metabolism MH - Humans MH - NADPH Oxidases/genetics/metabolism MH - Nitric Oxide Synthase/metabolism MH - Oxidative Stress MH - Plant Extracts/chemistry/pharmacology MH - Reactive Oxygen Species/*metabolism MH - Xanthine Oxidase/metabolism EDAT- 2014/12/18 06:00 MHDA- 2015/09/29 06:00 CRDT- 2014/12/18 06:00 PHST- 2013/12/03 00:00 [received] PHST- 2014/09/12 00:00 [accepted] PHST- 2014/12/18 06:00 [entrez] PHST- 2014/12/18 06:00 [pubmed] PHST- 2015/09/29 06:00 [medline] AID - 10.3892/mmr.2014.3095 [doi] PST - ppublish SO - Mol Med Rep. 2015 Apr;11(4):2845-51. doi: 10.3892/mmr.2014.3095. Epub 2014 Dec 16.