title: Screening SIRT1 Activators from Medicinal Plants as Bioactive Compounds against Oxidative Damage in Mitochondrial Function.
abstract: Sirtuin type 1 (SIRT1) belongs to the family of NAD(+) dependent histone deacetylases and plays a critical role in cellular metabolism and response to oxidative stress. Traditional Chinese medicines (TCMs), as an important part of natural products, have been reported to exert protective effect against oxidative stress in mitochondria. In this study, we screened SIRT1 activators from TCMs and investigated their activities against mitochondrial damage. 19 activators were found in total by in vitro SIRT1 activity assay. Among those active compounds, four compounds, ginsenoside Rb2, ginsenoside F1, ginsenoside Rc, and schisandrin A, were further studied to validate the SIRT1-activation effects by liquid chromatography-mass spectrometry and confirm their activities against oxidative damage in H9c2 cardiomyocytes exposed to tert-butyl hydroperoxide (t-BHP). The results showed that those compounds enhanced the deacetylated activity of SIRT1, increased ATP content, and inhibited intracellular ROS formation as well as regulating the activity of Mn-SOD. These SIRT1 activators also showed moderate protective effects on mitochondrial function in t-BHP cells by recovering oxygen consumption and increasing mitochondrial DNA content. Our results suggested that those compounds from TCMs attenuated oxidative stress-induced mitochondrial damage in cardiomyocytes through activation of SIRT1.
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Xinying
authors.initials: X
authors.lastname: Liang
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Yaqi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: College of Preclinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhao
mesh_terms: D001688:Biological Products / Q000302:isolation & purification* / Q000494:pharmacology*; D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000502:physiology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D010946:Plants, Medicinal / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D056564:Sirtuin 1 / Q000187:drug effects / Q000378:metabolism*
chemical_list: D001688:Biological Products; D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; C447939:SIRT1 protein, human; D056564:Sirtuin 1