title: YGS40, an active fraction of Yi-Gan San, reduces hydrogen peroxide-induced apoptosis in PC12 cells.
abstract: In our previous study, we have elucidated the chemical profile of YGS40, a fraction of Yi-Gan San (YGS), used for the treatment of Alzheimer's disease (AD). Oxidative stress-induced apoptosis is implicated in neurodegenerative disorders such as AD. The aim of the present study was to explore the protective effects of YGS40 against hydrogen peroxide (H2O2)-induced apoptosis in PC12 cells and the underlying mechanisms. PC12 cells were exposed to 100 μmol·L(-1) of H2O2 for 12 h with or without YGS40 pretreatment. Cytotoxicity was determined by MTT (3, (4, 5-dimethylthiazole-2-yl) 2, 5-diphenyl-tetrazolium bromide) and lactate dehydrogenase (LDH) release assays; apoptosis was detected by Annexin V/propidium iodide coupled staining and by determining caspase-3 activity and Bax and Bcl-2 protein levels. Mitochondrial membrane potential (MMP) was assessed by the retention of rhodamine123; and the activities of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured using commercially available enzymatic kits. Pretreatment with YGS40 significantly prevented H2O2-induced cytotoxicity and protected the cells against H2O2-triggered apoptosis characterized by externalization of membrane phosphatidylserine and caspase-3 activation and the increased ratio of Bax/Bcl-2 in PC12 cells. Further studies showed that YGS40 suppressed H2O2-induced MMP loss, increased SOD activity, and decreased MDA level. These findings suggest that YGS40 may be beneficial for the prevention and treatment of oxidative stress-mediated disorders.
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Yu-Rong
authors.initials: YR
authors.lastname: Zhao
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Qu
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Wen-Yuan
authors.initials: WY
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China. Electronic address: honghao@cpu.edu.cn.
authors.forename: Hao
authors.initials: H
authors.lastname: Hong
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China. Electronic address: fengsunlight@163.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Feng
authors.affiliation: New Technology Center of Chemical Pharmaceutical Shanghai Institute of Pharmaceutical Industry China State Institute of Pharmaceutical Industry, Shanghai 200437, China.
authors.forename: Han
authors.initials: H
authors.lastname: Chen
authors.affiliation: Jiangxi Qingfeng Pharmaceutical Corporation, Ganzhou 341000, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Xie
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000633:toxicity*; D008315:Malondialdehyde / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004365:Drugs, Chinese Herbal; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; C524644:Yi-Gan San; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D053148:Caspase 3
keywords: Antioxidant effects; Apoptosis; Hydrogen peroxide; YGS40; Yi-Gan San