title: Chikusetsu saponin V attenuates MPP+-induced neurotoxicity in SH-SY5Y cells via regulation of Sirt1/Mn-SOD and GRP78/caspase-12 pathways.
abstract: Studies have shown that saponins from Panax japonicus (SPJ) possess neuroprotective effects. However, whether Chikusetsu saponin V (CsV), the most abundant member of SPJ, can exert neuroprotective effects against 1-methyl-4-phenylpyridinium ion (MPP+)-induced cytotoxicity is not known. In this study, we aimed to investigate the neuroprotective effects of CsV on MPP+-induced cytotoxicity in human neuroblastoma SH-SY5Y cells and explore its possible mechanisms. Our results show that CsV attenuates MPP+-induced cytotoxicity, inhibits ROS accumulation, and increases mitochondrial membrane potential dose-dependently. We also found that levels of Sirt1 protein and Mn-SOD mRNA significantly decreased in MPP+-treated group but were restored with CsV treatment in a dose-dependent manner. Furthermore, GRP78 protein and Caspase-12 mRNA levels were elevated by MPP+ exposure but reversed by CsV treatment. CsV inhibited the MPP+-induced downregulation of Bcl-2 and up-regulation of Bax in a dose-dependent manner and, thus, increased the ratio of Bcl-2/Bax. Overall, these results suggest that Sirt1/Mn-SOD and GRP78/Caspase-12 pathways might be involved in the CsV-mediated neuroprotective effects.
authors: Department of Pharmacology, College of Medical Science, China Three Gorges University, Yichang 443002, China. yxyydyd@126.com.
authors: Ding
authors: D
authors: Yuan
authors: Department of Pharmacology, College of Medical Science, China Three Gorges University, Yichang 443002, China. 15071798496@163.com.
authors: Jing-Zhi
authors: JZ
authors: Wan
authors: Department of Pharmacology, College of Medical Science, China Three Gorges University, Yichang 443002, China. denglili3748@163.com.
authors: Li-Li
authors: LL
authors: Deng
authors: Department of Pharmacology, College of Medical Science, China Three Gorges University, Yichang 443002, China. greatwall@ctgu.edu.cn.
authors: Chang-Cheng
authors: CC
authors: Zhang
authors: Department of Pharmacology, College of Medical Science, China Three Gorges University, Yichang 443002, China. dyw891122@163.com.
authors: Yao-Yan
authors: YY
authors: Dun
authors: Department of Pharmacology, College of Medical Science, China Three Gorges University, Yichang 443002, China. dyw891122@163.com.
authors: Yan-Wen
authors: YW
authors: Dai
authors: Department of Pharmacology, College of Medical Science, China Three Gorges University, Yichang 443002, China. in_bud@ctgu.edu.cn.
authors: Zhi-Yong
authors: ZY
authors: Zhou
authors: Institute of Molecular Biology, China Three Gorges University, Yichang 443002, China. ctgulcq@163.com.
authors: Chao-Qi
authors: CQ
authors: Liu
authors: Department of Pharmacology, College of Medical Science, China Three Gorges University, Yichang 443002, China. tingting0301@126.com.
authors: Ting
authors: T
authors: Wang
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D053454:Caspase 12 / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D012503:Saponins; D051028:bcl-2-Associated X Protein; C588229:chikusetsusaponin V; D013482:Superoxide Dismutase; D053454:Caspase 12; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D015655:1-Methyl-4-phenylpyridinium