title: Cocktail of Four Active Components Derived from Sheng Mai San Inhibits Hydrogen Peroxide-Induced PC12 Cell Apoptosis Linked with the Caspase-3/ROCK1/MLC Pathway.
abstract: SMXZF, a combination of four active components including ginsenoside Rb1, ginsenoside Rg1, schizandrin, and DT-13 (6:9:5:4) that is derived from Sheng Mai San, has previously been shown to exhibit a neuroprotective effect against focal ischemia/reperfusion injury. Due to the key role of oxidative stress-induced neuronal apoptosis in the pathogenesis of stroke, we examined the effect of SMXZF in oxidative stress responses and related signaling pathways in differentiated pheochromocytoma (PC12) cells. Our results showed that incubation with 100 μM hydrogen peroxide (H2O2) for 12 hr could reduce cell viability and superoxide dismutase (SOD) activity with an increase of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA). In contrast, SMXZF alleviated oxidative stress by reducing the over-production of ROS and MDA in parallel to concentration dependently increasing SOD activity. In addition, SMXZF significantly attenuated H2O2-induced caspase-3 cleavage, Rho-associated coiled-coil-containing protein kinase-1 (ROCK1) activation, and myosin light-chain (MLC) phosphorylation. Inhibiting either caspase-3 or ROCK1 mimicked the effect. Consequently, our results suggest that SMXZF inhibits H2O2-induced neuronal apoptosis linked with the caspase-3/ROCK1/MLC pathway, which has also been confirmed to be a positive feedback loop in oxidative stress-injured PC12 cells. These findings support the pharmacological potential of SMXZF for neurodegenerative diseases and stroke.
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University , Nanjing, P.R. China .
authors.forename: Kai
authors.initials: K
authors.lastname: Shen
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University , Nanjing, P.R. China .
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University , Nanjing, P.R. China .
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University , Nanjing, P.R. China .
authors.forename: Huana
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University , Nanjing, P.R. China .
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Song
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University , Nanjing, P.R. China .
authors.forename: Zhengyu
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University , Nanjing, P.R. China .
authors.forename: Junping
authors.initials: J
authors.lastname: Kou
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University , Nanjing, P.R. China .
authors.forename: Boyang
authors.initials: B
authors.lastname: Yu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D042541:Intracellular Space / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism*; D009498:Neurotoxins / Q000633:toxicity; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; D018994:Myosin Light Chains; D009498:Neurotoxins; D017382:Reactive Oxygen Species; C009252:fructus schizandrae, radix ginseng, radix ophiopogonis drug combination; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D054460:rho-Associated Kinases; D053148:Caspase 3