Senkyunolide H protects against MPP+-induced apoptosis via the ROS-mediated mitogen-activated protein kinase pathway in PC12 cells

Autor: Xueqin Li, Weicheng Hu, Aftab Yaseen, Yufeng Cao, Wancai Zheng, Jianmei Zhang, Chuanling Si, Tingwu Liu, Fengting Sun, Yunyao Jiang, Yanyan Luo
Rok vydání: 2019
Předmět:
Zdroj: Environmental Toxicology and Pharmacology. 65:73-81
ISSN: 1382-6689
DOI: 10.1016/j.etap.2018.12.007
Popis: Senkyunolide H (SNH) is a phthalide isolated from the rhizome of Ligusticum chuanxiong Hort. that has been reported to have several pharmacological activities, including anti-atherosclerotic, antiproliferative, and cytoprotective effects. In this study, we investigated the neuroprotective effects and potential mechanisms of SNH against 1-methyl-4-phenylpyridinium (MPP+)-induced oxidative stress. We demonstrated that SNH pretreatment significantly attenuated MPP+-induced neurotoxicity and apoptosis in PC12 cells. In addition, SNH attenuated the effect of MPP+ on the expression of the pro-apoptotic factors Bax and caspase-3. Meanwhile, SNH prevented oxidative stress by reducing reactive oxygen species generation, mitochondrial membrane potential loss, cytochrome C release, and malondialdehyde levels while increasing antioxidant enzyme activity (e.g., superoxide dismutase, catalase, and glutathione peroxidase). In addition, SNH inhibited nuclear accumulation of nuclear factor-κB and c-Jun N-terminal kinase and phosphorylation p38 mitogen-activated protein kinases (MAPKs). Overall, this investigation provides novel evidence that SNH exerts neuroprotective effects via the ROS-mediated MAPK pathway and represents a potential preventive or therapeutic agent for neuronal disorders.
Databáze: OpenAIRE
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