Oleanolic Acid Alleviates Cerebral Ischemia/Reperfusion Injury via Regulation of the GSK-3β/HO-1 Signaling Pathway

被引:18
作者
Lin, Kaili [1 ]
Zhang, Zhang [2 ,3 ]
Zhang, Zhu [2 ,3 ]
Zhu, Peili [2 ,3 ]
Jiang, Xiaoli [2 ,3 ]
Wang, Ying [2 ,3 ]
Deng, Qiudi [4 ]
Lam Yung, Ken Kin [2 ,3 ]
Zhang, Shiqing [5 ]
机构
[1] Guangzhou Med Univ, Sch Publ Hlth, Guangzhou 511436, Peoples R China
[2] Hong Kong Baptist Univ HKBU, Fac Sci, Dept Biol, Kowloon Tong, Hong Kong 999077, Peoples R China
[3] HKBU, Golden Meditech Ctr Neuro Regenerat Sci, Kowloon Tong, Hong Kong 999077, Peoples R China
[4] Guangzhou Med Univ, GMU GIBH Joint Sch Life Sci, Dept Biochem & Mol Biol, Guangzhou 511436, Peoples R China
[5] Jinan Univ, Coll Pharm, JNU HKUST Joint Lab Neurosci & Innovat Drug Res, Guangzhou 510632, Peoples R China
关键词
oleanolic acid; cerebral ischemia/reperfusion; antioxidant properties; GSK-313/HO-1; pathway; OXIDATIVE STRESS; IN-VIVO; STROKE; THERAPY;
D O I
10.3390/ph15010001
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Oleanolic acid (OA), a bioactive ingredient of Panax ginseng, exhibits neuroprotective pharmacological effects. However, the protective role of OA in cerebral ischemia and involved mechanisms remain unclear. This study attempted to explore the therapeutic effects of OA both in vitro and in vivo. OA attenuated cytotoxicity and overproduction of intracellular reactive oxygen species (ROS) by regulation of glycogen synthase kinase-3 beta (GSK-3 beta)/heme oxygenase-1 (HO-1) signal in oxygen-glucose deprivation/reoxygenation (OGD/R)-exposed SH-SY5Y cells. Additionally, OA administration significantly reduced the area of cerebral infarction and the neurological scores in the rat models of cerebral ischemia with middle cerebral artery occlusion (MCAO). The OA administration group showed a higher percentage of Nissl(+) and NeuN(+) cells, along with lower TUNEL+ ratios in the infarct area of MCAO rats. Moreover, OA administration reduced ROS production while it suppressed the GSK-3 beta activation and upregulated the HO-1 expression in infarcted tissue. Our results illustrated that OA significantly counteracted cerebral ischemia-mediated injury through antioxidant effects induced by the regulation of the GSK-3 beta/HO-1 signaling pathway, implicating OA as a promising neuroprotective drug for the therapy of ischemic stroke.
引用
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页数:11
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