Eugenol Attenuates Cerebral Ischemia-Reperfusion Injury by Enhancing Autophagy via AMPK-mTOR-P70S6K Pathway

Frontiers in Pharmacology

Xiaowei Sun¹  Dongyan Wang²  Xuejian Lu³  Lili Ju³  Fangfang Duan³  Xiaotong Zhuang³  Tingting Zhang⁴  Xicheng Jiang⁵ 

[1] Department of Acupuncture and Moxibustion, The First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China;Department of Acupuncture and Moxibustion, The Second Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China;Department of Chinese Medicine Clinical Foundation, School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin, China;Department of Integrated Chinese and Western Medicine, The First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China;Department of Synopsis of the Golden Chamber, School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin, China;

关键词: eugenol;    cerebral I/R injury;    autophagy;    HT 22;    AMPK/mTOR/P70S6K pathway;   

DOI  :  10.3389/fphar.2020.00084

来源: DOAJ

【 摘 要 】

Eugenol, as an active compound isolated from Acorus gramineus, has been shown to protect against cerebral ischemia-reperfusion (I/R) injury. Nonetheless, the detailed neuroprotective mechanisms of eugenol in cerebral I/R injury have not been elaborated. In the present study, cerebral I/R injury model was established by middle cerebral artery occlusion (MCAO) in rats. HT22 cells were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) to mimic cerebral I/R injury in vitro. The results showed that eugenol pre-treatment relieved cerebral I/R injury as evidenced by improving neurological deficits and reducing infarct volume. Autophagy was induced by MCAO, which was further promoted by eugenol administration. Moreover, rapamycin, an activator of autophagy, promoted eugenol-induced decreases in neurological score, infarct volume, brain water content, and apoptosis. However, pretreatment with 3-MA, an inhibitor of autophagy, led to the opposite results. Similarly, eugenol pretreatment increased the viability and restrained apoptosis of OGD/R-challenged HT22 cells. OGD/R-induced autophagy was strengthened by eugenol. Mechanically, eugenol promoted autophagy through regulating AMPK/mTOR/P70S6K signaling pathway in vivo and in vitro. In conclusion, pretreatment with eugenol attenuated cerebral I/R injury by inducing autophagy via AMPK/mTOR/P70S6K signaling pathway.

【 授权许可】

Unknown