1. Academic Validation
  2. Eugenol Attenuates Cerebral Ischemia-Reperfusion Injury by Enhancing Autophagy via AMPK-mTOR-P70S6K Pathway

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

  • Front Pharmacol. 2020 Feb 21;11:84. doi: 10.3389/fphar.2020.00084.
Xiaowei Sun 1 Dongyan Wang 2 Tingting Zhang 3 Xuejian Lu 4 Fangfang Duan 4 Lili Ju 4 Xiaotong Zhuang 4 Xicheng Jiang 5
Affiliations

Affiliations

  • 1 Department of Acupuncture and Moxibustion, The First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China.
  • 2 Department of Acupuncture and Moxibustion, The Second Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China.
  • 3 Department of Integrated Chinese and Western Medicine, The First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China.
  • 4 Department of Chinese Medicine Clinical Foundation, School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin, China.
  • 5 Department of Synopsis of the Golden Chamber, School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin, China.
Abstract

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.

Keywords

AMPK/mTOR/P70S6K pathway; HT 22; autophagy; cerebral I/R injury; eugenol.

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