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Research Paper|Volume 16, Issue 8|pp 7474—7486

Mechanism of ameliorating cerebral ischemia/reperfusion injury by antioxidant inhibition of autophagy based on network pharmacology and experimental verification

Yuantie Zheng1, Zhicheng Huang2, Yang Zhao5, Lili Huang3, Jun Wang5, Heping Li5, Xing Chen5, Jingsong Wang5, Jingwen Xie1,4
  • 1Department of Pharmacy, The Second Affiliated Hospital and Yuying Children’s Hospital of the Wenzhou Medical University, Wenzhou, Zhejiang, China
  • 2Department of Pharmacy, Ezhou Central Hospital, Ezhou, Hubei, China
  • 3Department of Pharmacy, Lihuili Hospital Affiliated to Ningbo University, Ningbo, Zhejiang, China
  • 4Department of Health, Chongqing Industry and Trade Polytechnic, Chongqing, China
  • 5Department of Pharmacy, Guangyuan Central Hospital, Guangyuan, Sichuan, China
* Equal contribution
Received: November 20, 2023Accepted: March 18, 2024Published: April 25, 2024
https://doi.org/10.18632/aging.205773

Copyright: © 2024 Zheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Cerebral ischemia-reperfusion injury (CIRI) is one of the most difficult challenges in cerebrovascular disease research. It is primarily caused by excessive autophagy induced by oxidative stress. Previously, a novel compound X5 was found, and the excellent antioxidant activity of it was verified in this study. Moreover, network pharmacological analysis suggested that compound X5 was closely associated with autophagy and the mTOR pathway. In vitro, X5 could significantly inhibit the expression of autophagy proteins Beclin-1 and LC3-β, which are induced by H2O2, and promote the expression of SIRT1. In vivo, compound X5 significantly reduced the infarct size and improved the neurological function scores in the middle cerebral artery occlusion (MCAO) model of rats. In conclusion, ROS-induced autophagy is closely related to mTOR, SIRT1 and others, and X5 holds promise as a candidate for the treatment of CIRI.