文献类型：期刊文献

英文题名：Naoxintong capsule accelerates mitophagy in cerebral ischemia-reperfusion injury via TP53/PINK1/PRKN pathway based on network pharmacology analysis and experimental validation

作者：Shang, Jinfeng[1];Wen, Yinlian[1];Zhang, Xiaolu[1];Huang, Guijinfeng[1];Chen, Wenbin[1];Wang, Bohong[1];Wu, Kai[1];Xiang, Quan[2];Liu, Xin[1]

第一作者：Shang, Jinfeng

通信作者：Wu, K[1];Liu, X[1];Xiang, Q[2]

机构：[1]Beijing Univ Chinese Med, Gongchen St, Beijing 102488, Peoples R China;[2]Gansu Univ Chinese Med, Gansu 730101, Peoples R China

第一机构：Beijing Univ Chinese Med, Gongchen St, Beijing 102488, Peoples R China

通信机构：[1]corresponding author), Beijing Univ Chinese Med, Gongchen St, Beijing 102488, Peoples R China;[2]corresponding author), Gansu Univ Chinese Med, Gansu 730101, Peoples R China.|[10735]甘肃中医药大学;

年份：2025

卷号：336

外文期刊名：JOURNAL OF ETHNOPHARMACOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001306642900001)】；

基金：Funding This research was funded by Basic Research Foundation of Beijing University of Chinese Medicine (No. 2022-JYB-JBZR-005, funder: Xin Liu) and National Natural Science Foundation of China (No.81573726, funder: Xin Liu) .

语种：英文

外文关键词：Cerebral ischemia-reperfusion injury; Naoxintong capsule; Mitophagy; TP53/PINK1/PRKN pathway

摘要：Ethnopharmacological relevance: The incidence and mortality of cerebrovascular diseases are increasing year by year. Cerebral ischemia-reperfusion injury (CIRI) is common in patients with ischemic stroke. Naoxintong (NXT) is composed of a variety of Chinese medicines and has the ability to treat CIRI. Aim of the study: The aim of this study is to investigate whether NXT regulates mitophagy in CIRI based on network pharmacology analysis and experimental validation. Materials and methods: Oxygen and glucose deprivation/re-oxygenation (OGD/R, 2/22 h) model of PC12 cells and transient middle cerebral artery occlusion (tMCAO, 2/22 h) model of rats were established. Pharmacodynamic indicators include neurological deficit score, 2,3,5-triphenyte-trazoliumchloride (TTC) staining, hematoxylineosin (HE) staining and cell viability. Network pharmacology was used to predict pharmacological mechanisms. Pharmacological mechanism indexes include transmission electron microscopy (TEM), drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), immunohistochemistry (IHC), western blot (WB) and immunofluorescence (IF). Kevetrin (an agonists of p53) and pifithrin-alpha (an inhibitor of p53) used to detect the key role of p53 in mitophagy of NXT. Results: NXT (1% serum containing NXT and 110 mg/kg) improved the damage of OGD/R PC12 cells and tMCAO rats, and this protective effect was related to the anti-oxidation and ability to promote mitophagy of NXT. NXT and pifithrin-alpha increased the expression of promoting-mitophagy targets (PINK1, PRKN and LC3B) and inhibited the expression of inhibiting-mitophagy targets (p52) via restraining p53, and finally accelerated mitophagy caused by CIRI. Conclusion: This study demonstrates that NXT promotes mitophagy in CIRI through restraining p53 and promoting PINK1/PRKN in vivo and in vitro.