Lihan Wang, Jingyi Hou, He Xu, Qingqing Cai, Liangliang Tian, Xueli Li, Jingjing Zhang, Hongjun Yang
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引用次数: 0
Abstract
Ethnopharmacological relevance: Cerebral ischemia-reperfusion injury (CIRI) is an important pathological process in stroke treatment. Angong Niuhuang Pill (ANP), originating from Wenbing Tiaobian, has been shown to have neuroprotective effects, but its mechanism in alleviating CIRI remains unclear.
Aim of the study: This study aimed to elucidate the mechanism by which ANP alleviates CIRI using acetylomics and proteomics.
Materials and methods: The CIRI model was established using middle cerebral artery occlusion (MCAO). Neurological deficit scoring, TTC staining, regional cerebral blood flow (rCBF) measurement, and TUNEL staining were used to assess the neuroprotective effects of ANP pretreatment on CIRI. Acetylomics and proteomics analyses were performed to identify the potential mechanisms by which ANP reduces CIRI. Finally, the role of SIRT1-H4K16ac-mediated autophagy in the neuroprotective effects of ANP was validated by using a SIRT1 inhibitor, EX527.
Results: ANP pretreatment markedly lowered neurological deficit scores and cerebral infarct volumes, increased rCBF, and reduced apoptosis. Acetylomics and proteomics results suggested that ANP regulated autophagy at the transcriptional level by modulating H4K16ac. Immunofluorescence and Western blot analyses confirmed that ANP promoted the accumulation of sirtuin 1 (SIRT1). Specifically, ANP pretreatment reduced H4K16ac levels, decreased LC3B-II/I ratios, upregulated SQSTM1/p62, and suppressed the expression of ATG5 and ATG7. The ability of EX527 to counteract these effects underscored the importance of the SIRT1-H4K16ac pathway in mediating the protective action of ANP against CIRI.
Conclusions: ANP provides neuroprotection by modulating the SIRT1-H4K16ac pathway, thereby preventing the excessive autophagy triggered by CIRI.
期刊介绍：
The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.
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