PMID- 37467820 OWN - NLM STAT- MEDLINE DCOM- 20230918 LR - 20230918 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 318 IP - Pt A DP - 2024 Jan 10 TI - Sanpian decoction ameliorates cerebral ischemia-reperfusion injury by regulating SIRT1/ERK/HIF-1alpha pathway through in silico analysis and experimental validation. PG - 116898 LID - S0378-8741(23)00766-3 [pii] LID - 10.1016/j.jep.2023.116898 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: Cerebral ischemia-reperfusion injury (CIRI) is a complex pathophysiological process involving multiple factors, and becomes the footstone of rehabilitation after ischemic stroke. Sanpian decoction (SPD) has exhibited protective effects against CIRI, migraine, and other cerebral vascular diseases. However, the underlying mechanisms have not been completely elucidated. AIM OF THE STUDY: This study sought to explore the potential mechanisms underlying the effect of SPD against CIRI. MATERIALS AND METHODS: High-performance liquid chromatography (HPLC) and ultra-high-performance liquid chromatography (UPLC) were carried out to determine the chemical constituents of SPD. A network pharmacology approach combined with experimental verification was conducted to elucidate SPD's multi-component, multi-target, and multi-pathway mechanisms in CIRI occurrence. The pharmacodynamics of the decoction was evaluated by establishing the rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). In vivo and in vitro experiments were carried out, and the therapeutic effects of SPD were performed using 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, and Nissl staining. We used terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and flow cytometry to evaluate cortex apoptosis. The quantification of mRNA and corresponding proteins were performed using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot respectively. RESULTS: Our research showed that pretreatment with SPD improved neurological function and inhibited CIRI. Network pharmacology revealed that the hypoxia-inducible factor-1 (HIF-1) signaling pathway and mitogen-activated protein kinase (MAPK) signaling pathway-mediated apoptosis may be associated with CIRI. In vivo and in vitro experiments, we confirmed that SPD increased cerebral blood flow, improved neural function, and reduced neural apoptosis via up-regulating the expression of sirtuin 1 (SIRT1) and down-regulating phospho-extracellular regulated protein kinases (p-ERK)/ERK and HIF-1alpha levels in CIRI rats. CONCLUSION: Taken together, the present study systematically revealed the potential targets and signaling pathways of SPD in the treatment of CIRI using in silico prediction and verified the therapeutic effects of SPD against CIRI via ameliorating apoptosis by regulating SIRT1/ERK/HIF-1alpha. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Yang, Tong AU - Yang T AD - Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China. FAU - Liu, Xiaolu AU - Liu X AD - Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, College of Medicine and Health Sciences, China Three Gorges University, Yichang, 443002, Hubei, China; State Key Laboratory of Natural Medicines and School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, Jiangsu, China. FAU - Zhou, Yue AU - Zhou Y AD - Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China. FAU - Du, Lipeng AU - Du L AD - Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, College of Medicine and Health Sciences, China Three Gorges University, Yichang, 443002, Hubei, China. FAU - Fu, Yang AU - Fu Y AD - Xiangyang Hospital of Traditional Chinese Medicine, Xiangyang, 441000, Hubei, China. FAU - Luo, Yanan AU - Luo Y AD - Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, College of Medicine and Health Sciences, China Three Gorges University, Yichang, 443002, Hubei, China. FAU - Zhang, Wenli AU - Zhang W AD - School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China. FAU - Feng, Zhitao AU - Feng Z AD - Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, College of Medicine and Health Sciences, China Three Gorges University, Yichang, 443002, Hubei, China. Electronic address: fengzhitao2008@126.com. FAU - Ge, Jinwen AU - Ge J AD - Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China. Electronic address: 001267@hnucm.edu.cn. FAU - Mei, Zhigang AU - Mei Z AD - Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China; Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, College of Medicine and Health Sciences, China Three Gorges University, Yichang, 443002, Hubei, China. Electronic address: meizhigang@hnucm.edu.cn. LA - eng PT - Journal Article DEP - 20230717 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - EC 3.5.1.- (Sirtuin 1) SB - IM MH - Rats MH - Animals MH - Sirtuin 1/metabolism MH - Rats, Sprague-Dawley MH - *Brain Ischemia/metabolism MH - Signal Transduction/physiology MH - Apoptosis MH - Infarction, Middle Cerebral Artery/drug therapy/metabolism MH - *Reperfusion Injury/drug therapy/metabolism OTO - NOTNLM OT - Apoptosis OT - Cerebral ischemia-reperfusion injury OT - HIF-1 signaling pathway OT - MAPK signaling pathway OT - Network pharmacology OT - Sanpian decoction COIS- Declaration of competing interest The authors declare that no potential conflict of interest that could have appeared to influence the work reported in this paper. EDAT- 2023/07/20 01:06 MHDA- 2023/09/18 12:42 CRDT- 2023/07/19 19:22 PHST- 2023/04/11 00:00 [received] PHST- 2023/06/15 00:00 [revised] PHST- 2023/07/08 00:00 [accepted] PHST- 2023/09/18 12:42 [medline] PHST- 2023/07/20 01:06 [pubmed] PHST- 2023/07/19 19:22 [entrez] AID - S0378-8741(23)00766-3 [pii] AID - 10.1016/j.jep.2023.116898 [doi] PST - ppublish SO - J Ethnopharmacol. 2024 Jan 10;318(Pt A):116898. doi: 10.1016/j.jep.2023.116898. Epub 2023 Jul 17.