PMID- 34848358 OWN - NLM STAT- MEDLINE DCOM- 20220215 LR - 20240229 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 285 DP - 2022 Mar 1 TI - Beneficial effects of mijianchangpu decoction on ischemic stroke through components accessing to the brain based on network pharmacology. PG - 114882 LID - S0378-8741(21)01112-0 [pii] LID - 10.1016/j.jep.2021.114882 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: To explore the effective components, potential targets and neuroprotective related mechanisms of Mijianchangpu decoction (MJCPD), a well-known TCM used by the Chinese Hui minorities to treat stroke, on the prevention and treatment of ischemic stroke (IS) by using experimental models combined with network pharmacology. MATERIALS AND METHODS: The neuroprotective efficacy of MJCPD was estimated by applying the middle cerebral artery occlusion (MCAO) induced cerebral ischemia rats, and the neurological deficits score, TTC and HE staining as well as behavioral evaluation tests were employed to evaluate the beneficial effects. Meanwhile, the bioactive components of MJCPD responsible for the neuroprotective effects were identified by detecting the constituents in the brain of the MCAO rats with UHPLC-QTOF-MS/MS techniques, and these compounds were then underwent for network pharmacology analysis. Firstly, the targets of the bioactive compounds of MJCPD were predicted using Pharmmapper database, and simultaneously, the targets of IS disease were obtained from disease databases including DisGenet, OMIM, and GeneCards. Secondly, the protein-protein interaction (PPI) network between the targets and diseases were established to give the possible therapeutic targets for IS. Thirdly, the go function and KEGG pathway enrichment analysis were carried out and the compound-target-pathway network was constructed by Cytoscape software. Finally, the effective compounds, core targets and possible pathways were obtained by analyzing the connectivity of the network. More importantly, the core targets were verified by western blot experiments to validate the reliability of this study. RESULTS: MJCPD exhibited significant neuroprotective effect on IS, and 16 bioactive components of MJCPD were identified in the brain of the MCAO rats. 59 and 1982 targets related with IS disease were explored from Pharmapper and disease databases, respectively, and 32 intersecting targets were obtained as hypothetical therapeutic targets. Based on the results of the compound-target-pathway and PPI network with the degree was greater than the median, 8 effective compounds (suberic acid, epishyobunone, crocetin monomethyl ester, sfaranal, (Z)-6-octadccenoic acid, nerolidol and gurjunene) and 5 hub targets (SRC, MAPK8, MAPK14, EGFR and MAPK1) as well as 12 pathways were predicted. Western blot results showed that EGFR, p38, ERK and SRC proteins were expressed significantly different after MJCPD treatment as compared with the model group. CONCLUSION: The present study employed network pharmacology, pharmacodynamics and molecular biology techniques to predict and validate the core potential targets and signaling pathways as well as the bioactive components of MJCPD responsible for the treatment of IS. All of which are very helpful to clarify the neuroprotective mechanism of MJCPD, and obviously, the active compounds and targets in this study can also provide clues for the treatment of IS. CI - Copyright (c) 2021 Elsevier B.V. All rights reserved. FAU - Zhao, Xiaojun AU - Zhao X AD - Department of Pharmaceutical analysis, School of Pharmacy, Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University, 1160 Shenli Street, Yinchuan, 750004, China. Electronic address: zhaoxiaojunwr@163.com. FAU - Liu, Jingjing AU - Liu J AD - Department of Pharmaceutical analysis, School of Pharmacy, Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University, 1160 Shenli Street, Yinchuan, 750004, China; School of Pharmacy, Lanzhou University, 222 Tianshui South Road, Lanzhou, 730000, China. Electronic address: 1536263112@qq.com. FAU - Yang, Lingling AU - Yang L AD - Department of Pharmaceutical analysis, School of Pharmacy, Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University, 1160 Shenli Street, Yinchuan, 750004, China. Electronic address: 776974789@qq.com. FAU - Niu, Yang AU - Niu Y AD - Department of Pharmaceutical analysis, School of Pharmacy, Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University, 1160 Shenli Street, Yinchuan, 750004, China. Electronic address: niuyang0227@163.com. FAU - Ren, Ruru AU - Ren R AD - Department of Pharmaceutical analysis, School of Pharmacy, Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University, 1160 Shenli Street, Yinchuan, 750004, China. Electronic address: luckyrenrr@163.com. FAU - Su, Chao AU - Su C AD - Department of Pharmaceutical analysis, School of Pharmacy, Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University, 1160 Shenli Street, Yinchuan, 750004, China. Electronic address: 2483108578@qq.com. FAU - Wang, Yingli AU - Wang Y AD - Department of Pharmaceutical analysis, School of Pharmacy, Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University, 1160 Shenli Street, Yinchuan, 750004, China. Electronic address: 18737803095@163.com. FAU - Chen, Jianyu AU - Chen J AD - Fujian University of Traditional Chinese Medicine, No. 1, Huatuo Road, Minhoushangjie, Fuzhou, 350122, China. Electronic address: chenjianyu122@163.com. FAU - Ma, Xueqin AU - Ma X AD - Department of Pharmaceutical analysis, School of Pharmacy, Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University, 1160 Shenli Street, Yinchuan, 750004, China. Electronic address: maxueqin217@126.com. LA - eng PT - Journal Article DEP - 20211127 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Drugs, Chinese Herbal) RN - 57WA9QZ5WH (Nimodipine) RN - 0 (mijianchangpu) SB - IM MH - Animals MH - Male MH - *Brain Ischemia/drug therapy MH - *Drugs, Chinese Herbal/pharmacology MH - Gene Expression Regulation/drug effects MH - Infarction, Middle Cerebral Artery MH - *Network Pharmacology MH - Nimodipine MH - *Phytotherapy MH - Rats, Sprague-Dawley MH - Specific Pathogen-Free Organisms MH - *Stroke/drug therapy/pathology MH - Rats OTO - NOTNLM OT - Ischemic stroke OT - Mijianchangpu decoction OT - Network pharmacology OT - Pharmacodynamics OT - UHPLC-QTOF-MS/MS EDAT- 2021/12/02 06:00 MHDA- 2022/02/15 06:00 CRDT- 2021/12/01 06:04 PHST- 2021/07/05 00:00 [received] PHST- 2021/11/24 00:00 [revised] PHST- 2021/11/25 00:00 [accepted] PHST- 2021/12/02 06:00 [pubmed] PHST- 2022/02/15 06:00 [medline] PHST- 2021/12/01 06:04 [entrez] AID - S0378-8741(21)01112-0 [pii] AID - 10.1016/j.jep.2021.114882 [doi] PST - ppublish SO - J Ethnopharmacol. 2022 Mar 1;285:114882. doi: 10.1016/j.jep.2021.114882. Epub 2021 Nov 27.