The mechanisms of Huangqi Guizhi Wuwu decoction in treating ischaemic stroke based on network pharmacology and experiment verification

AbstractContext Huangqi Guizhi Wuwu Decoction (HGWD) is effective in treating ischaemic stroke (IS). However, its mechanism of action is still unclear.Objective Network pharmacology integrated with in vivo experiments were used to clarify the underlying mechanisms of HGWD for treating IS.Materials a...

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Main Authors: Weiguo Liao, Minchun Wang, Ying Wu, Jinyan Du, Yaxin Li, Anyu Su, Lanying Zhong, Zi Xie, Mingyu Gong, Junhui Liang, Pengcheng Wang, Zai Liu, Lisheng Wang
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:Pharmaceutical Biology
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/13880209.2023.2230477
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author Weiguo Liao
Minchun Wang
Ying Wu
Jinyan Du
Yaxin Li
Anyu Su
Lanying Zhong
Zi Xie
Mingyu Gong
Junhui Liang
Pengcheng Wang
Zai Liu
Lisheng Wang
author_facet Weiguo Liao
Minchun Wang
Ying Wu
Jinyan Du
Yaxin Li
Anyu Su
Lanying Zhong
Zi Xie
Mingyu Gong
Junhui Liang
Pengcheng Wang
Zai Liu
Lisheng Wang
author_sort Weiguo Liao
collection DOAJ
description AbstractContext Huangqi Guizhi Wuwu Decoction (HGWD) is effective in treating ischaemic stroke (IS). However, its mechanism of action is still unclear.Objective Network pharmacology integrated with in vivo experiments were used to clarify the underlying mechanisms of HGWD for treating IS.Materials and methods TCMSP, GeneCards, OMIM and STRING were used to retrieve and construct visual protein interaction networks for the key targets. The AutoDock tool was used for molecular docking between key targets and active compounds. The neuroprotective effect of HGWD were verified in a middle cerebral artery occlusion (MCAO) model rat. The Sprague-Dawley (SD) rats were divided into sham, model, low-dose (5 g/kg, i.g.), high-dose (20 g/kg, i.g.), and nimodipine (20 mg/kg, i.g.) groups once daily for 7 days. The neurological scores, brain infarct volumes, lipid peroxidation, inflammatory cytokines, Nissl bodies, apoptotic neurons, and signalling pathways were all investigated and evaluated in vivo.Results Network pharmacology identified 117 HGWD targets related to IS and 36 candidate compounds. GO and KEGG analyses showed that HGWD anti-IS effects were mainly associated with PI3K-Akt and HIF-1 signalling pathways. HGWD effectively reduced the cerebral infarct volumes (19.19%), the number of apoptotic neurons (16.78%), and the release of inflammatory cytokines, etc. in MCAO rats. Furthermore, HGWD decreased the levels of HIF-1A, VEGFA, Bax, cleaved caspase-3, p-MAPK1, and p-c-Jun while increasing the expression of p-PI3K, p-AKT1, and Bcl-2.Discussion and conclusion This study initially elucidated the mechanism of HGWD anti-IS, which contributed to the further promotion and secondary development of HGWD in clinical practice.
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spelling doaj.art-3bfad3e47a01423d965d1fc7a643f48f2024-03-29T11:10:26ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162023-12-016111014102910.1080/13880209.2023.2230477The mechanisms of Huangqi Guizhi Wuwu decoction in treating ischaemic stroke based on network pharmacology and experiment verificationWeiguo Liao0Minchun Wang1Ying Wu2Jinyan Du3Yaxin Li4Anyu Su5Lanying Zhong6Zi Xie7Mingyu Gong8Junhui Liang9Pengcheng Wang10Zai Liu11Lisheng Wang12College of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaCollege of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaCollege of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaCollege of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaCollege of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaCollege of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaCollege of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaCollege of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaCollege of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaCollege of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaCollege of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaPharmacy Department, Dongguan Hospital of Traditional Chinese Medicine, Dongguan, Guangdong, ChinaCollege of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaAbstractContext Huangqi Guizhi Wuwu Decoction (HGWD) is effective in treating ischaemic stroke (IS). However, its mechanism of action is still unclear.Objective Network pharmacology integrated with in vivo experiments were used to clarify the underlying mechanisms of HGWD for treating IS.Materials and methods TCMSP, GeneCards, OMIM and STRING were used to retrieve and construct visual protein interaction networks for the key targets. The AutoDock tool was used for molecular docking between key targets and active compounds. The neuroprotective effect of HGWD were verified in a middle cerebral artery occlusion (MCAO) model rat. The Sprague-Dawley (SD) rats were divided into sham, model, low-dose (5 g/kg, i.g.), high-dose (20 g/kg, i.g.), and nimodipine (20 mg/kg, i.g.) groups once daily for 7 days. The neurological scores, brain infarct volumes, lipid peroxidation, inflammatory cytokines, Nissl bodies, apoptotic neurons, and signalling pathways were all investigated and evaluated in vivo.Results Network pharmacology identified 117 HGWD targets related to IS and 36 candidate compounds. GO and KEGG analyses showed that HGWD anti-IS effects were mainly associated with PI3K-Akt and HIF-1 signalling pathways. HGWD effectively reduced the cerebral infarct volumes (19.19%), the number of apoptotic neurons (16.78%), and the release of inflammatory cytokines, etc. in MCAO rats. Furthermore, HGWD decreased the levels of HIF-1A, VEGFA, Bax, cleaved caspase-3, p-MAPK1, and p-c-Jun while increasing the expression of p-PI3K, p-AKT1, and Bcl-2.Discussion and conclusion This study initially elucidated the mechanism of HGWD anti-IS, which contributed to the further promotion and secondary development of HGWD in clinical practice.https://www.tandfonline.com/doi/10.1080/13880209.2023.2230477Chinese medicine formulamolecular dockingPI3K-Akt pathwayHIF-1 pathwaysinflammationapoptosis
spellingShingle Weiguo Liao
Minchun Wang
Ying Wu
Jinyan Du
Yaxin Li
Anyu Su
Lanying Zhong
Zi Xie
Mingyu Gong
Junhui Liang
Pengcheng Wang
Zai Liu
Lisheng Wang
The mechanisms of Huangqi Guizhi Wuwu decoction in treating ischaemic stroke based on network pharmacology and experiment verification
Pharmaceutical Biology
Chinese medicine formula
molecular docking
PI3K-Akt pathway
HIF-1 pathways
inflammation
apoptosis
title The mechanisms of Huangqi Guizhi Wuwu decoction in treating ischaemic stroke based on network pharmacology and experiment verification
title_full The mechanisms of Huangqi Guizhi Wuwu decoction in treating ischaemic stroke based on network pharmacology and experiment verification
title_fullStr The mechanisms of Huangqi Guizhi Wuwu decoction in treating ischaemic stroke based on network pharmacology and experiment verification
title_full_unstemmed The mechanisms of Huangqi Guizhi Wuwu decoction in treating ischaemic stroke based on network pharmacology and experiment verification
title_short The mechanisms of Huangqi Guizhi Wuwu decoction in treating ischaemic stroke based on network pharmacology and experiment verification
title_sort mechanisms of huangqi guizhi wuwu decoction in treating ischaemic stroke based on network pharmacology and experiment verification
topic Chinese medicine formula
molecular docking
PI3K-Akt pathway
HIF-1 pathways
inflammation
apoptosis
url https://www.tandfonline.com/doi/10.1080/13880209.2023.2230477
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