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Abstract
Context
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.
Authors’ contributions
WG Liao, LS Wang, and MC Wang coordinated and directed the project. WG Liao, Y Wu, Z Xie and MY Gong performed the network pharmacology and molecular docking. YX Li, JY Du, AY Su, and LY Zhong carried out the in vivo experiments; JH Liang, Z Liu and PC Wang collated data. All authors were involved in the writing of the article. All authors reviewed and approved the final version of the manuscript.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Additional information
Funding
Notes on contributors
Weiguo Liao
WG Liao is a Ph.D. student at Guangzhou University of Chinese Medicine, mainly engaged in scientific research in pharmacology and pharmacy. He has published 3 SCI articles as the first author and 1 SCI article as the corresponding author, involving the development of stroke and cancer drugs.
Minchun Wang
MC Wang, Y Wu, JY Du, YX Li, AY Su, PC Wang, JH Liang, and LY Zhong are current graduate students of Guangzhou University of Chinese Medicine, focussing on pharmacology and modern molecular biology.
Ying Wu
MC Wang, Y Wu, JY Du, YX Li, AY Su, PC Wang, JH Liang, and LY Zhong are current graduate students of Guangzhou University of Chinese Medicine, focussing on pharmacology and modern molecular biology.
Jinyan Du
MC Wang, Y Wu, JY Du, YX Li, AY Su, PC Wang, JH Liang, and LY Zhong are current graduate students of Guangzhou University of Chinese Medicine, focussing on pharmacology and modern molecular biology.
Yaxin Li
MC Wang, Y Wu, JY Du, YX Li, AY Su, PC Wang, JH Liang, and LY Zhong are current graduate students of Guangzhou University of Chinese Medicine, focussing on pharmacology and modern molecular biology.
Anyu Su
MC Wang, Y Wu, JY Du, YX Li, AY Su, PC Wang, JH Liang, and LY Zhong are current graduate students of Guangzhou University of Chinese Medicine, focussing on pharmacology and modern molecular biology.
Lanying Zhong
MC Wang, Y Wu, JY Du, YX Li, AY Su, PC Wang, JH Liang, and LY Zhong are current graduate students of Guangzhou University of Chinese Medicine, focussing on pharmacology and modern molecular biology.
Zi Xie
Z Xie and MY Gong are undergraduate students of Guangzhou University of Chinese Medicine majoring in TCM.
Mingyu Gong
Z Xie and MY Gong are undergraduate students of Guangzhou University of Chinese Medicine majoring in TCM.
Junhui Liang
MC Wang, Y Wu, JY Du, YX Li, AY Su, PC Wang, JH Liang, and LY Zhong are current graduate students of Guangzhou University of Chinese Medicine, focussing on pharmacology and modern molecular biology.
Pengcheng Wang
MC Wang, Y Wu, JY Du, YX Li, AY Su, PC Wang, JH Liang, and LY Zhong are current graduate students of Guangzhou University of Chinese Medicine, focussing on pharmacology and modern molecular biology.
Zai Liu
Z Liu is a chief pharmacist at Dongguan Hospital of Traditional Chinese Medicine, with deep academic attainment in the field of TCM.
Lisheng Wang
LS Wang is a professor at Guangzhou University of Chinese Medicine, mainly engaged in pharmacy and pharmacology research, and has achieved fruitful results in TCM against stroke. He has published more than 10 SCI papers as the corresponding author.