Xinglou Chengqi Decoction improves neurological function in experimental stroke mice as evidenced by gut microbiota analysis and network pharmacology.
10.1016/S1875-5364(21)60079-1
- Author:
Qiang GAO
1
;
Zhen-Yun HAN
2
;
Dan-Feng TIAN
1
;
Gan-Lu LIU
1
;
Zhen-Yi WANG
1
;
Jing-Feng LIN
1
;
Ze CHANG
1
;
Dan-Dan ZHANG
1
;
Ying-Zhen XIE
3
;
Yi-Kun SUN
4
;
Xing-Wei YAO
5
;
Da-Yong MA
6
Author Information
1. Beijing University of Chinese Medicine, Beijing 100029, China.
2. Shenzhen Hospital of Beijing University of Chinese Medicine (Longgang), Shenzhen 518172, China.
3. Department of Neurology, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China.
4. Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China.
5. Clinical Laboratory, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China.
6. Department of Neurology, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China. Electronic address: ponymdy@163.com.
- Publication Type:Journal Article
- Keywords:
Gut microbiota;
Ischemic stroke;
Network pharmacology;
Xinglou Chengqi Decoction
- MeSH:
Animals;
Drugs, Chinese Herbal/pharmacology*;
Gastrointestinal Microbiome;
Mice;
Mice, Inbred C57BL;
Molecular Docking Simulation;
Network Pharmacology;
Stroke/drug therapy*
- From:
Chinese Journal of Natural Medicines (English Ed.)
2021;19(12):881-899
- CountryChina
- Language:English
-
Abstract:
The current study was designed to explore the brain protection mechanism of Xinglou Chengqi Decoction (XCD) based on gut microbiota analysis and network pharmacology. A transient middle cerebral artery occlusion (MCAO) model of mice was established, followed by behavioral evaluation, TTC and TUNEL staining. Additionally, to investigate the effects of gut microbiota on neurological function after stroke, C57BL/6 mice were treated with anti-biotic cocktails 14 days prior to ischemic stroke (IS) to deplete the gut microbiota. High-throughput 16S rDNA gene sequencing, metabonomics technique, and flow multifactor technology were used to analyze bacterial communities, SCFAs and inflammatory cytokines respectively. Finally, as a supplement, network pharmacology and molecular docking were applied to fully explore the multicomponent-multitarget-multichannel mechanism of XCD in treating IS, implicated in ADME screening, target identification, network analysis, functional annotation, and pathway enrichment analysis. We found that XCD effectively improved neurological function, relieved cerebral infarction and decreased the neuronal apoptosis. Moreover, XCD promoted the release of anti-inflammatory factor like IL-10, while down-regulating pro-inflammatory factors such as TNF-α, IL-17A, and IL-22. Furthermore, XCD significantly increased the levels of short chain fatty acids (SCFAs), especially butyric acid. The mechanism might be related to the regulation of SCFAs-producing bacteria like Verrucomicrobia and Akkermansia, and bacteria that regulate inflammation like Paraprevotella, Roseburia, Streptophyta and Enterococcu. Finally, in the network pharmacological analysis, 51 active compounds in XCD and 44 intersection targets of IS and XCD were selected. As a validation, components in XCD docked well with key targets. It was obviously that biological processes were mainly involved in the regulation of apoptotic process, inflammatory response, response to fatty acid, and regulation of establishment of endothelial barrier in GO enrichment. XCD can improve neurological function in experimental stroke mice, partly due to the regulation of gut microbiota. Besises, XCD has the characteristic of "multi-component, multi-target and multi-channel" in the treatment of IS revealed by network pharmacology and molecular docking.
