Xinglou Chengqi Decoction improves neurological function in experimental stroke mice as evidenced by

• 作 者: GAO Qiang HAN Zhen-Yun TIAN Dan-Feng LIU Gan-Lu WANG Zhen-Yi LIN Jing-Feng CHANG Ze ZHANG Dan-Dan XIE Ying-Zhen SUN Yi-Kun YAO Xing-Wei MA Da-Yong
• 机 构: Beijing University of Chinese Medicine,Beijing 100029,China;Shenzhen Hospital of Beijing University
• 出 处: 中国天然药物
• 发表日期: 2021年12期
• 关键词: Xinglou Chengqi Decoction Ischemic stroke Gut microbiota Network pharmacology

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 de-plete 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 pharmaco-logy and molecular docking were applied to fully explore the multicomponent-multitarget-multichannel mechanism of XCD in treat-ing 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-a,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 bac-teria that regulate inflammation like Paraprevotella,Roseburia,Streptophyta and Enterococcu.Finally,in the network pharmacologic-al 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 pro-cess,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 char-acteristic of “multi-component,multi-target and multi-channel” in the treatment of IS revealed by network pharmacology and molecu-lar docking.