Xinglou Chengqi Decoction improves neurological function in experimental stroke mice as evidenced by gut microbiota analysis and network pharmacology / 中国天然药物

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.

[Systematic evaluation and Meta-analysis of efficacy and safety of Tianzhi Granules in treatment of vascular cognitive impairment].

Tianzhi Granules has effects in calming liver wind, nourishing liver and kidney and activating blood. At present, it is used for treatment of vascular cognitive impairment. However, its efficacy and safety remained to be verified. Therefore, this study aims to systematically analyze the efficacy and safety of Tianzhi Granules in the treatment of vascular cognitive impairment. CNKI, VIP, WanFang, SinoMed, PubMed and Cochrane Library, ClinicalTrials.gov were retrieved to screen out relevant randomized controlled trials about the effect of Tianzhi Granules on vascular cognitive impairment according to the inclusion criteria. Two researchers independently used the risk of bias assessment tool for quality assessment, and extracted and checked the data. Cochrane systematic evaluation software RevMan 5.3 was used for data analysis. Twenty-seven articles involving 2 741 subjects were included. The intervention measure was Tianzhi Granules alone, and the control measure was Western medicine alone or blank control. According to the results, Tianzhi Granules was better than blank control and brain metabolism promoter in clinical efficacy rate and improvement of MMSE score. And it was better than blank control and nimodipine in the improvement of event-related potential(ERP) P300. Within 3 months, Tianzhi Granules had better effects than Western medicine group and blank group, with a low incidence of adverse events. Tianzhi Granules can be recommended for clinical use. However, due to the low quality of the include literatures, these potential benefits need to be confirmed in future standardized clinical trials with a large sample size.