ABSTRACT
Stroke is a destructive cerebrovascular event caused by the interruption of cerebral blood flow caused by the blockage or rupture of cerebral vessels， which is easy to cause physical disability and multiple functional injuries. The mortality rate of stroke patients in China occupies the first place in the world. How to effectively treat stroke is one of the urgent health problems to be solved. In the clinic， academician WANG Yong-yan observed that 60% of stroke patients with heat-phlegm and sthenic-Fu syndrome. Most of the patients with heat-phlegm and sthenic-Fu syndrome are characterized by stagnation of stool， bad breath and dry pharynx， and so on， After clinical practice， Xinglou Chengqi decoction （XLCQD） was established to treat stroke patients with heat-phlegm and sthenic-Fu syndrome. XLCQD is one of the representative prescriptions for removing phlegm to relax bowels， which is composed of Rhei Radix et Rhizoma， Natrii Sulfas， Trichosanthis Fructus and Arisaema Cum Bile by the ratio of 5∶5∶15∶3. At present， the research on XLCQD is mainly focused on clinical observation and pharmacological mechanism， while the basic research of its pharmacodynamic substance is relatively weak. This paper intends to sort out the chemical composition and pharmacological mechanism of XLCQD， in order to provide the basis for the chemical component identification， drug target prediction and material basis screening of this compound in the later stage. In addition， through the case analysis of XLCQD and modified XLCQD in the treatment of stroke， its rules of clinical application were summarized， in order to provide reference for the clinical application of this compound.
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.
Subject(s)
Animals , Mice , Drugs, Chinese Herbal/pharmacology , Gastrointestinal Microbiome , Mice, Inbred C57BL , Molecular Docking Simulation , Network Pharmacology , Stroke/drug therapyABSTRACT
Objective To observe the changes of serum inflammatory cytokines and clincal effect of Jiawei-Xinglou-Chengqi decoction and Huoxue-Huatan decoction on the patients with acute cerebral infarction. Methods A total of 85 stroke patients were selected from April 2015 to April 2016 in our hospital and divided into the observation group (43 cases) and control group (42 cases) using the random number method. The control group was treated with conventional therapy, and the observation group combined Jiawei-Xinglou-Chengqi decoction and Huoxue-Huatan decoction based on the treatment of control group. Thetreatment last for 2 weeks. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the patients mental function defect, the Barthel Index (activities of daily living, ADL) to evaluate the ability of daily life, and the TC, TG, LDL-C, and the fibrinogen, platelet count, prothrombin time, clinical evaluation were detected and compared. Results The total effective rate of the observation group was 100.0％ (43/43), while the control group was 81.0％ (34/42), and the difference between both groups was statistically significant (χ2=9.041, P<0.01). After treatment, the NHISS (5.24 ± 2.61 vs.12.78 ± 3.93, t=10.443) in the observation group was significantly lower than the control group, and the ADL (89.75 ± 6.51 vs. 72.22 ± 5.24, t=14.197) in the observation group was significantly higher than the control group (P<0.01). The serum levels of TC (4.6 ± 0.9 mmol/L vs. 5.42 ± 0.7 mmol/L, t=21.538), TG (2.0 ± 0.8 mmol/L vs. 2.4 ± 0.6 mmol/L, t=8.585), LDL-C (2.7 ± 0.8 mmol/L vs. 3.1 ± 0.8 mmol/L, t=9.092) in the observation group were significantly lower than those in the control group (P<0.01). The fibrinogen (2.81 ± 0.46 g/L vs. 2.95 ± 0.51 g/L, t=8.592) in the observation group was significantly lower than that in the control group (P<0.01), and prothrombin time (16.14 ± 1.62 s vs. 15.34 ± 1.18 s, t=14.139) in the observation group was significantly longer than that in the control group (P<0.01). Conclusions The combination of Jiawei-Xinglou-Chengqi decoction and Huoxue-Huatan decoction could improve curative effect, reduce blood lipid, improve coagulation function, improve quality of life and promote recovery of nerve function in patients with acute cerebral infarction.