Ethnopharmacological relevance: Dahuang Huanglian Xiexin Decoction (XXD), derived from Zhang Zhongjing's Treatise on Typhoid Fever, has a long history of medicinal use and is widely used for digestive system diseases. It is mainly composed of three natural medicines, including Dahuang (Rheum palmatum L.), Huanglian (Coptis chinensis Franch.), and Huangqin (Scutellaria baicalensis Georgi). Modern pharmacological research shows that the active ingredients of XXD can have a positive effect on intestinal flora regulatory effect, but its mechanism of action is unclear.
Aims of this study: Clarify the effect of XXD on regulating dysbiosis, and elucidate the mechanism of XXD in alleviating dysbiosis based on network pharmacology, molecular docking and experimental verification.
Methods: Histopathological observation and intestinal high-throughput sequencing were used to observe the effect. Preliminary prediction of the mechanism of action of XXD in treating dysbiosis through network pharmacology and molecular docking. Finally, the effect of XXD on the IL-17 signaling pathway was verified through in vivo experiments.
Results: Histopathology and high-throughput sequencing of intestinal flora indicated that XXD has a good regulatory effect on bacterial dysbiosis. At the same time, network pharmacology identified a total of 40 active compounds, 14 of which may be key compounds for XXD to treat dysbiosis. In addition, the study also revealed 14 potential key targets as well as the top 5 therapeutic targets: IL-6, TNF-α, IL-1β, TP53 and PTGS2. GO and KEGG predicted the key pathway for IL-17 signaling pathway to play a role in XXD. In the verification of the prediction results, it was found that the above targets and the IL-17 target showed strong activity in molecular docking. Furthermore, it was found that XXD can reduce the levels of IL-17, IL-6, TNF-α, IL-1β, p53 and COX-2 in serum, while inhibiting the expression of IL-17, IL-17RA, Act-1 and NF-κB protein and the mRNA expression of IL-17, IL-17RA and Act-1 in colon tissue.
Conclusions: This study found that XXD has a good regulatory effect on dysbiosis and its induced symptoms. Network pharmacology was used to predict the key compounds and therapeutic targets of XXD, and preliminary experiments confirmed that XXD may regulate bacterial dysbiosis by inhibiting the IL-17 signaling pathway.
Keywords: Dahuang Huanglian Xiexin decoction; Dysbiosis; IL-17 signaling pathway; Molecular docking; Network pharmacology.
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