基于网络药理学和分子对接探讨桃红四物汤治疗慢性胆囊炎的机制

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Abstract Objective To explore the mechanism of Tao-Hong-Si-Wu Decoction (THSWD) in treating chronic cholecystitis based on network pharmacology and molecular docking, so as to save the cost for the research and development of new drugs and make the experiment more targeted. Methods The effective components of drugs were searched by TCMSP database, and their corresponding targets were predicted in wiss Target Prediction. Then the target of chronic cholecystitis is predicted by GeneCards database. After establishing the target database of drugs and diseases, PPI network diagram, drug composition-target diagram and G0 and KEGG enrichment analysis were drawn. According to the degree value, the target of the core component was screened out, and then the combination of the two was verified by molecular docking. Finally, LPS stimulated human gallbladder epithelial cells to induce inflammation, and Elisa kit was used to detect the concentration of inflammatory mediators in supernatant. Western blot was used to detect the expression of AKT and p-AKT after treatment with different concentrations of THSWD. Results 3,262 potential targets of 49 active components of THSWD were screened, and 665 potential targets were obtained after weight removal. There are 681 disease targets, and Go enrichment analysis shows that the target proteins are mainly involved in smooth muscle cell proliferation, MAPK cascade reaction, inflammatory reaction, protein kinase B signal regulation and so on. KEGG enrichment analysis found that the target was involved in 140 pathways, mainly involving AGE-RAGE signaling pathway, HIF-1 signaling pathway, PI3K-Akt signaling pathway and so on. The core targets screened according to the degree value are AKT1, TNF, TP53, VEGFA and IL-1B, and the core components are kaempferol, luteolin and quercetin. AKT1 with the highest degree was selected for molecular docking with kaempferol, and the results were visualized. CCK-8 experimental results showed that THSWD of 12.5ug/ml and 25ug/ml had no obvious toxic effect on gallbladder epithelial cells. The results of Elisa showed that the level of IL-6 increased significantly after lipopolysaccharide stimulation, but decreased significantly after THSWD treatment. Western blot showed that the expression of p-AKT increased in LPS-induced group and decreased in THSWD-treated group. Conclusion Based on the network pharmacology, molecular docking and cell experiments, it is found for the first time that THSWD is effective in the treatment of chronic cholecystitis, and AKT1 and Kaempferol may be its target and one of its effective components respectively.

Key words： network pharmacology molecular docking cholecystitis mechanism research

Received: 08 April 2023

PACS:

R657.4

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	HE Siyuan
	PENG Chuang

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HE Siyuan,PENG Chuang. Mechanism of Tao-Hong-Si-Wu Decoction in Treating Chronic Cholecystitis Based on Network Pharmacology and Molecular Docking[J]. HuNan ShiFan DaXue XueBao(YiXueBan), 2023, 20(5): 125-131.

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http://yxb.hunnu.edu.cn/EN/ OR http://yxb.hunnu.edu.cn/EN/Y2023/V20/I5/125

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