基于网络药理学和试验验证分析小檗碱治疗鸡沙门菌感染的作用机制

doi:10.11843/j.issn.0366-6964.2023.08.039

Abstract

Abstract: The objective of this study was to preliminaries verify the potential target and mechanism of berberine (BBR) in the intervention of enteritis in broilers by using network pharmacology, molecular docking and molecular dynamics simulation combined with Salmonella challenge test. Firstly, PharMapper database and Swisstargets database were used to predict drug targets. The disease targets were collected through the GeneCards database, and the intersection of drugs and disease targets was screened. The obtained intersection targets were used to construct protein interaction network and GO and KEGG enrichment analysis. Molecular docking verification and kinetic simulation were carried out for the selected core targets. Subsequently, the intestinal inflammation model of broilers was established to observe the morphology changes of intestinal tissue, and the effect of BBR on the mRNA expression of target protein was verified by qPCR test. Finally, 374 potential BBR targets were screened, and 174 overlapped with enteritis. GO and KEGG enrichment analysis obtained 197 items and 73 items, respectively, which mainly involved signal transduction, protein phosphorylation process, PI3K-Akt, chemokine and Ras signaling pathway. The results of molecular docking and kinetic simulation showed that BBR could bind well to the core target, mainly through hydrophobic force and hydrogen bond. The results of tissue section showed that BBR could significantly alleviate intestinal tissue injury. The results of RT-qPCR showed that the expression of HSP90AA1 was significantly decreased (P<0.001), and the expression of PIK3CA was significantly increased (P<0.01) in cecal tissue of the inflammatory model of broilers. Through network pharmacology and experimental verification, it was found that BBR may regulate the occurrence and development of intestinal inflammation by regulating the expression of HSP90AA1 and PIK3CA, which may involve PI3K-Akt, cAMP, AMPK and other signaling pathways, providing new ideas and methods for further research on the mechanism.

Key words: network pharmacology, berberine, enteritis, molecular docking, mechanism of action

CLC Number:

S853.74

ZHANG Xumei, WEI Yurong, XU Chenghui, YANG Tong, SHI Huijun, FU Qiang, YANG Li. To Analyze the Mechanism of Berberine in the Treatment of Salmonella Gallinarum Infection Based on Network Pharmacology and Experimental Verification[J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(8): 3557-3570.

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To Analyze the Mechanism of Berberine in the Treatment of Salmonella Gallinarum Infection Based on Network Pharmacology and Experimental Verification

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