基于网络药理学及分子对接探究益母草碱治疗肠道炎症的分子机制

doi:10.16431/j.cnki.1671-7236.2023.05.037

Abstract

Abstract: 【Objective】 The molecular mechanism of leonurine in the treatment of intestinal inflammation was investigated using network pharmacology,molecular docking and kinetic simulation techniques.【Method】Pubchem,PharmMapper and SwissTargetPrediction database were used to collect the potential targets of leonurine and intestinal inflammation,and obtain the intersection targets of leonurine in the treatment of intestinal inflammation in the Venny 2.1 online mapping tool platform system.The protein-protein interaction (PPI) relationship was obtained through STRING and DAVID databases,and the PPI network diagram of the intersection target was drawn.The GO function and KEGG pathway enrichment analysis of the intersection target was carried out,and the core target protein was screened by Cytascape 3.8.2 software.The core target was verified by molecular docking technology and molecular dynamics simulation.【Result】 A total of 379 potential target proteins related to leonurine and 15 464 potential targets related to intestinal inflammation were collected.170 potential intersection targets of leonurine for the treatment of intestinal inflammation were obtained.16 core targets including serine/threonine protein kinase 1(AKT1),tumor suppressor genes TP53,prostaglandin-endoperoxide synthase 2(PTGS2),mechanistic target of rapamycin (mTOR),poly ADP-ribose polymerase 1 (PARP1),etc. were screened.The results of GO function and KEGG pathway enrichment analysis showed that leonurine regulated 144 biological processes such as protein phosphorylation,cell proliferation,negative regulation of apoptosis,proteolysis,and inflammation,as well as 55 signal pathways,such as Fc epsilon RI signaling pathway and Fc γ-R-mediated phagocytosis including MAPK signaling pathway and mTOR signaling pathway to treat intestinal inflammation.Molecular docking results showed that leonurine had good docking results with the core targets PTGS2,mTOR and PARP1,and had strong binding activity.Molecular dynamics simulations had found that leonurine was mainly bound to the three proteins by hydrogen and hydrophobic bonds.【Conclusion】 Leonurine exerted its therapeutic effect on intestinal inflammation through multiple targets such as mTOR,PARP1 and PTGS2,and multiple signaling pathways and multiple pathways.The result of this study laid a foundation for the clinical application of leonurine.

Key words: leonurine; intestinal inflammation; network pharmacology; molecular docking; molecular dynamics simulation; action mechanism

CLC Number:

S859.7

XU Chenghui, ZHANG Xumei, YANG Tong, LI Jiahui, SUN Yawei, SHI Huijun, FU Qiang, YANG Li. Molecular Mechanism of Leonurine in the Treatment of Intestinal Inflammation Based on Network Pharmacology and Molecular Docking[J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(5): 2103-2113.

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Molecular Mechanism of Leonurine in the Treatment of Intestinal Inflammation Based on Network Pharmacology and Molecular Docking

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