基于网络药理学和分子对接探究白杨素和柚皮素抗PEDV的作用机制及试验验证

doi:10.16431/j.cnki.1671-7236.2024.04.043

Abstract

Abstract: 【Objective】 This study was objective to explore the target and mechanism of chrysin and naringenin against Porcine epidemic diarrhea virus (PEDV),and provide theoretical basis for further developing new anti-PEDV therapeutic drugs with chrysin and naringenin.【Method】 Online databases of PharmMapper,TCMSP,SEA Search Server and STITCH were used to obtain the potential targets of chrysin and naringenin,at the same time GeneCards database was searched to obtain the targets of PEDV on the host,and Draw Venny Diagram online program was used to obtain the intersection targets of chrysin,naringenin and disease.The target protein-protein interaction (PPI) network was constructed by STRING database and Cytoscape 3.9.1 software,and the key targets were screened,and the GO function and KEGG pathway enrichment of the targets were analyzed.The molecular docking of core targets and small molecules was carried out by AutoDock Vina v 1.2.0 software,and the binding energy and binding mode of chrysin and naringenin with target proteins were analyzed,and the docking results were visualized by PyMOL v 2.5.The effects of chrysin and naringenin on the expression of core target proteins were detected by Real-time quantitative PCR.【Result】 The results showed that there were 12 potential anti-PEDV targets of chrysin,among which albumin (ALB),estrogen receptor 1 (ESR1) and transforming growth factor β-1 protein (TGF-β1) might be the core targets of chrysin against PEDV.Naringenin had 18 potential anti-PEDV targets,among which ALB,Caspase-3 (CASP3) and peroxisome proliferator-activated receptor γ (PPARG) might be the core targets of naringenin against PEDV.The anti-PEDV target of chrysin involved 21 biological processes,5 cellular components and 6 molecular functions and obtained 11 signal pathways,while naringenin anti-PEDV targets involved 31 biological processes,8 cellular components and 19 molecular functions, and obtained 13 signal pathways.There was a strong interaction between the core targets and the two natural compounds due to hydrogen bonding and hydrophobic interaction.Chrysin and naringenin could extremely significantly reduce the expression of Caspase-3 (P<0.01),which might antagonize the apoptosis induced by PEDV by affecting the expression and activation of Caspase-3,and they extremely significantly increased the expression of TGF-β1 protein (P<0.01),which might treat PEDV infection by affecting the expression of TGF-β1 and anti-PEDV-induced inflammation.【Conclusion】This study revealed the mechanism of anti-PEDV effects of chrysin and naringenin through potential core targets ALB,ESR1,TGF-β1 and ALB, Caspase-3,PPARG,respectively, and IL17,PI3K-Akt and AMPK signaling pathways, providing new ideas for the development of novel anti-PEDV drugs.

Key words: Porcine epidemic diarrhea virus (PEDV); network pharmacology; molecular docking; chrysin; naringenin

CLC Number:

S853.74

ZHI Yupeng, LIU Yutong, CHEN Dishi, GONG Mengfei, XIA Xuemei, REN Yupeng. Study on the anti-PEDV Mechanism and Experimental Verification of Chrysin and Naringenin Based on Network Pharmacology and Molecular Docking[J]. China Animal Husbandry and Veterinary Medicine, 2024, 51(4): 1757-1772.

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Study on the anti-PEDV Mechanism and Experimental Verification of Chrysin and Naringenin Based on Network Pharmacology and Molecular Docking

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