生理病理状态下荭草活性物质对转运体表达的影响

doi:10.3976/j.issn.1002-4026.2025089

Abstract

Abstract: Polygonum orientale L. has an anti-myocardial ischemia effect, and the metabolic processes of its active constituents exhibits considerabledifferences under physiological and pathological conditions. Consideringthe role of transporters in the pathological process of myocardial ischemia and the metabolism of xenobiotics, this study aims to investigate the effects of the active constituents in Polygonum orientale L. on the expressions of liver transporters in rats under physiological and pathological conditions.Network pharmacology was used to screen myocardial ischemia-related targets, followed by protein–protein interaction (PPI) analysis, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Based on a literature review, hepatic transporters and pathways related to myocardial ischemia were identified. Morever, molecular docking was used to predict the binding affinity between the active constituents of Polygonum orientale L. and regulatory proteins of transporters. A rat model of myocardial ischemia was established, and the effects of Polygonum orientale L. extract on the expressions of hepatic transporters were detected using quantitative real-time PCR (qRT-PCR) and western blot. Results revealed that network pharmacology analysis identified 428 common target genes associated with myocardial ischemia and transport proteins. PPI analysis yielded 36 key nodes, and GO and KEGG analyses revealed substantial enrichment of these targets in inflammatory responses, ABC transporters, PPAR signaling pathway, among others. Based on the literature review, seven hepatic transporters, including BCRP, MRP, and P-gp, were observed to be associated with myocardial ischemia. Molecular docking suggested high binding affinity between active constituents of Polygonum orientale L. and upstream regulatory proteins of transporters. Furthermore, animal experiments revealedthat Polygonum orientale L. extract upregulated the expressions of MRP1, MRP2, OATP2, OCT1, OCT2, and P-gp in normal rats, and downregulated the protein expressions of BCRP, MRP2, OATP2, OCT1, OCT2, and P-gp in rats with myocardial ischemia. These results indicate that the active constituents of Polygonum orientale L. can regulate hepatic transporters under physiological and pathological conditions, and their mechanism may be related to their binding to upstream regulatory proteins of hepatic transporters.

Key words: Polygonum orientale L., myocardial ischemia, transporters, network pharmacology, molecular docking, qRT-PCR, western blot

CLC Number:

LUO Qiuyun, SUN Jia, LIU Donghui , LI Yongjun, XUE Weina. Effects of active constituents from Polygonum orientale L. on the expression of transporters under physiological and pathological conditions[J].Shandong Science, 0, (): 1-.

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Effects of active constituents from Polygonum orientale L. on the expression of transporters under physiological and pathological conditions

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