Investigation of Fructus sophorae extract’s therapeutic mechanism in atrophic vaginitis based on network pharmacology and experimental validation

ObjectiveThis study systematically elucidates the therapeutic mechanism of Fructus sophorae extract (FSE) against atrophic vaginitis (AV) by integrating network pharmacology with in vitro experimental validation.MethodsPotential drug targets of FS and AV-related disease targets were systematically r...

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Main Authors: Jiarui Zheng, Weiming Wang, Wenting Song, Yehao Zhang, Mingjiang Yao, Guangrui Wang, Zishan Huang, Feng Li, Junguo Ren, Li Lin, Xiaodi Fan, Jianxun Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1571976/full
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author Jiarui Zheng
Jiarui Zheng
Weiming Wang
Wenting Song
Yehao Zhang
Mingjiang Yao
Guangrui Wang
Zishan Huang
Feng Li
Junguo Ren
Li Lin
Xiaodi Fan
Jianxun Liu
author_facet Jiarui Zheng
Jiarui Zheng
Weiming Wang
Wenting Song
Yehao Zhang
Mingjiang Yao
Guangrui Wang
Zishan Huang
Feng Li
Junguo Ren
Li Lin
Xiaodi Fan
Jianxun Liu
author_sort Jiarui Zheng
collection DOAJ
description ObjectiveThis study systematically elucidates the therapeutic mechanism of Fructus sophorae extract (FSE) against atrophic vaginitis (AV) by integrating network pharmacology with in vitro experimental validation.MethodsPotential drug targets of FS and AV-related disease targets were systematically retrieved from TCMSP, SWISS Target Prediction, GeneCards, and DisGeNET databases. The putative therapeutic targets of FS against AV were identified through target overlap analysis between drug and disease targets. Functional enrichment analyses of GO terms, KEGG pathways, and disease associations were performed using DAVID database, with results visualized by Cytoscape software. Molecular docking validation and binding affinity visualization between FS components and target proteins were carried out using PubChem database and PyMOL software. The AV animal model was established by bilateral ovariectomy (OVX). To validate FS’s effects on target protein expression, immunohistochemical staining and Western blot analyses were performed.ResultsThrough target intersection analysis between 137 drug targets and 1,777 disease targets, a total of 100 potential therapeutic targets were identified for FS in AV treatment. Subsequent core gene screening revealed key targets, namely, EGFR, AKT1, ESR1, and TNF. GO and KEGG enrichment analyses demonstrated significantly enriched pathways, with the PI3K/AKT signaling pathway showing particular relevance. Molecular docking analysis revealed strong binding affinity between FS components and the functional domains of EGFR, AKT1, and ESR1. An OVX-induced rat AV model was successfully established, with pathological and molecular validation achieved via immunohistochemistry and Western blot analyses. FS treatment significantly normalized the dysregulated expression levels of p-PI3K/PI3K, p-AKT/AKT, ERα, EGF, and EGFR.ConclusionFS demonstrates multi-target regulatory capacity, specifically modulating p-PI3K/PI3K, p-AKT/AKT, ERα, EGF, and EGFR signaling pathways, which substantiates its potential as a promising therapeutic agent for AV. These findings provide mechanistic insights into FS’s therapeutic targets against AV, establishing a theoretical foundation for its translational application in AV therapy.
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spelling doaj-art-12141ebc56334fe79dfe3e53bdd4cfd82025-08-20T02:16:17ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-05-011610.3389/fphar.2025.15719761571976Investigation of Fructus sophorae extract’s therapeutic mechanism in atrophic vaginitis based on network pharmacology and experimental validationJiarui Zheng0Jiarui Zheng1Weiming Wang2Wenting Song3Yehao Zhang4Mingjiang Yao5Guangrui Wang6Zishan Huang7Feng Li8Junguo Ren9Li Lin10Xiaodi Fan11Jianxun Liu12Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing Key Laboratory of Pharmacology of Traditional Chinese Medicine, Beijing, ChinaInstitute of Chinese Medicine, Heilongjiang Academy of Traditional Chinese Medicine, Harbin, ChinaInstitute of Chinese Medicine, Heilongjiang Academy of Traditional Chinese Medicine, Harbin, ChinaInstitute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing Key Laboratory of Pharmacology of Traditional Chinese Medicine, Beijing, ChinaInstitute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing Key Laboratory of Pharmacology of Traditional Chinese Medicine, Beijing, ChinaInstitute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing Key Laboratory of Pharmacology of Traditional Chinese Medicine, Beijing, ChinaInstitute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing Key Laboratory of Pharmacology of Traditional Chinese Medicine, Beijing, ChinaInstitute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing Key Laboratory of Pharmacology of Traditional Chinese Medicine, Beijing, ChinaInstitute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing Key Laboratory of Pharmacology of Traditional Chinese Medicine, Beijing, ChinaInstitute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing Key Laboratory of Pharmacology of Traditional Chinese Medicine, Beijing, ChinaInstitute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing Key Laboratory of Pharmacology of Traditional Chinese Medicine, Beijing, ChinaInstitute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing Key Laboratory of Pharmacology of Traditional Chinese Medicine, Beijing, ChinaInstitute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing Key Laboratory of Pharmacology of Traditional Chinese Medicine, Beijing, ChinaObjectiveThis study systematically elucidates the therapeutic mechanism of Fructus sophorae extract (FSE) against atrophic vaginitis (AV) by integrating network pharmacology with in vitro experimental validation.MethodsPotential drug targets of FS and AV-related disease targets were systematically retrieved from TCMSP, SWISS Target Prediction, GeneCards, and DisGeNET databases. The putative therapeutic targets of FS against AV were identified through target overlap analysis between drug and disease targets. Functional enrichment analyses of GO terms, KEGG pathways, and disease associations were performed using DAVID database, with results visualized by Cytoscape software. Molecular docking validation and binding affinity visualization between FS components and target proteins were carried out using PubChem database and PyMOL software. The AV animal model was established by bilateral ovariectomy (OVX). To validate FS’s effects on target protein expression, immunohistochemical staining and Western blot analyses were performed.ResultsThrough target intersection analysis between 137 drug targets and 1,777 disease targets, a total of 100 potential therapeutic targets were identified for FS in AV treatment. Subsequent core gene screening revealed key targets, namely, EGFR, AKT1, ESR1, and TNF. GO and KEGG enrichment analyses demonstrated significantly enriched pathways, with the PI3K/AKT signaling pathway showing particular relevance. Molecular docking analysis revealed strong binding affinity between FS components and the functional domains of EGFR, AKT1, and ESR1. An OVX-induced rat AV model was successfully established, with pathological and molecular validation achieved via immunohistochemistry and Western blot analyses. FS treatment significantly normalized the dysregulated expression levels of p-PI3K/PI3K, p-AKT/AKT, ERα, EGF, and EGFR.ConclusionFS demonstrates multi-target regulatory capacity, specifically modulating p-PI3K/PI3K, p-AKT/AKT, ERα, EGF, and EGFR signaling pathways, which substantiates its potential as a promising therapeutic agent for AV. These findings provide mechanistic insights into FS’s therapeutic targets against AV, establishing a theoretical foundation for its translational application in AV therapy.https://www.frontiersin.org/articles/10.3389/fphar.2025.1571976/fullFructus sophorae extractatrophic vaginitisnetwork pharmacologymolecular dockingexperimental verification
spellingShingle Jiarui Zheng
Jiarui Zheng
Weiming Wang
Wenting Song
Yehao Zhang
Mingjiang Yao
Guangrui Wang
Zishan Huang
Feng Li
Junguo Ren
Li Lin
Xiaodi Fan
Jianxun Liu
Investigation of Fructus sophorae extract’s therapeutic mechanism in atrophic vaginitis based on network pharmacology and experimental validation
Frontiers in Pharmacology
Fructus sophorae extract
atrophic vaginitis
network pharmacology
molecular docking
experimental verification
title Investigation of Fructus sophorae extract’s therapeutic mechanism in atrophic vaginitis based on network pharmacology and experimental validation
title_full Investigation of Fructus sophorae extract’s therapeutic mechanism in atrophic vaginitis based on network pharmacology and experimental validation
title_fullStr Investigation of Fructus sophorae extract’s therapeutic mechanism in atrophic vaginitis based on network pharmacology and experimental validation
title_full_unstemmed Investigation of Fructus sophorae extract’s therapeutic mechanism in atrophic vaginitis based on network pharmacology and experimental validation
title_short Investigation of Fructus sophorae extract’s therapeutic mechanism in atrophic vaginitis based on network pharmacology and experimental validation
title_sort investigation of fructus sophorae extract s therapeutic mechanism in atrophic vaginitis based on network pharmacology and experimental validation
topic Fructus sophorae extract
atrophic vaginitis
network pharmacology
molecular docking
experimental verification
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1571976/full
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