{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T18:40:49Z","timestamp":1762800049200,"version":"build-2065373602"},"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Henan Province Traditional Chinese Medicine Inheritance and Innovation Talent Project","award":["CZ0237-02"],"award-info":[{"award-number":["CZ0237-02"]}]},{"name":"Henan Province Traditional Chinese Medicine Research Special Project","award":["20-21ZY1016"],"award-info":[{"award-number":["20-21ZY1016"]}]},{"name":"Zhengzhou City Collaborative Innovation Project","award":["2023XTCX048"],"award-info":[{"award-number":["2023XTCX048"]}]},{"name":"Henan University of Traditional Chinese Medicine 2022 Postgraduate Research Innovation Ability Improvement Plan","award":["2022KYCX043"],"award-info":[{"award-number":["2022KYCX043"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Drugs usually do not prevent extraocular muscle fibrosis in Graves\u2019 ophthalmopathy (GO), and surgical treatment has complications and does not cure extraocular muscle fibrosis. Triptolide (TPL) has shown antifibrotic effects; however, the mechanism by which it treats extraocular muscle fibrosis in GO remains unclear. The aim of this study was to investigate the therapeutic effect and potential mechanism of TPL through a combination of network pharmacology and experimental validation. Network pharmacology identified 10 potential therapeutic targets, 1767 gene ontology terms, and 95 signaling pathways, including the PI3K\/AKT pathway. Molecular docking revealed a strong affinity between core targets on the PI3K\/AKT pathway and TPL. The experimental results showed that TPL inhibited the proliferation of OFs in vitro in a concentration-dependent manner. It significantly inhibited the expression of TGF-\u03b21-induced fibrosis-related markers, such as FN, CTGF, \u03b1-SMA, and TIMP-1, while significantly down-regulating the expression of PI3K\/AKT signaling proteins. The use of inhibitors of the PI3K\/AKT pathway inhibited the expression of fibrosis-related markers. These findings suggest that TPL can resist extraocular muscle fibrosis in GO through multiple pathways, in which the PI3K\/AKT pathway plays a key role.<\/jats:p>","DOI":"10.1371\/journal.pone.0336487","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T18:23:48Z","timestamp":1762799028000},"page":"e0336487","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Network pharmacology and experiments verify the effect of triptolide on extraocular muscle 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