{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:22:00Z","timestamp":1793146920551,"version":"4.5.0"},"reference-count":58,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Walailak University under the New Researcher Development Scheme","award":["WU67275"],"award-info":[{"award-number":["WU67275"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background\/Objectives: Osteoporosis is a multifactorial skeletal disorder in which chronic inflammation, dysregulated cytokine signaling, and metabolic imbalance contribute to excessive bone resorption and impaired bone formation. Asiatic acid has demonstrated bone-protective effects, but its molecular mechanisms in osteoporosis remain incompletely understood. This study aimed to investigate the anti-osteoporotic mechanisms of asiatic acid using an integrative in silico strategy. Methods: Network pharmacology analysis was performed to identify osteoporosis-related molecular targets of asiatic acid. Molecular docking was used to predict the binding modes and affinities between asiatic acid and its target proteins. Molecular dynamics simulation was used to assess the structural stability and interaction persistence of the asiatic acid\u2013protein complex. Results: Network pharmacology identified 135 overlapping targets between asiatic acid and osteoporosis, with IL-6, STAT3, PPARG, and NFKB1 emerging as key hubs. KEGG analysis indicated the PPAR signaling pathway as a potential mechanism underlying the anti-osteoporotic effect. Molecular docking showed strong binding energies of asiatic acid with all predicted target proteins, with the highest affinity observed for IL-6, involving key residues ASN61, LEU62, GLU172, LYS66, and ARG168. Consistently, molecular dynamics simulation confirmed stable binding of asiatic acid to IL-6, with persistent interactions with ASN61, LYS66, LEU62, LEU64, and GLN154 mediated by hydrogen bonds, water bridges, and hydrophobic interactions. Conclusions: This integrative in silico study provides mechanistic insight into the potential anti-osteoporotic actions of asiatic acid, implicating IL-6 as a plausible upstream molecular target. These results establish a robust mechanistic framework for future translational studies exploring asiatic acid as a natural therapeutic candidate for osteoporosis.<\/jats:p>","DOI":"10.3390\/medsci14010041","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T11:13:21Z","timestamp":1768475601000},"page":"41","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["In Silico Investigation Reveals IL-6 as a Key Target of Asiatic Acid in Osteoporosis: Insights from Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2804-4921","authenticated-orcid":false,"given":"Wanatsanan","family":"Chulrik","sequence":"first","affiliation":[{"name":"Department of Medical Technology, School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand"},{"name":"Food Technology and Innovation Research Center of Excellence, Walailak University, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1350-1424","authenticated-orcid":false,"given":"Aman","family":"Tedasen","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand"},{"name":"Research Excellence Center for Innovation and Health Products (RECIHP), Walailak University, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7623-854X","authenticated-orcid":false,"given":"Nateelak","family":"Kooltheat","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand"},{"name":"Hematology and Transfusion Science Research Center, Walailak University, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2580-9477","authenticated-orcid":false,"given":"Rungruedee","family":"Kimseng","sequence":"additional","affiliation":[{"name":"Sanders Brown Center on Aging, College of Medicine, University of Kentucky, Lexington, KY 40536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7404-6664","authenticated-orcid":false,"given":"Thitinat","family":"Duangchan","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand"},{"name":"Hematology and Transfusion Science Research Center, Walailak University, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/S0140-6736(10)62349-5","article-title":"Osteoporosis: Now and the future","volume":"377","author":"Rachner","year":"2011","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/S0140-6736(18)32112-3","article-title":"Osteoporosis","volume":"393","author":"Compston","year":"2019","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Hsu, S.-H., Chen, L.-R., and Chen, K.-H. 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