{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:03:56Z","timestamp":1790859836724,"version":"4.1.0"},"reference-count":70,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T00:00:00Z","timestamp":1760745600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jilin Province Science and Technology Development Project","award":["YDZJ202401044ZYTS"],"award-info":[{"award-number":["YDZJ202401044ZYTS"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Rheumatoid arthritis (RA) is a systemic autoimmune disorder marked by chronic inflammation of small synovial joints, with frequent extra-articular involvement of the skin and eyes. Prolonged methotrexate therapy for RA is often accompanied by serious side effects. Therefore, new drugs with less toxicity and greater effectiveness need to be developed. The ginsenoside 20(R)-25-methoxyl-dammarane-3\u03b2,12\u03b2,20-triol (AD-1), purified from Panax ginseng berry, exhibits potent anti-inflammatory and anti-cancer activities. However, the pharmacological mechanism of AD-1 in RA remains unclear. This study explored the potential anti-RA effects of AD-1 using an integrative strategy that combined network pharmacology, molecular docking, molecular dynamics simulation, and in vitro pharmacological validation. Enrichment analyses of KEGG and GO terms based on network pharmacology pointed to the PI3K\/Akt signaling axis as a key regulatory pathway modulated by AD-1. Molecular docking and dynamics simulations revealed that AD-1 may have a close interaction with PIK3R1 and AKT1, demonstrating a stabilizing effect. Then, after experimental verification using human rheumatoid arthritis fibroblasts (MH7A), it was found that AD-1 suppressed cell proliferation, migration, and invasion and promoted apoptosis. Subsequent analysis of the RABC databases revealed that PIK3R1 and AKT1 were upregulated in RA, while AD-1 reduces phosphorylation of PI3K and Akt. In conclusion, these findings indicate that AD-1 exerts its anti-RA action, at least in part, through modulation of the PI3K\/Akt signaling pathway and induction of apoptosis in synovial cells. This study provides a basis and new strategies for the role of ginsenosides in the treatment of RA.<\/jats:p>","DOI":"10.3390\/cells14201625","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T08:18:54Z","timestamp":1760948334000},"page":"1625","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Ginsenoside Derivative AD-1 Suppresses Pathogenic Phenotypes of Rheumatoid Arthritis Fibroblast-like Synoviocytes by Modulating the PI3K\/Akt Signaling Pathway"],"prefix":"10.3390","volume":"14","author":[{"given":"Yuan","family":"Fu","sequence":"first","affiliation":[{"name":"Immunology Biology Key Laboratory, Yanbian University, Yanji 133002, China"},{"name":"Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji 133002, China"},{"name":"Department of Immunology and Pathogenic Biology, College of Medicine, Yanbian University, Yanji 133002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfang","family":"Li","sequence":"additional","affiliation":[{"name":"Immunology Biology Key Laboratory, Yanbian University, Yanji 133002, China"},{"name":"Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji 133002, China"},{"name":"Department of Immunology and Pathogenic Biology, College of Medicine, Yanbian University, Yanji 133002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Cui","sequence":"additional","affiliation":[{"name":"Immunology Biology Key Laboratory, Yanbian University, Yanji 133002, China"},{"name":"Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji 133002, China"},{"name":"Department of Immunology and Pathogenic Biology, College of Medicine, Yanbian University, Yanji 133002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongyu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji 133002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xizhu","family":"Fang","sequence":"additional","affiliation":[{"name":"Immunology Biology Key Laboratory, Yanbian University, Yanji 133002, China"},{"name":"Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji 133002, China"},{"name":"Department of Immunology and Pathogenic Biology, College of Medicine, Yanbian University, Yanji 133002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengnan","family":"Huang","sequence":"additional","affiliation":[{"name":"Immunology Biology Key Laboratory, Yanbian University, Yanji 133002, China"},{"name":"Key Laboratory of Natural Medicines 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