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Immunol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>With the aim of clarifying the therapeutic mechanisms of the American Ginseng-Achyranthes bidentata (AG&amp;amp;A) herbal pair in primary Sj\u00f6gren\u2019s syndrome (pSS), this study employs an integrated approach combining network pharmacology, molecular docking, molecular dynamics simulations, and animal experiments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Network pharmacology &amp;amp; LC-MS\/MS was utilized to identify the active components and potential targets of A&amp;amp;A. Molecular docking and dynamics simulations were performed to evaluate binding affinity and complex stability with key targets. Animal experiments using non-obese diabetic (NOD) mice were conducted to validate symptom improvement by critical active components.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Network pharmacology identified baicalin and quercetin as key active components. Molecular docking revealed strong binding affinities (binding energy \u2264 -8.0 kcal\/mol) between these compounds and apoptosis-related proteins, BAX and CASP3. Molecular dynamics simulations confirmed the stability of these complexes. Animal experiments demonstrated that baicalin can significantly reduce inflammatory cytokines of IL-18, TNF-\u03b1, IFN-\u03b1, and IFN-\u03b2,CXCL-10 (p &amp;lt; 0.05), decrease mtDNA release, and downregulate cGAS-STING pathway-related proteins including cGAS, STING, CASP3, ZBP1, TBK1, p-STING, p-TBK1, IRF3, p-IRF3 and BAX.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The critical components baicalin and quercetin from AG&amp;amp;A, particularly in aqueous extracts, exhibit therapeutic efficacy against pSS. This study provides experimental evidence for their action mechanism through modulating the mtDNA-cGAS-STING pathway. While highlighting their therapeutic potential, additional <jats:italic>in vivo<\/jats:italic> and clinical studies are warranted to validate these findings.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1675429","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T05:29:22Z","timestamp":1759469362000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Unveiling the mechanisms of American ginseng and achyranthes in treatment of primary Sjogren\u2019s syndrome via mtDNA-cGAS-STING pathway insights from network pharmacology, molecular dynamics, and experimental 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