Unveiling the mechanisms of American ginseng and achyranthes in treatment of primary Sjogren’s syndrome via mtDNA-cGAS-STING pathway insights from network pharmacology, molecular dynamics, and experimental validation

作者：Haotian Li, Congmin Xia, Yuewei Song, Jin Chen, Yanjun Liu · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1675429 · 被引用次数：6 · 研究领域：interferon and immune responses、Salivary Gland Disorders and Functions、GDF15 and Related Biomarkers

Objective With the aim of clarifying the therapeutic mechanisms of the American Ginseng-Achyranthes bidentata (AG&A) herbal pair in primary Sjögren’s syndrome (pSS), this study employs an integrated approach combining network pharmacology, molecular docking, molecular dynamics simulations, and animal experiments. Methods Network pharmacology & LC-MS/MS was utilized to identify the active components and potential targets of A&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. Results Network pharmacology identified baicalin and quercetin as key active components. Molecular docking revealed strong binding affinities (binding energy ≤ -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-α, IFN-α, and IFN-β,CXCL-10 (p < 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. Conclusion The critical components baicalin and quercetin from AG&A, particularly in aqueous extracts, exhibit therapeutic efficacy against pS...