[Efficacy of Zhufu Tongbi Granules in alleviating rheumatoid arthritis and its anti-atrophy mechanism based on theory of "spleen governing muscles"].

Zhufu Tongbi Granules is an empirical formula developed from the classic Wutou Guizhi Decoction by the nationally renowned TCM professor BAI Chang-chuan based on the theory of "treating Bi syndrome from the spleen". However, the modern scientific connotation of the "treatment based on regulating the spleen", particularly its mechanism of action on muscle atrophy, which is common in patients with rheumatoid arthritis(RA), remains elusive. This study integrated network pharmacology prediction with experimental validation. For the first time, a molecular network with "formula-herb-target-pathway-efficacy" for this formula was constructed. Myogenin(Myog) and tripartite motif-containing 63(TRIM63) were identified as core regulatory nodes for ameliorating muscle atrophy. In a complete Freund's adjuvant-induced arthritis(AIA) rat model, Zhufu Tongbi Granules not only significantly alleviated joint swelling, increased pain thresholds, reduced the levels of interleukin(IL)-6, tumor necrosis factor-α(TNF-α), and IL-17(P<0.05) in serum, corrected peripheral blood cell abnormalities, as well as ameliorated microstructural destruction of bones, but also demonstrated the multitarget advantages of "treatment based on regulating the spleen". It significantly improved gastric emptying and intestinal propulsion rates(P<0.01), corrected anemic status, and increased both the cross-sectional area of gastrocnemius fibers and the gastrocnemius/brain index(P<0.01). Mechanistic studies reveal that the formula significantly downregulates the overexpression of proteins Myog and TRIM63 in the gastrocnemius of AIA rats(P<0.05), thereby suppressing muscle protein degradation mediated by the ubiquitin-proteasome pathway. Importantly, no significant hepatorenal function injury was observed in the rats of groups with different doses. This study clarified the comprehensive efficacy of Zhufu Tongbi Granules in alleviating RA and revealed its molecular mechanism for improving muscle atrophy via regulating the Myog/TRIM63 pathway based on the theory of "spleen governing muscles". These findings provide experimental evidence for elucidating the modern connotation of the theory of "treating Bi syndrome from the spleen" and developing innovative anti-RA TCM with both anti-inflammatory and muscle-protective properties.