Guizhi-Shaoyao-Zhimu decoction attenuates rheumatoid arthritis by inhibiting mast cell degranulation

摘要

Background:In this study,we investigated whether prophylactic treatment with Guizhi-Shaoyao-Zhimu decoction(GSZ)could delay the onset of rheumatoid arthritis by targeting mast cells.Methods:Collagen-induced arthritis was used to evaluate the effect of GSZ in preventing arthritis and joint destruction.Immunohistochemical staining revealed the accumulation of histamine H4 receptor and tryptase alpha/beta-1 in the ankle joint of the model.Then,we explored the effect of GSZ serum on fibroblast-like synoviocytes using standard transwell invasion and migration assays.Real-time quantitative polymerase chain reaction and western blot were used to detect the expression of toll-like receptor 4(TLR4)/myeloid differentiationfactor 88(MyD88)/nuclear factor-κB p65(NF-κB p65).Results:The results showed that pre-rheumatoid arthritis treatment with GSZ could reduce inflammation and maintain cartilage structure in the collagen-induced arthritis model.Moreover,GSZ significantly blocked mast cell degranulation and inhibited the TLR4/MyD88/NF-κB p65 pathway.Since the combined activation of mast cells via TLR4 and immune complexes enhances inflammation in synovial tissue,we concluded that GSZ may block mast cell degranulation by inhibiting the TLR4/MyD88/NF-κB p65 pathway and thus influence rheumatoid arthritis onset.Conclusion:Taken together,our data suggested that GSZ may be a promising therapeutic decoction for the prophylactic treatment of rheumatoid arthritis.