Jianpi Qingre Tongluo Prescription (Huangqin Qingrechubi Capsule) alleviates inflammation and hypercoagulability by inhibiting the JAK2/STAT3 pathway via CircRNA 104633 downregulation in gouty arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Gouty arthritis (GA) is characterized by intermittent inflammatory pain, which dramatically compromises the quality of life of patients. Huangqin Qingrechubi Capsule (HQC) is an empirical traditional Chinese medicine prescription used to treat GA for over 20 years, with favorable efficacy. However, little is known about the specific mechanism of action of HQC in GA treatment.

PURPOSE: This study probed the mechanism of action of HQC in the treatment of GA from anti-inflammatory and anticoagulation aspects.

METHODS

Initially, a retrospective clinical analysis was performed to observe the effects of HQC on inflammatory and coagulation indexes in GA patients. Subsequently, the expression of CircRNA 104633 and inflammatory and coagulation factors was detected in peripheral blood mononuclear cells (PBMCs) harvested from recruited GA patients before and after HQC treatment, followed by the analysis of the correlation between CircRNA 104633 and other indexes. The anti-inflammatory and anticoagulation mechanisms of HQC in GA treatment via CircRNA 104633 were further investigated through a co-culture model composed of GA-PBMCs and fibroblast-like synoviocytes (FLSs). Finally, a rat model of monosodium urate-induced GA was established for in vivo verification.

RESULTS

HQC reduced the levels of HCRP, ESR, and D-D in GA patients. In the PBMCs of GA patients, HQC decreased CircRNA 104633 expression, and CircRNA 104633 expression was closely related to inflammatory and coagulation indexes. CircRNA 104633 upregulation fostered inflammation and hypercoagulability in GA by activating the JAK2/STAT3 pathway, whilst HQC reversed the imbalance of inflammatory and coagulation factors by downregulating CircRNA 104633. Furthermore, HQC played anti-inflammatory and anticoagulant roles in GA rats by blocking the JAK2/STAT3 pathway.

CONCLUSION

HQC protects against inflammation and hypercoagulability in GA by inhibiting CircRNA 104633 and the JAK2/STAT3 pathway, which supports the development of therapeutic targets and drugs for GA.