Therapeutic effects and mechanisms of Juanbilijieqing fang in ameliorating gouty arthritis in a murine model

Abstract This study aims to assess the safety, efficacy, and mechanisms of Juanbilijieqing Fang in a mouse model of gouty arthritis. C57BL/6 mice were allocated into six groups: control, gouty arthritis model, and treatment groups receiving varying doses of Juanbilijieqing Fang (low, medium, high), along with a positive control group treated with febuxostat. Gouty arthritis was induced via MSU crystal injection following a high-fat diet. Mice were treated with Juanbilijieqing Fang or febuxostat, and safety was evaluated by measuring spleen, kidney, and liver indices. Efficacy was assessed by monitoring foot thickness, pain threshold, and biochemical markers, including serum uric acid (UA), myeloperoxidase (MPO), xanthine oxidase (XOD), and adenosine deaminase (ADA). Serum pro-inflammatory cytokines were analyzed, and intestinal inflammation and barrier integrity were examined through histological and molecular assays. Juanbilijieqing Fang did not significantly affect spleen, kidney, or liver indices, indicating its safety. Therapeutically, it significantly reduced foot swelling, improved pain threshold, and decreased serum uric acid levels. It also lowered MPO activity in foot tissue and reduced XOD and ADA activity in the liver. Additionally, the formula downregulated pro-inflammatory cytokines, such as IL-1α, IL-1β, IL-6, TNF-α, and IFN-γ, demonstrating a strong anti-inflammatory effect. It ameliorated gut inflammation by decreasing NLRP3 inflammasome components (NLRP3, ASC, and Caspase-1) and enhanced gut mucosal integrity by upregulating ZO-1 and Occludin expression. Juanbilijieqing Fang is a safe and effective treatment for gouty arthritis, primarily through reducing systemic and intestinal inflammation and restoring gut barrier function.