Majoon Chobchini, a polyherbal Unani compound, has been used holistically in India to treat rheumatoid arthritis. However, the potential mechanism underlying the antiarthritic efficacy of Majoon Chobchini has not been elucidated so far. This study was aimed to explore the underlying molecular mechanism and scientifically validate the therapeutic basis of Majoon Chobchini in rheumatoid arthritis (RA). The anti-arthritic efficacy of Majoon Chobchini was demonstrated in vivo using complete Freund's adjuvant-induced arthritic rat model and adjuvant-induced arthritic fibroblast-like synoviocytes (AA-FLS). The expression of pro-inflammatory mediators and enzymes was evaluated in the serum and synovial tissues of adjuvant-induced arthritis (AIA) rats. In-vitro, AA-FLS, and bone marrow macrophages (BMMs) were co-cultured to evaluate the formation and activity of osteoclasts using TRAP staining analysis and pit formation assay, respectively. RANKL and OPG levels were detected using western blotting and qRT-PCR analysis. Furthermore, the involvement of JAK-STAT-3 signaling in the therapeutic efficacy of Majoon Chobchini was evaluated both in vivo and in vitro. Majoon Chobchini significantly reversed the physical symptoms in AIA rats with reduced expression of pro-inflammatory cytokines and enzymes. Notably, Majoon Chobchini alleviated cartilage degradation and bone erosion in AIA rats via inhibiting the activation of the JAK-STAT-3 signaling pathway in the AIA rats. Consistent with its effect in vivo, Majoon Chobchini decreased osteoclast inducing potential of AA-FLS and thus attenuated osteoclast formation and bone resorption in vitro. Taken together, our findings suggest that the JAK/STAT-3 signaling inhibition may underlie the mechanism through which Majoon Chobchini provides relief against RA symptoms.

Majoon Chobchini 是一种多草药 Unani 化合物，已在印度整体用于治疗类风湿性关节炎。然而，迄今为止尚未阐明 Majoon Chobchini 抗关节炎功效的潜在机制。本研究旨在探索潜在的分子机制，并科学验证 Majoon Chobchini 治疗类风湿关节炎 (RA) 的治疗基础。使用完全弗氏佐剂诱导的关节炎大鼠模型和佐剂诱导的关节炎成纤维细胞样滑膜细胞 (AA-FLS) 在体内证明了 Majoon Chobchini 的抗关节炎功效。在佐剂性关节炎 (AIA) 大鼠的血清和滑膜组织中评估促炎介质和酶的表达。体外，AA-FLS，和骨髓巨噬细胞 (BMM) 共培养，分别使用 TRAP 染色分析和凹坑形成测定来评估破骨细胞的形成和活性。使用蛋白质印迹和 qRT-PCR 分析检测 RANKL 和 OPG 水平。此外，在体内和体外都评估了 JAK-STAT-3 信号传导在 Majoon Chobchini 治疗功效中的作用。Majoon Chobchini 显着逆转了 AIA 大鼠的身体症状，促炎细胞因子和酶的表达减少。值得注意的是，Majoon Chobchini 通过抑制 AIA 大鼠 JAK-STAT-3 信号通路的激活，减轻了 AIA 大鼠的软骨退化和骨侵蚀。与其在体内的作用一致，Majoon Chobchini 降低了 AA-FLS 的破骨细胞诱导潜力，从而减弱了体外破骨细胞的形成和骨吸收。总之，我们的研究结果表明 JAK/STAT-3 信号传导抑制可能是 Majoon Chobchini 缓解 RA 症状的机制的基础。