Tujia ethnomedicine Xuetong (the stems of ) have been widely used in folk for rheumatoid arthritis (RA), which can alleviate rheumatic pain through liquor soaking in folk. In this study, we aimed to evaluate the pharmacological effects and underlying mechanism of Xuetongsu (a key chemical component of Xuetong) on bone destruction. In our previous study, it was found that Xuetong extract can reduce adjuvant arthritic rats paw swelling and inhibit inflammatory factors in serum. Furthermore, Xuetongsu has been demonstrated to inhibit the proliferation of fibroblast-like synoviocytes, but its potential to inhibit bone destruction has not been explored. To address this, we employed the STRING database to predict protein interactions and utilized Autodock software to simulate the binding of Xuetongsu to target proteins. In this study, administration of Xuetongsu significantly alleviated paw swelling and bone destruction in C57BL/6 mice with collagen-induced arthritis (CIA). Mechanistic studies have indicated that Xuetongsu promotes apoptosis of mature osteoclasts in joint tissues by activating Caspase-3 and Bax, while inhibiting Bcl-2. Additionally, Xuetongsu inhibits osteoclast differentiation by suppressing RANKL, RANK, -NF-κB, and NFATc1, and reduces bone resorption activity by inhibiting MMP-9, CTSK, and TRAP. Importantly, Xuetongsu exhibits good biocompatibility in major organs of mice. In summary, Xuetongsu has the potential to treat bone destruction by promoting apoptosis of mature osteoclasts, inhibiting osteoclast differentiation, and reducing bone resorption. This study reveals the pharmacological effects of Xuetongsu and its mechanism of action, which may contribute to the development of novel approaches for treating RA.

中文翻译：

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血通素通过抑制破骨细胞分化和促进破骨细胞凋亡减轻胶原诱导的关节炎小鼠骨破坏

土家族药雪痛（其茎）在民间广泛用于治疗类风湿性关节炎（RA），民间通过白酒浸泡可缓解风湿疼痛。在本研究中，我们旨在评估血通素（血通的关键化学成分）对骨质破坏的药理作用和潜在机制。我们前期研究发现血通提取物可以减轻佐剂性关节炎大鼠足爪肿胀并抑制血清中的炎症因子。此外，血通素已被证明可以抑制成纤维样滑膜细胞的增殖，但其抑制骨破坏的潜力尚未被探索。为了解决这个问题，我们利用STRING数据库来预测蛋白质相互作用，并利用Autodock软件来模拟血通素与目标蛋白质的结合。在这项研究中，服用血通素可显着减轻患有胶原诱导性关节炎 (CIA) 的 C57BL/6 小鼠的爪肿胀和骨质破坏。机制研究表明，血通素通过激活Caspase-3和Bax，同时抑制Bcl-2，促进关节组织中成熟破骨细胞的凋亡。此外，血通素通过抑制 RANKL、RANK、-NF-κB 和 NFATc1 来抑制破骨细胞分化，并通过抑制 MMP-9、CTSK 和 TRAP 来降低骨吸收活性。重要的是，血通素在小鼠主要器官中表现出良好的生物相容性。综上所述，血通素具有通过促进成熟破骨细胞凋亡、抑制破骨细胞分化、减少骨吸收来治疗骨质破坏的潜力。该研究揭示了血通素的药理作用及其作用机制，可能有助于开发治疗RA的新方法。