Abstract：
Inflammatory bowel disease is linked to a higher occurrence of bone loss. Oxyberberine can effectively improve experimental inflammatory bowel disease. However, no study has shown the effect of oxyberberine on inflammatory bowel disease induced bone loss. The present study was performed to investigate the role of oxyberberine in inflammatory bowel disease induced osteoporosis in chronic inflammatory bowel disease mice model. The inflammatory bowel disease mice were orally given two doses of oxyberberine daily. Blood, colon, and bone specimens were collected for biomarker assessments and histological examinations. Bone biomechanical properties and key proteins and genes involved in the receptor activator of nuclear factor kappa-B ligand/nuclear factor kappa-B signaling pathway were evaluated. Additionally, the binding characteristics of oxyberberine and receptor activator of nuclear factor kappa-B ligand were evaluated by in silico simulation. Results indicated that oxyberberine treatment significantly attenuated the macroscopic damage, colonic shortening, and histological injury from the colon. Furthermore, oxyberberine decreased serum inflammatory cytokine levels. The intervention with oxyberberine significantly mitigated the deterioration of bone mass, biomechanical properties, and microstructural parameters. Moreover, the upregulated osteoclast formation factors in model mice were significantly abolished by oxyberberine. In silico simulation results also showed that oxyberberine was firmly bound with target protein. Hence, our findings indicated that oxyberberine had the potential to mitigate inflammatory bowel disease induced inflammation in bone, inhibit osteoclast formation through regulating the receptor activator of nuclear factor kappa-B ligand/nuclear factor kappa-B signaling pathway, and might be a valuable approach in preventing bone loss associated with inflammatory bowel disease.
摘要：
炎症性肠病与较高的骨丢失发生率有关。氧连素能有效改善实验性炎症性肠病。然而,目前尚无研究表明羟色胺对炎症性肠病引起的骨丢失有影响。本研究旨在探讨氧连素在慢性炎症性肠病小鼠模型炎症性肠病所致骨质疏松中的作用。炎性肠病小鼠每天口服两次剂量的羟色胺。血，结肠,收集骨标本进行生物标志物评估和组织学检查。评价骨生物力学特性及参与核因子κB受体活化因子配体/核因子κB信号通路的关键蛋白和基因。此外,通过计算机模拟评估了羟小檗碱与核因子κB受体活化因子配体的结合特性。结果表明，氧连素治疗显著减轻了宏观损伤，结肠缩短,和结肠的组织学损伤。此外，氧小檗碱降低血清炎性细胞因子水平。用羟小檗碱干预可显着减轻骨量的恶化，生物力学特性，和微观结构参数。此外，模型小鼠破骨细胞形成因子的上调被氧连素显著消除。计算机模拟结果还表明，氧连素与靶蛋白牢固结合。因此，我们的研究结果表明，羟色胺具有减轻炎症性肠病引起的骨炎症的潜力，通过调节核因子κB受体活化因子配体/核因子κB信号通路抑制破骨细胞形成,并且可能是预防与炎症性肠病相关的骨丢失的一种有价值的方法。
