Department of Endocrinology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong 510000, China.
Department of Orthopedics, Yunfu Hospital of Traditional Chinese Medicine, Yunfu, Guangdong 527300, China.
Int Immunopharmacol. 2024 May 10;132:112027. doi: 10.1016/j.intimp.2024.112027. Epub 2024 Apr 11.
Osteoporosis (OP) is a frequent clinical problem for the elderly. Traditional Chinese Medicine (TCM) has achieved beneficial results in the treatment of OP. Ziyuglycoside II (ZGS II) is a major active compound of Sanguisorba officinalis L. that has shown anti-inflammation and antioxidation properties, but little information concerning its anti-OP potential is available. Our research aims to investigate the mechanism of ZGS II in ameliorating bone loss by inflammatory responses and regulation of gut microbiota and short chain fatty acids (SCFAs) in ovariectomized (OVX) mice.
We predicted the mode of ZGS II action on OP through network pharmacology and molecular docking, and an OVX mouse model was employed to validate its anti-OP efficacy. Then we analyzed its impact on bone microstructure, the levels of inflammatory cytokines and pain mediators in serum, inflammation in colon, intestinal barrier, gut microbiota composition and SCFAs in feces.
Network pharmacology identified 55 intersecting targets of ZGS II related to OP. Of these, we predicted IGF1 may be the core target, which was successfully docked with ZGS II and showed excellent binding ability. Our in vivo results showed that ZGS II alleviated bone loss in OVX mice, attenuated systemic inflammation, enhanced intestinal barrier, reduced the pain threshold, modulated the abundance of gut microbiota involving norank_f__Muribaculaceae and Dubosiella, and increased the content of acetic acid and propanoic acid in SCFAs.
Our data indicated that ZGS II attenuated bone loss in OVX mice by relieving inflammation and regulating gut microbiota and SCFAs.
骨质疏松症（OP）是老年人常见的临床问题。中药（TCM）在治疗 OP 方面取得了有益的效果。紫珠苷 II（ZGS II）是地榆中的一种主要活性化合物，具有抗炎和抗氧化作用，但关于其抗 OP 潜力的信息很少。我们的研究旨在通过炎症反应和调节肠道微生物群和短链脂肪酸（SCFAs）来研究 ZGS II 改善去卵巢（OVX）小鼠骨丢失的机制。
我们通过网络药理学和分子对接预测了 ZGS II 对 OP 的作用模式，并使用 OVX 小鼠模型验证了其抗 OP 功效。然后，我们分析了它对骨微结构、血清中炎症细胞因子和疼痛介质水平、结肠炎症、肠屏障、肠道微生物群组成和粪便中 SCFAs 的影响。
网络药理学鉴定出 55 个与 ZGS II 相关的 OP 交集靶点。其中，我们预测 IGF1 可能是核心靶点，它与 ZGS II 成功对接并显示出良好的结合能力。我们的体内结果表明，ZGS II 减轻了 OVX 小鼠的骨丢失，减轻了全身炎症，增强了肠屏障，降低了疼痛阈值，调节了涉及 norank_f__Muribaculaceae 和 Dubosiella 的肠道微生物群的丰度，并增加了 SCFAs 中乙酸和丙酸的含量。
我们的数据表明，ZGS II 通过缓解炎症和调节肠道微生物群和 SCFAs 来减轻 OVX 小鼠的骨丢失。
