PDF(Pubmed)
Abstract：
Osteoporosis is a global health challenge characterized by bone loss and microstructure deterioration, which urgently requires the development of safer and more effective treatments due to the significant adverse effects and limitations of existing drugs for long-term treatment. Traditional Chinese medicine, like Epimedium, offers fewer side effects and has been used to treat osteoporosis, yet its active compounds and pharmacological mechanisms remain unclear. In this study, 65 potential active compounds, 258 potential target proteins, and 488 pathways of Epimedium were identified through network pharmacology analysis. Further network analysis and review of the literature identified six potential active compounds and HIF-1α for subsequent experimental validation. In vitro experiments confirmed that 2″-O-RhamnosylIcariside II is the most effective compound among the six potential active compounds. It can promote osteoblast differentiation, bind with HIF-1α, and inhibit both HIF-1α gene and protein expression, as well as enhance COL1A1 protein expression under hypoxic conditions. In vivo experiments demonstrated its ability to improve bone microstructures and reduce bone loss by decreasing bone marrow adipose tissue, enhancing bone formation, and suppressing HIF-1α protein expression. This study is the first to describe the therapeutic effects of 2-O-RhamnosylIcariside II on osteoporosis, which was done, specifically, through a mechanism that targets and inhibits HIF-1α. This study provides a scientific basis for the clinical application of Epimedium and offers a new candidate drug for the treatment of osteoporosis. Additionally, it provides new evidence supporting HIF-1α as a therapeutic target for osteoporosis.
摘要：
骨质疏松症是以骨质流失和微结构恶化为特征的全球性健康挑战。这迫切需要开发更安全和更有效的治疗方法，因为长期治疗的现有药物具有显著的副作用和局限性。中药,比如淫羊藿,副作用较少，已被用于治疗骨质疏松症，然而，其活性化合物和药理机制仍不清楚。在这项研究中,65个潜在的活性化合物，258个潜在的靶蛋白，通过网络药理学分析鉴定了488条淫羊藿通路。进一步的网络分析和文献综述确定了六种潜在的活性化合物和HIF-1α用于随后的实验验证。体外实验证实2″-O-鼠李糖淫羊藿苷II是六种潜在活性化合物中最有效的化合物。它能促进成骨细胞分化，与HIF-1α结合，同时抑制HIF-1α基因和蛋白表达，以及在低氧条件下增强COL1A1蛋白表达。体内实验证明了其通过减少骨髓脂肪组织改善骨微结构和减少骨丢失的能力，增强骨形成，抑制HIF-1α蛋白表达。这项研究首次描述了2-O-鼠李糖苷II对骨质疏松症的治疗作用，已经完成了，具体来说,通过靶向和抑制HIF-1α的机制。本研究为淫羊藿的临床应用提供了科学依据,为骨质疏松的治疗提供了新的候选药物。此外,它提供了新的证据支持HIF-1α作为骨质疏松症的治疗靶点。
