植物药钩吻中抗骨质疏松性骨折先导结构的发现及其作用机制研究

随着我国人口老龄化的不断加剧，骨质疏松性骨折已成为危害公众健康的常见疾病。植物药钩吻民间常用于治疗跌打损伤以及骨折，申请者近年来发现其甲醇提取物能够抑制由RANKL诱导的破骨细胞生成，同时促进成骨细胞增殖，深入研究表明钩吻非碱可能是促成骨细胞生长的主要物质基础，而其总碱可能是抑制破骨细胞生成的主要活性部位，此外我们从该植物中分离得到了多个大量及新颖化合物，初步机制研究发现数个大量成分能够明显抑制OPG/RANKL/RANK系统的上游因子水平，提示钩吻可能通过OPG/RANKL/RANK系统调控成骨和破骨平衡，促进骨质疏松性骨折愈合。. 本项目以民间治疗骨折的植物药钩吻为研究对象，综合运用植物化学、有机合成、药理学以及分子生物学等研究手段，为从钩吻中发现具有自主知识产权的抗骨质疏松性骨折先导药物奠定了基础，为充实传统植物药的科学内涵提供新的思路。

With the increasing aging of the population in China, osteoporotic fracture has already become an important social problem, which is endangering public health. As a traditional treatment for fracture, the total extract of Gelsemium elegans was able to inhibit the osteoclast formation induced by RANKL and promote the proliferation of osteoblasts in our previous studies. In-depth biological guide research indicated that the non-alkali extracts of G. elegans might be the main chemical constituents for promoting the growth of osteoblasts, while its total alkaloids might be the main active compositions for inhibiting the formation of osteoclasts. In addition, we isolated and identified a lots of novel or/and known compounds from total alkaloids of G. elegans. Some compounds significantly inhibited the regulating factors of OPG/RANKL/RANK coupling system, suggesting that G. elegans may mediate the balance of osteogenesis and osteoclasts by the OPG/RANKL/RANK system. . Based on all above issues and our previous research, this project will work on the anti-osteoporotic fracture compounds and mechanism of G. elegans in detail though OPG/RANKL/RANK coupling pathway. Hope to discover the leading compounds with anti-osteoporotic fracture activities, meanwhile provide new ideas and references for the future research and development of bone metabolic drugs.