秦岭特色药材“荃皮”调节骨代谢及骨形成的物质基础与生物学机制的研究

Osteoporosis (OP) is a serious medical problem for its high morbidity and disability, and heavily affects the health and working ability of human being. ‘Quan-pi’ (the roots of Jasminum giraldill) as a unique herbal medicine in Qinling Mountains, was commonly used for the treatment of injuries, fractures and wounds... Our previous study revealed that on the estrogen deficiency animal model, the alcohol extraction of the roots of Jasminum giraldill could enhance the OPG protein expression and inhibit the RANKL protein expression in a dose-dependent manner, and resist the estrogen deficiency-induced weight gain, bone loss and deterioration of trabecular microarchitecture, maintain biomechanical competence of bone, and prevent bone fracture; moreover, the chemical constituents in the roots of Jasminum giraldill, such as iridoids and lignans, were also present strong bone protection. However, their structural diversity and the definite signal pathway of their effects have not been elucidated completely, and this hindered us to obtain their clear structure-activity relationship. Therefore, the feasibility of our project was verified by our previous work, however, further studies are needed to implement. In the present project, we will use serum pharmacology methods to discover the features of the effective components, use natural products research methods to explore novel bioactive compounds from the effective components, and finally use molecular biology research approach to clarify whether or not the compounds can regulate the balance on bone metabolism and bone formation between osteoblasts-osteoclasts, and whether or not their molecular mechanisms are played through RANKL-RANK-OPG signaling pathway... Our project will be helpful to reveal the material basis of ‘Quan-pi’ (the roots of Jasminum giraldill), provide scientific basis for the clinical application, and provide leading compounds for the prevention and treatment of OP.

骨质疏松症（OP）发病率与致残率极高，严重危害人类健康。秦岭特色药材荃皮具有活血祛瘀生肌之功效，中医临床常用于治疗跌倒损伤、骨折刀伤等。. 申请者前期对其抗OP药效进行了评价，结果表明醇提物能剂量性地提高大鼠成骨细胞OPG表达，抑制RANKL表达，显著对抗去势引起的骨丢失，保持骨矿密度；所含化学成分为环烯醚萜类、木脂素类等，部分呈现较强的骨保护作用，但结构多样性和作用机制尚未完全阐明，无法得到明确的构—效关系。. 本项目拟对其深入研究：①采用血清药理学方法发现并锁定荃皮抗OP作用的有效组分群；②进而采用活性追踪分离的方法，从中分离纯化出活性成分；③在成骨/破骨细胞共培养体系中，以RANKL-RANK-OPG信号通路为靶标，研究荃皮调节骨代谢与骨形成从而发挥抗OP作用的分子机制。. 该研究预期可揭示荃皮抗OP作用的物质基础，为中医临床应用提供科学依据，为发掘新型抗OP先导物做出贡献。

骨质疏松症（OP）严重危害人类健康，已被列为国家重点攻关的三大老年疾病之一。目前临床使用的药物存在诸多问题，引起广泛关注。秦岭特色中草药在治疗风湿骨痛、骨折刀伤方面疗效独特显著，本课题组长期以来以其为对象开展科学研究，以期寻找到防治OP安全有效的药物，保障我国日趋严峻的老龄化社会的健康。. 在长期与民间医生探讨及翻阅大量临床病案的基础上，发掘秦岭特色药材荃皮（民间誉称“山救驾”）接骨疗效显著，推测其具在治疗OP方面有潜在的应用价值。. 首先采用10月龄OVX大鼠模型模拟绝经后妇女OP，研究荃皮的药理药效。研究结果发现与模型组比较，荃皮不同剂量给药组骨形成与骨吸收血生化指标均显著下降，表明去势后大鼠高转化状态的骨重建过程获得了不同程度的抑制；大鼠股骨BMC和BMD显著升高，表明股骨骨骼质量得到明显提高；股骨干骺端骨计量学参数测量结果显示，骨小梁的数目、间隙、连接性等结构特征均得到明显改善；股骨头和骨干平均最大骨折负荷也显著升高，表明股骨骨骼强度显著增强。上述实验结果表明，荃皮对OVX导致的OP具有很好的防治作用，可以在OP的中医临床治疗及绝经后OP患者的预防中使用。. 在此基础上，本项目以血清药理学方法为指导，发现荃皮抗OP活性成分有三大类群，进而对荃皮防治OP的物质基础展开系统研究，从中分离鉴定了46个化合物，其中裂环环烯醚萜苷8个、苯丙素苷10个，木脂素及其糖苷6个，松香烷型二萜14个、黄酮和三萜各1个，其它简单类型化合物6个。分离鉴定的化合物中，3个为新颖骨架化合物，14个为新化合物。上述结果为新型OP药物的研发提供了线索。. 综上所述，本项目取得了两大研究成果：①研究证实了秦岭特色药材在防治OP的药理作用，为其中医临床应用提供了科学依据；②研究揭示了荃皮抗OP作用的物质基础，为发掘新型抗OP先导物作出了贡献。