Cao Sisi, Tian Xue-Lian, Yu Wen-Xuan, Zhou Li-Ping, Dong Xiao-Li, Favus Murray J, Wong Man-Sau
Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong.
State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, China.
Front Pharmacol. 2018 Dec 4;9:1435. doi: 10.3389/fphar.2018.01435. eCollection 2018.
Oleanolic acid (OA) and ursolic acid (UA) are the major chemical constituents in (FLL), a kidney-tonifying Chinese herb that is previously shown to improve bone properties and enhance calcium balance in aged female rats. The present study was designed to study if OA and UA act as the active ingredients in FLL to exert the positive effects on bone and mineral metabolism in aged rats. Aged (13-month-old) Sprague-Dawley female rats were randomly assigned to four groups with oral administration of drug or vehicle treatment for 12 weeks: medium calcium diet (MCD, 0.6% calcium), high calcium diet (HCD, 1.2% calcium), MCD + FLL (700 mg/kg/day), MCD + OA (23.6 mg/kg/day) + UA (8.6 mg/kg/day). A group of mature (3-month-old) female rats fed with MCD was included as positive control. The results demonstrated that FLL and OA+UA increased bone mineral density and improved microarchitectural properties of aged female rats. The osteoprotective effects of FLL and OA+UA might be, at least in part, associated with their actions on enhancing calcium balance and suppressing age-induced secondary hyperparathyroidism in aged female rats. FLL and OA+UA also significantly induced renal CYP27B1 protein expression and OA+UA treatment decreased CYP24A1 mRNA and protein expressions in aged female rats. In addition, FLL and OA+UA significantly increased the promoter activity, mRNA and protein expressions of renal CYP27B1 in human proximal tubule HKC-8 cells. The present findings suggest that OA+UA can be regarded as the active ingredients of FLL and might be a potential drug candidate for prevention and treatment of osteoporosis.
齐墩果酸（OA）和熊果酸（UA）是补肾中药女贞子（FLL）中的主要化学成分，先前的研究表明，该中药可改善老年雌性大鼠的骨骼特性并增强钙平衡。本研究旨在探讨OA和UA是否作为FLL中的活性成分，对老年大鼠的骨骼和矿物质代谢产生积极影响。将老年（13月龄）Sprague-Dawley雌性大鼠随机分为四组，口服药物或赋形剂治疗12周：中钙饮食（MCD，0.6%钙）、高钙饮食（HCD，1.2%钙）、MCD + FLL（700 mg/kg/天）、MCD + OA（23.6 mg/kg/天）+ UA（8.6 mg/kg/天）。一组喂食MCD的成熟（3月龄）雌性大鼠作为阳性对照。结果表明，FLL以及OA + UA可增加老年雌性大鼠的骨密度，并改善其微观结构特性。FLL和OA + UA的骨保护作用可能至少部分与其增强老年雌性大鼠钙平衡和抑制年龄诱导的继发性甲状旁腺功能亢进的作用有关。FLL和OA + UA还显著诱导老年雌性大鼠肾CYP27B1蛋白表达，且OA + UA处理可降低老年雌性大鼠CYP24A1 mRNA和蛋白表达。此外，FLL和OA + UA显著增加人近端小管HKC-8细胞中肾CYP27B1的启动子活性、mRNA和蛋白表达。本研究结果表明，OA + UA可被视为FLL的活性成分，可能是预防和治疗骨质疏松症的潜在候选药物。
