Abstract
Oleanolic acid (OA) and ursolic acid (UA) are the major chemical constituents in Fructus Ligustri Lucidi (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 vitro 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.
Highlights
Osteoporosis is a skeletal disorder characterized by low bone mass and microarchitectural deterioration of bone tissue which increases the risk of fracture
Mature rats have a much lower urinary calcium/creatinine (Ca/Cr) level compared to that in aged rats fed with the same diet (p < 0.001 vs. aged rat fed with medium calcium diet (MCD)) and Oleanolic acid (OA)+ursolic acid (UA) treatment significantly (p < 0.01 vs. MCD) suppressed age-related urinary calcium loss in rats
The present study demonstrates that oral administration of Fructus Ligustri Lucidi (FLL) or OA+UA for 12 weeks significantly reduced age-related bone loss and improved bone microarchitectural properties in aged female rats
Summary
Osteoporosis is a skeletal disorder characterized by low bone mass and microarchitectural deterioration of bone tissue which increases the risk of fracture. In China, the prevalence of osteoporosis is 50% in women and 22.5% in men aged > 50 years (Wang et al, 2009). It is estimated that 40% of Chinese women and 10% of Chinese men are expected to have a major osteoporotic fracture after turning 50 years old (Si et al, 2015). Calcium, vitamin D supplements, and pharmacological agents, such as bisphosphonates, teriparatide, and denosumab, are commonly used in the elderly. They exert beneficial effects on bones, the concerns about their potential side effects and safety of long-term use are rising (Tu et al, 2018). Given the rapid growth of the aging population, development of alternative approaches for management of bone health is pressing
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