Abstract
Oleanolic acid (OA) is a triterpenoid with reported bone anti-resorption activities. The present study aimed to characterize its bone protective effects in vivo and to study its effects on vitamin D metabolism, both in vivo and in vitro. OA significantly increased bone mineral density, improved micro-architectural properties, reduced urinary Ca excretion, increased 1,25(OH)₂D₃ and renal CYP27B1 mRNA expression in mature C57BL/6 ovariectomised (OVX) mice. OA also improved bone properties, Ca balance, and exerted modulatory effects on renal CYP27B1 and CYP24A1 expressions in aged normal female Sprague-Dawley rats. In addition, OA significantly increased renal CYP27B1 mRNA and promoter activity, and suppressed CYP24A1 mRNA and protein expressions in human proximal tubule HKC-8 cells. OA exerted bone protective effects in mature OVX mice and aged female rats. This action on bone might be, at least in part, associated with its effects on Ca and vitamin D metabolism. The present findings suggest that OA is a potential drug candidate for the management of postmenopausal osteoporosis.
Keywords:
aging; calcium; oleanolic acid; osteoporosis; ovariectomised; vitamin D.
MeSH terms
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25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
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25-Hydroxyvitamin D3 1-alpha-Hydroxylase / metabolism
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Animals
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Bone Density / drug effects*
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Bone Density Conservation Agents / pharmacology*
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Bone Remodeling / drug effects*
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Bone and Bones / diagnostic imaging
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Bone and Bones / drug effects*
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Bone and Bones / metabolism
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Bone and Bones / physiopathology
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Calcitriol / metabolism
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Calcium / urine
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Cell Line
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Duodenum / drug effects
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Duodenum / metabolism
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Female
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Humans
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Kidney Tubules, Proximal / drug effects
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Kidney Tubules, Proximal / enzymology
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Mice, Inbred C57BL
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Oleanolic Acid / pharmacology*
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Osteoporosis, Postmenopausal / diagnostic imaging
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Osteoporosis, Postmenopausal / drug therapy*
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Osteoporosis, Postmenopausal / metabolism
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Osteoporosis, Postmenopausal / physiopathology
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Ovariectomy
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Rats, Sprague-Dawley
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Vitamin D / metabolism*
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Vitamin D3 24-Hydroxylase / genetics
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Vitamin D3 24-Hydroxylase / metabolism
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X-Ray Microtomography
Substances
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Bone Density Conservation Agents
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Vitamin D
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Oleanolic Acid
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CYP24A1 protein, human
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Cyp24a1 protein, rat
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Vitamin D3 24-Hydroxylase
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25-Hydroxyvitamin D3 1-alpha-Hydroxylase
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CYP27B1 protein, human
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Calcitriol
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Calcium