Oleanolic Acid Exerts Osteoprotective Effects and Modulates Vitamin D Metabolism

Overview

Journal Nutrients

Date 2018 Feb 23

PMID 29470404

Citations 12

Authors

Sisi Cao

Xiao-Li Dong

Ming-Xian Ho

Wen-Xuan Yu

Ka-Chun Wong

Xin-Sheng Yao

Man-Sau Wong

Affiliations

Soon will be listed here.

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.

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References

Zhang Y, Dong X, Leung P, Che C, Wong M . Fructus ligustri lucidi extract improves calcium balance and modulates the calciotropic hormone level and vitamin D-dependent gene expression in aged ovariectomized rats. Menopause. 2008; 15(3):558-65. DOI: 10.1097/gme.0b013e31814fad27. View

Brenza H, DeLuca H . Regulation of 25-hydroxyvitamin D3 1alpha-hydroxylase gene expression by parathyroid hormone and 1,25-dihydroxyvitamin D3. Arch Biochem Biophys. 2000; 381(1):143-52. DOI: 10.1006/abbi.2000.1970. View

Bikle D . Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol. 2014; 21(3):319-29. PMC: 3968073. DOI: 10.1016/j.chembiol.2013.12.016. View

Zhao J, Zeng X, Wang J, Liu L . Association Between Calcium or Vitamin D Supplementation and Fracture Incidence in Community-Dwelling Older Adults: A Systematic Review and Meta-analysis. JAMA. 2017; 318(24):2466-2482. PMC: 5820727. DOI: 10.1001/jama.2017.19344. View

van Abel M, Hoenderop J, Dardenne O, St Arnaud R, van Os C, van Leeuwen H . 1,25-dihydroxyvitamin D(3)-independent stimulatory effect of estrogen on the expression of ECaC1 in the kidney. J Am Soc Nephrol. 2002; 13(8):2102-9. DOI: 10.1097/01.asn.0000022423.34922.2a. View

Veldurthy V, Wei R, Oz L, Dhawan P, Jeon Y, Christakos S . Vitamin D, calcium homeostasis and aging. Bone Res. 2016; 4:16041. PMC: 5068478. DOI: 10.1038/boneres.2016.41. View

Xu D, Lyu Y, Chen X, Zhu X, Feng J, Xu Y . Fructus Ligustri Lucidi ethanol extract inhibits osteoclastogenesis in RAW264.7 cells via the RANKL signaling pathway. Mol Med Rep. 2016; 14(5):4767-4774. DOI: 10.3892/mmr.2016.5849. View

Feng X, Lyu Y, Wu Z, Fang Y, Xu H, Zhao P . Fructus ligustri lucidi ethanol extract improves bone mineral density and properties through modulating calcium absorption-related gene expression in kidney and duodenum of growing rats. Calcif Tissue Int. 2013; 94(4):433-41. DOI: 10.1007/s00223-013-9825-4. View

Fleet J, Schoch R . Molecular mechanisms for regulation of intestinal calcium absorption by vitamin D and other factors. Crit Rev Clin Lab Sci. 2010; 47(4):181-95. PMC: 3235806. DOI: 10.3109/10408363.2010.536429. View

10.

Riggs B . Role of the vitamin D-endocrine system in the pathophysiology of postmenopausal osteoporosis. J Cell Biochem. 2003; 88(2):209-15. DOI: 10.1002/jcb.10345. View

11.

Tang B, Eslick G, Nowson C, Smith C, Bensoussan A . Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet. 2007; 370(9588):657-66. DOI: 10.1016/S0140-6736(07)61342-7. View

12.

Zhang Y, Li J, Zhao J, Wang S, Pan Y, Tanaka K . Synthesis and activity of oleanolic acid derivatives, a novel class of inhibitors of osteoclast formation. Bioorg Med Chem Lett. 2005; 15(6):1629-32. DOI: 10.1016/j.bmcl.2005.01.061. View

13.

Zhao Y, Huai Y, Jin J, Geng M, Li J . Quinoxaline derivative of oleanolic acid inhibits osteoclastic bone resorption and prevents ovariectomy-induced bone loss. Menopause. 2011; 18(6):690-7. DOI: 10.1097/gme.0b013e3181fd7f4b. View

14.

Nordin B . Calcium and osteoporosis. Nutrition. 1997; 13(7-8):664-86. DOI: 10.1016/s0899-9007(97)83011-0. View

15.

Chung M, Tang A, Fu Z, Wang D, Newberry S . Calcium Intake and Cardiovascular Disease Risk: An Updated Systematic Review and Meta-analysis. Ann Intern Med. 2016; 165(12):856-866. DOI: 10.7326/M16-1165. View

16.

Dong X, Zhang Y, Favus M, Che C, Wong M . Ethanol extract of Fructus Ligustri Lucidi increases circulating 1,25-dihydroxyvitamin D3 by inducing renal 25-hydroxyvitamin D-1α hydroxylase activity. Menopause. 2010; 17(6):1174-81. DOI: 10.1097/gme.0b013e3181e39a2b. View

17.

Wang J, Shan A, Liu T, Zhang C, Zhang Z . In vitro immunomodulatory effects of an oleanolic acid-enriched extract of Ligustrum lucidum fruit (Ligustrum lucidum supercritical CO2 extract) on piglet immunocytes. Int Immunopharmacol. 2012; 14(4):758-63. DOI: 10.1016/j.intimp.2012.10.006. View

18.

Armbrecht H, Boltz M, Bruns M . Effect of age and dietary calcium on intestinal calbindin D-9k expression in the rat. Arch Biochem Biophys. 2003; 420(1):194-200. DOI: 10.1016/j.abb.2003.09.025. View

19.

Drake M, Clarke B, Lewiecki E . The Pathophysiology and Treatment of Osteoporosis. Clin Ther. 2015; 37(8):1837-50. DOI: 10.1016/j.clinthera.2015.06.006. View

20.

Bikle D . Extraskeletal actions of vitamin D. Ann N Y Acad Sci. 2016; 1376(1):29-52. PMC: 5031366. DOI: 10.1111/nyas.13219. View