Both Oleanolic Acid and a Mixture of Oleanolic and Ursolic Acids Mimic the Effects of Fructus ligustri lucidi on Bone Properties and Circulating 1,25-Dihydroxycholecalciferol in Ovariectomized Rats.

Background Oleanolic acid (OA) and ursolic acid (UA) are major chemical constituents found in Fructus ligustri lucidi (FLL), a Chinese herb previously shown to increase bone properties and modulate calcium-vitamin D metabolism in rats. OA and UA have been reported to exert osteoprotective effects in vitro. Objective The present study was designed to determine whether OA or OA + UA mimicked the effects of FLL on bone and calcium homeostasis using ovariectomized rats. Methods Three-month-old ovariectomized Sprague-Dawley rats were stabilized for 2 mo and randomly assigned to 4 groups offered the same amount (15-17 g/d) of a control diet or experimental diets containing FLL (18.8 g/kg), OA (0.67 g/kg), or OA (0.67 g/kg) + UA (0.22 g/kg) for 6 wk. Serum was obtained for measurement of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] and bones were collected for micro-CT analysis. Calcium balance was measured at weeks 1 and 6. A calcium kinetic study using 45Ca was conducted at week 6 and modeled using WinSAAM software. Results Compared with the control group, rats fed the FLL-, OA-, and OA + UA-enriched diets had better bone properties and 51%, 31%, and 27% higher serum 1,25(OH)2D3 concentrations at week 6, respectively. These variables did not differ between the treatments. Calcium balance was not affected by diet at either week 1 or week 6. Kinetic modeling predicted that FLL and OA + UA diet-fed rats had 9% and 15% less endogenous excretion of calcium, respectively, compared with the control group. All 3 treatments resulted in a higher calcium mass of compartment 3 because of changes in transfer rate between compartments 2 and 3, and were positively associated with the serum 1,25(OH)2D3 concentration (R2 = 0.28; P < 0.01). Conclusion Similar to FLL, OA and OA + UA increase bone properties, serum 1,25(OH)2D3 concentration, and calcium use in ovariectomized rats, suggesting their potential role in management of osteoporosis.

[1]  X. Yao,et al.  Oleanolic Acid Exerts Osteoprotective Effects and Modulates Vitamin D Metabolism , 2018, Nutrients.

[2]  V. Pavone,et al.  Pharmacological Therapy of Osteoporosis: A Systematic Current Review of Literature , 2017, Front. Pharmacol..

[3]  X. Shang,et al.  Oleanolic Acid Enhances Mesenchymal Stromal Cell Osteogenic Potential by Inhibition of Notch Signaling , 2017, Scientific Reports.

[4]  S. Khosla,et al.  The impact of the new National Bone Health Alliance (NBHA) diagnostic criteria on the prevalence of osteoporosis in the USA , 2017, Osteoporosis International.

[5]  Jinqiu Feng,et al.  Fructus Ligustri Lucidi ethanol extract inhibits osteoclastogenesis in RAW264.7 cells via the RANKL signaling pathway. , 2016, Molecular medicine reports.

[6]  Xiao-Li Dong,et al.  Ethanol Extract of Fructus ligustri lucidi Increased Circulating 1,25(OH)2D3 Levels, but Did Not Improve Calcium Balance in Mature Ovariectomized Rats. , 2016, The American journal of Chinese medicine.

[7]  Emily E. Hohman,et al.  A grape-enriched diet increases bone calcium retention and cortical bone properties in ovariectomized rats. , 2015, The Journal of nutrition.

[8]  Xiaoqian Liu,et al.  Ligustri Lucidi Fructus as a traditional Chinese medicine: a review of its phytochemistry and pharmacology , 2015, Natural product research.

[9]  K. Ohnuki,et al.  Inhibitory effects of the leaves of loquat (Eriobotrya japonica) on bone mineral density loss in ovariectomized mice and osteoclast differentiation. , 2014, Journal of agricultural and food chemistry.

[10]  Xin Feng,et al.  Fructus Ligustri Lucidi (FLL) ethanol extract increases bone mineral density and improves bone properties in growing female rats , 2014, Journal of Bone and Mineral Metabolism.

[11]  Xin Feng,et al.  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 , 2013, Calcified Tissue International.

[12]  Yongjun Wang,et al.  Oleanolic acid exerts an osteoprotective effect in ovariectomy-induced osteoporotic rats and stimulates the osteoblastic differentiation of bone mesenchymal stem cells in vitro , 2012, Menopause.

[13]  C. Weaver,et al.  Insulin-like growth factor-1 increases bone calcium accumulation only during rapid growth in female rats. , 2011, The Journal of nutrition.

[14]  C. Che,et al.  Improvement of calcium balance by Fructus Ligustri Lucidi extract in mature female rats was associated with the induction of serum parathyroid hormone levels , 2011, British Journal of Nutrition.

[15]  Jian-Xin Li,et al.  Quinoxaline derivative of oleanolic acid inhibits osteoclastic bone resorption and prevents ovariectomy-induced bone loss , 2011, Menopause.

[16]  M. Favus,et al.  Ethanol extract of Fructus Ligustri Lucidi increases circulating 1,25-dihydroxyvitamin D3 by inducing renal 25-hydroxyvitamin D-1&agr; hydroxylase activity , 2010, Menopause.

[17]  C. Weaver,et al.  Tetracycline and calcium kinetics are comparable for estimating bone resorption in rats. , 2010, The Journal of nutrition.

[18]  Y. Kong.  Huangdi Neijing: A Synopsis with Commentaries , 2010 .

[19]  N. L. Fazzalari,et al.  Detecting early bone changes using in vivo micro-CT in ovariectomized, zoledronic acid-treated, and sham-operated rats , 2010, Osteoporosis International.

[20]  Jian-Xin Li,et al.  Synthesis and evaluation of a novel series of heterocyclic oleanolic acid derivatives with anti-osteoclast formation activity. , 2009, European journal of medicinal chemistry.

[21]  Sang-Joon Park,et al.  Anabolic activity of ursolic acid in bone: Stimulating osteoblast differentiation in vitro and inducing new bone formation in vivo. , 2008, Pharmacological research.

[22]  P. Leung,et al.  Fructus ligustri lucidi extract improves calcium balance and modulates the calciotropic hormone level and vitamin D-dependent gene expression in aged ovariectomized rats , 2008, Menopause.

[23]  Chunfu Wu,et al.  Improvement of bone properties and enhancement of mineralization by ethanol extract of Fructus Ligustri Lucidi , 2008, British Journal of Nutrition.

[24]  P. Leung,et al.  Improvement of Ca balance by Fructus Ligustri Lucidi extract in aged female rats , 2008, Osteoporosis International.

[25]  Chunfu Wu,et al.  Effects of Fructus Ligustri Lucidi extract on bone turnover and calcium balance in ovariectomized rats. , 2006, Biological & pharmaceutical bulletin.

[26]  Liu Han-lan.  Extracction and Content Determination of Triterpenoods in Fructus ligustri lucidi , 2006 .

[27]  Y. Zhang,et al.  Five new oleanolic acid glycosides from Achyranthes bidentata with inhibitory activity on osteoclast formation. , 2005, Planta medica.

[28]  Jian-Xin Li,et al.  Synthesis and activity of oleanolic acid derivatives, a novel class of inhibitors of osteoclast formation. , 2005, Bioorganic & medicinal chemistry letters.

[29]  C. Weaver,et al.  Calcium Bioavailability and Kinetics of Calcium Ascorbate and Calcium Acetate in Rats , 2004, Experimental biology and medicine.