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

J Nutr. 2018 Dec 1;148(12):1895-1902. doi: 10.1093/jn/nxy242.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Density
  • Bone and Bones / metabolism*
  • Calcitriol / blood*
  • Calcium / metabolism*
  • Female
  • Fruit
  • Ligustrum*
  • Oleanolic Acid / pharmacology*
  • Ovariectomy
  • Rats
  • Rats, Sprague-Dawley
  • Triterpenes / pharmacology*
  • Ursolic Acid

Substances

  • Triterpenes
  • Oleanolic Acid
  • Calcitriol
  • Calcium