A novel flavonoid, 6-C-beta-d-glucopyranosyl-(2S,3S)-(+)-3',4',5,7-tetrahydroxyflavanone, isolated from Ulmus wallichiana Planchon mitigates ovariectomy-induced osteoporosis in rats.

Abstract

OBJECTIVE:

The aim of this study was to determine the skeletal effect of 6-C-beta-d-glucopyranosyl-(2S,3S)-(+)-3',4',5,7-tetrahydroxyflavanone (GTDF)/Ulmoside A, a new compound isolated from the extract of Ulmus wallichiana in a rat model of postmenopausal bone loss.

METHODS:

GTDF (1.0 and 5.0 mg kg d) was given orally to ovariectomized (OVx) rats (180-200 g) for 12 weeks. Sham operated + vehicle, ovariectomy + 17beta-estradiol (2.5 microg kg d), and ovariectomy + vehicle groups served as various controls. Bone mineral density (BMD), trabecular microarchitecture, bone biomechanical strength, levels of bone turnover/resorption markers, uterotropic effect, and plasma pharmacokinetics were studied. One-way analysis of variance was used to test significance of effects.

RESULTS:

OVx rats treated with both doses of GTDF exhibited significantly higher BMD in the trabecular (distal femur, proximal tibia, and vertebrae) and cortical (femur shaft) regions compared with the ovariectomy + vehicle group. Micro-CT demonstrated that OVx rats treated with 5.0 mg kg day of GTDF had better bone microarchitectural parameters compared with the ovariectomy + vehicle group. Serum osteocalcin and urinary C-terminal teleopeptide of Type I collagen levels in OVx rats treated with GTDF (at both doses) were significantly lower than those in the ovariectomy + vehicle group. At neither of the two doses did GTDF exhibit uterine estrogenicity. A pharmacokinetic study revealed that GTDF achieved maximum plasma concentration (40.67 ng mL) at approximately 1 hour, indicating its slow absorption. Its absolute bioavailability was found to be 1.04% with a plasma elimination half-life of approximately 5 hours.

CONCLUSIONS:

GTDF, a novel compound isolated from U wallichiana extract, improves bone biomechanical quality through positive modifications of BMD and trabecular microarchitecture without a hyperplastic effect on the uterus.

• Authors: Kunal Sharan, Gaurav Swarnkar, Jawed A Siddiqui, Avinash Kumar, Preeti Rawat, Manmeet Kumar, Geet K Nagar, Lakshmi Manickavasagam, Sheelendra P Singh, Geetanjali Mishra, Wahajuddin, Girish K Jain, Rakesh Maurya, Naibedya Chattopadhyay
• Journal: Menopause (New York, N.Y.) (Menopause) 2010 May-Jun Vol. 17 Issue 3 Pg. 577-86 ISSN: 1530-0374 [Electronic] United States
• PMID: 20393370 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Flavonoids
• Glycosides
• Plant Extracts
• ulmoside A
• Osteocalcin

Topics

• Animals
• Bone Density (drug effects)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Female
• Flavonoids (administration & dosage, pharmacology)
• Glycosides (administration & dosage, pharmacology)
• Half-Life
• Osteoblasts (drug effects)
• Osteocalcin (blood)
• Osteogenesis (drug effects)
• Osteoporosis (drug therapy, prevention & control)
• Ovariectomy
• Plant Extracts (administration & dosage)
• Rats
• Rats, Sprague-Dawley
• Ulmus