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

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

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24 Scopus citations

Abstract

OBJECTIVE: The aim of this study was to determine the skeletal effect of 6-C-β-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-1 d-1) was given orally to ovariectomized (OVx) rats (180-200 g) for 12 weeks. Sham operated + vehicle, ovariectomy + 17β-estradiol (2.5 μg kg-1 d-1), 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 -1 day -1 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-1) at ∼1 hour, indicating its slow absorption. Its absolute bioavailability was found to be 1.04% with a plasma elimination half-life of ∼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.

Original languageEnglish
Pages (from-to)577-586
Number of pages10
JournalMenopause
Volume17
Issue number3
DOIs
StatePublished - May 1 2010

Keywords

  • Antiresorptive
  • Bioavailability
  • Bone strength
  • Estrogenicity
  • Phytoestrogen

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