title: 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.affiliation: Division of Endocrinology, Central Drug Research Institute (Council of Scientific and Industrial Research), Chattar Manzil, Lucknow, India.
authors.forename: Kunal
authors.initials: K
authors.lastname: Sharan
authors.forename: Gaurav
authors.initials: G
authors.lastname: Swarnkar
authors.forename: Jawed A
authors.initials: JA
authors.lastname: Siddiqui
authors.forename: Avinash
authors.initials: A
authors.lastname: Kumar
authors.forename: Preeti
authors.initials: P
authors.lastname: Rawat
authors.forename: Manmeet
authors.initials: M
authors.lastname: Kumar
authors.forename: Geet K
authors.initials: GK
authors.lastname: Nagar
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Manickavasagam
authors.forename: Sheelendra P
authors.initials: SP
authors.lastname: Singh
authors.forename: Geetanjali
authors.initials: G
authors.lastname: Mishra
authors.lastname: Wahajuddin
authors.forename: Girish K
authors.initials: GK
authors.lastname: Jain
authors.forename: Rakesh
authors.initials: R
authors.lastname: Maurya
authors.forename: Naibedya
authors.initials: N
authors.lastname: Chattopadhyay
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage* / Q000494:pharmacology; D006027:Glycosides / Q000008:administration & dosage* / Q000494:pharmacology; D006207:Half-Life; D010006:Osteoblasts / Q000187:drug effects; D015675:Osteocalcin / Q000097:blood; D010012:Osteogenesis / Q000187:drug effects; D010024:Osteoporosis / Q000188:drug therapy* / Q000517:prevention & control; D010052:Ovariectomy; D010936:Plant Extracts / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D034403:Ulmus
chemical_list: D005419:Flavonoids; D006027:Glycosides; D010936:Plant Extracts; C543953:ulmoside A; D015675:Osteocalcin