title: A naturally occurring rare analog of quercetin promotes peak bone mass achievement and exerts anabolic effect on osteoporotic bone.
abstract: The effect of quercetin C-glucoside (QCG) on osteoblast function in vitro and bone formation in vivo was investigated. QCG supplementation promoted peak bone mass achievement in growing rats and new bone formation in osteopenic rats. QCG has substantial oral bioavailability. Findings suggest a significant bone anabolic effect of QCG.
  
  
  BACKGROUND
  Recently, we showed that extracts of Ulmus wallichiana promoted peak bone mass achievement in growing rats and preserved trabecular bone mass and cortical bone strength in ovariectomized (OVx) rats. 3,3',4',5,7-Pentahydroxyflavone-6-C-β-D-glucopyranoside, a QCG, is the most abundant bioactive compound of U. wallichiana extract. We hypothesize that QCG exerts bone anabolic effects by stimulating osteoblast function.
  
  
  METHODS
  Osteoblast cultures were harvested from rat calvaria and bone marrow (BM) to study differentiation and mineralization. In vivo, growing female Sprague Dawley rats and OVx rats with osteopenia were administered QCG (5.0 or 10.0 mg kg(-1) day(-1)) orally for 12 weeks. Efficacy was evaluated by examining changes in bone microarchitecture using histomorphometric and microcomputed tomographic analyses and by determination of new bone formation by fluorescent labeling of bone. Plasma and BM levels of QCG were determined by high-performance liquid chromatography.
  
  
  RESULTS
  QCG was much more potent than quercetin (Q) in stimulating osteoblast differentiation, and the effect of QCG was not mediated by estrogen receptors. In growing rats, QCG increased BM osteoprogenitors, bone mineral density, bone formation rate, and cortical deposition. In osteopenic rats, QCG treatment increased bone formation rate and improved trabecular microarchitecture. Comparison with the sham group (ovary intact) revealed significant restoration of trabecular bone in osteopenic rats treated with QCG. QCG levels in the BM were ~50% of that of the plasma levels.
  
  
  CONCLUSIONS
  QCG stimulated modeling-directed bone accrual and exerted anabolic effects on osteopenic rats by direct stimulatory effect on osteoprogenitors likely due to substantial QCG delivery at tissue level following oral administration.
authors.affiliation: Division of Endocrinology, Central Drug Research Institute (Council of Scientific and Industrial Research), Chattar Manzil, P.O. Box 173, Lucknow, India.
authors.forename: J A
authors.initials: JA
authors.lastname: Siddiqui
authors.forename: G
authors.initials: G
authors.lastname: Swarnkar
authors.forename: K
authors.initials: K
authors.lastname: Sharan
authors.forename: B
authors.initials: B
authors.lastname: Chakravarti
authors.forename: A K
authors.initials: AK
authors.lastname: Gautam
authors.forename: P
authors.initials: P
authors.lastname: Rawat
authors.forename: M
authors.initials: M
authors.lastname: Kumar
authors.forename: V
authors.initials: V
authors.lastname: Gupta
authors.forename: L
authors.initials: L
authors.lastname: Manickavasagam
authors.forename: A K
authors.initials: AK
authors.lastname: Dwivedi
authors.forename: R
authors.initials: R
authors.lastname: Maurya
authors.forename: N
authors.initials: N
authors.lastname: Chattopadhyay
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D001851:Bone Diseases, Metabolic / Q000188:drug therapy*; D001853:Bone Marrow / Q000737:chemistry; D002853:Chromatography, Liquid; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects; D005960:Glucosides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D006614:Hindlimb; D010006:Osteoblasts / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects*; D010052:Ovariectomy; D011794:Quercetin / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects; D055114:X-Ray Microtomography
chemical_list: C570340:3,3',4',5,7-pentahydroxyflavone-6-C-beta-D-glucopyranoside; D005960:Glucosides; D011794:Quercetin