3-Piperidylethoxypterocarpan: A potential bone anabolic agent that improves bone quality and restores trabecular micro-architecture in ovariectomized osteopenic rats. (15th June 2017)

• Record Type: Journal Article
• Authors: Raghuvanshi, Ashutosh; Kumar, Amit; Tyagi, Abdul M.; Kureel, Jyoti; Awasthi, Pallavi; Purohit, Deepak; Mansoori, Mohd Nizam; Shukla, Priyanka; Srivastava, Kamini; Gautam, Abnish K.; Saxena, Ruchi; Dwivedi, Anila; Singh, Divya; Goel, Atul
• Is Part Of: Molecular and cellular endocrinology. Volume 448(2017)
• Page Start: 41
• Page End: 54
• Publication Date: 2017-06-15
• Subjects: Benzofurochromene -- Bone anabolic agent -- Osteoporosis -- Ovariectomized -- BMP-2 activator; BFC 6H-benzofuro[3, 2-c] chromenes -- BMD bone mineral density -- MAR mineral apposition rate -- BFR bone formation rate -- SERM selective estrogen receptor modulators -- PTH parathyroid hormone -- MAPK mitogen-activated protein kinases -- ALP alkaline phosphatase -- OVx ovariectomized -- TFSP tibio-fibula separating point -- μ-CT micro computed tomography -- B.Ar cortical mean cross section -- BV/TV percentage bone volume -- Cs.Th. cross-sectional cortical thickness -- T.Ar periosteal area -- T.Pm periosteal perimeter -- BMCs Bone marrow cells -- ER Estrogen Receptor -- BMP-2 Bone Morphogenetic Protein -- Tb. Pf Trabecular pattern factor -- Tb. Sp Trabecular separation -- SMI Structure model index -- DA Degree of anisotropy; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2017.03.010
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: A series of new 6 H -benzofuro[ 3, 2-c ]chromenes (BFC, pterocarpans) with structure-activity relationships were investigated for their potential use in osteoporosis treatment. One of the BFCs 3-piperidylethoxypterocarpan20 promotes osteoblast differentiation and mineralization at a dose as low as 1 pM via activation of ER/P38MAPK/BMP-2 pathway. When evaluated for in-vivo osteogenic activity in female Sprague-Dawley rats, BFC20 increased bone mineral density and new bone formation, compared with control at 1.0 and 10.0 mg/kg/body weight by oral gavage for 30 days. The compound was devoid of any uterotrophic effect and led to the new bone formation in adult ovariectomized osteopenic rats. BFC20 compound also inhibited bone resorption by reducing Ovx induced increase in urinary CTx, thus exhibiting both bone anabolic and anti-catabolic action. Finally, BFC20 treatment to Ovx rats led to improved trabecular microarchitectural restoration and exhibited therapeutic potential as a dual acting anti-osteoporotic agent for the management of osteoporosis. Highlights: 3-piperidylethoxy-pterocarpan20 promotes osteoblast differentiation and mineralization of bone matrix. Mode of action is via ERα-p38MAPK-BMP2 pathway. 3-piperidylethoxy-pterocarpan20 promotes bone formation and inhibits bone resorption in ovariectomized osteopenic SD rats.