title: 9-Demethoxy-medicarpin promotes peak bone mass achievement and has bone conserving effect in ovariectomized mice: Positively regulates osteoblast functions and suppresses osteoclastogenesis.
abstract: We report a new bone anabolic and anti-catabolic pterocarpan 9-demethoxy-medicarpin (DMM) for the management of postmenopausal osteoporosis. DMM promoted osteoblast functions via activation of P38MAPK/BMP-2 pathway and suppressed osteoclastogenesis in bone marrow cells (BMCs). In calvarial osteoblasts, DMM blocked nuclear factor kappaB (NFκB) signaling and inhibited the mRNA levels of pro-inflammatory cytokines. DMM treatment led to increased OPG (osteoprotegrin) and decreased transcript levels of TRAP (tartarate resistant acid phosphatase), RANK (receptor activator of NFκB) and RANKL (RANK ligand) in osteoblast-osteoclast co-cultures. Immature female SD rats administered with DMM exhibited increased bone mineral density, bone biomechanical strength, new bone formation and cortical bone parameters. Ovx mice administered with DMM led to significant restoration of trabecular microarchitecture and had reduced formation of osteoclasts and increased formation of osteoprogenitor cells in BMCs. DMM exhibited no uterine estrogenicity. Overall, these results demonstrate the therapeutic potential of DMM for the management of postmenopausal osteoporosis.
authors.affiliation: Medicinal & Process Chemistry, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi 110001, India. Electronic address: atul_goel@cdri.res.in.
authors.forename: Atul
authors.initials: A
authors.lastname: Goel
authors.affiliation: Medicinal & Process Chemistry, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Raghuvanshi
authors.affiliation: Medicinal & Process Chemistry, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Abnish
authors.initials: A
authors.lastname: Gautam
authors.affiliation: Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Kamini
authors.initials: K
authors.lastname: Srivastava
authors.affiliation: Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Kureel
authors.affiliation: Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Divya
authors.initials: D
authors.lastname: Singh
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002454:Cell Differentiation / Q000187:drug effects; D005260:Female; D006801:Humans; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy; D010052:Ovariectomy; D036343:Pterocarpans / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D000094162:Phytoalexins
chemical_list: D050071:Bone Density Conservation Agents; D036343:Pterocarpans; C047353:medicarpin; D000094162:Phytoalexins
keywords: Bone-anabolics; Bone-anticatabolics; Demethoxy-medicarpin; Osteoporosis; Pterocarpans