title: Osteogenic activity of natural diterpenoids isolated from Cupressus sempervirens fruits in calvarial derived osteoblast cells via differentiation and mineralization.
abstract: The aim of the present study was to investigate the antiosteoporotic activity of four structurally related diterpenoids: sugiol (1), trans-communic acid (2), 15-acetoxy imbricatolic acid (3) and imbricatolic acid (4). Their osteogenic effect was evaluated by using validated models including alkaline phosphatase (ALP) assay, mineralization assay and expression of osteogenic genes-bone morphogenetic protein-2 (BMP-2) and osteoblast transcription factor (RUNX2) - in primary calvarial cultures harvested from neonatal mice. Among them, compound 1 at a dose of 1.0 mg/kg body weight exhibited significant osteoprotective effects and did not show uterine estrogenicity at the same dose. Additionally, compound 1 treatment led to improved biomechanical properties as exhibited by increased power, energy and stiffness in femoral bones compared to untreated Ovx animals. Since osteoporotic compression fracture correlates with the mechanical characteristics of trabecular bone, so that it could effectively reduce the risk of this type of fracture by improving trabecular micro architecture in postmenopausal women. Therefore, our findings proposed that diterpenoids may be useful new chemical agents in the treatment of diseases associated with bone loss.
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Mohammad Faheem
authors.initials: MF
authors.lastname: Khan
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Kapil
authors.initials: K
authors.lastname: Dev
authors.affiliation: Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Shibani
authors.initials: S
authors.lastname: Lahiri
authors.affiliation: Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Manisha
authors.initials: M
authors.lastname: Dixit
authors.affiliation: Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Ritu
authors.initials: R
authors.lastname: Trivedi
authors.affiliation: Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Divya
authors.initials: D
authors.lastname: Singh
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India. Electronic address: mauryarakesh@rediffmail.com.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Maurya
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D002113:Calcification, Physiologic / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D029781:Cupressus / Q000737:chemistry*; D004224:Diterpenes / Q000494:pharmacology*; D005260:Female; D005638:Fruit / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D010006:Osteoblasts / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects*; D010052:Ovariectomy; D012886:Skull / Q000166:cytology
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D050659:Core Binding Factor Alpha 1 Subunit; D004224:Diterpenes; C493716:Runx2 protein, mouse; C461919:communic acid; C524691:imbricatolic acid; C501333:sugiol
keywords: Alkaline phosphatase; Cupressus sempervirens; Diterpenoids; Osteoblast differentiation; Osteoporosis; Sugiol