Osteogenic activity of natural diterpenoids isolated from Cupressus sempervirens fruits in calvarial derived osteoblast cells via differentiation and mineralization.

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.