Effect of <i>Pistacia Atlantica</i> Desf. Oleo-Gum-Resin Nanoformulation on Modulating Bone Metabolism in Ovariectomized Rats through OPG/ RANKL/RANK Pathway

Background: Pistacia atlantica Desf. is a widely used medicinal plant in traditional medicine and has long been used by native populations for various therapeutic purposes, including the treatment of osteoporosis and fractures. This study investigated the therapeutic effects of P. atlantica oleo-gum-resin on the gene expression and histological parameters in a postmenopausal osteoporosis model. Methods: Osteoporosis was induced in rats via ovariectomy. Rats received oral administration of P. atlantica oleo-gum-resin and its nanocapsulated form (50, 100, 200 mg/kg) for eight weeks. Stereological analysis was performed by evaluating total bone density, cortical bone thickness, trabeculated bone number, and total bone marrow density. Additionally, the number of osteocytes, osteoblasts, and osteoclasts was calculated. The expression of osteocalcin, Osteoprotegerin (OPG), Receptor Activator of Nuclear factor Kappa-B (RANK), and Receptor Activator of Nuclear factor Kappa-B ligand (RANKL) was detected by real-time polymerase chain reaction (Real-time PCR). Results: P. atlantica oleo-gum-resin and its encapsulated form, with a dose of 100 and 200 mg/kg, significantly increased the volumes of total bone, bone marrow, trabecular bone, cortical bone, and the numbers of osteocytes and osteoblasts of callus compared to the control rats. Additionally, mRNA expression of osteocalcin and OPG increased significantly, whereas RANK and RANKL decreased in the tibial callus compared with the control group. Conclusion: P. atlantica protected against bone loss in OVX-induced osteoporotic rats and could be considered as an anti-osteoporotic candidate for human osteoporotic disorders. However, further clinical studies are necessary to validate its effectiveness and safety in the treatment of postmenopausal osteoporosis.