Morin Improves the Bone Histomorphology and Biochemical Markers in an Animal Model of Ovariectomy‐Induced Osteoporosis by Suppressing Autophagy and Apoptosis

Osteoporosis (OP) is the most prevalent metabolic bone disease and an important postmenopausal consequence. This study aimed to investigate the effects of morin, a flavonoid with beneficial properties, on ovariectomy-induced OP. Animals were ovariectomized (OVX) and treated with different doses of morin (15, 30, and 45 mg/kg/day) or estradiol (10 μg/kg/day) for 10 weeks by gavage. Then bone histo-stereology, bone-related biochemical indicators, and gene and protein levels of autophagy and apoptosis-related markers were analyzed. In comparison to controls, OVX significantly decreased the number of osteoblasts (5.78 × 10⁶ vs. 1.66 × 10⁶) and osteocytes (32.55 × 10⁶ vs. 11.92 × 10⁶), whereas increasing the number of osteoclasts (83.38 × 10³ vs. 392.1 × 10³). Moreover, OVX caused a remarkable decrease in bone structures and Ca, P, and estradiol levels while increasing ALP and OC (<i>p</i> < 0.001). The administration of 45 mg/kg/day morin restored the effects of OP on bone histomorphology and biochemical markers (<i>p</i> < 0.05). Further studies revealed that morin caused a 7.1% and 36.6% decrease in the bone level of LC3 and BECN1 proteins, respectively, compared to the OVX group. Also, morin caused a significant decrease of 47.4% in the CASP3 level and a significant increase of 23.6% in the BCL-2 level compared to OVX animals (<i>p</i> < 0.001). The present findings showed that morin is potentially able to improve the bone-related histomorphological and biochemical changes caused by osteoporosis, which is probably attributed to the suppression of apoptosis- and autophagy-caused cell death.