Bioflavonoid Tangeretin regulates RANK/RANKL/OPG Signaling Proteins via Stimulating Estrogenic Activity in Ovariectomized Rats

Background Globally, osteoporosis has arisen as a significant health hazard, impacting over 200 million individuals. It is often reported in women, especially those who are in the postmenopausal stage. Even though numerous reasons are linked with osteoporosis etiology, estrogen deprivation is the prime inducer of osteoporosis. Objectives The present research was intended to detect the bioflavonoid tangeretin potency against ameliorating osteoporosis in ovariectomized rats. Materials and Methods Ovariectomy was performed in healthy female Sprague rats and treated with two different doses of the drug tangeretin. The body weight gain obtained by the experimental animals was noted throughout the experimental period. The uterus and vagina, the organ responsible for estrogen production and activity, were measured. Bone mineral density (BMD) and biomechanical properties of the femur were evaluated to study the impact of tangeretin. Bone biomarkers estradiol, bone GLA protein, and acid phosphatase were quantified to assess the impact of tangeretin on bone turnover. Serum phosphorous, calcium, creatinine, and tartrate-resistant acid phosphatase (TRAP), which are the osteoporosis risk factors, were analyzed in tangeretin-treated ovariectomized rats. Signaling proteins involved in the receptor activator of nuclear factor-κB (RANK)/receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) pathway, which is responsible for bone turnover, were quantified. Results Tangeretin treatment significantly inhibited excess weight gain and increased the uterus and vaginal weight. BMD and biomechanical analysis of the femur prove tangeretin treatment increased the BMD and upgraded the biomechanical properties in ovariectomized animals. Tangeretin increased the estradiol and decreased the bone GLA protein and acid phosphatase. It also increased serum phosphorous, calcium, and creatinine and decreased the TRAP levels, confirming its ameliorative potency against bone turnover. It inhibited RANKL protein and increased the levels of OPG and its signaling molecules in ovariectomized rats. The anti-inflammatory bioflavonoid tangeretin attenuated the inflammatory stimulating cytokines in ovariectomized rats. Conclusion Overall, our analysis confirms tangeretin possesses antiosteoporotic potency which effectively elevates estradiol and attenuates the bone turnover signaling pathway RANK/RANKL/OPG proteins in ovariectomized rats. The results of our research prove the establishment of a treatment strategy using tangeretin can improve bone health and prevent osteoporosis in menopausal women.