Effect of phytoestrogen-rich fraction of Ochna schweinfurthiana bark extract in attenuating retinoic acid - induced osteoporosis: Insights into estrogenic and antioxidative mechanisms

Abstract

Drug-induced osteoporosis poses a serious health and financial risk, yet many doctors are ignorant of how much routinely prescribed  drugs contribute to bone loss and fractures. This study evaluated the effect of phytoestrogen-rich fraction (PERF) of O. schweinfurthiana  bark extract on retinoic acid-induced osteoporosis. The methanol plant extract was fractionated into n-hexane, ethyl acetate, butanol and  water fractions using liquid-liquid fractionation. The phytoestrogens in the fractions were quantified using genistein as standard. Drug- induced osteoporosis was achieved by daily administration of retinoic acid suspension for 14 days. To determine the ability of retinoic  acid to induce osteoporosis and the dose - response effect of the PERF, factors such as body weight changes, relative uterine weight, bone turnover markers (Alkaline phosphatase, ALP, and Acid Phosphatase, ACP), bone mineral content and density, and lipid  peroxidation assays were used. The phytoestrogen content of the water fraction was the highest, more than ten times higher than that of  the other fractions. Treatment of the retinoic acid - induced osteoporosis with the phytoestrogen-rich fraction failed to restore the  bodyweights of the animals to pre-induction value contrary to significant (P<0.05) improvement recorded for the reference standard (40  mg/kg Alendronate) treated group. Significant (P<0.05) increase in serum estradiol following treatment with PERF produced  corresponding uterotrophic effect with a high median effective dose (ED50) of 1,180 mg/kg. Osteoprotective effect of PERF was evident  from the significant (P<0.05) increases in both bone mineral content and density corresponding with reduction in bone turnover markers.  PERF of O. schweinfurthiana showed osteoprotective effect against retinoic acid- induced osteoporosis, which may be  attributed to combination of its estrogenic and antioxidative mechanisms.