Osteogenic, antiresorptive, and toxicological evaluation of alpha-mangostin in MC3T3-E1 cells and medaka fish

Osteoporosis, characterized by excessive bone resorption, requires new therapeutic agents with high efficacy and favorable safety profiles. In this study, we isolated alpha-mangostin (aMG) from the peel of Garcinia mangostana L. and investigated its osteogenic, antiresorptive, and toxicological activities. The osteogenic effects were evaluated in vitro using MC3T3-E1 pre-osteoblast cells, whereas acute toxicity and bone-protective activity were assessed in vivo using medaka fish (Oryzias latipes) . In MC3T3-E1 cells, aMG promoted osteogenic differentiation by enhancing proliferation, alkaline phosphatase activity, collagen synthesis, and mineralization at 1 and 10 μM, whereas cytotoxicity was observed at 100 and 1,000 μM. In medaka embryos and larvae, aMG induced acute toxicity with LC50 values (concentrations causing 50% mortality) of 91.27 and 3.44 μM, and EC50 values (concentrations causing 50% of developmental abnormalities) of 103.66 and 3.3 μM, respectively, leading to tail deformities, hemorrhage, and reduced hatching and heart rates. At sub-toxic concentrations (0.25-1 μM), aMG significantly attenuated Rankl-induced bone loss in the neural arches of osteoporotic medaka larvae. Collectively, this study provides the first evidence of the dual osteogenic and antiresorptive actions of aMG, along with its toxicity profile, highlighting its potential as a plant-derived anti-osteoporosis agent.