| Objective To explore the potential effect of ergosteroid glycoside (MJZG) treatment on the reduction of bone mineral density and bone loss in ovariectomized rats, and to explore the possible mechanism. Methods A rat model of osteoporosis was constructed with bilateral ovariectomy. The rats were then randomly divided into sham operation group (Sham), ovariectomized group (OVX), and MJZG group, with 10 rats in each group. The rats in MJZG group received MJZG (100mg/kg) treatment for 12 weeks. The femoral specimens and blood samples were obtained at the end of the treatment to further detect femoral bone mass, bone strength, changes in bone metabolism indexes, and tissue protein expression. Results After 12 weeks of the operation, trabecular bone micro-parameters, bone mineral density, bone mineral content, and bone strength in OVX group reduced significantly compared to those in Sham group. BMD, BV /TV, Tb in MJZG group, N, Tb.Th, Tb.Sp and the maximum load and elastic modulus improved significantly compared to those in OVX group (P<0.05). The serum levels of BGP, ALP, TRACP-5b, and DPD of rats in MJZG group were significantly lower than those in OVX group, and the difference between the two groups was statistically significant (P<0.05). The protein levels of TRAF6, RANKL, NF-κB, and NFAT2 were down-regulated (P<0.05), while PI3K, AKT, and c-Fos were up-regulated (P<0.05) in MJZG group compared to those in OVX group with WB detection. Conclusion MJZG prevents and treats osteoporosis induced by ovariectomy by inhibiting RANKL/TRAF6/NF-κB and activating PI3K/AKT. |