Abstract: Objective To determine the therapeutic effect and mechanism of imperatorin on estrogen deficiency induced-osteoporosis. Methods Rats were randomly distributed into group control, OVX and OVX+Imp. Ten days after modeling, rats in group OVX+Imp,control and OVX were intravenously administrated with Imperatorin, 75 mg/kg or chloroform, twice per week, 10 weeks.Trabecular morphologyand indexes of distal femurs were analysed by μCT and HE staining. Mechanics strength of femurs and lumbars was analyzed by mechanical testing.Mineral deposition was labeling by calcein. Serum PINP and B-ALP were detected by ELISA. Ossification of BMMSCs was tested by ALP staining. mRNAs and proteins were tested by real-time PCR or Western blot respectively. New bone formation in subcutaneous implants was tested by HE staining. Results 1)Bone volume, trabecular indexes, mechanics strength of femurs and lumbars, mineral deposition, serum PINP and B-ALP of OVX were lower than control and OVX+Imp(P＜0.05).2)ALP activity, osteogenic genes and ectopic osteogenesis of endogenous BMMSCs from OVX were lower than control andO VX+Imp(P＜0.05).3) Autophagy of OVX was lower than control and OVX+Imp(P＜0.05).4) Autophagy BMMSCs+3-MA was lower than BMMSCs, and the osteogenesis correspondly decreased(P＜0.05);autophagy BMMSCs+3-MA+Imp was higher than BMMSCs+3-MA, and the osteogenesisc orrespondly increased(P＜0.05).Conclusions Imperatorin ameliorated estrogen deficiency induced-osteoporosis through osteogenesis promotion caused by elevation of autophagy.

Key words: Imperatorin, osteoporosis, BMMSCs, autophagy, osteogenesis