Effects of formononetin on P38MAPK/MMP-9 signaling pathway in ovariectomized rats / 中国临床药理学与治疗学

ABSTRACT

AIM:To observe the intervention effects of formononetin (FOR) on castration osteoporosis in rats,and the mechanism of osteoporosis prevention.METHODS:The bilateral ovariectomy was performed on female rats to induce osteoporosis rat model.Sixty female SD rats were divided into normal control group,osteoporosis model group,estradiol group (50 μg/kg) and formononetin in high,medium and low dose group (160,80,40 mg/kg),10 rats in each group.except the control group,All groups were administered with estradiol or formononetin treatment,(1 time a day) for 12 weeks one week after operation;rats serum tartrate resistant acid phosphatase (TRACP),change Ca2 +,Mg2 + and other indicators were detected 24 h after the last injection;the left femur was observed to detect MMP-9 and TNF-α,IL-6 mRNA expression by RT-PCR;Western-blot was used to detect P38MAPK,total bone tissue phosphorylation of P38MAPK,MMP-9,TNF-α,IL-6 protein;the right femoral bone was observed for density (bone mineral densit Y,BMD)determination.RESULTS:Compared with osteoporosis model rats,formononetin high dose group can increase the bone density of rats with osteoporosis,lower TRACP content in serum of rats with osteoporosis,and increase serum Mg2 +,Ca2 + content,reduce MMP-9,TNF-α and the bone IL-6,mRNA expression regulated by phosphorylation;P38MAPK mRNA protein expression.CONCLUSION:Formononetin has a good preventive and therapeutic effect on ovariectomized osteoporotic rats,and its mechanism may be related to inhibiting MMP-9 synthesis and secretion,osteoclast bone resorption and regulating P38-MAPK/MMP-9 signaling pathway.