Effects of formononetin on P38MAPK/MMP-9 signaling pathway in ovariectomized rats

Abstract

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 Ca ²⁺, Mg ²⁺ and other indicators were detected 24 h after the last injection;the left femur was observed to detect MMP-9 and TNF-alfa, IL-6 mRNA expression by RT-PCR;Western-blot was used to detect P38MAPK, total bone tissue phosphorylation of P38MAPK, MMP-9,TNF-alfa, 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 Mg ²⁺, Ca ²⁺ content, reduce MMP-9, TNF-alfa 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.

Key words: formononetin, castrated osteoporosis, MMP-9, P38MAPK

CLC Number:

R965.2

YU Qinyun, ZHAN Xiaofeng, HUANG Yan. Effects of formononetin on P38MAPK/MMP-9 signaling pathway in ovariectomized rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(12): 1371-1376.

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