Regulation and mechanism of 3-acetyl-11-keto-β-lactonic acid combined with Ginsenoside Rb2 on bone remodeling process in osteoporosis rats
Objective To explore the molecular mechanism of 3-acetyl-11-keto-β-mastic acid(AKBA)combined with ginsenoside Rb2 on bone remodeling in osteoporosis rats.Methods A total of 50 SD rats were randomly divided into blank group,model group,positive control group,and experimental low-dose and high-dose groups.Rats in model group,positive control group and experimental low and high dose groups were given retinoic acid solution at the dose of 70 mg/(kg·d)to establish a rat osteoporosis model,and the blank group was given 10 ml/kg normal saline intragastric administration for 14 days.The positive control group was given 0.36 mg/(kg·d)estradiol valerate by intragastric administration,the ex-perimental low dose and high dose groups were given different doses[5,20 mg/(kg·d)]of AKBA com-bined with ginsenoside Rb2 intraperitoneal injection,and the model group was given the same volume of normal saline treatment for 8 weeks.Bone mineral density(BMD)values of right femur in each group were measured by BMD meter.The protein expression levels of β-catenin,Runt-related transcription factor 2(Runx2),forkhead box protein O1(FoxO1),osteoprotegerin(OPG)and nuclear factor of activated T cells c1(NFATc1)in the right femur of rats before and after treatment were detected by Western blotting.Two independent samples t test was used for comparison between groups.Results Compared with the blank group,the BMD of the femur in the modeling group was significantly decreased(0.685±0.062 vs.0.367±0.038,t=5.314,P＜0.01).Compared with model group,the femur BMD of positive control group and experimental group was significantly increased(0.367±0.038 vs.0.584±0.041,0.522±0.034,0.637±0.055,t=4.453,4.216,5.622,P＜0.05).Western blotting analysis showed that com-pared with model group,AKBA combined with ginsenoside Rb2 could enhance β-catenin of rat femur(0.453±0.030 vs.0.707±0.031,0.728±0.037,t=5.285,6.342,P＜0.05),Runx2(0.272±0.018 vs.0.585±0.019,0.672±0.031,t=4.188,5.218,P＜0.05),FoxO1(0.477±0.028 vs.0.643±0.028,0.791±0.038,t=5.062,5.844,P＜0.05),OPG(0.436±0.022 vs.0.676±0.029,0.752±0.031,t=4.726,5.573,P＜0.05)protein expression.At the same time,the expression of NFATc1 was inhibited(0.593±0.030 vs.0.405±0.025,0.344±0.019,t=4.622,5.276,P＜0.05)in a dose-dependent manner(P＜0.05).Conclusion The combination of AKBA and ginsenoside Rb2 may promote osteoblast differentiation and inhibit osteoclast bone resorption by acting on Wnt/β-catenin,OPG/NFATc1 signaling pathway,and play a role in the prevention and treatment of osteoporosis.
Osteoporosis3-acetyl-11-keto-β-lactonic acidGinsenoside Rb2Bone remod-eling process
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