Role of asiatic acid in treating osteoporosis in ovariectomized osteoporotic rats
Objective To investigate the influence of asiatic acid on osteoprotegerin(OPG)/receptor activator of nuclear factor-κB ligand(RANKL)signaling pathway and its role in treating osteoporosis in ovariectomized osteoporotic rats.Methods Forty female SD rats,weighing 200-220 g,were randomly divided into the sham-surgery group,model group,asiatic acid group and estradiol group,with 10 rats in each group.The osteoporosis models were established in the model group,asiatic acid group and estradiol group by ovariectomy.The rats in the sham-surgery group only had the abdominal cavities opened without removing the ovaries.After successful modeling,the rats in the asiatic acid group received gavage with 120 mg/kg asiatic acid suspension,the rats in the estradiol group received gavage with 0.184 mg/kg estradiol tablet suspension,and the rats in the sham-surgery group and model group received gavage with the same amount of normal saline,once a day for 12 weeks.The bone mineral density(BMD)of the left proximal femur was measured in each group.ELISA was used to detect the serum levels of estradiol,bone formation markers[bone gamma-carboxyglutamic acid protein(BGP),procollagen type Ⅰ N-terminal propeptide(P Ⅰ NP)],and bone resorption markers[C-telopeptide of type Ⅰ collagen(CTX-Ⅰ),tartrate-resistant acid phosphatase-5b(TRAP-5b)].Micro-CT scan was done to measure the right femur bone volume fraction(BV/TV),trabecular number(Tb.N)and trabecular thickness(Tb.Th);three-point bending method was used to measure the biomechanics;Western blot was used to detect the relative expressions of OPG,RANKL and receptor activator of nuclear factor-κB(RANK)proteins.Results Before and after drug intervention,the left femur BMDs and serum estradiol levels showed significant differences among four groups(F=31.570-63.726,all P values＜0.05).After drug intervention,the BMDs[(241.95±27.35),(210.77±19.63),(173.49±18.54),(108.32±24.43)g/cm2]and serum estradiol levels[(475.93±84.50),(395.67±52.83),(321.88±46.42),(215.37±31.05)ng/L]decreased sequentially in the sham-surgery group,estradiol group,asiatic acid group and model group(P＜0.05),were higher than those before drug intervention in the asiatic acid group and estradiol group(P＜0.05),and showed no significant differences in the sham-surgery group and model group compared with those before drug intervention(P＞0.05).The serum levels of BGP,P Ⅰ NP,TRAP-5b and CTX-Ⅰ,the BV/TV,Tb.N,Tb.Th,maximum load and fracture deflection,and the relative expressions of RANKL,RANK and OPG proteins showed significant differences among four groups(F=14.556-332.330,all P values＜0.05).The serum BGP[(4.95±0.34)ng/L],PⅠ NP[(33.99±4.21)μg/L],BV/TV[(0.29±0.03)％],Tb.N(1.85±0.25),Tb.Th[(0.15±0.04)mm],maximum load[(138.44±11.05)N],fracture deflection[(220.47±14.95)N/mm],and relative expression of OPG protein(0.88±0.05)were higher in the sham-surgery group than those in the model group[(2.04±0.21)ng/L,(13.50±2.53)μg/L,(0.11±0.02)％,1.02±0.16,(0.07±0.01)mm,(71.35±9.21)N,(137.96±16.82)N/mm,0.32±0.05],asiatic acid group[(2.97±0.59)ng/L,(24.67±2.10)μg/L,(0.20±0.02)％,1.60±0.16,(0.11±0.03)mm,(118.48±9.46)N,(183.46±15.13)N/mm,0.78±0.06],and estradiol group[(3.18±0.53)ng/L,(26.82±2.53)μg/L,(0.22±0.04)％,1.65±0.14,(0.12±0.02)mm,(122.07±11.25)N,(194.75±15.76)N/mm,0.79±0.07](P＜0.05),and were higher in the asiatic acid group and estradiol group than those in the model group(P＜0.05).The serum levels of CTX-Ⅰ[(75.93±8.42)ng/L]and TRAP-5b[(11.84±3.46)μg/L],and relative expressions of RANK and RANKL proteins(0.23±0.04,0.26±0.03)were lower in the sham-surgery group than those in the model group[(147.24±11.30)ng/L,(30.51±5.22)μg/L,0.91±0.06,0.87±0.06],asiatic acid group[(112.83±6.22)ng/L,(21.76±3.42)μg/L,0.54±0.04,0.61±0.05],and estradiol group[(108.35±7.17)ng/L,(19.86±3.08)μg/L,0.56±0.05,0.63±0.06](P＜0.05),were lower in the asiatic acid group and estradiol group than those in the model group(P＜0.05),and showed no significant differences between the asiatic acid group and estradiol group(P＞0.05).Conclusion Asiatic acid can increase BMD of osteoporotic rats,repair trabecular microstructure,and improve bone metabolism,possibly by regulating OPG/RANKL signaling pathway.
osteoporosisasiatic acidosteoprotegerin/receptor activator of nuclear factor-κB ligand signaling pathwayovariectomizerats
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