Exploration Of The Mechanism Of Peiben Gushu Decoction In Treating Primary Osteoporosis Based On AGEs/RAGE/NF-κB Pathway

Objective:By observing the expressions of bone density,bone biomechanical indicators,bone metabolism indicators,and oxidative stress indicators in osteoporosis model rats,the possible mechanism and anti-osteoporosis effect of Peiben Gushu Decoction was explored based on the AGEs/RAGE/NF-κB pathway.Method:42 female SD rats were randomly divided into a sham operation group,a model control group,a low-dose group of Peiben Gushu decoction,a middle-dose group of Peiben Gushu decoction,a high-dose group of Peiben Gushu decoction,and a western medicine group,with 7 rats in each group.The osteoporosis model was established by removing bilateral ovaries.The sham operation group only removed about 1 g of adipose tissue near the ovary.The intervention was carried out 4 weeks after modeling,the equivalent dose in rats was converted by 6.3 times the adult daily dose.Low-dose group of Peiben Gushu decoction:Peiben Gushu prescription crude medicine 5.30g/Kg/d was given by gavage,middle-dose group of Peiben Gushu decoction:Peiben Gushu prescription medicinal medicine 10.61g/Kg/d was given by gavage,high-dose group of Peiben Gushu decoction:Peiben Gushu prescription crude medicine 21.21g/Kg/d was given by gavage,and the western medicine group:1 mL/Kg/d of alendronate sodium solution was given by gavage.Sham operation group and model control group:0.5mL/100g of 0.9%saline was given by gavage.Each group of medicines was gavaged for 8 weeks,then the uterine index was calculated,and femoral bone density and femoral biomechanical elastic load,ultimate load,elastic modulus and other indicators were measured.Serum bone metabolism indicators like TRACP5b,sRANKL,OPG,and oxidative stress indicators MDA and AGE,were measured by ELISA;WB was used to detect the expression of NF-κB and NFATc1.Result:Compared with the sham operation group,the model group’s uterine index,proximal femur and middle femur BMD,elastic load,and elastic modulus were significantly reduced(P<0.05),and the serum MDA and AGEs levels in the model group were significantly increased(P<0.01).The serum TRACP5b content was significantly increased(P<0.01),but the OPG and OPG/sRANKL ratios were decreased(P<0.01).The expression levels of the proteins NF-κB and NFATc-1 were significantly higher than those in the sham operation group.Compared with the model group:the uterine index and bone strength of all treatment groups were improved;the BMD of Peiben Gushu decoction increased significantly in the middle and high dose groups and the western medicine group(P<0.05);The TRACP5b content in the dose group and the western medicine group decreased(P<0.05),the OPG content increased(P<0.05),the sRANKL content decreased,and the OPG/sRANKL ratio increased(P<0.05).Serum MDA and AGEs levels were decreased(P<0.05);the expression levels of NFATc-1 and NF-κB proteins in the low-dose group of Peiben Gushu decoction were slightly lower than those in the model group,and there was no statistical significance between them;The level of histone expression was significantly lower than that in the model group(P<0.05),and the expression levels of NFATc-1 and NF-κB proteins in the high-dose Peiben Gushu decoction group were lower than those in the western medicine group,but there was no statistical significance between them.Conclusion:1.Peiben Gushu decoction can effectively increase bone density and bone strength,and improve bone metabolism.2.Peiben Gushu decoction can prevent osteoporosis by inhibiting the expression of related proteins on the NF-κB pathway and inhibiting osteoclast differentiation and maturation.3.Peiben Gushu decoction can can reduce the accumulation of AGEs in the body and reduce oxidative stress,and further reduce the expression of NF-κB through the AGEs/RAGE/NF-κB pathway.