| Purpose:To examine the effects of total flavonoids and saponins of Huangqi Gegen decoction on the contents of blood glucose,blood lipid,inflammatory factors and the related factors in the signal transduction pathway of insulin and adiponectin in skeletal muscle of diabetic rats,aiming to analyze the possible mechanism of the compatibility of total flavonoids and saponins on the metabolism of glucose and lipid and the inflammatory response of diabetic rats,so as to provide a solid basis for searching the potential target of antidiabetic drugs empirical basis.Material and method:The 86 SPF male SD rats according to blood glucose were randomly divided into 6 groups: Normal group(n=11),Model group(n=15),Positive control group(n=15),Huangqi Gegen decoction total flavonoids group(n=15),Huangqi Gegen decoction total saponins group(n=15),Huangqi Gegen decoction total flavonoids and total saponins group(n=15).Except for the normal group,the other groups were treated with a single dose of 46 mg/kg of STZ to induce diabetic model.At the same time,the total flavonoids group,the total saponins group,the total flavonoids and total saponins group were administered respectively at doses of 0.106,0.074,and 0.180 g/kg;the positive control group was given Jinqi Jiangtang tablet suspension 1.47 g/kg;the normal and the model group were given 10 m L/kg distilled water of equal volume,and each group was continuously given for 30 days.Blood glucose was detected by blood glucose analyzer;serum cholesterol(CHO)and triglyceride(TG)were detected by biochemical analyzer;insulin(Ins),adiponectin(ADPN)and tumor necrosis factor-?(TNF-?),interleukin-12(IL-12),interleukin-15(IL-15)were detected by Enzyme-linked immunosorbent assay(ELISA);phosphatidylinositol-3-kinase(PI3K),protein kinase B-2(Akt2),glycogen synthetase kinase-3?(GSK-3?)and adiponectin receptor 1(Adipo R1),AMP-activated protein kinase(AMPK),p38 mitogen activated protein kinase(p38MAPK)m RNA expression were detected by Real-time quantitative PCR(Real-time PCR).The SPSS software with version 17.0 was used to analyze the experimental data,and the test level was ?=0.05.Results: 1.Effect on blood glucose of diabetic rats The level of blood glucose in the model group was significantly increased(P<0.05);the levels of blood glucose in total flavonoids group and total saponins group were significantly decreased(P<0.05).There was no interaction between total flavonoids and total saponins(P>0.05).2.Effect on blood lipid of diabetic rats(1)Effect on the level of serum CHO in diabetic rats: The level of serum CHO in the model group was significantly increased(P<0.05);the level of serum CHO in total flavonoids group was significantly decreased(P<0.05),while the effect of total saponins group was not significant.There was no interaction between total flavonoids and total saponins(P>0.05).(2)Effect on the level of serum TG in diabetic rats: The level of serum TG in the model group was significantly increased(P<0.05);the levels of serum TG in total flavonoids group and total saponins group were significantly decreased(P<0.05).There was interaction between total flavonoids and total saponins(P<0.05),but the combination was not as good as the single drug.3.Effect on the content of Ins and ADPN in skeletal muscle of diabetic rats(1)Effect on the content of Ins in skeletal muscle of diabetic rats: The content of Ins in skeletal muscle of the model group was significantly decreased(P<0.05);the contents of Ins in skeletal muscle of total flavonoids group and total saponins group were significantly increased(P<0.05).There was interaction between total flavonoids and total saponins(P<0.05),and the combination was better than the single drug.(2)Effect on the content of ADPN in skeletal muscle of diabetic rats: The content of ADPN in skeletal muscle of the model group was significantly decreased(P<0.05);the contents of ADPN in skeletal muscle of total flavonoids group and total saponins group were significantly increased(P<0.05).There was interaction between total flavonoids and total saponins(P<0.05),but the combination was not as good as the single use of total flavonoids.4.Effect on the content of TNF-?,IL-12 and IL-15 in skeletal muscle of diabetic rats(1)Effect on the content of TNF-? in skeletal muscle of diabetic rats: The content of TNF-? in skeletal muscle of the model group was significantly increased(P<0.05);the contents of TNF-? in skeletal muscle of total flavonoids group and total saponins group were significantly decreased(P<0.05).There was interaction between total flavonoids and total saponins(P<0.05),but the combination was not as good as the single use of total flavonoids.(2)Effect on the content of IL-12 in skeletal muscle of diabetic rats: The content of IL-12 in skeletal muscle of the model group was significantly increased(P<0.05);the contents of IL-12 in skeletal muscle of total flavonoids group and total saponins group were significantly decreased(P<0.05).There was interaction between total flavonoids and total saponins(P<0.05),but the combination was not as good as the single use of total flavonoids.(3)Effect on the content of IL-15 in skeletal muscle of diabetic rats: The content of IL-15 in skeletal muscle of the model group was significantly increased(P<0.05);the contents of IL-15 in skeletal muscle of total flavonoids group and total saponins group were significantly decreased(P<0.05).There was interaction between total flavonoids and total saponins(P<0.05),but the combination was not as good as the single use of total flavonoids.5.Effect on the expression of PI3 K,Akt2 and GSK-3 ? m RNA in skeletal muscle of diabetic rats(1)Effect on the expression of PI3 K m RNA in skeletal muscle of diabetic rats: The expression of PI3 K m RNA in skeletal muscle of the model group was significantly decreased(P<0.05);the expression of PI3 K m RNA in skeletal muscle of total flavonoids group and total saponins group were significantly increased(P<0.05).There was interaction between total flavonoids and total saponins(P<0.05),but the combination was not as good as the single use of total flavonoids.(2)Effect on the expression of Akt2 m RNA in skeletal muscle of diabetic rats: The expression of Akt2 m RNA in skeletal muscle of the model group was significantly decreased(P<0.05);the expression of Akt2 m RNA in skeletal muscle of total flavonoids group was significantly increased(P<0.05),while the effect of total saponins group was not significant.There was interaction between total flavonoids and total saponins(P < 0.05),but the combination was not as good as the single use of total flavonoids.(3)Effect on the expression of GSK-3? m RNA in skeletal muscle of diabetic rats: The expression of GSK-3? m RNA in skeletal muscle of the model group was significantly increased(P<0.05);the expression of GSK-3? m RNA in skeletal muscle of rats in total flavonoids group and total saponins group were significantly decreased(P<0.05).There was interaction between total flavonoids and total saponins(P<0.05),but the combination was not as good as the single use of total flavonoids.6.Effect on the expression of Adipo R1,AMPK and p38 MAPK m RNA in skeletal muscle of diabetic rats(1)Effect on the expression of Adipo R1 m RNA in skeletal muscle of diabetic rats: The expression of Adipo R1 m RNA in skeletal muscle of the model group was significantly decreased(P<0.05);the expression of Adipo R1 m RNA in skeletal muscle of total flavonoids group was significantly increased(P<0.05),while the effect of total saponins group was not significant.There was no interaction between total flavonoids and total saponins(P>0.05).(2)Effect on the expression of AMPK m RNA in skeletal muscle of diabetic rats: The expression of AMPK m RNA in skeletal muscle of the model group was significantly decreased(P<0.05);the effect of total flavonoids group was not significant,while the expression of AMPK m RNA in skeletal muscle of the total saponins group was significantly increased(P<0.05).There was interaction between total flavonoids and total saponins(P<0.05),but the combination was not as good as the single use of total saponins.(3)Effect on the expression of p38 MAPK m RNA in skeletal muscle of diabetic rats: The expression of p38 MAPK m RNA in skeletal muscle of the model group was significantly increased(P<0.05);the expression of p38 MAPK m RNA expression in skeletal muscle of total flavonoids group and total saponins group were significantly decreased(P<0.05).There was interaction between total flavonoids and total saponins,but the combination was not as good as the single use of total flavonoids.Conclusion: 1.The compatibility of total flavonoids and saponins of Huangqi Gegen decoction can significantly reduce the blood glucose level of diabetic rats and improve the disorder of glucose metabolism in skeletal muscle,which may be related to the PI3K/Akt2/GSK-3? pathway mediated by Ins 2.The compatibility of total flavonoids and saponins of Huangqi Gegen decoction can significantly reduce the blood lipid level of diabetic rats and improve the disorder of lipid metabolism in skeletal muscle,which may be related to the Adipo R1/AMPK/p38 MAPK pathway mediated by ADPN.3.The compatibility of total flavonoids and saponins of Huangqi Gegen decoction may reduce the secretion of TNF-?,IL-12 and IL-15,inhibit the inflammatory reaction of skeletal muscle,improve insulin resistance.4.There was interaction between total flavonoids and saponins of Huangqi Gegen decoction and the related factors regulating the metabolism of glucose-lipid and the inflammatory reaction of skeletal muscle in diabetic rats(except Adipo R1).When regulating the level of Ins,the compatibility of total flavonoids and total saponins has synergistic effect;when regulating the levels of ADPN,PI3 K,Akt2,GSK-3?,p38 MAPK,TNF-?,IL-12 and IL-15,the total flavonoids have more advantages than total saponins and their compatibility;when regulating the level of AMPK,total saponins have more advantages than total flavonoids and their compatibility.It is suggested that the pharmacodynamic effect of group distribution may be synergetic,antagonistic or used separately. |
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