Yiqi Huazhuo Decoction alleviates oxidative stress through PI3K/Akt pathway to treat insulin resistance in T2DM rats
[Objective]This study aimed to investigate the effect and mechanism of Yiqi Huazhuo decoction(YD)in treating insulin resistance(IR)in rats with type 2 diabetes mellitus(T2DM).[Methods]The low-dose YD group[15 mg/(kg·d)]and the high-dose YD group[30 mg/(kg·d)]were established as two intervention groups in this study.Blood glucose,serum insulin,and blood lipid levels of rats in the high-dose YD group were measured,and the homeostasis model assessment-insulin resistance(HOMA-1R)index was calculated.superoxide dismutase(SOD)and malondialdehyde(MDA)levels were determined using a biochemical method,while reactive oxygen species(ROS)levels were measured using an immunofluorescence method.Western blot analysis was conducted to assess the activity of phosphatidylinositol 3-hydroxy kinase(PI3K)and protein kinase B(Akt),aiming to observe the effects of YD intervention on PI3K-p85,Akt protein activity,downstream oxidative stress factors,and liver tissue injury.[Results]YD significantly reduced blood glucose levels,HOMA-IR index,and blood lipid levels in T2DM-IR rats.High-dose YD increased SOD level by 138.3%compared to the model group;it also decreased MDA and ROS levels by 43.4%and 45.2%,respectively.Additionally,high-dose YD reduced liver histomorphological score by 46.6%in the model group.Furthermore,there was a significant increase in relative expression ratio of p-PI3K-p85Tyr458/PI3K-p85 and p-AktS473/Akt proteins in liver tissues;these ratios reached 316.6%and 248.8%,respectively for high-dose YD within the model group.[Conclusion]YD can reduce damage caused by oxidative stress to the insulin target organ-liver-and improve liver IR by regulating glucose and lipid metabolism.The mechanism through which YD regulates hepatic IR may involve activating PI3K/Akt pathway as well as regulating downstream proteins'expression along with antioxidant enzymes.