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Yiqi Huazhuo Decoction alleviates oxidative stress through PI3K/Akt pathway to treat insulin resistance in T2DM rats
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DOI   10.11656/j.issn.1672-1519.2024.10.17
Key Words   Yiqi Huazhuo Decoction;ROS;MDA;SOD;hepatic insulin resistance
Author NameAffiliationE-mail
LI Yan The Third School of Clinical Medicine, Zhejiang University of Traditional Chinese Medicine, Hangzhou 310053, China  
WENG Siying Ningbo Hospital of Traditional Chinese Medicine, Zhejiang University of Traditional Chinese Medicine, Ningbo 315010, China alicewsy@163.com 
Abstract
    [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-IR) 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.

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