Mechanism of action of quercetin in regulating cellular autophagy in multiple organs of Goto-Kakizaki rats through the PI3K/Akt/mTOR pathway

作者：Zhiqun Guo, Jingyu Zhang, M. Li, Zengwei Xing, Xi Li, Jiaqi Qing, Yuan Zhang, Lemei Zhu, Mingxu Qi, Xuemin Zou · 发表于：Frontiers in Medicine · 年份：2024 · DOI：10.3389/fmed.2024.1442071 · 被引用次数：11 · 研究领域：Autophagy in Disease and Therapy、Natural Antidiabetic Agents Studies、Bioactive Compounds in Plants

Objective: This experimental study investigated the protective function of quercetin on the liver, spleen, and kidneys of Goto-Kakizaki (GK) rats and explores its mechanism of action on autophagy-related factors and pathways. Materials and methods: GK rats were randomly divided into three groups: DM, DM + L-Que, and DM + H-Que, with age-matched Wistar rats serving as the control group. The control and DM groups were gavaged with saline, and the quercetin-treated group was gavaged with quercetin for 8 weeks each. Weekly blood glucose levels were monitored. Upon conclusion of the experiment, blood samples were gathered for lipid and hepatic and renal function analyses. The histopathologic morphology and lipid deposition in rats were examined. Disease-related targets were identified using molecular docking methods and network pharmacology analysis. Subsequently, immunohistochemical analysis was performed, followed by Western blotting to evaluate the levels of autophagy-related proteins and proteins in the AKT/PI3K/mTOR pathway, as well as their phosphorylation levels. Results: The results showed that, compared with the control group, the DM group exhibited significant increases in blood glucose, serum liver and kidney markers, liver fat vacuoles, and inflammatory cell infiltration. Immunohistochemistry (IHC) results indicated that quercetin reduced the extensive expression of AKT, P62, and mTOR in the liver and spleen of diabetic rats. The expression of autophagy and pathway-rel...