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ORIGINAL RESEARCH article

Front. Med.
Sec. Pathology
Volume 11 - 2024 | doi: 10.3389/fmed.2024.1442071

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

Provisionally accepted
Zhiqun Guo Zhiqun Guo 1,2Jingyu Zhang Jingyu Zhang 1,2*Mianxin Li Mianxin Li 1,2*Zengwei Xing Zengwei Xing 1,2*Xi Li Xi Li 1,2*Jiaqi Qing Jiaqi Qing 1,2*Yuan Zhang Yuan Zhang 1,2Lemei Zhu Lemei Zhu 1,2*Mingxu Qi Mingxu Qi 3*Xuemin Zou Xuemin Zou 1,2*
  • 1 Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha, Hunan Province, China
  • 2 School of Public Health, Changsha Medical University, Changsha, China
  • 3 Department of Cardiovascular Medicine, Affiliated Nanhua Hospital, University of South China, Hengyang,421001, China

The final, formatted version of the article will be published soon.

    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 autophagyrelated 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.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-related proteins, such as P62, PI3K, P-PI3K, Akt, P-AKT, mTOR, and P-mTOR, was upregulated, while the expression of LC3A/LC3B, Beclin-1, Pink-1, and Parkin was downregulated. Conversely, the quercetin group showed a reduction in liver and kidney injury serum markers by decreasing lipid deposition and cell necrosis, indicating that quercetin has protective effects on the liver, spleen, and kidneys of GK rats. Additionally, in the quercetin group, the expression of autophagy and pathway-related proteins such as LC3A/LC3B, Beclin-1, Pink-1, and Parkin was upregulated, while the expression of P62, PI3K, P-PI3K, Akt, P-AKT, mTOR, and P-mTOR was downregulated, with statistically significant correlations.Conclusion quercetin markedly ameliorates liver, spleen, and kidney damage in GK rats, potentially through the inhibition of the PI3K/Akt/mTOR pathway, promoting autophagy. This research offers a rationale to the therapeutic potential of quercetin in mitigating organ damage associated with diabetes.

    Keywords: Quercetin, Autophagy, diabetic liver injury, GK rat, PI3K/AKT/ mTOR pathway

    Received: 01 Jun 2024; Accepted: 01 Aug 2024.

    Copyright: © 2024 Guo, Zhang, Li, Xing, Li, Qing, Zhang, Zhu, Qi and Zou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Jingyu Zhang, Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha, 410219, Hunan Province, China
    Mianxin Li, Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha, 410219, Hunan Province, China
    Zengwei Xing, Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha, 410219, Hunan Province, China
    Xi Li, Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha, 410219, Hunan Province, China
    Jiaqi Qing, Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha, 410219, Hunan Province, China
    Lemei Zhu, Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha, 410219, Hunan Province, China
    Mingxu Qi, Department of Cardiovascular Medicine, Affiliated Nanhua Hospital, University of South China, Hengyang,421001, China
    Xuemin Zou, Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha, 410219, Hunan Province, China

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