Imrecoxib alleviates hepatic damage in type 2 diabetic rats by modulating PI3K/AKT/NF-κB signaling

Abstract

Objective: To investigate the influence and underlying mechanisms of imrecoxib on liver damage in rats with type 2 diabetes mellitus (T2DM).

Methods: A rat model of T2DM was established by a high-fat diet and streptozotocin administration. Rats were then treated with imrecoxib 10, 20, or 40 mg/kg for 5 weeks. Body weight and fasting blood glucose levels were measured. The analysis included serum liver function, blood lipid profiles, and the levels of inflammatory factors in the rats. Liver tissue histology was evaluated using hematoxylin and eosin staining. Western blotting was conducted to measure the liver expression of proteins such as AKT, PI3K, NF-κB, p-AKT, p-PI3K, and p-NF-κB.

Results: Rats treated with imrecoxib showed a greater weight gain compared to untreated diabetic rats. Compared to untreated diabetic rats, imrecoxib at all three doses reduced alanine aminotransferase, aspartate aminotransferase, triglycerides, cholesterol, tumor necrosis factor-α, interleukin (IL)-6, and IL-1β, and significantly increased the levels of IL-10 and IL-4. In imrecoxib-treated rats, the expression levels of AKT, PI3K, p-AKT, and p-PI3K were higher in comparison to the diabetes group, whereas the expression of p-NF-κB was lower.

Conclusions: Imrecoxib could alleviate hepatic damage in T2DM rats by modulating PI3K/AKT/NF-κB signaling.

Keywords

Type 2 diabetes / Liver injury / Imrecoxib / Inflammatory response / PI3K/AKT/NF-κB signaling pathway

Conflict of interest statement

The authors declare that there is no conflict of interest.

Funding

The research work is funded by the “Hengrui-Tianqing Medical Education Fund” of the Second Affiliated Hospital of Wannan Medical College (grant no.HXKT2022026) and Natural Science Research Program for Universities in Anhui Province (grant no.2023AH051739).

Data availability statement

The data supporting the findings of this study are available from the corresponding author upon request.

Authors’ contributions

Conceptualization was performed by XHS, MXL, TTL, and QY Design, data collection, analysis and interpretation were done by XHS, MXL, LLZ, TTL, and QY Funding acquisition was from TTL, and MXL. The first draft of the manuscript was written by XHS and QY. The previous version and revised version of the manuscript were commented by XHS, MXL, and QY. The final manuscript was read and approved by XHS, MXL, TTL, and QY.

Publisher’s note

The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Acknowledgments

The authors would like to acknowledge Qin Yin, Tingting Luo, Mengxue Liu and Lulu Zhou for skillful technical assistance.

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