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Abstract
Objective: This study utilized the zebrafish model to investigate the therapeutic effects of gardenoside on inflammatory damage in type 2 diabetes mellitus (T2DM) through the INS/NF-κB pathway.
Methods: The study employed 7-8-month-old AB strain zebrafish and induced T2DM models by continuous exposure to a 2% glucose solution for 14 days. Control, model, gardenoside low-, medium-, and high-dose groups (2.5 mg/L, 5 mg/L, 10 mg/L), and a metformin group were established. Parameters such as zebrafish body weight, fasting blood glucose levels, and behavioral analyses were monitored. Fructosamine levels were measured using ELISA, while real-time polymerase chain reaction (Real-time PCR) was employed to assess the relative expression levels of INS, IRS, NF-κB, IL-1β, and IL-6 genes. Intestinal histological examination was conducted to observe inflammation levels.
Results: Compared to the control group, the model group exhibited significantly increased blood glucose levels, weight gain, and fructosamine content. High-speed locomotion time increased, while low-speed locomotion time decreased. Relative expression levels of INS, NF-κB, IL-1β, and IL-6 genes were elevated (P < 0.0001), whereas IRS relative expression levels decreased (P < 0.001). In comparison to the model group, the gardenoside and metformin groups demonstrated reduced blood glucose levels and no significant change in body weight. The gardenoside low and medium dose groups, as well as the metformin group, showed reduced high-speed locomotion time and increased low-speed locomotion time. The relative expression levels of INS, NFκB, IL-1β, and IL-6 genes in the gardenoside and metformin groups decreased (P < 0.01 or P < 0.0001), while IRS relative expression levels increased (P < 0.001 or P < 0.0001).
Conclusion: Gardenoside may suppress inflammatory responses, alleviate insulin resistance, and ameliorate diabetes-related inflammatory symptoms, potentially through the regulation of the INS/NF-κB signaling pathway