Title:The Therapeutic Effects and Mechanisms of Gardenoside on Inflammatory
Injury via the INS/NF-κB Pathway in a T2DM Zebrafish Model
Volume: 10
Author(s): Ping Liu, Mirong Hou, Jiawei He, Jie Zhou, Anna Wang, Chunjiang Huo, Qiuhui Zhong, Jiaheng Zhang and Shaowu Cheng*
Affiliation:
- Hunan University of Chinese medicine, Changsha, Hunan, 410208, China
- Key Laboratory of Hunan Province for
Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases,
School of Integrated Chinese and Western Medicine, Hunan University of Chinese medicine, Changsha, Hunan,
410208, China
Keywords:
Type 2 Diabetes Mellitus, Gardenoside, Zebrafish, Glucose Metabolism, Inflammation, INS/NF-?B
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
