Effects of fenugreek extracts on ameliorating hepatic oxidative stress, inflammation and insulin resistance of type 2 diabetic mice

(1) Background: Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia and insulin resistance in target tissues. Fenugreek, a common edible plant in dietary consumption, can ameliorate diabetes and its associated complications. However, the mechanism of fenugreek extracts on improving T2DM have not been demonstrated. This study investigated the therapeutic effects and underlying cellular mechanisms of fenugreek extracts on hepatic oxidative stress, inflammation and insulin resistance in T2DM. (2) Methods: We established db/db mice model of T2DM using HFD-fed. Body weight and fasting blood glucose were observed, antioxidant and anti-inflammatory activity in serum and histological examination of the liver tissues was conducted in T2DM mice. Moreover, HepG2 insulin resistant cell model (HepG2/IRM) was established. Cell viability, glucose concentration and glycogen content of HepG2/IRM cells was performed after fenugreek extracts/metformin treatment. Moreover, western blot analysis of GSK-3beta, NRF2, PPARgamma, Ampkalpha proteins was performed. Bioinformatic analysis indicated that fenugreek extracts recovered multiple metabolic pathways. (3) Results: Our results suggested that metformin and fenugreek extract reduced body weight, blood sugar, oxidative stress, and liver inflammation in T2DM mice. In addition, after treatment with fenugreek extract, the pathological changes in the liver were significantly reduced, and the liver lobular structure, vacuolization, and fibrosis were improved. RT-qPCR and western blot analysis results revealed that fenugreek extract up-regulated the expression of p-PI3K, p-AKT, GSK-3beta, GLUT2, and AMPKalpha, and the same results were found in vitro studies. (4) Conclusions: These findings illustrated that fenugreek extracts could effectively ameliorate hepatic oxidative stress, inflammation and insulin resistance of T2DM mice.