Anthocyanins can prevent and ameliorate type 2 diabetes mellitus (T2DM), but its mechanism of action has not been fully established. IKK/NF-κB and JAK/Stat pathways have multiple effects, triggering T2DM. Liver abnormalities in individuals with T2DM are detrimental to glycemic control. We determined whether anthocyanins could improve the liver of individuals with T2DM using IKK/NF-κB and JAK/Stat. We established a T2DM mouse model using a high-fat diet and streptozotocin and then performed Aronia melanocarpa anthocyanin extracts' (AMAEs') administration for 5 weeks. AMAEs improved blood glucose and hyperinsulinemia of T2DM mice. In the liver of AMAE-administered T2DM mice, ROS, IKKβ/NF-κB p65, and JAK2/Stat3/5B signalings were down-regulated, thereby reducing the suppressor of cytokine signaling 3 (SOCS3), iNOS, and inflammatory mediators. AMAE-improved hyperinsulinemia also down-regulated SOCS3 by decreasing p-Stat5B in hepatocytes. AMAEs enhanced glucose uptake and conversion and decreased hepatocyte enlargement and inflammatory cells in the liver of T2DM mice. These indicated that AMAEs could alleviate oxidative stress, insulin resistance, inflammation, and tissue damage in the liver of T2DM mice through inhibiting NF-κB p65 and Stat3/5B.
Keywords: Aronia melanocarpa anthocyanin extracts; IKKβ/NF-κB p65; JAK2/Stat3/5B; T2DM; inflammation; insulin resistance; oxidative stress.