Pomegranate Flower Water Extract Modulates AHR/BNIP3 to Improve Hepatic Insulin Signaling in Diabetic Mice

Objective: To investigate the effects and mechanisms of pomegranate flower water extract on hepatic insulin signaling in type 2 diabetic mice. Methods: C57BL/6J was randomly divided into normal group, model group, metformin group (Met), pomegranate flower water extract low-dose group (PFWL) and pomegranate flower water extract high-dose group (PFWH). The drug was administered continuously for 11 weeks. Mice were tested for body mass, fasting blood glucose (FBG), insulin (INS), triglycerides (TG), total cholesterol (TC) and insulin resistance index (HOMA-IR) was calculated. Hematoxylin-eosin (HE) staining was used to observe the pathologic changes in hepatic tissue. The expression levels of insulin receptor substrate 1 (IRS1), p-IRS1 (Ser307), protein kinase B (AKT), p-AKT (Ser473), glycogen synthase kinase-3β (Gsk3β), p-Gsk3β (S9), aromatidic hydrocarbon receptor (AhR), phosphatidylethanolamine N-methyltransferase (PEMT), and Bcl-2/adenovirus E1B19-kDa interacting protein 3 (BNIP3) in mouse liver tissues were determined by Western blot. Results: Compared with the model group, the FBG, INS, HOMA-IR, TG and TC levels were significantly decreased in the PFWH group (P<0.01). Intracellular fat droplets were significantly decreased in the liver of mice in the PFWH group. Western blot results showed that compared with the model group, IRS1, p-AKT (Ser473)/AKT, p-Gsk3β (S9)/Gsk3β, and BNIP3 protein expression were significantly increased in the liver of the PFWH group (P<0.01), and p-IRS1 (Ser307)/IRS1, AHR, and PEMT protein expression were significantly decreased (P<0.01). Conclusion: PFW may inhibit hepatic lipid deposition by modulating AHR/BNIP3, and improve p-IRS1(Ser307)/p-AKT(Ser473)/p-GSK3β(S9) insulin signaling pathway transduction.