Malus toringoides (Rehd.) Hughes Ameliorates Nonalcoholic Fatty Liver Disease with Diabetes via Downregulation of SREBP-1c and the NF- κ B Pathway In Vivo and In Vitro

Diabetic patients are more prone to developing nonalcoholic fatty liver disease (NAFLD) compared with healthy people. As a plant homologous to both medicine and food, (Rehd.) Hughes has been used as an intervention for both NAFLD and diabetes. However, the effect and mechanism of on NAFLD on type 2 diabetes mellitus (T2DM) is unclear. The current investigation was designed to evaluate the ameliorative effects and mechanism of ethanol extract (CBTM-E375) on T2DM, and to identify the compounds in these extracts. The effects of CBTM-E375 on T2DM were verified using a high-fat diet-/streptozotocin-induced diabetic rat and free fatty acid (0.5 mM)-induced human hepatocellular carcinoma cell (HepG2) models. The components of CBTM-E375 were identified by high performance liquid chromatography-mass spectrometry/mass spectrometry. Our results demonstrate that CBTM-E375 ameliorated lipid accumulation (total cholesterol, triglyceride), oxidative stress (superoxide dismutase, catalase, malondialdehyde, glutathione peroxidase), and inflammation (tumor necrosis factor-α [TNF- ], interleukin [IL]-1 , IL-6, C-reactive protein [CRP]) and , these effects were associated with a CBTM-E375-mediated downregulation of SREBP-1c (sterol regulatory element binding protein 1c) and the NF- B (nuclear factor B) signaling pathway. A total of 20 chemical compounds were identified in CBTM-E375, including phlorizin, isoquercitrin, chlorogenic acid, quercetin, naringenin, and trigonelline, which have been reported to have positive effects on diabetes or on NAFLD.