Malus toringoides (Rehd.) Hughes Ameliorates Nonalcoholic Fatty Liver Disease with Diabetes via Downregulation of SREBP-1c and the NF-κB 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, Malus toringoides (Rehd.) Hughes has been used as an intervention for both NAFLD and diabetes. However, the effect and mechanism of M. toringoides on NAFLD on type 2 diabetes mellitus (T2DM) is unclear. The current investigation was designed to evaluate the ameliorative effects and mechanism of M. toringoides 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-α], interleukin [IL]-1β, IL-6, C-reactive protein [CRP]) in vivo and in vitro, these effects were associated with a CBTM-E375-mediated downregulation of SREBP-1c (sterol regulatory element binding protein 1c) and the NF-κB (nuclear factor κB) 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.