Protective effect of celastrol on type 2 diabetes mellitus with nonalcoholic fatty liver disease in mice

To investigate the protective effects of celastrol on mice with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), and to explore its underlying mechanism. The levels of low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), total cholesterol (TC), and triglyceride (TG) in serum were tested. Malondialdehyde (MDA) and superoxide dismutase (SOD), GOT, and GPT in serum were also detected. The histopathological changes of liver tissues were observed by HE staining. The apoptosis cell number of liver tissues was measured by TUNEL staining. Nrf‐2 and HO‐1 protein and mRNA expression were evaluated by IHC, WB, and RT‐PCR assay. Celastrol had effects to depress TG, TC, LDL‐C, GPT, GOT, and MDA concentration and increase HDL‐C and SOD concentration (p < .05, respectively) with dose‐dependent. Compared with model group, apoptosis cell number was significantly depressed in Cel‐treated groups with dose‐dependent (p < .05, respectively). Nrf‐2 and HO‐1 mRNA and protein expressions were significantly improved in Cel‐treated groups with dose‐dependent (p < .05, respectively). Celastrol can inhibit the oxidative stress reaction and liver cell apoptosis via regulation Nrf2/HO‐1 pathway in T2DM mice with NAFLD.