Acteoside inhibits hepatic lipid accumulation and oxidative stress in type 2 diabetic mice via the Nrf2/HO-1 Pathway

Acteoside, a naturally occurring compound found in various plants, was found to exert antihyperlipidemic effects; however, the underlying mechanisms in nonalcoholic fatty liver disease associated with type 2 diabetes remain to be elucidated. This study aimed to examine (1) acteoside initiated hepatoprotection in diabetic mice and (2) whether the beneficial actions involved activation of Nrf2/HO-1 signaling pathway. Male mice given a high fat diet were injected with streptozotocin (STZ 50 mg/kg) to initiate type 2 diabetes mellitus (T2DM). Animals were randomly assigned to four groups (10 animals per group): (1) control, (2) diabetes, (3) acteoside (70 mg/kg) and (4) metformin (250 mg/kg). In diabetic mice, a significant increase in plasma levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) was accompanied by a fall in high-density lipoprotein (HDL). In diabetes, malondialdehyde (MDA) content was elevated in serum, accompanied by a decrease in superoxide dismutase (SOD) activity. Treatment with acteoside was found to significantly reduce plasma levels TC, TG, LDL, and VLDL accompanied by elevation in HDL, lowered MDA content accompanied by a rise in SOD activity. The metabolic alterations induced by metformin, the drug of choice in T2DM were similar to those noted for acteoside. Results showed that beneficial effects of acteoside involved activation of the Nrf2/HO-1 pathway. The potent antioxidant properties and lipid-lowering effects attributed to acteoside in T2DM may be considered as a promising therapeutic candidate for diabetic liver disease.