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.

毛蕊花糖苷（Acteoside）是一种存在于多种植物中的天然化合物，已被证实具有降血脂作用；然而，其在2型糖尿病相关非酒精性脂肪肝中的潜在机制仍有待阐明。本研究旨在探讨（1）毛蕊花糖苷对糖尿病小鼠的肝脏保护作用，以及（2）其有益作用是否涉及Nrf2/HO-1信号通路的激活。给予高脂饮食的雄性小鼠注射链脲佐菌素（streptozotocin，STZ，50 mg/kg）以诱导2型糖尿病（type 2 diabetes mellitus，T2DM）。动物被随机分为四组（每组10只）：（1）对照组、（2）糖尿病组、（3）毛蕊花糖苷组（70 mg/kg）和（4）二甲双胍组（250 mg/kg）。在糖尿病小鼠中，血浆总胆固醇（total cholesterol，TC）、甘油三酯（triglycerides，TG）、低密度脂蛋白（low-density lipoprotein，LDL）和极低密度脂蛋白（very low-density lipoprotein，VLDL）水平显著升高，同时高密度脂蛋白（high-density lipoprotein，HDL）水平降低。糖尿病组小鼠血清中丙二醛（malondialdehyde，MDA）含量升高，同时超氧化物歧化酶（superoxide dismutase，SOD）活性降低。毛蕊花糖苷处理可显著降低血浆TC、TG、LDL和VLDL水平，同时升高HDL水平；降低MDA含量，同时提高SOD活性。二甲双胍（T2DM的首选药物）诱导的代谢变化与毛蕊花糖苷引起的变化相似。结果表明，毛蕊花糖苷的有益作用涉及Nrf2/HO-1通路的激活。毛蕊花糖苷在T2DM中表现出的强效抗氧化特性和降脂作用，使其有望成为糖尿病性肝病的潜在治疗候选药物。