氧化白藜芦醇的降血糖作用

The Hypoglycemic Effect of Oxyresveratrol

摘要:

为了探究氧化白藜芦醇（OXY）的降血糖功效。通过体外实验评估OXY的抗氧化活性及关键消化酶抑制作用及其类型，并构建高脂高糖饮食联合STZ注射诱导T2DM大鼠模型进行验证，持续灌胃28 d观察并记录大鼠体质量数据及多项生理生化指标，并对大鼠的肝和肾组织进行病理学观察。体外结果显示，OXY对DPPH和ABTS+自由基清除的IC50分别为7.139 μg·mL-1和16.59 μg·mL-1；对α-淀粉酶呈剂量依赖性抑制，IC50为1.41 mg·mL-1，并以非竞争方式抑制α-葡萄糖苷酶，IC50=66.59 μg·mL-1，Ki=60.82 μg·mL-1。动物实验表明，与模型组相比高剂量OXY干预后，FBG、FINS、TG、TC、LDL-C、AST、ALT、AGE、MDAs、AUC、HOME-IR水平和GSK-3β相对基因表达量分别降低32.1%，19.52%、25.13%、21.29%、32.71%、21.39%、28.9%、10.13%、31.37%、17.52%、39.32%、13.16%（P<0.05），GSH-Px、SOD水平和GYS2相对基因表达量分别提升40.2%、26.24%、18.37%（P<0.05）；组织病理学显示，OXY改善肝细胞脂肪变性及炎症细胞浸润和肾小管上皮细胞空泡化。综上所述，OXY具有降血糖功效和改善T2DM及相关症状的潜力，可为其在天然产物的开发应用中提供理论基础。

Abstract:

In order to explore the hypoglycemic effect of oxyresveratrol (OXY). In vitro experiments were conducted to evaluate the antioxidant activity of oxidized resveratrol (OXY) and characterize its inhibitory mechanisms on key digestive enzymes. A type 2 diabetes mellitus (T2DM) rat model was subsequently established through high-fat/high-sucrose diet feeding combined with streptozotocin (STZ) injection for pharmacological validation. Daily oral administration was maintained for 28 consecutive days, during which body weight fluctuations, multiple physiological and biochemical parameters were systematically monitored and recorded. Histopathological examinations were performed on hepatic and renal tissues to assess organ-specific therapeutic effects. In vitro results showed that the half-maximal inhibitory concentrations (IC50) of OXY for DPPH and ABTS+ radical scavenging were 7.139 μg·mL-1 and 16.59 μg·mL-1, respectively. The inhibitory effects of OXY on α-amylase were found to be dose-dependent, with an IC50 value of 1.41 mg·mL-1. Additionally, the inhibition of α-glucosidase by OXY was determined to be non-competitive, with an IC50 of 66.59 μg·mL-1 and a Ki value of 60.82 μg·mL-1. In animal experiments, it was demonstrated that, after intervention with high-dose OXY, the levels of fasting blood glucose (FBG), fasting insulin (FINS), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST), alanine aminotransferase (ALT), advanced glycation end products (AGE), malondialdehyde (MDAs), areas under the curve (AUC), homeostasis model assessment of insulin resistance (HOMA-IR), and the relative gene expression level of GSK-3β were reduced by 32.1%, 19.52%, 25.13%, 21.29%, 32.71%, 21.39%, 28.9%, 10.13%, 31.37%, 17.52%, 39.32%, and 13.16%, respectively, compared with the model group (P<0.05). Meanwhile, the levels of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and the relative gene expression level of GYS2 were increased by 40.2%, 26.24%, and 18.37%, respectively (P<0.05). Histopathological examination revealed that OXY improved hepatic steatosis, inflammatory cell infiltration, and vacuolation of renal tubular epithelial cells. Collectively, OXY has been evidenced to exert hypoglycemic effects and mitigate T2DM-related pathological manifestations, which lays a theoretical groundwork for its phytopharmaceutical exploration in natural product-derived therapeutics.