Diabetes mellitus is an increasing metabolic disease worldwide associated with central nervous system disorders. Coffee is a widely consumed beverage that enriched with antioxidants with numerous medicinal applications. Accordingly, the present study aimed to investigate the therapeutic potential of orally administered green coffee bean water extract (GCBWE) against cortical damage induced by high fat diet (HFD) followed by a single injection of streptozotocin (STZ) in rats. Metformin (Met) was used as standard antidiabetic drug. Animals were allocated into six groups: control, GCBWE (100 mg/kg), HFD/STZ (40 mg/kg), HFD/STZ + GCBWE (50 mg/kg), HFD/STZ + GCBWE (100 mg/kg) and HFD/STZ + Met (200 mg/kg) which were treated daily for 28 days. Compared to control rats, HFD/STZ-treated rats showed decreased levels of cortical dopamine, norepinephrine and serotonin with marked increases in their metabolites. Further, HFD/STZ treatment resulted in notable elevations in malondialdehyde, protein carbonyl and total nitrite levels paralleled with declines in antioxidant markers (SOD, CAT, GPx, GR and GSH) and down-regulations of Sod2, Cat, GPx1 and Gsr gene expression. Neuroinflammation was evident in diabetic animals by marked elevations in TNF-α, IL-1β and up-regulation of inducible nitric oxide synthase. Significant rises incaspase-3 and Bax with decline in Bcl-2 level were noticed in diabetic rats together with similar results in their gene expressions. Cortical histopathological examination supported the biochemical and molecular findings. GCBWE administration achieved noteworthy neuroprotection in diabetic animals in most assessed parameters. The overall results suggested that antioxidant, anti-inflammatory; anti-apoptotic activities of GCBWE restored the cortical neurochemistry in diabetic rats.

糖尿病是世界范围内与中枢神经系统疾病相关的一种日益增加的代谢疾病。咖啡是一种广泛消费的饮料，富含抗氧化剂，具有多种药用价值。因此，本研究旨在研究口服生咖啡豆水提取物 (GCBWE) 对大鼠高脂饮食 (HFD) 诱导的皮质损伤的治疗潜力，然后单次注射链脲佐菌素 (STZ)。二甲双胍（Met）被用作标准的抗糖尿病药物。动物被分为六组：对照组、GCBWE (100 mg/kg)、HFD/STZ (40 mg/kg)、HFD/STZ + GCBWE (50 mg/kg)、HFD/STZ + GCBWE (100 mg/kg)和 HFD/STZ + Met (200 mg/kg)，每天治疗 28 天。与对照组大鼠相比，HFD/STZ 治疗的大鼠皮质多巴胺水平降低，去甲肾上腺素和血清素的代谢物明显增加。此外，HFD/STZ 处理导致丙二醛、蛋白质羰基和总亚硝酸盐水平显着升高，同时抗氧化标志物（SOD、CAT、GPx、GR 和 GSH）的下降和Sod2、Cat、GPx1和Gsr基因表达。通过 TNF-α、IL-1β 的显着升高和诱导型一氧化氮合酶的上调，糖尿病动物的神经炎症很明显。在糖尿病大鼠中观察到随着 Bcl-2 水平下降而显着升高的 incaspase-3 和 Bax 以及它们的基因表达的相似结果。皮质组织病理学检查支持生化和分子发现。在大多数评估参数中，GCBWE 给药在糖尿病动物中实现了值得注意的神经保护。总体结果表明抗氧化、抗炎；GCBWE 的抗凋亡活性恢复了糖尿病大鼠的皮质神经化学。