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艾普利鳞毛蕨叶挥发油-β-环糊精包合物对链脲佐菌素诱导阿尔茨海默病动物模型的神经保护作用。

Eplingiella fruticosa leaf essential oil complexed with β-cyclodextrin exerts a neuroprotective effect in an Alzheimer's disease animal model induced by Streptozotocin.

机构信息

Department of Biosciences, Federal University of São Paulo, Santos, São Paulo, Brazil.

Department of Gerontology, Federal University of São Carlos, São Carlos, São Paulo, Brazil.

出版信息

Metab Brain Dis. 2024 Nov 23;40(1):40. doi: 10.1007/s11011-024-01484-8.

Abstract

Alzheimer's Disease (AD) is physiopathologically marked by an accumulation of beta-amyloid peptide (Aβ), hyperphosphorylation of tau protein, inflammation, and oxidative stress in the brain tissue. While new drugs for AD have been approved, novel treatments are still needed. Eplingiella fruticosa (EF) has demonstrated anti-inflammatory and antioxidant properties, which may be beneficial against AD. This study aimed to evaluate the effects of EF leaf essential oil complexed with β-cyclodextrin in a sporadic AD model induced by streptozotocin (STZ). Male Wistar rats (5-6 months old) received an intracerebroventricular STZ injection (3 mg/kg) or vehicle, and were orally treated with vehicle, EF (5 mg/kg), or donepezil (5 mg/kg) for 14 days. Behavioral tests included olfactory discrimination, open field, novel object recognition, sucrose preference, and spontaneous alternation. Upon completion, rats were euthanatized, and their brains were analyzed for Aβ, tau, and IL-1β via immunohistochemistry, and for oxidative stress markers. STZ-treated rats showed memory deficits and anhedonia, accompanied by increased Aβ, tau, and IL-1β immunoreactivity in the olfactory bulb, cortex, hippocampus, and increased TBARS levels in the hippocampus. On the other hand, EF treatment improved short-term and working memory (p < 0.001), and reduced depressive-like behavior (p = 0.02). Additionally, EF treatment decreased Aβ, tau, and IL-1β immunoreactivity in the olfactory bulb, hippocampus and cortex (p < 0.05), and reduced TBARS levels (p = 0.04) and total oxidant status in the hippocampus (p = 0.03), and increased total antioxidant status in the cortex (p = 0.04). These findings suggest EF has neuroprotective effects against STZ-induced damage, indicating its potential as a novel compound for AD treatment.

摘要

阿尔茨海默病(AD)的病理生理学特征是脑内β-淀粉样肽(Aβ)积聚、tau 蛋白过度磷酸化、炎症和氧化应激。虽然已经批准了治疗 AD 的新药,但仍需要新的治疗方法。Eplingiella fruticosa(EF)具有抗炎和抗氧化特性,可能对 AD 有益。本研究旨在评估 EF 叶用β-环糊精包合物对链脲佐菌素(STZ)诱导的散发性 AD 模型的影响。雄性 Wistar 大鼠(5-6 月龄)接受侧脑室 STZ 注射(3mg/kg)或载体,连续 14 天经口给予载体、EF(5mg/kg)或多奈哌齐(5mg/kg)。行为测试包括嗅觉辨别、旷场、新物体识别、蔗糖偏好和自发交替。完成后,处死大鼠,通过免疫组化分析其大脑中的 Aβ、tau 和 IL-1β,并分析氧化应激标志物。STZ 处理的大鼠表现出记忆缺陷和快感缺失,嗅球、皮质、海马中 Aβ、tau 和 IL-1β 免疫反应性增加,海马中 TBARS 水平增加。另一方面,EF 治疗改善了短期和工作记忆(p<0.001),并减少了抑郁样行为(p=0.02)。此外,EF 治疗降低了嗅球、海马和皮质中 Aβ、tau 和 IL-1β 的免疫反应性(p<0.05),降低了海马中 TBARS 水平(p=0.04)和总氧化应激状态(p=0.03),并增加了皮质中的总抗氧化状态(p=0.04)。这些发现表明 EF 对 STZ 诱导的损伤具有神经保护作用,表明其作为 AD 治疗的新化合物具有潜力。

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