关键词: Allium jesdianum Alzheimer’s disease Bax Bcl-2 Mitochondria Radial Arm Water Maze microRNA (miRNA)

来  源:   DOI:10.1016/j.neulet.2023.137491

Abstract:
Alzheimer\'s disease (AD) is a complex disorder with multiple underlying mechanisms. Existing treatment options mostly address symptom management and are associated with numerous side effects. Therefore, exploring alternative therapeutic agents derived from medicinal plants, which contain various bioactive compounds with diverse pharmacological effects, holds promise for AD treatment. This study aims to assess the protective effects of the hydroalcoholic extract of Allium jesdianum on cognitive dysfunction, mitochondrial and cellular parameters, as well as genetic parameters in an intracerebroventricular Streptozotocin (icv-STZ) induced rat model of AD. Male Wistar rats were injected with a single dose of STZ (3 mg/kg, icv) to establish a sporadic AD model. A. jesdianum extract (100, 200, and 400 mg/kg/day) and donepezil (5 mg/kg/day) were orally administered for 14 days following model induction. Cognitive function was evaluated using the radial arm water maze test. Mitochondrial toxicity parameters in various brain regions (whole brain, frontal cortex, hippocampus, and cerebellum) were assessed. Gene expression analysis of miR-330, miR-132, Bax, and Bcl-2 in isolated rat brain neurons was performed using RT-qPCR. A. jesdianum extract significantly attenuated cognitive dysfunction and mitigated mitochondrial toxicity induced by icv-STZ administration. Following STZ injection, there was upregulation of Bax gene expression and downregulation of miR-330, miR-132, and Bcl-2 gene expression. Treatment with A. jesdianum extract resulted in the reversal of the expression of these microRNAs and genes, indicating its potential for improving AD and reducing neuronal apoptosis. This study demonstrates the neuroprotective capabilities of A. jesdianum against STZ-induced oxidative stress and cognitive impairment in rats, highlighting its therapeutic potential in the management of AD.
摘要:
阿尔茨海默病(AD)是一种具有多种潜在机制的复杂疾病。现有的治疗方案主要解决症状管理,并与许多副作用相关。因此,探索来自药用植物的替代治疗剂,其中含有各种具有不同药理作用的生物活性化合物,有望治疗AD。本研究旨在评估大蒜水醇提取物对认知功能障碍的保护作用,线粒体和细胞参数,以及侧脑室内链脲佐菌素(icv-STZ)诱导的AD大鼠模型的遗传参数。雄性Wistar大鼠单剂量注射STZ(3mg/kg,icv)建立零星AD模型。在模型诱导后口服给药A.jesdianum提取物(100、200和400mg/kg/天)和多奈哌齐(5mg/kg/天)14天。使用radial臂水迷宫测试评估认知功能。不同大脑区域的线粒体毒性参数(全脑,额叶皮质,海马体,和小脑)进行评估。miR-330、miR-132、Bax基因表达分析,和Bcl-2在分离的大鼠脑神经元中使用RT-qPCR进行。A.jesdianum提取物显着减轻认知功能障碍并减轻icv-STZ给药引起的线粒体毒性。STZ注射后,Bax基因表达上调,miR-330,miR-132和Bcl-2基因表达下调.用A.jesdianum提取物处理导致这些microRNAs和基因的表达逆转,表明其改善AD和减少神经元凋亡的潜力。这项研究证明了A.jesdianum对STZ诱导的大鼠氧化应激和认知障碍的神经保护能力,强调其在AD管理中的治疗潜力。
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