PDF(Pubmed)
Abstract：
Osthole, a natural coumarin found in various medicinal plants, has been previously reported to have neuroprotective effects. However, the specific mechanism by which Osthole alleviates dysmnesia associated with Alzheimer\'s disease (AD) remains unclear. This study aimed to investigate the neuroprotective properties of Osthole against cognitive impairment in rats induced by D-galactose and elucidate its pharmacological mechanism. The rat model was established by subcutaneously injecting D-galactose at a dose of 150 mg/kg/day for 56 days. The effect of Osthole on cognitive impairment was evaluated by behavior and biochemical analysis. Subsequently, a combination of in silico prediction and experimental validation was performed to verify the network-based predictions, using western blot, Nissl staining, and immunofluorescence. The results demonstrate that Osthole could improve memory dysfunction induced by D-galactose in Sprague Dawley male rats. A network proximity-based approach and integrated pathways analysis highlight two key AD-related pathological processes that may be regulated by Osthole, including neuronal apoptosis, i.e., neuroinflammation. Among them, the pro-apoptotic markers (Bax), anti-apoptotic protein (Bcl-2), the microgliosis (Iba-1), Astro-cytosis (GFAP), and inflammatory cytokines (TNF-R1) were evaluated in both hippocampus and cortex. The results indicated that Osthole significantly ameliorated neuronal apoptosis and neuroinflammation in D-galactose-induced cognitive impairment rats. In conclusion, this study sheds light on the pharmacological mechanism of Osthole in mitigating D-galactose-induced memory impairment and identifies Osthole as a potential drug candidate for AD treatment, targeting multiple signaling pathways through network proximity and integrated pathways analysis.
摘要：
蛇床子素,一种在各种药用植物中发现的天然香豆素，以前曾报道过具有神经保护作用。然而,蛇床子素减轻与阿尔茨海默病(AD)相关的记忆障碍的具体机制尚不清楚。本研究旨在探讨蛇床子素对D-半乳糖所致大鼠认知功能障碍的保护作用及其药理机制。以150mg/kg/天的剂量皮下注射D-半乳糖,连续56天建立大鼠模型。通过行为和生化分析评估蛇床子素对认知功能障碍的影响。随后，将计算机预测和实验验证相结合，以验证基于网络的预测，使用蛋白质印迹，尼氏染色,和免疫荧光。结果表明，蛇床子素能改善D-半乳糖诱导的SD大鼠记忆障碍。基于网络接近度的方法和综合通路分析突出了两个关键的AD相关病理过程，这两个过程可能受到蛇床子素的调控。包括神经元凋亡，即，神经炎症。其中,促凋亡标志物（Bax），抗凋亡蛋白（Bcl-2），小胶质细胞增生（Iba-1），星形细胞增多症（GFAP），在海马和皮质评估炎性细胞因子（TNF-R1）。结果表明，蛇床子素能显著改善D-半乳糖致认知功能障碍大鼠的神经细胞凋亡和神经炎症反应。总之,这项研究揭示了蛇床子素减轻D-半乳糖诱导的记忆障碍的药理机制，并确定蛇床子素是治疗AD的潜在候选药物，通过网络邻近性和整合通路分析靶向多个信号通路。
