Khalifa Mhasen, Fayed Rabie H, Ahmed Yasmine H, Abdelhameed Mohamed F, Essa Ahmed F, Khalil Heba M A
Department of Veterinary Hygiene and Management, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt.
Cytology and Histology Department, Faculty of Vet. Medicine, Cairo University, Giza, 12211, Egypt.
Psychopharmacology (Berl). 2025 Mar;242(3):461-480. doi: 10.1007/s00213-024-06697-4. Epub 2024 Oct 23.
This study investigated the neuroprotective effect of ferulic acid (FA) against bisphenol A (BPA) induced Alzheimer's disease-like pathology in male rats.
Rats were allocated into four groups, control, BPA, BPA + FA, and FA, respectively, for 40 days. Spatial working memory and recognition memory were evaluated. Moreover, the brain levels of oxidative stress biomarkers, proinflammatory cytokines, extracellular signal-regulated kinase (ERK), and phosphorylated serine/threonine protein kinase (p-Akt) were measured. We also determined the brain neuropathological protein levels, including Beta-Amyloid 1-42, total Tau (tTau), and phosphorylated Tau (pTau) proteins. Furthermore, brain levels of Acetylcholinesterase (AChE) and Beta-secretase (BACE) were assessed. Brain histological investigation and immunohistochemistry determination of glial fibrillar acidic protein (GFAP) were also performed. Moreover, docking simulation was adapted to understand the inhibitory role of FA on AChE, BACE-1, and ERK1/2.
Interestingly, the BPA + FA treated group showed a reversal in the cognitive impairments induced by BPA, which was associated with improved brain redox status. They also exhibited a significant decrease in brain inflammatory cytokines, ERK, and p-Akt levels. Moreover, they revealed a decline in beta-amyloid 1-42 and a significant improvement in tTau expression and pTau protein levels in the brain tissue. Further, the brain levels of AChE and BACE were substantially reduced in BPA + FA rats. The neuroprotective effect of FA was confirmed by restoring the normal architecture of brain tissue, which was associated with decreasing GFAP.
FA could be a potent neuroprotectant agent against AD with a possible prospect for its therapeutic capabilities and nutritional supplement value due to its antioxidant and antiapoptotic properties.
本研究调查了阿魏酸（FA）对双酚A（BPA）诱导的雄性大鼠阿尔茨海默病样病理的神经保护作用。
将大鼠分为四组，分别为对照组、BPA组、BPA + FA组和FA组，持续40天。评估空间工作记忆和识别记忆。此外，测量大脑中氧化应激生物标志物、促炎细胞因子、细胞外信号调节激酶（ERK）和磷酸化丝氨酸/苏氨酸蛋白激酶（p-Akt）的水平。我们还测定了大脑神经病理蛋白水平，包括β-淀粉样蛋白1-42、总tau蛋白（tTau）和磷酸化tau蛋白（pTau）。此外，评估大脑中乙酰胆碱酯酶（AChE）和β-分泌酶（BACE）的水平。还进行了脑组织学研究和胶质纤维酸性蛋白（GFAP）的免疫组化测定。此外，采用对接模拟来了解FA对AChE、BACE-1和ERK1/2的抑制作用。
有趣的是，BPA + FA处理组显示出BPA诱导的认知障碍有所逆转，这与改善大脑氧化还原状态有关。它们还表现出大脑炎症细胞因子、ERK和p-Akt水平显著降低。此外，它们显示出β-淀粉样蛋白1-42水平下降，脑组织中tTau表达和pTau蛋白水平显著改善。此外，BPA + FA大鼠大脑中AChE和BACE的水平大幅降低。FA的神经保护作用通过恢复脑组织的正常结构得到证实，这与GFAP减少有关。
由于其抗氧化和抗凋亡特性，FA可能是一种有效的抗阿尔茨海默病神经保护剂，具有治疗潜力和营养补充价值。
