Journal Article

Ferulic acid ameliorates bisphenol A (BPA)-induced Alzheimer’s disease-like pathology through Akt-ERK crosstalk pathway in male rats

Khalil, Heba M. A., Khalifa, Mhasen, Ahmed, Yasmine H., Abdelhameed, Mohamed F., Essa, Ahmed F., Fayed, Rabie H.

2025

Overview

Objectives This study investigated the neuroprotective effect of ferulic acid (FA) against bisphenol A (BPA) induced Alzheimer’s disease-like pathology in male rats. Methods 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. Results 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. Conclusion 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.

• Publisher: Springer Berlin Heidelberg,Springer,Springer Nature B.V
• Subject: Acetylcholinesterase / Acetylcholinesterase - metabolism / AKT protein / Alzheimer Disease - chemically induced / Alzheimer Disease - drug therapy / Alzheimer Disease - metabolism / Alzheimer Disease - pathology / Alzheimer's disease / Amyloid beta-Peptides - metabolism / Amyloid Precursor Protein Secretases - metabolism / Animals / Benzhydryl Compounds - toxicity / Biomedical and Life Sciences / Biomedicine / Bisphenol A / Bisphenol A Compounds / Brain - drug effects / Brain - metabolism / Brain - pathology / Brain architecture / Causes of / Complications and side effects / Composition / Coumaric Acids - pharmacology / Cytokines / Dietary supplements / Disease Models, Animal / Drug therapy / Extracellular signal-regulated kinase / Ferulic acid / Glial fibrillary acidic protein / Immunohistochemistry / Kinases / Male / MAP Kinase Signaling System - drug effects / Memory / Memory, Short-Term - drug effects / Molecular Docking Simulation / Neurodegenerative diseases / Neuroprotection / Neuroprotective agents / Neuroprotective Agents - pharmacology / Neurosciences / Original Investigation / Oxidative stress / Oxidative Stress - drug effects / Pathology / Pharmacology/Toxicology / Phenols - toxicity / Protein-serine/threonine kinase / Proteins / Proto-Oncogene Proteins c-akt - metabolism / Psychiatry / Rats / Rats, Wistar / Secretase / Short term memory / Spatial memory / Tau protein / tau Proteins - metabolism / Testing / Tissues / β-Amyloid / β-Site APP-cleaving enzyme 1