Neochlorogenic acid ameliorates Alzheimer's disease-like pathology via scavenging oxidative stress and restoring blood-brain barrier function in zebrafish

Abstract

Alzheimer's disease is the most widespread neurodegenerative disease characterized by insidious onset and slow progression. At present, most available medications serve to attenuate the progression of Alzheimer's disease with side effects and drug resistance. Neochlorogenic acid is a natural polyphenolic compound with excellent antioxidant properties. Based on zebrafish Alzheimer's disease model induced by AlCl₃, we found that neochlorogenic acid significantly improved motor dysfunction, reduced brain cell apoptosis, and Aβ plaque. Because of antioxidant stress and improvement of blood-brain barrier dysfunction are important in treating Alzheimer's disease, we explored the interaction between these two mechanisms in alleviating the pathological course of Alzheimer's disease. Neochlorogenic acid inhibited the overproduction of reactive oxygen species, suppressed the gene expression encoding antioxidant-related proteins, and protected brain cell integrity while enhancing Nrf2, improving blood-brain barrier nerve resilience. Meanwhile, neochlorogenic acid attenuated blood-brain barrier dysfunction in Alzheimer's disease zebrafish by reducing blood hemoglobin leakage and upregulating the gene expression encoding blood-brain barrier endothelial cell-related proteins, resulting in reactive oxygen species in a controllable state. In conclusion, our research suggests that neochlorogenic acid ameliorates Alzheimer's disease-like pathology by inhibiting oxidative stress and restoring blood-brain barrier function, indicating that neochlorogenic acid may be a potential drug for treating Alzheimer's disease.