Neuroprotective effect of Licochalcone A against aluminum chloride-induced neurotoxicity by reducing Aβ accumulation, oxidative stress and inflammatory reaction

Abstract

Excessive aluminum exposure is a contributing factor in several neurodegenerative diseases. Natural plant compounds such as Licochalcone A have been shown to have significant neuroprotective effects in vivo and in vitro. In this study, we aim to elucidate the neuroprotective effect of Licochalcone A against aluminum chloride-induced neurotoxicity and its possible mechanism. Adult zebrafish and PC12 cells were used as animal and cell models. Zebrafish and PC12 cells were treated with excessive aluminum trichloride (100 μg/L aluminum chloride hexahydrate solutions for zebrafish or 500 μM Al-malt solution for PC12 cells) to cause neuronal damage. The neuroprotective effect of Licochalcone A was evaluated by measuring ROS production, Aβ_1–42 accumulation, inflammatory cytokines, neuronal apoptosis-associated genes, and MAPK pathway-related proteins to elucidate the mechanism of Licochalcone A against aluminum chloride-induced neurotoxicity. Licochalcone A effectively reduced the level of ROS production and inflammatory cytokines in both zebrafish and PC12 cells treated with excessive aluminum trichloride. In addition, Licochalcone A reduced the expression of BACE1 and generation of Aβ_1–42 as well as the expression of p-JNK and MAPK, the key factor of the MAPK pathway. These results indicated that Licochalcone A has a remarkable neuroprotective effect against neurotoxicity induced by aluminum and has a high potential in the development of therapeutic drugs for neurodegenerative diseases.