Asiatic acid improves mitochondrial function, activates antioxidant response in the mouse brain and improves cognitive function in beta-amyloid overexpressing mice

Abstract

AbstractExtracts of the plantCentella asiaticacan enhance mitochondrial function, promote antioxidant activity and improve cognitive deficits. Asiatic acid (AA) is one of the constituent triterpene compounds present in the plant. In this study we explore the effects of increasing concentrations of AA on brain mitochondrial function, antioxidant response and cognition in healthy mice and a single concentration of AA in the beta-amyloid overexpressing 5xFAD mouse line. Associative memory and overall activity were assessed. Hippocampal mitochondrial bioenergetics and the expression of mitochondrial and antioxidant response genes was determined. In the 5xFAD line, total beta-amyloid plaque burden after AA treatment was also evaluated. In healthy mice, we report dose responsive effects of increasing concentrations of AA on enhanced associative memory and a dose dependent increase in basal and maximal mitochondrial respiration, mitochondrial gene expression and antioxidant gene expression. Results from the highest AA dose (1% AA) were similar to what was observed with CAW. The high AA dose was then evaluated in the context of Aβ accumulation in 5xFAD mice. Improvements in mitochondrial and antioxidant response genes were favored in females over males without significant alleviation of Aβ plaque burden.