Oleanolic Acid Exerts a Neuroprotective Effect Against Microglial Cell Activation by Modulating Cytokine Release and Antioxidant Defense Systems

Abstract

Microglia respond to adverse stimuli in order to restore brain homeostasis and, upon activation, they release a number of inflammatory mediators. Chronic microglial overactivation is related to neuroinflammation in Alzheimer's disease. In this work, we show that oleanolic acid (OA), a natural triterpene present in food and medicinal plants, attenuates the activation of BV2 microglial cells induced by lipopolysaccharide (LPS). Cell pretreatment with OA inhibited the release of IL-1β, IL-6, TNF-α, and NO, which was associated with the downregulation of the expression of genes encoding for these cytokines and inducible nitric oxide synthase (iNOS), and the reinforcement of the endogenous antioxidant cell defense. These findings advocate considering OA as a novel neuroprotective agent to inhibit oxidative stress and inflammatory response in activated microglia associated with Alzheimer's disease.