Abstract

Microglia, the brain’s resident macrophages, contribute to immune surveillance and the response to disease and injury. These immune cells play a dual role in the nervous system, having both neurotoxic and neuroprotective effects. Activation of microglia results in the production of inflammatory molecules and neurotoxic factors that often cause or contribute to neurodegenerative diseases. Inhibition of neurotoxic microglia activation and consequent inflammatory processes may represent an important therapeutic target. Phosphatidylserine (PS), an aminophospholipid of plasma membranes, and curcumin, the yellow pigment isolated from the rhizome of the turmeric plant, have both been reported to suppress microglial activation by reducing pro-inflammatory mediator production and release. In this study we analyzed the effects of PS, curcumin, and their association on microglial activation induced by the bacterial toxin lipopolysaccharide. Primary rat cortical microglial cells were treated with increasing concentrations of PS-liposomes and curcumin, alone or in combination, and their effects on pro-inflammatory cytokine release from unstimulated and lipopolysaccharide-stimulated microglia were evaluated by enzyme-linked immunosorbent assay. Isobolographic analysis was performed to investigate the effect of PS-liposomes and curcumin combination. PS and curcumin inhibited the release of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α induced by lipopolysaccharide. Furthermore, PS and curcumin in combination exerted a synergistic effect in down-regulating IL-1β release. These results suggest that the association of PS with curcumin could be of potential therapeutic utility against diseases associated with microglial activation.

Keywords: Curcumin, cytokines, isobolograms, lipopolysaccharide, microglia, neuroinflammation, phosphophatidylserine, synergism.