Phosphatidylserine and Curcumin Act Synergistically to Down-Regulate Release of Interleukin-1β from Lipopolysaccharide-Stimulated Cortical Primary Microglial Cells
Giulia Mercanti, Eugenio Ragazzi, Gino Toffano, Pietro Giusti and Morena Zusso
Affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Largo E. Meneghetti 2, 35131 Padua, Italy.
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,
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