Propane-2-sulfonic acid octadec-9-enyl-amide, a novel PPARα/γ dual agonist, reverses neuroinflammation in lipopolysaccharide-induced mice

Our previous study showed that propane-2-sulfonic acid octadec-9-enyl-amide (N15), a novel peroxisome proliferator-activated receptor alpha and gamma (PPAR alpha/gamma) dual agonist, inhibits inflammatory responses in tumor necrosis factor alpha (TNF alpha)-induced vascular endothelial cells or lipopolysaccharide (LPS)-induced human myeloid leukemia mononuclear cells-1. However, little is known about whether N15 applies to other pathological or neuroinflammatory conditions. In the present study, we detected the effect of N15 on the LPS-induced neuroinflammatory response in mice and further investigated whether the effect of N15 on neuroinflammation and neuronal cells survival was related to PPAR alpha/gamma dual pathways. We found that N15 decreased the mRNA expression of the proinflammatory cytokines IL-1 beta, IL-6, TNF alpha, inducible nitric oxide synthase and cyclooxygenase-2; inhibited microglial activation; and ameliorated neuronal apoptosis in the hippocampus and cortex of LPS-induced mice. In addition, PPAR alpha antagonist MK886 or PPAR gamma antagonist T0070907 partially eliminated the effect of N15. These results demonstrate that N15 exerts an anti-inflammatory effect, at least in part, by enhancing PPAR alpha/gamma dual signaling. Our study reveals that N15 may be a promising neuronal protective drug for the treatment of neuroinflammatory diseases. Copyright (c) 2020 Wolters Kluwer Health, Inc. All rights reserved.