In Vivo and in Vitro Characterization of the Anti-inflammatory and Neuroprotective Effects of TPNA10168

Abstract

Neuroinflammation contributes to the pathogenesis of various central nervous system disorders. TPNA10168, a novel nuclear factor erythroid 2-related factor 2 activator, exhibits neuroprotective effects in vitro and in vivo and anti-inflammatory activity in vitro. In this study, we examined the in vivo efficacy of TPNA10168 in a mouse model of systemic inflammation established by lipopolysaccharide (LPS) treatment. TPNA10168 attenuated the LPS-induced expression of several proinflammatory cytokines, such as tumor necrosis factor-α in the liver and interleukin-1β in the brain, and upregulated heme oxygenase-1 in both tissues. Although it did not suppress microglial activation in the brain, TPNA10168 reduced LPS-induced motor deficits without affecting anxiety-like or anhedonic behavior. In primary mesencephalic cultures, TPNA10168 inhibited microglial activation and nitric oxide production and protected dopaminergic neurons against LPS/interferon-γ-induced toxicity. The results suggest that TPNA10168 exerts partial anti-inflammatory effects in vivo and protects dopaminergic neurons from inflammation-induced damage in vitro, which indicates its potential as a therapeutic agent for inflammation-related neurological disorders.