Previous investigations have demonstrated the anti-inflammatory effects of
cholinergic agonists, such as
nicotine. In the present study, we investigated the potential anti-inflammatory activity of
anatabine, a minor tobacco
alkaloid also present in plants of the Solanacea family which displays a chemical structural similarity with
nicotine. Our data show that
anatabine prevents STAT3 and NFκB phosphorylation induced by
lipopolysaccharide (LPS) or TNF-α in SH-SY5Y, HEK293, human microglia and human blood mononuclear cells. Using human whole blood, we found that
anatabine prevents IL-1β production induced by LPS. We assessed
anatabine's anti-inflammatory activity in vivo using an acute model of
inflammation by challenging wild-type mice with LPS. We observed that
anatabine reduces pro-inflammatory
cytokine production (IL-6, IL-1β and TNF-α) in the plasma, kidney and spleen of the animals following the injection of LPS and concomitantly opposes STAT3 phosphorylation induced by LPS in the spleen and kidney. We also investigated the impact of
anatabine on
neuroinflammation using a transgenic mouse model of
Alzheimer's disease (Tg APPsw) that displays elevated
cytokine levels in the brain. Following a chronic oral treatment with
anatabine, a reduction in brain TNF-α and
IL-6 levels compared to untreated Tg APPsw mice was observed. Moreover, an increased STAT3 phosphorylation was detected in the brains of Tg APPsw mice compared to wild-type littermates and was inhibited by
anatabine treatment. Overall our data show that the anti-inflammatory activity of
anatabine in vitro and in vivo is mediated in part via an inhibition of STAT3 phosphorylation.