Lauric acid prevents the production of IL‐8 and IL‐13 and the increase of kynurenine/tryptophan ratio in LPS‐stimulated human astrocytes

Abstract

The interest in the ketogenic diet and coconut oil for the treatment of several neurological and neurodegenerative diseases is increasing. Lauric acid (LA) is a medium-chain-fatty-acid (MCFA), the most prevalent in coconut oil. LA has a neuroprotective effect, probably because it can be an alternative source of energy to the neurons through ketone bodies production from astrocytes. However, the mechanism involving LA neuroprotection is still unclear. Inflammation and kynurenine pathway activation are common features of neurodegenerative diseases. Then, the present study aimed to evaluate the LA effect on cytokine production and the kynurenine pathway in human foetal astrocytes challenged with LPS. Primary cultures of human astrocytes were pre-treated with LA and 1 hour after challenged with LPS. Cell toxicity was measured using a bioluminescent kit (RealTime-Glo™, Promega) to evaluate cell viability in real time. 24 hours after pre-treatment the astrocytes supernatant was collected. Kynurenine pathway metabolites were evaluated by ultra-high-performance liquid chromatography. The levels of GM-CSF, IL-1β, IL-5, IL-6, IL-8, IL-13, MCP-1, TNF-α in the astrocyte supernatant were evaluated using a cytokine array assay performed by Eve technologies (Calgary, Canada). Cell viability was not affected up to 72 hours after pre-treatment with LA or LPS treatment. LA prevented the increase in kynurenine and kynurenine/tryptophan ratio induced by LPS. In addition, LA prevented the increase of IL-8 and IL-13 LPS-induced. The effect of LA on reducing cytokine production was not remarkable, since it was observed only in two cytokines evaluated. However, we demonstrated for the first time LA can prevent the increase of tryptophan/kynurenine ratio in LPS-activated astrocytes. These data shed light on possible mechanisms LA may have a protective effect in neurodegenerative diseases.