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Local administration of p-coumaric acid decreases lipopolysaccharide-induced acute lung injury in mice: In vitro and in silico studies

Abstract : Acute lung injury (ALI) remains to cause a high rate of mortality in critically ill patients. It is known that inflammation is a key factor in the pathogenesis of lipopolysaccharide (LPS)-induced ALI, which makes it a relevant approach to the treatment of ALI. In this study, we evaluated the potential of nasally instilled p-coumaric acid to prevent LPS-induced ALI in mice, by evaluating its effects on cellular and molecular targets involved in inflammatory response via in vitro and in silico approaches. Our results demonstrated that p-coumaric acid reduced both neutrophil accumulation and pro-inflammatory cytokine abundance, and simultaneously increased IL-10 production at the site of inflammation, potentially contributing to protection against LPS-induced ALI in mice. In the in vitro experiments, we observed inhibitory effects of p-coumaric acid against IL-6 and IL-8 production in stimulated A549 cells, as well as reactive oxygen species generation by neutrophils. In addition, p-coumaric acid treatment decreased neutrophil adhesion on the TNF-α-stimulated endothelial cells. According to the in silico predictions, p-coumaric acid reached stable interactions with both the ATP-binding site of IKKβ as well as the regions within LFA-1, critical for interaction with ICAM-1, thereby suppressing the production of proinflammatory mediators and hindering the neutrophil infiltration, respectively. Collectively, these findings indicate that p-coumaric acid is a promising anti-inflammatory agent that can be used for developing a pharmaceutical drug for the treatment of ALI and other inflammatory disorders.
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https://hal-univ-rennes1.archives-ouvertes.fr/hal-03157629
Contributor : Laurent Jonchère <>
Submitted on : Wednesday, March 3, 2021 - 12:23:50 PM
Last modification on : Thursday, August 12, 2021 - 5:12:04 PM

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Tácio Souza, Flávio Santos, Polyane Alves, Jamylle Ferro, Ana Carolina C. Correia, et al.. Local administration of p-coumaric acid decreases lipopolysaccharide-induced acute lung injury in mice: In vitro and in silico studies. European Journal of Pharmacology, Elsevier, 2021, 897, pp.173929. ⟨10.1016/j.ejphar.2021.173929⟩. ⟨hal-03157629⟩

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