Biological Effect of Licochalcone C on the Regulation of PI3K/Akt/eNOS and NF-κB/iNOS/NO Signaling Pathways in H9c2 Cells in Response to LPS Stimulation.

Sara Franceschelli,Alfredo Grilli,Alessio Ferrone,Mario Felaco,Antonia Patruno,José Luis Quiles,Maria Anna De Lutiis,Mirko Pesce,Lorenza Speranza,Daniela Maria Pia Gatta

doi:10.3390/ijms18040690

Sara Franceschelli, Alfredo Grilli + Show 8 more

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https://doi.org/10.3390/ijms18040690

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Abstract

Polyphenols compounds are a group molecules present in many plants. They have antioxidant properties and can also be helpful in the management of sepsis. Licochalcone C (LicoC), a constituent of Glycyrrhiza glabra, has various biological and pharmacological properties. In saying this, the effect of LicoC on the inflammatory response that characterizes septic myocardial dysfunction is poorly understood. The aim of this study was to determine whether LicoC exhibits anti-inflammatory properties on H9c2 cells that are stimulated with lipopolysaccharide. Our results have shown that LicoC treatment represses nuclear factor-κB (NF-κB) translocation and several downstream molecules, such as inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Moreover, LicoC has upregulated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/endothelial nitric oxide synthase (eNOS) signaling pathway. Finally, 2-(4-Morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002), a specific PI3K inhibitor, blocked the protective effects of LicoC. These findings indicate that LicoC plays a pivotal role in cardiac dysfunction in sepsis-induced inflammation.

Highlights

Sepsis is a final common pathway to death from infection
The activation of these signaling cascades has been implicated in the release of genes activated by nuclear factor-κB (NF-κB), such as inducible nitric oxide synthase, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) [8]
When cells were treated with Licochalcone C (LicoC), ranging from 1–500 μM for 48 h, cell viability did not change significantly with respect to the control up to 250 μM (Figure 1A)

Summary

Introduction

Sepsis is a final common pathway to death from infection. It is characterized by a systemic inflammatory disorder, which leads to multiorgan failure with immune dysfunction [1]. The activation of these signaling cascades has been implicated in the release of genes activated by NF-κB, such as inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) [8]. These molecules are present in elevated quantities in patients with an inflammatory state, such as sepsis, and may have detrimental effects on cardiomyocytes, leading to sepsis-associated myocardial dysfunction [9]. We investigated in vitro effects of LicoC on H9c2 cells protection and to elucidate its underlying mechanisms

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