Suppression of Pro-Inflammatory M1 Polarization of LPS-Stimulated RAW 264.7 Macrophage Cells by Fucoxanthin-Rich Sargassum hemiphyllum

Abstract

Macrophages play an important role in managing the onset and progression of chronic inflammatory diseases. The primary objective of this study is to explore the antioxidant potential and anti-inflammatory properties of Sargassum hemiphyllum ethanol extract (SHE) and its fraction. SHE and its five constituent fractions were assessed for overall antioxidant capabilities and inhibitory effects on LPS-induced inflammation by modulating macrophages polarization in both RAW 264.7 macrophages and bone-marrow-derived macrophages (BMDM). Among the organic solvent fractions of SHE, the ethyl acetate fraction displayed the highest total phenolic content and total antioxidant capacity. Notably, the n-hexane (Hex) fraction showed the most substantial suppression of LPS-induced tumor necrosis factor alpha secretion in BMDM among the five fractions of SHE. The SHE and Hex fraction significantly reduced the heightened expression of pro-inflammatory cytokines and inflammation-inducible enzymes induced by LPS in RAW 264.7 macrophages. In particular, the SHE and Hex fraction inhibited M1 macrophage polarization by reducing the mRNA expression of M1 macrophage markers in macrophages that were polarized toward the M1 phenotype. Furthermore, the SHE and Hex fraction attenuated the induction in nuclear factor E2-related factor 2 and its target genes, which was accompanied by an alteration in antioxidant gene expression in M1-polarized BMDM. The findings suggest that both SHE and its Hex fraction exhibit inhibitory effects on LPS-triggered inflammation and oxidative stress by modulating the polarization of M1 macrophages within macrophage populations.