Phytol from Scoparia dulcis prevents NF-κB-mediated inflammatory responses during macrophage polarization

Macrophages are primary immune cells that mediate a wide range of inflammatory diseases through their polarization potential. In this study, phytol isolated from Scoparia dulcis has been explored against 7-ketocholesterol and bacterial lipopolysaccharide-induced macrophage polarization in IC-21 cells. Isolated phytol has been characterized using GC–MS, TLC, HPTLC, FTIR, ¹H-NMR, and HPLC analyses. The immunomodulatory effects of viable concentrations of phytol were tested on oxidative stress, arginase activity, nuclear and mitochondrial membrane potentials in IC-21 cells in addition to the modulation of calcium and lipids. Further, gene and protein expression of atherogenic markers were studied. Results showed that the isolated phytol at a viable concentration of 400 µg/ml effectively reduced the production of nitric oxide, superoxide anion (ROS generation), calcium and lipid accumulation, stabilized nuclear and mitochondrial membranes, and increased arginase activity. The atherogenic markers including iNOS, COX-2, IL-6, IL-1β, MMP-9, CD36, and NF-κB were significantly downregulated at the levels of gene and protein expression, while macrophage surface and nuclear receptor markers (CD206, CD163, and PPAR-γ) were significantly upregulated by phytol pre-treatment in macrophages. Therefore, the present pharmacognostic study supports the role of phytol isolated from Scoparia dulcis in preventing M2–M1 macrophage polarization under inflammatory conditions, making it a promising compound.