Anti-Inflammatory Effect of a Polysaccharide Derived from Artocarpus heterophyllus Lam. Pulp on Lipopolysaccharide-Stimulated RAW264.7 Macrophages Through Inhibiting MAPK/ERK Signaling Pathway

Background: Inflammation is a critical pathological process implicated in numerous diseases. Methods: In this study, a water-soluble polysaccharide was extracted from the fruit pulp of Artocarpus heterophyllus Lam. (namely, JFP-Ps), and the anti-inflammatory properties and underlying mechanisms were investigated. Inflammatory responses were induced in RAW264.7 macrophages through lipopolysaccharide (LPS) stimulation. Results: JFP-Ps markedly diminished the production of nitric oxide (NO) and reactive oxygen species (ROS); reduced LPS-induced cell apoptosis by increasing glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activity; and decreased pro-inflammatory cytokine levels, including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). JFP-Ps decreased inflammatory responses by inhibiting the production of gene and protein expression associated with the MAPK/ERK pathway. Additionally, metabolomic profiling revealed that LPS stimulation increased ether lipid metabolism while it decreased pantothenate and coenzyme A biosynthesis. These metabolic changes were partially reversed by JFP-Ps through inhibiting the synthesis of branched-chain amino acids. Conclusions: JFP-Ps may exert anti-inflammatory effects by concurrently modulating oxidative stress, inflammatory signaling, and metabolic reprogramming in macrophages.