Neutral Polysaccharide from Platycodonis Radix-Ameliorated PM_2.5-Induced Lung Injury by Inhibiting the TLR4/NF-κB p65 Pathway and Regulating the Lung and Gut Microbiome

Platycodonis radix (PR) has been reported to play a protective role in lung injury. However, much less is known about the protective effect and mechanism of its main component PR polysaccharides (PRPs) in particulate matter (PM2.5)-induced lung injury. Here, a neutral polysaccharide (MW: 244.56 kDa) was isolated from PR, mainly composed of Rha, Ara, Gal, Glc, Xyl, and Man. PRPs significantly improved PM2.5-induced pulmonary edema, oxidative damage, and cell apoptosis and downregulated inflammatory factor levels in bronchoalveolar lavage fluid. Mechanistically, PRPs reduced intestinal mucosal barrier damage, thereby lowering serum lipopolysaccharide levels and inhibiting the overactivation of the TLR4/NF-κB signaling pathway in the lung tissue. Notably, PRPs could optimize the composition of pulmonary and intestinal microbiota. Oral administration of PRPs resulted in enrichment of short-chain fatty acid (SCFA)-producing bacteria, thereby upregulating the levels of acetate, butyrate, and isovalerate. Taken together, PRPs have great potential in preventing and repairing the lung injury caused by PM2.5.