Neutral Polysaccharide\nfrom Platycodonis Radix-Ameliorated\nPM<sub>2.5</sub>-Induced Lung Injury by Inhibiting the TLR4/NF-κB\np65 Pathway and Regulating the Lung and Gut Microbiome

Platycodonis radix (PR) has been reported to play a protective\nrole in lung injury. However, much less is known about the protective\neffect and mechanism of its main component PR polysaccharides (PRPs)\nin particulate matter (PM2.5)-induced lung injury. Here, a neutral\npolysaccharide (MW: 244.56 kDa) was isolated from PR, mainly composed\nof Rha, Ara, Gal, Glc, Xyl, and Man. PRPs significantly improved PM2.5-induced\npulmonary edema, oxidative damage, and cell apoptosis and downregulated\ninflammatory factor levels in bronchoalveolar lavage fluid. Mechanistically,\nPRPs reduced intestinal mucosal barrier damage, thereby lowering serum\nlipopolysaccharide levels and inhibiting the overactivation of the\nTLR4/NF-κB signaling pathway in the lung tissue. Notably, PRPs\ncould optimize the composition of pulmonary and intestinal microbiota.\nOral administration of PRPs resulted in enrichment of short-chain\nfatty acid (SCFA)-producing bacteria, thereby upregulating the levels\nof acetate, butyrate, and isovalerate. Taken together, PRPs have great\npotential in preventing and repairing the lung injury caused by PM2.5.