Lycium ruthenicum Murr. Polysaccharide Attenuated Inflammatory Response and Intestinal Flora Dysbiosis in LPS-Induced Acute Lung Injury in Mice

<b>Background/Objectives:</b> Acute lung injury (ALI) represents a life-threatening respiratory syndrome characterized by dysregulated pulmonary inflammation, alveolar-capillary barrier dysfunction, and gut-lung axis impairment. Although <i>Lycium ruthenicum</i> polysaccharide (LRP) possesses documented anti-inflammatory properties, its role in ALI remains systematically unexplored. This study aimed to investigate the protective effects of LRP against lipopolysaccharide (LPS)-induced ALI. <b>Methods:</b> In vitro, A549 cells were subjected to injury induction with 10 μg/mL LPS. In vivo, male C57BL/6J mice were randomly allocated to four groups and, respectively, administered 100 mg/kg LRP, 400 mg/kg LRP, or normal saline for 7 days prior to ALI induction via intratracheal LPS instillation (5 mg/kg). <b>Results:</b> LRP restored viability in LPS-injured A549 cells and attenuated their inflammatory responses. Histopathological analysis demonstrated that high-dose LRP (H-LRP) significantly reduced alveolar collapse and inhibited inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF) compared to the LPS group. The H-LRP group exhibited marked downregulation of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) concomitant with upregulation of the anti-inflammatory cytokine IL-10. Intestinal microbiome sequencing confirmed LRP-mediated restoration of gut microbiota homeostasis, evidenced by a 2.2-fold increase in commensal Bacteroides and decreased abundance of pathogenic Escherichia-Shigella. <b>Conclusions:</b> These findings establish LRP as a protective agent against ALI and suggest its potential utility as an adjuvant therapeutic candidate for enhanced pulmonary protection.