Background/Objectives: 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 Lycium ruthenicum 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. Methods: 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). Results: 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. Conclusions: These findings establish LRP as a protective agent against ALI and suggest its potential utility as an adjuvant therapeutic candidate for enhanced pulmonary protection.

[Introduction] The study aimed to investigate the protective effect of Lycium ruthenicum polysaccharides (LRPs) against carbon tetrachloride (CCl₄)-induced acute liver injury (ALI). [Method] After LRP was extracted and characterized, a CCl₄-induced cell damage and mouse ALI model was established to evaluate its anti-inflammatory and antioxidant capacities. [Results] The results demonstrated that LRP markedly attenuated hepatocyte necrosis, alleviated cellular edema and degeneration, and preserved nuclear integrity to sustain hepatic function, thereby restoring hepatic architecture. It downregulated serum ALT and AST levels, reduced MDA content in liver tissue, and enhanced SOD activity. Additionally, LRP inhibited the expression of pro-inflammatory cytokines TNF-α and IL-6, while upregulating the anti-inflammatory cytokine IL-10. [Conclusions] These findings suggest that LRP effectively alleviates CCl₄-induced ALI through both antioxidant and anti-inflammatory effects, demonstrating its potential as a novel liver-protective agent.