A study on Glycyrrhiza uralensis polysaccharide: The structure elucidation, anti-inflammation effects and treatment mechanism of LPS-induced pneumonia mice

Acute lung injury (ALI) is a life-threatening inflammatory pulmonary disorder characterised by diffuse alveolar damage, pulmonary oedema, and excessive immune responses. This study aimed to investigate the therapeutic potential of a purified polysaccharide, Glycyrrhiza polysaccharide fraction 2 (GCP-2), derived from Glycyrrhiza uralensis (liquorice), in a murine model of LPS-induced ALI. GCP-2 was obtained through a multi-step purification process involving aqueous extraction, ethanol precipitation, ion-exchange chromatography, and size-exclusion chromatography. ALI was induced in mice via intranasal administration of lipopolysaccharide (LPS), followed by GCP-2 treatment. Key outcomes were assessed using ELISA, qPCR, histopathology, and western blotting, while gut microbiota changes were evaluated by 16S rRNA sequencing. The results demonstrated that GCP-2 significantly alleviated lung injury, reduced pulmonary and systemic levels of pro-inflammatory cytokines, restored barrier-related proteins such as Zonula occludens-1 (ZO-1) and occludin, and improved histopathological features. Mechanistic studies revealed that these effects were mediated through the selective inhibition of the TLR4/NF-κB signalling pathway. Additionally, GCP-2 modulated gut microbiota composition by increasing beneficial taxa such as Bacteroidetes , Lactobacillus , and Bifidobacteria , while suppressing Firmicutes and Proteobacteria . These findings suggest that GCP-2 is a safe and effective plant-derived polysaccharide that mitigates LPS-induced ALI through anti-inflammatory and gut–lung axis regulatory mechanisms, supporting its potential as a therapeutic candidate for treating inflammatory lung diseases.