Pueraria lobata extract ameliorates D-GalN/LPS-induced liver injury through targeting TLR4/NF-κB signalling pathway and regulating gut microbiota

Abstract

AbstractKudzu root (Pueraria lobata), known for its dual role as a medicinal herb and food ingredient, has proven anti-inflammatory and antioxidant properties. This study explored the effects of P. lobata extract (PLE) on D-galactose/lipopolysaccharide (D-GalN/LPS)-induced liver inflammation and oxidative stress in mice, along with its impact on gut microbiota. The in vivo studies indicated that PLE significantly reduced hepatic levels of pro-inflammatory cytokines (tumour necrosis factor-α, interleukin-1β, and interleukin-6) and increased the anti-inflammatory cytokine interleukin-10. It also lowered serum aspartate aminotransferase and alanine aminotransferase activities, indicating reduced liver damage, and mitigated oxidative stress by decreasing malondialdehyde levels while restoring superoxide dismutase activity. Western blot analysis revealed that PLE inhibited the phosphorylation of NF-κB pathway proteins (p65 and IκB) and suppressed TLR4 expression, highlighting its role in this inflammatory pathway. Additionally, PLE ameliorated D-GalN/LPS-induced gut microbiota dysbiosis, reducing Proteobacteria abundance and promoting beneficial genera such as Lactobacillus, Bifidobacterium, and Akkermansia. These findings suggest that PLE protects against liver inflammation and oxidative stress, while improving gut microbiota composition, offering potential therapeutic strategies for liver-related diseases.