Sepsis-induced acute lung injury (ALI) poses a common and formidable challenge in clinical practice, currently lacking efficacious therapeutic approaches. This study delves into the evaluation of (+)-afzelechin (AZC), a natural compound derived from Bergenia ligulata with a diverse array of properties, encompassing antioxidant, anticancer, antimicrobial, and cardiovascular effects to ascertain its effectiveness and underlying mechanisms in mitigating sepsis-induced ALI through animal experimentation. An ALI mouse model induced by sepsis was established through lipopolysaccharide (LPS) administration, and various analytical techniques, including quantitative real-time polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay were employed to gauge inflammatory cytokine levels, lung injury, and associated signaling pathways. The animal experiments revealed that AZC offered safeguards against lung injury induced by LPS while reducing inflammatory cytokine levels in both blood serum and lung tissue. Western blotting experiments revealed AZC's downregulation of the toll-like receptor (TLR)4/NF-κB pathway and the upregulation of PI3K/Akt, coupled with inhibition of the Hippo and Rho signaling pathways. These findings underscore AZC's efficacy in ameliorating sepsis-induced ALI by modulating cytokine storms and curtailing inflammation via the regulation of TLR4/NF-κB, PI3K/Akt, Hippo, and Rho signaling pathways. This work serves as a foundation for additional exploration into AZC's mechanisms and its potential as a therapy for sepsis-induced ALI. Animals in accordance with Kyungpook National University (IRB No. KNU 2022-174).
Keywords: (+)-afzelechin; Hippo; Rho; acute lung injury; sepsis.