Apigenin Attenuates Lipopolysaccharide-Induced Acute Lung Injury in Mice by Inhibiting the TLR4/MyD88/NFκB Signaling Pathway

Background Acute lung injury (ALI) is a severe clinical syndrome characterized by excessive inflammation and high mortality. The TLR4/MyD88/NF-κB signaling pathway plays a pivotal role in the pathogenesis of LPS-induced ALI. This study aimed to investigate the protective effects of apigenin (API) against LPS-induced ALI in mice and to explore whether these effects are mediated through the inhibition of the TLR4/MyD88/NF-κB pathway. Methods An ALI model was established in C57BL/6 mice via intratracheal instillation of LPS (10 mg/kg). Mice were pretreated with API at doses of 25, 50, and 100 mg/kg or dexamethasone (5 mg/kg) via intraperitoneal injection. Assessments included lung wet/dry weight ratio, bronchoalveolar lavage fluid (BALF) protein concentration, Evans Blue leakage assay, histopathological evaluation, ELISA for inflammatory cytokines TNF-α, IL-6 and IL-1β, as well as oxidative stress markers MDA, SOD, CAT, GSH-Px, and qPCR analysis of TLR4, Myd88, and NF-κB mRNA expression, and Western blot for TLR4, MyD88, total NF-κB p65, and phosphorylated NF-κB p65 (p-NF-κB p65) protein levels. Results API pretreatment dose-dependently attenuated LPS-induced pulmonary edema, vascular hyperpermeability, and histopathological damage. API significantly suppressed the elevated levels of pro-inflammatory cytokines TNF-α, IL-6 and IL-1β in BALF and mitigated oxidative stress by reducing MDA content while enhancing the activities of antioxidant enzymes SOD, CAT and GSH-Px. Furthermore, qPCR analysis revealed that API inhibited the LPS-induced upregulation of Tlr4, Myd88, and Nfkb1 mRNA expression in lung tissue. Western blot analysis confirmed that API dose-dependently inhibited LPS-induced upregulation of TLR4, MyD88, and p-NF-κB p65 protein levels. Conclusion Apigenin effectively attenuated LPS-induced acute lung injury in mice by inhibiting the TLR4/MyD88/NF-κB signaling pathway, thereby reducing inflammation and oxidative stress. These findings provide preclinical evidence supporting the potential of Apigenin as a therapeutic agent for ALI.