Proteotranscriptomics Analysis Reveals the Key Pathways and Genes Involved in Apigenin’s Anti-Liver Fibrosis Effects

Liver fibrosis is a global health issue with limited
treatments.
While apigenin has demonstrated potential in alleviating liver fibrosis,
its mechanisms remain unclear. This study employed an integrated proteotranscriptomic
approach to elucidate the molecular mechanisms underlying apigenin’s
protective effects against CCl4-induced liver fibrosis. Liver tissues
from mice with CCl4-induced fibrosis treated with different doses
of apigenin (10, 20, and 40 mg/kg) were analyzed using transcriptomics
and proteomics. Results demonstrated dose-dependent antifibrotic effects
of apigenin. Notably, numerous genes and proteins were inversely regulated
by CCl4 and apigenin, with generally low and variable mRNA-protein
abundance correlations. We identified 82 biological processes or molecular
functions that were inversely regulated by CCl4 and high-dose apigenin
at both mRNA and protein levels. Among the 48 key proteins (KPs) involved,
11 and 14 KPs correlated with liver fibrosis in mouse and human data
sets, respectively. Six KPs maintained consistent correlations with
fibrosis severity across both species, highlighting their potential
as both biomarkers for fibrosis progression and translational targets.
These findings underscore apigenin’s therapeutic potential
and emphasize the importance of multiomics approaches in understanding
complex diseases like liver fibrosis. This study also provides valuable
insights for developing improved therapeutic strategies and diagnostic
tools for liver fibrosis.