Nanostructured propolis attenuates experimental liver fibrosis and is associated with changes in LC3 and p62 expression

BACKGROUNDLiver fibrosis is characterized by persistent activation of hepatic stellate cells and excessive extracellular matrix deposition, and effective antifibrotic therapies remain limited. AIMTo investigate whether nanostructuring enhances the antifibrotic efficacy of propolis against carbon tetrachloride (CCL4)-induced liver fibrosis and examined its association with changes in the autophagy-related markers microtubule-associated protein 1 light chain 3 (LC3) and sequestosome 1 (p62). METHODSMale Sprague-Dawley rats were exposed to CCL4 for eight weeks with or without concomitant administration of conventional propolis or propolis nanoparticles.Biochemical, histopathological, oxidative stress, and molecular analyses were performed, including assessment of LC3 and p62 expression at the mRNA and immunohistochemical protein levels. RESULTSCCL4 administration induced marked hepatic injury, oxidative stress, and liver fibrosis, accompanied by increased LC3 expression and reduced p62 expression.Both propolis formulations attenuated these alterations; however, propolis nanoparticles produced more pronounced improvements in biochemical, histopathological, oxidative stress, and molecular parameters than conventional propolis and were associated with partial attenuation of the CCL4-induced changes in LC3 and p62 expression.5 / 59 CONCLUSION These findings suggest that nanoformulation may improve the antifibrotic efficacy of propolis in experimental liver fibrosis.The observed alterations in LC3 and p62 were associated with the protective effects of propolis nanoparticles; however, because autophagic flux was not directly assessed, these findings should be interpreted as changes in autophagy-related marker expression rather than definitive evidence of altered autophagic activity.Further studies are warranted to clarify the underlying mechanisms and evaluate the translational potential of this approach.