Naringin exhibited various pharmacological activities. However, its
biological function and underlying mechanism in regulating macrophage polarization remain elusive. This study aimed to investigate the regulatory network between
naringin and macrophage polarization in
sepsis-induced intestinal injury. Cecal
ligation and
puncture (CLP) was used to establish the animal model of
sepsis.
Chromatin immunoprecipitation and a
luciferase reporter assay were used to determine the interplay between
peroxisome proliferator-activated receptor γ (PPARγ) and miR-21 promoter, as well as miR-21 and its target genes.
Naringin enhanced the overall survival of septic mice and alleviated the CLP-induced inflammatory response and intestinal damage. This was accompanied by the increased expression of PPARγ in the intestines and the stimulation of ileal macrophages toward the M2 phenotype. Furthermore, in
lipopolysaccharide-stimulated bone marrow-derived macrophages,
naringin stimulated M2 polarization. Mechanistically, PPARγ inhibition attenuated the promotion of M2 polarization caused by
naringin, and the
naringin/PPARγ regulatory work was compromised by miR-21 inhibition. The present study suggested that
naringin promoted M2 polarization via the PPARγ/miR-21 axis, thus relieving
sepsis-induced intestinal injury. This study provides novel insights into the mechanism by which
naringin alleviated
sepsis-induced intestinal injury through regulation of macrophage polarization.