Naringin improves sepsis-induced intestinal injury by modulating macrophage polarization via PPARγ/miR-21 axis

Abstract

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.

Direct osteogenesis and immunomodulation dual function via sustained release of naringin from the polymer scaffold

“…In addition, it was reported that the anti-inflammatory effects of NG are regulated by multiple mechanisms including (1) the promotion of macrophage M2 polarization through PI3K/AKT/mTOR signaling pathways; (2) inhibition of multiple inflammation-related signaling pathways (such as NF-κB and MAPK pathways) to reduce the production of inflammation-related factors, thereby suppressing inflammation, and (3) adjustment of the peroxisome proliferator-activated receptor (PPAR)/miR-21 pathway participating in the regulation of inflammation. 46–49…”

“…In addition, it was reported that the anti-inflammatory effects of NG are regulated by multiple mechanisms including (1) the promotion of macrophage M2 polarization through PI3K/AKT/ mTOR signaling pathways; (2) inhibition of multiple inflammation-related signaling pathways (such as NF-kB and MAPK pathways) to reduce the production of inflammation-related factors, thereby suppressing inflammation, and (3) adjustment of the peroxisome proliferator-activated receptor (PPAR)/miR-21 pathway participating in the regulation of inflammation. [46][47][48][49] Bone regeneration involves three successive phases in the induction of new bone regeneration: inflammation, repair, and remodeling phases. As shown in earlier research, prolonged chronic inflammation caused by macrophages of M1 type could induce the absorption of bone tissue, which causes the formation of a fibrous envelope, blocks the combination of bone cells and implants, and ultimately leads to the failure of bone repair.…”

Diabetes exacerbated sepsis-induced intestinal injury by promoting M1 Macrophage Polarization via miR-3061/Snail1 signaling

“…It is considered that transcription factors are fully involved in macrophage activation [32,33]. Recently studies have shown that the key transcription factor Snail1 is essential for macrophage polarization and metastasis in breast cancer though altered GM-CSF secretion [34].…”

Plants’ bioactive secondary metabolites in the management of sepsis: Recent findings on their mechanism of action

“…Naringin at dose of 200 mg/kg produced an anti-inflammatory effect by inducing HO-1 expression in macrophages through the AMPK, p38, and Nrf-2 signaling pathways. Naringin also improved sepsis-induced intestinal injury by modulating macrophage polarization via PPARγ/ miR-21 axis (Li et al, 2021).…”