Unraveling the Protective Effect of Hesperetin In Experimentally Induced Colitis: Inhibition of NF-κB and NLRP3 Inflammasome Activation

被引：0
作者：
Mohanad, Marwa [1 ]
El-Awdan, Sally A. [2 ]
Aboulhoda, Basma E. [3 ]
Nossier, Ahmed Ibrahim [1 ]
Elesawy, Wessam H. [4 ]
Ahmed, Maha A. E. [4 ]
机构：
[1] Misr Univ Sci & Technol MUST, Coll Pharmaceut Sci & Drug Mfg, Dept Biochem, Giza, Egypt
[2] Natl Res Ctr, Dept Pharmacol, Giza, Egypt
[3] Cairo Univ, Fac Med, Dept Anat & Embryol, Cairo, Egypt
[4] Misr Univ Sci & Technol MUST, Coll Pharmaceut Sci & Drug Mfg, Dept Pharmacol & Toxicol, Giza, Egypt
来源：
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY | 2025年 / 39卷 / 03期
关键词：
acetic acid-induced colitis rat model; hesperetin; macrophage modulation; NF-kappa B/NLRP3 inflammasome; pyroptosis; BOWEL-DISEASE; ULCERATIVE-COLITIS; MACROPHAGE; EXPRESSION; BIOMARKERS; MODEL;
D O I：
10.1002/jbt.70229
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
This study aimed to investigate the protective effects of hesperetin (HES) against acetic acid (AA)-induced colitis (AAC) in rats through suppression of nuclear factor kappa B (NF-kappa B) and modulation of the NOD-like receptor pyrin-containing protein 3 (NLRP3) inflammasome. Forty-eight rats were allocated into four groups: control, AAC, HES-treated, and HES pre-treatment followed by AAC. Disease activity index (DAI), macroscopic and histological colonic changes were assessed. Moreover, inflammatory markers, and signaling pathways were evaluated through qRT-PCR, Western blot analysis, ELISA, and immunohistochemistry.HES pre-treatment significantly decreased the DAI by 61.31%, macroscopic colonic damage by 61.25% and the histological score by 41.86% compared to the AAC group. HES also reduced the expression of miR-155 by 73.79%, NLRP3 by 66.07%, Apoptosis-associated speck-like protein containing CARD (ASC) by 66.09%, cleaved caspase-1 by 63.86%, and the pyroptosis marker gasdermin-N (GSDMD-N) by 61.29%. Concurrently, HES attenuated the NF-kappa B pathway, reducing NF-kappa B-positive cells by 74.47% and p-inhibitory kappa B kinase alpha (I kappa B alpha)/I kappa B alpha and p-Inhibitor of nuclear factor kappa-B kinase subunit alpha (IKK alpha/beta)/IKK alpha/beta levels by 43.77% and 38.68%, respectively. Inflammatory cytokines IL-1 beta and IL-18 were diminished by 73.41% and 71.88%, respectively. HES pre-treatment increased peroxisome proliferator-activated receptors-gamma (PPAR-gamma) expression by 259.97%, while reducing CD68+ macrophage infiltration by 72.72%.In conclusion, HES alleviated AAC in rats by targeting the NF-kappa B and NLRP3 inflammasome signaling pathways. This protective effect was mediated through the downregulation of miR-155 expression and the concurrent enhancement of PPAR-gamma expression, resulting in reduced inflammation and pyroptosis. These findings highlight HES as a potential therapeutic protective agent for colitis.
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页数：16
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