Therapeutic Potential of Quercetin Loaded Nanoparticles: Novel Insights in Alleviating Colitis in an Experimental DSS Induced Colitis Model

载槲皮素纳米粒子的治疗潜力:在实验性 DSS 诱发的结肠炎模型中缓解结肠炎的新见解

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作者:Safaa I Khater, Marwa M Lotfy, Maher N Alandiyjany, Leena S Alqahtani, Asmaa W Zaglool, Fayez Althobaiti, Tamer Ahmed Ismail, Mohamed Mohamed Soliman, Saydat Saad, Doaa Ibrahim

Abstract

Oxidative stress is considered the main etiologic factor involved in inflammatory bowel disease (IBD). Integration of nanocarriers for natural therapeutic agents with antioxidant and anti-inflammatory potential is a novel promising candidate for curing IBD. Herein, the colonic antioxidant and anti-inflammatory effects of different concentrations of quercetin nanoparticles (QT-NPs) were evaluated using a dextran sulfate sodium (DSS)-induced colitis model. Following colitis induction, the efficacy and mechanistic actions of QT-NPs were evaluated by assessing lesion severity, molecular aids controlling oxidative stress and inflammatory response, and histopathological and immunohistochemistry examination of colonic tissues. Administration of QT-NPs, especially at higher concentrations, significantly reduced the disease activity index and values of fecal calprotectin marker compared to the colitic group. Colonic oxidant/antioxidant status (ROS, H2O2, MDA, SOD, CAT, GPX and TAC) was restored after treatment with higher concentrations of QT-NPs. Moreover, QT-NPs at levels of 20 mg/kg and, to a lesser extent, 15 mg/kg reduced Nrf2 and HO-1 gene expression, which was in line with decreasing the expression of iNOS and COX2 in colonic tissues. Higher concentrations of QT-NPs greatly downregulated pro-inflammatory cytokines; upregulated genes encoding occludin, MUC-2 and JAM; and restored the healthy architectures of colonic tissues. Taken together, these data suggest that QT-NPs could be a promising alternative to current IBD treatments.

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