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橙皮苷甲基查尔酮对实验性溃疡性结肠炎的抗氧化和抗炎作用。

Antioxidant and anti-inflammatory effects of hesperidin methyl chalcone in experimental ulcerative colitis.

机构信息

Laboratório de Dor, Inflamação, Neuropatia e Câncer, Departamento de Ciências Patológicas, Universidade Estadual de Londrina, Londrina, PR, Brazil.

Laboratório de Dor, Inflamação, Neuropatia e Câncer, Departamento de Ciências Patológicas, Universidade Estadual de Londrina, Londrina, PR, Brazil; Laboratório de Antioxidantes e Inflamação, Departamento de Ciências Farmacêuticas, Universidade Estadual de Londrina Londrina, Londrina, PR, Brazil.

出版信息

Chem Biol Interact. 2021 Jan 5;333:109315. doi: 10.1016/j.cbi.2020.109315. Epub 2020 Nov 7.

Abstract

Neutrophil infiltration, pro-inflammatory cytokines, and reactive oxygen species (ROS) production have been implicated in development and progression of ulcerative colitis (UC), an inflammatory bowel disease (IBD) characterized by ulcerating inflammation of the mucosal layer generally restricted to the colon. The side effects, safety and human intolerance are limitations of the currently approved treatments for UC. Hesperidin methyl chalcone (HMC) is a flavonoid used to treat chronic venous disease, which shows anti-inflammatory, analgesic, and antioxidant properties in pre-clinical studies, however, its effects on colitis have never been described. Therefore, we aimed to evaluate the protective effects of HMC in a mouse model of acetic acid-induced colitis. Treatment with HMC significantly reduced neutrophil infiltration, edema, colon shortening, macro and microscopic damages induced by intracolonic administration of acetic acid. The improvement of colitis after HMC treatment is related to the increase in colon antioxidant status, and the inhibition of pro-inflammatory cytokines TNF-α, IL-6, IL-1β, and IL-33 in the colon. We observed, moreover, that HMC inhibited NF-κB activation in the colon, which might explain the reduction of the cytokines we observed. Finally, these results demonstrate a novel applicability of HMC to increase antioxidant response and reduce inflammation during acetic acid-induced colitis suggesting it as a promising therapeutic approach for the treatment of ulcerative colitis.

摘要

中性粒细胞浸润、促炎细胞因子和活性氧(ROS)的产生与溃疡性结肠炎(UC)的发展和进展有关,UC 是一种炎症性肠病(IBD),其特征是黏膜层的溃疡性炎症,通常局限于结肠。目前批准的 UC 治疗方法存在副作用、安全性和人体不耐受等问题。橙皮苷甲查尔酮(HMC)是一种用于治疗慢性静脉疾病的类黄酮,在临床前研究中显示出抗炎、镇痛和抗氧化特性,但它对结肠炎的作用从未被描述过。因此,我们旨在评估 HMC 在乙酸诱导的结肠炎小鼠模型中的保护作用。HMC 治疗可显著减少中性粒细胞浸润、水肿、结肠缩短、经结肠内给予乙酸引起的宏观和微观损伤。HMC 治疗后结肠炎的改善与结肠抗氧化状态的增加以及结肠中促炎细胞因子 TNF-α、IL-6、IL-1β 和 IL-33 的抑制有关。此外,我们观察到 HMC 抑制了 NF-κB 在结肠中的激活,这可能解释了我们观察到的细胞因子减少的原因。最后,这些结果表明 HMC 具有增加抗氧化反应和减轻乙酸诱导的结肠炎炎症的新应用,提示其可能是治疗溃疡性结肠炎的一种有前途的治疗方法。

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