Protective effect of ShaoYao decoction on colitis-associated colorectal cancer by inducing Nrf2 signaling pathway

Protective effect of ShaoYao decoction on colitis-associated colorectal cancer by inducing Nrf2 signaling pathway
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芍药汤诱导Nrf2信号通路对结肠炎相关结直肠癌的保护作用

DOI:
10.1016/j.jep.2020.112600
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发表时间:
2020-04-24
影响因子:
5.4
通讯作者:
Li, Weidong
Li, Weidong
中科院分区:
医学2区
文献类型:
--
作者:
Wang, Xiaoyan;Saud, Shakir M.;Li, Weidong

文献摘要

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民族药理学相关性:溃疡性结肠炎易于发展为溃疡相关性结直肠癌,死亡风险高。芍药汤是一种具有抗大肠癌作用的中药复方。因此,本研究通过体内外实验研究了芍药汤对溃疡性结肠炎(UC)大鼠氧化损伤和炎症反应的保护作用。炎性细胞中活性氧(ROS)水平的增加可能会导致癌症的发展。核因子-红细胞2相关因子2(Nrf 2)已成为预防结直肠癌(CRC)的新靶点。本研究通过体内和体外实验,探讨了SYD对结肠炎相关性大肠癌的抗氧化作用。结肠癌模型和体外H2 O2诱导的HT-29细胞氧化应激模型。结果:体内外实验均表明,SYD通过激活Nrf 2通路,上调Nrf 2下游基因的表达,发挥抗氧化作用。SYD被证明对结肠炎相关的结直肠cancer.Conclusions的预防作用:这些观察结果表明,SYD是有效的,通过激活Nrf 2通路和上调Nrf 2下游II相酶的表达增强抗氧化能力。SYD的抗炎和抗氧化作用共同有助于预防和治疗溃疡相关的结直肠癌。
Ethnopharmacological relevance: Ulcerative colitis were prone to develop into ulcerrelated colorectal cancer with high risk of mortality. Shaoyao Decoction (SYD), a compound prescription of Chinese traditional medicine, was reported to have anti-colorectal cancer effect. Thus this study mainly investigated the protective and preventive effect of SYD against oxidative damages and inflamatory response through in vivo and in vitro experiments.Aim of the study: Shaoyao decoction (SYD), a compound prescription of traditional Chinese medicine, is effective in treating ulcerative colitis. The increased levels of reactive oxygen species (ROS) in inflammatory cells potentially drive the development of carcinomas. Nuclear factor-erythroid 2-related factor 2 (Nrf2) has became a novel target for the prevention of colorectal cancer (CRC). In this study, we assessed the antioxidation effect of SYD against colitis associated colorectal cancer through in vivo and in vitro experiments.Materials and methods: In vivo AOM/DSS-induced murine. model of colon cancer and in vitro H2O2-induced oxidative stress in HT-29 cells model were conducted. To determine the antioxidant activity of SYD, protein expression of Nrf2 and its downstream genes were detected by western blot, RT-PCR and Enzyme-linked immunosorbent assay.Results: Both in vivo and in vitro experiments demonstrated that SYD exerts antioxidant effect through activation of Nrf2 pathway and upregulation expression of Nrf2 downstream genes. SYD is shown to have preventive effect against colitis-associated colorectal cancer.Conclusions: These observations suggest that SYD is effective in the enhancement of antioxidant ability via activation of Nrf2 pathway and the up-regulation of Nrf2-downstream phase II enzymes expression. The anti inflammation and antioxidant action of SYD together contributes to the prevention and treatment of ulcerrelated colorectal cancer.