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芍药汤通过诱导 Nrf2 信号通路对结肠炎相关结直肠癌的保护作用。

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

机构信息

Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5, Beixiange Road, Xicheng District, Beijing, 100053, China; Department of Medical Security Management, Wangjing Hospital, China Academy of Chinese Medical Sciences, No.6, Zhonghuan South Road, Chaoyang District, Beijing, 100102, China.

Department of Family Medicine, Contra Costa Regional Medical Center, Martinez, CA, 94553, USA.

出版信息

J Ethnopharmacol. 2020 Apr 24;252:112600. doi: 10.1016/j.jep.2020.112600. Epub 2020 Jan 22.

Abstract

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 HO-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.

摘要

民族药理学相关性

溃疡性结肠炎易发展为伴有高死亡率的溃疡性结直肠癌。芍药汤(SYD)是一种中药复方,据报道具有抗结直肠癌作用。因此,本研究主要通过体内和体外实验研究 SYD 对氧化损伤和炎症反应的保护和预防作用。

研究目的

芍药汤(SYD)是一种中药复方,对溃疡性结肠炎有效。炎症细胞中活性氧(ROS)水平的升高可能会促进结肠癌的发展。核因子红细胞 2 相关因子 2(Nrf2)已成为预防结直肠癌(CRC)的新靶点。在这项研究中,我们通过体内和体外实验评估了 SYD 对结肠炎相关结直肠癌的抗氧化作用。

材料和方法

采用体内 AOM/DSS 诱导的结肠癌小鼠模型和体外 HO 诱导的 HT-29 细胞氧化应激模型。通过 Western blot、RT-PCR 和酶联免疫吸附试验检测 Nrf2 及其下游基因的蛋白表达,以确定 SYD 的抗氧化活性。

结果

体内和体外实验均表明,SYD 通过激活 Nrf2 通路和上调 Nrf2 下游基因的表达发挥抗氧化作用。SYD 对结肠炎相关结直肠癌具有预防作用。

结论

这些观察结果表明,SYD 通过激活 Nrf2 通路和上调 Nrf2 下游相 II 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溃疡性结直肠癌的预防和治疗。

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