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对甲氧基肉桂酸作为一种活性苯丙素,对 1,2-二甲基肼诱导的大鼠结肠癌发生的抗炎和抗癌作用。

Anti-inflammatory and anticancer effects of p-methoxycinnamic acid, an active phenylpropanoid, against 1,2-dimethylhydrazine-induced rat colon carcinogenesis.

机构信息

Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tamilnadu, 608 002, India.

出版信息

Mol Cell Biochem. 2019 Jan;451(1-2):117-129. doi: 10.1007/s11010-018-3398-5. Epub 2018 Jul 6.

Abstract

p-methoxycinnamic acid (p-MCA) is an active phenolic acid found in rice bran, turmeric, brown rice, Kaempferia galanga, buckwheat inflorescence, etc. Earlier, we have reported that p-methoxycinnamic acid possesses antioxidant and antilipidperoxidative effects on 1,2-dimethylhyrdrazine (DMH)-induced colon carcinogenesis. The purpose of this study is to unravel the anti-inflammatory and anticancer properties of p-MCA against DMH-induced colon carcinogenesis. Male albino Wistar rats were randomly divided into six groups. Group 1 served as control, group 2 rats received 40 mg/kg b.wt. of p-MCA in 0.1% carboxymethylcellulose (CMC) every day, and colon cancer was induced in groups 3-6 using DMH at the dose of (20 mg/kg b.wt. subcutaneously) once a week for 15 weeks. In addition, along with DMH, groups 4 (initiation), 5 (post initiation) and 6 (entire period) rats received p-MCA (40 mg/kg b.wt.) p.o. every day during different time periods for the total experimental period of 30 weeks. Colon of animals treated with DMH showed an increased number of aberrant crypt foci (ACFs), increased nuclear translocation of transcription factor NF-κB p65 subunit, increased expression of inflammatory markers (iNOS, COX-2), cytokines (tumour necrosis factor-α, interleukin-6), cyclin D1, antiapoptotic protein (Bcl-2), metastasis marker (matrix metalloproteinase-2 (MMP-2)) and angiogenic marker (vascular endothelial growth factor VEGF) and decreased expression of pro-apoptotic proteins (Bax, caspases 3 and 9). On supplementing with p-MCA (40 mg/kg b.wt.) throughout the entire experimental period, DMH-induced pathological alterations reversed significantly to normal.

摘要

对甲氧基肉桂酸(p-MCA)是一种存在于米糠、姜黄、糙米、蓬莪术、荞麦花序等中的活性酚酸。早期,我们已经报道过对甲氧基肉桂酸具有抗氧化和抗脂质过氧化作用,可抑制 1,2-二甲基肼(DMH)诱导的结肠癌发生。本研究旨在揭示 p-MCA 对 DMH 诱导的结肠癌发生的抗炎和抗癌特性。雄性白化 Wistar 大鼠随机分为六组。第 1 组作为对照,第 2 组大鼠每天接受 40mg/kg b.wt. 的 p-MCA,溶于 0.1%羧甲基纤维素(CMC)中,第 3-6 组大鼠每周皮下给予 DMH(20mg/kg b.wt.)一次,共 15 周。此外,在给予 DMH 的同时,第 4 组(起始)、第 5 组(起始后)和第 6 组(整个时期)大鼠每天口服给予 p-MCA(40mg/kg b.wt.),持续整个实验期 30 周。用 DMH 处理的动物的结肠显示出异常隐窝病灶(ACF)数量增加,转录因子 NF-κB p65 亚单位的核转位增加,炎症标志物(iNOS、COX-2)、细胞因子(肿瘤坏死因子-α、白细胞介素-6)、细胞周期蛋白 D1、抗凋亡蛋白(Bcl-2)、转移标志物(基质金属蛋白酶-2(MMP-2))和血管生成标志物(血管内皮生长因子 VEGF)的表达增加,而促凋亡蛋白(Bax、caspases 3 和 9)的表达减少。在整个实验期间补充 p-MCA(40mg/kg b.wt.)可显著逆转 DMH 诱导的病理改变至正常。

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