School of Chemical and Biotechnology, SASTRA University, Thirumalaisamudram, Thanjavur, 613401, Tamil Nadu, India.
Central Animal Facility, SASTRA University, Thirumalaisamudram, Thanjavur, 613401, Tamil Nadu, India.
Biomed Pharmacother. 2017 Oct;94:577-588. doi: 10.1016/j.biopha.2017.07.146. Epub 2017 Aug 4.
Oxidative stress and gut microbial enzymes are intricately linked to the onset of colon carcinogenesis. Phytochemicals that modulate these two factors hold promise for the development of such agents as anticancer drugs. The present study evaluates the chemopreventive potential of p-coumaric acid (p-CA) - a phenolic acid in rats challenged with the colon specific procarcinogen DMH (1,2 di-methyl hydrazine). Rats were randomized into six groups (n=7/group). Group 1 (control); Group 2 (p-CA 200mg/kg b.w.); Group 3 (DMH 40mg/kg b.w.); Groups 4 (DMH+p-CA 50mg/kg b.w.) and Group 5 (DMH+p-CA 100mg/kg b.w.) and Group 6 (DMH+p-CA 200mg/kg b.w.). After the experimental duration of 15 weeks' rats were subjected to necropsy and tissues were collected for the histological and biochemical investigations. DMH induced colonic preneoplastic lesions viz., aberrant crypt foci (ACF), dysplastic ACF (DACF), mucin depleted foci (MDF) and beta catenin accumulated crypts (BCAC) were significantly suppressed by p-CA supplementation. Glucuronide conjugation of DMH in liver and its subsequent deconjugation mediated by microbes in the colon induced the formation of colonic preneoplastic lesions. p-CA inhibited these lesions and protected the rat colon against genotoxic insult by scavenging the free radicals via its strong antioxidant response and detoxification mechanism as measured by TBARS and enzymic antioxidants in control and experimental rats. Of the three tested doses, p-CA at a dose of 100mg/kg body weight is found to exhibit a significant optimum effect compared to the other two doses 50mg/kg body weight and 200mg/kg body weight.
氧化应激和肠道微生物酶与结肠癌的发生有着错综复杂的联系。调节这两个因素的植物化学物质为开发抗癌药物等药物提供了希望。本研究评估了对香豆酸（p-CA）的化学预防潜力，p-CA 是一种在大鼠中用结肠特异性前致癌物 DMH（1,2 二甲基肼）进行挑战时的酚酸。大鼠被随机分为六组（每组 n=7）。第 1 组（对照组）；第 2 组（p-CA 200mg/kg b.w.）；第 3 组（DMH 40mg/kg b.w.）；第 4 组（DMH+p-CA 50mg/kg b.w.）、第 5 组（DMH+p-CA 100mg/kg b.w.）和第 6 组（DMH+p-CA 200mg/kg b.w.）。经过 15 周的实验后，对大鼠进行尸检并收集组织进行组织学和生化研究。p-CA 补充显著抑制了 DMH 诱导的结肠前肿瘤病变，即异常隐窝病灶（ACF）、发育不良 ACF（DACF）、粘蛋白耗竭病灶（MDF）和β-连环蛋白积累隐窝（BCAC）。DMH 在肝脏中的葡萄糖醛酸化及其随后在结肠微生物中的去结合，诱导了结肠前肿瘤病变的形成。p-CA 通过其强烈的抗氧化反应和解毒机制抑制这些病变并保护大鼠结肠免受遗传毒性损伤，通过 TBARS 和实验大鼠的酶抗氧化剂来测量。在三种测试剂量中，与其他两种剂量 50mg/kg 体重和 200mg/kg 体重相比，p-CA 100mg/kg 体重的剂量表现出显著的最佳效果。
