Inhibitory effect of nordihydroguaiaretic acid, a plant lignan, on Helicobacter pylori-associated gastric carcinogenesis in Mongolian gerbils
Inhibitory effect of nordihydroguaiaretic acid, a plant lignan, on Helicobacter pylori-associated gastric carcinogenesis in Mongolian gerbils
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DOI：
10.1111/j.1349-7006.2007.00599.x
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发表时间：
2007-11-01
期刊：
影响因子：
5.7
通讯作者：
Tatematsu, Masae
中科院分区：
文献类型：
--
作者：
Toyoda, Takeshi;Tsukamoto, Tetsuya;Tatematsu, Masae
最近的流行病学研究表明，食用某些天然产品可以降低人类患癌症的风险。例如，植物来源的木脂素在体外和体内都被证明对癌症具有化学预防作用。本研究以蒙古沙土鼠为实验动物，研究了三种木脂素对幽门螺杆菌的增殖和预防幽门螺杆菌相关性胃癌的作用。这三种木脂素分别为牛至苷、牛至皂苷元和去甲二氢愈创木酸。为了研究牛膝皂苷元和NDGA在胃癌发生中的作用，将无特定病原体的雄性5周龄沙土鼠感染幽门螺杆菌，每晚10点。在它们的饮用水中加入N-甲基-N-亚硝脲，并喂食含有不同浓度木脂素的饲料，直到52周后被杀死。在0.25%的饮食水平下，NDGA显著降低了胃腺癌的发病率。相比之下，牛至皂苷元在0.1%的水平上未能减弱肿瘤的形成。在0.25和0.05%(NDGA)和0.1%(牛至皂苷元)剂量下，NDGA和牛至皂苷元均能显著降低小鼠血清8-羟基-2‘-脱氧鸟苷水平。0.25%NDGA显著抑制胃窦部和胃体部肠化生的形成。三种木脂素均呈剂量依赖性抑制幽门螺杆菌的体外增殖，但三种木脂素抗H.幽门螺杆菌抗体或幽门螺杆菌特异性尿素酶A基因在所有幽门螺杆菌感染组中的数量。这些结果提示，NDGA可能具有预防胃癌发生的作用。可能的机制似乎与抑制胃炎进展和抗氧化活性有关，而不是直接的抗菌影响。
Recent epidemiological studies have demonstrated that consumption of certain natural products can lower cancer risk in humans. For example, plant-derived lignans have been shown to exert chemopreventive effects against cancer in vitro and in vivo. In the present study, the effects of three such lignans, termed arctiin, arctigenin, and nordihydroguaiaretic acid (NDGA), on the proliferation of Helicobacter pylori and the prevention of H. pylori-associated gastric cancer were investigated in Mongolian gerbils. To examine the effects of arctigenin and NDGA on stomach carcinogenesis, specific pathogen-free male, 5-week-old gerbils were infected with H. pylori, administered 10 p.p.m. N-methyl-N-nitrosourea in their drinking water and fed diets containing various concentrations of lignans until they were killed after 52 weeks. At a dietary level of 0.25%, NDGA significantly decreased the incidence of gastric adenocarcinomas. Arctigenin, in contrast, failed to attenuate neoplasia at a level of 0.1%. Both NDGA and arctigenin significantly reduced serum 8-hydroxy-2'-deoxyguanosine levels at doses of 0.25 and 0.05% (NDGA), and 0.1% (arctigenin). Administration of 0.25% NDGA significantly suppressed the formation of intestinal metaplasia both in the antrum and the corpus. Although all three lignans dose-dependently inhibited the in vitro proliferation of H. pylori, there were no differences in the titers of anti-H. pylori antibodies or the amount of the H. pylori-specific urease A gene among all H. pylori-infected groups. These results suggest that NDGA might be effective for prevention of gastric carcinogenesis. The possible mechanisms appear to be related to inhibitory effects on progression of gastritis and antioxidative activity rather than direct antimicrobial influence.