Department of Animal Science and Biotechnology and School of Applied Biosciences, Kyungpook National University, Daegu, Republic of Korea.
J Med Food. 2009 Oct;12(5):1038-45. doi: 10.1089/jmf.2009.0072.
Our previous study demonstrated that methanolic extract of Inula helenium (Elecampane) has the potential to induce detoxifying enzymes such as NAD(P)H:(quinone acceptor) oxidoreductase 1 (EC 1.6.99.2) (NQO1, QR) activity and glutathione S-transferase (GST) and found isoalantolactone and alantolactone as the active components. In this study we investigated the detoxifying enzyme-inducing potential of isoalantolactone, which is present in I. helenium and has a structure similar to that of alantolactone. The compound induced QR in a dose-dependent manner in both Hepa1c1c7 cells and its mutant BPRc1 cells lacking the arylhydrocarbon receptor translocator. Like with most phase 2 enzyme inducers, other phase 2 detoxifying enzymes, including GST, glutathione reductase, gamma-glutamylcysteine synthetase, and heme oxygenase-1, were also induced by isoalantolactone in a dose-dependent manner in the cultured cells. Furthermore, isoalantolactone caused a proportionate increase in luciferase activity depending upon concentration and exposure time in the reporter assay in which HepG2-C8 cells, transfectants carrying antioxidant response element-luciferase gene, were used. The nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) was stimulated by the compound and attenuated by phosphatidylinositol 3-kinase inhibitors such as LY294002 and wortmannin. In conclusion, isoalantolactone is a candidate for chemoprevention and acts as potent phase 2 enzyme inducer by stimulating the accumulation of Nrf2 in the nucleus.
我们之前的研究表明，土木香甲醇提取物（土木香）具有诱导解毒酶的潜力，如 NAD(P)H：（醌受体）氧化还原酶 1（EC 1.6.99.2）（NQO1，QR）活性和谷胱甘肽 S-转移酶（GST），并发现异土木香内酯和土木香内酯是其活性成分。在这项研究中，我们研究了异土木香内酯的解毒酶诱导潜力，异土木香内酯存在于土木香中，其结构与土木香内酯相似。该化合物在 Hepa1c1c7 细胞及其缺乏芳烃受体转位蛋白的突变体 BPRc1 细胞中以剂量依赖的方式诱导 QR。与大多数二期酶诱导剂一样，其他二期解毒酶，包括 GST、谷胱甘肽还原酶、γ-谷氨酰半胱氨酸合成酶和血红素加氧酶-1，也在培养细胞中以剂量依赖的方式被异土木香内酯诱导。此外，异土木香内酯在报告基因检测中，当 HepG2-C8 细胞（携带抗氧化反应元件-荧光素酶基因的转染细胞）被用于检测时，根据浓度和暴露时间，使荧光素酶活性呈比例增加。该化合物刺激核因子-E2 相关因子 2（Nrf2）的核易位，并被磷脂酰肌醇 3-激酶抑制剂如 LY294002 和渥曼青霉素减弱。总之，异土木香内酯是化学预防的候选物，通过刺激 Nrf2 在核内的积累，作为一种有效的二期酶诱导剂发挥作用。
