Induction of quinone reductase by withanolides isolated from Physalis philadelphica (tomatillos)
Induction of quinone reductase by withanolides isolated from Physalis philadelphica (tomatillos)
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DOI：
10.1021/jf970246w
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发表时间：
1997-10-01
影响因子：
6.1
通讯作者：
Kinghorn, AD
中科院分区：
文献类型：
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作者：
Kennelly, EJ;Gerhauser, C;Kinghorn, AD
费城Physalis philphilica的果实，通常被称为番茄，是调味品“salsa verde”的一种成分。作为一项正在进行的发现天然产品癌症化学预防剂的项目的一部分，在培养的Hepa 1c1c7小鼠肝癌细胞中，发现了一种醋酸乙酯可溶性提取物，该提取物可诱导醌还原酶活性。利用液相色谱/质谱技术对果实的乙酸乙酯提取物进行生物测定定向分离，分离出一系列结构相关的金甾醇类化合物。分离得到1个新化合物2,3-二氢-3-甲氧基withysacarpin(1)和2个已知化合物withysacarpin(2)和24,25-二氢withasanolide D(3)，其结构为1。所有三种withanolides都能显著诱导小鼠肝癌细胞Hepa 1c1c7、TAPclBP(r)c1和BP(r)cl中的醌还原酶活性，这表明这些化合物是单功能诱诱剂，特异性地提高负责解毒的II期酶，而不影响可能激活致癌物的I期酶。
The fruits of Physalis philadelphica, known commonly as tomatillos, are an ingredient of the condiment ''salsa verde''. As part of an ongoing project to discover natural product cancer chemopreventive agents, an ethyl acetate-soluble extract of the commercially available fresh fruits of P. philadelphica was found to induce quinone reductase activity in cultured Hepa 1c1c7 murine hepatoma cells. Bioassay-directed fractionation of an EtOAc extract of the fruits, aided by LC/MS, led to the isolation of a series of structurally related withanolides. One novel substance, 2,3-dihydro-3-methoxywithaphysacarpin (1), and two known compounds, withaphysacarpin (2) and 24,25-dihydrowithanolide D (3), were isolated, with the structure of 1 characterized spectroscopically. All three withanolides significantly induced quinone reductase activity in Hepa 1c1c7, TAPclBP(r)c1, and BP(r)cl murine hepatoma cells, suggesting that these compounds are monofunctional inducers, specifically elevating phase II enzymes responsible for detoxification, while not influencing phase I enzymes that may activate carcinogens.