二苯甲醯基甲烷經由小鼠肝臟微粒體酵素作用之代謝途徑研究   全文下載

Metabolic Pathway of Dibenzoylmethane, a â-diketone Analogue of Curcumin, by NADPH-dependent Cytochrome P450 Enzymes in Mouse Liver Microsomes

二苯甲醯基甲烷（DBM）為一薑黃素之β-二酮類結構類似物，從以往本實驗室研究結果顯示DBM可有效抑制7,12-二甲基苯并蔥（DMBA）誘發之小鼠乳腺腫瘤。研究其中之作用機制顯示DBM可能扮演肝臟代謝酵素Phase I系統中之調節劑。此報告中，我們分析DBM經由小鼠肝臟中NADPH-相關細胞色素代謝酵素（NADPH-dependent cytochrome P450 enzymes）所得之代謝產物。結果顯示利用化學儀器NMR、GC-MS和LCMS，可分離出DBM還原型式之主要代謝產物DBMH2，和一些副產物，並了解DBM之代謝途徑。由此結果，我們推論DBM可視為一抑制劑，經由與cytochrome P450還原酵素作用，達到抑制DMBA氧化代謝成活性致癌物，並可解釋其誘發小鼠乳腺腫瘤之可能作用機制。"

Dibenzoylmethane (DBM), a curcumin-related β-diketone analogue, has been reported to exhibit a remarkable inhibitory effect on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumorigenesis in Sencar mice. Investigation of the underlying mechanisms of DBM in the prevention of mammary tumorigenesis implied its role as an effector of Phase I enzymatic system. In this report, the metabolic fate of DBM by NADPH-dependent cytochrome P450 enzymes in mouse liver microsomes was demonstrated. Isolation of the major reductive metabolites of DBM (DBMH2), together with several minor metabolites identified by NMR, GC and LC-MS, explained the potential role of DBM as a modulator of the cytochrome P450 reductase that is required for the function of oxidase to metabolize DMBA. These might also contribute to the result of the inhibitory effect of DBM on DMBA-induced mouse mammary tumorigenesis.