Cinnamophilin 對C57BL/6J 鼷鼠肝藥物代謝之體外及體內之作用

Effects of Cinnamophilin on Mouse Hepatic Drug-Metabolizing Enzymes in Vitro and in Vivo

Cinnamophilin（ CIN）具有抗氧化傷害之保護作用。細胞色素 P450（ P450）及 glutathione硫 -轉移{^FA5B^}（ GST）為重要之藥物代謝{^FA5B^}，藥物代謝{^FA5B^}之調控影響是產生藥物交互作用之重要因素。為評估 CIN因影響藥物代謝{^FA5B^}而產生藥物交互作用之可能性，因而研究 CIN對鼷鼠 C57BL/6J肝 P450 及 GST 之影響，體外實驗之結果顯示 CIN 對微粒體 nifedipine oxidation 活性有抑制作用，其 IC50值為 17.3 ± 1.8 μ M。以餵管給藥方式，將鼷鼠處理 CIN，結果顯示以 100 毫克 /公斤 /天 CIN 連續處理鼠 5 天後，對鼠肝微粒體 P450 含量及 NADPH-P450 還原{^FA5B^}活性無影響。這處理不影響鼠肝微粒體 P450 氧化代謝 7-ethoxyresorufin， 7-methoxyresorufin， coumarin， tolbutamide， N-nitrosodimethylamine 及 nifedipine 等的活性， CIN 處理對鼠肝細胞質液 GST 活性亦無影響。這些結果顯示 CIN 在體外抑制 nifedipine oxidation 活性，但以口服處理鼠， CIN對鼠肝 P450 及 GST 活性均無影響。Cinnamophilin (CIN) showed protective effect against oxidative damage. Cytochrome P450-dependent monooxygenase (P450) and glutathione S-transferase (GST) are important drug-metabolizing enzymes and P450 plays an important role in drug-drug interactions. To assess the possible drug interactions, effects of CIN on mouse P450 and GST were studied. In vitro, CIN inhibited liver microsomal nifedipine oxidation activity with an IC50 of 17.3 ± 1.8 μM. However, CIN had no effect on 7-ethoxyresorufin O-deethylation and coumarin hydroxylation activities. In vivo, oral administration of CIN had no effects on liver microsomal P450 content and NADPH-P450 reductase activity. Hepatic P450-catalyzed oxidations of 7-ethoxyresorufin, 7-methoxyres-orufin, coumarin, tolbutamide, N-nitrosodimethylamine, and nifedipine were not affected by CIN. These results revealed that CIN was a mouse CYP3A inhibitor in vitro without affecting P450 and GST activities in vivo.