Ueng Y F, Shyu C C, Lin Y L, Park S S, Liao J F, Chen C F
National Research Institute of Chinese Medicine, Taipei, Taiwan, ROC.
Life Sci. 2000 Sep 22;67(18):2189-200. doi: 10.1016/s0024-3205(00)00809-2.
Effects of baicalein and wogonin, the major flavonoids of Scutellariae radix, on cytochrome P450 (CYP), UDP-glucuronosyl transferase (UGT), and glutathione S-transferase (GST) were studied in C57BL/6J mice. One-week treatment of mice with a liquid diet containing 5 mM baicalein resulted in 29%, 14%, 36%, 28%, and 46% decreases of hepatic benzo(a)pyrene hydroxylation (AHH), benzphetamine N-demethylation (BDM), N-nitrosodimethylamine N-demethylation (NDM), nifedipine oxidation (NFO), and erythromycin N-demethylation (EMDM) activities, respectively. Treatment with a liquid diet containing 5 mM wogonin resulted in 43%, 22%, 21%, 24%, and 35% decreases of hepatic AHH, BDM, NDM, NFO, and EMDM activities, respectively. However, hepatic 7-methoxyresorufin O-demethylation (MROD) activity was increased and decreased by baicalein- and wogonin-treatments, respectively. Similar modulation was observed with caffeine 3-demethylation (CDM) activity. Immunoblot analysis showed that the levels of hepatic CYP2E1 and CYP3A proteins were decreased by both baicalein- and wogonin-treatments. Hepatic CYP1A2 protein level was increased by baicalein but decreased by wogonin. In extrahepatic tissues, renal AHH activity was decreased by wogonin whereas pulmonary AHH, 7-ethoxyresorufin O-deethylation (EROD), and MROD activities were increased by both flavonoids. Both baicalein and wogonin strongly increased CYP1A protein level in mouse lung. Hepatic and renal UGT activities toward p-nitrophenol were suppressed by baicalein- and wogonin-treatments. However, cytosolic GST activity was not affected by flavonoids. These results suggest that ingestion of baicalein or wogonin can modulate drug-metabolizing enzymes and the modulation shows tissue specificity.
在C57BL/6J小鼠中研究了黄芩的主要黄酮类化合物黄芩素和汉黄芩素对细胞色素P450（CYP）、尿苷二磷酸葡萄糖醛酸基转移酶（UGT）和谷胱甘肽S-转移酶（GST）的影响。用含5 mM黄芩素的液体饲料对小鼠进行为期一周的处理，导致肝脏苯并(a)芘羟化（AHH）、苄非他明N-脱甲基（BDM）、N-亚硝基二甲胺N-脱甲基（NDM）、硝苯地平氧化（NFO）和红霉素N-脱甲基（EMDM）活性分别降低29%、14%、36%、28%和46%。用含5 mM汉黄芩素的液体饲料处理，导致肝脏AHH、BDM、NDM、NFO和EMDM活性分别降低43%、22%、21%、24%和35%。然而，黄芩素和汉黄芩素处理分别使肝脏7-甲氧基试卤灵O-脱甲基（MROD）活性升高和降低。咖啡因3-脱甲基（CDM）活性也观察到类似的调节作用。免疫印迹分析表明，黄芩素和汉黄芩素处理均降低了肝脏CYP2E1和CYP3A蛋白水平。黄芩素使肝脏CYP1A2蛋白水平升高，而汉黄芩素使其降低。在肝外组织中，汉黄芩素降低了肾脏AHH活性，而两种黄酮类化合物均增加了肺组织的AHH、7-乙氧基试卤灵O-脱乙基（EROD）和MROD活性。黄芩素和汉黄芩素均强烈增加小鼠肺组织中CYP1A蛋白水平。黄芩素和汉黄芩素处理均抑制了肝脏和肾脏对对硝基苯酚的UGT活性。然而，细胞溶质GST活性不受黄酮类化合物影响。这些结果表明，摄入黄芩素或汉黄芩素可调节药物代谢酶，且这种调节具有组织特异性。
