Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
Saudi Pharm J. 2010 Jul;18(3):167-71. doi: 10.1016/j.jsps.2010.05.008. Epub 2010 May 31.
To investigate the potential effects of eleven of the most commonly used Saudi folk herbal medications on the metabolic activity of CYP2C9 in human liver microsomes.
CYP2C9-mediated 4'-hydroxylation of tolbutamide (TB) to 4'-hydroxytolbutamide (4-OH-TB) was utilized to assess the metabolic activity of CYP2C9. In the present study, an initial screening of the eleven herbs was carried out by incubating TB with microsomes and NADPH in absence or presence of a fixed concentration (25 μg/ml) of alcoholic extracts of different herbs and the metabolite formed was measured by HPLC. Herbs that showed significant effects were further investigated at a lower range of concentration.
Among the investigated herbal extracts, only aniseed and curcuma showed statistically significant effects on the formation of 4-OH-TB in human liver microsomes. Curcuma produced a potent inhibition on the metabolite formation and its maximum (about 45% inhibition) was observed at the highest extract concentrations (10 and 25 μg/ml). On the other hand, aniseed significantly activates the formation of 4-OH-TB and the maximum activation (about 55%) was observed at 2.5 μg/ml of aniseed extract.
The results of this study have shown that alcoholic extracts of curcuma and aniseed were capable of inhibiting and activating; respectively, the CYP2C9-mediated 4-OH-TB formation in human liver microsomes, suggesting that these herbs have the potential to interact with CYP2C9 drug substrates. None of the other nine investigated herbs was able to produce any statistically significant effect.
研究 11 种最常用的沙特草药对人肝微粒体 CYP2C9 代谢活性的潜在影响。
利用甲苯磺丁脲（TB）的 4′-羟化作用（CYP2C9 介导）生成 4′-羟甲苯磺丁脲（4-OH-TB），来评估 CYP2C9 的代谢活性。在本研究中，通过在缺乏或存在固定浓度（25μg/ml）的不同草药醇提物的情况下，将 TB 与微粒体和 NADPH 孵育，对 11 种草药进行了初步筛选，并通过 HPLC 测定形成的代谢物。对显示出显著效果的草药进一步在较低浓度范围内进行研究。
在所研究的草药提取物中，只有八角茴香和姜黄对人肝微粒体中 4-OH-TB 的生成有统计学意义的影响。姜黄对代谢产物的形成有很强的抑制作用，在最高提取物浓度（10 和 25μg/ml）下，其最大抑制率（约 45%）。另一方面，八角茴香显著激活了 4-OH-TB 的形成，在 2.5μg/ml 的八角茴香提取物中观察到最大激活（约 55%）。
本研究结果表明，姜黄和八角茴香的醇提物能够抑制和激活分别在人肝微粒体中 CYP2C9 介导的 4-OH-TB 形成，提示这些草药有可能与 CYP2C9 药物底物相互作用。其他 9 种研究草药均未产生任何有统计学意义的影响。
