Abstract

Smoking is a public health concern, and even though smoking cessation methods exist, nicotine replacement therapy (NRT) is often ineffective. Smoking behavior is related to the nicotine metabolizing enzyme (NME) P450 2A6 (mouse 2A5) polymorphisms. Accordingly, fast metabolizers are nicotine dependent, and have low quitting rates compared to slow metabolizers. In this study we examined the ability of Ginkgo biloba L (GB) and its constituents to inhibit the NME, using mouse liver microsomes containing the 2A5 enzyme. Our results indicate that GB can inhibit 2A5 (25% inhibition at 5%v/v), with the flavonoids quercetin, isorhamnetin, and kaempferol being responsible for this inhibition (23.5%, 10.7%, 25.2% inhibition at 60 ng/μL, respectively). Importantly, the flavonoids inhibited 2A5 via mechanism based inhibition (for quercetin 30 ng/μl inhibition increased from 20.8% to 26.9% within 15 minutes). Our results suggest that GB if consumed on a regular basis can help NRT enhancement particularly in fast nicotine metabolizers.

摘要

吸烟是一个公共卫生问题，尽管存在戒烟方法，但尼古丁替代疗法 (NRT) 通常无效。吸烟行为与尼古丁代谢酶 (NME) P450 2A6 (mouse 2A5) 多态性有关。因此，快速代谢者依赖尼古丁，与慢代谢者相比，戒烟率低。在这项研究中，我们检查了银杏叶的能力(GB) 及其成分抑制 NME，使用含有 2A5 酶的小鼠肝微粒体。我们的结果表明 GB 可以抑制 2A5（在 5%v/v 时抑制 25%），其中黄酮类化合物槲皮素、异鼠李素和山柰酚负责这种抑制（在 60 ng/μL 时抑制 23.5%、10.7%、25.2%，分别）。重要的是，黄酮类化合物通过基于机制的抑制作用抑制 2A5（对于槲皮素 30 ng/μl 的抑制作用在 15 分钟内从 20.8% 增加到 26.9%）。我们的结果表明，如果定期食用 GB，可以帮助 NRT 增强，特别是在快速尼古丁代谢者中。