Ginkgo biloba L. flavonoids inhibit CYP 2A5; potential dietary supplement for nicotine replacement therapy enhancement

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.