Inhibition of Cytochrome P450 2E1 and Cytochrome P450 2A6 by essential oils: tarragon (Artemisia dracunculus) and basil (Ocimum basilicum)

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Mohammad Mazamal Khan (Creator)
The University of North Carolina at Greensboro (UNCG )
Web Site:
Gregory Raner

Abstract: Cytochrome P450 enzymes are involved in the metabolism of foreign substances that are present within living organisms. These P450s are classified as Phase I metabolizing enzymes that are found mainly in the liver, they belong to a superfamily of heme containing monoxygenases that are required for metabolism for a number of xenobiotics. Mechanistic approach by these enzymes involves carrying out the oxidation of carbon and nitrogen groups usually resulting in the addition of an alcohol. Cytochrome P450 enzymes have been involved in the bioactivation of inactive compounds to active electrophiles that can contribute to the production of reactive oxygen species, such as superoxide, free radicals, and peroxides. These ROS can contribute to oxidative stress, which leads to hepatic cell necrosis, lipid peroxidation, and DNA adduct formation. This study focuses on two specific Cytochrome P450s, CYP2E1 and CYP2A6. These enzymes have shown to have one of the highest rates of uncoupling among all P450s, this uncoupling leads to the production of ROS. This study focuses on finding potential inhibitors that decrease the chances of these uncoupling reactions from occurring. Human, rat, and rabbit liver microsomes were used for these studies. A series of essential oils were screened with these P450s to determine their inhibitory affects on the enzyme. From these studies, tarragon (Artemisia dracunculus) and basil (Ocimum basilicum) showed the highest inhibitory affects on the enzyme. The major constituent for both these oils was estragole, this was also confirmed via GCMS testing, because of this it was thought that it was a major reason to why the enzyme activity is being inhibited. With the initial screening data showing inhibition of CYP2E1 and CYP2A6, next goal was to determine how potent these oils were and what is the mode of inhibition, reversible or irreversible. The results of CYP2E1 and CYP2A6 with human, rat, and rabbit concluded that both essential oils and estragole inhibited the activity of the enzyme. Estragole was the most potent inhibitor of both enzymes in all 3 species. The KI value for estragole with CYP2E1 in humans was 22.4 µM, in rat 143 µM, and in rabbit 108 µM. The KI value for estragole with CYP2A6 in humans was 27.5 µM and in rabbit was 49.3 µM. Results show that the mode of inhibition shown by both these essential oils and estragole was non-competitive and a reversible type of interaction occurred with both Cytochrome P450 enzymes.

Additional Information

Language: English
Date: 2014
Basil, CYP2A6, CYP2E1, Cytochrome P450, Estragole, Tarragon
Cytochrome P-450 $x Inhibitors
Cytochrome P-450 CYP2E1 $x Inhibitors
Enzyme inhibitors
Basil $x Physiological effect
French tarragon $x Physiological effect
Essences and essential oils $x Physiological effect

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