Inhibition of Cytochrome P450 2C9 by essential oils

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

Abstract: Cytochrome P450 enzymes (CYP450) are the prominent member of a family of xenobiotic metabolizing enzymes that are collectively referred to as Phase 1 enzymes (1). Phase 1 enzymes are responsible for taking reactive oxygen molecules and introducing them to inactive nonpolar substrates. By doing this, this makes the substrate more polar which it allows it to be easily excreted from the body (1). They catalyze a monooxygenase reaction that involves a substrate (RH) that is oxidized by the addition of one oxygen from molecular oxygen (O2). These redox reactions can result in the production of reactive oxygen species which can cause oxidative stress in cells (1). This study was designed to better understand the effect that essential oils had on the activity of Cytochrome P450 2C9. The goal was to determine the potency of essential oils that caused the activity of CYP2C9 to drop to 50% or lower. The sixty essential oils were tested were: all spice, anise, bergamot, birch, camphor, cardamom, carrot seed, cedarwood, cinnamon leaf, citronella, clary sage, clove bud, coriander, p-Cymene, cypress, dill seed, douglas fir, elemi, eucalyptus lemon, eugenol, fennel, frankincense, geranium bourbon, ginger, grapefruit, hyssop, jasmine absolute, juniper berry, lavender, lemongrass, lime, mandarin, marjoram, melissa pure, myrtle, myrrh, neroli, oregano vulgare, patchouli, pepper (black), pennyroyal, peppermint, petitgrain, pine needle, ravensara, roman chamomile, rose absolute, rosemary, rosemary verbenon, rosewood, sage, sandalwood, spearmint, spruce needle, tangerine, thyme borneal, vanilla absolute, wintergreen, and ylang ylang. An initial screening process was done on all sixty essential oils to see which oils inhibited the activity of CYP2C9 by 50% or more. The screening process found that there were seventeen oils that had the potential to be potent inhibitors of CYP2C9. Those oils were: all spice, bergamot, cardamom, carrot seed, cinnamon leaf, citronella, clary sage, clove bud, elemi, eugenol, geranium bourbon, ginger, neroli, oregano vulgare, and vanilla absolute. The seventeen oils that decreased the activity of CYP2C9 to 50% or less were then analyzed using Michaelis-Menten kinetics to determine the Ki of the oils. Of the seventeen oils tested, four oils, cinnamon leaf, clary sage, elemi, and oregano vulgare, had Ki values of 10 µg/mL or below. Having a Ki of 10 µg/mL or below shows that these four oils have the potential to be potent inhibitors of drug metabolism for CYP2C9. Oregano vulgare was found to be the most potent inhibitor with a Ki value of 7 µg/mL and vanilla absolute was found to be the least potent inhibitor with a Ki value of 135 µg/mL. The Michaelis-Menten kinetics also allowed for the type of inhibition to be classified as well. Following the Michaelis-menten kinetics, reversibility studies and rate of inactivation studies were done on select essential oils to further classify the oils.

Additional Information

Language: English
Date: 2015
Cytochrome P450, Essential Oils, Natural Products
Cytochrome P-450 $x Inhibitors
Enzyme inhibitors
Essences and essential oils $x Physiological effect

Email this document to