Metabolism of terpenoids in animal models and humans

Terpenoids are main constituents of plant-derived essential oils. Because of their pleasant odor, they are widely used in the food, fragrance, and pharmaceutical industry. Furthermore, in traditional medicine, terpenoids are also well known for their anti-inflammatory, antibacterial, antifungal, antitumor, and sedative activities. Although large amounts are used in the industry, the knowledge about their biotransformation in humans is still scarce. Yet, metabolism of terpenoids can lead to the formation of new biotransformation products with unique structures and often different flavor and biological activities compared to the parent compounds. All terpenoids easily enter the human body by oral absorption, penetration through the skin, or inhalation very often leading to measurable blood concentrations. A number of different enzymes, however, readily metabolize these compounds to more water-soluble molecules. Although nearly every tissue has the ability to metabolize drugs, the liver is the most important organ of drug biotransformation. In general, metabolic biotransformation occurs at two major categories called Phase I and Phase II reactions (Spatzenegger and Jäger, 1995). Phase I concerns mostly cytochrome P450 (CYP)-mediated oxidation as well as reduction and hydrolysis. Phase II is a further step where a Phase I product is completely transformed to high water solubility. This is done by attaching already highly water-soluble endogenous entities such as sugars (glucuronic acids) or salts (sulfates) to the Phase I intermediate and forming a Phase II final product. It is not always necessary for a compound to undergo both Phases I and II; indeed for many terpenoids, one or the other is enough to eliminate these volatile plant constituents. In the following concise review, special emphasis will be put on metabolism of selected mono- and sesquiterpenoids not only in animal and in vitro models but also in humans.