Bioactive natural products are consumed as food, dietary supplements and to a lesser extent as pharmaceutical products. A vast number of phytochemicals present in plant-based functional foods and dietary supplements exert not only desired biological effects but also complex interactions, which demonstrate themselves as pharmacological effects. Phytochemicals can alter the pharmacokinetic properties of conventional pharmaceuticals by enzyme inhibition/activation (cytochrome P450, glutathione S-transferase, glucuronyl transferase), P-glycoprotein (Pgp) activation or inhibition, altered Pgp expression and membrane fluidity, modulated drug solubility and uptake, and others.1,2) The most common users of herbal medicines are elderly patients prone to conditions treated by chronic therapy with conventional medicines. Therefore, the interactions of herbal medicines with prescribed drugs are very likely in this subpopulation and could result in cases of clinically adverse reactions. 3,4) It is also important since the consumption of herbal medicines (such as the best selling representatives St. John's worth, ginseng, garlic, Echinacea, saw palmetto and kava) is rising continuously. 3,5) P-glycoprotein and multidrug resistance associated protein 2 (MRP-2) are ATP-dependent multidrug transporter proteins, expressed in several cancer cell lines and in normal tissues of liver, kidney, blood-brain barrier, placenta and small intestine.2,6,7) The intestinal secretion of drugs and/or their metabolites from enterocytes into the intestinal lumen by apically located efflux proteins constitutes a potential biochemical barrier that can limit the rate and extent of drug absorption.2,7) The modulatory effect of several food components has been established, especially on Pgp, while data on MRP-2 are sparse.2,8) High-throughput screening essays, utilizing Pgp, human liver microsomes and cDNA expressed cytochromes, have shown the influence of garlic, garlic preparations and other phytochemicals on Pgp activity and on cytochrome P (CyP) 450 2C9, 2C19, 2D, and 3A4 enzyme function.2,5,9,10) Garlic also significantly increased the activity of lipase and amylase, and decreased the activity of chymotrypsin, lactase and maltase.11) An interaction of garlic with CyP3A4 metabolism and Pgp transport was even suspected to cause the case of extreme gastrointestinal toxicity of ritonavir.
12)Garlic and its extracts are used in particular because of their cholesterol and blood pressure lowering effects and their ability to prevent infections, atherosclerotic processes and to improve circulation.3) Garlic supplements are available as powder, garlic essential oil, macerated garlic oil and as aged garlic extract (AGE).2,5,13) AGE is formulated by soaking sliced raw garlic (Allium sativum) in 5-20% aqueous ethanol for up to 20 months at room temperature. The extract is then filtered and concentrated under reduced pressure at low temperature. The content of water soluble compounds is relatively high, while that of oil-soluble compounds is low. 14) In the m...
