Improving metabolic stability of cancer chemoprotective polyphenols.
Dietary flavonoids and other polyphenols have the potential to be developed as effective food supplements as well as drugs for the prevention, as well as treatment of, cancer and other disease conditions. However, their very poor oral bioavailability, mainly due to extensive conjugation by glucuronidation and sulfation, is a severe limiting factor. First, this review shows the use of a simple, commercially available model system, the human hepatic S9 fraction, by which metabolic stability can be assessed effectively and accurately. Second, permethylation of the polyphenols effectively blocks the metabolic conjugation reactions, thereby dramatically increasing both metabolic stability and intestinal absorption, while maintaining or even increasing the biologic activities. Thus, permethylated polyphenols may have a future as chemoprotective agents.
Walle
Thomas
T
Medical University of South Carolina, Department of Cell and Molecular Pharmacology and Experimental Therapeutics, 173 Ashley Avenue, Charleston, SC 29425, USA. wallet@musc.edu
Wen
Xia
X
Walle
U Kristina
UK
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D005419:Flavonoids / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D006801:Humans; D007408:Intestinal Absorption; D008099:Liver / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism; D008745:Methylation; D015394:Molecular Structure; D010636:Phenols / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D059808:Polyphenols
D000970:Antineoplastic Agents; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols