Received for publication September 21, 2007.
Revised March 5, 2008.
Accepted for publication March 17, 2008.

Metabolism of boswellic acids in vitro and in vivo

Abstract

Boswellia serrata resin dry extract is among the few herbal remedies designated with an orphan drug status for the treatment of peritumoral brain edema. In addition, boswellic acids (BA), the main active ingredients of Boswellia serrata extracts, have potent anti-inflammatory properties, and may represent promising agents for the treatment of inflammatory diseases. Pharmacokinetic studies, however, revealed poor bioavailability, especially of 11-keto--boswellic acid (KBA) and 3-acetyl-11-keto--boswellic acid (AKBA), the most potent BAs. To address the question whether BAs are extensively metabolized, we determined the metabolic stability of KBA and AKBA in vitro, investigated the in vitro metabolism of BAs and compared the metabolic profiles of KBA and AKBA with those obtained in rats in vivo. In rat liver microsomes and hepatocytes as well as in human liver microsomes, we found that KBA but not AKBA undergoes extensive phase I metabolism. Oxidation to hydroxylated metabolites is the principal metabolic route. In vitro, KBA yielded similar metabolic profiles to those obtained in vivo in rat plasma and liver, whereas no metabolites of AKBA could be identified in vivo. Furthermore, AKBA is not deacetylated to KBA. This study indicates that the efficacy of Boswellia serrata extract may be enhanced by increasing the bioavailability of AKBA.

Key words: analytical chemistry, anti-inflammatory drugs, bioavailability, HPLC, liver microsomes, mass spectrometry, metabolite identification, microsomes