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Drug Metabolism and Disposition Fast Forward
First published on March 20, 2008; DOI: 10.1124/dmd.107.018424

0090-9556/08/3606-1135-1142$20.00
DMD 36:1135-1142, 2008

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Metabolism of Boswellic Acids in Vitro and in Vivo

Phillip Krüger, Rambod Daneshfar, Gunter P. Eckert, Jochen Klein, Dietrich A. Volmer, Ute Bahr, Walter E. Müller, Michael Karas, Manfred Schubert-Zsilavecz, and Mona Abdel-Tawab

Central Laboratory of German Pharmacists, Eschborn, Germany (P.K., M.S.-Z., M.A.-T.); Institutes of Pharmacology (G.P.E., J.K., W.E.M.) and Pharmaceutical Chemistry (U.B., M.K., M.S.-Z.), J. W. Goethe-University, Center for Drug Research, Development and Safety, Frankfurt, Germany; Institute for Marine Biosciences, National Research Council, Nova Scotia, Halifax, Canada (R.D.); and Medical Research Council, Department of Human Nutrition Research, Cambridge, United Kingdom (D.A.V.)

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 (BAs), the main active ingredients of B. 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-β-boswellic acid (KBA) and 3-acetyl-11-keto-β-boswellic acid (AKBA), the most potent BAs. To address the question of 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 metabolic profiles similar 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 B. serrata extract may be enhanced by increasing the bioavailability of AKBA.

Address correspondence to: Dr. Mona Abdel-Tawab, Zentrallaboratorium Deutscher Apotheker, Carl-Mannich-Strasse 20, D-65760 Eschborn, Germany. E-mail: m.tawab{at}zentrallabor.com






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