Metabolism of Boswellic Acids in Vitro and in Vivo

Abstract

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 (BAs), the main active ingredients of B. serrata extracts, have potent antiinflammatory 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 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.

Boswellia serrata acts on cerebral edema in patients irradiated for brain tumors

“…It was further shown that boswellic acids possess potent anti-inflammatory properties in vitro by inhibiting 5-lipoxygenase, human leukocyte elastase, and the NF-jB pathway. 10,11 Cathepsin G was identified as another target of boswellic acids. 11 In clinical research, positive effects of boswellic acids in the treatment of inflammatory diseases could be shown.…”

Inhibition of microsomal prostaglandin E2 synthase‐1 as a molecular basis for the anti‐inflammatory actions of boswellic acids from frankincense

“…Similarly, AKBA and KBA failed to suppress PGE2 formation in human whole blood and in rats, despite significant inhibition of mPGES1 in the cellfree assay. The failure of KBA and AKBA to suppress LT and PGE2 formation in vivo could be related to the marginal permeability of AKBA and moderate absorption of KBA (Kruger et al, 2009), resulting in poor bioavailability (Kruger et al, 2008) with fairly low plasma concentrations (0.3 and <0.1 mM) (Buchele and Simmet, 2003;Tausch et al, 2009). The marked loss of activity of AKBA in whole blood might be related to its strong plasma protein binding .…”

Posttreatment with 11-Keto-β-Boswellic Acid Ameliorates Cerebral Ischemia–Reperfusion Injury: Nrf2/HO-1 Pathway as a Potential Mechanism

“…According to the published studies, 25 mg/kg KBA administered to rats (corresponding to about 350 mg B. serrata extract/kg) could reach to physiological concentrations in the plasma and brain [14,15]. Vehicle of 2 ml/kg physiological saline (vehicle + I/R group) and 25 mg/kg KBA (KBA+I/R group) were given 1 h after reperfusion.…”