Investigation of Molecular Properties that Influence the Permeability and Oral Bioavailability of Major β-Boswellic Acids

Eur J Drug Metab Pharmacokinet. 2020 Apr;45(2):243-255. doi: 10.1007/s13318-019-00599-z.


Background and objectives: Boswellic acids (BAs) include β-boswellic acid (BA), 3-acetyl-β-boswellic acid, 11-keto-β-boswellic acid, 3-acetyl-11-keto-β-boswellic acid, β-boswellic alcohol, and 3-acetyl-11-hydroxy-β-BA from Boswellia species, and are the main active ingredients of Boswellia serrata extracts (BSE). BSE have been used for the treatment of different inflammatory diseases; however, their pharmaceutical development has been severely limited by their poor oral bioavailability. The aims of this study were to investigate the molecular properties of six BAs, and to determine their experimental aqueous solubility, partition coefficient (Log P), gastrointestinal stability, adsorption-desorption kinetics, and permeability studies.

Methods: The physicochemical properties of six BAs were obtained from SMILES representations using ChemDraw, and MarvinSketch. The molecular properties were also determined experimentally. The permeability studies were performed using parallel artificial membrane permeability assay (PAMPA), and Caco-2 cells.

Results: The experimental Log P values of BAs correlated well (R2 = 0.94) with the calculated Log P values. Metabolic stability data confirmed that BAs were found to be unstable in simulated gastrointestinal fluids and intestinal S9 fractions. The apparent permeability (Papp) range of BAs in both PAMPA and Caco-2 for the apical (AP) to basolateral (BL) was in the range of 0.52 ± 0.05 × 10-6 to 2.84 ± 0.14 × 10-6cm/s. The efflux ratio of Papp (BL → AP) to Papp (AP → BL) for all BAs was < 2 in Caco-2 cells, suggesting greater permeability in the absorptive direction. Caco-2 cell adsorption studies confirmed the accumulation of BAs (35-55%) inside the enterocytes. These compounds exhibited a strong correlation between PAMPA and Caco-2 cell monolayer permeation data.

Conclusions: The results of the present study have shown an empirical relationship between the molecular properties and intestinal absorption of BAs for the first time.

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
  • Biological Availability
  • Boswellia / chemistry*
  • Caco-2 Cells
  • Humans
  • Intestinal Absorption
  • Male
  • Permeability
  • Plant Extracts / chemistry
  • Rats
  • Rats, Sprague-Dawley
  • Solubility
  • Triterpenes / administration & dosage*
  • Triterpenes / chemistry
  • Triterpenes / pharmacokinetics


  • Anti-Inflammatory Agents, Non-Steroidal
  • Plant Extracts
  • Triterpenes
  • boswellic acid