Single-dose comparative pharmacokinetic/pharmacodynamic study of a micellar formulation versus a native Boswellia serrata dry extract in healthy volunteers

Phytomedicine. 2024 Sep:132:155863. doi: 10.1016/j.phymed.2024.155863. Epub 2024 Jul 20.

Abstract

Background: Extracts of oleogum resins of Boswellia trees possess anti-inflammatory activities. Micellar formulations have been developed to increase the oral bioavailability of bioactive boswellic and lupeolic acids.

Purpose: The current single-dose crossover clinical trial compares for the first time pharmacokinetics/pharmacodynamics of two Boswellia serrata nutraceuticals, native Biotikon® BS-85 and micellar Boswellia-Loges®.

Methods: After oral administration of the study preparations (800 mg) to 20 healthy volunteers, plasma concentrations of 8 boswellic and lupeolic acids were measured by using HPLC-MS/MS for up to 48 h Blood samples collected 2 and 5 h after drug administration were stimulated for 24 h with endotoxic lipopolysaccharide. The release of proinflammatory cytokines analyzed by flow cytometry was used as readout of the pharmacodynamic properties of the preparations.

Registration: German Clinical Trials Register (DRKS) No. DRKS00027369.

Results: Administration of the micellar extract significantly increased Cmax, AUC0-48, and shortened Tmax for all boswellic and lupeolic acids compared to native extract. Accordingly, their relative bioavailability increased to 1,720-4,291 % with the highest difference for acetyl-11-keto-β-boswellic acid (AKBA). Both preparations reduced the release of TNF-α and the native formulation diminished also IL-1β and IL-6. However, no significant differences were observed between the preparations, except for a higher decrease in IL-1β by the native formulation Biotikon® BS-85. In a lymphocytic gene reporter cell line, both nutraceuticals similarly inhibited the NF-κB transcription factor activity as well as the TNF-α release, yet the native formulation Biotikon®BS-85 was more efficient in inhibiting TNF-α.

Conclusion: Administration of the micellar Boswellia serrata nutraceutical increased the oral bioavailability of boswellic and lupeolic acids. Yet, the increase in plasma concentration did not enhance the anti-inflammatory efficacy of the micellar extract compared to the native extract in this ex vivo model.

Keywords: Boswellia; Cytokines; Inflammation; Pharmacodynamics; Pharmacokinetics; Polysorbate.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Administration, Oral
  • Adult
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacokinetics
  • Anti-Inflammatory Agents / pharmacology
  • Biological Availability
  • Boswellia* / chemistry
  • Cross-Over Studies*
  • Cytokines / blood
  • Dietary Supplements
  • Female
  • Healthy Volunteers
  • Humans
  • Male
  • Micelles*
  • Plant Extracts* / administration & dosage
  • Plant Extracts* / chemistry
  • Plant Extracts* / pharmacokinetics
  • Plant Extracts* / pharmacology
  • Triterpenes* / pharmacokinetics
  • Triterpenes* / pharmacology
  • Young Adult

Substances

  • Anti-Inflammatory Agents
  • boswellic acid
  • Cytokines
  • Micelles
  • Plant Extracts
  • Triterpenes