Assessing Potential Herb-Drug Interactions Using a Common Framework Approach: Boswellia serrata as a Case Study
As the use of dietary supplements increases, herb-drug interaction (HDI) potential should be evaluated using a systematic approach. Considerations such as history of safe use, literature data, and extract/constituent characterization may guide whether to assess HDIs experimentally. Boswellia serrata extract (BSE) is traditionally used for inflammatory diseases (e.g., arthritis). Potent in vitro inhibition (≥65%) across major drug metabolizing enzymes (e.g., CYP3A4/5, CYP2C9) using pooled human liver microsomes (PHLM) have been reported in the literature for levels of BSE. This potent inhibition contrasted with a history of safe use of BSE, led us to question the relevance of the results using PHLM. We chose to study the in vitro inhibition potential of BSE against CYP3A4/5 and CYP2C9, using a sandwich-cultured human hepatocyte (SCHH) system, and compare generated IC50 values between SCHH and PHLM. In SCHH, direct inhibition of CYP3A4/5 by BSE was observed resulting in an IC50= 17.2 µg/mL, versus IC50= 1.4 µg/mL with PHLM. IC50 values for CYP2C9 inhibition by BSE were > 75 µg/mL versus 11 µg/mL using SCHH or PHLM; respectively. Analytical characterization of BSE used in these in vitro studies has been conducted which includes identification of the major boswellic acids. Further work is underway to analyze SCHH cell lysates to determine intracellular concentrations of key boswellic acids (e.g., β-boswellic acid and 11-Keto-β-boswellic acid). An overall prediction of HDI relevant to BSE used in dietary supplement products may be further defined by combining data from in vitro studies, analytical characterization of extracts, published clinical data, and product formulation considerations. In summary, our proposed integrated and sophisticated approach for assessing HDI potential of dietary supplement ingredients can be consistently applied across herbal extracts.