An Evaluation of Potential Inhibition of CYP3A4/5 and CYP2C9 Enzymatic Activity by Boswellia serrata Extract

Amy L Roe,Jonathan P Jackson,Christopher B Black,Ashley G Herman,Hong Dai,Jason M Price,Rachel Wilcox,Lijuan Li,Kenneth R Brouwer,Weslyn W Friley,Kimberly M Freeman

doi:10.1089/aivt.2018.0023

Amy L Roe, Jonathan P Jackson + Show 9 more

Open Access

https://doi.org/10.1089/aivt.2018.0023

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Abstract

Abstract Introduction: As the use of dietary supplements increases, botanical–drug interaction (BDI) potentials should be evaluated. Boswellia serrata extract (BSE) is traditionally used as an anti...

Highlights

As the use of dietary supplements increases, botanical–drug interaction (BDI) potentials should be evaluated
Our data would suggest that BDI with Boswellia serrata extract (BSE) is low for most drugs, narrow therapeutic drugs such as warfarin should still be used with caution when combined with BSE
We focused our work on CYP2C9 and CYP3A4 since previous studies indicated that these isoforms were inhibited by BSE, and both are important in the metabolism of nonsteroidal anti-inflammatory drug (NSAID) such as ibuprofen

Summary

Introduction

As the use of dietary supplements increases, botanical–drug interaction (BDI) potentials should be evaluated. BSE has been shown to reduce the activity (55% to ‡65%) across major CYP450 enzymes, including CYP3A4/5 and CYP2C9, using baculovirus-infected insect cells. These reported results, contrasted with a seemingly history of safe use of BSE, led us to question the relevance of the results using pooled human liver microsomes (PHLM), when compared to a more physiologically relevant model such as primary human hepatocytes. Methods: This study compared PHLM and sandwich-cultured human hepatocytes (SCHH) by evaluating BSE potential inhibitory effects on CYP3A4/5 and CYP2C9 enzymatic activity. It is known that boswellic acids are absorbed from oral administration since circulating levels of several of these constituents have been documented in human plasma (Table 1).[1,2,3,4,5,6,7,8,9] To date, much focus has been on the activity of 11-keto-b-boswellic acid (KBA) and acetyl-11keto-b-boswellic acid; b-boswellic acid (BBA) levels have been shown to be 100-fold higher in human plasma.[1]

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