Potential inhibition of major human cytochrome P450 isoenzymes by selected tropical medicinal herbs—Implication for herb–drug interactions

The potential of aqueous extracts of tropical medicinal herbs in inhibiting Cytochrome P450 isoenzymes in vitro and the implication for herb–drug interaction was studied. Of the nine selected widely used medicinal herbs, three (Picralima nitida, Mangifera indica, and Alstonia boonei) showed significant in vitro inhibition of major human cytochrome P450. Furthermore, in vivo investigations are required for these three herbs.

Abstract

Background

Increasing use of medicinal herbs as nutritional supplements and traditional medicines for the treatment of diabetes, hypertension, hyperlipidemia, and malaria fever with conventional drugs poses possibilities of herb–drug interactions (HDIs). The potential of nine selected widely used tropical medicinal herbs in inhibiting human cytochrome P450 (CYP) isoenzymes was investigated.

Materials and methods

In vitro inhibition of eight major CYP isoenzymes by aqueous extracts of Allium sativum, Gongronema latifolium, Moringa oleifera, Musa sapientum, Mangifera indica, Tetracarpidium conophorum, Alstonia boonei, Bauhinia monandra, and Picralima nitida was estimated in human liver microsomes by monitoring twelve probe metabolites of nine probe substrates with UPLC/MS‐MS using validated N‐in‐one assay method.

Results

Mangifera indica moderately inhibited CYP2C8, CYP2B6, CYP2D6, CYP1A2, and CYP2C9 with IC₅₀ values of 37.93, 57.83, 67.39, 54.83, and 107.48 μg/ml, respectively, and Alstonia boonei inhibited CYP2D6 (IC₅₀ = 77.19 μg/ml). Picralima nitida inhibited CYP3A4 (IC₅₀ = 45.58 μg/ml) and CYP2C19 (IC₅₀ = 73.06 μg/ml) moderately but strongly inhibited CYP2D6 (IC₅₀ = 1.19 μg/ml). Other aqueous extracts of Gongronema latifolium, Bauhinia monandra, and Moringa oleifera showed weak inhibitory activities against CYP1A2. Musa sapientum, Allium sativum, and Tetracarpidium conophorum did not inhibit the CYP isoenzymes investigated.

Conclusion

Potential for clinically important CYP‐metabolism‐mediated HDIs is possible for Alstonia boonei, Mangifera indica, and Picralima nitida with drugs metabolized by CYP 2C8, 2B6, 2D6, 1A2, 2C9, 2C19, and 3A4. Inhibition of CYP2D6 by Picralima nitida is of particular concern and needs immediate in vivo investigations.

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