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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Potent inhibition of CYP1A2 by Frutinone A, an active ingredient of the broad spectrum antimicrobial herbal extract from P. fruticosa
Xenobiotica, Volume 42, No. 10, Year 2012
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Description
Frutinone is an active ingredient extracted from the lipophilic fraction of the Polygala Fruticosa demonstrating various antibacterial and fungal properties. The aim of this study was to characterize its metabolism in an effort to understand metabolism based drugherb interactions. In vitro metabolic clearance and metabolite identification studies were done using cryopreserved hepatocytes. Reaction phenotyping and inhibition studies were done using human liver microsomes and recombinant cytochrome P450s (CYPs). Frutinone A-CYP1A2 interactions were rationalized using docking simulations. Hepatic clearance was predicted to be low (7.17 mL/min/kg), with reaction phenotyping studies indicating no clearance by the enzymes tested. Frutinone was identified as a potent inhibitor of CYP1A2 with moderate effects on CYP2C19, 2C9, 2D6 and 3A4. CYP1A2 inhibition was reversible and characterised by an IC50 of 0.56 M. Inhibition was differential showing mixed (Ki = 0.48 M) and competitive (Ki = 0.31 M) inhibition with 3-cyano-7-ethoxycoumarin and ethoxyresorufin, respectively. Two binding sites, one for inhibitors and the other for substrates were identified in silico. The potent CYP1A2 inhibition by Frutinone A could be predictive of the potential drugherb interaction risk in the use of herbal extracts from P. fruticosa. The data suggest future pharmacological research on this chromocoumarin should take metabolic properties into account. © 2012 Informa UK, Ltd.
Authors & Co-Authors
Thelingwani, Roslyn Stella
Zimbabwe, Harare
African Institute of Biomedical Science and Technology Aibst
South Africa, Cape Town
University of Cape Town
Dhansay, Kariema
South Africa, Cape Town
University of Cape Town
Smith, Peter John
South Africa, Cape Town
University of Cape Town
Chibale, Kelly
South Africa, Cape Town
University of Cape Town
Masimirembwa, Collen Mutowembwa
Zimbabwe, Harare
African Institute of Biomedical Science and Technology Aibst
South Africa, Cape Town
University of Cape Town
Statistics
Citations: 21
Authors: 5
Affiliations: 2
Identifiers
Doi:
10.3109/00498254.2012.681077
ISSN:
00498254
e-ISSN:
13665928
Research Areas
Noncommunicable Diseases