Moringa oleifera leaf extracts inhibit 6beta-hydroxylation of testosterone by CYP3A4.
BACKGROUND
Moringa oleifera is a tropical tree often used as a herbal medicine, including by people who test positive for HIV. Since herbal constituents may interact with drugs via inhibition of metabolizing enzymes, we investigated the effects of extracts of M. oleifera on the CYP3A4-mediated 6beta-hydroxylation of testosterone.


METHODS
Methanolic and aqueous leaf and root of extracts of M. oleifera with concentrations between 0.01 and 10 mg/ml were incubated with testosterone and mixed-sex human liver microsomes in the presence of NADPH. Metabolite concentrations were determined by HPLC. The cytotoxicity of the extracts was tested with HepG2 cells using the MTT formazan assay.


RESULTS
Significant CYP3A4 inhibitory effects were found, with IC50 values of 0.5 and 2.5 mg/ml for leaf-methanol and leaf-water extracts, respectively. Root extracts were less active. Cytotoxicity was observed only with the leaf-water extract (IC50 = 6 mg/ml).


CONCLUSIONS
Further investigation is warranted to elucidate the potential of M. oleifera for clinically significant interactions with antiretroviral and other drugs.
Monera
Tsitsi G
TG
University of Zimbabwe, School of Pharmacy, Harare, Zimbabwe. moneratg@yahoo.co.uk.
Wolfe
Alan R
AR
Maponga
Charles C
CC
Benet
Leslie Z
LZ
Guglielmo
Joseph
J
D023241:Antiretroviral Therapy, Highly Active; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D065692:Cytochrome P-450 CYP3A Inhibitors; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D006900:Hydroxylation; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D029588:Moringa oleifera; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000009:adverse effects*; D018515:Plant Leaves; D018517:Plant Roots; D013739:Testosterone / Q000737:chemistry / Q000378:metabolism*
D065692:Cytochrome P-450 CYP3A Inhibitors; D010936:Plant Extracts; D013739:Testosterone; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human