Moringa oleifera leaf extracts inhibit 6beta-hydroxylation of testosterone by CYP3A4 - PubMed (original) (raw)

Moringa oleifera leaf extracts inhibit 6beta-hydroxylation of testosterone by CYP3A4

Tsitsi G Monera et al. J Infect Dev Ctries. 2008.

Abstract

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.

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Conflict of interest statement

Conflict of interest: No conflict of interest is declared.

Figures

Figure 1

Figure 1. Inhibitory effect of methanolic extracts of Moringa oleifera leaf and root on the CYP3A-mediated 6β-hydroxylation of testosterone

As described in Materials and Methods, 100 μM of testosterone was incubated with 0.4 mg/ml of human liver microsomes for 60 minutes, and metabolite formation was measured by HPLC. The inhibition vs. time data was fitted to equation (1), for root extract, or equation (2), for leaf extract, using nonlinear regression; this gives an IC50 value of 0.5 mg/ml for methanolic leaf extract.

Figure 2

Figure 2. Inhibitory effect of aqueous extracts of Moringa oleifera leaf and root on the CYP3A-mediated 6β-hydroxylation of testosterone by human liver microsomes

As described in Materials and Methods, 100 μM of testosterone was incubated with 0.4 mg/ml of human liver microsomes for 60 minutes, and metabolite formation was measured by HPLC. The inhibition vs. time data was fitted to equation (1) using nonlinear regression, giving an IC50 value of 2.5 mg/ml for aqueous leaf extract.

Figure 3

Figure 3. Cytotoxicity of methanolic and aqueous extracts of Moringa oleifera leaf and root on HepG2 human hepatocellular carcinoma cells as measured by the MTT assay

As described in Materials and Methods, HepG2 cells were exposed to Moringa extracts at the concentrations shown for 48 hours, then exposed to MTT for 3 hours, and the formation of formazan was measured. IC50 values for the aqueous leaf extract and the positive control paracetamol (obtained by fitting the data to equation (1) using nonlinear regression) were 6 mg/ml and 12 mM, respectively. Standard deviations for triplicate determinations are indicated.

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