Andrographolide inhibits the expression and metabolic activity of cytochrome P450 3A4 in the modified Caco-2 cells

Aim of the studyThe aim of this study is to examine the effects of andrographolide on intestinal enzyme cytochrome P450 3A4 (CYP3A4) and predict whether oral administration of andrographolide-containing remedy leads to herb–drug interaction.Materials and methodsCaco-2 cells are treated with 1α, 25-dihydroxyvitamin D3 for 3 wks to induce the expression of CYP3A4, and then andrographolide (1, 10, 100 μM) is added and treated for 72 h. Upon the further 4-h testosterone (250 μM) or nifedipine (200 μM) treatment, the basolateral medium samples and the Caco-2 monolayers are collected for analyses.ResultsAndrographolide (1, 10, 100 μM) significantly down-regulates the mRNA level and protein level of CYP3A4, and inhibits nifedipine oxidation and testosterone 6β-hydroxylation.ConclusionOral administration of andrographolide likely leads to reduction of the metabolic activity of intestinal CYP3A4, therefore herb preparations containing andrographolide may result to herb–drug interactions in combination therapy.

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