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

• Published in: Journal of ethnopharmacology Vol. 141; no. 2; pp. 709 - 713
• Main Authors: Qiu, Feng, Hou, Xiao-Long, Takahashi, Kyoko, Chen, Li-Xia, Azuma, Junichi, Kang, Ning
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.06.2012
• Subjects: 1α, 25-dihydroxyvitamin D3; Administration, Oral; Andrographolide; Caco-2; Caco-2 Cells; Calcitriol - pharmacology; CYP3A4; Cytochrome P-450 CYP3A - genetics; Cytochrome P-450 CYP3A - metabolism; Cytochrome P-450 CYP3A Inhibitors; Diterpenes - administration & dosage; Diterpenes - pharmacology; Dose-Response Relationship, Drug; Down-Regulation; Drugs, Chinese Herbal - administration & dosage; Drugs, Chinese Herbal - pharmacology; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - pharmacology; Gene Expression Regulation, Enzymologic - drug effects; Herb-Drug Interactions; Humans; Hydroxylation; Intestines - drug effects; Intestines - enzymology; Medicine, Chinese Traditional; Nifedipine - metabolism; Oxidation-Reduction; Plants, Medicinal; RNA, Messenger - metabolism; Testosterone - metabolism; Time Factors; 1α, 25-dihydroxyvitamin D3; Andrographolide; CYP3A4; Caco-2
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2011.09.002

The 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. Caco-2 cells are treated with 1α, 25-dihydroxyvitamin D3 for 3 wks to induce the expression of CYP3A4, and then andrographolide (1, 10, 100μM) is added and treated for 72h. Upon the further 4-h testosterone (250μM) or nifedipine (200μM) treatment, the basolateral medium samples and the Caco-2 monolayers are collected for analyses. Andrographolide (1, 10, 100μM) significantly down-regulates the mRNA level and protein level of CYP3A4, and inhibits nifedipine oxidation and testosterone 6β-hydroxylation. Oral 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.