Mulberry (Morus alba L.): Risk of herb–drug interactions via alteration of phase I and II metabolizing enzymes and transporters in HepG2 cells

Wachirawit Udomsak Waranya Chatuphonprasert Wipawee Tukum-mee Jintanaporn Wattanathorn Kanokwan Jarukamjorn   

Open Access   

Published:  Sep 04, 2022

DOI: 10.7324/JAPS.2022.121202

Mulberry (Morus alba Linn; MA) is a food supplement that may cause herb–drug interactions (HDIs). Potential interactions of MA, its constituents cyanidin 3-glucoside (C3G) and rutin, and four common pharmacologically active agents were examined in HepG2 cells. Cells were incubated with 1–10 μM C3G, 1–10 μM rutin, and 125–500 μg/ ml MA alone and in combination with 5 mM acetaminophen (APAP), 5 mM aspirin (ASA), 10 μM simvastatin (SV), or 50 μM caffeine (CF) for 72 hours. The expressions of phase I and II metabolizing enzymes and transporters were determined by RT/qPCR. When tested alone, MA significantly upregulated the expression of CYP1A2 and UDP-glucuronosyltransferase 1A6 (UGT1A6). Cotreatment of HepG2 cells with APAP, ASA, SV, or CF, and MA resulted in upregulation of CYP1A2 and N-acetyltransferase 1 expression and downregulation of ATP-binding cassette B1 and solute carrier organic anion 1B1 expression. Combining MA with APAP, ASA, or SV elevated CYP2C19 expression, and MA and ASA coinduced the expression of CYP2D6. Coadministration of MA with APAP or ASA increased UGT1A6 expression. C3G and rutin did not affect the expression of any tested genes. Consequently, MA is recommended to be taken at a low dosage due to the feasibility of MA HDIs arising from concomitant use with APAP, ASA, SV, or caffeine.

Keyword:     Rutin cyanidin 3-glucoside metabolizing enzyme herb–drug interaction cytochrome P450 transporter


Udomsak W, Chatuphonprasert W, Tukum-mee W, Wattanathorn J, Jarukamjorn K. Mulberry (Morus alba L.): Risk of herb–drug interactions via alteration of phase I and II metabolizing enzymes and transporters in HepG2 cells. J Appl Pharm Sci, 2022;

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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