Interactions between cytochromes P450, glutathione S-transferases and Ghanaian medicinal plants

• Published in: Food and chemical toxicology Vol. 46; no. 12; pp. 3598 - 3603
• Main Authors: Appiah-Opong, Regina, Commandeur, Jan N.M., Axson, Civianny, Vermeulen, Nico P.E.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.12.2008; Elsevier
• Subjects: aerial parts; Animals; Anti-Inflammatory Agents, Non-Steroidal - metabolism; Antitussive Agents - metabolism; Biological and medical sciences; Cassia alata; Cassia siamea; cytochrome P-450; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System - biosynthesis; Cytochromes P450; Dextromethorphan - metabolism; Diclofenac - metabolism; Enzyme inhibition; Enzyme Inhibitors; Escherichia coli; General pharmacology; Ghana; Glutathione S-transferases; glutathione transferase; Glutathione Transferase - antagonists & inhibitors; Glutathione Transferase - biosynthesis; Herb-drug interactions; herbal medicines; herbs; Hydroxylation; In Vitro Techniques; Indicators and Reagents; Lactuca; leaves; Medical sciences; medicinal plants; Membranes - drug effects; Membranes - enzymology; Momordica charantia; Morinda lucida; nutrient-drug interactions; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Phyllanthus amarus; plant extracts; Plant Extracts - chemistry; Plant Extracts - pharmacology; Plant poisons toxicology; Plants, Medicinal - chemistry; Plasmids - genetics; Rats; roots; Senna alata; Senna siamea; stems; Toxicology; traditional medicine; Ghana; Africa; Herb-drug interactions; Enzyme inhibition; DBF; GST; Glutathione S-transferases; CDNB; CYP; GSH; HPLC; Cytochromes P450; Enzyme; Transferases; Cytochrome P450; Medicinal plant; Glutathione transferase; Plant origin; Inhibitor; Drug interaction; Inhibition
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2008.09.002

Inhibition of cytochrome P450s (CYPs) is a major cause of adverse drug-drug interactions. Alternatively, inhibition of glutathione S-transferases (GSTs) may increase harmful effects of electrophilic compounds or metabolites. In the present study, aqueous extracts of seven Ghanaian medicinal plants were investigated for their inhibitory potential towards recombinant human CYP1A2, CYP2C9, CYP2D6 and CYP3A4, heterologously expressed in Escherichia coli. Effects of these extracts on recombinant human GSTA1-1, GSTM1-1, GSTP1-1, human and rat cytosolic GSTs were also investigated. Seven extracts, including Phyllanthus amarus whole plant, leaf, stem and root, Cassia siamea and Momordica charantia, inhibited CYP1A2 and CYP2C9 with IC50 values ranging between 28.3–134.3 μg/ml and between 63.4–425.9 μg/ml, respectively. Similarly, both CYP2D6 and CYP3A4 were inhibited by five extracts including Phyllanthus amarus whole plant, leaf, stem and root and Cassia alata, with IC50 values ranging between 45.8–182.0 μg/ml and between 79.2–158.8 μg/ml respectively. Human and rat liver cytosolic GSTs were inhibited with IC50 values ranging between 25.2–95.5 μg/ml and between 8.5–139.4 μg/ml, respectively. GSTM1-1 was most susceptible to the inhibition by the extracts, with IC50 values ranging between 3.6–50.0 μg/ml, whilst IC50 values of 8.9–159.0 μg/ml and 68.6–157.0 μg/ml were obtained for GSTA1-1 and GSTP1-1, respectively. These findings show a significant potential both for CYP- and GST-mediated herb–drug interactions of the Ghanaian medicinal plants investigated.