Interactions between cytochromes P450, glutathione S-transferases and Ghanaian medicinal plants.
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 28.3-134.3microg/ml and between 63.4-425.9microg/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 45.8-182.0microg/ml and between 79.2-158.8microg/ml respectively. Human and rat liver cytosolic GSTs were inhibited with IC50 values ranging between 25.2-95.5microg/ml and between 8.5-139.4microg/ml, respectively. GSTM1-1 was most susceptible to the inhibition by the extracts, with IC50 values ranging between 3.6-50.0microg/ml, whilst IC50 values of 8.9-159.0microg/ml and 68.6-157.0microg/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.
Appiah-Opong
Regina
R
Department of Pharmacochemistry, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands.
Commandeur
Jan N M
JN
Axson
Civianny
C
Vermeulen
Nico P E
NP
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism; D000996:Antitussive Agents / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D003915:Dextromethorphan / Q000378:metabolism; D004008:Diclofenac / Q000378:metabolism; D004791:Enzyme Inhibitors; D005869:Ghana; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D006900:Hydroxylation; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008566:Membranes / Q000187:drug effects / Q000201:enzymology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry*; D010957:Plasmids / Q000235:genetics; D051381:Rats
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000996:Antitussive Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D010936:Plant Extracts; D004008:Diclofenac; D003915:Dextromethorphan; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase