Publication: Inhibitory effects of phyllanthus amarus and its major lignans on human microsomal cytochrome P450 activities: Evidence for CYP3A4 mechanism-based Inhibition
Issued Date
2011-01-01
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18800920
13474367
13474367
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2-s2.0-79955711858
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Mahidol University
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SCOPUS
Bibliographic Citation
Drug Metabolism and Pharmacokinetics. Vol.26, No.2 (2011), 154-161
Suggested Citation
Theerada Taesotikul, Weeraya Dumrongsakulchai, Nitsupa Wattanachai, Vichien Navinpipat, Aimon Somanabandhu, Wongwiwat Tassaneeyakul, Wichittra Tassaneeyakul Inhibitory effects of phyllanthus amarus and its major lignans on human microsomal cytochrome P450 activities: Evidence for CYP3A4 mechanism-based Inhibition. Drug Metabolism and Pharmacokinetics. Vol.26, No.2 (2011), 154-161. doi:10.2133/dmpk.DMPK-10-RG-107 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/12762
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Title
Inhibitory effects of phyllanthus amarus and its major lignans on human microsomal cytochrome P450 activities: Evidence for CYP3A4 mechanism-based Inhibition
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Abstract
Phyllanthus amarus has long been used as a herbal medicine in several countries. Phytochemicals in herbal medicine may interact with cytochromes P450 (CYP) and thus raise the potential of herb-drug interactions; therefore, the inhibitory effects of P. amarus and its major phytochemicals phyllanthin and hypophyllanthin on CYP isoforms were determined using human liver microsomes and selective substrates. Both ethanolic and aqueous extracts of P. amarus inhibited CYP1A2, CYP2D6, CYP2E1 and CYP3A4 in a dose-dependent manner. Compared to known CYP3A inhibitors, the IC 50 values of the ethanolic and aqueous extracts on testosterone 6β-hydroxylation were higher than that of ketoconazole but were lower than those of erythromycin and clarithromycin. Both extracts were weak inhibitors of CYP1A2, CYP2D6 and CYP2E1. In addition, phyllanthin and hypophyllanthin were potent mechanism-based inhibitors of CYP3A4 with K I values of 1.75 ± 1.20 μM and 2.24 ± 1.84 μM and kinact values of 0.18 ± 0.05 min -1 and 0.15 ± 0.06 min -1 , respectively. The k inact /K I ratios of these lignans were higher than those reported for some therapeutic drugs that act as mechanism-based inhibitors of CYP3A4. These results suggest that co-administration of P. amarus with drugs that are metabolized by CYP3A4 may potentially result in herb-drug interactions. © 2011 by the Japanese Society for the Study of Xenobiotics (JSSX).