Inhibitory effects of Thai herbal extracts on the cytochrome P450 3A-mediated the metabolism of gefitinib, lapatinib and sorafenib
Herbal products are widely used in cancer patients via co−administration with chemotherapy. Previous studies have demonstrated that pharmacokinetic interactions between herbs and anticancer drugs exist due to inhibition of drug−metabolizing enzymes, particularly cytochrome P450s (CYPs). The aim of t...
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Elsevier
2022-01-01
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| Series: | Toxicology Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214750022002001 |
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| author | Chumaphorn Rodseeda Paveena Yamanont Darawan Pinthong Porntipa Korprasertthaworn |
| author_facet | Chumaphorn Rodseeda Paveena Yamanont Darawan Pinthong Porntipa Korprasertthaworn |
| author_sort | Chumaphorn Rodseeda |
| collection | DOAJ |
| description | Herbal products are widely used in cancer patients via co−administration with chemotherapy. Previous studies have demonstrated that pharmacokinetic interactions between herbs and anticancer drugs exist due to inhibition of drug−metabolizing enzymes, particularly cytochrome P450s (CYPs). The aim of this study was to determine the inhibitory effects of Andrographis paniculata, Curcuma zedoaria, Ganoderma lucidum, Murdannia loriformis and Ventilago denticulata extracts on the metabolism of gefitinib, lapatinib and sorafenib. The activities of CYP3A in human liver microsome on the metabolism of gefitinib, lapatinib and sorafenib in the absence and presence of Thai herbal extracts were assayed using high-performance liquid chromatography analysis. Curcuma zedoaria extract potently inhibited CYP3A−mediated lapatinib and sorafenib metabolism with IC50 values of 4.18 ± 3.20 and 7.59 ± 1.23 μg/mL, respectively, while the metabolism of gefitinib was strongly inhibited by Murdannia loriformis and Ventilago denticulata extracts with IC50 values of 7.53 ± 2.87 and 7.06 ± 1.23 μg/mL, respectively. Andrographis paniculata and Ganoderma lucidum extracts had less effect on the metabolism of the tested anticancers (IC50 values >10 μg/mL). In addition, kinetic analysis of the ability of Curcuma zedoaria extract to inhibit CYP3A-mediated metabolism of anticancer drugs was best described by the noncompetitive and competitive inhibition models with Ki values of 20.08 and 11.55 μg/mL for the metabolism of gefitinib and sorafenib, respectively. The present study demonstrated that there were potential pharmacokinetic interactions between tyrosine kinase inhibitors and herbal extracts. |
| first_indexed | 2024-04-11T06:22:29Z |
| format | Article |
| id | doaj.art-fac47667ba22412b90045a110713435e |
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| issn | 2214-7500 |
| language | English |
| last_indexed | 2024-04-11T06:22:29Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
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| series | Toxicology Reports |
| spelling | doaj.art-fac47667ba22412b90045a110713435e2022-12-22T04:40:32ZengElsevierToxicology Reports2214-75002022-01-01918461852Inhibitory effects of Thai herbal extracts on the cytochrome P450 3A-mediated the metabolism of gefitinib, lapatinib and sorafenibChumaphorn Rodseeda0Paveena Yamanont1Darawan Pinthong2Porntipa Korprasertthaworn3Graduate Program in Toxicology, Faculty of Science, Mahidol University, Bangkok, Thailand; Department of Occupational Health and Safety, School of Public Health, University of Phayao, Phayao, Thailand; Center of Excellence on Environmental Health and Toxicology (EHT), OPS, MHESI, ThailandDepartment of Pharmacology, Faculty of Science, Mahidol University, Bangkok, ThailandDepartment of Pharmacology, Faculty of Science, Mahidol University, Bangkok, ThailandGraduate Program in Toxicology, Faculty of Science, Mahidol University, Bangkok, Thailand; Center of Excellence on Environmental Health and Toxicology (EHT), OPS, MHESI, Thailand; Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand; Correspondence to: Department of Pharmacology, Faculty of Science, Mahidol University, 272 Rama VI Road, Ratchathewi, Bangkok 10400, Thailand.Herbal products are widely used in cancer patients via co−administration with chemotherapy. Previous studies have demonstrated that pharmacokinetic interactions between herbs and anticancer drugs exist due to inhibition of drug−metabolizing enzymes, particularly cytochrome P450s (CYPs). The aim of this study was to determine the inhibitory effects of Andrographis paniculata, Curcuma zedoaria, Ganoderma lucidum, Murdannia loriformis and Ventilago denticulata extracts on the metabolism of gefitinib, lapatinib and sorafenib. The activities of CYP3A in human liver microsome on the metabolism of gefitinib, lapatinib and sorafenib in the absence and presence of Thai herbal extracts were assayed using high-performance liquid chromatography analysis. Curcuma zedoaria extract potently inhibited CYP3A−mediated lapatinib and sorafenib metabolism with IC50 values of 4.18 ± 3.20 and 7.59 ± 1.23 μg/mL, respectively, while the metabolism of gefitinib was strongly inhibited by Murdannia loriformis and Ventilago denticulata extracts with IC50 values of 7.53 ± 2.87 and 7.06 ± 1.23 μg/mL, respectively. Andrographis paniculata and Ganoderma lucidum extracts had less effect on the metabolism of the tested anticancers (IC50 values >10 μg/mL). In addition, kinetic analysis of the ability of Curcuma zedoaria extract to inhibit CYP3A-mediated metabolism of anticancer drugs was best described by the noncompetitive and competitive inhibition models with Ki values of 20.08 and 11.55 μg/mL for the metabolism of gefitinib and sorafenib, respectively. The present study demonstrated that there were potential pharmacokinetic interactions between tyrosine kinase inhibitors and herbal extracts.http://www.sciencedirect.com/science/article/pii/S2214750022002001Herbal extractTyrosine kinase inhibitorCytochrome P450 3ADrug−herb interaction |
| spellingShingle | Chumaphorn Rodseeda Paveena Yamanont Darawan Pinthong Porntipa Korprasertthaworn Inhibitory effects of Thai herbal extracts on the cytochrome P450 3A-mediated the metabolism of gefitinib, lapatinib and sorafenib Toxicology Reports Herbal extract Tyrosine kinase inhibitor Cytochrome P450 3A Drug−herb interaction |
| title | Inhibitory effects of Thai herbal extracts on the cytochrome P450 3A-mediated the metabolism of gefitinib, lapatinib and sorafenib |
| title_full | Inhibitory effects of Thai herbal extracts on the cytochrome P450 3A-mediated the metabolism of gefitinib, lapatinib and sorafenib |
| title_fullStr | Inhibitory effects of Thai herbal extracts on the cytochrome P450 3A-mediated the metabolism of gefitinib, lapatinib and sorafenib |
| title_full_unstemmed | Inhibitory effects of Thai herbal extracts on the cytochrome P450 3A-mediated the metabolism of gefitinib, lapatinib and sorafenib |
| title_short | Inhibitory effects of Thai herbal extracts on the cytochrome P450 3A-mediated the metabolism of gefitinib, lapatinib and sorafenib |
| title_sort | inhibitory effects of thai herbal extracts on the cytochrome p450 3a mediated the metabolism of gefitinib lapatinib and sorafenib |
| topic | Herbal extract Tyrosine kinase inhibitor Cytochrome P450 3A Drug−herb interaction |
| url | http://www.sciencedirect.com/science/article/pii/S2214750022002001 |
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