Inhibitory Activities of Thai Medicinal Plants with Promising Activities Against Malaria and Cholangiocarcinoma on Human Cytochrome P450.
Malaria and cholangiocarcinoma remain important public health problems in tropical countries including Southeast Asian nations. Newly developed chemotherapeutic and plant-derived drugs are urgently required for the control of both diseases. The aim of the present study was to investigate the propensity to inhibit cytochrome P450-mediated hepatic metabolism (CYP1A2, CYP2C19, CYP2D6 and CYP3A4) of the crude ethanolic extract of eight Thai medicinal plants with promising activities against malaria and cholangiocarcinoma, using human liver microsomes in vitro. Piper chaba Linn. (PC) and Atractylodes lancea (thung.) DC. (AL) exhibited the most potent inhibitory activities on CYP1A2-mediated phenacetin O-deethylation with mean IC50 of 0.04 and 0.36 µg/mL, respectively. Plumbago indica Linn. (PI) and Dioscorea membranacea Pierre. (DM) potently inhibited CYP2C19-mediated omeprazole 5-hydroxylation (mean IC50 4.71 and 6.92 µg/mL, respectively). DM, Dracaena loureiri Gagnep. (DL) and PI showed the highest inhibitory activities on dextromethorphan O-demethylation (mean IC50 2.93-9.57 µg/mL). PC, DM, DL and PI exhibited the most potent inhibitory activities on CYP3A4-mediated nifedipine oxidation (mean IC50 1.54-6.43 µg/mL). Clinical relevance of the inhibitory potential of DM, PC and PI is of concern for the further development of these plants for the treatment of malaria and/or cholangiocarcinoma.
Graduate Program in Biomedical Sciences, Faculty of Allied Health Sciences, Thammasat University, Pathumthani, 12121, Thailand.
Wiriyaporn
W
Sumsakul
Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University, Pathumthani, 12121, Thailand.
Wiratchanee
W
Mahavorasirikul
Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University, Pathumthani, 12121, Thailand.
Kesara
K
Na-Bangchang
D000962:Antimalarials / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D031174:Atractylodes / Q000737:chemistry; D001650:Bile Duct Neoplasms / Q000201:enzymology / Q000473:pathology; D018281:Cholangiocarcinoma / Q000201:enzymology* / Q000473:pathology; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D027742:Dioscorea / Q000737:chemistry; D031409:Dracaena / Q000737:chemistry; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D010615:Phenacetin; D031701:Piper / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry*; D029606:Plumbaginaceae / Q000737:chemistry
D000962:Antimalarials; D000972:Antineoplastic Agents, Phytogenic; D065607:Cytochrome P-450 Enzyme Inhibitors; D010936:Plant Extracts; D003577:Cytochrome P-450 Enzyme System; D010615:Phenacetin
cholangiocarcinoma; cytochrome P450; enzyme inhibition; malaria; medicinal plants