Graduate Program in Biomedical Sciences, Faculty of Allied Health Sciences, Thammasat University, Pathumthani, 12121, Thailand.
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.
Phytother Res. 2015 Dec;29(12):1926-33. doi: 10.1002/ptr.5485. Epub 2015 Oct 22.
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.
疟疾和胆管癌仍然是包括东南亚国家在内的热带国家的重要公共卫生问题。迫切需要新开发的化疗药物和植物来源的药物来控制这两种疾病。本研究的目的是使用人肝微粒体在体外研究 8 种具有抗疟疾和胆管癌活性的泰国药用植物的粗乙醇提取物对细胞色素 P450 介导的肝代谢（CYP1A2、CYP2C19、CYP2D6 和 CYP3A4）的抑制倾向。Piper chaba Linn. (PC) 和 Atractylodes lancea (thung.) DC. (AL) 对 CYP1A2 介导的苯乙酮 O-去乙基化表现出最强的抑制活性，其平均 IC50 分别为 0.04 和 0.36 μg/mL。Plumbago indica Linn. (PI) 和 Dioscorea membranacea Pierre. (DM) 强烈抑制 CYP2C19 介导的奥美拉唑 5-羟化（平均 IC50 分别为 4.71 和 6.92 μg/mL）。DM、Dracaena loureiri Gagnep. (DL) 和 PI 对右美沙芬 O-去甲基化显示出最高的抑制活性（平均 IC50 为 2.93-9.57 μg/mL）。PC、DM、DL 和 PI 对硝苯地平氧化的抑制活性最强（平均 IC50 为 1.54-6.43 μg/mL）。DM、PC 和 PI 的抑制潜力的临床相关性令人关注，因为这些植物可能会进一步开发用于治疗疟疾和/或胆管癌。
