Ahmmed Sk Milan, Mukherjee Pulok K, Bahadur Shiv, Kar Amit, Mukherjee Kakali, Karmakar Sanmoy, Bandyopadhyay Arun
Department of Pharmaceutical Technology, School of Natural Product Studies, Jadavpur University, Kolkata, West Bengal, India.
Indian Institute of Chemical Biology, Jadavpur, Kolkata, India.
Indian J Pharmacol. 2015 Sep-Oct;47(5):530-4. doi: 10.4103/0253-7613.165179.
The seeds of Trigonella foenum-graecum (TFG) (family: Leguminosae) are widely consumed both as a spice in food and Traditional Medicine in India. The present study was undertaken to evaluate the inhibitory effect of standardized extract of TFG and its major constituent trigonelline (TG) on rat liver microsome (RLM) and cytochrome P450 (CYP450) drug metabolizing isozymes (CYP3A4 and CYP2D6), which may indicate the possibility of a probable unwanted interaction.
Reverse phase-high performance liquid chromatography method was developed to standardize the hydroalcoholic seed extract with standard TG. The inhibitory potential of the extract and TG was evaluated on RLM and CYP isozymes using CYP450-carbon monoxide (CYP450-CO) complex assay and fluorescence assay, respectively.
The content of TG in TFG was found to be 3.38% (w/w). The CYP-CO complex assay showed 23.32% inhibition on RLM. Fluorescence study revealed that the extract and the biomarker had some inhibition on CYP450 isozymes e.g. CYP3A4 and CYP2D6 (IC50 values of the extract: 102.65 ± 2.63-142.23 ± 2.61 µg/ml and TG: 168.73 ± 4.03-180.90 ± 2.49 µg/ml) which was very less compared to positive controls ketoconazole and quinidine. Inhibition potential of TFG was little higher than TG but very less compared to positive controls.
From the present study, we may conclude that the TFG or TG has very less potential to inhibit the CYP isozymes (CYP3A4, CYP2D6), so administration of this plant extract or its biomarker TG may be safe.
葫芦巴（豆科）种子在印度作为食品香料和传统药物被广泛食用。本研究旨在评估葫芦巴标准化提取物及其主要成分胡芦巴碱（TG）对大鼠肝微粒体（RLM）和细胞色素P450（CYP450）药物代谢同工酶（CYP3A4和CYP2D6）的抑制作用，这可能表明存在潜在不良相互作用的可能性。
采用反相高效液相色谱法用标准TG对水醇提取物进行标准化。分别使用CYP450 - 一氧化碳（CYP450 - CO）复合物测定法和荧光测定法评估提取物和TG对RLM和CYP同工酶的抑制潜力。
发现葫芦巴中TG的含量为3.38%（w/w）。CYP - CO复合物测定显示对RLM有23.32%的抑制作用。荧光研究表明，提取物和生物标志物对CYP450同工酶如CYP3A4和CYP2D6有一定抑制作用（提取物的IC50值：102.65±2.63 - 142.23±2.61μg/ml，TG：168.73±4.（此处原文有误，应为4.03） - 180.90±2.49μg/ml），与阳性对照酮康唑和奎尼丁相比非常低。葫芦巴的抑制潜力略高于TG，但与阳性对照相比非常低。
从本研究中，我们可以得出结论，葫芦巴或TG抑制CYP同工酶（CYP3A4、CYP2D6）的潜力非常低，因此给予这种植物提取物或其生物标志物TG可能是安全的。
