Glutathione sulfotransferase inhibition activity of a self-fermented beverage, Kanji

Context:Kanji, a liquid preparation of roots of Daucus carota L. ssp. sativus (Hoffm.) Arcang. var. vavilovii Mazk. (Apiaceae), may inhibit glutathione sulfotransferase (GST) activity due to ferulic acid content. Objectives: GST inhibition activity and characterization of Kanji and methanol extract of D. carota roots, and oral absorption pattern of ferulic acid from Kanji in rats. Materials and methods: GST inhibition activity of Kanji and methanol extract of D. carota roots in concentration range 0.001–100.00 mg/mL was determined using Sprague Dawley rat liver cytosolic fraction. Methanol extract upon column chromatography gave ferulic acid, which was used to characterize Kanji and determine its oral absorption pattern in Wistar rats. Results: The GST inhibition activity of Kanji (100.00 μg/mL), methanol extract of D. carota roots (100.00 μg/mL) and tannic acid (10.00 μg/mL, positive control) was found to be 0.162 ± 0.016, 0.106 ± 0.013 and 0.073 ± 0.004 μM/min/mg, respectively. Different Kanji samples and methanol extract contained ferulic acid (0.222–0.316 mg/g) and 0.77 mg/g, respectively. Ferulic acid did not appear in plasma after oral administration of Kanji. Discussion:Kanji having solid contents 80.0 μg/mL, equivalent to 0.0025 μg/mL ferulic acid, does not inhibit the activity of GST. The oral administration of Kanji, in human equivalent dose (528 mg/kg, 16.67 μg ferulic acid), to rats indicated poor absorption of ferulic acid. Conclusion:Kanji having solid contents 14–36 mg/mL does not inhibit GST activity, hence may not interfere with drugs that are the substrates of GST, if taken concomitantly.

背景：Kanji是由伞形科（Apiaceae）胡萝卜（Daucus carota L. ssp. sativus (Hoffm.) Arcang. var. vavilovii Mazk.）的根制备得到的液体制剂，因其含有阿魏酸（ferulic acid），可能会抑制谷胱甘肽磺基转移酶（glutathione sulfotransferase, GST）的活性。
研究目的：对Kanji及胡萝卜根甲醇提取物进行成分表征并测定其GST抑制活性，同时探究阿魏酸经Kanji给药后在大鼠体内的口服吸收规律。
材料与方法：采用斯波雷-道利（SD）大鼠肝胞质组分，测定浓度范围为0.001~100.00 mg/mL的Kanji及胡萝卜根甲醇提取物的GST抑制活性。对胡萝卜根甲醇提取物进行柱层析分离得到阿魏酸，以此作为对照物质完成Kanji的成分表征，并探究阿魏酸经Kanji给药后在Wistar大鼠体内的口服吸收规律。
实验结果：当给药浓度为100.00 μg/mL时，Kanji、胡萝卜根甲醇提取物以及阳性对照鞣酸（tannic acid，10.00 μg/mL）的GST抑制活性分别为0.162±0.016、0.106±0.013及0.073±0.004 μM/min/mg。不同批次Kanji样品及胡萝卜根甲醇提取物中的阿魏酸含量分别为0.222~0.316 mg/g与0.77 mg/g。经口给予Kanji后，大鼠血浆中未检测到阿魏酸。
讨论：当固体含量为80.0 μg/mL（对应阿魏酸浓度为0.0025 μg/mL）时，Kanji不会抑制GST活性。以人体等效剂量（528 mg/kg，含阿魏酸16.67 μg）给大鼠经口给予Kanji，结果显示阿魏酸的口服吸收情况较差。
结论：固体含量为14~36 mg/mL的Kanji不会抑制GST活性，因此若与作为GST底物的药物联合使用，可能不会产生药物相互作用。