Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH, USA.
School of Pharmacy, Institute of Material Medica, North Sichuan Medical College, Nanchong, Sichuan, China.
Planta Med. 2021 May;87(6):498-506. doi: 10.1055/a-1351-0618. Epub 2021 Feb 11.
Radix Bupleuri is one of the most widely used herbal medicines in China for the treatment of fever, pain, and/or chronic inflammation. Quercitrin, epicatechin, and rutin, the flavonoids present in Radix Bupleuri, have been reported to display anti-inflammatory, antitumor, and antioxidant biological activities among others. Sulfation has been reported to play an important role in the metabolism of flavonoids. In this study, we aimed to systematically identify the human cytosolic sulfotransferase enzymes that are capable of catalyzing the sulfation of quercitrin, epicatechin, and rutin. Of the thirteen known human cytosolic sulfotransferases, three (cytosolic sulfotransferase 1A1, cytosolic sulfotransferase 1C2, and cytosolic sulfotransferase 1C4) displayed sulfating activity toward quercitrin, three (cytosolic sulfotransferase 1A1, cytosolic sulfotransferase 1A3, and cytosolic sulfotransferase 1C4) displayed sulfating activity toward epicatechin, and six (cytosolic sulfotransferase 1A1, cytosolic sulfotransferase 1A2, cytosolic sulfotransferase 1A3, cytosolic sulfotransferase 1B1, cytosolic sulfotransferase 1C4, and cytosolic sulfotransferase 1E1) displayed sulfating activity toward rutin. The kinetic parameters of the cytosolic sulfotransferases that showed the strongest sulfating activities were determined. To investigate the effects of genetic polymorphisms on the sulfation of quercitrin, epicatechin, and rutin, individual panels of cytosolic sulfotransferase allozymes previously prepared were analyzed and shown to display differential sulfating activities toward each of the three flavonoids. Taken together, these results provided a biochemical basis underlying the metabolism of quercitrin, epicatechin, and rutin through sulfation in humans.
柴胡是中国最广泛使用的草药之一，用于治疗发热、疼痛和/或慢性炎症。柴胡中的黄酮类化合物如槲皮素、表儿茶素和芦丁已被报道具有抗炎、抗肿瘤和抗氧化等生物活性。硫酸化被报道在黄酮类化合物的代谢中起着重要作用。在这项研究中，我们旨在系统地鉴定能够催化槲皮素、表儿茶素和芦丁硫酸化的人细胞质硫转移酶酶。在 13 种已知的人细胞质硫转移酶中，有 3 种（细胞质硫转移酶 1A1、细胞质硫转移酶 1C2 和细胞质硫转移酶 1C4）对槲皮素具有硫酸化活性，3 种（细胞质硫转移酶 1A1、细胞质硫转移酶 1A3 和细胞质硫转移酶 1C4）对表儿茶素具有硫酸化活性，6 种（细胞质硫转移酶 1A1、细胞质硫转移酶 1A2、细胞质硫转移酶 1A3、细胞质硫转移酶 1B1、细胞质硫转移酶 1C4 和细胞质硫转移酶 1E1）对芦丁具有硫酸化活性。确定了显示最强硫酸化活性的细胞质硫转移酶的动力学参数。为了研究遗传多态性对槲皮素、表儿茶素和芦丁硫酸化的影响，分析并显示先前制备的细胞质硫转移酶同工酶个体面板对三种黄酮类化合物均具有不同的硫酸化活性。总之，这些结果为槲皮素、表儿茶素和芦丁通过人硫酸化代谢提供了生化基础。
