Zhang Qisong, Zhu Lijun, Gong Xia, Ruan Yanjiao, Yu Jia, Jiang Huangyu, Wang Ying, Qi XiaoXiao, Lu Linlin, Liu Zhongqiu
Department of Pharmaceutics, School of Pharmaceutical Sciences, Southern Medical University , Guangzhou, Guangdong 510515, China.
International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine , Guangzhou, Guangdong 510006, China.
J Agric Food Chem. 2017 Jun 21;65(24):4921-4931. doi: 10.1021/acs.jafc.7b00854. Epub 2017 Jun 8.
Acacetin, an important component of acacia honey, exerts extensive therapeutic effects on many cancers. However, the sulfonation disposition of acacetin has rarely been reported. Therefore, this study aimed to investigate the sulfonation disposition of acacetin systematically. The results showed that acacetin-7-sulfate was the main metabolite mediated primarily by sulfotransferases (SULT) 1A1. Dog liver S9 presented the highest formation rate of acacetin-7-sulfate. Compared with that in wild-type Friend Virus B (FVB) mice, plasma exposure of acacetin-7-sulfate decreased significantly in multidrug resistance protein 1 knockout (Mrp1) mice vut increased clearly in breast cancer resistance protein knockout (Bcrp) mice. In Caco-2 monolayers, the efflux and clearance of acacetin-7-sulfate was reduced distinctly by the BCRP inhibitor Ko143 on the apical side and by the MRP1 inhibitor MK571 on the basolateral side. In conclusion, acacetin sulfonation was mediated mostly by SULT1A1. Acacetin-7-sulfate was found to be transported mainly by BCRP and MRP1. Hence, SULT1A1, BCRP, and MRP1 are responsible for acacetin-7-sulfate exposure in vivo.
刺槐素是刺槐蜂蜜的一种重要成分，对多种癌症具有广泛的治疗作用。然而，刺槐素的磺化代谢情况鲜有报道。因此，本研究旨在系统地研究刺槐素的磺化代谢情况。结果表明，刺槐素 -7- 硫酸盐是主要代谢产物，主要由磺基转移酶（SULT）1A1介导。犬肝S9对刺槐素 -7- 硫酸盐的生成率最高。与野生型Friend病毒B（FVB）小鼠相比，多药耐药蛋白1基因敲除（Mrp1）小鼠体内刺槐素 -7- 硫酸盐的血浆暴露量显著降低，而乳腺癌耐药蛋白基因敲除（Bcrp）小鼠体内则明显增加。在Caco-2单层细胞中，BCRP抑制剂Ko143在顶侧显著降低了刺槐素 -7- 硫酸盐的外排和清除率，而MRP1抑制剂MK571在基底外侧也有此作用。总之，刺槐素磺化主要由SULT1A1介导。发现刺槐素 -7- 硫酸盐主要由BCRP和MRP1转运。因此，SULT1A1、BCRP和MRP1决定了体内刺槐素 -7- 硫酸盐的暴露水平。
