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.
Keywords: acacetin; metabolism; pharmacokinetics; sulfonation; transport.