title: Selective reduction in the expression of UGTs and SULTs, a novel mechanism by which piperine enhances the bioavailability of curcumin in rat.
abstract: Curcumin (CUR) is known to exert numerous health-promoting effects in pharmacological studies, but its low bioavailability hinders the development of curcumin as a feasible therapeutic agent. Piperine (PIP) has been reported to enhance the bioavailability of curcumin, but the underlying mechanism remains poorly understood. In an attempt to find the mechanism by which piperine enhances the bioavailability of curcumin, the dosage ratio (CUR: PIP) and pre-treatment with piperine were hypothesized as key factors for improving the bioavailability in this combination. Therefore, combining curcumin with piperine at various dose ratios (1:1 to 100:1) and pre-dosing with piperine (0.5-8 h prior to curcumin) were designed to investigate their contributions to the pharmacokinetic parameters of curcumin in rats and their effects on the expression of UGT and SULT isoforms. It was shown that the Cmaxand AUC0-tof curcumin were slightly increased by 1.29 and 1.67 fold at a ratio of 20:1, while curcumin exposure was enhanced significantly in all the piperine pre-treated rats (0.5-8 h), peaking at 6 h (a 6.09-fold and 5.97-fold increase in Cmaxand AUC0-t, p < 0.01), regardless of the unchanged t1/2and Tmax. Also observed was a time-dependent inhibition of the hepatic expression of UGT1A6, 1A8, SULT1A1, 1A3, and the colonic expression of UGT1A6 that occurred within 6 h of piperine pre-treatment but was reversed at 8 h, which correlated with the changes in curcumin exposure. Similarly, the inhibitory effect of piperine on most of the UGTs and SULTs are time-dependent in Caco-2 and HepG2 cells. It is concluded that piperine pre-treatment time-dependently improves the bioavailability of curcumin through the reversible and selective inhibition of UGTs and SULTs. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Guangdong Province Engineering Technology Research Institute of Traditional Chinese Medicine, Guangzhou, Guangdong, 510095, PR China.|Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, Guangzhou, Guangdong, 510095, PR China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Guangdong Province Engineering Technology Research Institute of Traditional Chinese Medicine, Guangzhou, Guangdong, 510095, PR China.|Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, Guangzhou, Guangdong, 510095, PR China.
authors.forename: Dake
authors.initials: D
authors.lastname: Cai
authors.affiliation: Department of Nephrology, The Second Clinical College, Guangzhou University of Chinese Medicine and Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, PR China.|Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, PR China.
authors.forename: Qiaohuang
authors.initials: Q
authors.lastname: Zeng
authors.affiliation: Guangdong Province Engineering Technology Research Institute of Traditional Chinese Medicine, Guangzhou, Guangdong, 510095, PR China.|Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, Guangzhou, Guangdong, 510095, PR China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou, 510006, PR China.
authors.forename: Guoping
authors.initials: G
authors.lastname: Zhong
authors.affiliation: Guangdong Province Engineering Technology Research Institute of Traditional Chinese Medicine, Guangzhou, Guangdong, 510095, PR China.|Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, PR China.
authors.forename: Juncheng
authors.initials: J
authors.lastname: Zhuo
authors.affiliation: Guangdong Province Engineering Technology Research Institute of Traditional Chinese Medicine, Guangzhou, Guangdong, 510095, PR China.|Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, Guangzhou, Guangdong, 510095, PR China.
authors.forename: Haining
authors.initials: H
authors.lastname: Gan
authors.affiliation: Guangdong Province Engineering Technology Research Institute of Traditional Chinese Medicine, Guangzhou, Guangdong, 510095, PR China.|Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, Guangzhou, Guangdong, 510095, PR China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Huang
authors.affiliation: Guangdong Province Engineering Technology Research Institute of Traditional Chinese Medicine, Guangzhou, Guangdong, 510095, PR China.|Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, Guangzhou, Guangdong, 510095, PR China.
authors.forename: Ziming
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Guangdong Province Engineering Technology Research Institute of Traditional Chinese Medicine, Guangzhou, Guangdong, 510095, PR China.|Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, Guangzhou, Guangdong, 510095, PR China.
authors.forename: Nan
authors.initials: N
authors.lastname: Yao
authors.affiliation: Guangdong Province Engineering Technology Research Institute of Traditional Chinese Medicine, Guangzhou, Guangdong, 510095, PR China.|Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, Guangzhou, Guangdong, 510095, PR China.
authors.forename: Dane
authors.initials: D
authors.lastname: Huang
authors.affiliation: Guangdong Province Engineering Technology Research Institute of Traditional Chinese Medicine, Guangzhou, Guangdong, 510095, PR China.|Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, PR China.
authors.forename: Chengzhe
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Guangdong Province Engineering Technology Research Institute of Traditional Chinese Medicine, Guangzhou, Guangdong, 510095, PR China.|Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, Guangzhou, Guangdong, 510095, PR China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Sun
authors.affiliation: Guangdong Province Engineering Technology Research Institute of Traditional Chinese Medicine, Guangzhou, Guangdong, 510095, PR China.|Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, Guangzhou, Guangdong, 510095, PR China.
authors.forename: Yuxing
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D015239:Arylsulfotransferase / Q000378:metabolism*; D052117:Benzodioxoles / Q000494:pharmacology*; D001682:Biological Availability; D018938:Caco-2 Cells; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D003474:Curcumin / Q000493:pharmacokinetics*; D004347:Drug Interactions; D014453:Glucuronosyltransferase / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley
chemical_list: D000470:Alkaloids; D052117:Benzodioxoles; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D014453:Glucuronosyltransferase; D015239:Arylsulfotransferase; C573795:Sult1a1 protein, rat; C403170:monoamine-sulfating phenol sulfotransferase; D003474:Curcumin; C008922:piperine
keywords: SULT; UGT; bioavailability; curcumin; piperine