title: SGLT-1 Transport and Deglycosylation inside Intestinal Cells Are Key Steps in the Absorption and Disposition of Calycosin-7-O-β-d-Glucoside in Rats.
abstract: Hydrolysis by lactase-phloridzin hydrolase (LPH) is the first and critical step in the absorption of isoflavonoid glucosides. However, the absorption characteristics of calycosin-7-O-β-d-glucoside (CG) slightly differ from other isoflavonoid glucosides. In this study, we used the rat intestinal perfusion model and performed pharmacokinetic studies and in vitro experiments to determine the factors influencing CG absorption and disposition. After oral administration of isoflavonoid glucosides, LPH was found to play minimal or no role on the hydrolysis of CG, in contrast to that of daidzin. CG was mainly transported into the small intestinal cells by sodium-dependent glucose transporter 1 (SGLT-1) as intact. This pathway could be the main mechanism underlying the high permeability of CG in the small intestine. CG was likely to be hydrolyzed in enterocytes to its aglycone calycosin by broad-specific β-glucuronides (BSβG) and glucocerebrosidase or rapidly metabolized. Calycosin was also rapidly and extensively metabolized to 3'-glucuronide in the enterocytes and liver, and the glucuronidation rates of calycosin and CG were much higher in the former. The metabolites were also transported into lumen by breast cancer resistance protein and multidrug resistance-associated protein 2. In conclusion, the enterocytes could be an important site for CG absorption, deglycosylation, and metabolism in rats. This study could contribute to the theoretical foundation and mechanism of absorption and disposition of flavonoid compounds.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, PR China (J.S., T.M.Y., Z.Q.L); International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, PR China (J.S., H.H.Z., J.Y., L.J.Z., T.M.Y., P.W., L.L.L., Y.W., M.H., Z.Q.L.); and Department of Pharmacological and Pharmaceutical Science, College of Pharmacy, University of Houston, Houston, Texas (M.H.).
authors.forename: Jian
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, PR China (J.S., T.M.Y., Z.Q.L); International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, PR China (J.S., H.H.Z., J.Y., L.J.Z., T.M.Y., P.W., L.L.L., Y.W., M.H., Z.Q.L.); and Department of Pharmacological and Pharmaceutical Science, College of Pharmacy, University of Houston, Houston, Texas (M.H.).
authors.forename: Haihui
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, PR China (J.S., T.M.Y., Z.Q.L); International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, PR China (J.S., H.H.Z., J.Y., L.J.Z., T.M.Y., P.W., L.L.L., Y.W., M.H., Z.Q.L.); and Department of Pharmacological and Pharmaceutical Science, College of Pharmacy, University of Houston, Houston, Texas (M.H.).
authors.forename: Jia
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, PR China (J.S., T.M.Y., Z.Q.L); International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, PR China (J.S., H.H.Z., J.Y., L.J.Z., T.M.Y., P.W., L.L.L., Y.W., M.H., Z.Q.L.); and Department of Pharmacological and Pharmaceutical Science, College of Pharmacy, University of Houston, Houston, Texas (M.H.).
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, PR China (J.S., T.M.Y., Z.Q.L); International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, PR China (J.S., H.H.Z., J.Y., L.J.Z., T.M.Y., P.W., L.L.L., Y.W., M.H., Z.Q.L.); and Department of Pharmacological and Pharmaceutical Science, College of Pharmacy, University of Houston, Houston, Texas (M.H.).
authors.forename: Tongmeng
authors.initials: T
authors.lastname: Yan
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, PR China (J.S., T.M.Y., Z.Q.L); International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, PR China (J.S., H.H.Z., J.Y., L.J.Z., T.M.Y., P.W., L.L.L., Y.W., M.H., Z.Q.L.); and Department of Pharmacological and Pharmaceutical Science, College of Pharmacy, University of Houston, Houston, Texas (M.H.).
authors.forename: Peng
authors.initials: P
authors.lastname: Wu
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, PR China (J.S., T.M.Y., Z.Q.L); International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, PR China (J.S., H.H.Z., J.Y., L.J.Z., T.M.Y., P.W., L.L.L., Y.W., M.H., Z.Q.L.); and Department of Pharmacological and Pharmaceutical Science, College of Pharmacy, University of Houston, Houston, Texas (M.H.).
authors.forename: Linlin
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, PR China (J.S., T.M.Y., Z.Q.L); International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, PR China (J.S., H.H.Z., J.Y., L.J.Z., T.M.Y., P.W., L.L.L., Y.W., M.H., Z.Q.L.); and Department of Pharmacological and Pharmaceutical Science, College of Pharmacy, University of Houston, Houston, Texas (M.H.).
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, PR China (J.S., T.M.Y., Z.Q.L); International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, PR China (J.S., H.H.Z., J.Y., L.J.Z., T.M.Y., P.W., L.L.L., Y.W., M.H., Z.Q.L.); and Department of Pharmacological and Pharmaceutical Science, College of Pharmacy, University of Houston, Houston, Texas (M.H.).
authors.forename: Ming
authors.initials: M
authors.lastname: Hu
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, PR China (J.S., T.M.Y., Z.Q.L); International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, PR China (J.S., H.H.Z., J.Y., L.J.Z., T.M.Y., P.W., L.L.L., Y.W., M.H., Z.Q.L.); and Department of Pharmacological and Pharmaceutical Science, College of Pharmacy, University of Houston, Houston, Texas (M.H.) liuzq@gzucm.edu.cn.
authors.forename: Zhongqiu
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D020895:Enterocytes / Q000378:metabolism; D005960:Glucosides / Q000378:metabolism*; D005962:Glucosylceramidase / Q000378:metabolism; D020719:Glucuronides / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology; D007421:Intestine, Small / Q000378:metabolism*; D007529:Isoflavones / Q000378:metabolism*; D008297:Male; D010539:Permeability; D021381:Protein Transport / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051269:Sodium-Glucose Transporter 1 / Q000502:physiology*
chemical_list: D005960:Glucosides; D020719:Glucuronides; D007529:Isoflavones; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1; C526426:calycosin-7-O-beta-D-glucoside; C013908:daidzin; D005962:Glucosylceramidase