Comparison of Intestinal Absorption and Disposition of Structurally Similar Bioactive Flavones in Radix Scutellariae

Abstract

Abstract. Radix Scutellariae is a commonly used herbal medicine. Baicalein, wogonin, and oroxylin A are three major bioactive flavones in Radix Scutellariae and share similar chemical structures. The intestinal absorption and disposition of baicalein have been systematically investigated by our group before. In this study, the intestinal absorption and disposition of wogonin and oroxylin A were further explored and compared with the profiles of baicalein to find potential structure-activity relationship. Absorptive models including Caco-2 cell monolayer model and rat in situ single-pass intestinal perfusion model as well as in vitro enzymatic kinetic study were employed in the current study. The absorption of baicalein, wogonin, and oroxylin A were favorable with wogonin showing the highest permeability based on two absorptive models. However, three flavones underwent a fast and extensive phase II metabolism. The intestinal metabolism of three flavones exhibited species difference between human and rat. Oroxylin A demonstrated the highest intrinsic clearance of glucuronidation among three flavones. The multidrug resistance proteins might be involved in the efflux of their intracellularly formed conjugated metabolites. The pathway of intestinal absorption and disposition of B, W, and OA was similar. However, the extent of permeability and metabolism was different among three flavones which might be due to the number and position of the hydroxyl group.

Fasiglifam (TAK-875) Inhibits Hepatobiliary Transporters: A Possible Factor Contributing to Fasiglifam-Induced Liver Injury

“…Human embryonic kidney (HEK293) cells were individually transfected with human (h) OATP1B1, hOATP1B3, hOATP2B1, and a control vector (mock-transfected cells), and the functions of these transporters were validated using positive substrates and inhibitors. Madin-Darby canine kidney (MDCK) cells overexpressing MRP2 (MDCK-MRP2 cells) (Li et al, 2012) were a kind gift from Prof. Zhong Zuo (The Chinese University of Hong Kong, Hong Kong, China). The assay kits of total bile acid (TBA), alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were purchased from Nanjing Jiancheng Bioengineering Institute (Jiangsu, China).…”

Multiple ABC Transporters Efflux Baicalin

“…Phase II metabolism of flavonoids in the intestinal cells and in hepatocytes as well as transport by ABC transporters greatly affects the disposition and bioavailability of flavonoids (Li et al, 2012). The purpose of the present study was to provide data on the interaction of BG with BCRP, MDR1, MRP2, MRP3 and MRP4, efflux transporters playing a role in intestinal and hepatic transport and reported to interact with BG (Akao et al, 2009;Li et al, 2012;Zhang et al, 2007).…”

“…The purpose of the present study was to provide data on the interaction of BG with BCRP, MDR1, MRP2, MRP3 and MRP4, efflux transporters playing a role in intestinal and hepatic transport and reported to interact with BG (Akao et al, 2009;Li et al, 2012;Zhang et al, 2007).…”

“…In recent studies, BG was shown to inhibit very efficiently BCRP-, MRP2-and MRP3-mediated vesicular transport and to activate the ATPase activity of BCRP, MRP2 and MRP3. This indicates that MRP3 could play a role in the basolateral transport of BG from intestinal cells while MRP2 and BCRP might be the transporters effluxing BG on the apical side of enterocytes (Akao et al, 2007;Li et al, 2012;Zhang et al, 2007) and hepatocytes (Akao et al, 2009). The ATPase assay, however, is not a transport assay and requires confirmation by a transport assay such as vesicular transport for low passive permeability substrates.…”

Evaluation of potential herb-drug interactions between oseltamivir and commonly used anti-influenza Chinese medicinal herbs

“…Effects of herb/herbal components on hydrolysis, transport and uptake of OS For inhibition of OS hydrolysis, OSA formation rate were calculated by the molar amount of OSA divided by reaction time and volume of rat plasma (or protein amount of RLM and hCE1). For P-gp transport study, apparent permeability coefficient (P app ) was obtained as we described before (Li et al, 2012) to estimate the potential modification of OS by herbs/herbal components. For uptake study, the cell uptake amount of OS was obtained and compared between the groups in the absence and presence of herbs/herbal components.…”