Transepithelial Transport of Theasinensins through Caco-2 Cell Monolayers and Their Absorption in Sprague–Dawley Rats after Oral Administration

Abstract

The aim of this study is to illustrate the in vivo and in vitro absorption of theasinensins B and A that are (-)-epigallocatechin-3-O-gallate (EGCG)-(-)-epigallocatechin (EGC) dimer and EGCG dimer, respectively, and their transport pathway across the intestinal membrane. Our animal study by a single oral administration to rats demonstrated the intact absorption of theasinensins into the blood system, which was estimated to be a >10-fold lower absorption amount than EGCG. The in vitro absorption study indicated that theasinensins can be transported across Caco-2 cell monolayers, while their permeability coefficients were also >10-fold lower than those of EGCG and EGC. Transport experiments using cytochalasin D or quercetin as a tight junction (TJ) modulator and a non-saturable permeation revealed that theasinensins were transported across Caco-2 cells in a TJ paracellular diffusion route. In conclusion, the dimers of condensed catechins, theasinensins B and A, can be absorbed intact into rat blood and transported across Caco-2 cell monolayers probably through a TJ paracellular pathway.

A-type ECG and EGCG dimers disturb the structure of 3T3-L1 cell membrane and strongly inhibit its differentiation by targeting peroxisome proliferator-activated receptor γ with miR-27 involved mechanism

“…It was reported that a concentration of 25 μg/ml of proanthocyanidins is need in vitro to reach the significant regulation of miRNA [56]. Results from Qiu et alindicated that after a single oral administration of 100 mg/kg body weight for each compound, the plasma concentrations of EGC and EGCG dimer were 7.5 and 9.3 nmol/L, separately [57]. and their metabolites (about 17.18 μmol/L in total) were five times higher than that in the cell media at 25 μg/ml of proanthocyanidins [56].…”

Condensed catechins and their potential health-benefits

“…Thus far, no study has been conducted on theasinensin absorption, except for a report by Qiu et al (2012), who outlined the intact absorption of dimeric catechins (TSA and TSB) in SpragueDawley (SD) rats (100 mg/kg) via TJ-paracellular passive diffusion (Fig. 2).…”

“…Absorption experiment of theasinensins to SD rat was performed by a single oral administration of TSA (100 mg/kg). The inserted chromatogram by electrochemical detector-high performance liquid chromatography (HPLC-ECD, 500 mV for working electrode) shows rat plasma profile obtained at 60 min after the administration of TSA (cited from the report by Qiu et al (2012)). An LC-TOF-MS chromatogram of theaflavins was obtained from Caco-2 cell transport experiments, in which transport of 1 mM TF3′G across Caco-2 cell monolayers for 60 min was performed, and solutions obtained at apical and basolateral sides analyzed by MS in negative ionization mode.…”

“…In contrast, there was no study investigating the activities of condensed catechins or intact theasinensins (Fig. 2, Qiu et al, 2012) on glucose uptake in muscle. It has been reported that TSA (a dimer of EGCG) demonstrated a potent promoting effect on glucose uptake in skeletal muscle cells (L6 myotubes) (Qiu et al, 2014).…”

Transport of ginkgolides with different lipophilicities based on an hCMEC/D3 cell monolayer as a blood–brain barrier cell model

“…Transport experiments on hCMEC/D cell monolayer were conducted as described previously with minor modifications (Qiu et al, 2012). After hCMEC/D cell monolayers were observed on the transwells of 24 wells using a hemocytometer under a microscope, hCMEC/D3 cell monolayer integrities were examined by measuring transepithelial electrical resistances (TEER) with an electrical resistance system.…”