Phenolics-Rich Extracts of Dietary Plants as Regulators of Fructose Uptake in Caco-2 Cells via GLUT5 Involvement

Abstract

The latest data link the chronic consumption of large amounts of fructose present in food with the generation of hypertension and disturbances in carbohydrate and lipid metabolism, which promote the development of obesity, non-alcoholic fatty liver disease, insulin resistance, and type 2 diabetes. This effect is possible after fructose is absorbed by the small intestine cells and, to a lesser extent, by hepatocytes. Fructose transport is dependent on proteins from the family of glucose transporters (GLUTs), among which GLUT5 selectively absorbs fructose from the intestine. In this study, we examined the effect of four phenolic-rich extracts obtained from A. graveolens, B. juncea, and M. chamomilla on fructose uptake by Caco-2 cells. Extracts from B. juncea and M. chamomilla most effectively reduced fluorescent fructose analogue (NBDF) accumulation in Caco-2, as well as downregulated GLUT5 protein levels. These preparations were able to decrease the mRNA level of genes encoding transcription factors regulating GLUT5 expression-thioredoxin-interacting protein (TXNIP) and carbohydrate-responsive element-binding protein (ChREBP). Active extracts contained large amounts of apigenin and flavonols. The molecular docking simulation suggested that some of identified phenolic constituents can play an important role in the inhibition of GLUT5-mediated fructose transport.

Oenothein B in Eucalyptus Leaf Extract Suppresses Fructose Absorption in Caco-2 Cells

“…At this dose, ELE-treated cells did not show different morphological features, as confirmed by transepithelial/endothelial electrical resistance (TEER) and microscopic analyses; before and after fructose permeation, the TEER values of the blank and ELE (1 mg/mL) were retained by 91% and 81%, respectively. Many studies have reported various polyphenols derived from edible plants with inhibitory activity against fructose absorption [ 32 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ]. We examined the effects of the ELE with reduced polyphenolic substances.…”

GLUT5: structure, functions, diseases and potential applications

“…In-depth studies have shown that the MSNBA binding site is close to the active center of the GLUT5 protein and is responsible for substrate recognition by residue H387, as well as residues such as Ser143, Thr171, Gln288, Gln289, Asn294 and Tyr297 involved in the binding process of MSNBA-GLUT5 [95] . Recently, researchers have found that some phenolic-rich dietary plant extracts can reduce the transcript levels of the gene encoding ChREBP, thereby inhibiting GLUT5 protein expression and its mediated fructose transport [96] . This may contribute to our better understanding of the regulation of GLUT5 expression by plant compounds present in the human diet.…”

Dietary Polyphenols and In Vitro Intestinal Fructose Uptake and Transport: A Systematic Literature Review

“…Table 2 summarizes the data available on the effect of PP-rich products on FRU uptake and transport in intestinal cells. Gallic acid (8.1 mg/100 mL), caffeic acid (11.1 mg/100 mL), caftaric acid (20.8 mg/100 mL), epicatechin (7.9 mg/100 mL), quercetin-3-O-glucoside (5.9 mg/100 mL), quercetin-3,4-O-diglucoside (4.2 mg/100 mL), quercetin-3-O-glucuronide (4.9 mg/100 mL), quercetin (30 mg/100 mL), isorhamnetin (12.6 mg/100 mL), piceid (2.2 mg/100 mL), resveratrol Gallic acid (8.9 mg/100 mL), caffeic acid (12.8 mg/100 mL), caftaric acid (25.1 mg/100 mL), epicatechin (12.6 mg/100 mL), quercetin-3-O-glucoside (7.8 mg/100 mL), quercetin-3,4-O-diglucoside (4.3 mg/100 mL), quercetin-3-O-glucuronide (3.8 mg/100 mL), quercetin (34.3 mg/100 mL), isorhamnetin (13.1 mg/100 mL), piceid (4.3 mg/100 mL), resveratrol (5.1 mg/100 mL), cyanidin-3,5-O-diglucoside (710 ng/100 mL), cyanidin-3-O -glucoside (106.9 ng/100 mL), cyanidin-3-O-acetyl-glucoside (40.8 ng/100 mL), peonidin-3,5-O-diglucoside (150.4 ng/100 mL), peonidin-3-O-glucoside (19.2 ng/100 mL), peonidin-3-O-acetyl glucoside (15.9 ng/100 mL), delphinidin-3-O-glucoside (877.4 ng/100 mL), delphinidin-3-O-acetyl-glucoside (210.3 ng/100 mL), delphinidin-3-O-p-coumaroyl-5-O-diglucoside (212.1 ng/100 mL), delphinidin-3-O-p-coumaroyl glucoside (211.7 ng/100 mL), petunidin-3-O-glucoside (210.1 ng/100 mL), petunidin-3-O-acetyl-glucoside (61.9 ng/100 mL), petunidin-3-O-p-coumaroyl-5-O-diglucoside (58.2 ng/100 mL), malvidin-3-O-glucoside (168.4 ng/100 mL), malvidin- Similar to studies on individual PPs, there are only a limited number of studies (9) evaluating the effect of extracts [30,32,33,36,[40][41][42] and of a phenolic-rich juice [31,43]. All of these studies were conducted in cell lines (six with Caco-2 cells and three with Caco-2/TC7 cells), and the experimental conditions differed considerably among the various studies.…”

“…The total PP concentration ranged from approximately 0.01 mg/mL [32,41] to 10 mg/mL [32], whereas the FRU concentration varied from 54 nM [41] to 130 mM [31]. Similarly, the method and duration of supplementation varied from co-supplementation with FRU for only 10 min [36] to pretreatment with phenolic extract for 24 h and subsequent incubation with FRU for 3 h [40]. Even though the use of different approaches makes it difficult to draw general conclusions, most studies reported a pronounced effect of most PP-rich products on both FRU uptake [32,36,[40][41][42] and transport [30,33,42,43].…”

“…Similarly, the method and duration of supplementation varied from co-supplementation with FRU for only 10 min [36] to pretreatment with phenolic extract for 24 h and subsequent incubation with FRU for 3 h [40]. Even though the use of different approaches makes it difficult to draw general conclusions, most studies reported a pronounced effect of most PP-rich products on both FRU uptake [32,36,[40][41][42] and transport [30,33,42,43]. However, sugarcane extract supplementation was determined to result in an upregulation of GLUT5 mRNA and a downregulation of GLUT2 mRNA expression [32].…”