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

Abstract

Inhibition of fructose absorption may suppress adiposity and adiposity-related diseases caused by fructose ingestion. Eucalyptus leaf extract (ELE) inhibits intestinal fructose absorption (but not glucose absorption); however, its active compound has not yet been identified. Therefore, we evaluated the inhibitory activity of ELE obtained from Eucalyptus globulus using an intestinal fructose permeation assay with the human intestinal epithelial cell line Caco-2. The luminal sides of a cell monolayer model cultured on membrane filters were exposed to fructose with or without the ELE. Cellular fructose permeation was evaluated by measuring the fructose concentration in the medium on the basolateral side. ELE inhibited 65% of fructose absorption at a final concentration of 1 mg/mL. Oenothein B isolated from the ELE strongly inhibited fructose absorption; the inhibition rate was 63% at a final concentration of 5 μg/mL. Oenothein B did not affect glucose absorption. In contrast, the other major constituents (i.e., gallic acid and ellagic acid) showed little fructose-inhibitory activity. To our knowledge, this is the first report that oenothein B in ELE strongly inhibits fructose absorption in vitro. ELE containing oenothein B can prevent and ameliorate obesity and other diseases caused by dietary fructose consumption.

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

“…The number of available studies is limited to nine cases. Six of them used Caco-2 cells [30,32,[34][35][36][37]; two relied on Caco-2/TC7 cells [31,33], and only one was performed on an ex-vivo rat jejunum mounted in an Ussing chamber [38]. Most of these studies did not consider the simultaneous presence of more than one PP species (a common occurrence in a PP-rich diet) and the possible occurrence of competition/synergy among individual PP species [39].…”

“…In addition, the methods and the duration of supplementation were not consistent. Some studies involved the pretreatment of intestinal cells with PP [32,33,35] in contrast with co-supplementation with FRU [30,31,34,36,37], whereas exposure times ranged from 5 min [37] to 24 h [35]. Despite these limitations, PP supplementation studies generally resulted in a concentration-dependent decrease in FRU uptake [32,[34][35][36][37] and transport [30,31,33,34,38].…”

“…Some studies involved the pretreatment of intestinal cells with PP [32,33,35] in contrast with co-supplementation with FRU [30,31,34,36,37], whereas exposure times ranged from 5 min [37] to 24 h [35]. Despite these limitations, PP supplementation studies generally resulted in a concentration-dependent decrease in FRU uptake [32,[34][35][36][37] and transport [30,31,33,34,38]. Also noteworthy is that supplementation with quercetin, apigenin, and chrisyn was reportedly associated with decreased expression of GLUT2 and GLUT5 mRNA [32,35].…”

“…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.…”

Oenothein B ameliorates hepatic injury in alcoholic liver disease mice by improving oxidative stress and inflammation and modulating the gut microbiota

“…Oenothein B (OEB) is a macrocyclic ellagitannin dimer produced by members of the plant kingdom. In 1990, OEB was first identified in the leaves of Oenothera erythrosepala ( 14 ), and it was subsequently found in plants from the families Onagraceae, Lythraceae, and Myrtaceae ( 15 – 17 ). Several previous studies have revealed that OEB possesses diverse biological properties including antioxidant, anti-inflammation, antitumor, immunomodulatory, and antimicrobial activities ( 18 – 23 ).…”