d-Fagomine lowers postprandial blood glucose and modulates bacterial adhesion

Abstract

D-Fagomine is an iminosugar originally isolated from seeds of buckwheat (Fagopyrum sculentum Moench), present in the human diet and now available as a pure crystalline product. We tested D-fagomine for activities connected to a reduction in the risk of developing insulin resistance, becoming overweight and suffering from an excess of potentially pathogenic bacteria. The activities were: intestinal sucrase inhibition in vitro (rat mucosa and everted intestine sleeves), modulation of postprandial blood glucose in rats, bacterial agglutination and bacterial adhesion to pig intestinal mucosa. When ingested together with sucrose or starch, D-fagomine lowered blood glucose in a dose-dependent manner without stimulating insulin secretion. D-Fagomine reduced the area under the curve (0-120 min) by 20 % (P,0·01) and shifted the time to maximum blood glucose concentration (T max ) by 15 min at doses of 1 -2 mg/kg body weight when administered together with 1 g sucrose/kg body weight. Moreover, D-fagomine (0·14 mM) agglutinated 60 % of Enterobacteriaceae (Escherichia coli, Salmonella enterica serovar Typhimurium) populations (P, 0·01), while it did not show this effect on Bifidobacterium spp. or Lactobacillus spp. At the same concentration, D-fagomine significantly (P,0·001) inhibited the adhesion of Enterobacteriaceae (95 -99 % cells in the supernatant) and promoted the adhesion of Lactobacillus acidophilus (56 % cells in the supernatant) to intestinal mucosa. D-Fagomine did not show any effect on bacterial cell viability. Based on all this evidence, D-fagomine may be used as a dietary ingredient or functional food component to reduce the health risks associated with an excessive intake of fast-digestible carbohydrates, or an excess of potentially pathogenic bacteria.Key words: Fagomine: Iminosugars: Insulin resistance: Weight management: Microbiota D-Fagomine (1,2-dideoxynojirimycin) is a six-membered ring iminocyclitol that was first isolated from seeds of buckwheat (Fagopyrum sculentum Moench, Polygonaceae) (1) and is also present in other plant sources such as mulberry (Morus Alba, Moraceae) leaves (2) and gogi (Lycium chinense) roots (3) . Iminocyclitols, also referred to as iminosugars, are carbohydrate analogues in which the endocyclic oxygen has been replaced by nitrogen (Fig. 1) and the spatial configurations of the hydroxyl groups are coincident with those of sugars (e.g. glucose, galactose, fucose and mannose).D-Fagomine was the first iminosugar found in plants and it is present in the human diet, since buckwheat flour is used in the elaboration of many traditional foods including Japanese soba noodles, French galletes de Bretagne and Italian polenta. Another common iminocyclitol is 1-deoxynojirimycin (DNJ), which is the most abundant iminosugar found in mulberry (4) . D-Fagomine presents the molecular configuration of D-glucose and D-mannose on carbons 3, 4 and 5, while DNJ is a sugar mimetic of D-glucose. D-Fagomine and DNJ are particularly stable compounds, both chemically and metabolically (5) .DNJ...

Effect of d‐fagomine on excreted enterobacteria and weight gain in rats fed a high‐fat high‐sucrose diet

“…d‐ Fagomine (1,2‐dideoxynojirimycin) is a six‐membered ring iminosugar; the spatial configuration of its hydroxyl groups coincides with those of d ‐glucose and d‐ mannose. d ‐Fagomine selectively agglutinates fimbriated enterobacteria (e.g., E. coli ) and inhibits their adhesion to the intestinal mucosa ; the reason for this is probably related to its structural similarity with lectin‐binding saccharides (e.g., mannose). As d ‐fagomine inhibits the adhesion of E. coli in vitro , we hypothesized that it could counteract the overgrowth of Enterobacteriales induced by HFHS.…”

In vitro evaluation of the effect of the buckwheat protein hydrolysate on bacterial adhesion, physiology and cytokine secretion of Caco-2 cells

“…Gomez et al [38] demonstrated that it significantly inhibited the adhesion of bacteria from the Enterobacteriaceae family and stimulated the adhesion of Lactobacillus acidophilus to intestinal mucosa. The induction of metabolic pathways in bacteria is driven differently by proteins and carbohydrates, similarly as their adhesive potential.…”

Transforming Flask Reaction into Cell-Based Synthesis: Production of Polyhydroxylated Molecules via Engineered Escherichia coli

“…60−63 For example, D-fagomine can effectively reduce the blood glucose peak when taken together with sucrose or starch, without stimulating insulin release and can help to eliminate the excess of enterobacteria and lower weight gain by selectively agglutinating fimbriated enterobacteria and inhibiting their adhesion to the intestinal mucosa. 64,65 Miglitol, Nhydroxyethyl DNJ, is currently used as a potent secondgeneration digestive α-glucosidase inhibitor for treatment of type II diabetes; Miglustat, N-butyl DNJ, is currently used for treatment of type 1 Gaucher disease (GD1) and Niemann− Pick type C (NPC) disease. 66−68 By simple deprotection and reductive amination, product 2, 3, and 4 were transformed to Dfagomine, DMJ and DNJ respectively with high yields, and no other diastereomers were detected by 1 H NMR analysis (Scheme 4).…”