Fagomine is a glycosidase inhibitor. The Ki of the iminosugar Fagomine is 70 μM, 39 μM, and 4.8 μM for Isomaltase (yeast), β-Glucosidase (bovine), and Amyloglucosidase (A.niger), respectively.

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). Fagomine is capable of altering this effect of high-fat high-sucrose diet (HFHS) on the proportion of Enterobacteriales and E.coli [2].

Compare to the standard group, rats fed a high-fat high-sucrose diet (HFHS) with Fagomine gain significantly less weight (15.3%) than those fed HFHS (20.9%) [2]. Fagomine counteracts the short-term effects of a high-energy-dense diet on body weight, fasting blood glucose levels and the proportion of gut Enterobacteriales [3].

Lysosomal enzyme activities in cell lysates are determined. Briefly, cells are scraped in ice-cold 0.1% Triton X-100 in water. After centrifugation (6000 rpm for 15 min at 4°C) to remove insoluble materials, protein concentrations are determined using Protein Assay Rapid Kit. The lysates are incubated at 37°C with the corresponding 4-methylumbelliferyl β-D-glycopyranoside solution in 0.1 M citrate buffer (pH 4). The liberated 4-methylumbelliferone is measured with a fluorescence plate reader (excitation 340 nm; emission 460 nm). For enzyme inhibition assay, cell lysates from normal skin fibroblasts are mixed with the 4-methylumbelliferyl β-D-glycopyranoside substrates in the absence or presence of increasing concentrations of Fagomine [1].

Human skin fibroblasts from a healthy and three Gaucher disease patients (with N188S/G183W, V230G/R296X, and L444P/L444P mutations) are maintained in DMEM supplemented with 10% FBS as the culture medium. For enzyme activity enhancement assay, cells are cultured in the presence of different concentrations of Fagomine or DMSO alone (as a control) for 5 days and harvested by scraping. Cytotoxicity of Fagomine is monitored by measuring the lactate dehydrogenase activities in the cultured supernatants [1].

Sprague-Dawley rats (male, 22 weeks old) are randomly assigned to one of the three dietary groups: the control group fed a standard diet (STD); a group fed HFHS (modified high-fat high-sucrose diet); a group fed HFHS supplemented with 0.065% Fagomine (HFHS+FG). The percentage of Fagomine is adjusted so that its ratio to sucrose is 2 mg/g, as defined before from the results of post-prandial tests. The modified diets are processed. Feed consumption is monitored every day throughout the experiment and body weight is measured before and at the end of the nutritional intervention. All animal manipulations are carried out in the morning to minimize the effects of circadian rhythms [3].

53185-12-9

C6H13NO3

147.17

D-Fagomine;荞麦碱

H2O:35 mg/mL (237.82 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years