Synthesis of a new glycosphingolipid, neurosporaside, from Neurospora crassa.

The glycosphingolipid neurosporaside (α-D-Glcp-(1 → 2)-ß-D-Galp-(1 → 6)-ß-D-Galp-(1 → 6)-ß-D-Galp-(1 →)-Cer) occurs in Neurospora crassa. We attempted to synthesize neurosporaside by block synthesis (route A) and linear synthesis (route B). Oligosaccharide derivatives were synthesized using trimethylsilyltrifluoromethanesulfonate and N-iodosuccinimide/trifluoromethane sulfonic acid as promoters. The target tetrasaccharide could not be attained via route A, but route B showed potential: glycosidic bonds (ß-D-Galp-(1 → 6)-ß-D-Galp-(1 → 6)-ß-D-Galp) were formed stereoselectively, leading to the synthesis of glycosphingolipid 2.

Anti-allergic effects of enzymatically modified isoquercitrin (α-oligoglucosyl quercetin 3-O-glucoside), quercetin 3-O-glucoside, α-oligoglucosyl rutin, and quercetin, when administered orally to mice.

Quercetin, a flavonol distributed widely in edible and medicinal plants, has beneficial biological activities in vitro. However, the low water solubility of quercetin limits its bioavailability to exhibit activity in vivo. We evaluated the anti-allergic effects of quercetin, quercetin 3-O-glucoside (isoquercitrin, IQC), α-oligoglucosyl rutin (αOR), and enzymatically modified isoquercitrin (α-oligoglucosyl isoquercitrin; EMIQ) in the murine ear passive cutaneous anaphylaxis (PCA) reaction using ovalbumin as an antigen. The substances to be tested were dissolved or suspended in water, and administered orally to mice (4 mmol 10 ml⁻¹ kg⁻¹). EMIQ exhibited a significant inhibitory effect on the PCA reaction. We detected 600 µM IQC and 95.1 µM Q3Glcn in the plasma of mice 30 min after EMIQ treatment, suggesting that IQC and Q3Glcn might be the genuine active compounds mediating the anti-allergic effects of EMIQ. Oral treatments of quercetin and αOR at this dosage exhibited no anti-allergic effect, and IQC showed less effect than EMIQ. Since IQC and quercetin cannot completely dissolve in water at this concentration, the water solubilities of these substances might affect their biological activities. αOR dissolved well in water at the concentration used but plasma concentrations of quercetin metabolites in mice orally treated with αOR were low, suggesting that αOR might not be converted to IQC or quercetin by the enzymes in small intestine and thus not exhibit any activity. Glycosyl conjugation of quercetin with specific sugar motifs is an effective strategy to improve the biological activity of quercetin in vivo.

Enzymatically modified isoquercitrin, alpha-oligoglucosyl quercetin 3-O-glucoside, is absorbed more easily than other quercetin glycosides or aglycone after oral administration in rats.

Quercetin, a flavonol contained in various vegetables and herbal medicines, has various biological activities including anti-cancer, anti-allergic and anti-oxidative activities. However, low oral bioavailability of quercetin due to insolubility in water has limited its use as a food additive or dietary supplement. Since the water solubility is enhanced by glycosyl conjugation, in the present study, we evaluated the bioavailability of several quercetin glycosides with different sugar moieties in rats. Quercetin, quercetin-3-O-rutinoside (rutin), and quercetin-3-O-glucoside (isoquercitrin, IQC) in suspension, and quercetin-3-O-maltoside (Q3M), quercetin-3-O-gentiobioside (Q3G), alpha-monoglucosyl rutin (alphaMR), alpha-oligoglucosyl rutin (alphaOR), and enzymatically modified isoquercitrin (alpha-oligoglucosyl isoquercitrin, EMIQ) dissolved in water, were orally administered to rats under anesthesia. Bioavailability (F value) was calculated from the concentrations of total quercetin in plasma from 0 to 12 h after the administration. F value of quercetin was 2.0%, and those of IQC, Q3M and EMIQ were 12%, 30%, and 35%, respectively. Although Q3G, alphaMR and alphaOR have high water solubility, their F values were low (3.0%, 4.1%, 1.8%, respectively). In the in vitro study, the homogenate of rat intestinal epithelium rapidly hydrolyzed IQC, Q3M and EMIQ to quercetin, and alphaMR and alphaOR to rutin. However, it could not hydrolyze Q3G or rutin to quercetin. Elongation of alpha-linkage of glucose moiety in IQC enhances the bioavailability of quercetin, and intestinal epithelial enzymes such as lactase-phrolizin hydrolase or mucosal maltase-glucoamylase would play important roles in the hydrolysis and absorption of these flavonol glycosides.