Synthesis and pharmacological evaluation of glycosides of resveratrol, pterostilbene, and piceatannol

• Published in: Annals of the New York Academy of Sciences Vol. 1348; no. 1; pp. 141 - 149
• Main Authors: Shimoda, Kei, Kubota, Naoji, Uesugi, Daisuke, Hamada, Hatsuyuki, Tanigawa, Masato, Hamada, Hiroki
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01-08-2015; Wiley Subscription Services, Inc
• Subjects: Animals; Anti-Allergic Agents - chemistry; Anti-Allergic Agents - metabolism; Anti-Allergic Agents - pharmacology; Cells, Cultured; Drug Evaluation, Preclinical; Free Radical Scavengers - chemistry; Free Radical Scavengers - metabolism; Free Radical Scavengers - pharmacology; glycoside; Glycosides - biosynthesis; Glycosides - chemistry; Glycosides - pharmacology; Glycosylation; Histamine; Inhibitory Concentration 50; pharmacological activity; Phosphodiesterase Inhibitors - chemistry; Phosphodiesterase Inhibitors - metabolism; Phosphodiesterase Inhibitors - pharmacology; Phytolacca americana - cytology; Phytolacca americana - metabolism; piceatannol; Plant Extracts - biosynthesis; Plant Extracts - chemistry; Plant Extracts - pharmacology; pterostilbene; Rats; resveratrol; Rodents; Solubility; Stilbenes - chemistry; Stilbenes - metabolism; Stilbenes - pharmacology; synthesis; synthesis; pharmacological activity; piceatannol; glycoside; resveratrol; pterostilbene
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/nyas.12836

To enhance their water solubility and pharmacological activities, the stilbenes resveratrol, pterostilbene, and piceatannol were glycosylated to their monoglucosides (β‐glucosides) and diglycosides (β‐maltosides) by cultured cells and cyclodextrin glucanotransferase (CGTase). Cultured cells of Phytolacca americana and glucosyltransferase (PaGT) were capable of glucosylation of resveratrol to its 3‐ and 4′‐β‐glucosides. Pterostilbene was slightly transformed into its 4′‐β‐glucoside by P. americana cells. Piceatannol was readily converted into piceatannol 4′‐β‐glucoside, with the highest yield among the three substrates. The 3‐ and 4′‐β‐glucosides of resveratrol were subjected to further glycosylation by CGTase to give 3‐ and 4′‐β‐maltoside derivatives. The inhibitory action of resveratrol and pterostilbene toward histamine release induced with compound 48/80 from rat peritoneal mast cells was improved by β‐glucosylation and/or β‐maltosylation (i.e., the inhibitory activity for histamine release of the 3‐ and 4′‐β‐glucosides of resveratrol, the 3‐ and 4′‐β‐maltosides of resveratrol, and the 4′‐β‐glucoside of pterostilbene was higher than that of the corresponding aglycones, resveratrol and pterostilbene, respectively). In addition, the phosphodiesterase (PDE) inhibitory activity of resveratrol and pterostilbene was enhanced by β‐glucosylation and/or β‐maltosylation (i.e., the PDE inhibitory activities of the 3‐ and 4′‐β‐glucosides of resveratrol, the 4′‐β‐maltoside of resveratrol, and the 4′‐β‐glucoside of pterostilbene were higher than those of the corresponding aglycones, resveratrol and pterostilbene, respectively).