Revisiting dietary proanthocyanidins on blood glucose homeostasis from a multi-scale structural perspective

Multi-dimensional studies have consistently indicated the benefits of dietary proanthocyanidins on blood glucose homeostasis through consumption of them from fruits, cereals and nuts. Proanthocyanidins from various sources possess different structures, but even the minor variations in structures influence their regulation on blood glucose, including the degree of polymerization, galloacylation at C3, number of hydroxyl groups in B ring and linkage type. Therefore, this Review details the role of three types of proanthocyanidins (procyanidins, prodelphinidins and propelargonidins) in blood glucose control and their underlying mechanisms, and various structural features contribute to. Due to the extremely low bioavailability, proanthocyanidins mainly ameliorate high blood glucose by luminal effects: inhibit enzyme activities, improve the structure of gut microbiota, and protect the intestinal barrier function. A few absorbed proanthocyanidins exert insulin-like effects on targeted organs. Prodelphinidin gallates exhibit greater hypoglycemic activities than others, due to their galloacylation at C3 and high amounts of hydroxyl groups in B ring. Because of different action pathways, comprehensive consideration on the degree of polymerization, linkage type and density of hydroxyl groups was required. Further understanding of these relationships can concrete diet therapeutic opportunities for proanthocyanidins. • The structure of proanthocyanidins is highly dependent on their sources. • Minor variations in structure affect the hypoglycemic effect of proanthocyanidins. • Proanthocyanidins mainly ameliorate high blood glucose by luminal effects. • Absorbable proanthocyanidins exert insulin-like effects on targeted organs. • Density of phenolic hydroxyl groups is positively correlated with their activities.