The structures of two polysaccharides from Angelica sinensis and their effects on hepatic insulin resistance through blocking RAGE

This study found two novel homogeneous polysaccharides from Angelica sinensis, APS-1I and APS-2II, binding to RAGE with a dissociation constant of 2.02 +/- 0.2 and 85.92 +/- 0.2 mu M, respectively. APS-1I is a 17.0 kDa heteropolysaccharide, whose backbone is composed of alpha-1,6-Glcp, alpha-1,3,6-Glcp, alpha-1,2-Glcp, alpha-1,4-Galp, and alpha-1,3-Rhap, and whose two branches contain alpha-1,3,5-Araf, alpha-1,3-Araf, andp-1,4-Glcp. APS-2II is a 10.0 kDa linear glucan, that contains alpha-1,6-Glcp, alpha-1,3-Glcp, alpha-1,2-Glcp, and alpha-T-Glcp. In vitro, APS-1I demonstrated better promotion on glucose absorption and stronger repression on p-IRS-1 (Ser307), p-IRS-2 (Ser731), p-JNK, and p-P38 than APS-2II in insulin resistance (IR)-HepG2 cells. Furthermore, APS-1I treatment couldn't further decrease the inhibition on the phosphorylation of JNK and P38 produced by RAGE siRNA in IR-HepG2 cells. In vivo, APS-1I markedly improved IR and reversed the livers RAGE-JNK/p38-IRS signaling in highfat-diet and streptozotocin-induced diabetic rats, suggesting that APS-1I could be a potential agent for improving IR in type 2 diabetes.