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

Abstract

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 μM, respectively. APS-1I is a 17.0 kDa heteropolysaccharide, whose backbone is composed of α-1,6-Glcp, α-1,3,6-Glcp, α-1,2-Glcp, α-1,4-Galp, and α-1,3-Rhap, and whose two branches contain α-1,3,5-Araf, α-1,3-Araf, α-1,4-Galp, β-1,3-Galp, and β-1,4-Glcp. APS-2II is a 10.0 kDa linear glucan, that contains α-1,6-Glcp, α-1,3-Glcp, α-1,2-Glcp, and α-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 high-fat-diet and streptozotocin-induced diabetic rats, suggesting that APS-1I could be a potential agent for improving IR in type 2 diabetes.

• Authors: Wenjuan Liu, Zezhi Li, Caixia Feng, Shengwei Hu, Xin Yang, Kaimin Xiao, Qiuna Nong, Qianhan Xiao, Kehan Wu, Xiao-Qiang Li, Wei Cao
• Journal: Carbohydrate polymers (Carbohydr Polym) Vol. 280 Pg. 119001 (Mar 15 2022) ISSN: 1879-1344 [Electronic] England
• PMID: 35027136 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.

Chemical References

• AGER protein, human
• Ager protein, rat
• Hypoglycemic Agents
• Insulin
• Insulin Receptor Substrate Proteins
• Polysaccharides
• Receptor for Advanced Glycation End Products
• Janus Kinases
• p38 Mitogen-Activated Protein Kinases
• Glucose

Topics

• Angelica sinensis (chemistry)
• Animals
• Carbohydrate Sequence
• Diabetes Mellitus, Type 2 (metabolism)
• Glucose (metabolism)
• Hep G2 Cells
• Humans
• Hypoglycemic Agents (chemistry, pharmacology)
• Insulin (metabolism)
• Insulin Receptor Substrate Proteins (metabolism)
• Insulin Resistance
• Janus Kinases (metabolism)
• Liver (drug effects, metabolism)
• MAP Kinase Signaling System
• Male
• Polysaccharides (chemistry, metabolism, pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptor for Advanced Glycation End Products (antagonists & inhibitors, metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)