Angelica gigas Ameliorates Hyperglycemia and Hepatic Steatosis in C57BL/KsJ-db/db Mice via Activation of AMP-Activated Protein Kinase Signaling Pathway

Am J Chin Med. 2016;44(8):1627-1638. doi: 10.1142/S0192415X16500919. Epub 2016 Nov 16.

Abstract

The prevention and management of type 2 diabetes mellitus has become a major global public health challenge. Decursin, an active compound of Angelica gigas Nakai roots, was recently reported to have a glucose-lowering activity. However, the antidiabetic effect of Angelica gigas Nakai extract (AGNE) has not yet been investigated. We evaluated the effects of AGNE on glucose homeostasis in type 2 diabetic mice and investigated the underlying mechanism by which AGNE acts. Male C57BL/KsJ-db/db mice were treated with either AGNE (10 mg/kg, 20 mg/kg, and 40 mg/kg) or metformin (100 mg/kg) for 8 weeks. AGNE supplementation (20 and 40 mg/kg) significantly decreased fasting glucose and insulin levels, decreased the areas under the curve of glucose in oral glucose tolerance and insulin tolerance tests, and improved homeostatic model assessment-insulin resistant (HOMA-IR) scores. AGNE also ameliorated hepatic steatosis, hyperlipidemia, and hypercholesterolemia. Mechanistic studies suggested that the glucose-lowering effect of AGNE was mediated by the activation of AMP activated protein kinase, Akt, and glycogen synthase kinase-3[Formula: see text]. AGNE can potentially improve hyperglycemia and hepatic steatosis in patients with type 2 diabetes.

Keywords: AMPK; Angelica gigas Nakai; Hepatic Steatosis; Hypoglycemic Effects; Insulin Resistance.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Angelica / chemistry*
  • Animals
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Fatty Liver / drug therapy*
  • Glucose / metabolism
  • Humans
  • Hyperglycemia / drug therapy*
  • Hyperlipidemias / drug therapy
  • Hypoglycemic Agents*
  • Insulin / metabolism
  • Insulin Resistance
  • Male
  • Mice, Inbred C57BL
  • Phytotherapy*
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use*
  • Signal Transduction / drug effects*

Substances

  • Hypoglycemic Agents
  • Insulin
  • Plant Extracts
  • AMP-Activated Protein Kinases
  • Glucose