Chikusetsu saponin IVa regulates glucose uptake and fatty acid oxidation: implications in antihyperglycemic and hypolipidemic effects

J Pharm Pharmacol. 2015 Jul;67(7):997-1007. doi: 10.1111/jphp.12392. Epub 2015 Feb 12.

Abstract

Objectives: The aim of this study is to investigate antidiabetic effects and molecular mechanisms of the chemical Chikusetsu saponin IVa (CHS) that isolated from root bark of Aralia taibaiensis, which has multiple pharmacological activity, such as relieving rheumatism, promoting blood circulation to arrest pain and antidiabetic action.

Methods: Rats with streptozotocin/nicotinamide-induced type 2 diabetes mellitus (T2DM) and insulin-resistant myocytes were used. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) and acetyl-CoA carboxylase were quantified by immunoblotting. Assays of glucose uptake, fatty acid oxidation, glucose transporter 4 (GLUT4) translocation and carnitine palmitoyl transferase-1 (CPT-1) activity were performed.

Key findings: Chronic oral administration of CHS effectively decreases blood glucose, triglyceride, free fatty acid (FFA) and low density lipoprotein-cholesterol levels in T2DM rats. In both normal and insulin-resistant C2C12 myocytes, CHS activates AMPK, and increases glucose uptake or fatty acid oxidation through enhancing membrane translocation of GLUT4 or CPT-1 activity respectively. Knockdown of AMPK significantly diminishes the effects of CHS on glucose uptake and fatty acid oxidation.

Conclusions: CHS is a novel AMPK activator that is capable of bypassing defective insulin signalling and could be useful for the treatment of T2DM or other metabolic disorders.

Keywords: Adenosine monophosphate activated protein kinase; Chikusetsu saponin IVa; Glucose transporter 4; carnitine palmitoyl transferase-1; glucose and lipid metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aralia / chemistry
  • Blood Glucose / drug effects
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / chemically induced
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism
  • Fatty Acids / metabolism*
  • Fatty Acids, Nonesterified / blood
  • Glucose / metabolism*
  • Hypoglycemic Agents / pharmacology*
  • Hypolipidemic Agents / pharmacology*
  • Insulin / metabolism
  • Insulin Resistance / physiology
  • Male
  • Oleanolic Acid / analogs & derivatives*
  • Oleanolic Acid / pharmacology
  • Oxidation-Reduction / drug effects*
  • Plant Bark / chemistry
  • Plant Roots / chemistry
  • Rats
  • Rats, Wistar
  • Saponins / pharmacology*
  • Streptozocin / pharmacology
  • Triglycerides / blood

Substances

  • Blood Glucose
  • Fatty Acids
  • Fatty Acids, Nonesterified
  • Hypoglycemic Agents
  • Hypolipidemic Agents
  • Insulin
  • Saponins
  • Triglycerides
  • chikusetsu saponin IVa
  • Streptozocin
  • Oleanolic Acid
  • Glucose