Antihyperglycemic and antidyslipidemic agent from Aegle marmelos

Bioorg Med Chem Lett. 2007 Mar 15;17(6):1808-11. doi: 10.1016/j.bmcl.2006.12.037. Epub 2006 Dec 15.

Abstract

The plant Aegle marmelos belongs to the family of Rutaceae. From the leaves of A. marmelos an alkaloidal-amide, Aegeline 2, was isolated and found to have antihyperglycemic activity as evidenced by lowering the blood glucose levels by 12.9% and 16.9% at 5 and 24h, respectively, in sucrose challenged streptozotocin induced diabetic rats (STZ-S) model at the dose of 100mg/kg body weight. Aegeline 2 has also significantly decreased the plasma triglyceride (Tg) levels by 55% (P<0.001), total cholesterol (TC) by 24% (P<0.05), and free fatty acids (FFA) by 24%, accompanied with increase in HDL-C by 28% and HDL-C/TC ratio by 66% in dyslipidemic hamster model at the dose of 50mg/kg body weight. The reasonable mapping of compound 2 to validated pharmacophoric hypothesis and 3D QSAR model with an estimated activity (283nM) suggest that the compound 2 might be a beta(3)-AR agonist.

MeSH terms

  • Adrenergic beta-3 Receptor Agonists
  • Adrenergic beta-Agonists / isolation & purification
  • Adrenergic beta-Agonists / pharmacology
  • Aegle / chemistry*
  • Animals
  • Blood Glucose / metabolism
  • Cholesterol / blood
  • Cholesterol, HDL / blood
  • Cricetinae
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / drug therapy
  • Dietary Fats
  • Fatty Acids, Nonesterified / blood
  • Hypoglycemic Agents / isolation & purification*
  • Hypoglycemic Agents / pharmacology*
  • Hypolipidemic Agents / isolation & purification*
  • Hypolipidemic Agents / pharmacology*
  • Male
  • Models, Molecular
  • Phospholipids / blood
  • Rats
  • Rats, Sprague-Dawley
  • Triglycerides / blood

Substances

  • Adrenergic beta-3 Receptor Agonists
  • Adrenergic beta-Agonists
  • Blood Glucose
  • Cholesterol, HDL
  • Dietary Fats
  • Fatty Acids, Nonesterified
  • Hypoglycemic Agents
  • Hypolipidemic Agents
  • Phospholipids
  • Triglycerides
  • Cholesterol