Antihyperglycemic and antidyslipidemic agent from Aegle marmelos.
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.
Narender
T
T
Division of Medicinal and Process Chemistry, Central Drug Research Institute, Lucknow 226 001 (UP), India. tnarender@rediffmail.com
Shweta
S
S
Tiwari
P
P
Papi Reddy
K
K
Khaliq
T
T
Prathipati
P
P
Puri
A
A
Srivastava
A K
AK
Chander
R
R
Agarwal
S C
SC
Raj
K
K
D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000302:isolation & purification / Q000494:pharmacology; D045471:Aegle / Q000737:chemistry*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D006224:Cricetinae; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified / Q000097:blood; D007004:Hypoglycemic Agents / Q000302:isolation & purification* / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000302:isolation & purification* / Q000494:pharmacology*; D008297:Male; D008958:Models, Molecular; D010743:Phospholipids / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood
D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D001786:Blood Glucose; D008076:Cholesterol, HDL; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D010743:Phospholipids; D014280:Triglycerides; D002784:Cholesterol