Naturally Occurring Carbazole Alkaloids from Murraya koenigii as Potential Antidiabetic Agents.

Abstract

This study identified koenidine (4) as a metabolically stable antidiabetic compound, when evaluated in a rodent type 2 model (leptin receptor-deficient db/db mice), and showed a considerable reduction in the postprandial blood glucose profile with an improvement in insulin sensitivity. Biological studies were directed from the preliminary in vitro evaluation of the effects of isolated carbazole alkaloids (1-6) on glucose uptake and GLUT4 translocation in L6-GLUT4myc myotubes, followed by an investigation of their activity (2-5) in streptozotocin-induced diabetic rats. The effect of koenidine (4) on GLUT4 translocation was mediated by the AKT-dependent signaling pathway in L6-GLUT4myc myotubes. Moreover, in vivo pharmacokinetic studies of compounds 2 and 4 clearly showed that compound 4 was 2.7 times more bioavailable than compound 2, resulting in a superior in vivo efficacy. Therefore, these studies suggested that koenidine (4) may serve as a promising lead natural scaffold for managing insulin resistance and diabetes.

• Authors: Om P S Patel, Akansha Mishra, Ranjani Maurya, Deepika Saini, Jyotsana Pandey, Isha Taneja, Kanumuri S R Raju, Sanjeev Kanojiya, Sanjeev K Shukla, Mahendra N Srivastava, M Wahajuddin, Akhilesh K Tamrakar, Arvind K Srivastava, Prem P Yadav
• Journal: Journal of natural products (J Nat Prod) Vol. 79 Issue 5 Pg. 1276-84 (05 27 2016) ISSN: 1520-6025 [Electronic] United States
• PMID: 27136692 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkaloids
• Blood Glucose
• Carbazoles
• Glucose Transporter Type 4
• Hypoglycemic Agents
• Insulin
• koenidine
• Streptozocin
• Proto-Oncogene Proteins c-akt
• Glucose

Topics

• Alkaloids (pharmacology)
• Animals
• Blood Glucose (metabolism)
• Carbazoles (chemistry, isolation & purification, pharmacology)
• Diabetes Mellitus, Experimental (metabolism)
• Glucose (metabolism)
• Glucose Transporter Type 4 (metabolism)
• Hypoglycemic Agents (chemistry, isolation & purification, pharmacology)
• Insulin (pharmacology)
• Insulin Resistance
• Male
• Mice
• Molecular Structure
• Murraya (chemistry)
• Muscle Fibers, Skeletal (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats
• Signal Transduction (drug effects)
• Streptozocin (pharmacology)