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

Autor: Patel OP; Division of Medicinal and Process Chemistry, ‡Division of Biochemistry, §Division of Pharmacokinetics and Metabolism, ∥Sophisticated Analytical Instrument Facility, and ⊥Division of Botany, CSIR-Central Drug Research Institute , Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India., Mishra A; Division of Medicinal and Process Chemistry, ‡Division of Biochemistry, §Division of Pharmacokinetics and Metabolism, ∥Sophisticated Analytical Instrument Facility, and ⊥Division of Botany, CSIR-Central Drug Research Institute , Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India., Maurya R; Division of Medicinal and Process Chemistry, ‡Division of Biochemistry, §Division of Pharmacokinetics and Metabolism, ∥Sophisticated Analytical Instrument Facility, and ⊥Division of Botany, CSIR-Central Drug Research Institute , Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India., Saini D; Division of Medicinal and Process Chemistry, ‡Division of Biochemistry, §Division of Pharmacokinetics and Metabolism, ∥Sophisticated Analytical Instrument Facility, and ⊥Division of Botany, CSIR-Central Drug Research Institute , Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India., Pandey J; Division of Medicinal and Process Chemistry, ‡Division of Biochemistry, §Division of Pharmacokinetics and Metabolism, ∥Sophisticated Analytical Instrument Facility, and ⊥Division of Botany, CSIR-Central Drug Research Institute , Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India., Taneja I; Division of Medicinal and Process Chemistry, ‡Division of Biochemistry, §Division of Pharmacokinetics and Metabolism, ∥Sophisticated Analytical Instrument Facility, and ⊥Division of Botany, CSIR-Central Drug Research Institute , Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India., Raju KS; Division of Medicinal and Process Chemistry, ‡Division of Biochemistry, §Division of Pharmacokinetics and Metabolism, ∥Sophisticated Analytical Instrument Facility, and ⊥Division of Botany, CSIR-Central Drug Research Institute , Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India., Kanojiya S; Division of Medicinal and Process Chemistry, ‡Division of Biochemistry, §Division of Pharmacokinetics and Metabolism, ∥Sophisticated Analytical Instrument Facility, and ⊥Division of Botany, CSIR-Central Drug Research Institute , Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India., Shukla SK; Division of Medicinal and Process Chemistry, ‡Division of Biochemistry, §Division of Pharmacokinetics and Metabolism, ∥Sophisticated Analytical Instrument Facility, and ⊥Division of Botany, CSIR-Central Drug Research Institute , Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India., Srivastava MN; Division of Medicinal and Process Chemistry, ‡Division of Biochemistry, §Division of Pharmacokinetics and Metabolism, ∥Sophisticated Analytical Instrument Facility, and ⊥Division of Botany, CSIR-Central Drug Research Institute , Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India., Wahajuddin M; Division of Medicinal and Process Chemistry, ‡Division of Biochemistry, §Division of Pharmacokinetics and Metabolism, ∥Sophisticated Analytical Instrument Facility, and ⊥Division of Botany, CSIR-Central Drug Research Institute , Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India., Tamrakar AK; Division of Medicinal and Process Chemistry, ‡Division of Biochemistry, §Division of Pharmacokinetics and Metabolism, ∥Sophisticated Analytical Instrument Facility, and ⊥Division of Botany, CSIR-Central Drug Research Institute , Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India., Srivastava AK; Division of Medicinal and Process Chemistry, ‡Division of Biochemistry, §Division of Pharmacokinetics and Metabolism, ∥Sophisticated Analytical Instrument Facility, and ⊥Division of Botany, CSIR-Central Drug Research Institute , Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India., Yadav PP; Division of Medicinal and Process Chemistry, ‡Division of Biochemistry, §Division of Pharmacokinetics and Metabolism, ∥Sophisticated Analytical Instrument Facility, and ⊥Division of Botany, CSIR-Central Drug Research Institute , Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
Jazyk: angličtina
Zdroj: Journal of natural products [J Nat Prod] 2016 May 27; Vol. 79 (5), pp. 1276-84. Date of Electronic Publication: 2016 May 03.
DOI: 10.1021/acs.jnatprod.5b00883
Abstrakt: 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.
Databáze: MEDLINE