title: 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.affiliation: 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.
authors.forename: Om P S
authors.initials: OP
authors.lastname: Patel
authors.affiliation: 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.
authors.forename: Akansha
authors.initials: A
authors.lastname: Mishra
authors.affiliation: 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.
authors.forename: Ranjani
authors.initials: R
authors.lastname: Maurya
authors.affiliation: 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.
authors.forename: Deepika
authors.initials: D
authors.lastname: Saini
authors.affiliation: 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.
authors.forename: Jyotsana
authors.initials: J
authors.lastname: Pandey
authors.affiliation: 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.
authors.forename: Isha
authors.initials: I
authors.lastname: Taneja
authors.affiliation: 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.
authors.forename: Kanumuri S R
authors.initials: KS
authors.lastname: Raju
authors.affiliation: 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.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kanojiya
authors.affiliation: 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.
authors.forename: Sanjeev K
authors.initials: SK
authors.lastname: Shukla
authors.affiliation: 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.
authors.forename: Mahendra N
authors.initials: MN
authors.lastname: Srivastava
authors.affiliation: 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.
authors.forename: M
authors.initials: M
authors.lastname: Wahajuddin
authors.affiliation: 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.
authors.forename: Akhilesh K
authors.initials: AK
authors.lastname: Tamrakar
authors.affiliation: 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.
authors.forename: Arvind K
authors.initials: AK
authors.lastname: Srivastava
authors.affiliation: 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.
authors.forename: Prem P
authors.initials: PP
authors.lastname: Yadav
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002227:Carbazoles / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D015394:Molecular Structure; D032101:Murraya / Q000737:chemistry*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013311:Streptozocin / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D001786:Blood Glucose; D002227:Carbazoles; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; C000619751:koenidine; D013311:Streptozocin; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose