Naturally Occurring Carbazole Alkaloids from Murraya koenigii as Potential Antidiabetic Agents

被引：76

作者：

Patel, Om P. S. ^{[1
]}

Mishra, Akansha ^{[2
]}

Maurya, Ranjani ^{[1
]}

Saini, Deepika ^{[1
]}

Pandey, Jyotsana ^{[2
]}

Taneja, Isha ^{[3
]}

Raju, Kanumuri S. R. ^{[3
]}

Kanojiya, Sanjeev ^{[4
]}

Shulda, Sanjeev K. ^{[4
]}

Srivastava, Mahendra N. ^{[5
]}

Wahajuddin, M. ^{[3
]}

Tamrakar, Akhilesh K. ^{[2
]}

Srivastava, Arvind K. ^{[2
]}

Yadav, Prem P. ^{[1
]}

机构：

[1] CSIR Central Drug Res Inst, Div Med & Proc Chem, Sect 10,Sitapur Rd, Lucknow 226031, Uttar Pradesh, India

[2] CSIR Central Drug Res Inst, Div Biochem, Sect 10,Sitapur Rd, Lucknow 226031, Uttar Pradesh, India

[3] CSIR Central Drug Res Inst, Div Pharmacokinet & Metab, Sect 10,Sitapur Rd, Lucknow 226031, Uttar Pradesh, India

[4] CSIR Central Drug Res Inst, Sophisticated Analyt Instrument Facil, Sect 10,Sitapur Rd, Lucknow 226031, Uttar Pradesh, India

[5] CSIR Central Drug Res Inst, Div Bot, Sect 10,Sitapur Rd, Lucknow 226031, Uttar Pradesh, India

来源：

JOURNAL OF NATURAL PRODUCTS | 2016年 / 79卷 / 05期

关键词：

GLUCOSE-UPTAKE; MAHANIMBINE; APOPTOSIS; LIGNANS; LEAVES;

D O I：

10.1021/acs.jnatprod.5b00883

中图分类号：

Q94 [植物学];

学科分类号：

071001 ;

摘要：

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.

引用

页码：1276 / 1284

页数：9

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