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J Ethnopharmacol. 2013 Oct 28;150(1):285-97. doi: 10.1016/j.jep.2013.08.043. Epub 2013 Sep 5.

Natural product vindoline stimulates insulin secretion and efficiently ameliorates glucose homeostasis in diabetic murine models.

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  • 1Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

Catharanthus roseus (L). Don (Catharanthus roseus) is a traditional anti-diabetic herb widely used in many countries, and the alkaloids of Catharanthus roseus are considered to possess hypoglycemic ability.

AIM OF THE STUDY:

To systematically investigate the potential anti-diabetic effects and the underlying anti-diabetic mechanisms of vindoline, one of the alkaloids in Catharanthus roseus.

MATERIALS AND METHODS:

The regulation of vindoline against the glucose-stimulated insulin secretion (GSIS) was examined in insulinoma MIN6 cells and primary pancreatic islets. Insulin concentration was detected by Elisa assay. Diabetic models of db/db mice and type 2 diabetic rats induced by high-fat diet combining with streptozotocin (STZ/HFD-induced type 2 diabetic rats) were used to evaluate the anti-diabetic effect of vindoline in vivo. Daily oral treatment with vindoline (20mg/kg) to diabetic mice/rats for 4 weeks, body weight and blood glucose were determined every week, oral glucose tolerance test (OGTT) was performed after 4 weeks.

RESULTS:

Vindoline enhanced GSIS in both glucose- and dose-dependent manners (EC50 = 50 μM). It was determined that vindoline acted as a Kv2.1 inhibitor able to reduce the voltage-dependent outward potassium currents finally enhancing insulin secretion. It protected β-cells from the cytokines-induced apoptosis following its inhibitory role in Kv2.1. Moreover, vindoline (20mg/kg) treatment significantly improved glucose homeostasis in db/db mice and STZ/HFD-induced type 2 diabetic rats, as reflected by its functions in increasing plasma insulin concentration, protecting the pancreatic β-cells from damage, decreasing fasting blood glucose and glycated hemoglobin (HbA1c), improving OGTT and reducing plasma triglyceride (TG).

CONCLUSION:

Our findings suggested that vindoline might contribute to the anti-diabetic effects of Catharanthus roseus, and this natural product may find its more applications in the improvement of β-cell dysfunction and further the potential treatment of type 2 diabetes.

© 2013 Elsevier Ireland Ltd. All rights reserved.

KEYWORDS:

Catharanthus roseus; Catharanthus roseus (L). Don; FSK; GSIS; Glucose-stimulated insulin secretion; Gly; HFD; HbA(1c); LAME; OGTT; STZ; TEA; TG; Type 2 diabetes; Vindoline; forskolin; glucose-stimulated insulin secretion; glybenclamide; glycated hemoglobin; high-fat diet; linoleic acid methyl ester.; oral glucose tolerance test; plasma triglyceride; streptozotocin; tetraethylammonium chloride; β-cell dysfunction

PMID:
24012527
[PubMed - indexed for MEDLINE]
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