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Preventive effects of andrographolide on the development of diabetes in autoimmune diabetic NOD mice by inducing immune tolerance.

Abstract
Andrographolide, an active component in traditional anti-diabetic herbal plants, is a diterpenoid lactone isolated from Andrographis paniculata because of its potent anti-inflammatory and hypoglycemic effects. However, the effect of andrographolide on the development of diabetes in autoimmune non-obese diabetic (NOD) mice remains unknown. This study aimed to investigate the protective effects of andrographolide on the development of autoimmune diabetes and clarify the underlying mechanism. NOD mice were randomly divided into four groups and administered with water and andrographolide at 50, 100, and 150mg/kg body weight for four weeks. ICR mice were also selected as the control group. Oral glucose tolerance and histopathological insulitis were examined. Th1/Th2/Th17 cytokine secretion was determined by ELISA. The transcriptional profiles of T-bet, GATA3, and RORγt in the pancreatic lymphatic node samples derived from the NOD mice were detected by RT-PCR. After four weeks of oral supplementation, andrographolide significantly inhibited insulitis, delayed the onset, and suppressed the development of diabetes in 30-week-old NOD mice in a dose dependent manner. This protective status was correlated with a substantially decreased production of interferon (IFN)-γ and interleukin (IL)-2, increased IL-10 and transforming growth factor (TGF)-β, and a reduced IL-17. Andrographolide also increased GATA3 mRNA expression but decreased T-bet and RORγt mRNA expressions. Our results suggested that andrographolide prevented type 1 diabetes by maintaining Th1/Th2/Th17 homeostasis.
AuthorsChengliang Zhang, Ling Gui, Yanjiao Xu, Tao Wu, Dong Liu
JournalInternational immunopharmacology (Int Immunopharmacol) Vol. 16 Issue 4 Pg. 451-6 (Aug 2013) ISSN: 1878-1705 [Electronic] Netherlands
PMID23707775 (Publication Type: Journal Article)
CopyrightCopyright © 2013 Elsevier B.V. All rights reserved.
Chemical References
  • Cytokines
  • Diterpenes
  • Hypoglycemic Agents
  • andrographolide
Topics
  • Administration, Oral
  • Animals
  • Cytokines (blood, immunology)
  • Diabetes Mellitus, Experimental (immunology, prevention & control)
  • Diabetes Mellitus, Type 1 (immunology, prevention & control)
  • Diterpenes (administration & dosage, chemistry, therapeutic use)
  • Dose-Response Relationship, Drug
  • Female
  • Hypoglycemic Agents (administration & dosage, chemistry, therapeutic use)
  • Immune Tolerance (drug effects)
  • Islets of Langerhans (drug effects, immunology, pathology)
  • Mice
  • Mice, Inbred ICR
  • Mice, Inbred NOD
  • Molecular Structure

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