Andrographolide ameliorates diabetic retinopathy by inhibiting retinal angiogenesis and inflammation.

Abstract

BACKGROUND:

Andrographolide (Andro) is the main compound distributed in medicinal herb Andrographis paniculata. This study aims to observe the amelioration of Andro on streptozotocin (STZ)-induced diabetic retinopathy (DR) in mice.

METHODS:

STZ-induced non-proliferative DR (NPDR) for 2 months and proliferative DR (PDR) for 5 month in C57BL/6 mice were used in this study, respectively. Retinal vessels were observed by immunofluorescence staining for cluster of differentiation 31 (CD31). Evans blue permeation assay was used to detect the breakdown of blood-retinal barrier (BRB). Real-time PCR and immune-blot were used to detect mRNA and protein expression. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β.

RESULTS:

Retinal immunofluorescence staining with CD31 showed that Andro reduced the increased retinal vessels in STZ-induced PDR mice. Evans blue permeation results demonstrated that Andro attenuated the breakdown of BRB in STZ-induced NPDR mice. In STZ-induced PDR mice, Andro decreased the increased vascular endothelial growth factor (VEGF) in serum and vitreous cavity, and reduced the increased retinal mRNA expression of VEGF and its receptors. In STZ-induced NPDR mice, Andro abrogated the nuclear translocation of nuclear factor κB (NF-κB) p65 and early growth response-1 (Egr-1), and reduced the increased phospho-NF-κBp65, -inhibitor of kappa B (IκB), and -IκB kinase (IKK). Andro also decreased the increased serum and retinal mRNA expression of TNF-α, IL-6, IL-1β, serpine1, and tissue factor (TF).

CONCLUSIONS:

Andro ameliorates DR via attenuating retinal angiogenesis and inflammation, and VEGF, NF-κB, and Egr1 signaling pathways all play important roles in this process.

• Authors: Zengyang Yu, Bin Lu, Yuchen Sheng, Lingyu Zhou, Lili Ji, Zhengtao Wang
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1850 Issue 4 Pg. 824-31 (Apr 2015) ISSN: 0006-3002 [Print] Netherlands
• PMID: 25641276 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Angiogenesis Inhibitors
• Anti-Inflammatory Agents
• Diterpenes
• Early Growth Response Protein 1
• Egr1 protein, mouse
• NF-kappa B
• Vascular Endothelial Growth Factor A
• andrographolide
• Streptozocin

Topics

• Angiogenesis Inhibitors (pharmacology)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Diabetes Mellitus, Experimental
• Diabetic Retinopathy (drug therapy, physiopathology)
• Diterpenes (pharmacology)
• Early Growth Response Protein 1 (physiology)
• Mice
• Mice, Inbred C57BL
• NF-kappa B (physiology)
• Retinal Vessels (drug effects, physiopathology)
• Streptozocin
• Vascular Endothelial Growth Factor A (analysis, physiology)