title: 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: The Shanghai Key Laboratory of Complex Prescription and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors: Zengyang
authors: Z
authors: Yu
authors: The Shanghai Key Laboratory of Complex Prescription and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors: Bin
authors: B
authors: Lu
authors: Center for Drug Safety Evaluation and Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors: Yuchen
authors: Y
authors: Sheng
authors: The Shanghai Key Laboratory of Complex Prescription and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors: Lingyu
authors: L
authors: Zhou
authors: The Shanghai Key Laboratory of Complex Prescription and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: lichenyue1307@126.com.
authors: Lili
authors: L
authors: Ji
authors: The Shanghai Key Laboratory of Complex Prescription and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors: Zhengtao
authors: Z
authors: Wang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000503:physiopathology; D004224:Diterpenes / Q000494:pharmacology*; D051766:Early Growth Response Protein 1 / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000502:physiology; D012171:Retinal Vessels / Q000187:drug effects* / Q000503:physiopathology; D013311:Streptozocin; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000502:physiology
chemical_list: D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D004224:Diterpenes; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D016328:NF-kappa B; D042461:Vascular Endothelial Growth Factor A; C030419:andrographolide; D013311:Streptozocin
keywords: Andrographolide; Angiogenesis; Diabetic retinopathy; Inflammation