title: Andrographolide and 14-deoxy-11,12-didehydroandrographolide from Andrographis paniculata attenuate high glucose-induced fibrosis and apoptosis in murine renal mesangeal cell lines.
abstract: BACKGROUND
  Extracts of Andrographis paniculata Nees are used for various ethnomedical conditions including hyperglycemia and hypertension complications.
  
  
  OBJECTIVE
  The purpose of this study is to evaluate the anti-diabetic nephropathy effect of diterpene lactones andrographolide (AP1) and 14-deoxy-11,12-didehydroandrographolide (AP2) from Andrographis paniculata.
  
  
  METHODS
  MES-13, a SV40-transformed murine glomerular mesangial cell line, was cultured in high concentration of glucose to induce diabetic nephropathy phenotypes, which include secretion of extracellular matrix protein fibronectin, cytokine TGF-β, states of oxidative stress, and apoptosis marker caspase-3.
  
  
  RESULTS
  Our data suggest that addition of compounds AP1 or AP2 reduces the phenotypes indicating diabetic nephropathy in MES-13 cells. The compound AP2 showed potent activity than AP1 in the reduction of apoptosis marker caspase-3, fibrosis marker TGF-β, and PAI-1. Furthermore, AP1 and AP2 do not have antioxidant ability in acellular environment; however, addition of AP1 and AP2 reduced intracellular oxidative states in high glucose cultured MES-13 cells.
  
  
  CONCLUSIONS
  This is the first report on anti-diabetic nephropathy effect of AP1 and AP2 in part due to the regulation of intracellular signaling transduction, not mere clearance of reactive oxygen species. Thus, this study may be useful for drug development or food supplement for diabetes and nephropathy from Andrographis paniculata.
authors.affiliation: Institute of Biochemical Sciences and Technology, Chaoyang University of Technology, 168 Gifeng East Road, Wufeng, Taichung County 413, Taiwan, ROC.
authors.forename: Meng-Jen
authors.initials: MJ
authors.lastname: Lee
authors.forename: Yerra Koteswara
authors.initials: YK
authors.lastname: Rao
authors.forename: Keru
authors.initials: K
authors.lastname: Chen
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Lee
authors.forename: Yi-Shuan
authors.initials: YS
authors.lastname: Chung
authors.forename: Yew-Min
authors.initials: YM
authors.lastname: Tzeng
mesh_terms: D035685:Andrographis; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002461:Cell Line, Transformed; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004224:Diterpenes / Q000494:pharmacology*; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis; D006943:Hyperglycemia / Q000150:complications*; D050527:Mesangial Cells / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D035261:Plant Components, Aerial; D010936:Plant Extracts / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C495626:14-deoxy-11,12-didehydroandrographolide; D004224:Diterpenes; D005353:Fibronectins; D010936:Plant Extracts; D017395:Plasminogen Activator Inhibitor 1; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; C030419:andrographolide