Andrographolide and 14-deoxy-11,12-didehydroandrographolide from Andrographis paniculata attenuate high glucose-induced fibrosis and apoptosis in murine renal mesangeal cell lines.
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.
Lee
Meng-Jen
MJ
Institute of Biochemical Sciences and Technology, Chaoyang University of Technology, 168 Gifeng East Road, Wufeng, Taichung County 413, Taiwan, ROC.
Rao
Yerra Koteswara
YK
Chen
Keru
K
Lee
Yi-Ching
YC
Chung
Yi-Shuan
YS
Tzeng
Yew-Min
YM
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
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