Effect of protopanaxadiol derivatives in high glucose-induced fibronectin expression in primary cultured rat mesangial cells: role of mitogen-activated protein kinases and Akt.
A lot of anti-diabetic agents using natural plants have been extensively studied. Ginsenosides are known to be used as a remedy for diabetes in Asian countries and American Societies. Diabetic nephropathy is a major complication of diabetes mellitus. Extracellular matrix in mesangial cells is mainly composed of fibronectin and the increase of fibronectin is a hallmark of diabetic nephropathy. Protopenaxadiol (PPD) is a major component of total ginseng. Thus, we examined the regulatory mechanism of PPD derivatives-induced preventive effect of fibronectin expression in mesangial cells cultivated under diabetic condition. In present study, ginsenoside Rb1 prevented the high glucose-induced increase of fibronectin expression in mesangial cells. Ginsenoside Rb2 and Rg3 also mildly inhibited it. However, ginsenoside Rc and Rd did not prevent the high glucose-induced increase of fibronectin expression in mesangial cells. In addition, ginsenoside Rb1 prevented high glucose-induced phosphorylation of p44/42 mitogen activated protein kinase (MAPK), p38 MAPK, JNK/SAPK, and Akt. These results suggest that ginsenoside Rb1 is the most powerful component of PPD derivatives. In conclusion, ginsenoside Rb1 prevented high glucose-induced increase of fibronectin expression via the inhibition of MAPK-Akt signaling cascade.
Park
Min Jung
MJ
Bio-therapy Human Resources Center, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Korea.
Bae
Chun Sik
CS
Lim
Seul Ki
SK
Kim
Dong Il
DI
Lim
Jae Cheong
JC
Kim
Jong Choon
JC
Han
Ho Jae
HJ
Moon
Jae Hak
JH
Kim
Kye Yeop
KY
Yoon
Kyung-Chul
KC
Park
Soo Hyun
SH
D000818:Animals; D015153:Blotting, Western; D002240:Carbohydrate Sequence; D005353:Fibronectins / Q000096:biosynthesis*; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D008969:Molecular Sequence Data; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012502:Sapogenins / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects
D005353:Fibronectins; D012333:RNA, Messenger; D012502:Sapogenins; D012313:RNA; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D005947:Glucose; C062916:protopanaxadiol