Protopanaxatriol ginsenosides inhibit glucose uptake in primary cultured rabbit renal proximal tubular cells by arachidonic acid release.
Ginsenosides are involved in protective action against renal dysfunction and the regulation of renal functions. However, the effects of ginsenosides on glucose reabsorption are not yet known in renal proximal tubular cells. The aim of this study was to examine the effects of ginsenosides, protopanaxadiol (PD) saponin and protopanaxatriol (PT) saponin, on alpha-methyl-D-glucopyranoside (alpha-MG) uptake and its mechanism of action in primary cultured rabbit renal proximal tubular cells (PTCs). The alpha-MG uptake was inhibited by 90% by 0.5mM phloridizin and by removal of Na+ in the PTCs. These are typical characteristics described for the proximal tubule. To determine the time- and dose-dependent effects of PD and PT saponins on alpha-MG uptake, PTCs were incubated with different concentrations of PD and PT saponins (10-100 microg/ml) and for different time periods (from 10 min to 24 h). PT saponin (>/=50 microg/ml) from 30 min inhibited alpha-MG uptake; however, PD saponin did not alter the alpha-MG uptake at any doses and time periods. In the kinetic analysis of alpha-MG uptake, PT saponin produced a significant decrease in Vmax. The PT saponin induced inhibition of alpha-MG uptake was blocked by mepacrine, a phospholipase A2 inhibitor. In addition, PT saponin increased [3H] arachidonic acid release by 218% of that of control, and this effect was also completely blocked by mepacrine. In conclusion, PT saponin inhibited, in part, alpha-MG uptake through the phospholipase A2 signal pathway in primary cultured rabbit renal PTCs.
Han
H J
HJ
College of Veterinary Medicine, Chonnam National University, Kwangju, Korea. hjhan@chonnam.chonnam.ac.kr
Park
S H
SH
Koh
H J
HJ
Nah
S Y
SY
Shin
D H
DH
Choi
H S
HS
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D002478:Cells, Cultured; D002491:Central Nervous System Agents / Q000494:pharmacology*; D002794:Choline / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D036145:Ginsenosides; D005947:Glucose / Q000378:metabolism*; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D005894:Panax / Q000737:chemistry*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism; D054467:Phospholipases A2; D010946:Plants, Medicinal; D011796:Quinacrine / Q000494:pharmacology; D011817:Rabbits; D012502:Sapogenins / Q000494:pharmacology*; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes
D002491:Central Nervous System Agents; D004791:Enzyme Inhibitors; D036145:Ginsenosides; D012502:Sapogenins; D012503:Saponins; D014315:Triterpenes; D016718:Arachidonic Acid; C081552:protopanaxatriol; D010741:Phospholipases A; D054467:Phospholipases A2; D011796:Quinacrine; D005947:Glucose; D002794:Choline