KIOM-79 inhibits high glucose or AGEs-induced VEGF expression in human retinal pigment epithelial cells.
We evaluated whether KIOM-79, a mixture of extracts obtained from Puerariae lobata, Magnolia officinalis, Glycyrrhiza uralensis and Euphorbia pekinensis, could inhibit vascular endothelial growth factor (VEGF) expression in human retinal pigment epithelial (RPE) cells cultured under high glucose (HG, 25mM) or S100b (a specific ligand of the receptor for advance glycation end products (RAGE), 5microg/ml). In this study, the effect of KIOM-79 on HG or S100b-induced VEGF expression was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, RT-PCR, ELISA, and Western blot on human RPE cells. The MTT assay (p<0.01) revealed that KIOM-79 (up to 1mg/ml) had no effect on cell growth. HG or S100b induced an increase in expression of VEGF at both mRNA and protein levels (p<0.05; p<0.01 versus control). The increase in VEGF expression by HG or S100b was dose- and time-dependently prevented by KIOM-79 (p<0.05 versus 25mM glucose; p<0.01 versus S100b). Also, KIOM-79 inhibited protein kinase C (PKC)-alpha/beta(alpha) and p38 mitogen-activated protein kinase (MAPK) activation. Our results demonstrate that KIOM-79 can inhibit VEGF expression via inhibition of the MAPK and PKC pathway.
Kim
Young Sook
YS
Department of Herbal Pharmaceutical Development, Korea Institute of Oriental Medicine, 461-24 Jeonmin-dong, Yuseng-gu, Daejeon 305-811, Republic of Korea.
Jung
Dong Ho
DH
Kim
Nan Hee
NH
Lee
Yun Mi
YM
Jang
Dae Sik
DS
Song
Gyu-Yong
GY
Kim
Jin Sook
JS
D015153:Blotting, Western; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D009414:Nerve Growth Factors / Q000494:pharmacology*; D010857:Pigment Epithelium of Eye / Q000187:drug effects* / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D017127:Glycation End Products, Advanced; C517978:KIOM 79; D008024:Ligands; D009414:Nerve Growth Factors; D010936:Plant Extracts; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; D042461:Vascular Endothelial Growth Factor A; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose