7,8-didehydrocimigenol from Cimicifugae rhizoma inhibits TNF-α-induced VCAM-1 but not ICAM-1expression through upregulation of PPAR-γ in human endothelial cells.
Activators of PPAR have been demonstrated to inhibit the induction of VCAM-1 but not ICAM-1 in human endothelial cells (EC). During the screening of anti-inflammatory activity of traditional herbs, we found 7,8-didehydrocimigenol (7,8-DHC), one of active triterpenoids of Cimicifugae rhizoma (C. rhizoma) increases PPAR-γ expression in EC in a time- and dose-dependent manner. Therefore, we asked whether 7,8-DHC selectively inhibits the expression of VCAM-1 but not ICAM-1 in TNF-α-activated EC via upregulation of PPAR-γ. Treatment with 7,8-DHC or PPAR-γ agonists (GW1929, troglitazone) inhibited the expression of VCAM-1 but not ICAM-1. Furthermore, the selective inhibition of VCAM-1 expression was inhibited by PPAR-γ antagonist, GW9662, or siPPAR-γ-transfected cells. 7,8-DHC significantly inhibited NF-kB activity via inhibition of phosphorylation of IkB and it also inhibited phosphorylation of ERK1/2 and Akt but not PKC. Finally, attachment of monocytes (U937) to EC by TNF-α was significantly reduced by 7,8-DHC. These results indicate that upregualtion of PPAR-γ by 7,8-DHC in EC inhibits NF-kB activity of TNF-α-activated EC which leads to selective inhibition of VCAM-1 expression. In addition, ERK1/2 and Akt signal pathways are involved in differential regulation by 7,8-DHC. We concluded that 7,8-DHC can be used for the treatment of cardiovascular disorders such as atherosclerosis.
Department of Pharmacology, School of Medicine, Gyeongsang National University, Jinju, Republic of Korea.
Lidiya
L
Mun
Min Soo
MS
Jun
Young Min
YM
Kim
Young Soo
YS
Lee
Hye Jung
HJ
Kim
Han Geuk
HG
Seo
Jae Heun
JH
Lee
Kun Ho
KH
Son
Dong Hwa
DH
Lee
Yeong Shik
YS
Kim
Kyungok
K
Park
Ki Churl
KC
Chang
D000813:Anilides / Q000494:pharmacology; D001483:Base Sequence; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D031885:Cimicifuga / Q000737:chemistry*; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D047495:PPAR gamma / Q000819:agonists*; D011494:Protein Kinases / Q000378:metabolism; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D015854:Up-Regulation / Q000187:drug effects*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
C457499:2-chloro-5-nitrobenzanilide; C557978:7,8-didehydrocimigenol; D000813:Anilides; D017931:DNA Primers; D047495:PPAR gamma; D034741:RNA, Small Interfering; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D011494:Protein Kinases