Asymmetric dimethylarginine induces TNF-alpha production via ROS/NF-kappaB dependent pathway in human monocytic cells and the inhibitory effect of reinioside C.
Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase (NOS) inhibitor, has been implicated in vascular inflammation through induction of reactive oxygen species (ROS) and proinflammatory genes in endothelial cells. However, relatively few attentions have been paid to the effect of ADMA on monocytes, one of the important cells throughout all stages of atherosclerosis. In the present study, we found that reinioside C, the main component extracted from Polygala fallax Hemsl., dose-dependently inhibited tumor necrosis factor-alpha (TNF-alpha) production induced by ADMA in monocytes, Furthermore, reinioside C attenuated ADMA-induced generation of reactive oxygen species and activation of nuclear factor-kappaB (NF-kappaB) activity in monocytes in a dose-dependent manner, this effect was inhibited by l-arginine (NOS substrate) and PDTC (inhibitor of NF-kappaB). These data suggest that reinioside C could attenuate the increase of TNF-alpha induced by exogenous ADMA through inhibition ROS/NF-kappaB pathway in monocytes.
Zhang
Guo-Gang
GG
Department of Cardiovascular Medicine, Xiangya Hospital of Central South University, Changsha 410008, China.
Bai
Yong-Ping
YP
Chen
Mei-Fang
MF
Shi
Rui-Zhen
RZ
Jiang
De-Jian
DJ
Fu
Qiong-Mei
QM
Tan
Gui-Shan
GS
Li
Yuan-Jian
YJ
D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D031801:Polygala / Q000737:chemistry; D011759:Pyrrolidines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012503:Saponins / Q000494:pharmacology*; D013859:Thiocarbamates / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D011759:Pyrrolidines; D017382:Reactive Oxygen Species; D012503:Saponins; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; C530274:reinioside C; C020972:pyrrolidine dithiocarbamic acid; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase