Cryptotanshinone inhibits endothelin-1 expression and stimulates nitric oxide production in human vascular endothelial cells.
The Chinese herb Salvia miltiorrhiza (SM) has been found to have beneficial effects on the circulatory system. In the present study, we investigated the effects of cryptotanshinone (derived from SM) on endothelin-1 (ET-1) expression in human umbilical vein endothelial cells (HUVECs). The effect of cryptotanshinone on nitric oxide (NO) in HUVECs was also examined. We found that cryptotanshinone inhibited basal and tumor necrosis factor-alpha (TNF-alpha) stimulated ET-1 secretion in a concentration-dependent manner. Cryptotanshinone also induced a concentration-dependent decrease in ET-1 mRNA expression. Cryptotanshinone increased basal and TNF-alpha-attenuated NO production in a dose-dependent fashion. Cryptotanshinone induced a concentration-dependent increase in endothelial nitric oxide synthase (eNOS) expression without significantly changing neuronal nitric oxide synthase (nNOS) expression in HUVECs in the presence or absence of TNF-alpha. NOS activities in the HUVECs were also induced by cryptotanshinone. Furthermore, decreased ET-1 expression in response to cryptotanshinone was not antagonized by the NOS inhibitor l-NAME. A gel shift assay further showed that TNF-alpha-induced Nuclear Factor-kappaB (NF-kappaB) activity was significantly reduced by cryptotanshinone. These data suggest that cryptotanshinone inhibits ET-1 production, at least in part, through a mechanism that involves NF-kappaB but not NO production.
Zhou
Zhe
Z
Laboratory of Biotechnology, Beijing Institute of Radiation Medicine, Taiping road 27#, Haidian district, Beijing 100850, PR China.
Wang
Sheng-Qi
SQ
Liu
Yong
Y
Miao
Ai-Dong
AD
D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects; D019332:Endothelin-1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D052248:Nitric Oxide Synthase Type I / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D010616:Phenanthrenes / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D027561:Salvia miltiorrhiza / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins
D004365:Drugs, Chinese Herbal; D019332:Endothelin-1; D016328:NF-kappa B; D010616:Phenanthrenes; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C037886:cryptotanshinone; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III