Effects of esculetin and baicalein on cellualr signal transduction and growth factor genes expression

• Main Authors: Ling-Mein Hsieh, 謝玲勉
• Other Authors: Huei-Chen Huang
• Format: Others
• Language: zh-TW
• Published: 1994
• Online Access: http://ndltd.ncl.edu.tw/handle/74826297723461092954

碩士 === 國立臺灣大學 === 藥理學研究所 === 82 === 1.細胞的增生是癌瘤和動脈粥狀硬化產生病理變化之一。我們發現兩種中 藥成份茵陳之Artemisia scoparia成份的esculetin(6,7- dihydroxycoumar in)和黃芩(Scutellaris 份baicalein(5,6,7- trihydroxy a抑制血管平滑肌細胞及癌細胞的增生。本篇將研究escul- tin、baicalein 抑制 增生之機轉。在 10% 胎牛血清刺激CEM cells增生 下，esculetin和baicalein在10-4M能達極大抑制作用(分別為62.2 ±2.8%,IC50M和4.7±0.5m M。此外也能在 10-6-10-4M 劑量範圍內抑制 protein tyrosine 74.1±3.3% vs. 64.6±2.8%抑制10-4M)，依劑量之增 加而抑制作用增大。而phobor-12-myristate 13-acetate激活之protein kinase相關性抑制作用。所以esculetin,baicalein可能部份經由抑制 protein tyrosine kinase pathway來抑制CEM cells增生。而baicalein 對protein tyrosine kinase活性抑制較esculetin強。以逆轉錄-聚合酵 素連鎖反應方法分析platelet-derived growth factor (PDGF-A)和TGF- beta mRNAs表現，baicalein esculetin更能抑制CEM cell之PDGF-A mRNA 表現，卻都不影響TGF-beta mRNA表現。esculetin和baica -lein 在CEM cells能經由抑制protein tyrosine kinase和 PDGF-A mRNA表現活 性來抑制CEM cells 2.Esculetin(6,7-dihydroxycoumarin)是中藥材茵陳 的成份之一。本篇將研究esculetin在大白鼠胸部大動脈之作用及機轉。 Esculetin能引起血管弛部份作用會受到去除內皮的減弱。 Esculetin(10-4M)20分鐘前處理可抑的作用是部份抑制phenylepherine產 生的血管收縮，但對serotonin ,pota ssium chloride引起血管收縮並無 影嚮。因此，esculetin可能釋放EDRF來抑制phenylepherine產生的血管 收縮.esculetin(10-4M)前處理能抑制 alloxan引起superoxide ion產生 。所以，esculetin可能有free radical scavenger-like之活性。 esculetin(10-5M)增加basal cyclic GMPlevel,因此、esculetin可能經 由增加cyclic GMP使血管鬆弛。 1.The increased cell proliferation plays an important role in the development of neoplasia and atherosclerosis. We have previoiously reported that esculetin and baicalein exhibit antiproliferative effects on vascular smooth muscle cells. It is interesing to compare the antiproliferative effects of esculetin and baicalein on neoplasm and atheroma. The possible mechanisms of antiproliferative effect on esculetin and baicalein were in studied in human T-lymphoid leukemia cells(CEM cells). Esculetin and baicalein exhibited the greatest antiproliferative activities in CEM cells containing 10% FCS stimulated. The protein tyrosine kinase activity in the CEM cells was significantly reduced by esculetin and baicalein. Baicalein exhibited a greater inhibitory activity on the protein tyrosine kianse than did esculetin. On the other hand, the protein kinase C activity stimulated by phorbol-12-myristate 13-acetate was reduced by directly incubating with esculetin and baicalein. However, the inhibitory activities on protein kinase C did not show a dose-dependency. The reverse transcrription- polymerase chain reaction analysis of PDGF-A and TGF-beta1 mRNA levels demonstrates that esculetin and baicalein reduced the PDGF-A mRNA level,but less affected the TGF-beta1 mRNA.It is suggested that esculetin and baicalein may affected cell proliferation by direct inhibition of growth- related signal, protein kinase, as well as reduction of mRNA exp- ression of growth factor,PDGF. 2.The possible mechanisms of vasodilator effect of esculetin we- re investigated.The presence of endothelium partially facilitat- ed the vasodilator effect.Both vasoconstriction and O2 producti- on induced by alloxan,were depressed by esculetin at 10-5 M. It appears that esculetin exhibited a free radical scavenger -like property.