紅花對於心肌細胞保護作用及抗病毒活性之探討

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题名:	紅花對於心肌細胞保護作用及抗病毒活性之探討 Studies on the protective effect on Cardiomyocytes and antivirus activity of Carthamus tinctorius L
作者:	田芸禎;Tien, Yun-Chen
贡献者:	中國藥學暨中藥資源學系博士班
关键词:	紅花;心肌細胞;細胞凋亡;內毒素;心臟纖維化;人類免疫缺乏症候群;Carthamus tinctorius L.;Cardiomyocytes;HIV;HCV
日期:	2012-07-27
上传时间:	2012-08-31 16:10:23 (UTC+8)
出版者:	中國醫藥大學
摘要:	敗血病為?床上對於發炎反應所引起的全身性?續複雜的生?與病?現象。其特徵在於增加心臟輸出?，?低全身系統血管阻?、體溫?常、造成低血壓及敗血性休克，進而引發多重器官衰竭並導致死亡。心臟衰竭是敗血病患中經常併發的病症造成病患的左右心室收縮舒張功能急速減低。一般良床上抗內毒素的藥物大部分為抗生素，抗生素長期使用會有抗藥性的問題產生，因此開發抗內毒素的藥物，為目前臨床上主要的考量。紅花味多辛、苦，性多溫平。主歸肝、心經。性善走散通行，具活血化瘀之功能。本研究主要針對紅花乙醇粗萃物 ( FCEtOH)是否對於內毒素誘導心肌細胞凋亡、纖維化有抑制作用，並且進一步探討其藥理機轉。實驗結果發現，紅花乙醇粗萃物 ( FCEtOH )具有顯著抑制心肌細胞凋亡的功效，主要透過來抑制LPS所活化的JNK1/2，進一步抑制IκB降解與NFκB進核、阻止LPS誘發TNFα和active caspase-3的表現與心肌細胞凋亡。同時亦發現紅花乙醇粗萃物 ( FCEtOH ) 同時有穩定粒線體膜電位，抑制粒腺體細胞凋亡之功效。接下來進一步證實紅花乙醇粗萃物 ( FCEtOH ) 具有抗心肌纖維化的作用。實驗結果證實，紅花乙醇粗萃物( FCEtOH ) ，主要透過來抑制LPS所活化的ERK1/2，進一步抑制FGF、 uPA、MMP-2 及 MMP-9，達到進一步抑制心肌細胞纖維化。人類免疫缺乏症候群(human immunodeficiency virus 1 ) 及C型肝炎交叉感染已經成為公共衛生主要的問題。目前全球大約有10萬人為交叉感染之病患，本研究進一步探討活血化瘀藥是否具有抗病毒之功效，本研究使用紅花乙醇粗萃物( FCEtOH ) ，對於抗HIV及HCV之活性做進一步的探討，結果顯示本研究使用紅花乙醇粗萃物( FCEtOH ) 沒有任何抗病毒之功能，因此我們推測可能與本研究使用紅花乙醇粗萃物( FCEtOH ) 之成份有關。同時我們也證實活血化瘀類的中藥，不具有抗病毒之功效。 Severe and potentially fatal hypotension and cardiac contractile dysfunction are common symptoms in patients with sepsis. Our previous study we found that estradiol and estrogen- receptorαhave cardio protective effects in myocardial cells exposed to LPS. Estradiol supplementation has been shown to induce breast and cervical cancers. Carthami Flos, the flower of Carthamus tinctorius L. (Compositae) is an important traditional Chinese medicine used for the treatment of heart disease and inflammation, and therefore might be a potential alternative to Estradiol in the prevention of heart damage. This study investigated the effect of Carthami Flos ( FCEtOH) ethanolic extract on LPS-induced apoptosis in H9c2 cardiomyoblast induced apoptosis with LPS administration (1μg/ml). H9c2 cells were divided into five groups: Control, LPS (1μg/ml), and three FCEtOH ( 31.25, 62.5, and 125 μg/ml). We detected apoptosis using MTT, LDH, TUNEL assay. JC-1 staining and Western blot were used to detect pro-apoptosis proteins, anti-apoptosis proteins, MAPK proteins (JNK, ERK, and P38), and NF-κB expression. FCEtOH (62.5 ug/ml) inhibited LPS-induced apoptosis by suppressing JNK1/2 activity, which resulted in the reduction of both IκB degradation and NFκB activation. In addition , FCEtOH led to the activation of anti-apoptotic proteins, Bcl-2 , Bcl-xL , the stabilization of the mitochondria membrane and the down regulation of extrinsic and intrinsic pro-apoptotic proteins, such as TNFα, active caspase-8, t-Bid , Bax , active caspase-9, and active caspase-3. Carthami Flos possesses the ability to suppress JNK activity and inhibit LPS-induced TNF α activation and apoptosis in H9c2 cardiomyoblast cells. Carthami Flos could potentially serve as a cardio protective agent against LPS- induced apoptosis. Our previous study we found that LPS dramatically upregulates FGF-2, uPA, MMP-2 and MMP-9 in primary cardiac fibroblasts. MMPs are capable of denaturing and degrading fibrillar collagens and other components of the extracellular matrix (ECM). Studies show that dysregulation of MMPs is involved in the development of myocardial extracellular matrix remodelling and cardiac fibrosis, thus contributing to the progression of heart failure. This study was designed to investigate the effect of Carthami Flos (abbrev. FCEtOH) ethanolic extract on LPS-induced primary Cardiac Fibroblasts fibrosis. Here we show that LPS challenge increased the protein levels of FGF-2, uPA, MMP-2 and MMP-9, and induced the activity of MMP-2 and MMP-9 in H9c2 cardiomyoblast cells and primary cardiac fibroblasts. Administration of FCEtOH (62.5, and 125 μg/ml) downregulated expression of FGF-2, uPA, MMP-2 and MMP-9 in cardiac fibroblasts. Carthami Flos possesses the ability to suppress ERK activity and inhibit LPS-induced fibrosis in H9c2 cardiomyoblast cells and primary cardiomyo blast cells. Carthami Flos regulates blood circulation and addresses various disorders caused by blood stagnation, including gynecological or cardiovascular disorders, and the formation of nodules of blood stagnation. Coinfection with both human immunodeficiency virus 1 (HIV) and hepatitis C virus (HCV) has become a public health challenge, afflicting more than 10 million people worldwide. This study was designed to investigate FCEtOH anti-virus activity. Here we show that FCEtOH showed little to no antiviral activity.
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