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國立中興大學 森林學系所 王升陽所指導 古山吉的 紅果釣樟果實成分Lucidone之抗發炎、護肝及抑制黑色素形成活性 (2010),提出switch prod.keys dow關鍵因素是什麼,來自於絲裂原活化蛋白激酶、絲裂原活化蛋白激酶、絲裂原活化蛋白激酶、絲裂原活化蛋白激酶、絲裂原活化蛋白激酶、絲裂原活化蛋白激酶、絲裂原活化蛋白激酶、絲裂原活化蛋白激酶。
最後網站Activating a Product on Steam則補充:How do I register a CD Key to activate a product on Steam? Please follow these instructions to activate a new retail purchase on Steam:.
紅果釣樟果實成分Lucidone之抗發炎、護肝及抑制黑色素形成活性
為了解決switch prod.keys dow 的問題,作者古山吉 這樣論述:
Lucidone是紅果釣樟果實之主成分,已被初步證實具有抗發炎的活性,本論文進一步的探討Lucidone的生物活性及其作用機制。首先我們利用細胞及動物試驗來分析Lucidone抗發炎活性的機制。在以脂多醣(LPS)誘導發炎的小鼠巨噬細胞(Raw cell 264.7)及肝臟組織中,其一氧化氮自由基(NO)和前列腺素(PGE2)的含量明顯的降低了。此外,在發炎小鼠巨噬細胞中也發現Lucidone能夠降低Tumor necrosis factor-α (TNF-α)的含量。由mRNA和蛋白的表現分析結果也可證實,無論在細胞及動物試驗中,Inducible nitric oxide synthas
e (iNOS)和Cyclooxygenase-2 (COX-2)之蛋白及mRNA表現,都受到Lucidone的抑制並呈現劑量相關性。另外Lucidone也降低了Nuclear factor-kappa B (NF –κB)含量,並減少了Inhibitor kappa B (IκB)的降解,進而降低了細胞核內p65/p50 (NF –κB)的含量。因此證明Lucidone可以藉由抑制NF –κB啟動因子之活性來達到抑制NF –κB的效果。此外,Lucidone可以抑制由c-JUN活化之N-terminal kinase (JNK)和p38 MAPKs之蛋白表現,進而抑制NO、PGE2和TNF-
α的產生,同時Lucidone也抑制了NF –κB和activator protein-1 (AP-1)的活化。綜合上述,我們得知在細胞及動物試驗中Lucidone可藉由抑制一系列的發炎因子及其調節之信號路徑來達到抗發炎的效果。接著續利用細胞及動物證實,Lucidone具有保護小鼠之肝臟因酒精誘導產生病變之活性。細胞試驗中,將HepG2細胞以Lucidone (1-10 μg/mL) 處理並使用乙醇 (100 mM) 誘導其病變;另外在體內試驗中,同樣使用乙醇 (80 % v/v) 來誘導ICR公鼠之肝臟病變。而由一些與乙醇誘導肝臟病變相關之細胞激素 (如ROS、MDA、ALT和AST) 的表
現得知,Lucidone可以顯著地對肝臟細胞產生保護作用並呈現劑量相關性。此外,Licidone可增加肝臟細胞在酒精傷害後穀胱甘肽(GSH)的含量以及降低丙二醛(MDA)和活性氧(ROS)的生成。另外根據蛋白表現分析及RT-PCR的結果顯示,在受到Lucidone處理後也同時提高細胞中HO-1及Nrf-2之蛋白及mRNA的表現。對於乙醇所引起的肝臟病變,Nrf-2信號途徑及其所調節之HO-1的表現可以提供確實的保護作用,這些結果也進而證明了Lucidone確實具有保護肝臟的能力。最後,本論文並探討Lucidone是否可抑制酪氨酸酶(tyrosinase)和抗黑色素生成(anti-melanog
enic)的能力。研究結果發現,Lucidone能有效的抑制Mammalian yrosinase的活性,我們使用了α-MSH-induced B16 murine melanoma cells來探討Lucidone對Mammalian tyrosinase的活性之機制。藉由蛋白質表現分析本論文發現Lucidone減少了Tyrosinase和MIFF(Microphthalmia-associated Transcription Factor)蛋白之表現並呈現劑量相關性,因此Lucidone透過抑制Tyrosinase的活性來減少B16細胞中黑色素的含量,另外由RT-PCR的分析證實Lucid
one能夠抑制tyrosinase之mRNA表現並呈現劑量相關性。此外,本論文並分析了Lucidone對ERK1/2這個MIFF轉錄抑制因子的影響,結果顯示Lucidone未能使ERK1/2蛋白的活化,而參考藥物ascorbic acid則明顯的活化了ERK1/2的表現。因此我們的試驗結果也清楚的證明了Lucidone是藉由抑制tyrosinase的活性來達到抗黑色素生成的效果。綜合以上結果可知,Lucidone具有抗發炎、保肝、抗氧化和抗黑色素生成的活性,因此Lucidone具有作為先導化合物來開發成為藥物的潛力。
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