类黄酮抑制LPS及TPA所引发大鼠神经胶质瘤细胞(glioma C6).docVIP

類黃酮抑制LPS及TPA所引發大鼠神經膠質瘤細胞 glioma C6 發炎反應 Flavonoids inhibit LPS and TPA- mediated inflammation in rat glioma C6 cells 研究生：江美靜 Chiang Mei-Ching 指導教授：黃卓治 Huang Tzou-Chi 堅果類、種子、豆類或茶及酒類12-O-tetradecanoylphorbol 13-acetate 共同誘導發炎反應，偵測其NO nitric oxide 與iNOS inducible NO synthase 、COX-2 cyclo- oxygenase-2 、MMP-9 matrix metallo-proteinases-9 表現量。實驗結果顯示抑制NO產生的能力為Quercetin＞Luteolin＞Genistein＞Daidzein,但四種類黃酮均不具抑制iNOS酵素活性之能力。Luteolin 可明顯抑制iNOS、COX-2、MMP-9 mRNA表現量。經由Zymography偵測MMP-9表現量，結果顯示40?M Luteolin可明顯抑制MMP-9產生。LPS/TPA可在30分鐘時誘發I?B?降解與磷酸化，?B?蛋白質表現。此抑制作用可能與類黃酮降低LPS/TPA誘發NF-?B活化，進而影響NF-?B之轉錄活性有關。 由以上結果推論在glioma C6 cell中，Quercetin 與Luteolin 抗發炎及抑制惡性腫瘤轉形作用能力可能與其結構上有關。Quercetin 與Luteolin A環的5、7 位上有hydroxyl group，B環的3，4鄰位有取代基，C環的2、3 位有雙鍵，因此抑制NO產生之活性高於Genistein與Daidzein。因C3，C5，C7，C3’，C4’位上都有-OH group，因此很容易與其標的蛋白質 如 iNOS, COX-2 形成氫鍵，而使得蛋白質立體結構改變，造成蛋白質不活化而抑制下游產物，如NO的產生，而達到抑制發炎及惡性腫瘤轉移作用。 關鍵字：神經膠質瘤細胞、類黃酮、轉形、發炎、結構與活性 【Abstract】 To date, more than 6000 flavonoids have been identified. Flavonoids are large group of phenolic plant constituents and widely distributed in fruit, vegetables, seeds, legumes, tea, red wine and medical herb. All of them have long been recognized to possess antioxidant, anti-inflammatory, antiallergic , hepatoprotective, antiviral and anticarcinogenic activities. However, there are few reports about the relationships between structure and activity. Glial cell which play a pivotal role in immunological defense ,rapidly become activated upon neuronal injury or inflammatory stimulation and release immune modulators such as potentially damaging nitric oxide NO , thereby further contributing to transformation of glioma. Therefore, in this study, we attempt to investigate the effect of Genistein, Daidzein, Quercetin, and Luteolin on anti-inflammation and inhibitory of malignant tumor transformation activity in vitro. Analysis the role of flavonoids on chemoprevention and structure activity relationships. It may be helpful to syntheaize useful anti-inflammator