桑葉多酚降低大鼠細菌性及化學性肝損傷之作用

近年來許多的研究都已證實肝臟發炎與許多疾病相關，而其中慢性發炎反應更是造成肝癌的最主要原因之一，而最近桑葉萃取物（MLE）也被研究出對於許多疾病具有抗氧化及抗發炎的成效。因此本研究在於探討桑葉萃取物對於大鼠肝臟抗發炎之影響。以八週齡體重約200-250 克雄性Sprague-Dawley（S.D.） rats 與Wistar rats 進行動物實驗。先於飼料中加入0.5%、1%、2% MLE 餵食一週後，再利用腹腔注射脂多醣體（LPS）、乙醯氨酚（APAP）兩種不同實驗模式去誘導大鼠產生肝損傷。結果發現個別單獨腹腔注射LPS、APAP 的組別（誘導組）其肝功能指數AST、ALT、促發炎反應激素（TNF-α、IL-6）、腎功能指標（BUN、CRE）與發炎蛋白（iNOS、COX-2、NF-κB）都呈現顯著上升，在肝臟酵素的部分，過氧化氫酶（CAT）、超氧化物歧化酶（SOD）、麩胱甘肽過氧化物酶（GSH-Px）其酵素活性皆顯著下降。而在添加MLE 的組別（MLE 組）血清中的肝功能指數、促發炎反應激素均有明顯降低（p<0.05），且肝臟中的發炎蛋白也呈現顯著抑制趨勢（p<0.01）；此外腎功能指標（BUN、CRE）在給予MLE的組別中也有下降；而其肝臟酵素的部分，抗氧化酵素活性都有回升的現象。綜合以上結果，證實MLE 可以有效減少LPS 及APAP 誘發的發炎反應進而改善大鼠肝損傷的程度。接著透過細胞實驗來檢測桑葉萃取物作用的分子標的，在給予TNF-α 誘導細胞發炎的情況下，處理桑葉多酚後藉由西方墨點法觀察，結果顯示MyD88、JNK、STAT3 都有顯著抑制的趨勢，因此證實桑葉多酚主要作用是透過抑制MyD88 後進而抑制發炎反應的產生。

There are many researches prove that liver inflammation has beenassociated with many diseases. Moreover sustained chronic inflammationcan cause one of the most common and deadly cancers in human,Hepatocellular carcinoma (HCC). There are many evidence showed thatthe water extract of mulberry leaves (MLE) has the ability of anti-oxidantand anti-inflammation for many diseases. Hence, we aimed to examinethe effect of MLE on anti-inflammation in the liver of rats. First, maleSprague-Dawley (S.D.) rats and Wistar rats (200 ± 50 g body weight)were induced liver injury by intraperitoneal injection LPS(Lipopolysaccharide) or APAP (Acetaminophen) and then wesupplemented with 0.5, 1 and 2% MLE for one week. The results showedthat LPS raised the level of AST, ALT, TNF-α, IL-6, BUN and CRE. Andthe proteins of NF-κB pathway also increased in the liver. Then, catalase(CAT), superoxide dismutases (SOD), glutathione peroxidase (GSH-Px),the enzyme activity of the liver showed decreased trend. While, treatMLE possessed the abilities to attenuate liver and kidney injury, as showby the reduction of AST, ALT, blood urine nitrogen (BUN), and theTNF-α, IL-6 in serum with the reduction trend. Moreover, SOD, GSH-Px,catalase level showed increased trend by MLE treatment. Based on theresults, MLE can reduce LPS, APAP-induced liver inflammation toameliorate thes seventy of liver injury. Then, we exam the mechanism ofMLPE by cell culture. In the present of TNF-α, treating MLPE inhibitsthe expression of MyD88, JNK, STAT3. Thus we prove that MLPEinhibits the inflammation by downregulating MyD88.