桑葉抽出物及主要綠原酸衍生物藉由增加caveolin-1 signals及抑制氧化壓力減少慢性酒精性肝炎之作用

過量的酒精攝取引發肝細胞毒性，最終導致多種肝臟疾病，如脂肪性肝炎和肝硬化。在此，我們研究的目地在探討桑葉抽出物及其主要成分綠原酸和新綠原酸對酒精性脂肪性肝炎的影響。我們使用液相色譜 - 質譜分析確定桑葉抽出物的組成，其顯示桑葉抽出物主要由綠原酸衍生物和其他多酚組成。接下來，我們使用高酒精飼料小鼠模型，證實桑葉抽出物緩解酒精誘導肝細胞疾病之作用，可導致肝損傷標記物和脂質累積下降。此外，桑葉抽出物減少脂質過氧化，同時升高肝臟超氧化物歧化酶的酵素活性。免疫組織化學染色顯示桑葉抽出物增加第一型小窩蛋白的表達，但減少表皮生長因子受體、信號轉導和轉錄激活子3，誘導型一氧化氮合酶和受體相互作用蛋白1/3的表現。桑葉抽出物的主要成分，綠原酸和新綠原酸，不僅發揮與桑葉抽出物相似的生物活性，而且抑製酒精誘導的促凋亡信號。總之，桑葉抽出物及其綠原酸衍生物增加第一型小窩蛋白的表達並減少表皮生長因子受體 /信號轉導和轉錄激活子3 /誘導型一氧化氮合酶的信號傳導，此可能有助於肝臟脂質累積和過氧化的下降及抑制促凋亡信號。

Excessive alcohol uptake exerts hepatocellular toxicity, ultimately leading to multiple liver diseases such as steatohepatitis and liver cirrhosis. Here, we aimed to explore the effects of mulberry leaf extract (MLE) and its major component chlorogenic acid (CGA) and neochlorogenic acid (nCGA) on the alcoholic steatohepatitis. We determined the composition of MLE using liquid chromatography - mass spectrometric (LC-MS) analysis, which showed that MLE consisted of mainly chlorogenic acid derivatives and other polyphenols. Next, we utilized high alcohol-fed mouse model and demonstrated that MLE alleviated alcohol-induced hepatocellular disorders, resulting inthe lowered hepatic injury markers and lipid accumulation. In addition, MLE reduced the lipid peroxidation and meanwhile elevated hepatic superoxide dismutase (SOD). Immunohistochemical (IHC) staining revealed that MLE elevated expression of caveolin-1 but reduced expression of epidermal growth factor receptor (EGFR), signal transducer and activator of transcription (STAT), inducible nitric oxide synthase (iNOS) and receptor interacting protein (RIP)1/3. Major components of MLE, CGA and nCGA, not only exerted the similar biological activity as MLE but also inhibited alcohol-induced pro-apoptotic signals. In conclusion, MLE and its chlorogenic derivatives CGA and nCGA upregulate caveolin-1 expression and diminish EGFR/STAT3/iNOS signaling, which may contribute to the lowered hepatic lipid accumulation and peroxidation and the inhibited pro-apoptotic cascades.