Department of Pathology, Chung Shan Medical University Hospital, Taichung, Taiwan and Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan.
Department of Pathology, Chung Shan Medical University Hospital, Taichung, Taiwan and Department of Pathology, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Food Funct. 2017 Jan 25;8(1):397-405. doi: 10.1039/c6fo01539e.
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 components chlorogenic acid (CGA) and neochlorogenic acid (nCGA) on 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 a high alcohol-fed mouse model and demonstrated that MLE alleviated alcohol-induced hepatocellular disorders, resulting in lowered hepatic injury markers and lipid accumulation. In addition, MLE reduced lipid peroxidation and meanwhile elevated hepatic superoxide dismutase (SOD). Immunohistochemical (IHC) staining revealed that MLE elevated the expression of caveolin-1 but reduced the expressions 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 a similar biological activity as MLE but also inhibited alcohol-induced pro-apoptotic signals. Involvement of caveolin-1 in MLE, CGA and nCGA was demonstrated by using specific small inhibitory RNA. In conclusion, MLE and its chlorogenic derivatives CGA and nCGA upregulate caveolin-1 expression and diminish EGFR/STAT3/iNOS signalling, which may contribute to lowered hepatic lipid accumulation and peroxidation and inhibited pro-apoptotic cascades.
过量饮酒会对肝细胞造成毒性，最终导致多种肝脏疾病，如脂肪性肝炎和肝硬化。在这里，我们旨在探讨桑叶提取物（MLE）及其主要成分绿原酸（CGA）和新绿原酸（nCGA）对酒精性脂肪性肝炎的影响。我们使用液相色谱-质谱联用（LC-MS）分析确定了 MLE 的组成，结果表明 MLE 主要由绿原酸衍生物和其他多酚组成。接下来，我们利用高酒精喂养的小鼠模型表明 MLE 减轻了酒精引起的肝细胞紊乱，导致肝损伤标志物和脂质积累降低。此外，MLE 减少了脂质过氧化，同时提高了肝超氧化物歧化酶（SOD）。免疫组织化学（IHC）染色显示 MLE 上调了 caveolin-1 的表达，但降低了表皮生长因子受体（EGFR）、信号转导和转录激活因子（STAT）、诱导型一氧化氮合酶（iNOS）和受体相互作用蛋白（RIP）1/3 的表达。MLE 的主要成分 CGA 和 nCGA 不仅表现出与 MLE 相似的生物学活性，还抑制了酒精诱导的促凋亡信号。通过使用特异性小干扰 RNA 证实了 MLE、CGA 和 nCGA 中 caveolin-1 的参与。总之，MLE 及其绿原酸衍生物 CGA 和 nCGA 上调 caveolin-1 的表达，减少 EGFR/STAT3/iNOS 信号通路，这可能有助于降低肝脂质积累和过氧化作用，并抑制促凋亡级联反应。
