Abstract：
Liver fibrosis, a progressive process of fibrous scarring, results from the accumulation of extracellular matrix proteins (ECM). If left untreated, it often progresses to diseases such as cirrhosis and hepatocellular carcinoma. Lycorine, a natural alkaloid derived from medicinal plants, has shown diverse bioactivities by targeting JAK2/STAT3 signaling, but its pharmacological effects and potential molecular mechanisms in liver fibrosis remains largely unexplored. The purpose of this study is to elucidate the pharmacological activity and molecular mechanism of lycorine in anti-hepatic fibrosis. Findings indicate that lycorine significantly inhibited hepatic stellate cells (HSCs) activation by reducing the expression of α-SMA and collagen-1. In vivo, lycorine treatment alleviated carbon tetrachloride (CCl4) -induced mice liver fibrosis, improving liver function, decreasing ECM deposition, and inhibiting fibrosis-related markers\' expression. Mechanistically, it was found that lycorine exerts protective activity through the JAK2/STAT3 and PI3K/AKT signaling pathways, as evidenced by transcriptome sequencing technology and small molecule inhibitors. These results underscore lycorine\'s potential as a therapeutic drug for liver fibrosis.
摘要：
肝纤维化,纤维性瘢痕形成的渐进过程，细胞外基质蛋白（ECM）积累的结果。如果不及时治疗，它通常会发展为肝硬化和肝细胞癌等疾病。石蒜碱,从药用植物中提取的天然生物碱，通过靶向JAK2/STAT3信号传导显示出多种生物活性，但其在肝纤维化中的药理作用和潜在的分子机制仍未被探索。目的阐明石蒜碱抗肝纤维化的药理活性及分子机制。结果表明，石蒜碱通过降低α-SMA和胶原蛋白1的表达显着抑制肝星状细胞（HSC）的活化。在体内,石蒜碱治疗减轻四氯化碳（CCl4）诱导的小鼠肝纤维化，改善肝功能,减少ECM沉积，并抑制纤维化相关标志物的表达。机械上,发现石蒜碱通过JAK2/STAT3和PI3K/AKT信号通路发挥保护活性,转录组测序技术和小分子抑制剂证明了这一点。这些结果强调了石蒜碱作为肝纤维化治疗药物的潜力。
