现代医学研究表明肝纤维化既是各种慢性肝病发展的共同结果，又是肝硬化的必经阶段，更是肝细胞癌的前兆。临床抗肝纤维化药物的疗效并不理想，药物昂贵，不良反应大等阻碍了肝纤维化的治疗。申请人在前期研究工作中发现三七总皂苷水解产物25-OCH3-PPD可显著抑制大鼠肝星状细胞（t-HSC/Cl-6）增值，减少平滑肌肌动蛋白（α-SMA）、TGF-β、TIMP-1的表达，调节NF-κB重分布，同时可显著逆转CCl4诱导的大鼠肝纤维化程度。本项目拟对该类苷元的抗肝纤维化作用机制和靶点进行研究（主要研究否是通过经p38 MAPK调节TGF-β/Smad通路发挥抗肝纤维化作用，精确的作用靶点）。同时，以关键药效团以及活性位点为指导，有针对性的对活性较好的化合物进行结构修饰和优化，通过活性测试和与生物大分子反相对接等方法探讨该类化合物的构效关系，推测其作用机理和靶点，进而发现理想的肝纤维化保护剂先导化合物。

Modern medical research shows that liver fibrosis is a common result of the development of various chronic liver disease, but also the necessary stage of cirrhosis, liver cancer is a precursor. Clinical anti-liver fibrosis drug efficacy is not ideal, expensive drugs, adverse reactions and other obstacles to the treatment of liver fibrosis. (T-HSC / Cl-6) increased the proliferation of rat hepatic stellate cells (α-SMA), and the results showed that the total saponin hydrolyzate 25-OCH3-PPD could significantly inhibit the proliferation of rat hepatic stellate cells (t-HSC / TGF-β, TIMP-1 expression, regulation of NF-κB redistribution, and can significantly reverse the CCl4-induced rat liver fibrosis. The aim of this study is to study the anti-hepatic fibrosis mechanism and target of this kind of aglycone (mainly to study the effect of p38 MAPK on TGF-β / Smad pathway to play an anti-hepatic fibrosis effect and accurate target). At the same time, with the guidance of key pharmacophores and active sites, the compounds with better activity were modified and optimized. The activity of the compounds was investigated by means of activity test and reverse alignment with biological macromolecules. Relationship, presumption of its mechanism and target, and then to find the ideal liver fibrosis protective agent lead compounds.