土家药四楞麻抗肝纤维化活性成分及作用机制研究

Many chronic liver diseases are featured with the hepatic fibrosis(HF) during the pathological progress. Due to the complexity of the pathogenesis of hepatic fibrosis, the development of effective anti-HF medicines remains an ongoing challenge. Guiding by the anti-HF activity, the study will investigate the anti-HF bioactive components from the medical plant of Phlomis umbrosa Turcz, using the method of natural products chemistry bioactivity tracing and separation. The study will separate the bioactive phenylethanoid glycosides from P. umbrosa by the phytochemical methods, such as the macroporous adsorption resin, reverse phase preparative chromatography etc. The pure isolated compounds will be elucidated by spectrum analysis methods, NMR, IR, HR-MS and so on. The anti-HF mechanisms of bioactive phenylethanoid glycosides of the P. umbrosa will be investigated using the methods including anti-virus and HSC inhibitory analysis in vitro, the influence of collagenic content and serum indicators in vivo, anti-lipid peroxidation and down-regulation of cellular factors expression etc. Based on the above study, the computer aided design software will be used to estimate the anti-HF structure–activity relationship of phenylethanoid glycosides. The study will explore the anti-HF mechanisms and working targets of active glycosides from P. umbrosa, find the potential anti-HF candidate compounds, lay foundations for the research and development of new drugs in the chronic liver diseases treatment.

肝纤维化是慢性肝病重要的病理特征，防治肝纤维化是临床治疗慢性肝病的关键环节，由于肝纤维化发病机制的复杂性，临床上仍缺乏有效的治疗药物。本项目基于前期的研究基础，采用天然产物生物活性跟踪分离方法对土家药四楞麻中具有抗肝纤维化作用的苯乙醇苷类化合物进行研究。在抗肝纤维化活性指导下，采用大孔吸附树脂、反相制备色谱等方法分离土家药四楞麻中苯乙醇苷类物质，运用NMR、HR-MS等波谱解析方法鉴定分离得到的单体化合物的结构；采用体外抗病毒作用和抑制HSC作用研究，体内对胶原的含量和血清指标的影响，抗脂质过氧化作用及抑制细胞因子的表达等方法考察糙苏中苯乙醇苷类化学成分的抗肝纤维化作用及作用机制；在此基础上，运用计算机辅助药物设计软件进一步阐明抗肝纤维化构效关系。寻找潜在的抗肝纤维化活性化合物(组合化合物)，为治疗慢性肝病创新药物的研究开发奠定基础。

肝纤维化是慢性肝病重要的病理特征，防治肝纤维化是临床治疗慢性肝病的关键环节，由于肝纤维化发病机制的复杂性，临床上仍缺乏有效的治疗药物。本项目采用中药生物活性跟踪分离方法对土家族民间药材四楞麻中具有抗肝纤维化作用的苯乙醇苷类化合物采用大孔吸附树脂、反相制备色谱等中药化学成分研究方法分离四楞麻中苯乙醇苷类物质，运用NMR、HR-MS等波谱解析方法鉴定分离得到的单体化合物的结构；采用抑制HSC作用研究，以及对胶原的含量和血清指标的影响，抗脂质过氧化作用及抑制细胞因子的表达等方法考察四楞麻中苯乙醇苷类化学成分的抗肝纤维化作用的作用机制。研究结果表明，土家药四楞麻中的苯乙醇苷类化合物具有较好的抗肝纤维化活性作用，具有重要的研究开发价值。苯乙醇苷类化合物有可能成为防治慢性肝病的一类重要的活性化合物，通过对这类化合物防治肝病深入的研究，可以为中药治疗慢性肝病创新药物的研究开发奠定基础。