基于补气助阳功效辨析中药人参和红参“生熟异治”的物质基础

It is of great significance to explore the correlation between the change of chemical composition and difference of pharmacological effects on promoting the improvement of processing technology of not processed and processed Chinese medicine. Red ginseng is the processed product of ginseng. There are significant differences in clinical application between ginseng and red ginseng. Ultimately, the different clinical efficacy was caused by the different exposure profile of active ingredients in vivo after processing. In the previous study, it was found that ginseng and red ginseng had significantly different therapeutic effects on qi-deficient animals, and the content proportion of constituents absorbed into blood was significantly different from that in medicine. Therefore, it was speculated that the different active component groups of ginseng and red ginseng in the body were the direct material basis for the difference in efficacy. Taking the effect on tonifying qi and invigorating yang as the breakthrough point, this project identified the components absorbed into blood and focused on the correlation analysis by combining different activity of monomer composition in blood with the overall efficacy of ginseng and red ginseng. The effective material foundation of different effect will be discriminated. The study will be helpful for the formulation of scientific quality standards that can reflect the difference in clinical application. The research will also provide a reference for investigating “not processed and processed chinese medicine used in different situation” of traditional herb medicine with modern theory.

探究中药“生熟”药效变化的物质基础对于推动中药炮制工艺的改进具有重要意义。红参是中药人参采收后的蒸制加工品，在临床应用时与人参存在着显著的差异。疗效的差异归根结底是因为炮制前后进入体内的活性成分暴露轮廓的不同。本项目前期研究发现人参和红参对于气虚动物的治疗效果有明显的差异，并且体内入血成分的含量比例与药材中含量比例显著不同，据此推测人参和红参在体内入血成分的种类和含量差异是引起药效差异的重要的物质基础。因此本项目以中药人参、红参为研究对象，以人参和红参补气助阳活性为切入点，通过对体内各自的入血成分进行定性和定量表征，对入血单体成分的补气活性进行评价，再与人参和红参整体药效进行相关性分析，辨析人参和红参药效差异的物质基础，为制订能体现临床应用差异的科学的质量标准提供依据，也为其他中药“生熟异治”用现代理论阐释提供借鉴。

本研究以人参和红参为研究对象，以与临床应用相关的补气助阳药效差异为切入点，运用代谢组学技术对人参和红参吸收入血的成分差异进行系统表征，采用气虚模型小鼠，高脂模型小鼠和心力衰竭模型小鼠对人参和红参补气助阳药效进行评价，对人参和红参吸收入血的主要差异成分单体（Rg5和Rk1等）的体外和体内药效评价，进行相关性分析，辨析人参和红参各自发挥药效的活性化学成分。研究表明，人参和红参口服给药后吸收入血的成分均是以Rb1，Rb2，Rc等大极性皂苷成分为主，差异成分体现在以Rg5和Rk1为代表的小极性皂苷成分。人参提取物和红参提取物可显著增强气虚小鼠的耐力，可明显缩短强迫游泳实验中动物静止不动的时间，增加运动的时间。.与HFD 模型组相比，红参醇提物均能显著减少小鼠脂肪组织重量；人参及红参醇提物均能改善小鼠肝脏及外周脂肪组织的脂质沉积；红参醇提物能降低小鼠血清和肝脏甘油三酯水平，而人参醇提物能降低小鼠肝脏甘油三酯和血清胆固醇的水平，在降低体重指标上，红参效果要优于人参。.原人参三醇（PPT）是通过激活AMPK/ PGC-1α/ PPAR-γ信号通路对去氧肾上腺素诱导的心肌肥厚具有保护作用，提示PPT可能是一种治疗心肌肥厚的理想化合物。对作用机制的研究发现是通过抑制NADPH氧化酶活性和上调内源性抗氧化途径来预防pe诱导的氧化应激。