基于仿生手段界定“生熟异用”五味子中“五味”的 特征成分群及功效关系

According to ancient writings, the sour and sweet taste exist in Schisandra chinensis flesh, the bitter and pungency taste in seed and all of them have salty. As a traditional Chinese medicine, the tonic effect of Schisandra chinensis is from processed products, and the raw as a cough medicine. The research of pharmacodynamics before and after processing have been reported, but none reported on the relationship between five flavours, components and functions. Traditional Chinese medicine theory and modern technical methods were combined in this project. Schisandrae Chinensis, rich in taste and different functions in raw and processed products, as experimental materials. The crude, vinegar product and different parts as the object of study. In order to clear the relationship between five flavours and components, multiple types of characteristic components were separated by modern methods, qualitative and quantitative analysis were conducted by UPLC/MS and GC/MS, and five flavours were difined by bionics such as electronic tongue and electronic nose. To further clarify the correlation of five tastes, characteristic components and efficacy, chronic obstructive pulmonary disease model, ammonia induced cough model and aging model were applied in functional verification. The acquired data would provide theory basis in processing principle and rational clinical application.

五味子，古籍既载有“皮肉甘酸，核中辛苦，都有咸味”之说，又有“入补药熟用，入嗽药生用”之效。目前关于五味子炮制前后的药效学性能已有报道，但关于五味子中“五味”的物质基础和药效之间的相关性未见报道。本项目将传统中医药理论与现代科技手段相结合，以“五味俱全，生熟异用”的五味子为实验材料，以生五味、醋五味及其不同部位为研究对象，利用电子舌、电子鼻等现代仿生技术界定各种制品中“酸、苦、甘、辛、咸”的物质基础，采用现代分离分析方法获得“五味”的不同类型特征成分群，并通过UPLC/MS、GC/MS等色谱手段进行定性定量分析，明确“五味”与特征成分群之间的关系。应用慢性阻塞性肺病模型、氨水引咳模型和衰老模型，对五味子生熟制品进行药效学功能验证，阐明“五味—特征成分群—功效”三者之间的物性关系，为五味子“生熟异用”的炮制原理及临床合理应用提供理论依据。

五味子，古籍既载有“皮肉甘酸，核中辛苦，都有咸味”之说，又有“入补药熟用，入嗽药生用”之效。目前关于五味子炮制前后的药效学性能已有报道，但关于五味子中“五味”的物质基础和药效之间的相关性报道较少。本项目将传统中医药理论与现代科技手段相结合，以 “五味俱全，生熟异用”的五味子为实验材料，以五味子、炮制品及其不同组分为研究对象，利用电子舌、电子鼻等现代仿生技术界定各种制品中“酸、苦、甘、辛、咸”的物质基础，采用现代分离分析方法获得“五味”的不同类型特征成分群，并通过UPLC/MS、GC/MS等色谱手段进行定性定量分析，明确“五味”与特征成分群之间的关系。应用细胞生物学、动物模型，对五味子进行药效学功能验证，为五味子“生熟异用”的炮制原理及临床合理应用提供理论依据。本项目采用HPLC、UPLC、GC、MS色谱技术建立了五味子中所含物质基础的检测方法，包括木脂素、核苷、香气成分和脂肪酸类成分的种类和含量的变化。电子鼻、电子舌的实验结果表明，五味子中主要味觉指标为酸味、咸味、涩味，其中酸味传感器贡献率最高，其次是咸味传感器。其中五味子、炮制品及其各类成分的五味各有一定的趋向。历代本草著作记载五味子具有敛肺止咳、补肾宁心等传统功效，故本实验结合现代药理学检测其改善肺损伤和肾损伤的作用机制。结果表明五味子乙素对脂多糖诱导的Beas-2B人肺上皮细胞的损伤具有保护作用，能够抑制LPS诱导的Beas-2B人肺上皮氧化损伤、炎性反应及细胞凋亡，可调整凋亡通路相关蛋白以及NF-κB信号通路相关蛋白的表达。同时，五味子乙素对脂多糖诱导的小鼠急性肺损伤有保护作用，可显著抑制LPS诱导的肺W/D比值、MPO活性和炎性细胞因子TNF-α、IL-6 和IL-1β的表达，提高SOD、GSH和CAT活力，活化NF-κB通路的相关蛋白表达。五味子醇甲对过氧化氢诱导的HK-２人肾皮质近曲小管上皮细胞的损伤具有保护作用，对细胞毒活性、凋亡、周期、氧化指标等均有一定影响，改善肾细胞损伤。