北沙参木脂素类功效成分的代谢网络及其产地加工对质量影响的研究

The quality related factors of Glehnia Radix and its evaluation methods need to be further investigated due to the notable distinction detected in different resources at present market. Our previous research indicated that the major effective components of Glehnia Radix should be lignan and neolignan glycosides such as glehlinosides A-J, which exhibted activities of anti-gastric ulcer，anti-inflammation and ameliorating memory deficits. In an attempt to develop a future efficient quality control methods,the present research focus on the following: optimization of LC (HPLC and UPLC), LC-MS and NMR spectroscopic analysis methods for glehlinosides, using multiple detection systems to ensure a wide coverage of glehlinosides (including the minor derivatives)；metabolomic analysis of the glehlinosides biosynthetic pathway,fluctuation and accumulation pattern during the roots developmental stage, exploring their related local specialized factors such as environmental stress，cultivation and collection, elucidation of glehlinosides metabolic profiling，and then development of “essential node compound”-based quality control methods；assessment the rationality and effects of preliminary processing on quality and activities of Glehnia littoralis (including the activities of anti-gastric ulcer and ameliorating memory deficits）to ensure efficacy and safety of Glehnia Radix.

目前，市场上的北沙参药材规格和质量差异显著，其资源品质的影响因素和评价方法尚待深入考察。前期，我们发现了北沙参特征性的木脂素苷和异木脂素苷类药效成分群，如glehlinosides A—J等，其抗胃溃疡、抗炎和改善记忆障碍作用明显。为今后能够有效地控制药材质量，拟开展以下研究内容：考察液相色谱、液相色谱-质谱联用、核磁共振谱等分析条件，建立多种方法相结合的分析系统，完整而专属性地检测北沙参木脂素成分群（包括其中的微量同系物），同时，应用代谢组学方法，考察药材生长期内北沙参木脂素的生物合成途径、转化和积累模式，以及环境胁迫、栽培和采收等产地特化影响因素，解析北沙参木脂素的代谢网络，并建立基于代谢网络节点化合物的药材质量控制方法；考察产地加工方法对药材质量和药效作用水平的影响（包括抗胃溃疡作用和和改善记忆障碍作用），探讨产地加工方法是否合理，解决北沙参规格不一、质量和疗效无法保证的问题。

本项目通过探索北沙参木脂素的代谢网络和影响因素，揭示了北沙参资源品质特征和形成机制，研究结果表明，在一年生长期内，北沙参木脂素的含量呈现上升趋势，其代谢网络“节点”化合物 (-)-secoisolariciresinol-4-O-β-D-glucopyranoside的含量变化最明显，可作为指导采收和栽培的指标成分；建立了北沙参木脂素的多元分析方法，其中，红外光谱和近红外光谱法结合多元统计分析，能够直观、快捷、准确、整体性地评价北沙参药材质量，特别适合多批量药材的质量评价；建立了一种有机聚合物固相萃取方法，用于北沙参木脂素类成分分析检测前的样品预处理，提高了分析效能；建立了木脂素类成分专属性的液相色谱-质谱联用分析检测方法，特别是针对其中的微量同系物, 解决了北沙参木脂素组成复杂、同系物化学性质相近、难于分析的问题；阐明了产地初加工方法的合理性，即加工后药材的抗炎作用更显著，且诱导过敏性皮炎的香豆素类成分的含量显著降低，研究结果为确保药材临床应用的安全有效，解决北沙参药材规格不统一等问题提供了理论依据。