Qiu Zi-Dong, Wei Xu-Ya, Chen Ze-Yan, Guo Juan, Huang Lu-Qi, Lai Chang-Jiang-Sheng
State Key Laboratory Breeding Base of Dao-di Herbs, National Resource Centre for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, PR China.
State Key Laboratory Breeding Base of Dao-di Herbs, National Resource Centre for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, PR China.
Phytomedicine. 2022 Jun;100:154059. doi: 10.1016/j.phymed.2022.154059. Epub 2022 Mar 15.
The synergic action of compound prescriptions is an important feature and core advantage of traditional medicine. Ginseng-Fuzi decoction is a classic compatible phytomedicine in China, of which Ginseng can effectively reduce the toxicity of Fuzi in clinical, but the detoxification chemical mechanism is still unclear.
Develop a novel method for real-time tracking and monitoring of complex substances in the decoction system of traditional Chinese medicine to uncover the detoxification effect Ginseng on Fuzi and explore the possible chemical reaction mechanism of Ginseng-Fuzi co-decoction.
A novel real-time monitoring system, online filtration electrospray ionization mass spectrometry, was developed for extremely complex substances analysis in the decoction of traditional medicine compounds to uncover the directionally detoxification effect and the mechanism of compatibility interaction.
Nine key alkaloids and 7 ginsenosides in Ginseng-Fuzi decoction were simultaneously in-situ monitoring in positive ion mode or negative ion mode respectively. Both types of targeted analytes had satisfactory MS signal response for real-time qualitative and quantitative analysis with high precision (RSD < 14.04%) and low LLODs (0.002 ng/ml-10 ng/ml). Through long-term tracking analysis, the exact detoxification and synergistic effect of Ginseng-Fuzi decoction were confirmed as the concentration of main toxic alkaloids decreased (e.g. the content of mesaconitine has been reduced by about 38%) and the main active monoester alkaloids increased obviously. More importantly, the possible molecular mechanism of the detoxification effect of Ginseng compatibility was revealed for the first time, which was the nucleophilic substitution reaction of diester alkaloids catalyzed by fatty acids.
This study revealed the exact effect of co-decoction of Ginseng and Fuzi at the molecular level and the chemical reaction mechanism of fatty acid-catalyzed degradation of toxic diester-type alkaloids. The comprehensive multi-component real-time monitoring strategy for complex traditional medicine compounds developed and implemented here has important demonstration significance for revealing the scientific connotation of the compatibility of compound traditional medicine.
复方的协同作用是传统医学的一个重要特征和核心优势。参附汤是我国一种经典的配伍中药，其中人参在临床上能有效降低附子的毒性，但其解毒化学机制仍不清楚。
开发一种用于实时跟踪和监测中药汤剂系统中复杂物质的新方法，以揭示人参对附子的解毒作用，并探索参附合煎的可能化学反应机制。
开发了一种新型实时监测系统——在线过滤电喷雾电离质谱，用于分析中药复方汤剂中极其复杂的物质，以揭示其定向解毒作用和配伍相互作用机制。
分别在正离子模式或负离子模式下同时原位监测了参附汤中的9种关键生物碱和7种人参皂苷。两类目标分析物均具有令人满意的质谱信号响应，可用于高精度（相对标准偏差<14.04%）和低检测限（0.002 ng/ml - 10 ng/ml）的实时定性和定量分析。通过长期跟踪分析，证实了参附汤确切的解毒和协同作用，即主要有毒生物碱浓度降低（如中乌头碱含量降低了约38%），主要活性单酯生物碱明显增加。更重要的是，首次揭示了人参配伍解毒作用的可能分子机制，即脂肪酸催化二酯生物碱的亲核取代反应。
本研究在分子水平上揭示了人参和附子合煎的确切效果以及脂肪酸催化有毒二酯型生物碱降解反应的化学机制。本文开发并实施的针对复杂中药复方的多成分实时综合监测策略，对揭示复方中药配伍的科学内涵具有重要的示范意义。
