The MOE Key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
The MOE Key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Guangxi Wuzhou Pharmaceutical (Group) Co., Ltd, Wuzhou, 543000, China.
J Ethnopharmacol. 2024 Jan 30;319(Pt 1):117126. doi: 10.1016/j.jep.2023.117126. Epub 2023 Sep 15.
Panax notoginseng (Burk.) F. H. Chen, a valuable Chinese herb medicine, shows a characteristic bi-directional regulation of hemostasis and activating blood circulation with ginsenosides as the predominant bioactive compounds and is a typical representative of "processing triggered heteropotency".
Processing triggered heteropotency, one of the unique theories and practices in traditional Chinese medicine, refers to that the processing will lead to change in physical and chemical properties, and eventually disparate efficacy of the crude drugs, yet the optimum process and underlying mechanism remains unclear. In this study, using Panax notoginseng (PN) as a representative sample, a processing-(chemical) profiling-pharmacodynamics (3-P) relationship was proposed to investigate the processing mechanism of PN.
Firstly, a temperature programmed steaming process was designed to evaluate the steaming triggered chemical transformation of triterpene saponins and the corresponding enhancement in anti-platelet aggregation activity. The steaming process was programed from the conventional 100 °C-150 °C in a time course of 0-12 h, aiming to achieve the maximized conversion of rare ginsenosides (RGs), and dynamic profile of ginsenosides were constructed by a UPLC-Q-TOF-MS/MS analysis. Then, a processing-(chemical) profiling-pharmacodynamics (3-P) relationship was assessed by using the grey relational analysis (GRA) and orthogonal projections to latent structures (OPLS), and validated by bioactive fraction of 140 °C steamed PN. Subsequently, the P2Y-ligand binding affinity of potential candidates was analyzed by molecular docking. Finally, the dynamic changes of ginsenosides during steaming of SPN were quantitatively detected by UPLC-QQQ-MS/MS.
A total of 48 differential ginsenosides were characterized and monitored including the primary and secondarily transformed saponins. The higher temperature steaming especially at 140 °C induces not only the predominant production of the RGs, but also the stronger anti-platelet aggregation activity. The 3-P relationship showed the fraction (3) of 140 °C steamed PN rich in RGs exhibits the most predominant efficacy, in which, a series of RGs including ginsenosides Rg5, Rk1, 20(S/R)-Rg3 were proven to be potent components. Molecular docking analysis suggested that ginsenosides Rg5 and Rk1 showed more strong interaction with the platelet P2Y receptor. Quantitative analysis found 140 °C-2h PN possessed highest contents of Rk1 and Rg5 and total RGs.
The integrated 3-P strategy uncovered the promising ginsenosides with anti-platelet effect, thereby revealing the material basis of PN steaming, which could provide a new enlightenment for the investigation of processing mechanism of traditional Chinese medicines.
三七（Burk.）F. H. Chen，一种有价值的中国草药，以人参皂苷为主要生物活性化合物，表现出止血和活血的双向调节作用，是“炮制触发异效”的典型代表。
炮制触发异效是中药的独特理论和实践之一，是指炮制会导致中药材的物理化学性质发生变化，最终导致疗效不同，但最佳炮制方法和潜在机制仍不清楚。本研究以三七（PN）为代表样本，提出了一种炮制（化学）谱-药效（3-P）关系，以研究 PN 的炮制机制。
首先，设计了温度程序蒸制工艺，以评估三萜皂苷的蒸制触发化学转化及其对抗血小板聚集活性的增强作用。蒸制过程从 100°C-150°C 的常规温度编程，时间为 0-12 小时，旨在实现稀有皂苷（RGs）的最大转化率，并通过 UPLC-Q-TOF-MS/MS 分析构建人参皂苷的动态图谱。然后，通过灰色关联分析（GRA）和正交投影到潜在结构（OPLS）评估炮制（化学）谱-药效（3-P）关系，并通过 140°C 蒸制 PN 的生物活性部分进行验证。随后，通过分子对接分析潜在候选物的 P2Y 配体结合亲和力。最后，通过 UPLC-QQQ-MS/MS 定量检测 SPN 蒸制过程中人参皂苷的动态变化。
共鉴定和监测了 48 种差异人参皂苷，包括初级和次级转化皂苷。较高温度的蒸制，特别是 140°C，不仅会导致主要的 RG 产生，而且会导致更强的抗血小板聚集活性。3-P 关系表明，富含 RG 的 140°C 蒸制 PN 的部分（3）显示出最主要的功效，其中包括一系列 RG，包括人参皂苷 Rg5、Rk1、20(S/R)-Rg3，被证明是有效的成分。分子对接分析表明，人参皂苷 Rg5 和 Rk1 与人血小板 P2Y 受体有更强的相互作用。定量分析发现，140°C-2h PN 具有最高含量的 Rk1 和 Rg5 以及总 RG。
综合 3-P 策略揭示了具有抗血小板作用的有前途的人参皂苷，从而揭示了 PN 蒸制的物质基础，为传统中药炮制机制的研究提供了新的启示。
