Guo Yaqing, Wu Kai, Yang Haoran, Lin Xiaoyu, Yang Huiying, Wu Xianfu
National Institutes for Food and Drug Control, Beijing 102629, China.
College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan 430081, China.
Int J Mol Sci. 2024 Dec 10;25(24):13231. doi: 10.3390/ijms252413231.
Ginsenoside Re was the major bioactive component found rich in C. A. Meyer, which exerted excellent cardiovascular protection, anti-inflammatory, and anti-oxidation effects. The generation of unexpected degradation products (DPs) may influence the therapeutic effect of Re, or even bring toxic effects to patients. However, to date, only a few reports were available about the stability of Re. The present study aims to systematically investigate the degradation behaviors of Re under different stress conditions, including hydrolysis (acidic, basic, and neutral), oxidation, humidity, thermal, and photolytic (ultraviolet and visible light) conditions. A total of thirteen DPs were putatively identified, and among them, nine were discovered for the first time in our study. The results showed that Re was sensitive to exposure to acidic, basic, and oxidation conditions. It underwent a series of chemical degradation reactions, including deglycosylation, dehydration, addition, oxidation at the double bond, and isomerization under various stress conditions. Structural characterization of these DPs was carried out by UHPLC-DAD-CAD and LC-LTQ/Orbitrap. A plausible mechanism of their formation was proposed to support the structures of all DPs of Re. In silico toxicity prediction and metabolism behavior assessment were done by Derek Nexus and Meteor Nexus software. Re and DP-1 to DP-6 were predicted to possess potential skin irritation/corrosion toxicity. DP-11 and DP-12 bear the potential for carcinogenicity, mutagenicity, irritation, hepatotoxicity, and skin sensitization. The observation of these DPs updates our knowledge regarding the stability of Re, which provides valuable information for quality control and to choose suitable storage conditions.
人参皂苷Re是在刺五加中发现的主要生物活性成分，具有出色的心血管保护、抗炎和抗氧化作用。意外降解产物（DPs）的产生可能会影响Re的治疗效果，甚至给患者带来毒性作用。然而，迄今为止，关于Re稳定性的报道很少。本研究旨在系统地研究Re在不同应激条件下的降解行为，包括水解（酸性、碱性和中性）、氧化、湿度、热和光解（紫外线和可见光）条件。总共推定鉴定出13种DPs，其中9种是在我们的研究中首次发现的。结果表明，Re对酸性、碱性和氧化条件敏感。在各种应激条件下，它经历了一系列化学降解反应，包括去糖基化、脱水、加成、双键氧化和异构化。通过UHPLC-DAD-CAD和LC-LTQ/Orbitrap对这些DPs进行了结构表征。提出了一个合理的形成机制来支持Re所有DPs的结构。通过Derek Nexus和Meteor Nexus软件进行了计算机毒性预测和代谢行为评估。预测Re和DP-1至DP-6具有潜在的皮肤刺激/腐蚀毒性。DP-11和DP-12具有致癌性、致突变性、刺激性、肝毒性和皮肤致敏性的潜力。对这些DPs的观察更新了我们对Re稳定性的认识，为质量控制和选择合适的储存条件提供了有价值的信息。
