Organic Synthesis and Mass Spectrometry Laboratory (S2MOs), University of Mons-UMONS, 23 Place du Parc, 7100 Mons, Belgium.
Molecules. 2023 Feb 23;28(5):2087. doi: 10.3390/molecules28052087.
Escins constitute an abundant family of saponins (saponosides) and are the most active components in (horse chestnut-HC) seeds. They are of great pharmaceutical interest as a short-term treatment for venous insufficiency. Numerous escin congeners (slightly different compositions), as well as numerous regio-and stereo-isomers, are extractable from HC seeds, making quality control trials mandatory, especially since the structure-activity relationship (SAR) of the escin molecules remains poorly described. In the present study, mass spectrometry, microwave activation, and hemolytic activity assays were used to characterize escin extracts (including a complete quantitative description of the escin congeners and isomers), modify the natural saponins (hydrolysis and transesterification) and measure their cytotoxicity (natural vs. modified escins). The aglycone ester groups characterizing the escin isomers were targeted. A complete quantitative analysis, isomer per isomer, of the weight content in the saponin extracts as well as in the seed dry powder is reported for the first time. An impressive 13% in weight of escins in the dry seeds was measured, confirming that the HC escins must be absolutely considered for high-added value applications, provided that their SAR is established. One of the objectives of this study was to contribute to this development by demonstrating that the aglycone ester functions are mandatory for the toxicity of the escin derivative, and that the cytotoxicity also depends on the relative position of the ester functions on the aglycone.
七叶皂苷由大量的甾体皂苷（皂角苷）组成，是马栗树种子中最具活性的成分。作为静脉功能不全的短期治疗方法，它们具有重要的药用价值。从马栗树种子中可以提取出许多七叶皂苷的同系物（略有不同的成分）和许多区域和立体异构体，这使得质量控制试验成为强制性的，尤其是因为七叶皂苷分子的结构-活性关系（SAR）仍然描述得很差。在本研究中，采用质谱、微波激活和溶血活性测定法来表征七叶皂苷提取物（包括对七叶皂苷同系物和异构体的完整定量描述），修饰天然皂苷（水解和酯交换）并测量其细胞毒性（天然七叶皂苷与修饰七叶皂苷）。针对七叶皂苷异构体的糖苷配基酯基进行了靶向研究。首次报道了在皂苷提取物以及种子干粉中，对同系物逐个进行的完整定量分析。在干种子中，七叶皂苷的含量高达 13%，这证实了马栗树七叶皂苷必须绝对考虑用于高附加值应用，前提是要建立其 SAR。本研究的目的之一是通过证明糖苷配基酯基对于七叶皂苷衍生物的毒性是必需的，以及细胞毒性还取决于酯基在糖苷配基上的相对位置，从而为这一发展做出贡献。
