OncoWitan, Lille (Wasquehal), 59290, France.
University of Lille, Inserm, INFINITE - U1286, Institut de Chimie Pharmaceutique Albert Lespagnol (ICPAL), Faculté de Pharmacie, 3 rue du Professeur Laguesse, BP-83, F-59006, Lille, France.
Phytomedicine. 2020 Dec;79:153343. doi: 10.1016/j.phymed.2020.153343. Epub 2020 Sep 21.
Esculentosides and related phytolaccosides form a group of oleanene-type saponins isolated from plants of the Phytolaccaceae family, essentially Phytolacca esculenta, P. americana and P. acinosa. This chemical family offers a diversity of glycosylated compounds, including molecules with a mono-, di- or tri-saccharide unit at position C-3, and with or without a glucose residue at position C-28. The esculentosides, which derive essentially from the sapogenin jaligonic acid or its 30-methyl ester phytolaccagenin, exhibit anti-inflammatory, antifungal and anticancer activities.
The objective of the review was to identify the 26 esculentosides (ES) and phytolaccosides known to date, including 16 monodesmosidic and 10 bidesmosidic saponins, and to review their pharmacological properties and molecular targets.
The retrieval of potentially relevant studies was done by systematically searching of scientific databases like Google Scholar and PubMed in January-May 2020. The main keywords used as search terms were related to esculentosides, phytolaccosides and Phytolaccaceae. The systematic search retrieved about 110 papers that were potentially relevant and after an abstract-based selection, 68 studies were analyzed in details and discussed.
The structural relationship between the compounds and their sapogenin precursors has been studied. In addition, the pharmacological properties of the main ES, such as ES-A, -B and -H, have been analyzed to highlight their mode of action and potential targets. ES-A is a potent inhibitor of the release of cytokines and this anti-inflammatory activity contributes to the anticancer effects observed in vitro and in vivo. Potential molecular targets of ES-A/B include the enzymes cyclooxygenase 2 (COX-2) and casein kinase 2 (CK2). In addition, the targeting of the protein high-mobility group box 1 (HGMB1) by ES-A/B is proposed, based on molecular modeling and the structural analogy with the related saponin glycyrrhizin, a potent HGMB1 alarmin inhibitor.
More work is needed to properly characterize the molecular targets but otherwise compounds like ES-A and ES-H emerge as potent anti-inflammatory and anticancer agents and ES-B as an antifungal agent. A preclinical development of these three compounds should be considered.
Esculentosides 和相关的 phytolaccosides 是一组从 Phytolaccaceae 科植物中分离出来的齐墩果烷型皂苷，主要来源于商陆（Phytolacca esculenta）、美洲商陆（P. americana）和白商陆（P. acinosa）。该化学家族提供了多种糖基化化合物，包括在 C-3 位具有单糖、二糖或三糖单元的分子，以及在 C-28 位具有或不具有葡萄糖残基的分子。Esculentosides 主要来源于皂苷元 jaligonic 酸或其 30-甲酯 phytolaccagenin，具有抗炎、抗真菌和抗癌活性。
本综述的目的是确定迄今为止已知的 26 种 esculentosides（ES）和 phytolaccosides，包括 16 种单糖苷和 10 种双糖苷皂苷，并综述其药理学特性和分子靶标。
通过系统搜索科学数据库（如 Google Scholar 和 PubMed），于 2020 年 1 月至 5 月检索潜在相关研究。使用的主要关键词与 esculentosides、phytolaccosides 和 Phytolaccaceae 相关。系统检索检索到约 110 篇潜在相关的论文，在基于摘要的选择后，分析了 68 项研究并进行了讨论。
研究了化合物与其皂苷元前体之间的结构关系。此外，还分析了 ES-A、-B 和 -H 等主要 ES 的药理学特性，以突出其作用模式和潜在靶标。ES-A 是细胞因子释放的有效抑制剂，这种抗炎活性有助于体外和体内观察到的抗癌作用。ES-A/B 的潜在分子靶标包括环氧化酶 2（COX-2）和酪蛋白激酶 2（CK2）等酶。此外，基于分子建模和与相关皂苷甘草酸的结构相似性，提出 ES-A/B 靶向高迁移率族盒 1（HGMB1），甘草酸是一种有效的 HGMB1 警报素抑制剂。
需要进一步研究以正确表征分子靶标，但 ES-A 和 ES-H 等化合物作为有效的抗炎和抗癌药物，ES-B 作为抗真菌药物脱颖而出。应考虑对这三种化合物进行临床前开发。
