α-常春藤皂苷抗肿瘤活性研究进展

Research Progress on Anti-Tumor Activity ofα-Hederin

α-常春藤皂苷(α-hederin)是一种单桥糖三萜皂苷,存在于常春藤叶片,具有广泛的药理活性。其中,人们发现α-常春藤皂苷最诱人的功能是其极高的抗肿瘤活性。目前,α-常春藤皂苷被发现的抗肿瘤机制包括自噬激活、一氧化氮调控、上皮间质转化阻滞、Hippo-Yap信号通路激活和促进活性氧积累等,且不仅于此。在这些细胞效应中,活性氧是α-常春藤皂苷发挥功能的核心桥梁。有足够的证据表明,α-常春藤皂苷诱导的肿瘤细胞凋亡、糖代谢水平下调、氧化应激发生和铁死亡敏感性上调都是由ROS所介导的;同时,也有理由相信,ROS还可能参与了α-常春藤皂苷诱导的Hippo信号通路激活和自噬启动。近年来,有一些研究对α-常春藤皂苷进行了改良,包括靶向递送的设计,生物利用度的调整和溶血活性的规避等。这给α-常春藤皂苷的开发和应用增加了更多的可能性。目前,关于α-常春藤皂苷的抗肿瘤药理研究仍然在广泛地开展,其丰富的生物学功能和极高的生物学活性使之成为一种十分具有前景的化合物。以近些年α-常春藤皂苷在抗肿瘤药理学上的成果作一综述,以期为该先导化合物的后续研发和临床应用提供理论参考依据,并提供新的思路。

Theα-Hederin is a mono-bridgesaccharide triterpene saponin found in ivy leaves and has a wide range of pharmacological activities.One of the most attractive functions ofα-hederin has been found is its extremely high antitumour activity.At present,the anti-tumour mechanisms identified forα-hederin include autophagy activation,nitric oxide modulation,epithelial mesenchymal transition blockade,Hippo-Yap signalling pathway activation and promotion of reactive oxygen species accumulation,and not just these.Among these cellular effects,reactive oxygen species are a central bridge for the function ofα-hederin.There is sufficient evidence to suggest thatα-hederin induced apoptosis,down-regulation of glucose metabolism levels,oxidative stress onset and up-regulation of Ferroptosis sensitivity in tumour cells are all mediated by ROS.Also,there is a reason to believe that ROS may also be involved inα-hederin induced Hippo signaling pathway activation and autophagy initiation.In recent years,a number of studies have been conducted to improveα-hederin,including the design of targeted delivery,adjustment of bioavailability and circumvention of haemolytic activity.This has added more possibilities to the development and application ofα-hederin.At present,the anti-tumour pharmacological studies onα-hederin are still widely carried out,and its rich biological functions and extremely high biological activities make it a very promising compound.In this paper,it reviewed the recent results on the anti-tumour pharmacology ofα-hederin in order to provide theoretical references and new ideas for the subsequent development and clinical application of this pioneering compound.