Department of Biochemistry and Microbiology, University of Chemistry and Technology Prague, Technická 3, 166 28 Prague 6, Czech Republic.
Biomolecules. 2021 Apr 29;11(5):659. doi: 10.3390/biom11050659.
Cardiac glycosides (CGs) are natural steroid compounds occurring both in plants and animals. They are known for long as cardiotonic agents commonly used for various cardiac diseases due to inhibition of Na/K-ATPase (NKA) pumping activity and modulating heart muscle contractility. However, recent studies show that the portfolio of diseases potentially treatable with CGs is much broader. Currently, CGs are mostly studied as anticancer agents. Their antiproliferative properties are based on the induction of multiple signaling pathways in an NKA signalosome complex. In addition, they are strongly connected to immunogenic cell death, a complex mechanism of induction of anticancer immune response. Moreover, CGs exert various immunomodulatory effects, the foremost of which are connected with suppressing the activity of T-helper cells or modulating transcription of many immune response genes by inhibiting nuclear factor kappa B. The resulting modulations of cytokine and chemokine levels and changes in immune cell ratios could be potentially useful in treating sundry autoimmune and inflammatory diseases. This review aims to summarize current knowledge in the field of immunomodulatory properties of CGs and emphasize the large area of potential clinical use of these compounds.
强心苷（CGs）是天然甾体化合物，存在于植物和动物中。由于抑制 Na+/K+-ATP 酶（NKA）泵活动和调节心肌收缩力，它们作为强心剂已为人所知很长时间，常用于各种心脏疾病。然而，最近的研究表明，CGs 可治疗的疾病谱要广泛得多。目前，CGs 主要作为抗癌药物进行研究。它们的抗增殖特性基于 NKA 信号体复合物中多个信号通路的诱导。此外，它们与免疫原性细胞死亡密切相关，这是一种诱导抗癌免疫反应的复杂机制。此外，CGs 还具有各种免疫调节作用，其中最重要的作用是通过抑制核因子 kappa B 来抑制 T 辅助细胞的活性或调节许多免疫反应基因的转录。细胞因子和趋化因子水平的这种调节以及免疫细胞比例的变化可能对治疗各种自身免疫和炎症性疾病有用。本综述旨在总结 CGs 的免疫调节特性的现有知识，并强调这些化合物具有广泛的临床应用潜力。
