钠/钾-ATP酶被发现可作为信号转导器后，我们开始研究强心甾类结构多样性并研究其配体效应。通过钠/钾-ATP酶活性测定引导的分离法，我们从青春草中共分离出20种强心甾类化合物，包括未描述的juventasoside B (10: ) 和19种已知的强心甾类。它们的结构已被阐明。利用我们纯化的钠/钾-ATP酶平台和LLC-PK1细胞模型，我们发现，处于引起不到10%的钠/钾-ATP酶抑制作用浓度的10: ，能够刺激钠/钾-ATP酶/Src受体复合物并选择性激活下游通路，最终改变前列腺癌细胞的生长。通过评估分离的强心甾类化合物的配体效应，我们发现对细胞存活力的调节与其抑制钠/钾-ATP酶活性的效力无关，而是与它们与钠/钾-ATP酶受体的配体结合能力相关。基于这一发现，我们确定了一种独特的活性强心甾类化合物，地高辛（1: ），并验证了它能够保护LLC-PK1细胞免受缺氧损伤，表明其在缺血/再灌注损伤和促进人体真皮成纤维细胞胶原合成方面的潜在用途，进一步证实化合物2: 是青春草伤口愈合活性的分子基础。专利所有，转载请注明出处。

The discovery that Na/K-ATPase acts as a signal transducer led us to investigate the structural diversity of cardiotonic steroids and study their ligand effects. By applying Na/K-ATPase activity assay-guided fractionation, we isolated a total of 20 cardiotonic steroids from Streptocaulon juventas, including an undescribed juventasoside B (10: ) and 19 known cardiotonic steroids. Their structures have been elucidated. Using our platform of purified Na/K-ATPase and an LLC-PK1 cell model, we found that 10: , at a concentration that induces less than 10% Na/K-ATPase inhibition, can stimulate the Na/K-ATPase/Src receptor complex and selectively activate downstream pathways, ultimately altering prostate cancer cell growth. By assessing the ligand effect of the isolated cardiotonic steroids, we found that the regulation of cell viability by the isolated cardiotonic steroids was not associated with their inhibitory potencies against Na/K-ATPase activity but reflected their ligand-binding affinity to the Na/K-ATPase receptor. Based on this discovery, we identified a unique active cardiotonic steroid, digitoxigenin (1: ), and verified that it can protect LLC-PK1 cells from hypoxic injury, implicating its potential use in ischemia/reperfusion injury and inducing collagen synthesis in primary human dermal fibroblast cells, and implicating that compound 2: is the molecular basis of the wound healing activity of S. juventas.Thieme. All rights reserved.