Bioassay-Guided Fractionation and Biological Activity of Cardenolides from Streptocaulon juventas.

Autor:	Xu Y; Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA., Xu J; Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, China., Zhu W; College of Pharmacy, Changchun University of Chinese Medicine, Changchun, China., Yan Y; Departments of Clinical & Translational Sciences, Biomedical Sciences and Medicine, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, United States., Jiang X; Department of Medicinal Chemistry, Anhui University of Chinese Medicine, Hefei, China., Xie Z; Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA., Feng F; Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, China., Zhang J; Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, China.
Jazyk:	angličtina
Zdroj:	Planta medica [Planta Med] 2023 Dec; Vol. 89 (15), pp. 1444-1456. Date of Electronic Publication: 2023 Sep 14.
DOI:	10.1055/a-2114-5371
Abstrakt:	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 . Competing Interests: The authors declare that they have no conflict of interest. (Thieme. All rights reserved.)
Databáze:	MEDLINE
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