title: New Knowledge About Old Drugs: The Anti-Inflammatory Properties of Cardiac Glycosides.
abstract: In the 19th century, cardio-active steroid glycosides, shortly cardiac glycosides, were scientifically established as drugs against heart failure. Theirin vivo, cellular, and molecular actions as well as their predominant target, Na+-K+-ATPase, have been comprehensively investigated in the 20th century and the discovery of endogenous cardiac glycosides has fostered this research field. In the last years, however, results from clinical trials and meta-analyses have questioned their therapeutic value due to efficacy and safety issues. This has led to a considerable decline of their usage. Beyond the cardiovascular system, cardiac glycosides have been increasingly recognized as antitumor compounds and Na+-K+-ATPase has evolved into a promising drug target in oncology. A wealth of review articles exists that intensively discuss these topics. Surprisingly, the anti-inflammatory actions of cardiac glycosides, which were discovered in the 1960s, have so far hardly been perceived and have not yet been summarized. This review provides an overview of thein vivoandin vitroactions of cardiac glycosides on inflammatory processes and of the signaling mechanisms responsible for these effects: cardiac glycosides have been found to decrease inflammatory symptoms in different animal models of acute and chronic inflammation. Regarding the underlying mechanisms most research has focused on leukocytes. In these cells, cardiac glycosides primarily inhibit cell proliferation and the secretion of proinflammatory cytokines.
authors.affiliation: Institute of Pharmaceutical Biology, Biocenter, Goethe University, Frankfurt/Main.
authors.forename: Robert
authors.initials: R
authors.lastname: Fürst
authors.affiliation: Institute of Pharmaceutical Biology, Biocenter, Goethe University, Frankfurt/Main.
authors.forename: Ilse
authors.initials: I
authors.lastname: Zündorf
authors.affiliation: Institute of Pharmaceutical Biology, Biocenter, Goethe University, Frankfurt/Main.
authors.forename: Theo
authors.initials: T
authors.lastname: Dingermann
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D002301:Cardiac Glycosides / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004070:Digitalis / Q000737:chemistry*; D006321:Heart / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D009206:Myocardium / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
chemical_list: D000893:Anti-Inflammatory Agents; D002301:Cardiac Glycosides; D000254:Sodium-Potassium-Exchanging ATPase