A Short Review on Cardiotonic Steroids and Their Aminoguanidine Analogues

Melero, Concepción P.; Medarde, Manuel; Feliciano, Arturo San

doi:10.3390/50100051

Cited by 114 publications

(87 citation statements)

References 90 publications

(59 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These headings were interchanged with the word "herbal," and limits were placed on keywords so that only human cases were brought forward. Using a list contained within a review by Melero et al of CAS, we constructed our list of CAS sources [9]. Papers published in languages other than English were translated.…”

Section: Methodsmentioning

confidence: 99%

Cardioactive steroid poisoning: A comparison of plant- and animal-derived compounds

et al. 2006

View full text Add to dashboard Cite

Introduction: Cardioactive steroids (CASs) are found in plants, animals, and insects. Their affinity for Na+-K+ ATPase is attenuated by the type of lactone at carbon 17 (C17) of the steroid backbone: those with 5-membered lactone rings, or cardenolides, are derived mostly from plants with 6-membered rings or from animals with bufadienolides. A systematic review of CAS poisoning was performed to compare the mortality rate of cardenolides and bufadienolides.Methods: MEDLINE was searched for articles using commonly reported names of CASs, and keywords were limited to human cases only. We searched cases from 1982 to 2003, so that supportive care was similar and digoxin-specific Fab was available. Identified reports of CAS poisoning were read to exclude cases involving licensed pharmaceuticals. Inclusion criteria included hyperkalemia, gastrointestinal symptoms, electrocardiographic evidence of CAS toxicity, digoxin serum concentration, or history of exposure to a substance containing a CAS. Clinical data was collected, including information about treatment with digoxin-specific Fab and treatment outcome.Results: Fifty-nine articles, describing 924 patients, were identified. Eight hundred ninety-seven patients (97%) ingested a CAS with a 5-membered lactone ring, and mortality was 6% (n = 54). Twenty-seven patients (2.9%) ingested a CAS with a 6-membered lactone ring, and mortality was 29.6% (n = 8). The difference in mortality rates was statistically significant (p < 0.001, [X 2 ]). CASs with 6-member rings accounted for the highest percentage of nonsuicidal exposures.Conclusion: Although cardenolides accounted for the majority of exposures, bufadienolides were five times more lethal than cardenolides.

show abstract

Section: Methodsmentioning

confidence: 99%

Cardioactive steroid poisoning: A comparison of plant- and animal-derived compounds

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Generally, this steroid core is double-substituted with an unsaturated lactone ring at position 17 and a sugar portion at position 3; and this lactone moiety of cardiac glycosides is critical for their potent inhibition of Na + /K + -ATPase. Although the sugar moiety does not greatly influence their biological activity, the addition of sugars to the steroid core affects the pharmacodynamic and pharmacokinetic profile of each glycoside [28] .…”

Section: Introductionmentioning

confidence: 99%

Active ingredients in Chinese medicines promoting blood circulation as Na+/K+-ATPase inhibitors

Chen¹,

Jinn

Chen³

et al. 2011

Acta Pharmacol Sin

View full text Add to dashboard Cite

The positive inotropic effect of cardiac glycosides lies in their reversible inhibition on the membrane-bound Na + /K + -ATPase in human myocardium. Steroid-like compounds containing a core structure similar to cardiac glycosides are found in many Chinese medicines conventionally used for promoting blood circulation. Some of them are demonstrated to be Na + /K + -ATPase inhibitors and thus putatively responsible for their therapeutic effects via the same molecular mechanism as cardiac glycosides. On the other hand, magnesium lithospermate B of danshen is also proposed to exert its cardiac therapeutic effect by effectively inhibiting Na + /K + -ATPase. Theoretical modeling suggests that the number of hydrogen bonds and the strength of hydrophobic interaction between the effective ingredients of various medicines and residues around the binding pocket of Na + /K + -ATPase are crucial for the inhibitory potency of these active ingredients. Ginsenosides, the active ingredients in ginseng and sanqi, substantially inhibit Na + /K + -ATPase when sugar moieties are attached only to the C-3 position of their steroid-like structure, equivalent to the sugar position in cardiac glycosides. Their inhibitory potency is abolished, however, when sugar moieties are linked to C-6 or C-20 position of the steroid nucleus; presumably, these sugar attachments lead to steric hindrance for the entrance of ginsenosides into the binding pocket of Na + /K + -ATPase. Neuroprotective effects of cardiac glycosides, several steroid-like compounds, and magnesium lithospermate B against ischemic stroke have been accordingly observed in a cortical brain slice-based assay model, and cumulative data support that effective inhibitors of Na + /K + -ATPase in the brain could be potential drugs for the treatment of ischemic stroke.

show abstract

“…9,10) Thus far, the biological actions of cardenolide aglycones on the NF-κB-dependent gene expression induced by proinflammatory cytokines have been poorly characterized. We found that ouabagenin, digitoxigenin, and digoxigenin inhibit the TNF-α-induced ICAM-1 expression.…”

mentioning

confidence: 99%

“…8) Cardiac glycosides are a family of compounds that function as allosteric inhibitors of Na + /K + -ATPase. 9) Cardiac glycosides possess common structures, including a steroid core, an unsaturated lactone ring, and a sugar moiety, and are classified into two groups: cardenolides (five-membered butyrolactone ring) and bufadienolides (six-membered pyrone ring). 10,11) It has been reported that the cardenolide glycoside ouabain is able to activate the NF-κB signaling pathway at concentrations that do not inhibit Na + /K + -ATPase activity.…”

mentioning

confidence: 99%

Cardenolide Aglycones Inhibit Tumor Necrosis Factor α-Induced Expression of Intercellular Adhesion Molecule-1 at the Translation Step by Blocking Na+/K+-ATPase

et al. 2015

View full text Add to dashboard Cite

Cardiac glycosides, which are inhibitors of Na /K -ATPase, are classified into cardenolides and bufadienolides. We have recently shown that two cardenolide glycosides, ouabain and odoroside A, inhibit Na / K -ATPase, thereby preventing nuclear factor κB-inducible protein expression by blocking Na -dependent amino acid transport. In this study, we investigated the mechanism of action of cardenolide aglycones in tumor necrosis factor α (TNF-α)-induced gene expression. Ouabagenin, digitoxigenin, and digoxigenin were found to inhibit the TNF-α-induced cell-surface expression of intercellular adhesion molecule-1 (ICAM-1) in human lung carcinoma A549 cells. Those cardenolide aglycones did not inhibit the TNF-α-induced expression of ICAM-1 mRNA, but strongly inhibited the TNF-α-induced expression of ICAM-1 as translation product. The inhibition of the TNF-α-induced ICAM-1 expression by ouabagenin, digitoxigenin, and digoxigenin was significantly reversed by the ectopic expression of ouabain-resistant rat Na /K -ATPase α1 isoform. Moreover, knockdown of Na /K -ATPase α1 isoform augmented the inhibition of the TNF-α-induced ICAM-1 expression by ouabagenin or ouabain. These results clearly indicate that cardenolide aglycones inhibit the TNF-α-induced ICAM-1 expression at the translation step by blocking Na /K -ATPase.

show abstract

A Short Review on Cardiotonic Steroids and Their Aminoguanidine Analogues

Abstract: A short review on cardiotonic steroids and their analogues is presented. The natural, semisynthetic and synthetic derivatives, as well as their mechanism of action and structure-activity relationships are shown, with a special reference to aminoguanidine derivatives.

Cited by 114 publications

References 90 publications

Cardioactive steroid poisoning: A comparison of plant- and animal-derived compounds

Cardioactive steroid poisoning: A comparison of plant- and animal-derived compounds

Active ingredients in Chinese medicines promoting blood circulation as Na+/K+-ATPase inhibitors

Cardenolide Aglycones Inhibit Tumor Necrosis Factor α-Induced Expression of Intercellular Adhesion Molecule-1 at the Translation Step by Blocking Na+/K+-ATPase

Contact Info

Product

Resources

About