Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (780 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
Cyclopentanophenanthrenes with a 5- or 6-membered lactone ring attached at the 17-position and sugars attached at the 3-position. Plants they come from have long been used in congestive heart failure. They increase the force of cardiac contraction without significantly affecting other parameters, but are very toxic at larger doses. Their mechanism of action usually involves inhibition of the NA(+)-K(+)-exchanging atpase and they are often used in cell biological studies for that purpose.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Glycosides, Cardiac; Cardiotonic Steroid; Steroid, Cardiotonic; Cardiotonic Steroids; Steroids, Cardiotonic; Cardiac Glycoside; Glycoside, Cardiac.
Where it fits in the MeSH classification
- Broader topics
- Cardanolides; Glycosides
- Narrower topics
- Bufanolides; Cardenolides; Digitalis Glycosides; Proscillaridin; Strophanthins
Related concepts
- Sugars
- Exchanging Atpase
Research landscape
PubMed indexes 45,391 records tagged with the MeSH heading “Cardiac Glycosides” (counts retrieved 2026-10-31). 1,581 of them (3.5%) were published from 2020 onward, and the busiest period so far is through 1999 with 36,416 records.
Reviews account for 2,823 records (6.2%) and meta-analyses for 45. Randomized controlled trials number 700 (1.5%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 36,416 |
| 2000-2009 | 4,137 |
| 2010-2019 | 3,257 |
| 2020 onward | 1,581 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 2,823 | 6.2% |
| Meta-analyses | 45 | 0.1% |
| Randomized controlled trials | 700 | 1.5% |
Method: PubMed query "Cardiac Glycosides"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in drugs and chemicals
Studies of a chemical or drug can answer very different questions: what it is and how it behaves in cells and animals, how the body handles it, and whether it changes outcomes in people. Laboratory and animal findings often do not carry over to patients, and observational studies of exposures are confounded by who uses a substance and why. Nothing on this page is a recommendation to use, avoid, start or stop any substance or medicine; talk to a qualified clinician or pharmacist about your own situation. Check the dose, the species, the comparison group and whether a patient-relevant outcome was measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
Identification and characterization of Cardiac Glycosides as senolytic compounds [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Compounds with specific cytotoxic activity in senescent cells, or senolytics, support the causal involvement of senescence in aging and offer therapeutic interventions.
- Closing excerpt
- This experimental approach allows the identification of compounds with senolytic activity that could potentially be used to develop effective treatments against age-related diseases.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (149 words)
Compounds with specific cytotoxic activity in senescent cells, or senolytics, support the causal involvement of senescence in aging and offer therapeutic interventions. Here we report the identification of Cardiac Glycosides (CGs) as a family of compounds with senolytic activity. CGs, by targeting the Na+/K+ATPase pump, cause a disbalanced electrochemical gradient within the cell causing depolarization and acidification. Senescent cells present a slightly depolarized plasma membrane and higher concentrations of H+, making them more susceptible to the action of CGs. These vulnerabilities can be exploited for therapeutic purposes as evidenced by the in vivo eradication of tumors xenografted in mice after treatment with the combination of a senogenic and a senolytic drug. The senolytic effect of CGs is also effective in the elimination of senescence-induced lung fibrosis. This experimental approach allows the identification of compounds with senolytic activity that could potentially be used to develop effective treatments against age-related diseases.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 31636264 · DOI · PMC6803708
Oleandrin, a cardiac glycoside, induces immunogenic cell death via the PERK/elF2α/ATF4/CHOP pathway in breast cancer [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Chemotherapeutic agents have been linked to immunogenic cell death (ICD) induction that is capable of augmenting anti-tumor immune surveillance.
- Closing excerpt
- Oleandrin combined with immune checkpoint inhibitors might improve the efficacy of immunotherapy.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (222 words)
Chemotherapeutic agents have been linked to immunogenic cell death (ICD) induction that is capable of augmenting anti-tumor immune surveillance. The cardiac glycoside oleandrin, which inhibits Na+/K+-ATPase pump (NKP), has been shown to suppress breast cancer growth via inducing apoptosis. In the present study, we showed that oleandrin treatment triggered breast cancer cell ICD by inducing calreticulin (CRT) exposure on cell surface and the release of high-mobility group protein B1 (HMGB1), heat shock protein 70/90 (HSP70/90), and adenosine triphosphate (ATP). The maturation and activation of dendritic cells (DCs) were increased by co-culturing with the oleandrin-treated cancer cells, which subsequently enhanced CD8+ T cell cytotoxicity. Murine breast cancer cell line EMT6 was engrafted into BALB/c mice, and tumor-bearing mice were administered with oleandrin intraperitoneally every day. Oleandrin inhibited tumor growth and increased tumor infiltrating lymphocytes including DCs and T cells. Furthermore, the differential mRNA expression incurred by oleandrin was investigated by mRNA sequencing and subsequently confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. Mechanistically, oleandrin induced endoplasmic reticulum (ER) stress-associated, caspase-independent ICD mainly through PERK/elF2α/ATF4/CHOP pathway. Pharmacological and genetic inhibition of protein kinase R-like ER kinase (PERK) suppressed oleandrin-triggered ICD. Taken together, our findings showed that oleandrin triggered ER stress and induced ICD-mediated immune destruction of breast cancer cells. Oleandrin combined with immune checkpoint inhibitors might improve the efficacy of immunotherapy.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 33762577 · DOI · PMC7990929
Therapeutic potential of targeting membrane-spanning proteoglycan SDC4 in hepatocellular carcinoma [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Syndecan-4 (SDC4) functions as a major endogenous membrane-associated receptor and widely regulates cytoskeleton, cell adhesion, and cell migration in human tumorigenesis and development, which represents a charming anti-cancer therapeutic target.
- Closing excerpt
- Our results indicate that membrane-spanning proteoglycan SDC4 is a promising druggable target for HCC, and pharmacological regulation of SDC4/DDX23 signaling axis with small-molecule holds great potential to benefit HCC patients.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (156 words)
Syndecan-4 (SDC4) functions as a major endogenous membrane-associated receptor and widely regulates cytoskeleton, cell adhesion, and cell migration in human tumorigenesis and development, which represents a charming anti-cancer therapeutic target. Here, SDC4 was identified as a direct cellular target of small-molecule bufalin with anti-hepatocellular carcinoma (HCC) activity. Mechanism studies revealed that bufalin directly bond to SDC4 and selectively increased SDC4 interaction with substrate protein DEAD-box helicase 23 (DDX23) to induce HCC genomic instability. Meanwhile, pharmacological promotion of SDC4/DDX23 complex formation also inactivated matrix metalloproteinases (MMPs) and augmented p38/JNK MAPKs phosphorylation, which are highly associated with HCC proliferation and migration. Notably, specific knockdown of SDC4 or DDX23 markedly abolished bufalin-dependent inhibition of HCC proliferation and migration, indicating SDC4/DDX23 signaling axis is highly involved in the HCC process. Our results indicate that membrane-spanning proteoglycan SDC4 is a promising druggable target for HCC, and pharmacological regulation of SDC4/DDX23 signaling axis with small-molecule holds great potential to benefit HCC patients.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 33990545 · DOI · PMC8121893
DIGitoxin to Improve ouTcomes in patients with advanced chronic Heart Failure (DIGIT-HF): Baseline characteristics compared to recent randomized controlled heart failure trials [4]
Abstract reading summary — source excerpts
- Opening excerpt
- AimsThis report presents the baseline characteristics of patients enrolled in the DIGIT-HF trial and compares them with participants from recent trials with improved outcomes in patients with heart failure (HF) and a reduced ejection fraction (HFrEF).
- Closing excerpt
- Clinical trial registrationEudraCT (2013-005326-38).
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (253 words)
AimsThis report presents the baseline characteristics of patients enrolled in the DIGIT-HF trial and compares them with participants from recent trials with improved outcomes in patients with heart failure (HF) and a reduced ejection fraction (HFrEF).Methods and resultsDIGIT-HF, a randomized, double-blind, placebo-controlled, multicentre trial enrolling patients with symptomatic HFrEF (New York Heart Association [NYHA] functional class II and left ventricular ejection fraction [LVEF] ≤30%, or NYHA class III-IV and LVEF ≤40%), compares the efficacy and safety of digitoxin versus placebo in addition to standard treatment. Most baseline characteristics of the intention-to-treat population (1212 patients, mean age 66 ± 11 years, 20% women, mean LVEF 29 ± 7%) were similar to those in recent HFrEF trials. The distribution of NYHA class II, III, and IV was 30%, 66% and 4%, respectively, and indicates that the patients were sicker than in comparator HFrEF trials. Less patients had atrial fibrillation (27%) than those in recent HFrEF trials, but prescription rates of background therapy with beta-blockers (96%), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (95%), mineralocorticoid receptor antagonists (76%), and diuretics (87%) were high and similar. Overall, 40% of patients were on angiotensin receptor-neprilysin inhibitors, 19% on sodium-glucose cotransporter 2 inhibitors, and 9% on ivabradine. Rates of implantable cardioverter-defibrillator (ICD, 64%) and cardiac resynchronization therapy (CRT, 25%) devices were much higher than in recent HFrEF trials.ConclusionsPatients included in DIGIT-HF display a more severe HF symptom burden and higher rates of ICD/CRT implants compared to participants in recent HFrEF trials, while pharmacotherapy was largely similar.Clinical trial registrationEudraCT (2013-005326-38).
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 40389288 · DOI · PMC12370576
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Endogenous and exogenous cardiac glycosides: their roles in hypertension, salt metabolism, and cell growth [5]
- Research article Cardiac glycosides as novel cancer therapeutic agents [6]
- Research article Toxic cardenolides: chemical ecology and coevolution of specialized plant-herbivore interactions [7]
- Research article The physiological significance of the cardiotonic steroid/ouabain-binding site of the Na,K-ATPase [8]
- Research article Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data [9]
- Research article Digoxin-associated mortality: a systematic review and meta-analysis of the literature [10]
References
- Triana-Martínez F, Picallos-Rabina P, Da Silva-Álvarez S, Pietrocola F, Llanos S, Rodilla V, et al.. Identification and characterization of Cardiac Glycosides as senolytic compounds. . 2019. PMID 31636264 · DOI · PMC6803708
- Li X, Zheng J, Chen S, Meng FD, Ning J, Sun SL. Oleandrin, a cardiac glycoside, induces immunogenic cell death via the PERK/elF2α/ATF4/CHOP pathway in breast cancer. . 2021. PMID 33762577 · DOI · PMC7990929
- Yang H, Liu Y, Zhao MM, Guo Q, Zheng XK, Liu D, et al.. Therapeutic potential of targeting membrane-spanning proteoglycan SDC4 in hepatocellular carcinoma. . 2021. PMID 33990545 · DOI · PMC8121893
- Bavendiek U, Thomas NH, Berliner D, Liu X, Schwab J, Rieth A, et al.. DIGitoxin to Improve ouTcomes in patients with advanced chronic Heart Failure (DIGIT-HF): Baseline characteristics compared to recent randomized controlled heart failure trials. . 2025. PMID 40389288 · DOI · PMC12370576
- Schoner W, Scheiner-Bobis G. Endogenous and exogenous cardiac glycosides: their roles in hypertension, salt metabolism, and cell growth. Am J Physiol Cell Physiol. 2007. PMID 17494630 · DOI
- Newman RA, Yang P, Pawlus AD, Block KI. Cardiac glycosides as novel cancer therapeutic agents. Mol Interv. 2008. PMID 18332483 · DOI
- Agrawal AA, Petschenka G, Bingham RA, Weber MG, Rasmann S. Toxic cardenolides: chemical ecology and coevolution of specialized plant-herbivore interactions. New Phytol. 2012. PMID 22292897 · DOI
- Lingrel JB. The physiological significance of the cardiotonic steroid/ouabain-binding site of the Na,K-ATPase. Annu Rev Physiol. 2010. PMID 20148682 · DOI · PMC3079441
- Ziff OJ, Ziff OJ, Lane DA, Samra M, Griffith M, Kirchhof P, et al.. Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data. BMJ. 2015. PMID 26321114 · DOI · PMC4553205
- Vamos M, Erath JW, Hohnloser SH. Digoxin-associated mortality: a systematic review and meta-analysis of the literature. Eur Heart J. 2015. PMID 25939649 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
See how EvidenceLib is built. Spotted an error? Email support@evidencehelix.com.
Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.