Cardiac glycosides with target at direct and indirect interactions with nuclear receptors

Karaś, Kaja; Sałkowska, Anna; Dastych, Jarosław; Bachorz, Rafał A.; Ratajewski, Marcin

doi:10.1016/j.biopha.2020.110106

Cited by 21 publications

(18 citation statements)

References 152 publications

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“…Importantly, the interaction of ECS with the Na + , K + -ATPase results not only in the inhibition of the ion pumping function, but causes the activation of several signal transduction cascades, including mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), protein kinase B, and oroto-oncogene tyrosine-protein kinase pathways [34,35]. In addition, a substantial body of studies has demonstrated that ECS also act by directly and indirectly affecting the activity of the nuclear receptor superfamily of transcription factors [36,37].…”

Section: Resultsmentioning

confidence: 99%

Endogenous Cardiac Steroids in Bipolar Disorder: State of the Art

El‐Mallakh

Sampath²,

Horesh³

et al. 2022

IJMS

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Bipolar disorder (BD) is a severe psychiatric illness with a poor prognosis and problematic, suboptimal, treatments. Treatments, borne of an understanding of the pathoetiologic mechanisms, need to be developed in order to improve outcomes. Dysregulation of cationic homeostasis is the most reproducible aspect of BD pathophysiology. Correction of ionic balance is the universal mechanism of action of all mood stabilizing medications. Endogenous sodium pump modulators (collectively known as endogenous cardiac steroids, ECS) are steroids which are synthesized in and released from the adrenal gland and brain. These compounds, by activating or inhibiting Na+, K+-ATPase activity and activating intracellular signaling cascades, have numerous effects on cell survival, vascular tone homeostasis, inflammation, and neuronal activity. For the past twenty years we have addressed the hypothesis that the Na+, K+-ATPase-ECS system may be involved in the etiology of BD. This is a focused review that presents a comprehensive model pertaining to the role of ECS in the etiology of BD. We propose that alterations in ECS metabolism in the brain cause numerous biochemical changes that underlie brain dysfunction and mood symptoms. This is based on both animal models and translational human results. There are data that demonstrate that excess ECS induce abnormal mood and activity in animals, while a specific removal of ECS with antibodies normalizes mood. There are also data indicating that circulating levels of ECS are lower in manic individuals, and that patients with BD are unable to upregulate synthesis of ECS under conditions that increase their elaboration in non-psychiatric controls. There is strong evidence for the involvement of ion dysregulation and ECS function in bipolar illness. Additional research is required to fully characterize these abnormalities and define future clinical directions.

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Section: Resultsmentioning

confidence: 99%

Endogenous Cardiac Steroids in Bipolar Disorder: State of the Art

El‐Mallakh

Sampath²,

Horesh³

et al. 2022

IJMS

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“…These TFs interact with other proteins involved in the general transcription machinery such as TBP (TATA-binding protein), coactivators and corepressors, etc. [ 13 ]. However, the exact role played by CGs on these nuclear receptors is yet to be proven.…”

Section: Modulation Of Transcription Factor Activity Through Cardiac Glycosidesmentioning

confidence: 99%

“…Some phytochemically derived anticancer compounds like calebin A, nobiletin, garcinol, CG, and many others target TFs precisely [ 9 , 10 , 11 , 12 ]. Cardiac glycosides (CGs) are of particular interest because of their potential as drug repurposing candidates derived from plant and animal sources and are used in various human ailments [ 13 ]. CGs are principally involved in the inhibition of the Na + /K + ATPase pump during muscle contraction in heart failure, and thus, they are clinically approved for the treatment of cardiovascular diseases [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Emergence of Cardiac Glycosides as Potential Drugs: Current and Future Scope for Cancer Therapeutics

et al. 2021

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Cardiac glycosides are natural sterols and constitute a group of secondary metabolites isolated from plants and animals. These cardiotonic agents are well recognized and accepted in the treatment of various cardiac diseases as they can increase the rate of cardiac contractions by acting on the cellular sodium potassium ATPase pump. However, a growing number of recent efforts were focused on exploring the antitumor and antiviral potential of these compounds. Several reports suggest their antitumor properties and hence, today cardiac glycosides (CG) represent the most diversified naturally derived compounds strongly recommended for the treatment of various cancers. Mutated or dysregulated transcription factors have also gained prominence as potential therapeutic targets that can be selectively targeted. Thus, we have explored the recent advances in CGs mediated cancer scope and have considered various signaling pathways, molecular aberration, transcription factors (TFs), and oncogenic genes to highlight potential therapeutic targets in cancer management.

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“…These secondary compounds are produced in plants, insects and animals. In the past, plant or animal extracts comprising cardiac glycosides were used for diuretics, emetics, as poison on arrows and darts and for suicide or murder [ 124 ].…”

Section: Phytochemicals Of Drimia Sppmentioning

confidence: 99%

Bulbous Plants Drimia: “A Thin Line between Poisonous and Healing Compounds” with Biological Activities

et al. 2021

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Drimia (synonym Urginea) plants are bulbous plants belonging to the family Asparagaceae (formerly the family Hyacinthaceae) and are distinctive, powerful medicinal plants. Just some species are indigenous to South Africa and have been traditionally utilized for centuries to cure various diseases and/or ailments. They have been recognized among the most famous and used medicinal plants in South Africa. Traditionally, the plants are used for various illnesses such as dropsy, respiratory disease, bone and joint complications, skin disorders, epilepsy and cancer. A number of studies have reported biological properties such as antiviral, antibacterial, antioxidant and anti-inflammatory, immunomodulatory, and anticancer activities. Their bulbs are a popular treatment for colds, measles, pneumonia, coughs, fever and headaches. However, some plant species are regarded as one of the six most common poisonous plants in Southern Africa that are toxic to livestock and humans. Due to the therapeutic effects of the Drimia plant bulb, research has focused on the phytochemicals of Drimia species. The principal constituents isolated from this genus are cardiac glycosides. In addition, phenolic compounds, phytosterols and other phytochemical constituents were identified. This study constitutes a critical review of Drimia species’ bioactive compounds, toxicology, biological properties and phytochemistry, advocating it as an important source for effective therapeutic medicine. For this purpose, various scientific electronic databases such as ScienceDirect, Scopus, Google Scholar, PubMed and Web of Science were researched and reviewed to conduct this study. Despite well-studied biological investigations, there is limited research on the toxic properties and the toxic compounds of certain Drimia species. Searching from 2017 to 2021, Google Scholar search tools retrieved 462 publications; however, only 3 investigated the toxicity and safety aspects of Drimia. The aim was to identify the current scientific research gap on Drimia species, hence highlighting a thin line between poisonous and healing compounds, dotted across numerous publications, in this review paper.

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Cardiac glycosides with target at direct and indirect interactions with nuclear receptors

Cited by 21 publications

References 152 publications

Endogenous Cardiac Steroids in Bipolar Disorder: State of the Art

Endogenous Cardiac Steroids in Bipolar Disorder: State of the Art

Emergence of Cardiac Glycosides as Potential Drugs: Current and Future Scope for Cancer Therapeutics

Bulbous Plants Drimia: “A Thin Line between Poisonous and Healing Compounds” with Biological Activities

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