Repurposing Drugs to Treat Heart and Brain Illness

Cantrell, Maranda S.; Soto-Avellaneda, Alejandro; Wall, Jackson; Ajeti, Aaron D.; Morrison, Brad; Warner, Lisa; McDougal, Owen M.

doi:10.3390/ph14060573

Cited by 4 publications

(2 citation statements)

References 92 publications

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“…Thus, colchicine is an established anti-inflammatory drug, which attenuates the NLRP3 inflammasome and also inhibits collagen synthesis [333][334][335]. The anti-inflammatory potential of colchicine has most recently been studied in patients with chronic coronary artery disease, displaying remarkable activity in terms of reducing cardiovascular events [335][336][337][338][339][340][341][342][343][344][345][346][347][348][349][350][351][352][353] and lowering a large number of inflammatory proteins, including CRP, IL1beta, and IL-6 [344]. Colchicine preferably accumulates in neutrophils, interfering with neutrophil adhesion, mobilization, and recruitment and inhibiting neutrophil chemotaxis and superoxide production.…”

Section: Colchicinementioning

confidence: 99%

Revisiting Circulating Extracellular Matrix Fragments as Disease Markers in Myelofibrosis and Related Neoplasms

Hasselbalch,

Junker,

Skov

et al. 2023

Cancers

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Philadelphia chromosome-negative chronic myeloproliferative neoplasms (MPNs) arise due to acquired somatic driver mutations in stem cells and develop over 10–30 years from the earliest cancer stages (essential thrombocythemia, polycythemia vera) towards the advanced myelofibrosis stage with bone marrow failure. The JAK2V617F mutation is the most prevalent driver mutation. Chronic inflammation is considered to be a major pathogenetic player, both as a trigger of MPN development and as a driver of disease progression. Chronic inflammation in MPNs is characterized by persistent connective tissue remodeling, which leads to organ dysfunction and ultimately, organ failure, due to excessive accumulation of extracellular matrix (ECM). Considering that MPNs are acquired clonal stem cell diseases developing in an inflammatory microenvironment in which the hematopoietic cell populations are progressively replaced by stromal proliferation—“a wound that never heals”—we herein aim to provide a comprehensive review of previous promising research in the field of circulating ECM fragments in the diagnosis, treatment and monitoring of MPNs. We address the rationales and highlight new perspectives for the use of circulating ECM protein fragments as biologically plausible, noninvasive disease markers in the management of MPNs.

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Section: Colchicinementioning

confidence: 99%

Revisiting Circulating Extracellular Matrix Fragments as Disease Markers in Myelofibrosis and Related Neoplasms

Hasselbalch,

Junker,

Skov

et al. 2023

Cancers

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“…However, none of the drugs tested to date have been definitively proven to improve long-term survival in CHF patients, even in those with mild symptoms. Given the complex and dynamic progression of CHF induced by cardiovascular diseases and the increasing clinical interventions for drugs, there is an urgent need to develop new, more effective drugs 10 .…”

Section: Introductionmentioning

confidence: 99%

Exploring the pathways of drug repurposing and Panax ginseng treatment mechanisms in chronic heart failure: a disease module analysis perspective

Xie,

Zhang,

Zhu

et al. 2024

Sci Rep

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Chronic Heart Failure (CHF) is a significant global public health issue, with high mortality and morbidity rates and associated costs. Disease modules, which are collections of disease-related genes, offer an effective approach to understanding diseases from a biological network perspective. We employed the multi-Steiner tree algorithm within the NeDRex platform to extract CHF disease modules, and subsequently utilized the Trustrank algorithm to rank potential drugs for repurposing. The constructed disease module was then used to investigate the mechanism by which Panax ginseng ameliorates CHF. The active constituents of Panax ginseng were identified through a comprehensive review of the TCMSP database and relevant literature. The Swiss target prediction database was utilized to determine the action targets of these components. These targets were then cross-referenced with the CHF disease module in the STRING database to establish protein–protein interaction (PPI) relationships. Potential action pathways were uncovered through Gene Ontology (GO) and KEGG pathway enrichment analyses on the DAVID platform. Molecular docking, the determination of the interaction of biological macromolecules with their ligands, and visualization were conducted using Autodock Vina, PLIP, and PyMOL, respectively. The findings suggest that drugs such as dasatinib and mitoxantrone, which have low docking scores with key disease proteins and are reported in the literature as effective against CHF, could be promising. Key components of Panax ginseng, including ginsenoside rh4 and ginsenoside rg5, may exert their effects by targeting key proteins such as AKT1, TNF, NFKB1, among others, thereby influencing the PI3K-Akt and calcium signaling pathways. In conclusion, drugs like dasatinib and midostaurin may be suitable for CHF treatment, and Panax ginseng could potentially mitigate the progression of CHF through a multi-component-multi-target-multi-pathway approach. Disease module analysis emerges as an effective strategy for exploring drug repurposing and the mechanisms of traditional Chinese medicine in disease treatment.

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