Steroidal alkaloids: Exploring new therapeutic frontiers in cardiovascular diseases.

A drug-drug interaction (DDI) is a pharmacokinetic or pharmacological influence of 1 medication on another that differs from the known or anticipated effects of each agent alone.1 A DDI may result in a change in either drug efficacy or drug toxicity for 1 or both of the interacting medications.2 Pharmacokinetic DDIs result in altered absorption, distribution, metabolism, or excretion of a medication. A pharmacodynamic DDI occurs when 1 medication modifies the pharmacological effect of another in an additive, a synergistic, or an antagonistic fashion. It is estimated that ≈2.8% of hospital admissions occur as a direct result of DDIs.3 However, the actual incidence of hospitalization secondary to clinically significant DDIs is likely to be highly underestimated because medication-related issues are more commonly reported as adverse drug reactions. Complex underlying disease states also may make recognizing a DDI more challenging, further contributing to a lower reported incidence. The overall clinical impact of a DDI can range from mild to life-threatening. Therefore, not all DDIs require a modification in therapy. The variability in the clinical significance of a DDI depends on both medication-specific and patient-specific factors. Medication-specific factors include the individual pharmacokinetic characteristics of each medication implicated in the DDI (eg, binding affinity, half-life [t1/2]), dose of the medications, serum concentrations, timing and sequence of administration, and duration of therapy. Patient-specific factors include age, sex, lifestyle, genetic polymorphisms causing differences in enzyme expression or activity, and disease impairment affecting drug metabolism (eg, hepatic or renal impairment, cardiac failure) or predisposition to differences in efficacy or safety (eg, statin intolerance in patients with a history of myopathy). Clinically significant DDIs are usually preventable. To optimize patient safety, healthcare providers must have an understanding of the mechanisms, magnitude, and potential consequences of any given DDI. Interpreting this information …

Cardiovascular disease (CVD) and periodontal disease have a common pathogenesis with inflammation and resolution steps. Although the relationships among periodontal disease, CVD, and specialized pro-resolving lipid mediator (sPRLM)s are well known, there is no study about the combined effects of cardiovascular and periodontal treatments on sPRLM levels. It was aimed to evaluate the effects of periodontal and cardiovascular therapies on sPRLMs (lipoxin A4, protectin (PD)1, resolvin (Rv) E1, RvD1, and maresin (MaR)1) in patients with CVD and periodontal disease. This observational study consisted of fifty-five patients with CVD and mild or moderate periodontitis. The clinical periodontal parameters (plaque index, gingival index, probing pocket depth, percentage of bleeding on probing, and clinical attachment level) and blood and unstimulated total saliva samples were obtained at baseline, at 3months (following only cardiovascular therapy), and at 6months (following cardiovascular and periodontal therapies). The blood count and serum levels of cardiometabolic biomarkers (white blood cell, neutrophil/lymphocyte, serum total cholesterol (TC), triglyceride, and low and high-density lipoprotein (HDL) levels) were evaluated. sPRLMs were evaluated by ELISA. There were significant decreases in body mass index, clinical periodontal parameters, WBC, LDL, PD1, and RvD1 at 6months compared to baseline. The decreases in TC/HDL, RvE1, and MaR1 levels were significant at 3 and 6months compared to baseline (p < 0.05). The combination of cardiovascular and periodontal treatments leads to significant reductions in clinical periodontal and cardiometabolic parameters and sPRLMs. Our report, which is the first in their field, suggested that cardiovascular and periodontal therapies provide an important contribution via decreasing the periodontal and atherosclerotic inflammation modulating sPRLMs. This finding will be a big step toward increasing the quality of life in these patients by drawing attention to importance of public health associated with oral hygiene, periodontal health, and systemic phase of periodontal treatment.

Drug interactions in cardiovascular therapy

Dear Friends and Colleagues, Dear Readers, I hope you will not mind me starting this Editorial with addressing, at first, Friends and Colleagues. This reflects the spirit of our new Journal. Our Friends and Colleagues have actively participated, over the last years, in our regional and national consultations on how to choose the best diagnostic and management path for patients with rare cardiovascular disorders. We believe that some examples of our prior work included in the present issue will attract your interest. We also hope that the format of these reports will find your approval. Each issue will also include regular papers and reviews on different aspects of rare cardiovascular diseases. What the last years have taught us is that it is necessary to record the “spoken words” into writing in order to create a formal platform for a wider flow of information and exchange of expertise. There is also no doubt that what is needed is a formal collaboration between centers that professionally take care of “orphan” patients to establish optimal and common diagnostic and management paths. What is also needed is planning and executing common registries that will lead to better understanding of the history of the disease. These are the main reasons for establishing the Journal. Launching the Journal of Rare Cardiovascular Diseases fits in the current priorities of the European Commission (Priority 8 – Interregional Cooperation). Indeed, the Journal stems from a recent EU project‚ Establishing a European Network for Orphan Cardiovascular Diseases’ (MRP0.08.02.00‑12-424/10) and from establishing a regional Center for Rare Cardiovascular Diseases in Krakow (Poland) as part of this Project. The Journal is an independent educational initiative and it is registered under European laws. The Journal of Rare Cardiovascular Diseases is a peer‑reviewed journal. We will aim for at least one reviewer from the country different than that of the manuscript submitting author. We are committed to fertilizing the development of knowledge and its usefulness to YOU and YOUR patients. We will warmly welcome your participation. At a time of continuously increasing online scientific communication, and where success is based on establishing an efficient mutual communication, the Journal of Rare Cardiovascular Diseases joins the growing family of internet‑based journals. We start with quarterly publication, and we aim to be indexed in the major medical data‑bases with an impact factor. The label of “ orphan ” should no longer be used. Editing a journal is a major challenge, and we are very glad that a number of authorities have already accepted our invitation to the Editorial Board. We remain open, and will remain open to your suggestions to include those you know for their work with patients with rare cardiovascular disease. In conclusion, this Journal is about quality and about evolution of high‑quality, common, standards in managing patients with rare cardiovascular disease. The idea to launch the Journal of Rare Cardiovascular Diseases crystallized at the first Satellite Meeting on Rare Cardiovascular Disease at the ESC in Paris in 2011. Not without a reason the first issue of the Journal coincides with the International Conference on Rare Cardiovascular Diseases in Krakow (October 18th–19th, 2012). We hope you will enjoy reading the first issue of the Journal of Rare Cardiovascular Diseases. It includes work from several centers in countries such as Lithuania, France, Poland and the UK. I encourage you to read some original work on the shortcomings of the nitric oxide test in candidates for heart transplantation with severe pulmonary hypertension due to left ventricular systolic dysfunction, a review on the myocardial involvement in Fabry diseases, and case reports on practical aspects of managing patients with several rare cardiovascular disorders.

Our task as clinicians would be simple if all we had to do was to follow the logical sequence of identifying a biological target, finding a drug or treatment specifically affecting that target, testing the efficacy of the drug or treatment in appropriately designed clinical trials, and then prescribing only those drugs or treatments with proven efficacy and an acceptable safety profile. Drugs that affect a given biological target could be considered as a “class,” with those that show “efficacy” in clinical trials considered as therapeutic alternatives within that class. Unfortunately, the real world is not that simple. Defining precisely what we mean by class effect and efficacy becomes increasingly problematic, for example, as we have recently witnessed with calcium channel blockers, β-blockers, angiotensin-converting enzyme inhibitors, HMG CoA reductase inhibitors, glycoprotein IIb/IIIa antagonists, low-molecular-weight heparins, and direct thrombin antagonists.1 If we identify a drug that demonstrates efficacy, are the benefits of that drug generalizable to all drugs with similar biological targets?2 If benefits are present in one clinical circumstance, are those benefits generalizable to all circumstances in which that class of drugs can be applied?3 In the modern cost-conscious arena, can we substitute less expensive, mechanistically similar agents that may not have the same weight of clinical evidence support or even the same degree of clinical benefit? When is it acceptable to generalize to a class effect, or should we adhere strictly to evidence-based therapy with individual compounds? These issues can be viewed from both scientific and clinical perspectives. ### Definition of Biological Target As our scientific knowledge grows, our traditional grouping of drugs has become, to a large extent, obsolete. For example, there are 9 different calcium channel blockers that are approved for clinical use in the United States, which can be divided into 5 general groups on the basis of …

This study presents a literature review on the therapeutic potential of five medicinal plants-Astrocaryum aculeatum (tucumã), Plectranthus barbatus (Brazilian boldo), Myrciaria dubia (camu-camu), Ilex paraguariensis (yerba mate), and Passiflora incarnata (passionflower)-in the management of cardiodiabesity, a complex condition that interconnects type 2 diabetes mellitus and cardiovascular diseases. The methodology involved systematic searches in PubMed, Scopus, and Web of Science platforms, using descriptors related to medicinal plants, clinical conditions associated with cardiodiabesity, and their potential therapeutic effects. Cardiodiabesity represents a growing challenge for global public health, with alarming rates of morbidity and mortality, especially in low- and middle-income countries. Since 1990, the global prevalence of diabetes in adults has more than doubled, accompanied by simultaneous increases in cases of hypertension, dyslipidemia, and cardiovascular mortality. Effective management of this syndrome requires a holistic approach, including lifestyle modifications, pharmacological interventions, and complementary therapies. The review highlights the specific mechanisms of action of each plant: Astrocaryum aculeatum, rich in unsaturated fatty acids and phenolic compounds, demonstrates anti-inflammatory and antioxidant properties in preclinical studies; Plectranthus barbatus, containing forskolin as its main bioactive compound, presents vasodilatory and blood pressure modulating effects through adenylyl cyclase activation and ion channel modulation; Myrciaria dubia, with high content of vitamin C, anthocyanins, and flavonoids, exhibits antioxidant, anti-inflammatory, hypoglycemic, and hypolipidemic potential; Ilex paraguariensis demonstrates beneficial effects on endothelial function, lipid metabolism, and blood pressure; and Passiflora incarnata presents anxiolytic, hypotensive, and antioxidant properties. Despite the promising potential of these medicinal plants, the study identifies significant gaps in current knowledge, primarily due to the scarcity of clinical trials in humans, variability in plant chemical composition, and a lack of standardized extracts. The manuscript concludes that, although preclinical studies suggest potential benefits of these plants in the context of cardiodiabesity, more well-designed clinical studies are needed to validate their efficacy and safety, establish appropriate dosages, and better understand the molecular mechanisms involved in their therapeutic effects.

The development of targeted drug delivery systems represents a significant advancement in cardiovascular therapy, effectively overcoming the limitations of conventional pharmaceutical administration. This review examines recent innovations in nanoparticle‐based systems aimed at improving the efficacy and specificity of therapeutic agents for cardiovascular diseases. We categorize various nanoparticle types, including liposomes, polymeric nanoparticles, and metal‐based nanoparticles, emphasizing their distinct properties that enable targeted delivery to cardiac tissues. In addition to nanoparticle systems, we investigate the potential of stem cell approaches in cardiovascular therapy. Stem cells possess the remarkable ability to differentiate into various cell types, including cardiomyocytes and endothelial cells, which makes them crucial for tissue regeneration and repair processes. Notably, exosomes derived from stem cells have emerged as natural nanocarriers for therapeutic agents, offering advantages in targeted drug delivery and promoting tissue healing. The combination of stem cell‐based therapies with nanoparticle systems has also shown synergistic potential, as it can enhance site‐specific drug accumulation and improve overall therapeutic outcomes. Moreover, the incorporation of targeting moieties such as antibodies and peptides into these delivery platforms further refines their selectivity, enabling precise targeting of diseased cells while minimizing adverse effects on healthy tissues. We address the challenges related to the clinical translation of these systems, such as biocompatibility, stability, and regulatory considerations. By synthesizing current research findings, this review aims to illuminate future directions for nanoparticle‐based targeted drug delivery and stem cell strategies in cardiovascular therapy. We underscore the potential for improved patient outcomes through personalized medicine approaches that harness the advantages of both targeted delivery systems and regenerative therapies, supported by quantitative findings from recent studies. © 2026 Society of Chemical Industry.

Targeting metabolic diseases with celastrol: A comprehensive review of anti-inflammatory mechanisms and therapeutic potential.

Cardiovascular disease (CVD) is comprised of a group of disorders affecting the heart and blood vessels of the human body and is one of the leading causes of death worldwide. Current therapy for CVD is limited to the treatment of already established disease, and it includes pharmacological and/or surgical procedures, such as percutaneous coronary intervention with stenting and coronary artery bypass grafting. However, lots of complications have been raised with these modalities of treatment, including systemic toxicity with medication, stent thrombosis with percutaneous coronary intervention and nonsurgical candidate patients for coronary artery bypass grafting. Nanomedicine has emerged as a potential strategy in dealing with these obstacles. Applications of nanotechnology in medicine are already underway and offer tremendous promise. This review explores the recent developments of nanotechnology in the field of CVD and gives an insight into its potential for diagnostics and therapeutics applications. The authors also explore the characteristics of the widely used biocompatible nanomaterials for this purpose and evaluate their opportunities and challenges for developing novel nanobiotechnological tools with high efficacy for biomedical applications, such as radiological imaging, vascular implants, gene therapy, myocardial infarction and targeted delivery systems.

Synergistic action of propranolol with quinidine

Drug-drug interactions (DDIs) caused by the co-administration of multiple drugs are major safety concerns in the clinic. Several drugs have been withdrawn from the market due to perpetrator or victim DDIs. Strategies have been developed to assess DDI risks early in drug discovery to reduce DDI liabilities. High-to-medium throughput assays are available to identify undesirable scaffolds and to guide structural modifications to minimize DDIs. Definitive methods are used at later stages of drug discovery and development to provide a more accurate measurement of DDI parameters and to enable clinical translations. Physiologically based pharmacokinetic modeling and simulations are powerful tools to accurately predict DDIs and to assess risks in the clinic. Although significant advances have been made over the years, many challenges remain for clinical DDI translations. This includes DDIs involving non-cytochrome P450 enzymes, transporters, enzyme-transporter interplay, indirect effects from biologics, and pharmacodynamic based DDI. This review focuses on methods that are used to assess hepatic DDIs caused by enzyme inhibition and induction.

<i>Circulation</i> Editors’ Picks

To the Editor: Recently, an update from the Framingham study could not find uric acid to be an independent risk factor for cardiovascular disease.1 While serum uric acid levels correlated significantly with the risk for cardiovascular events and mortality in women, this relationship became insignificant after factoring for 11 additional variables including hypertension, body mass index, and diuretic use.1 Both the authors1 and an accompanying editorial2 interpreted these findings as showing that uric acid is not a true risk factor for cardiovascular disease and that it should not be routinely measured to assess cardiovascular risk. The careful analysis of the Framingham study is to be commended, but one must be cautious in the interpretation of the findings. While some epidemiologic studies such as the current one have not been able to show uric acid to be an independent risk factor for cardiovascular disease, other studies using multivariate analyses3 4 5 6 came to an opposite conclusion. Another recently completed study, the Worksite,7 also found uric acid to be an independent risk factor for cardiovascular events and mortality, especially in women. One might look for subtle explanations to account for the differences in these various studies, as Culleton et al1 have attempted, but most of the studies examined the very same variables. A more central issue is whether one should interpret the finding that a risk factor is not statistically independent to mean that it should not be considered biologically important. We would argue that this is not true in several situations. First, if the risk factors are causally linked, then one may not be able to show that they are independent of each other. For example, although smoking is a risk factor for mortality, it might no longer be independent if it is …

Cardiovascular Protection in People With Diabetes.

Interactions of drugs with the classical epigenetic mechanism of DNA methylation or histone modification are increasingly being elucidated mechanistically and used to develop novel classes of epigenetic therapeutics. A data science approach is used to synthesize current knowledge on the pharmacological implications of epigenetic regulation of gene expression. Computer-aided knowledge discovery for epigenetic implications of current approved or investigational drugs was performed by querying information from multiple publicly available gold-standard sources to (i) identify enzymes involved in classical epigenetic processes, (ii) screen original biomedical scientific publications including bibliometric analyses, (iii) identify drugs that interact with epigenetic enzymes, including their additional non-epigenetic targets, and (iv) analyze computational functional genomics of drugs with epigenetic interactions. PubMed database search yielded 3051 hits on epigenetics and drugs, starting in 1992 and peaking in 2016. Annual citations increased to a plateau in 2000 and show a downward trend since 2008. Approved and investigational drugs in the DrugBank database included 122 compounds that interacted with 68 unique epigenetic enzymes. Additional molecular functions modulated by these drugs included other enzyme interactions, whereas modulation of ion channels or G-protein-coupled receptors were underrepresented. Epigenetic interactions included (i) drug-induced modulation of DNA methylation, (ii) drug-induced modulation of histone conformations, and (iii) epigenetic modulation of drug effects by interference with pharmacokinetics or pharmacodynamics. Interactions of epigenetic molecular functions and drugs are mutual. Recent research activities on the discovery and development of novel epigenetic therapeutics have passed successfully, whereas epigenetic effects of non-epigenetic drugs or epigenetically induced changes in the targets of common drugs have not yet received the necessary systematic attention in the context of pharmacological plasticity.