Cardiovascular & Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Cardiovascular & Hematological Agents) - Current Issue

Natural medicine (NM) has been used since ancient times for therapeutic purposes worldwide. Presently, the combination of clopidogrel and NM with a reasonable synergistic effect has gained increasing acceptance in clinical therapeutics.

Here, we have performed a comprehensive retrieval of literature published in both English and Chinese databases until August 1, 2022, studying the synergistic interactions of clopidogrel and NM through pharmacokinetic/pharmacodynamic (PK-PD) analyses. We retrieved 7, 3, and 5 studies on PK analysis and 3, 3, and 8 studies on PD analysis for the interaction of clopidogrel with single herbal medicines, bioactive compounds, and herbal prescriptions, respectively. Most studies on NM have been found to mainly focus on preclinical observations, and there have been fewer clinical PK analyses.

A potential drug-herb interaction has been observed to occur when clopidogrel and NM were metabolized by an enzyme network comprising P-gp, CES1, and CYP450. In contrast, most PD studies have focused on clinical observations, and few preclinical findings have been reported. Some cases have suggested that the combination of the two types of drugs would alter the antiplatelet efficacy and adverse effects. Studies on PK, however, have shown significant or slightly varying results for the drug prototype and its metabolites.

In the combination therapies, the interaction between clopidogrel and NM was found to alter antiplatelet aggregation pathways and P2Y12 receptor function.

The antihypertensive activity of Daphne gnidium was tested.

Daphne gnidium (Thymelaeaceae) is used against hypertension.

The antihypertensive effect of Daphne gnidium was evaluated in this study.

The effect of Daphne gnidium aqueous extract (DGAE, 100 and 180 mg/kg) on blood pressure was evaluated in rats. In addition, the vasorelaxant effect of this extract was also tested.

DGAE lowered blood pressure in hypertensive rats and exhibited vasorelaxant activity. In addition, cumulative concentrations of DGAE induced vasodilatation through receptor-activated calcium channels (ROCCs) without affecting ACE-2.

The aqueous extract of Daphne gnidium exhibits antihypertensive activity and induces vasodilatation via the inhibition of Ca²⁺ entry.

Dysbiosis of the gastrointestinal microbiota is not only related to the pathogenesis of intestinal disorders but also associated with extra-intestinal diseases. Various studies have revealed the role of an imbalance of intestinal microbiota and their metabolites including bile acids, indole derivatives, polyamines, and trimethylamine in the progression of various diseases. The elevated plasma level of the oxidized form of trimethylamine is associated with the increased risk of cardiovascular diseases. Literature supports that herbal medicines can modulate human health by altering the diversity of gut microbiota and their metabolites and proposes the use of prebiotics to improve dysbiotic conditions as a new way of therapeutic strategy.

In silico studies including drug likeliness, toxicity prediction, and molecular interaction of phytochemicals against trimethylamine lyase enzyme have been done. Antimicrobial activity of extracts of selected plant i.e. Syzygium aromaticum was done by disc diffusion and the protective effects of plant compounds were examined on trimethylamine-n-oxide a bacterial metabolic product and high glucose induced toxicity.

The current study has found that the phytochemicals of S. aromaticum identified as nontoxic and followed the standard rules of drug likeliness and showed a significant binding affinity against trimethylamine-n-oxide producing enzymes. Furthermore, S. aromaticum extract was found to have antimicrobial potential and cardioprotective effects by reducing the production of intracellular reactive oxygen species and correcting the distorted nuclear morphology in the presence of high trimethylamine-n-oxide.

Conclusively, our study explored the herbal intervention in intestinal dysbiosis and suggested a natural therapy against dysbiosis associated with cardiac disease, and S, aromaticum was found to have exceptional cardioprotective potential against TMAO induced gut dysbiosis, which provides a novel future therapeutic intervention for treating cardiovascular complications.

The absolute oral bioavailability of rosuvastatin (RST), a second-generation statin, is low i.e. 20% and only 10% is recovered as metabolite N-desmethy l rosuvistatin. Since it is a hydrophilic statin, RST relies on the organic anion transporting polypeptide-1B1 (OATP-1B1), as the key mechanism for active transport into hepatocytes. Quercetin (QUE) being a bio enhancer and inhibitor of OATP1B1 can augment the bioavailability and pharmacokinetics of RST.

The present study includes the development of a simple and validated bioanalytical Reverse Phase High-Performance Liquid Chromatography (RP-HPLC) method for the estimation of RST and to study the effect of co-administration of QUE as a bio enhancer on its bioavailability.

An analytical column of Kromasil 100, C18 (250 mm × 4.6 mm, 5 μm), was used for chromatographic separationand acetonitrile (ACN): acetic acid buffer pH 3.0 adjusted with glacial acetic acid (55:45 Vol. %) as mobile phase with flow rate 1.0 ml/min monitored at 242 nm. The ACN: methanol (50:50 Vol. %) was employed as the final solvent for extraction. The developed method has been successfully applied in a study on the pharmacokinetics of the drug RST in rats after co-administration of QUE, which was carried out using non-compartmental analysis in order to estimate the blood concentration of the drug.

The pharmacokinetics of RST was found to be altered significantly (highest concentration of RST in the blood (Cmax) = 67.3 ng/ml to 122.2 ng/ml) (p < 0.001), area under curve (AUC)0-t (p < 0.0001) and AUC0-inf (p = 0.0005) when co-administered with QUE at 120 min (tmax).

The results are in accordance with the fact that QUE increases plasma levels in rats through herb-drug interactions.

Numerous complications, such as postoperative arrhythmia and stroke, have been observed following coronary artery bypass graft (CABG) surgery.

This study sought to examine the impact of aging on the incidence of post-coronary artery shunt complications.

Aging is a physiological process experienced by every living cell, beginning early in development. Age plays a crucial role in determining postoperative complications, including those related to CABG.

A retrospective analysis was conducted on 290 patients who underwent CABG at the Mordovian Republic Hospital between 2017 and 2021. The sample was divided into two age-based groups: the first group comprised 126 patients (mean age range: 55.21-60.00), and the second group included 163 patients (mean age range: 66.11-80.00). Statistical analyses employed in this study encompassed descriptive statistics, Chi-square test, T-test, one-way ANOVA test, ROC analysis, and Pearson correlation using Statistica 12 software.

Elderly patients in the second group demonstrated a higher incidence of post-CABG arrhythmia (p < 0.012528). Moreover, the second group experienced markedly longer ICU and total hospitalization days following CABG, with p-values of less than 0.000000 and 0.000072, respectively. Notably, elderly individuals in the second group faced an increased risk of developing psychosis after CABG surgery (p < 0.007379). Furthermore, psychosis was found to be significantly associated with longer ICU hospitalization (p < 0.000140). Postoperative stroke occurred more frequently among the elderly (second group) with a p-value of less than 0.037736. Consequently, postoperative stroke was associated with extended ICU hospitalization (p < 0.000747). The usage of internal thoracic arteries (ITAs) was lower among the elderly (second group), with a p-value of less than 0.016145. Regarding correlations, a direct association was observed between age and ICU days, total hospitalization days, and the number of complications, with correlation coefficients (r) of 0.189046, 0.141415, and 0.138565, respectively.

Elderly individuals in the second group who undergo CABG face a greater risk of developing psychosis, arrhythmia, prolonged total and ICU hospitalization, and stroke. The presence of arrhythmia, which is commonly observed in patients aged 63 years and older, significantly affects total hospitalization days. The number of complications is influenced by age, cardiopulmonary bypass (CPB) time, aortic cross-clamp time, ICU hospitalization, and total hospitalization duration.

Type 2 diabetes has become a concern issue that affects the quality of life and can increase the risk of cardiac insufficiency elevating the threat to the life safety of patients. A recognized cause of cardiac insufficiency is diabetic cardiomyopathy, chronic hyperglycemia, and myocardial lipotoxicity which can reduce the myocardial contractile performance, and enhance the cardiomyocyte hypertrophy and interstitial fibrosis. The cause of diabetic cardiomyopathy is multi-factorial which includes oxidative stress, insulin resistance, inflammation, apoptosis, and autophagy. Recent clinical studies have suggested the dysbiosis of gut microbiota, secretion of metabolites, and their diffusion in to the host as to have direct detrimental effects on the cardiac contractility.

In the present paper, we have done in silico studies including molecular interaction of phytoconstituents of Tinospora cordifolia against reactive oxygen species producing proteins. Whereas, in vitro studies were conducted on H9C2 cardiac cells including cell morphological examination, level of reactive oxygen species, cell count-viability, apoptotic status, in the presence of high glucose, trimethylamine-n-oxide, and plant extracts which were determined through cell analyzer and microscopic assays.

The treatment of high glucose and trimethylamine-n-oxide was found to be increase the cardiac stress approximately two fold by attenuating hypertrophic conditions, oxidative stress, and apoptosis in rat cardiomyocytes, and Tinospora cordifolia was found to be a cardioprotective agent.

Conclusively, our study has reported that the Indian medicinal plant Tinospora cordifolia has the ability to treat diabetic cardiomyopathy. Our study can open up a new herbal therapeutic strategy against diabetic cardiomyopathy.

Hypercholesterolemia is one of the main risk factors for vascular thrombosis in individuals. Therefore, the use of statins is very effective in reducing cholesterol and can reduce the risk of thrombosis in these patients. Rosuvastatin, a member of the statin family which, inhibits cholesterol synthesis. Very few studies have been done in relation to how rosuvastatin can affect thrombosis. So, this research has been tried whether rosuvastatin can have an effect on coagulation factors and homocysteine as risk factors for thrombosis in hypercholesterolemia?

In this experimental study, 60 patients (30 men and 30 women with a mean age of 40-70 years) diagnosed with hypercholesterolemia (cholesterol > 250 mg/dl) participated in this research. 30 patients were prescribed rosuvastatin (20 mg/day), and 30 patients were simultaneously taken placebo for three months. All parameters, including FVIII, FV, Fibrinogen, D-Dimer, plasma homocysteine level and lipid profile, were measured before and after treatment. All the results were statistically compared between the two groups.

In patients who took rosuvastatin, the drug was able to significantly reduce the concentrations of total cholesterol, triglycerides, and low-density lipoprotein (LDL) (P < 0.001). Also, rosuvastatin was able to reduce the concentrations of homocysteine significantly, D-Dimer (P < 0.001), coagulation factor VIII and factor V (P < 0.05). In patients with hypercholesterolemia who took the placebo, did not affect the mentioned variables (P > 0.05).

According to the results, it seems that rosuvastatin may be able to reduce the risk of thrombosis in patients by affecting coagulation factors and homocysteine levels.

Beta-blockers are essential agents in the management of cardiovascular diseases, such as heart failure, acute myocardial infarction (MI), and cardiac arrhythmias. However, there are diurnal variations in the cardioprotective effects of the subgroups as a result of their different pharmacokinetic, pharmacodynamic, and pharmacogenetic profiles.

We aimed to compare metoprolol and bisoprolol in terms of electrocardiogram (ECG) outcomes.

A retrospective cross-sectional study was conducted at Prince Sultan Cardiac Center. The trial included 404 patients who met the inclusion criteria (204 in the metoprolol arm and 200 in the bisoprolol arm). Using case record forms that had already been created, information, such as patient demographics, medical histories, and treatment histories, was taken from their medical files. The most recent ECG records were also gathered. The ethical approval for this study was obtained from Qassim ethical committee (approval number: 45-44-902).

There was no significant difference found between the patients in both arms in terms of baseline characteristics, age, or sex.

In this retrospective cross-sectional study, we have compared the effects of metoprolol and bisoprolol beta blockers on ECG changes. The findings have indicated no difference between metoprolol and bisoprolol groups in terms of all ECG readings, particularly PR/ms, QTC-ms, and ventricular rate. Further studies are required to confirm these findings.