Cardiovascular & Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Cardiovascular & Hematological Agents) - Volume 14, Issue 3, 2016

Cardiovascular patients frequently use herbal medicinal products, in order to contribute to the improvement of their chronic condition without medical intervention. However, they are likely to suffer from adverse effects from natural products and herb-drug interactions. In this work we present the results collected from a public campaign “Learning Health, among Plants and Medicines”, carried out by the Observatory of Herb-Drug Interactions (www.oipm.uc.pt), to alert cardiovascular patients and healthcare providers for the potential occurrence of herb-drug interactions with cardiovascular therapy. From the data received, it was highlighted the prevalence of certain natural products used by many cardiovascular patients in Portugal, particularly goji berries, green tea, mangosteen and rooibos that have significant cardiovascular effects. For this reason their intake should be carefully monitored in these patients. This prevalence of consumption suggests a pattern in their use in Portugal and a prevention of herb-drug interactions should be carried out by the health professionals. The ending results also indicate that there is still a lack of knowledge about the possible risks of herbal products intake, which may adversely affect the health of any patient. Thus becomes clear the value of the role of health professionals in the screening of such interactions.

On an annual basis, 13.2% of all deaths are attributable to coronary artery disease (CAD), which makes CAD - with 7.4 million deaths – the leading cause of death in the world. In this review, we discuss current knowledge in the pathophysiology of atherosclerosis with its progression to stable CAD and its destabilization and complication with thrombus formation – myocardial infarction (MI). Next, we describe mechanisms of myocardial cell death in MI, the ischemia-reperfusion injury, leftventricular remodeling and complications of MI. Furthermore, we add acute management strategies concentrating on medical therapy, a decision on the reperfusion strategy, timing and cardiac protection by ischemic preconditioning, post-conditioning and remote ischemic conditioning.

Background: This article is a study of adverse effects associated with the abuse of recreational drugs such as anabolic androgenic steroids. Nandrolone decanoate is one such drug often abused by athletes and bodybuilders seeking enhanced physical strength or appearance. The use of such steroids has increased dramatically over the years. Objective: The present study was conducted to investigate the impact of nandrolone decanoate when consumed at an abused dose, upon serum aldosterone concentration in albino mice. Sodium and potassium ion concentrations were also monitored with the same experimental dosage. Method: 0.1ml of 25 mg Nandrolone decanoate was administered to the animals twice a week for a period of 90 days. Blood samples for obtaining the serum from both normal and treated group of animals were collected at an interval of 15 days upto the 90th day. Result: The present investigation revealed a significant increase (p<0.01) in the serum aldosterone and sodium ion concentrations in the treated group of animals compared to that in the normal group. Potassium ion concentration in the treated group did not exhibit a significant alteration when compared with the untreated animals. Conclusion: From the above observation, nandrolone decanoate abuse could be suggested as one of the causes of aldosterone and electrolyte imbalance in the body that could possibly be a serious risk factor for cardiovascular related disorders.

Background: One of the alarming difficulties in the field of hematology is the Coagulant disorders. Despite the availability of clinically proven existing anticoagulants, their limitations have prompted a continuous search for novel anticoagulants. Objective: The primary objective of the study is to synthesize a series of 2-amino-4H-chromen-4- ylphosphonate derivatives and to test their anticoagulant activity depending on PT measurements considering commercial heparin as positive control. Method: 2-Amino-4H-chromen-4-ylphosphonates were synthesized by the reaction of salicylaldehyde derivatives (1), malononitrile (2) and dialkyl phosphite (3) in ethanol using piperazine as a catalyst by ultra-sonication at room temperature. All the title compounds (4a-l) were tested for anticoagulant activity. Results: The results of the anticoagulant activity of the title compounds revealed that 4j, 4h and 4g showed prolonged prothrombin time 87.28, 81.81 and 78.42 sec when compared with that of the standard heparin which has prothrombin time of 121.50 sec. Conclusion: The findings from this study highlight that ultrasonication of the one pot three component reaction of salicylaldehyde derivatives, malononitrile and dialkyl phosphite with piperazine as a catalyst for the synthesis of 2-amino-4H-chromen-4-ylphosphonates is the best method. In vitro coagulant assay in terms of prothrombin time (PT) revealed that 4j, 4h and 4g possess promising anticoagulant properties. Other compounds (4a-l) were also found to have significant anticoagulant effect when compared with the heparin as positive control. Thus, these compounds qualify for further clinical studies to be used as the blood anticoagulants.

Background: Prolylcarboxypeptidase (PRCP, EC:3.4.16.2) is a cardioprotective protease. Plasma PRCP levels are elevated in type 2 diabetes (T2D) mellitus and cardiovascular diseases. Objective: Since diabetic cardiomyopathy is a late complication of uncontrolled diabetes, we tested the hypothesis that glucose and free fatty acid related risk factors for T2D mellitus and cardiovascular disease may reduce the cardioprotective property of PRCP. Method: We examined the effects of glucose, saturated fatty acids, and unsaturated fatty acids on PRCP expression in cultured H9c2 cells as an in-vitro model for pharmacological studies. Selective inhibitors, known cardioprotective agents and saturating amounts of neutralizing antibodies were used to validate the effect of free fatty acids on the expression and function of PRCP. Results: The palmitate-mediated reduction of PRCP was concentration and time-dependent. Next, we explored the cardioprotective potential of thyroxin (T4) and insulin. Both T4 and insulin were able to prevent the palmitate-mediated reduction of PRCP expression in H9c2 cells. Inhibition of NF-kB with its specific inhibitor Bay 11-7082 or blockade of palmitate with polyunsaturated fatty acids was ineffective in preventing palmitate-mediated decreases in PRCP expression. Conclusion: Our data indicate that elevated palmitate inhibits PRCP expression in rat cardiomyocyte. From this inference PRCP level should be monitored in obese or diabetic patients because this simple measure could identify individuals at high risk of developing health problems, such as heart failure.

Background: The present study aims to evaluate the in vitro vasorelaxant effect of Artemisia herba alba (Ah) aqueous extract. Method: Aortic rings were isolated from spontaneously hypertensive rats and incubated in aqueous Ah extract at the following doses: 3, 5, 10 and 20 mg/ml. Incubation of aqueous Ah extract for 30 minutes produced a significant shift of the dose response curve to Norepinephrine (NE) (10^-8 to 10^-5 M) (p<0.001). Results: Endothelium ablation significantly reduced the vasorelaxant effect of aqueous Ah extract (p<0.001). In addition, inhibition of vascular nitric oxide by N^w-Nitro-L-Arginine Methyl (LNAME) produced a significant reduction in the vasorelaxant effect of aqueous Ah extract (p<0.001). Conclusion: We conclude that aqueous Ah extract at a dose of 20 mg/ml possess an in vitro vasorelaxant effect which seems to be dependent on the endothelium vasorelaxant factors involving nitric oxide synthesis.