Cardiovascular & Hematological Agents in Medicinal Chemistry - Volume 20, Issue 3, 2022

Rheumatic valve disease is present in 0.4 % of the word population, mainly in lowincome countries. Rheumatic mitral stenosis affects more women and between 40 to 75 % of patients may have atrial fibrillation (AF), more frequently in upper-middle income countries. This rhythm disturbance is due to increased atrial pressure, chronic inflammation, fibrosis, and left atrial enlargement. There is also an increase in the prevalence of AF with age in patients with mitral stenosis. The risk of stroke is 4 % per year. Success rates for cardioversion, Cox-Maze procedure, and catheter ablation are low. Therefore, anticoagulation with vitamin K antagonist is mandatory for Evaluated Heart valves, Rheumatic or Artificial (EHRA) classification type 1. However, this anticoagulation is used by less than 80 % of those eligible and less than 30 % have the international normalized ratio in the therapeutic range. The safety and efficacy of using rivaroxaban, a direct factor Xa inhibitor anticoagulant, were demonstrated in the RIVER trial with a sample of 1005 patients with AF and bioprosthetic mitral valve. The indication for valve replacement, that is, if severe mitral stenosis or severe mitral regurgitation, was not specified. A randomized, open-label study (DAVID-MS) is underway to compare the effectiveness and safety of dabigatran and warfarin therapy for stroke prevention in patients with AF and moderate or severe mitral stenosis. Thus, the applicability of the use of direct anticoagulants in patients with AF and mitral stenosis and also in those undergoing mitral bioprostheses surgery will be the subject of further studies. The findings may explain if specific atrial changes of mitral stenosis even after the valve replacement will influence thromboembolic events with direct anticoagulants.

The post-COVID neurological syndrome has been coined, which describes the functional and structural sequelae of coronavirus infection disease-19 (COVID-19) in the brain. Mild/severe manifestations of the post-COVID neurological syndrome have been identified in approximately 33.00% of COVID-19 survivors. The presence of neurological complications after COVID allowed neuropathologists to investigate in-depth the role of viral infection in neurons. The pathophysiology of the post-COVID neurological syndrome involved the development of a systematic response, including coagulopathy characterized by the formation of microthrombi. Coagulopathy, an old term for a new disease, describes the discrepancy between pro-coagulant and anticoagulant systems due to overexpression of pro-coagulant substances and or their receptors in addition to suppression of the anticoagulant molecules and or their receptors. Vascular endothelial cells and hepatocytes play a central role in the regulation of hemostasis that is disrupted during the acute phase response (APR) of coronavirus-19 (COVID-19). Currently, coagulopathy and inflammation are termed together since both form a complementary system, indicated by the elevation of inflammatory biomarkers (APR) and fibrinolysis biomarkers (D-dimer/fibrin). The later events of the post-COVID neurological syndrome are primarily induced by coagulopathy and direct viral tropism. Therefore, the paper introduces the hypothesis of coagulopathy induced post-COVID neurological syndrome.

Introduction: Thromboembolic events are one of the important complications in COVID-19 patients, especially in severe cases. Aspirin affects platelet function by irreversibly inhibiting cyclooxygenase activity, reducing the risk of thrombosis. The current systematic review aimed to evaluate aspirin's effectiveness in preventing pro-thrombotic states in COVID-19 hospitalized patients. Methods: The systematic search was done in PubMed/Medline, EMBASE, and Medrxiv until September 27, 2021. The following keywords were used: “COVID-19”, “SARS-CoV-2”, “2019 Novel Coronavirus”, “Aspirin,” and “Acetylsalicylic Acid.” Results: Twelve studies were included. In COVID-19 patients, aspirin can reduce CRP, IL-6 levels, and platelet aggregation by inhibiting thromboxane A2. It can also improve antiviral immunity by hindering the biosynthesis of prostaglandins and lipoxin. Eight out of twelve articles indicated that aspirin provided a beneficial effect on COVID-19. Most studies consider lowered mechanical ventilation needs, ICU admission, illness severity, overt thrombosis, and clinical outcomes in COVID-19 patients receiving aspirin. Conclusion: Aspirin as an antiplatelet and anti-inflammatory agent may reduce the mortality rates in hospitalized patients with severe COVID-19. Further observational studies are necessary to determine the effect of aspirin on the prevention of pro-thrombotic states in hospitalized COVID- 19 patients.

Aims: The study aimed to assess the antihyperglycemic activity of Pulicaria mauritanica. Background: Pulicaria mauritanica is a medicinal and aromatic plant used for the treatment of many diseases such as inflammation, diabetes, and intestinal disorders. Objective: The main goals of this present paper were to confirm the antihyperglycemic capacity of aqueous extract from Pulicaria mauritanica in normoglycemic and diabetic rats over a period of time (7 days of treatment). Methods: The effect of the aqueous extract of Pulicaria mauritanica from aerial parts (AEPM) on glucose and lipid metabolism was tested using an acute test (single dose during 6 hours) and subchronic assay (repeated oral administration for seven days) at a dose of 60 mg/kg and the serum glucose levels were measured in normoglycemic and streptozotocin(STZ)-induced diabetic rats. In addition, the glycogen content in the liver, extensor digitorum longus (EDL), and soleus was evaluated. The antioxidant activity, phytochemical screening, and quantification of some secondary metabolites of this extract were also performed. Results: AEPM at a dose of 60 mg/kg reduced the plasma glucose concentrations significantly in STZ-induced diabetic rats after a single oral administration (p<0.05). This lowering effect became more significant during the repeated oral administration in hyperglycemic rats (p<0.0001). Also, the findings showed that this plant exhibited a significant increase in liver and skeletal soleus muscle glycogen content in diabetic rats. AEPM revealed a remarkable antioxidant activity in addition to the presence of polyphenol compounds such as flavonoids, tannins, saponins, sterols, glucides, terpenoids, quinones, anthraquinones, and mucilage. Conclusion: The study shows that AEPM exhibits antihyperglycemic activity in diabetic rats, and it increases liver and muscle glycogen content.

Objective: The study was performed to assess if hematological mechanisms such as blood flow modulation, P50 and Oxygen haemoglobin dissociation are involved in Artocarpus altilis leaf extract amelioration of Isoproterenol-Induced Myocardial Damage in rats. Methods: Twenty (20) adult male Sprague-Dawley rats were randomly divided into 5 groups. Group 1 served as the control, group 3 and 5 received 50 and 100 mg/kg Artocarpus altilis water extract, respectively, after being induced with Isoproterenol twice (85 mg/ kg) at a 24-hour period. Group 2 received 85mg/kg isoproterenol only, while group 4 received 50 mg/kg Artocarpus altilis extract only for 6 days. The Hematological parameters were assessed using an automatic Coulter Counter, blood flow was assessed with the CODA machine using the tail cuff method, while blood viscosity was measured at native hematocrit and the oxygen haemoglobin dissociation curves were assessed with the BioProfiler and Hemox Analyzer at the end of seven days. Results: Artocarpus altilis treatment ameliorated the ISO induced increases in viscosity, increased the ISO induced decreased blood flow and influenced oxygen release through its effects on the P50 of the oxygen hemoglobin dissociation curve, AA treatment also reversed the ISO induced weight loss. Apart from the changes in MCH, MCV, there were no significant differences in hematological parameters. Conclusion: This study reported the effects of Artocarpus atilis on the improvement of oxygen availability, the reduction of blood viscosity, and the improvement of blood flow through its influence on endothelial functions and NO availability. Our study further highlights The usefulness of A.atilis, as having a beneficial cardiovascular and haematological outcome in experimental myocardial infarction and as such, potential drug discovery for diseases of cardiovascular & hematological involvement.

Aims: The study aimed to assess the antihypertensive activity of Calamintha officinalis. Background: Calamintha officinalis (CO) is a medicinal and aromatic herb as well as an antihypertensive plant that is widely used for its medicinal properties in several regions. Objective: This study aimed to evaluate the effect of the aqueous extract of Calamintha officinalis (AECO) on vasorelaxant activity and arterial blood pressure under normal and hypertensive states in rats. Additionally, the effect of AECO on vascular angiotensin-converting enzyme 2 (ACE-2) was assessed. Methods: In the current study, AECO (100 mg/Kg) was prepared, and its antihypertensive ability was assessed in L-N^G-Nitro arginine methyl ester (L-NAME)-induced hypertensive rats. Blood pressure and heart rate were recorded for 6 h for the acute experiment and during seven days for the subchronic treatment. Results: The results indicated that AECO reduced the systolic, diastolic, and mean arterial blood pressure in hypertensive rats. In addition, the study showed that AECO exerts a vasorelaxant ability through the sGC-cGMP induction pathway, vascular cyclooxygenase pathway, and the opening of K+ channels. However, AECO had no inhibitory effect on aortic ACE-2. Conclusion: The study illustrates the beneficial action of AECO as an antihypertensive and vasorelaxant agent.

Aims: Many pharmaceutical plants belonging to this region are used as the traditional drug by traditional physicians of the Urmia city in order to treat signs of disorders and cardiovascular system diseases. Background: The Ghasemloo valley located in Urmia city is one of the typical areas in northwestern Iran and includes many pharmaceutical and plant species. Objective: Many pharmaceutical plants belonging to this region are used as the traditional drug by traditional physicians of the Urmia city in order to treat several symptoms of disorders and cardiovascular system diseases. Method: A study was performed among 35 grocers in Urmia city to identify effective and famous pharmaceutical plants in the treatment of cardiovascular and related diseases. Firstly, a complete list of Urmia grocers was prepared by the Food and Drug Administrator of the Urmia University of Medical Sciences. The direct observation and interview, alongside collecting herbarium samples of usual and effective indigenous medicinal plants, were used to identify disorders and different signs of cardiovascular diseases. Questionnaires included personal information of grocers, and completed indigenous plants list containing information, including the plant’s local name, the used organ, method of use, and the traditional therapeutic effect. Herbarium samples mentioned in the questionnaire were collected from the region and sent to the Jahad-e-Keshavarzi Research Centers and the Agriculture Faculty of Urmia university to determine the genus and species. After identifying and confirming the plant species, data related to the plant and results of cardiovascular research conducted on them were collected and recorded with reference to valid scientific sites. Data were entered into the Excel 2010 program and then analyzed. Result: 60 medicinal plants of 26 families in Urmia were identified as effective in the treatment of cardiovascular diseases from interviews and questionnaires; some plants mentioned in this study had known traditional therapeutic effects on cardiovascular disorders in the literature and some were identified with new effects. Results showed that the most therapeutic effects in cardiovascular diseases belonged to families Rosaceae (15%), Fabaceae (13%), Asteraceae (13%), and Apiaceae (10%). The most used organs of plants were the leave (23%) and fruit (19%). Plants were used mainly as an infusion (68%) in the traditional method. Most plants of this study were used to treat the blood cholesterol (29%), hypertension (9%), blood coagulation, prevention of bleeding (9%), and decrease in abdominal fat (9%). Conclusion: Some herbs introduced in this study have new therapeutic effects introduced for the first time. It is necessary to study the therapeutic effects of indigenous plants presented in this research in order to prove studied and mentioned therapeutic effects and provide a study field for researchers in relation to identifying effective substances and studying claimed clinical effects of these plants on different cardiovascular diseases.