Cardiovascular and Hematological Agents in Medicinal Chemistry最新文献

Introduction: Essential oils are complex mixtures of volatile compounds, primarily composed of terpenes and abundant aromatic plants. For example, Cymbopogon citratus (lemongrass) is an aromatic plant that produces a monoterpene-rich essential oil, and studies show that this essential oil has excellent antioxidant activity. Erythrocytes incubated under high sugar levels are constantly exposed to reactive oxygen species, which results in the oxidation of their membranes.

Objective: The aim of this article is to investigate the antioxidant activity of lemongrass essential oil and its protective effect on erythrocytes exposed to high levels of glucose.

Materials and methods: The essential oil was obtained by steam dragging distillation; blood cell suspensions were incubated with glucose 5, 20, 50, and 100 mmol/L. The amount of TBARS produced was measured at 532 nm. In addition, the percentage of antioxidant activity was assessed by DPPH free radical assay.

Results: Lemongrass essential oil showed an increase in the antioxidant activity up to 240 mg/ml, while ascorbic acid used as positive control showed a dose-dependent increase in antioxidant activity starting at 1 mmol/L up to 18 mmol/L. However, such a lemongrass dose prevented peroxidation in erythrocytes incubated under a high glucose media, whereas ascorbic acid showed a protective effect only at a concentration of 1 mmol/L.

Conclusion: Lemongrass essential oil has high antioxidant activity compared to standard antioxidant as ascorbic acid, and also acts as a protective agent against erythrocyte lipoperoxidation due to hyperglycemia in vitro.

Direct (New-generation) Oral Anticoagulants (DOACs) have emerged as effective agents which are used in place of vitamin-K antagonists in treatment and prophylaxis of Venous Thromboembolism (VTE), atrial fibrillation and other thrombotic diseases. Among them, the FIIa- direct thrombin inhibitor dabigatran and FXa inhibitors (rivaroxaban, apixaban, edoxaban) are the most broadly used. Anticoagulant dosing may differ under special considerations. The patients' physiological reserves, organ functional status and failures should be taken into account in clinical decision-making processes. The advantages and drawbacks of each specific agent should be weighed with special regard to metabolism, pharmacokinetics and pharmacodynamics, along with the efficiency of the agents in different indications. This article aims to review the most recent literature to highlight the usage and efficacy of the agents in different clinical conditions.

Atherosclerosis, a major contributor to cardiovascular disease, is a global alarm causing mortality worldwide. Being a progressive disease in the arteries, it mainly causes the recruitment of monocytes to the inflammatory sites and subsides pathological conditions. Monocyte-derived macrophage mainly acts in foam cell formation by engorging the LDL molecules, oxidizes it into Ox-LDL and leads to plaque deposit development. Macrophages in general differentiate, proliferate and undergo apoptosis at the inflammatory site. Frequently two subtypes of macrophages M1 and M2 have to act crucially in balancing the micro-environmental conditions of endothelial cells in arteries. The productions of pro-inflammatory mediators like IL-1, IL-6, TNF-α by M1 macrophage have atherogenic properties majorly produced during the early progression of atherosclerotic plaques. To counteract cytokine productions and M1-M2 balance, secondary metabolites (phytochemicals) from plants act as a therapeutic agent in alleviating atherosclerosis progression. This review summarizes the fundamental role of the macrophage in atherosclerotic lesion formation along with its plasticity characteristic as well as recent therapeutic strategies using herbal components and anti-inflammatory cytokines as potential immunomodulators.

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 men

Background: Diabetic cardiotoxicity is commonly associated with oxidative injury, inflammation, and endothelial dysfunction. L-ergothioneine (L-egt), a diet-derived amino acid, has been reported to decrease mortality and risk of cardiovascular injury, provides cytoprotection to tissues exposed to oxidative damage, and prevents diabetes-induced perturbation.

Objective: This study investigated the cardioprotective effects of L-egt on diabetes-induced cardiovascular injuries and its probable mechanism of action.

Methods: Twenty-four male Sprague-Dawley rats were divided into non-diabetic (n = 6) and diabetic groups (n = 18). Six weeks after the induction of diabetes, the diabetic rats were divided into three groups (n = 6) and administered distilled water, L-egt (35mg/kg), and losartan (20mg/kg) by oral gavage for six weeks. Blood glucose and mean arterial pressure (MAP) were recorded pre-and post-treatment, while biochemical, ELISA, and RT-qPCR analyses were conducted to determine inflammatory, injury-related and antioxidant biomarkers in cardiac tissue after euthanasia. Also, an in-silico study, including docking and molecular dynamic simulations of L-egt toward the Keap1- Nrf2 protein complex, was done to provide a basis for the molecular antioxidant mechanism of Legt.

Results: Administration of L-egt to diabetic animals reduced serum triglyceride, water intake, MAP, biomarkers of cardiac injury (CK-MB, CRP), lipid peroxidation, and inflammation. Also, Legt increased body weight, antioxidant enzymes, upregulated Nrf2, HO-1, NQO1 expression, and decreased Keap1 expression. The in-silico study showed that L-egt inhibits the Keap1-Nrf2 complex by binding to the active site of Nrf2 protein, thereby preventing its degradation.

Conclusion: L-egt protects against diabetes-induced cardiovascular injury via the upregulation of the Keap1-Nrf2 pathway and its downstream cytoprotective antioxidants.

Background & objectives: Nitric Oxide (NO) is frequently produced by the enzyme nitric oxide synthase (NOS) and is crucial for the control and effectiveness of the cardiovascular system. However, there is a substantial reduction in NOS activity with aging that can lead to the development of hypertension and other cardiovascular obstacles. Fortunately, NO can also be produced by sequential reduction of inorganic nitrates supplementation. This proves that NO from inorganic nitrate supplements can compensate for inadequate NOS activity, thus providing cardio protective benefits.

Discussion: This review focuses on the general information about nitrous oxide, its types and mechanism of action and the fact that overview of inadequate NOS activity for cardio protective benefits was often studied for cardiovascular treatments.

Conclusion: We concluded that the natural plant NO is essential for cardiovascular activity to target site with desired concentration. Moreover, the researchers focused on evidence that suggested that nitrate supplementation could help regulate blood pressure, limit progression of atherosclerosis, and improve myocardial contractility in both healthy individuals and those with cardiovascular diseases.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of anti-diabetic agents that block the reabsorption of glucose in the proximal convoluted tubule of the nephron, thereby contributing to glycosuria and lowering blood glucose levels. SGLT2 inhibitors have been associated with improved cardiovascular outcomes in patients with diabetes, including a reduced risk of cardiovascular death and hospitalizations for heart failure. Recently, DAPA-HF and EMPEROR REDUCED trials showed the beneficial cardiovascular effect of SGLT2 inhibitors in patients with heart failure with consistently reduced ejection fraction (HFrEF) regardless of the presence of diabetes. Moreover, some exploratory studies suggested that these drugs improve Left Ventricular (LV) systolic function and oppose LV adverse remodeling in patients with HFrEF. However, the exact mechanisms that mediated for this benefit are not fully understood. Beyond glycemic control, enhanced natriuresis, increased erythropoiesis, improved endothelial function and changes in myocardial metabolism may all play an active role in SGLT2 inhibitors' cardiovascular benefits. A deep understanding of the pathophysiological interplay is key to define which HF phenotype could benefit more from SGLT2 inhibitors. Current evidence on the comparison of different HF etiologies is limited to posthoc subgroup analysis of DAPA-HF and EMPEROR-REDUCED, which showed similar outcomes in patients with or without ischemic HF. On the other hand, in earlier studies of patients suffering from diabetes, rates of classic ischemic endpoints, such as myocardial infarction, stroke or coronary revascularization, did not differ between patients treated with SGLT2 inhibitors or placebo. The aim of this review is to discuss whether SGLT2 inhibitors may improve prognosis in patients with ischemic HF, not only in terms of reducing re-hospitalizations and improving LV function but also by limiting coronary artery disease progression and ischemic burden.

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.