Cardiovascular & Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Cardiovascular & Hematological Agents) - Volume 20, Issue 2, 2022

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.

Background and Objective: Direct (new) Oral Anticoagulants (DOACs) have emerged as a contemporary and promising option in the treatment of thromboses and VTE, while protecting the coagulation cascade against untoward bleeding events. They are used in the management and prophylaxis of Venous Thromboembolism (VTE) and other thrombotic diseases. The most prominent complication of these agents is bleeding. These agents have similar or lower rates of major intracranial hemorrhages, while they had a higher risk of major gastrointestinal bleeding when compared to warfarin. This manuscript is aimed to revise and update the literature findings to outline the side effects of DOACs in various clinical scenarios. Methods: A narrative review of currently published studies was performed. Online database searches were performed for clinical trials published before July 2021, on the efficacy and adverse effects attributed to the anticoagulant treatment, especially DOACs. A literature search via electronic databases was carried out, beginning with the usage of the agents in the Western Languages papers. The search terms initially included direct (new) oral anticoagulants, dabigatran, rivaroxaban, apixaban, edoxaban, idarucizumab, andexanet, prothrombin complex concentrates, and fresh frozen plasma. Papers were examined for methodological soundness before being included. Results: Severe bleeding episodes require aggressive interventions for successful management. Therefore, bleeding should be evaluated in special regard to the location and rate of hemorrhage, and total volume of blood loss. Patient's age, weight and organ dysfunctions (e.g., kidney/liver failure or chronic respiratory diseases) directly affect the clinical course of overdose. Conclusion: Management recommendations for hemorrhage associated with DOAC use vary, depending on the class of the culprit agent (direct thrombin inhibitor vs. FXa inhibitor), the clinical status of the patient (mild/ moderate vs. severe/life-threatening), and capabilities of the institution. Specific reversal agents (i.e., idarucizumab and andexanet alfa) can be used if available, while prothrombin complex concentrates, fresh frozen plasma and/ or tranexamic acid can also be employed as nonspecific replacement agents in the management of DOAC-related bleeding diathesis.

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.

Aims: The aim of the study was to evaluate the antihyperglycemic effect of Chenopodium quinoa. Background: Chenopodium quinoa is a pseudocereal plant with several medicinal properties. Objective: The goal of this investigation was to determine the antihyperglycemic activity of Chenopodium quinoa in both normal and streptozotocin (STZ)-induced diabetic rats. Methods: In this study, the effect of the aqueous extract of Chenopodium quinoa seeds (AECQS) (60 mg/kg) on blood glucose levels was evaluated in both normal and diabetic rats after a single (6 hours) and repeated oral administration (7 days of treatment). The effect of this herb on glucose tolerance and lipid profile was also studied. Additionally, histopathological examination of the liver was carried out using the Hematoxylin-Eosin method. Furthermore, the in vitro antioxidant activity as well as, preliminary phytochemical screening and quantification of some secondary metabolites (phenolic compounds, flavonoids and tannins) were performed according to standard methods. Results: AECQS produced a significant lowering effect on plasma glucose levels in STZ-induced diabetic rats. In addition, this extract exhibited a remarkable amelioration on hepatic histopathology in diabetic rats. In addition, the extract exerted a remarkable antioxidant activity which could be due to the presence of some compounds found in this herb. Conclusion: In conclusion, this study demonstrates that the aqueous extract of Chenopodium quinoa seeds has a favorable effect in controlling diabetes mellitus.

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: This study aimed to investigate the potential bioactivity and the ameliorative role of Galaxaura oblongata (G. oblongata) against LPS-induced toxicity using hematological parameters. Objective: The objective of this study is to examine its protective effect using the immunohistochemistry of the liver and lungs as biomarkers in male BALB/C albino mice. Materials and Methods: The current study was carried out using different in-vitro and in-vivo assays, such as phytochemicals, antioxidants and anti-inflammatory for in-vitro where the hematological and immunohistochemistry for lung and liver were investigated in vivo. Results: No previous studies were performed to investigate the in vivo and in vitro effects of the G. oblongata extracts as antioxidant and anti-inflammatory due to their rareness compared to other red algae. LPS treated mice revealed a significant decrease in the total number of WBCs, RBCs, platelets, and HGB%, MPV, MCV and MCHC compared to the control group. In contrast, the HCT and MCHC were increased in the induction group, which was treated with LPS compared to the control group. Furthermore, the immunohistochemistry results of the present study revealed the protective effect of G. oblongata compared to the induction group. G. oblongata can be used as protective marine natural products against the toxicity induced by LPS. Conclusion: It exhibited a significant ameliorative role against the alterations in the hematological parameters and immunohistochemistry of the liver and lungs, and reduced as well as coordinated the acute inflammations caused by TNF.

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.