Cardiovascular & Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Cardiovascular & Hematological Agents) - Volume 20, Issue 1, 2022

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: To study the role of cytokines and vascular inflammatory biomarkers in unstable carotid plaque. Background: Clinical studies showed that not only the degree of stenosis but also the type of carotid plaque can be responsible for ipsilateral ischemic stroke. Objective: The objective of this study is to suggest a role for vulnerable carotid atherosclerotic disease in the occurrence of ischemic stroke. Methods: PubMed, Embase, Cochrane library, and reference lists have been used to evaluate articles published until February 15, 2021. Results: Several factors may be involved in unstable plaque. Clinical studies support the involvement of brain inflammatory biomarkers as well as cytokines in the unstable carotid plaque. Conclusions: Biomarkers could help to stratify patients with a vulnerable carotid plaque and to personalize the drug treatment. In this review, we briefly discuss the characteristics of vulnerable plaque and the role of biomarkers in the vulnerable carotid plaque.

Despite the marked improvement in overall survival rates of paediatric patients with haematological malignancies that has been achieved during the last decades, there is still a pressing need for novel therapeutic approaches for the subset of patients with relapsed or refractory disease. Immune checkpoint inhibitors aim to induce potent anti-tumour immune responses by targeted blocking of inhibitory receptors and have shown promising results in preclinical models and studies on the adult population. However, paediatric malignancies present unique features, and so far, experience with these agents is limited. In the current review, we present an overview of efficacy and safety data from case reports, case series, and clinical trials employing the use of immune checkpoint inhibitors in children, adolescents, and young adults with haematological malignancies. We also discuss new possibilities involving novel targets and combination treatments and provide a summary of the currently registered clinical trials.

Objective: Salvia miltiorrhiza (SM) is a traditional Chinese medicine used clinically to treat cardiovascular diseases, including atherosclerosis and myocardial infarction. Its therapeutic effect has been confirmed by many clinical and pharmacological studies. However, the optimal formulation of active ingredients in SM for treating cardiovascular diseases remains unclear. In this study, we determined the ratio of the optimal compatibility of SM ingredients DSS, Sal-A, Sal-B, and PAL (SABP)with a uniform and orthogonal optimized experimental design. In addition, we determined the anti-oxidation effect of SABP using Adventitial Fibroblasts (AFs). Methods: By using a combination of uniform and orthogonal designs, we determined the optimal formulation of aqueous extract from SM. MTT assay was used to determine the inhibitory effects of these 4 components of SM on the AFs, which were isolated and cultured from the aorta. The reactive oxygen species (ROS) production in AFs was compared before and after SABP treatment. Results: The optimal formulation of these 4 aqueous extracts from SM were 150 : 7 : 300 : 500, and their concentrations were S(1.5×10-4 mol/L), A(7×10-6 mol/L), B(3×10-4 mol/L), and P(5×10-4 mol/L). There were some synergies between these 4 components. Moreover, SABP decreased ROS production in AFs. Conclusion: These findings suggest that SABP inhibits the proliferation and oxidation stress in AFs. The present study provides new evidence that the efficacy and function generated from the optimal formulation of active ingredients in SM are better than lyophilized powder of SM.

Aim: The aim of this study was to evaluate the in vitro effect of coumarin and 15 monosubstituted derivatives on the inhibition of human platelet aggregation induced by various proaggregatory agonists, particularly by epinephrine. Background: The emergence of residual platelet reactivity during the use of conventional antiplatelet agents (acetylsalicylic acid and clopidogrel) is one of the main causes of double therapy´s therapeutic failure. Platelet adrenoceptors participate in residual platelet reactivity. Therefore, it is necessary to develop new antiplatelet agents that inhibit epinephrine-induced platelet aggregation as a new therapeutic strategy. Information on the antiplatelet activity of coumarins in inhibiting epinephrine-induced aggregation is limited. Objective: The objective of this study was to establish the structure-activity relationship (SAR) of coumarin derivatives with hydroxy, methoxy, and acetoxy groups in different positions of the coumarin nucleus to identify the most active molecules. Moreover, this study aimed to use in silico studies to suggest potential drug targets to which the molecules bind to produce antiplatelet effects. Methods: The platelet aggregation was performed using a Lumi-aggregometer; the inhibitory activity of 16 compounds were evaluated by inducing the aggregation of human platelets (250 × 103/μl) with epinephrine (10 μM), collagen (2 μg/ml) or ADP (10 μM). The aggregation of control platelets was considered 100% of the response for each pro-aggregatory agonist. Results: Eleven molecules inhibited epinephrine-induced aggregation, with 3-acetoxycoumarin and 7-methoxycoumarin being the most active. Only coumarin inhibited collagen-induced platelet aggregation, but no molecule showed activity when using ADP as an inducer. Conclusions: In silico studies suggest that most active molecules might have antagonistic interactions in the α2 and β2 adrenoceptors. The antiplatelet actions of these coumarins have the potential to reduce residual platelet reactivity and thus contribute to the development of future treatments for patients who do not respond adequately to conventional agents.

Aims: The aim of the study was to assess the effect of Cleome arabica on lipid metabolism. Background: Cleome arabica (L.) is a medicinal plant used traditionally by the population of North Africa for managing diabetes mellitus. Objective: This study was designed to evaluate the antidyslipidemic and antiatherogenic capacities of Cleome arabica (L.) in normal and streptozotocin(STZ)-induced diabetic rats. Methods: The hypolipidemic, antihyperglycemic and antiatherogenic effects of oral administration of the aqueous extract of Cleome arabica (CAAE) (100 mg/kg) were evaluated in normal and diabetic rats. In addition, the quantification of polyphenols, flavonoids and tannins as well as the antioxidant activity were performed. Results: The results showed that the extract (CAAE) revealed an antidyslipidemic action by attenuating plasma levels of Total Cholesterol (TC), Triglycerides (TGs), Low-Density Lipoprotein cholesterol (LDL-c), Very low-density lipoprotein cholesterol (VLDL-c) and glucose. Additionally, CAAE exhibited a potent antiatherogenic activity by reducing Atherogenic Coefficient (AC), Castelli’s Risk index-I (cri-I), and Castelli’s Risk Index-II (CRI-II). Furthermore, the findings indicated that CAAE is abundant with polyphenols, flavonoids and tannins, and exhibited an important antioxidant capacity. Conclusion: The study demonstrates that aqueous Cleome arabica extract was able to ameliorate lipid abnormalities associated with diabetes mellitus. This pharmacological activity might be due to the antioxidant capacities of phytochemical compounds.

Aims: The study targeted to evaluate the antihyperglycemic activity of Salvia hispanica. Background: Salvia hispanica L. (Lamiaceae) is a medicinal plant with many beneficial properties on human health. Objective: This objective of the study was to investigate the antihyperglycemic effect of the aqueous extract of Salvia hispanica (S. hispanica) seeds and its capacity to improve lipid profile in normal and STZ-induced diabetic rats. Material and Methods: The seed aqueous extract of S. hispanica (SHSAE) at a dose of 100 mg/kg was administered orally in normal and diabetic rats. The effect of oral SHSAE treatment on blood glucose and lipid levels during 15 days was assessed in normal and streptozotocin-induced diabetic rats. The oral glucose tolerance test (OGTT) was carried out. The antioxidant activity of SHSAE was also examined. Results: The decrease of glycemia in rats following the administration of the plant extract suggested that the studied extract possesses antidiabetic effect. The extract of S. hispanica produced hypolipidemic effect with a significant lowering effect on plasma total cholesterol levels and increased on HDL-cholesterol levels. SHSAE was also able to enhance glucose tolerance using OGTT. Moreover, SHSAE possesses a potential antioxidant effect in vitro. Conclusion: In conclusion, this study demonstrates the antihyperglycemic and antilipidemic effects of SHSAE in rats.

Background: Diabetes mellitus is one of the major and common metabolic and chronic disorders in the world. Several medicinal plants have been used globally for the management of diabetes mellitus. The current study aimed to study the antihyperglycemic and antihyperlipidemic effects of Bersama abyssinica. Methods: Antidiabetic effect of 80% methanolic crude extract of Bersama abyssinica was studied in a repeated dose-treated STZ-induced diabetic mice model. The activities of Bersama abyssinica on serum lipid level and body weight were investigated on STZ-induced diabetic mice. Data were analyzed using one-way ANOVA and were significant when the p-value was less than 0.05. Results: All doses of the crude 80% methanolic extract of Bersama abyssinica (100 mg/kg, 200 mg/kg, and 400 mg/kg) exhibited a noticeable BGL reduction when compared with baseline blood glucose level and diabetic control on the 7th and 14th days of administration. Moreover, higher dose of the extract (at 400 mg/kg) significantly (p < 0.001, 54.3%) decreased the BGL in STZ-induced diabetic mice. The maximum decrement in fasting BGL was achieved at the 14th days: 34.92%, 41.10%, 54.30%, and 59.66%, respectively for BAC 100 mg/kg, BAC 200 mg/kg, BAC 400 mg/kg, and GLC 5 mg/kg treated groups. Bersama abyssinica also displayed a significant (p < 0.05) improvement of serum lipid levels and body weight. Conclusion: Bersama abyssinica crude extract exhibited a significant antidiabetic effect and prevented body weight loss in streptozotocin-induced diabetic mice. The finding also confirmed the valuable biochemical activity of Bersama abyssinica by improving serum lipid levels.

Background: Antioxidants are beneficial in myocardial infarction (MI). It is suggestive that Theobroma cacao (TC) with rich antioxidant properties can be of health benefits in myocardial injury. Aim: The study investigated the effect of Theobroma cacao on cardioprotection in isoproterenol-induced myocardial infarction in rats. Material and methods: Male Wistar rats divided into four groups of 6 rats were used for the study. In group 1, 0.9% normal saline placebo was administered via oral gavage to the control. Group 2 was the MI induced group that was given 100 mg/kg body weight isoproterenol subcutaneously twice at an interval of 24 hours. Group 3 was administered TC for 2 weeks at 100 mg/kg bodyweight via the oral route. Group 4 was pretreated with TC (100 mg/kg) via oral route for 2 weeks, immediately followed by the administration of 100 mg/kg body weight isoproterenol subcutaneously twice at an interval of 24 hours. The rats were sacrificed using chloroform anesthesia, and blood samples collected via cardiac puncture. The serum was analyzed for troponin level, lactate dehydrogenase (LDH), and malondialdehyde (MDA) level. Results: The serum troponin, LDH, and MDA levels were found to be significantly (p<0.01) increased in the MI group compared with the control. Pretreatment with TC before MI induction significantly (p<0.01) prevented increased serum troponin, LDH, and MDA levels when compared with the MI group. There was also a significant (p<0.01) decrease in MDA in the TC group compared with the control. Conclusion: These results suggest that Theobroma cacao protects against isoproterenol-induced myocardial injury, possibly by preventing oxidative stress and consequent lipid peroxidation.