Cardiovascular & Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Cardiovascular & Hematological Agents) - Volume 18, Issue 1, 2020

Nature is an amazing source for food, shelter, clothing and medicine. An impressive number of modern drugs are isolated from many sources like plants, animals and microbes. The development of natural products from traditional medicines is of great importance to society. Modern concepts and methodologies with abundant clinical studies, unique diversity of chemical structures and biological activities aid the modern drug discovery process. Kedrostis foetidissima (Jacq.) Cogn., a traditional medicinal plant of the Cucurbitaceae family, is found in India, Sri Lanka, Ethiopia and Western Malaysia. Almost all parts of the plant are used in traditional systems of medicines and reported having medicinal properties in both in vitro and in vivo studies. In the last few years, extensive research work had been carried out using extracts and isolated phytoconstituents from Kedrostis foetidissima to confirm its pharmacology and biological activities. Many scientific reports show that crude extracts and extensive numbers of phytochemical constituents isolated from Kedrostis foetidissima have activities like antimicrobial, antioxidant, anticancer, gastroprotective, anti-inflammatory and various other important medicinal properties. The therapeutic properties of the plants are mainly attributed to the existence of phytoconstituents like phenols, alkaloids, flavonoids, tannins, terpenoids and steroids. This comprehensive review in various aspects gave a brief overview of phytoconstituents, nutritional values and medicinal property of the plant and might attract the researchers to explore its medicinal activity by discovering novel biologically active compounds that can serve as a lead compound in pharmaceutical and food industry.

Background: Imbalanced diets have contributed to the increased prevalence of obesity and other metabolic disorders in the modern world including trace element metabolism. However, the underlying mechanisms are not fully understood. Aim and Objectives: The present study investigated the effects of Biochanin A (BCA) on the changes in element metabolism induced by HFD-induced obese rats. Methods: BCA was administered orally for 30 days to experimental obese rats. Changes in body weight, glucose, insulin resistance and lipid profiles of plasma, as well as the level of trace elements (Fe, Zn, Mg and Cu) in various tissues (liver, kidney, heart and pancreas) and hepsidine and heme oxygenase, were observed in experimental rats. Results: The administration of BCA elicited a significant (p<0.05) reduction in, glucose, insulin, ferritin, total cholesterol, phospholipids, free fatty acids, VLDL-C, LDL-C, triglycerides and hepsidin. Significant alterations were observed in trace elements level, HDL-C, transferrin, bilirubin and HO - 1 level. Conclusion: These findings suggested that HFD results in derangement of trace elements in the tissues of rats fed with HFD. BCA may alleviate the derangement of HFD induced trace elements metabolism by modulating hyperglycemic and insulin resistance status and altering hepcidin and HO-1.

Background: This study determined the effect of Biochanin A (BCA) on isoproterenol (ISO) induced Myocardial Infarction (MI) in male Wistar rats. Methods: Animals (weighing 150-180 g) were divided into four groups, with six animals in each group and pretreated with BCA (10mg/kg Body Weight [BW]) and α-tocopherol (60mg/kg BW) for 30 days; and ISO (20mg/kg BW) was administrated subcutaneously on the 31st and 32nd day. Results: ISO-induced MI rats demonstrated the significant elevation of serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, lactate dehydrogenase, creatine kinase-MB and cardiac troponin; however, concomitant pretreatment with BCA protected the rats from cardiotoxicity caused by ISO. Activities of antioxidant enzymes, such as superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and glutathione reductase significantly reduced in the heart with ISO-induced MI. Pretreatment with BCA produced a marked reversal of these antioxidant enzymes related to MI-induced by ISO. Conclusion: In conclusion, this study suggested that BCA exerts cardioprotective effects through modulating lipid peroxidation, enhancing antioxidants, and detoxifying enzyme systems.

Background: The present study was conducted to evaluate the mitigating effects of Asiatic Acid (AA), on the changes in carbohydrate metabolism, insulin signaling molecules and renal function markers in Streptozotocin (STZ)-Nicotinamide (NAD) induced diabetic rats. Methods: AA (20 mg/kg BW) was supplemented orally to the diabetic rats for 42 days. The levels of plasma glucose, Hemoglobin (Hb), glycosylated hemoglobin (HbA1c) insulin and renal function markers, carbohydrate metabolic enzymes in the kidney and insulin signaling molecules in skeletal muscle were measured. Results: The administration of AA elicited a significant decrease in the levels of plasma glucose, insulin resistance, HbA1c, urea, uric acid, creatinine, glycogen, glycogen synthase, glucose-6- phosphatase, and fructose-1,6-bisphosphatase and a significant increase of body weight development, insulin, Hb, hexokinase, and glycogen phosphorylase and mRNA expressions of insulin signaling molecule like insulin receptor 1, insulin receptor 2 and glucose transporter-4 in the STZ-NAD induced diabetic rats. Further, the protective effect of AA was evidenced by its histological annotation of the kidney tissues. Conclusion: Hence, this study concluded that AA can protect against renal dysfunction by attenuating carbohydrate metabolic disorder and subsequently enhances glucose utilization and renal function in STZ-NAD-induced diabetic rats.

Aims: The present research work discussed the preparation of lomustine loaded with chitosan nanoparticles (LNCp) by ionic gelation method with homogenization using the design on experiments by Box-Behnken design. Methods: The nanoparticles are evaluated by particle size, zeta potential, surface morphology, drug content, entrapment efficiency and in-vitro drug release. Results: The FT-IR results support that drug have no interaction with excipients, which are used in the preparation of nanoparticle. The particle size, drug content and encapsulation efficiency of the developed nanoparticles ranged from 190 to 255 nm, 80.88% to 94.02%, and 77.12 to 88.74%, respectively. The drug release rate is diffusion-controlled over 8 hours. The F-value for all of the responses shows that the models are significant. The p-value, less than 0.05 for all the responses reveals the significance of the models. Graphical optimisation is done by desirability plot and overlay plot, which contains optimal values of independent variables with the desirability of 1. Conclusion: In conclusion, the results suggested that the optimised lomustine loaded chitosan nanoparticles are useful for brain targeting hence hold the potential for further research and clinical application.

Background: Buxus sempervirens L. is a medicinal plant with several beneficial effects on health and is widely used in Moroccan folklore as an antidiabetic plant. Objective: The aim of this study was to evaluate the antidiabetic effect of both aglycone and glycoside flavonoid enriched extracts of this plant in the experimental diabetic state. Methods: In the current work, the effect of aglycone and glycoside flavonoid-enriched extracts from the leaves of Buxus sempervirens L. (AFBS and GFBS) (10 mg/kg) on blood glucose levels has been evaluated in normal and streptozotocin (STZ) diabetic rats. Moreover, the histopathological changes in the liver and pancreas have been assessed in STZ diabetic rats. The ability of AFBS and GFBS to improve glucose tolerance in normal rats was also evaluated. Results: In normal rats, both a single and repeated administration of AFBS and GFBS (10 mg/kg) showed no significant effects on blood glucose levels. However, both single and repeated oral administration of the two fractions showed a significant blood glucose lowering effect (p<0.0001) in STZ rats. In addition, histopathological analysis has demonstrated the beneficial impact of AFBS and GFBS on the pancreas and liver. Whereas, the oral glucose tolerance test demonstrated no significant ability of these extracts to improve the increase in blood glucose levels in normal and diabetic treated rats. In the current study, no significant changes in body weight in normal and STZ rats have been shown. In addition, the antioxidant activity of both AFBS and GFBS revealed the antioxidant effect of both extracts. Furthermore, both flavonoid-enriched fractions had no significant effect on blood lipid levels. Conclusion: In conclusion, AFBS and GFBS exhibited an interesting antidiabetic effect on streptozotocin rats and GFBS which seems to be more effective than AFBS.

We present a 10-year-old boy with syncope who was found to have long-QT syndrome and severe Pulmonary Hypertension (PH) both in the absence of a secondary cause; to our knowledge, this is the first report with this unusual coexistence. His genetic tests were positive for hereditary hemorrhagic telangiectasia and Long QT Syndrome (LQTS) without any family history of PH or LQTS. We demonstrated that digital subtraction pulmonary angiography was more useful compared to CT angiogram to demonstrate pulmonary vascular changes which correlated with a noresponse to acute vasoreactivity testing during right heart catheterization. He has been stable for the last 2 years on Ambrisentan, Sildenafil, and Nadolol without recurrence of symptoms.