Cardiovascular & Haematological Disorders - Drug Targets - Volume 23, Issue 1, 2023

Myocardial infarction and its sequalae remain the leading cause of death worldwide. Myocardial infarction (MI) survivors continue to live a poor quality of life due to extinguished heart failure. The post-MI period involves several changes at the cellular and subcellular levels, of which autophagy dysfunction. Autophagy is involved in the regulation of post-MI changes. Physiologically, autophagy preserves intracellular homeostasis by regulating energy expenditure and sources. Furthermore, dysregulated autophagy is considered the hallmark of the post-MI pathophysiological changes, which leads to the known short and long post-MI reperfusion injury sequalae. Autophagy induction strengthens self-defense mechanisms of protection against energy deprivation through economic energy sources and uses alternative sources of energy through the degradation of intracellular components of the cardiomyocyte. The protective mechanism against post-MI injury includes the enhancement of autophagy combined with hypothermia, which induces autophagy. However, several factors regulate autophagy, including starvation, nicotinamide adenine dinucleotide (NAD+), Sirtuins, other natural foods and pharmacological agents. Autophagy dysregulation involves genetics, epigenetics, transcription factors, small noncoding RNAs, small molecules, and special microenvironment. Autophagy therapeutic effects are signaling pathway-dependent and MI stage dependent. The paper covers recent advances in the molecular physiopathology of autophagy in post-MI injury and its potential target as a future therapeutic strategy.

Background: Natural products and their derived pure phytochemicals have enormous potential to treat human disorders and associated secondary complications. Natural products are widely consumed by humans due to their rich phytochemical content, diverse therapeutic potential and cost-effectiveness compared to allopathic medicine. Flavonoids are a well-known class of polyphenolic compounds widely present in the plant kingdom. Tectochrysin is an important class of dietary flavonoids present in foods and fruits. Tectochrysin has anti-tumor, anti-Alzheimer’s, and antimicrobial activities in medicine. Pharmacological studies have signified the biological application of tectochrysin in health sectors for the treatment of hepatic and gastrointestinal complications. Methods: This current review summarizes the updated scientific information on the medicinal importance and pharmacological activities of tectochrysin. Scientific information on tectochrysin was collected from PubMed, Science Direct, Google Scholar, and Google with some additional resources, including books, dissertations, and scientific reports in the present work. Collected scientific information was further categorized into medicinal uses, pharmacological activities, and analytical aspects in the present paper. Furthermore, detailed pharmacological activities of tectochrysin were discussed in the present work, with analytical aspects used for the separation, isolation and identification of tectochrysin in order to explore its therapeutic potential in medicine. Results: Phytochemical analysis of propolis, Alpinia oxyphyllaand Lychnophora markgraviiled to the isolation of tectochrysin. This present work signified the anticancer activity of tectochrysin on prostate cancer, human colon cancer, and breast cancer. Moreover, its anti-osteoporosis, antiinflammatory, anti-oxidant, anti-microbial, anti-diarrheal, and hepatoprotective activity were also discussed in the present work. Further effectiveness of tectochrysin in Alzheimer's disease, SARSCoV- 2, nitric oxide production, aryl hydrocarbon receptor, and age-related diseases was further explored in the present work. It has been found that experimental animal data also supports its antimicrobial, anti-oxidant, and metabolic functions. Analytical data indicated its separation, isolation, and identification in different samples. Conclusion: Scientific data presented in this review signifies the biological importance and therapeutic potential of tectochrysin in medicine.

Background: Past few decades have witnessed the co-existence of diabetes and hypertension leading to other health disorders. Hence, it is imperative to look into new therapies for the treatment of both hypertension and diabetes simultaneously in order to gradually reduce the pill burden and subsequent side effects. Objective: The goal of the current work was to use several in silico methods to develop new entities that have both anti-diabetic and anti-hypertensive activity. Methods: Structure activity relationship was drawn from the literature considering Thiazolidinones (Anti diabetes), Indole (Antihypertensive) and naturally occurring polyphenols (Dual activity) for simultaneous management of hypertension and diabetes. Fifty-six new chemical entities were designed and subjected to ADME and docking studies. Based on the Lipinski filter, bioavailability and lead likeness nineteen molecules were further docked into three PDB’s (5Y2T, 4BVN, 1O8A). Results: The majority of the NCE’s have shown higher binding affinities than the standard drugs, with Compound 42 having the best results. Among nineteen NCE’s, 50% of the compounds have shown the involvement of Thiazolidinone, Indole and Catechol pharmacophores with prominent hydrogen bonds, hydrophobic, electrostatic and pi-pi stacking interactions with all three PDB’s signifying their potential dual activity. Most favourable interactions were shown by compound 42. Conclusion: The results obtained are encouraging for further exploration of the hit molecules for simultaneous treatment of the two diseases.

Background: The association of obesity with left ventricular (LV) diastolic dysfunction is fully understood, but there are few investigations regarding its effect on LV systolic function in the absence of other risk factors. This study aimed to identify the global longitudinal strain (GLS) changes in isolated overweight and obese people in the absence of other risk factors. Methods: A total of 120 individuals, including 60 obese, 30 overweight, and 30 healthy controls with no underlying disease and no history of hypertension, diabetes, CAD, or CKD were included in the study. Echocardiographic findings were measured, including apical 2-, 3- and 4-chamber GLS, GLS total, LV diameter, interventricular septum thickness, and PAP. These findings were then compared between the three groups (obese, overweight, and normal controls). Results: Analyses showed that LV diameter in healthy controls was significantly lower compared to overweight (p= 0.02) and obese (p< 0.0001) participants. Also, the interventricular septal thickness was significantly increased in overweight (p= 0.007) and obese (p< 0.0001) individuals compared to healthy controls. The mean and standard deviation (Mean ± SD) of total GLS values were - 22.29% ± 1.89% for normal weight, -22.09% ± 1.91% for overweight, and -19.88% ± 2.34% for obese individuals. The total GLS of obese participants was significantly lower than overweight and normal controls (p< 0.0001). It was observed that the GLS values were significantly lower in people with BMI higher than 40. The mean ± SD of total GLS values were -20.68% (1.84%) for BMI ≤ 40 patients and -18.51% (2.52%) for BMI > 40 patients. Conclusion: Data revealed that all GLS values had a moderately strong correlation with BMI values. Also, subclinical LV dysfunction was detected in overweight and obese subjects.

Aims: The study aimed to analyze the analgesic activity of Cistus ladaniferL. Background: Cistus ladaniferL. is a fragrant shrub of the Cistaceae family widespread in the Mediterranean basin, it has various biological activities, including antidiabetic and antihypertensive effects. Objectives: The objective of this work was to study the phytochemical profile, the acute toxicity and the analgesic power of the ethanolic extract of the species Cistus ladaniferL. (C. ladanifer) collected in Northern Morocco. Methods: The evaluation of antinociceptive activity in mice was performed using two validated models, the formalin-induced paw-licking model and the acetic acid-provoked writhing test. Results: According to the results, five phenolic compounds were identified in the ethanolic extract by HPLC-MS/MS. As regards the acute toxicity study, the results showed no mortality or clinical symptoms in mice treated to compare the control group at doses up to 5,000 mg/kg BW. Regarding the analgesic effect, the ethanolic extract at the doses of 400 and 800 mg/kg, BW showed a statistically significant (p<0.05) and dose-dependent analgesic effect in two nociceptive tests. On the other hand, in the syrup of ethanolic extract at the dose of 800 mg/kg, BW expressed the most superior pain-inhibiting effect in both tests, producing an analgesic effect equivalent to that of the reference drug (indomethacin). Conclusion: These findings provide pharmacological justification that might aid in the development of a natural anti-nociceptive medication as an alternative to chemical analgesic drugs.

Aims: The study aimed to assess the antihyperglycemic and antidyslipidemic activities of Artemisia mesatlantica. Background: Artemisia mesatlanticais an endemic plant of Morocco used in traditional medicine as an alternative treatment for diabetes. Objective: The study was designed to examine the antihyperglycemic and antidyslipidemicability of aqueous extract of Artemisia mesatlantica(AMAE) in experimental animal models. Methods: The effect of the single and repeated oral administration (7 days of treatment) of AMAE (60 mg/kg) on blood glucose and lipid profile were assessed in normal and streptozotocin-induced diabetic rats. Furthermore, to confirm the antidyslipidemic effect of Artemisia mesatlantica, a model of hyperlipidemia induced by tyloxapol (Triton WR-1339) in rats was used. Results: The AMAE (60 mg/kg) was able to significantly reduce glycaemia, improve lipid profile and increase hepatic glycogen content in STZ-induced diabetic rats. In addition, pretreatment of rats for 7 consecutive days with an aqueous extract of Artemisia mesatlantica(600 mg/kg) prior to tyloxapol injection prevented increases in plasma levels of total cholesterol, triglycerides and LDL-c. Conclusion: From these observed results, it can be deduced that Artemisia mesatlanticapossesses remarkable antidiabetic and antihyperlipidemic properties.

Introduction: Vitamin B deficiency causes cardiac hypertrophy, reduced cardiac contractility, and arrhythmias.The purpose of this study is to perform a network meta-analysis of randomized controlled trials of vitamin B supplements in a group of 150 patients who meet the eligibility criteria.The study also aims to describe the effect of synthetic multivitamins (pyridoxine, folic acid, and cyanocobalamin) on the laboratory findings reflecting the severity of chronic heart failure (cholesterol, glucose, and fibrinogen). Methods: The experiment involved a group of people (150 individuals) diagnosed with chronic heart failure with reduced left ventricular ejection fraction. The study compared serum levels of B vitamins measured after the therapy and at baseline. The second part of the study focused on the assessment of the laboratory findings reflecting the severity of cardiovascular pathology and indicating an increased risk of vascular catastrophes. Results: Clinical trials among patients diagnosed with chronic heart failure showed that the intake of synthetic forms of pyridoxine, folic acid, and cyanocobalamin slightly increases systolic, diastolic and central venous pressure while decreasing the heart rate and increasing LVEF. Thiamine acts as a vasodilator. It reduces the cardiac afterload and improves heart function. Conclusion: The results obtained can be useful in terms of improving the comprehensive treatment strategy for chronic heart failure and further investigation of the effects produced by the intake of B vitamins.

Background: Bernard Soulier Syndrome (BSS) is a rare autosomal recessive disorder due to deficiency or dysfunction of the glycoprotein GPIb-V-IX complex on the platelet surface. It is also known as hemorrhagiparous thrombocytic dystrophy or congenital hemorrhagiparous thrombocytic dystrophy. The patient usually presents with severe and prolonged bleeding along with characteristics of giant blood platelets and low platelet counts. Manifestations of BSS include epistaxis, gum bleeding, purpuric rashes, menorrhagia, rarely melena, and hematemesis. On the other hand, immune thrombocytopenic purpura (ITP) is an acquired autoimmune disorder in which there is accelerated platelet destruction and reduced platelet production. Isolated thrombocytopenia without fever, lymphadenopathy, and organomegaly usually lead to the diagnosis of immune thrombocytopenia. Case Presentation: A 20 years old female presented with complaints of recurrent episodes of epistaxis since childhood and menorrhagia during menarche. She was misdiagnosed as ITP elsewhere. Later, based on thorough clinical examination and investigation, the diagnosis was confirmed as BSS. Conclusion: BSS should always be taken in the differential diagnosis of ITP, especially when persistent, refractory, and treated unsuccessfully with steroids or splenectomy.