Cardiovascular & Haematological Disorders - Drug Targets - Online First

Drug repurposing involves investigating new indications or uses for drugs that have already been approved for clinical use. Empagliflozin is a C-glycosyl compound characterized by the presence of a beta-glucosyl residue. It functions as a sodium-glucose co-transporter 2 inhibitor and is utilized to enhance glycemic control in adults diagnosed with type 2 diabetes mellitus. Additionally, it is indicated for the reduction of cardiovascular mortality risk in adult patients who have both type 2 diabetes mellitus and pre-existing cardiovascular disease.

The study's objective revolves around exploring the repurposing potential of a novel SGLT2 inhibitor acting as an antidiabetic drug named Empagliflozin through computational methods, with a specific focus on its interaction with cardioprotective key target proteins.

The study was performed by docking the empagliflozin with different target proteins (NHE1-CHP1, BIRC5, GLUT1, and XIAP) by using Autodock, and different values were recorded. The docked files were analysed by the BIOVIA Discovery Studio Visualizer. The in silico analysis conducted in this study examines the binding free energy values of Empagliflozin with key target proteins.

Results revealed that NHE1-CHP1 exhibits the lowest binding free energy, followed by BIRC5, GLUT1, and XIAP, with the highest value. This descending order of binding energies suggests varying degrees of effectiveness in binding molecules, with lower energies indicative of more potent biological activity. The analysis underscores the importance of intermolecular interactions, particularly hydrogen bond formations facilitated by oxygen, nitrogen, and carbonyl groups in compound structures. Notably, NHE1-CHP1 demonstrates superior binding interactions with Empagliflozin compared to the other target proteins, highlighting its potential as a cardioprotective agent.

These findings offer valuable insights into the therapeutic possibilities of Empagliflozin in cardioprotection, indicating promising avenues for further research and development in this domain.

This study aimed to assess the hypoglycemic effects of methanolic extract of Foeniculum vulgare in male Wistar rats that were diabetic due to streptozotocin.

Experimental diabetes was initially induced in male Wistar rats by intravenous injection of streptozotocin (55 mg/kg). Subsequently, the rats received daily oral administration of the methanolic extract of Foeniculum vulgare (250 mg/kg) and the standard drug metformin (300 mg/kg) for 28 days. Furthermore, a tolerance test was carried out.

The study findings suggest that the diabetic rats in the untreated control group showed hyperglycemia and significant weight loss, as well as polydipsia, polyphagia, and polyuria. However, rats treated with methanolic extract of Foeniculum vulgare for 28 days showed a significant reduction in blood glucose levels and a marked improvement in body weight. Additionally, there was a notable decrease in the daily rate of food consumption and water intake and a significant reduction in serum glucose level, triglycerides, total cholesterol, creatinine, urea, AST, and ALT levels compared to the untreated diabetic control group. Histopathological examination revealed that after 28 days of treatment with 250 mg/kg of methanolic extract of the Foeniculum vulgare, the size of the islets of Langerhans in the pancreas tissue was decreased. Moreover, liver tissue demonstrated normalization with a normal central lobular structure, and kidney tissue showed normalization with a normal Bowman's capsule.

These findings suggest that the methanolic extract of Foeniculum vulgare can potentially treat diabetes and should be evaluated further for drug development.

Thromboembolism with solid malignancies is a commonly associated feature, which is less common in hematological malignancies. Disseminated intravascular coagulation (DIC) causing thrombotic events is characteristically associated with certain hematological malignancies (e.g., acute promyelocytic leukemia (APL). Acute myeloid leukemia (AML) presenting as extensive thromboembolism is not a common clinical presentation. Anticoagulation in these subsets of patients remains a major challenge since patients often have thrombocytopenia and bleeding manifestations, requiring close monitoring.

A 54-year-old male with a known case of ischemic heart disease on regular anti-platelet therapy presented with acute onset progressive shortness of breath with mild anemia. On further evaluation, the patient was diagnosed with bilateral pulmonary artery and venous thrombosis along with left complete renal and partial inferior vena cava (IVC) thrombosis. The patient was started safely on anticoagulant therapy with normal platelet counts. Later, peripheral smear and immunophenotyping by flow cytometry revealed the diagnosis of acute myeloid leukemia, and the patient started its treatment.

Extensive arterial and venous thrombosis at presentation of acute myeloid leukemia is an uncommon finding and needs anticoagulation therapy along with the treatment of the underlying disease. Close monitoring of bleeding and maintaining an adequate platelet count is required, especially in hematological malignancies.