Diosmin and its aglycone form Diosmetin as potential therapeutics for cardiovascular diseases

Cardiovascular disease (CVD) is the principal etiology of death worldwide. Flavonoids are phytochemicals existing in vegetables, tea, fruits, cocoa, and wines that have been linked to positive pharmacological properties, counting antithrombotic, antioxidant, anti-inflammatory, hepatoprotective, anti-allergic, antiviral/bacterial, and anti-cancer activity. We explored the pharmacological activity of Diosmin and Diosmetin in the treatment of venous and arterial cardiovascular diseases by assessing in vitro, clinical, and in vivo papers found in major electronic databases from inception to September 2025. Diosmin reduces vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1), as well as phospho-c-Jun N-terminal kinases (p-JNK) and phospho-nuclear factor-kappa B (p-NF-κB) proteins, thereby improving vascular function and protecting the heart. The antioxidant and anti-apoptotic effects of Diosmin and Diosmetin were achieved by raising the ratios of phospho-protein kinase B (AKT)/AKT and phospho-nuclear factor erythroid 2-related factor 2 (Nrf2)/Nrf2. Furthermore, diosmetin can decrease autophagy by preventing the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway and endothelial-mesenchymal transformation (EndMT) via the Src targeting pathway. The collected findings emphasize the function of Diosmin and Diosmetin in defending against heart failure, atherosclerosis, hyperlipidemia, vascular dysfunction, and chronic venous insufficiency, suggesting a novel therapeutic and preventive agent for CVD.