Chitosan Nanocapsules Boost Capsaicins Efficacy against Diabetes-Induced Cardiotoxicity in Rats

Abstract

Background: Capsaicin is known for its therapeutic benefits, including anti-inflammatory, antioxidant, and cholesterol-lowering effects. However, its clinical application is limited by poor bioavailability, primarily due to its low solubility in water. Objective: To evaluate the efficacy of our newly optimized capsaicin-loaded chitosan nanocapsules (CAP@CS) in mitigating cardiotoxicity induced by type 2 diabetes mellitus (T2DM) and a high-fat diet in male Sprague Dawley rats. Methods: Nanocapsules containing capsaicin and chitosan were synthesized using the micro-emulsion technique and characterized using dynamic light scattering (DLS) and transmission electron microscopy (TEM), were administered to sixty male rats, which assigned to five groups: control, diabetic, diabetic with rosuvastatin, diabetic with capsaicin (CAP), and diabetic with CAP@CS. The inflammatory markers and biochemical indicators associated with myocardial damage, tissue oxidative stress, and inflammation were assessed. Results: DLS analysis revealed an average size of ~260 nm and a zeta potential of ~+18 mV. TEM images depicted circular and uniform nanocapsules. The diabetic + CAP@CS group showed more significant reductions in blood glucose and lipid levels compared to other diabetic groups, and markedly increased the concentrations of the antioxidant enzymes superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx), reduced glutathione, and upregulated nuclear factor erythroid 2-related factor 2 (NRF-2), and heme oxygenase-1 (HO-1) expressions more significantly than the diabetic + CAP group. CAP@CS upregulated nitric oxide concentrations and its bioregulator, inducible nitric oxide synthase (iNOS), demonstrating enhanced cardioprotection. The formula exhibited a more pronounced anti-inflammatory impact, as demonstrated by the tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) assessment. Histological investigations employing hematoxylin and eosin stain, Masson trichrome (MTC), and immunohistochemical analysis of α-smooth actin and desmin revealed the notable superiority of the new formula (CAP@CS) over capsaicin (CAP) in mitigating the myocardial damage mediated by diabetes. This efficacy was substantiated by assessments of myocardial protein content, malondialdehyde (MDA), heat shock protein 70 (HSP70) determination, alanine transaminase (ALT), aspartate transaminase (AST), and troponin levels. Conclusion: CAP@CS nanocapsules present a promising therapeutic strategy, improving for cardioprotection in T2DM, offering potential benefits such as improved efficacy, bioavailability, and reduced side effects.