Rutin Nanoparticles: A Promising Modulator of Inflammatory and Oxidative Stress Biomarkers and Key Gene Expression mRNAs in ISO-induced Cardiovascular Disease in Mice

Abstract

Introduction: Rutin, a natural flavonoid, exhibits promising cardioprotective properties but suffers from poor solubility and bioavailability, limiting its therapeutic potential. This study evaluates the efficacy of Rutin nanoparticles (Rutin-NPs) as a novel intervention against isoproterenol (ISO)-induced cardiac damage in mice. Methods: Rutin-NPs were synthesized and characterized using transmission electron microscopy (TEM), UV-Vis spectroscopy, and Fourier-transform infrared spectroscopy (FT-IR). The median lethal dose (LD50) was determined. Cardioprotective effects were assessed by measuring plasma biomarkers (CK-MB, cTnT, LDH, BNP), oxidative stress markers (MDA, TGF-β1, VEGF), antioxidant levels (GSH, SOD, GPx), and gene expression profiles (miRNA-145, miRNA-181, miRNA- 221). Histopathological analysis evaluated structural restoration. Results: Characterization confirmed the formation of spherical Rutin-NPs (48.29±5.28 nm) with a zeta potential of +17.9 mV. At 59.25 mg/kg (1/20 LD50), Rutin-NPs significantly reduced cardiac biomarkers (CK-MB: -41.2%, cTnT: -60.5%, LDH: -26.7%, BNP: -57.7%) and oxidative stress markers (MDA: -45%, TGF-β1: -52%, VEGF: -49%), while enhancing antioxidant defenses (GSH: +100.5%, SOD: +115.1%, GPx: +128.1%). Gene expression analysis indicated a reversal of ISO-induced dysregulation (mRNA-145: +213%, mRNA-181: +172%, mRNA-221: -62%). Histopathological evaluation confirmed restoration of cardiac architecture. Discussion: These findings demonstrate the potential of Rutin-NPs as a nano-therapeutic for cardiovascular diseases, offering multi-targeted antioxidant, anti-inflammatory, and gene-regulatory actions. The improved bioavailability and enhanced therapeutic effects highlight its translational relevance. However, further investigation is needed to optimize clinical formulations and explore combinatorial treatment approaches. Conclusion: Rutin-NPs exhibit dose-dependent cardioprotection in ISO-induced cardiac injury, reducing oxidative stress, inflammation, and key plasma biomarkers while restoring antioxidant defenses and gene expression balance. The optimal dose (59.25 mg/kg) offers substantial efficacy with a five-fold safety margin, supporting its potential for therapeutic applications in cardiovascular disease management.