Molecular Dynamics Insight and In Vivo Investigation of Empagliflozin on Cardiometabolic and Inflammatory Marker in Metabolic Syndrome

Metabolic syndrome (MetS) is a complex disorder characterized by a cluster of conditions, including diabetes mellitus (DM), obesity, and cardiovascular disease (CVD). Empagliflozin is a sodium-glucose cotransporter ۲ (SGLT۲) inhibitor that is widely used to treat DM. This study aimed to evaluate the effects of empagliflozin based on a molecular docking study and in vivo study in a MetS animal model at different dosages to improve MetS conditions. A molecular docking study revealed that empagliflozin binds to SGLT۲ with a binding affinity value of –۹.۴ kcal/mol, whereas it can also bind to interleukin (IL)-۱ β receptor (IL۱R۱), IL-۱۸ receptor ۱ (IL۱۸R۱), and C-reactive protein (CRP) with lower binding affinities of–۷.۱, –۷.۱, and–۸.۰ kcal/mol, respectively. The RMSD, RMSF, Radius of gyration (Rg), SASA, and number of H bond analysis by molecular dynamic shows that Empagliflozin is stable at all protein- complexes. In vivo study in a MetS animal model revealed that the positive control group had lower high-density lipoprotein (HDL) and higher fasting blood glucose (FBG), triglyceride (TG), IL-۱β, IL-۱۸, hs-CRP, systolic and diastolic blood pressure, and heart weight compared with the healthy rat group. Administration of empagliflozin at a regular dosage (۱ mg/kg body weight in rats) showed significant improvement in MetS conditions, including a reduction in heart weight, which is an important marker for improving cardiac fibrosis. This study also found that a high dosage of empagliflozin (۳۰ mg/kg BW in rats) did not show significant differences in most of the evaluated parameters.

کلیدواژه ها:

Molecular Dynamics ، Metabolic Syndrome ، Empagliflozin ، Inflammatory ، cardiometabolic