Deciphering the potential of Cymbopogon citratus (DC.) Stapf as an anti-obesity agent: phytochemical profiling, in vivo evaluations and molecular docking studies

Based on its anti-inflammatory and antioxidant properties, (DC) Stapf is commonly used in traditional and modern medicine to cure different diseases. The present study investigates the potential of organic extract as an anti-obesity drug in a HCHFD (high-carbohydrate, high-fat diet) model for obese rats. Its negative hypolipidemic effect has been confirmed through biochemical and histological methods. Fifty male albino rats were randomly divided into five groups (10 rats each) Group I (Control group), Group II (HCHFD group), Group III ( group), Group IV (HCHFD + group) and Group V (HCHFD + Orlistat group). Serum glucose levels and lipid profiles were quantified using a spectrophotometer. Insulin, apelin, and adiponectin parameters were measured using ELISA (enzyme-linked immunosorbent assay) kits, while real-time PCR following extraction and purification was used for apelin, apelin receptor genes (APJ), and adiponectin gene expression evaluation. Besides, methanolic extract was subjected to untargeted metabolic profiling RP-HPLC-QTOF-MS and MS/MS, disclosing the presence of 52 secondary metabolites where they mainly belonged to phenolic compounds , flavones and hydroxycinnamic acids, among other metabolites with predominance of derivatives of luteolin and -coumaroyl- -feruloylglycerol. Our findings were further strengthened by computational-based virtual screening protocols that included molecular docking (MDock) and Structure-Activity Relationships (SARs). The MDock studies revealed that the three main flavone-containing metabolites, each with a luteolin 6-glycosylation core featuring two sugar units (16, 25, and 31), outperformed the positive control (8EH, a triazole derivative) known to bind to the APJ protein. These metabolites exhibited exceptional binding affinities, with estimated free binding energy (Δ ) values of -9 kcal mol or lower, likely due to potential hydrogen bond interactions with the Arg168 residue of the APJ protein. Additionally, the pharmacokinetic, physicochemical, and toxicity profiles of the 11 major metabolites from leaf extract were assessed, revealing a profile like that of the positive control in the three selected flavone metabolites. Based on the acquired data, it can be concluded that shows strong potential as a hypolipidemic agent and could play a significant role in managing obesity and mitigating its associated complications.