Comprehensive characterization of the chemical composition of Ela tablet and its metabolites, with molecular docking screening of potential bioactive components for erectile dysfunction treatment

Abstract

Erectile dysfunction (ED) is a disorder involving both physiological and psychological implications, and phosphodiesterase 5 (PDE5) inhibitors serve as the primary treatment. The Ela tablet, a traditional herbal formulation, has demonstrated promising PDE5 inhibitory effects, yet its bioactive constituents and metabolic fate remain unclear. A four-step strategy combining offline two-dimensional supercritical fluid chromatography (SFC) and ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS) was established to characterize the chemical composition of the Ela tablet. This was followed by in vivo metabolic profiling in rats to determine prototype compounds and metabolites. Molecular docking analysis was then conducted to evaluate the interaction of blood-absorbable prototype compounds with PDE5. A total of 362 compounds were identified, including flavonoids, alkaloids, terpenoids, organic acids and other classes of compounds. In vivo metabolic profiling revealed 70 compounds of prototype and metabolites, with hydrolysis and glucuronidation as the predominant metabolic pathway. Icaritin glycoside analogs underwent extensive metabolism producing Icaritin glucuronide conjugates as the major circulating forms, while N-alkylamides primarily remained in their prototype state. Molecular docking analysis revealed N-isobutyl-(2E,4E)-tetradecadienamide, Anacyclin, Dodeca-2E,4E-dienoic acid isobutylamide, Pellitorine, N-isobutyl-2–6–8-decatrienamide, Icaritin, and Desmethylicaritin as potential PDE5 inhibitors. These findings provide insights into the metabolic transformation and pharmacological mechanisms of the Ela tablet, supporting its potential clinical application in ED treatment. Future research should focus on pharmacokinetics, mechanistic validation, and clinical evaluation to further establish its therapeutic efficacy.