Exploring the Efficacy of Citrus reticulata L. (Mandarin Orange) Flowers Essential Oils for Erectile Dysfunction (ED) With GC/MS Analysis: In Vitro and In Silico Studies.

Erectile dysfunction (ED) poses a significant challenge to male sexual health globally, prompting the exploration of alternative treatments beyond conventional pharmaceutical interventions targeting the phosphodiesterase-5 (PDE5) enzyme. This study comparatively investigates the efficacy of essential oils hydrodistilled from expanded and unexpanded flowers (EF and UF) of Citrus reticulata L. in addressing ED by targeting two key enzymes: Rho-kinase II (ROCK-II) and PDE5A1. Gas chromatography-mass spectrometry (GC/MS) was utilized to analyze the chemical composition of these oils and revealed the presence of 35 and 40 compounds in EF and UF, respectively, across various classes. Monoterpene hydrocarbons are deemed to be the dominant class, constituting 64.33% and 71.93% of the total oil composition in EF and UF, respectively. The results highlight the significant efficacy of UF, represented by their ability to modulate ROCK-II and PDE5A1 activities with IC50 values of 2.64 ± 0.09 and 0.42 ± 0.015 µg/mL, respectively, compared to sildenafil citrate (IC50 = 0.97 ± 0.03 and 0.042 ± 0.001 µg/mL). Besides, two molecular docking processes were applied to evaluate the activity of major identified volatile constituents toward PDE5A1 and ROCK-II target receptors. These findings offer valuable insights into future therapeutic strategies in ED management.