Molecular mechanisms underlying the erectogenic effects of nutraceutical lunamarine, a novel PDE5 inhibitor derived from watermelon (Citrullus lanatus)

The research paper investigates the phytochemicals of watermelon (Citrullus lanatus) as potential novel inhibitors of phosphodiesterase type 5 (PDE5), which is essential for treating erectile dysfunction and pulmonary arterial hypertension. A total of 150 compounds were screened against five PDE5 enzyme structures using molecular docking techniques with Chimera and AutoDock Vina. Interactions were visualized with Chimera and PyMOL, while SwissADME was employed to predict pharmacokinetic properties, and ProTox-II was utilized to assess toxicity. Lunamarine has emerged as a promising candidate for PDE5 inhibition, demonstrating superior pharmacokinetics and favorable toxicity profiles. It exhibited high gastrointestinal absorption and permeability across the blood–brain barrier, potentially outperforming existing inhibitors. The binding energies ranged from − 9.421 to − 9.55 kcal/mol across various PDE5 targets, indicating comparable efficacy. Structural analyses revealed significant hydrophobic interactions with PHE820 and LEU725, as well as hydrogen bonding with TYR612, which are crucial for the formation of the binding pocket. Lunamarine’s effect on catalytic zinc coordination was evidenced by receptor-ligand distances of 3.6 to 3.7 Å. These findings suggest that lunamarine may provide advantages over current therapies, particularly regarding its penetration of the central nervous system. The study recommends further in vitro and in vivo validation of lunamarine's efficacy and safety, as well as an exploration of its potential in other conditions related to PDE5. This research could pave the way for the development of watermelon-derived nutraceuticals for disorders associated with PDE5.