Molecular Docking Analysis of Onion Bioactives and Amino Acids to PDE-5, iNOS, AR, and D2R in Diabetic Erectile Dysfunction: A Multi-Targeted Approach

Background

Diabetic erectile dysfunction is a complex disorder involving impaired nitric oxide bioavailability, endothelial dysfunction, altered androgen signaling, and neurohormonal dysregulation. Conventional phosphodiesterase-5 inhibitors show reduced efficacy in diabetic patients and do not adequately target these interconnected molecular pathways. A multitarget strategy using natural bioactives and amino acids may provide broader therapeutic coverage.

Objectives

To investigate the multitarget binding potential of selected onion-derived bioactives and amino acids against key molecular targets implicated in diabetic erectile dysfunction.

Materials and Methods

An in silico molecular docking analysis was performed using quercetin, allicin, diallyl trisulfide, citrulline, and norvaline. Docking was carried out against phosphodiesterase-5, inducible nitric oxide synthase, androgen receptor, and dopamine D2 receptor. Binding energies and interaction profiles at functional domains were analyzed to assess target affinity and stability.

Results

Quercetin, citrulline, and norvaline demonstrated notable binding affinities toward phosphodiesterase-5, ranging from -6.9 to -7.9 kcal/mol, with interactions at key active site residues. Quercetin showed the strongest affinity for the androgen receptor with a binding energy of -9.4 kcal/mol. Citrulline and norvaline exhibited favorable interactions with inducible nitric oxide synthase and dopamine D2 receptor, indicating potential modulation of nitric oxide signaling and neurohormonal pathways. Allicin and diallyl trisulfide displayed weak or negligible interactions across the studied targets.

Conclusion

The docking outcomes suggest that quercetin, citrulline, and norvaline possess complementary multitarget potential relevant to diabetic erectile dysfunction. These findings justify further experimental validation through in vivo and clinical investigations.