European Journal of Biomedical and Pharmaceutical Sciences

IN SILICO MOLECULAR DOCKING AND ADME PROFILING OF SELECTED SIDDHA HERBAL PHYTOCONSTITUENTS AGAINST PHOSPHODIESTERASE-5 AND NITRIC OXIDE SYNTHASE TARGETS FOR APHRODISIAC ACTIVITY

Renuga*, C. Karthick, K. Vignesh, A. Balamurugan

ABSTRACT

Background: Male sexual dysfunction, including erectile dysfunction, reduced libido, and impaired reproductive performance, represents a growing global health concern that adversely affects quality of life and psychosocial well-being. Penile erection is primarily regulated by nitric oxide (NO)-mediated vasodilation and cyclic guanosine monophosphate (cGMP) signaling pathways. Phosphodiesterase-5 (PDE-5), which hydrolyzes cGMP, and Nitric Oxide Synthase (NOS), which catalyzes nitric oxide production, are recognized as key therapeutic targets for the management of erectile dysfunction. Siddha medicine describes several medicinal plants under the concepts of Thaathu Viruthi (enhancement of reproductive tissues) and Aanmai Perukki (promotion of virility), which are traditionally used to improve sexual vigor, fertility, and reproductive health. Objective: The present study aimed to evaluate the aphrodisiac potential of selected Siddha medicinal phytoconstituents through molecular docking and ADME profiling against PDE-5 and NOS targets. Materials and Methods: Major phytoconstituents, namely Aegeline, Arginine, L-DOPA, Smilagenin, and Quercetin, derived from Aegle marmelos, Prunus dulcis, Mucuna pruriens, Smilax china, and Hibiscus rosa-sinensis, respectively, were selected based on their traditional use and reported pharmacological activities. Molecular docking studies were performed using AutoDock Vina against PDE-5 (PDB ID: 2ZOB) and NOS (PDB ID: 2FLQ). Pharmacokinetic characteristics and drug-likeness properties were evaluated using SwissADME. Results: Among the investigated compounds, Smilagenin demonstrated the strongest binding affinity toward PDE-5 (-9.1 kcal/mol) and NOS (-10.6 kcal/mol), indicating superior interaction stability with both molecular targets. Quercetin (-8.1 kcal/mol) and Aegeline (-7.4 kcal/mol) also exhibited significant binding affinity against PDE-5, while Aegeline (-10.3 kcal/mol) and Quercetin (-9.3 kcal/mol) showed strong interactions with NOS. ADME analysis revealed favorable pharmacokinetic profiles, high gastrointestinal absorption, and acceptable drug-likeness characteristics for most compounds. Conclusion: The findings suggest that Smilagenin, Aegeline, and Quercetin possess promising aphrodisiac potential through modulation of nitric oxide signaling and cGMP-mediated erectile pathways. The study provides scientific evidence supporting the traditional Siddha use of these medicinal plants in enhancing male reproductive health and highlights their potential for further development as natural therapeutic agents for sexual dysfunction.

Keywords: Aphrodisiac activity, Siddha medicine, Phosphodiesterase-5, Nitric Oxide Synthase, Molecular docking, ADME profiling, Erectile dysfunction, Male reproductive health.