Ex-vivo antioxidant, enzyme inhibitory properties and computational analysis unveil the molecular mechanism of cardiac and penile phosphodiesterase-5 inhibition by bacterial strain HOKA1 extract as an aphrodisiac's agent.

Abstract

The study uses in-vitro antioxidant, ex-vivo enzyme kinetics and in-silico approach using standard protocols to understand their inhibitory mechanism better. The study revealed that bacterial strain HOKA1 isolated from Oniru beach, grown in nutrient agar supplemented with sodium chloride (30%NaCl). Moreso, the bacterial strain HOKA1 extract showed better antioxidant capability and greatly reduced the penile and cardiac cGMP with the highest penile and cardiac concentration between 0.013 and 0.183 μM/Min as compared to the sildenafil citrate (0.00-0.203 μM/Min). Moreover, the kinetic parameters (V_max and K_m) effects revealed that bacterial strain HOKA1 extract inhibited PDE-5 activities better than sildenafil citrate. The GC-MS analysis revealed twenty-nine bioactive compounds in the extract, and these compounds could provide comprehensible supporting evidence for the antioxidant and inhibitory potential of the strain HOKA1 extract on PDE-5 activity. Molecular docking study revealed majority of the GC-MS-identified bioactive constituents from the HOKA1 extract showed high binding energy or lower bonding affinities (-6.8 to -3.3 kcal/mol) compared to reference drug sildenafil citrate (-9.6 kcal/mol), except campesterol (-10.0 kcal/mol); also, ergostane (-9.9 kcal/mol). The results of 100 ns simulation (RMSF, RMSD, Rg and H-bond) show extraordinary stability of PDE-5 with campesterol and ergostane, so also complimentary binding energy of MM-PBSA (campesterol -65.92±4.09 kcal/mol; ergostane -57.23±4.70 kcal/mol) indicating their probability of acting promising PDE-5 inhibitors. Therefore, the study revealed that bacterial strain HOKA1 extract showed a better aphrodisiac property, and its bioactive compounds (campesterol and ergostane) should be considered in upcoming rational development and design of more active selective PDE-5 inhibitors, making a treatment for erectile dysfunction.