Procyanidin Improves Erectile Function in Rats by Inhibiting PDE5A Activity
Abstract
Purpose: Erectile dysfunction (ED), a prevalent form of male sexual dysfunction, is predominantly treated with Phosphodiesterase type 5 inhibitors (PDE5Is). Our previous research highlighted procyanidin, a natural compound, as a notably effective PDE5I. In the current study, we intend to further validate the inhibitory activity of procyanidin on PDE5A through in vitro and in vivo assessments. This study aims to validate the efficacy of procyanidin as a treatment for ED.
Methods: The binding affinity of procyanidin for PDE5A was assessed by molecular docking, molecular dynamics (MD) simulations, and microscale thermophoresis (MST) assay. The toxicity of procyanidin on penile corpus cavernosum smooth muscle (CCSM) cells (n=5) was evaluated. Additionally, its effects on intracellular cyclic guanosine monophosphate (cGMP) levels in CCSM cells (n=5) were evaluated. The absorption of procyanidin was evaluated by measuring plasma levels at various times after oral gavage to Sprague-Dawley (SD) rats (n=6). Subsequently, the effects of procyanidin on intracavernous pressure (ICP) and cGMP levels in penile cavernous tissue were evaluated in SD rats (n=6).
Results: Procyanidin forms three hydrogen bonds with PDE5A and stabilizes the complex structure, exhibiting equilibrium dissociation constants (KD) value of 7.77 ± 2.39 µmol/L. Additionally, procyanidin exhibits minimal cytotoxicity toward CCSM cells and significantly elevates intracellular cGMP levels compared to the control group.…
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