Osthole improves erectile function by increasing endogenous H2S production

Background

Phosphodiesterase type-5 inhibitors, first-line treatments for erectile dysfunction (ED), are insufficient in 30–40 % of patients, highlighting an unmet therapeutic need. Hydrogen sulfide (H₂S) compensates for NO deficiency and improves erectile function. We hypothesized that H₂S contributes to the smooth muscle relaxation in penile arteries and erectile tissue induced by osthole.

Methods

We investigated the effects of osthole on H₂S-producing enzyme expression and H₂S production in murine erectile tissues by Western blot and H₂S microsensor experiments. To evaluate the role of H₂S in osthole-induced relaxations, myography was conducted on mouse corpus cavernosum (MCC) and rat pudendal artery (RPA). While monitoring vascular responses, endogenous H₂S production was simultaneously measured by an H₂S microsensor inserted in the RPA lumen. Intracavernosal pressure was measured in anesthetized rats to evaluate the effect of osthole on erectile function.

Results

Osthole induced relaxation by increasing H₂S synthesis and enhancing the expression of H₂S-producing enzymes, as well as promoting H₂S formation in murine erectile tissues. Osthole relaxed RPA while simultaneously increasing H₂S levels in the arterial lumen. Osthole also amplified L-cysteine- and Na₂S-induced relaxations and increased luminal H₂S levels. Additionally, osthole increased endothelium-dependent and independent relaxations by inducing H₂S synthesis. Osthole improved erection by facilitating erectile responses in rats.

Conclusion

Our novel approach, based on simultaneous measurements of endogenous H₂S production in the arterial lumen and vascular contractility, suggests that H₂S contributes to osthole-induced relaxation of penile tissue, proposing that osthole may be a promising drug candidate for treating ED, particularly when caused by endothelial dysfunction.