English translation of the study:
https://pubmed.ncbi.nlm.nih.gov/29551532/
The study, carried out by Monica G. Ferrini and her team, explores the effect of COMP-4, a dietary supplement based on natural compounds including ginger, Paullinia cupana, muira puama and L-citrulline, on the modulation of the inducible nitric oxide (iNOS)-NO-cGMP pathway in rat penile smooth muscle cells. Administered long-term in aged rats, COMP-4 was shown to a) upregulate iNOS in penile smooth muscle cells, b) reverse apoptosis and fibrosis of penile smooth muscle cells. corpora cavernosa associated with corporal veno-occlusive dysfunction (CVOD), and c) improve the resulting erectile function.
To understand how COMP-4 and its individual components modulate the iNOS-cGMP pathway, an in vitro study was conducted using a primary culture of smooth muscle cells from the corpus cavernosum of rats. The effect on nitric oxide synthase (NOS), soluble guanylate cyclase (sGC), cGMP and phosphodiesterase 5 (PDE5) enzyme was determined.
Primary smooth muscle cell cultures were incubated with or without COMP-4 or its ingredients alone for up to 24 hours. The study found that compared to control values, COMP-4 upregulated cGMP expression by 85%, induced a 42-fold increase in sGC as well as a 15-fold increase in cGMP content. iNOS protein and mRNA, while decreasing the content of PDE5 mRNA and protein by 50%. L-NIL, an inhibitor of iNOS activity, completely inhibited the effect of COMP-4 on cGMP production. COMP-4 had the most profound effect in modulating specific steps within the iNOS-cGMP pathway relative to each of its four individual components.
In conclusion, this in vitro study demonstrates that COMP-4 is capable of activating the endogenous iNOS-cGMP pathway in MSC cells, which is believed to be responsible for the reduction of fibrosis and apoptosis as well as the CVOD observed in aging rat penis. Additional studies will be needed to determine whether daily COMP-4 supplementation could be beneficial in stopping or reversing this age-related erectile dysfunction in a clinical setting.