The pro-erectile and anti-fibrotic effects of the nutraceutical Revactin® are mediated by activation of the iNOS-cGMP pathway
Garcia, E1; Abraham, A1; Nguyen, S1; Artaza, J.N2; Ferrini, M.G2
1: Charles R. Drew University, United States; 2: Charles R. Drew University, UCLA, United States
Introduction: It was recently reported that long-term daily treatment with Revactin®, a newly formulated nutraceutical combination comprising of ginger, muira puama, Paullinia cupana and L-citrulline, enhanced erectile function in the aged rat. The treated animals demonstrated a significant a) increase in intra-corporal pressure following papaverine injection, b) decrease in the drop rate as measured by cavernosometry, and c) increase in the cavernosal smooth muscle (CSM) content and CSM to collagen ratio. To determine whether these pro-erectile, and anti-fibrotic outcomes with Revactin® could be the result of an effect on the NO-cGMP pathway, an in vitro study using a rat corporal SMC culture was conducted.
Materials and Methods: Primary CSM cell cultures were initiated from the corpora cavernosa of 2 month-old rats. The CSM cells were grown in Dulbecco media with 20% fetal calf serum and then incubated with or without Revactin® (ginger: 0.225 mg/ml; muira puama, Paullinia cupana and L-citrulline each at 0.9 mg/ml) for 24 hours. mRNA and proteins were extracted and used for the determination of iNOS, eNOS and nNOS. cGMP content was determined by ELISA. Nitrites were measured by the Griess reaction. L-NAME (3mM) was used as an inhibitor of NOS activity. DETA NONOate (1mM) was used as an exogenous NO donor.
Results: When treated CSM cells were compared to non-treated CSM cells, cGMP and nitrite levels were increased by 2 and 1.8 fold, respectively, after exposure to 24 hours of Revactin® regardless of whether or not exogenous NO was added to the assay. L-NAME blocked the production of cGMP by Revactin®. Furthermore, when mRNA levels for the three isoforms of NOS were measured, Revactin® had no effect on the eNOS or nNOS levels but had a marked stimulatory effect on iNOS. The increase in iNOS expression was further corroborated by western blot.
Conclusions: These data demonstrate that in the aged rat the previously reported improvement in the morphological and physiological characteristics of the erectile mechanism by long-term Revactin® administration is most likely due to its stimulatory effect on the endogenous production of iNOS and its resultant production of intracellular NO by the corporal CSM cells themselves. Further work needs to be done in order to establish whether long-term treatment with Revactin® in the clinics would also result in similar outcomes.
Work supported by industry: yes, by KLRM, LLC (industry funding only - investigator initiated and executed study).Go Back