(003) NUTRACEUTICAL AND LOW ENERGY SHOCKWAVE TREATMENTS IMPROVED SEXUAL FUNCTION RECOVERY IN A RAT PELVIC NEUROVASCULAR INJURY MODEL
Authors: Crisostomo-Wynne T , Hertz A , Ferrini M , Brand T , Salgar S 
Published: December 2024

Abstract

Introduction
Pelvic trauma can have long-lasting debilitating effects, including severe erectile dysfunction (ED) in men. Rates of ED in men who suffer pelvic trauma are reported to be greater than 80%. While there are effective treatments for most men with ED, these treat the symptoms but do not always offer restoration to their previous state. Those who suffer from an acute traumatic injury to the neurovascular supply to the penis are a unique population that may uniquely benefit from regenerative therapy following the injury. COMP4 is an all-natural herbal compound (combination of Muira puama, Paullinia cupana, Ginger, and L-Citrulline), which has been shown to improve erectile function (EF) recovery in aged men. ED is associated with progressive apoptosis or loss of smooth muscle cells and replacement with collagen. Ginger, Paullinia cupana, and Muira puama increase the expression of iNOS (anti-apoptotic and anti-fibrotic factor) in the corpora, and L-citrulline promotes NO synthesis, thus enabling enhanced penile vascular, smooth muscle, and neuronal regeneration. Low energy shockwave (LESW) contributes to nerve regeneration and angiogenesis by activating and differentiating the stem/progenitor cells in the penis. COMP4 and LESW, as a combination therapy untested, could have a high potential to improve EF recovery following pelvic trauma.

Objective
Our objective was to determine the effects of the nutraceutical compound COMP4 and low energy shockwave (LESW) for the treatment of ED after simulated pelvic trauma in a rat model.

Methods
The experimental design included five groups (Lewis rats aged 10-12 weeks; n = 8/group): 1) Sham, 2) Injury control, 3) Peanut Butter (PNB; Vehicle) Control, 4) COMP4, and 5) COMP4 + LESW. Pelvic neurovascular injury (PNVI) was induced by performing bilateral cavernous nerve crush injury and internal pudendal bundle ligation under general anesthesia. One week after PNVI rats received COMP4 (~45 mg/kg b.wt./day) orally via PNB and/or LESW (1000 pulses at 0.06 mJ/mm2, 3 Hz, three times/week locally) for six weeks. After one week of washout period, EF was assessed via intracavernous pressure (ICP; mmHg) measurements during artificially stimulated (electrostimulation) erection. Following ICP measurements, rats were euthanized, and penile tissues were collected for cellular/molecular analyses.

Results
There was a significant (P &lt; 0.01) improvement in ICP with COMP4 (153.6 ± 26.6) and COMP4 + LESWT (174.1 ± 38.2) treatments compared to vehicle (PNB) control (109.4 ± 32.6). COMP4 + LESW combination therapy markedly enhanced EF compared to COMP4 alone. The base level ICP recorded at two weeks post-PNVI before the start of treatments in Group 2 was 117.3 ± 6 and was significantly (p &lt; 0.01) lower than sham (165 ± 43.8) and COMP4 & COMP4 + LESW treated rats. Masson's Trichrome staining of the corpus cavernosum penis demonstrated significantly reduced (P &lt; 0.001) smooth muscle-to-collagen ratio in injury control (no treatment) and PNB control groups compared to the sham group. COMP4 treatment following PNVI showed a significant increase (P &lt; 0.05) in smooth muscle-to-collagen ratio. Adding LESW and COMP4 further enhanced the smooth muscle-to-collagen ratio significantly (P &lt; 0.01), suggesting reduced fibrosis. Western blot analysis revealed a significant increase in endothelial Nitric Oxide Synthase (eNOS) and α-SMA (α-Smooth Muscle Actin) in the corpus cavernosum with COMP4 and COMP4 + LESW treatments following PNVI compared to PNB control.

Conclusions
COMP4 and LESW treatments appear to be promising approaches to improve EF recovery following pelvic trauma.

Disclosure
No.