Crisostomo-Wynne TC. et al., 2024: Nutraceutical and low energy shockwave treatments improved sexual function recovery in a rat pelvic neurovascular injury model.

Jens Rassweiler

Thursday, 05 June 2025

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Theodore C Crisostomo-Wynne 1, Alexandria M Hertz 1, Monica G Ferrini 2, Timothy C Brand 1, Shashikumar K Salgar 3
1Department of Surgery, Madigan Army Medical Center, Tacoma, Washington 98431, United States.
2Department of Health and Life Sciences, Charles R. Drew University, Los Angeles, California 90059, United States.
3Department of Clinical Investigation, Madigan Army Medical Center, Tacoma, Washington 98431, United States.

Abstract

Background: Pelvic trauma can have long-lasting debilitating effects, including severe erectile dysfunction (ED) in men. While there are effective treatments for ED, these treat the symptoms not the cause. Those who suffer from an acute traumatic injury to the neurovascular supply of penis, may benefit from regenerative therapy. COMP4 is an all-natural herbal compound (Muira puama, Paullinia cupana, Ginger, and L-Citrulline) has potential to enhance penile vascular/smooth muscle/neuronal regeneration via Nitric Oxide synthesis. Low energy shockwave (LESW) therapy promotes nerve regeneration/angiogenesis by activating stem/progenitor cells.

Aim: To investigate the effects of the COMP4 and LESW for the treatment of ED in a rat pelvic trauma 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 per week to the pelvis around penis) for 6 weeks. After 1 week of washout period, erectile function (EF) was assessed via intracavernous pressure (ICP; mmHg) measurements; rats euthanized, penile tissues collected for analyses.

Outcomes: COMP4 and LESW treatments improved EF recovery.

Results: There was a significant (P < .01) improvement in EF (ICP) with COMP4 (153.6 ± 26.6) and COMP4 + LESW (174.1 ± 38.2) treatments compared to vehicle (PNB) control (109.4 ± 32.6). COMP4 + LESW treatment enhanced EF compared to COMP4 alone. The base level ICP before treatments (Group 2) was 117.3 ± 6 and was lower (P < .01) than sham (165 ± 43.8) and COMP4 & COMP4 + LESW treated rats. Masson's trichrome staining of corpus cavernosum penis demonstrated reduced (P < .001) smooth muscle-to-collagen (SM:C) ratio in injury and PNB controls compared to sham. COMP4 treatment following PNVI showed an increase (P < .05) in SM:C ratio. Adding LESW and COMP4 enhanced (P < .01) the SM:C ratio, suggesting a reduction in fibrosis. Western blot analysis revealed a significant increase in Endothelial Nitric Oxide Synthase and α-Smooth Muscle Actin (α-SMA) in the corpus cavernosum with COMP4 and COMP4 + LESW treatments compared to PNB control.

Clinical implications: COMP4 and/or LESW can serve as an adjunct therapy to mitigate ED.

Strengths and limitations: Identified novel treatment option to improve EF recovery. Unable to address in-depth cellular/molecular mechanisms.

Conclusions: COMP4 and LESW treatments appear to be promising to improve clinical EF recovery in pelvic trauma.

Sex Med. 2025 Jan 21;12(6):qfaf001. doi: 10.1093/sexmed/qfaf001. eCollection 2024 Dec.
PMID: 39845379 FREE ARTICLE

Comments 1

Jens Rassweiler on Thursday, 05 June 2025 11:00

This very interesting preclinical study investigates the potential of a nutraceutical compound, COMP4, and low energy shockwave (LESW) therapy in promoting erectile function (EF) recovery following pelvic neurovascular injury (PNVI) in a rat model.
Study Design
Pelvic neurovascular injury (PNVI) was simulated by bilateral cavernous nerve crush and internal pudendal bundle ligation in 40 male Lewis rats (10–12 weeks old). The animals were divided into five groups (n=8 per group):
1. Sham (no injury)
2. Injury control
3. Peanut butter (PNB) vehicle control
4. COMP4 treatment
5. COMP4 + LESW treatment
.
The Treatment Protocol include
COMP4: An herbal compound containing Muira puama, Paullinia cupana, ginger, and L-citrulline, administered orally at 45 mg/kg/day via peanut butter.
LESW: Applied to the pelvic area around the penis (1000 pulses at 0.06 mJ/mm², 3 Hz) via EMS Swiss DolorClast compact electrohydraulic extracorporeal shockwave source (DolorClast Human system, Electromedical Systems, Dallas, TX). Low energy radial shockwave therapy was applied to the pelvis, including the penis, as described previously. Thus, radial shock wave treatment was administered about three times a week (∼10 minutes per session) for 6 consecutive weeks.
Assessment: After a one-week washout period, EF was evaluated using intracavernous pressure (ICP) measurements. Penile tissues were analyzed histologically and via Western blot.
Key Findings
Erectile Function: COMP4 treatment significantly improved ICP (153.6 ± 26.6 mmHg) compared to vehicle control (109.4 ± 32.6 mmHg). The combination of COMP4 + LESW further enhanced ICP (174.1 ± 38.2 mmHg), approaching levels observed in the sham group (165 ± 43.8 mmHg).
Histological Analysis: Masson's trichrome staining revealed that the smooth muscle-to-collagen (SM:C) ratio was significantly reduced in injury and PNB controls, indicating fibrosis. COMP4 treatment increased the SM:C ratio, suggesting reduced fibrosis.The combination of COMP4 + LESW further enhanced the SM:C ratio, indicating synergistic antifibrotic effects.
Molecular Markers: Western blot analysis showed increased expression of endothelial nitric oxide synthase (eNOS) and α-smooth muscle actin (α-SMA) in the corpus cavernosum with COMP4 and COMP4 + LESW treatments, indicating improved endothelial function and smooth muscle content.
Clinical Implications
The study suggests that COMP4 and LESW, individually and in combination, may serve as promising adjunct therapies to enhance EF recovery following pelvic trauma. The combination therapy demonstrated synergistic effects, improving both functional and structural parameters associated with erectile function.
Limitations
The study was conducted in a rat model; thus, results may not directly translate to humans. The exact cellular and molecular mechanisms underlying the observed effects were not fully elucidated. Moreover, the was no arm with LESW alone.
Conclusion
The combination of the nutraceutical compound COMP4 and LESW therapy appears to be a promising strategy for promoting erectile function recovery after pelvic neurovascular injury. Further research, including clinical trials, is warranted to explore the potential application of these therapies in human patients

Jens Rassweiler

This very interesting preclinical study investigates the potential of a nutraceutical compound, COMP4, and low energy shockwave (LESW) therapy in promoting erectile function (EF) recovery following pelvic neurovascular injury (PNVI) in a rat model.
Study Design
Pelvic neurovascular injury (PNVI) was simulated by bilateral cavernous nerve crush and internal pudendal bundle ligation in 40 male Lewis rats (10–12 weeks old). The animals were divided into five groups (n=8 per group):
1.	Sham (no injury)
2.	Injury control
3.	Peanut butter (PNB) vehicle control
4.	COMP4 treatment
5.	COMP4 + LESW treatment
.
The Treatment Protocol include
COMP4: An herbal compound containing Muira puama, Paullinia cupana, ginger, and L-citrulline, administered orally at 45 mg/kg/day via peanut butter.
LESW: Applied to the pelvic area around the penis (1000 pulses at 0.06 mJ/mm², 3 Hz) via EMS Swiss DolorClast compact electrohydraulic extracorporeal shockwave source (DolorClast Human system, Electromedical Systems, Dallas, TX). Low energy radial shockwave therapy was applied to the pelvis, including the penis, as described previously. Thus, radial shock wave treatment was administered about three times a week (∼10 minutes per session) for 6 consecutive weeks. 
Assessment: After a one-week washout period, EF was evaluated using intracavernous pressure (ICP) measurements. Penile tissues were analyzed histologically and via Western blot. 
Key Findings
Erectile Function: COMP4 treatment significantly improved ICP (153.6 ± 26.6 mmHg) compared to vehicle control (109.4 ± 32.6 mmHg). The combination of COMP4 + LESW further enhanced ICP (174.1 ± 38.2 mmHg), approaching levels observed in the sham group (165 ± 43.8 mmHg).
Histological Analysis: Masson's trichrome staining revealed that the smooth muscle-to-collagen (SM:C) ratio was significantly reduced in injury and PNB controls, indicating fibrosis. COMP4 treatment increased the SM:C ratio, suggesting reduced fibrosis.The combination of COMP4 + LESW further enhanced the SM:C ratio, indicating synergistic antifibrotic effects.
Molecular Markers: Western blot analysis showed increased expression of endothelial nitric oxide synthase (eNOS) and α-smooth muscle actin (α-SMA) in the corpus cavernosum with COMP4 and COMP4 + LESW treatments, indicating improved endothelial function and smooth muscle content.
Clinical Implications
The study suggests that COMP4 and LESW, individually and in combination, may serve as promising adjunct therapies to enhance EF recovery following pelvic trauma. The combination therapy demonstrated synergistic effects, improving both functional and structural parameters associated with erectile function.
Limitations
The study was conducted in a rat model; thus, results may not directly translate to humans. The exact cellular and molecular mechanisms underlying the observed effects were not fully elucidated. Moreover, the was no arm with LESW alone.
Conclusion
The combination of the nutraceutical compound COMP4 and LESW therapy appears to be a promising strategy for promoting erectile function recovery after pelvic neurovascular injury. Further research, including clinical trials, is warranted to explore the potential application of these therapies in human patients

Jens Rassweiler									</div>

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