Investigation of the potential therapeutic effect of chlorogenic acid on erectile dysfunction in a rat model of bilateral cavernous nerve injury

Radical prostatectomy is a commonly performed surgical method in the treatment of localized prostate cancer. However, damage to the cavernous nerves (CNs) during this procedure often leads to postoperative erectile dysfunction (ED). ED is a significant clinical problem with a multifactorial etiology that severely affects the quality of life in men. Its pathophysiology involves nerve injury, oxidative stress, inflammation, and fibrosis. Oxidative stress and inflammatory processes following CN injury cause endothelial dysfunction and smooth muscle deterioration, resulting in the loss of structural integrity in penile tissue. Chlorogenic acid (CGA) is a natural phenolic compound found in various plant sources, particularly coffee beans. Known for its antioxidant and anti-inflammatory effects, CGA enhances cellular defense against oxidative stress primarily by activating the NRF2/HO-1 signaling pathway and suppresses the expression of pro-inflammatory cytokines. These features make CGA a promising neuroprotective and antifibrotic agent. In this study, the potential protective and therapeutic effects of CGA on erectile function via the NRF2/HO-1 pathway were investigated at functional, histopathological, and molecular levels in a bilateral cavernous nerve injury (BCNI) rat model. Thirty male Wistar albino rats were divided into control, BCNI-control, and CGA treatment groups (10, 30, and 100 mg/kg). CGA was administered intraperitoneally. 14 days post-surgery, intracavernosal pressure and mean arterial pressure were measured, and Maximum Intracavernous Pressure / Mean Arterial Pressure and Total Intracavernous Pressure / Mean Arterial Pressure ratios were calculated. ELISA was used to determine IL-6, TNF-α, and malondialdehyde levels. Histopathological evaluation was performed using Masson's trichrome staining, and protein expression levels were analyzed via Western blot CGA reduced oxidative stress, upregulated NRF2/HO-1, and decreased fibrosis markers in penile tissue after BCNI. CGA improved erectile function dose-dependently by activating the NRF2/HO-1 pathway, reducing oxidative stress and inflammation, and preserving penile tissue. Keywords: Erectile dysfunction, chlorogenic acid, cavernous nerve injury, NRF2/HO-1, oxidative stress, radical prostatectomy