Fisetin-mediated PPAR-γ upregulation: a novel therapeutic approach for corpus cavernosum smooth-muscle-cell apoptosis and restoration of erectile function after cavernous nerve injury
Year: 2025
Type: article
Abstract: Background: The development of neurogenic erectile dysfunction (NED) is closely associated with apoptosis and fibrosis of corpus cavernosum smooth muscle cells (CCSMCs) following cavernous nerve injury (CNI). This study aimed to examine the preventative effects of fisetin on CCSMC apoptosis and fibrosis, as well as its ameliorative effects on NED, using a rat model of CNI. Methods: Twenty-four male Sprague-Dawley rats were randomly assigned into three groups: a control group (n=8), a model group (CNI; n=8), and a fisetin group [2.5 mg/(kg·day) of fisetin administered via gavage; n=8]. The animal model was established through clamping of the bilateral cavernous nerves. The control and model groups were given an equivalent volume of saline. Erectile function (EF) was evaluated as the ratio of intracavernous pressure to mean arterial pressure (ICP/MAP). Penile tissue samples were collected for Western blotting, Real-time polymerase chain reaction (RT-qPCR), and fluorescence analysis to assess the expression levels of apoptotic proteins, messenger RNA (mRNA), collagen types I (Col-1) and III (Col-3), and peroxisome proliferator-activated receptor gamma (PPAR-γ). Apoptosis in CCSMCs was evaluated using TUNEL staining, while the collagen content in corporal tissue was assessed using Masson staining. Results: experiments showed that the addition of the PPAR-γ inhibitor T0070907 negated the effects of fisetin in reducing the apoptosis rate and collagen deposition in CCSMCs. Conclusions: Fisetin may exert a protective effect against CNI-induced apoptosis in CCSMCs, ameliorate the fibrosis of the corporal tissue, and enhance EF, primarily through the upregulation of PPAR-γ expression.
Authors: Yijia Fu, Xin Zhang, Runnan Xu, Bodong Lv
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4410839468