Erectile dysfunction is a complex and prevalent complication of diabetes, and effective treatments are lacking. Oxidative stress, fibrosis, and apoptosis are closely associated with the development of diabetes mellitus-related erectile dysfunction (DMED). Notably, ginsenoside Rb1 (Rb1) exerts antioxidant effects and displays promise in the treatment of DMED. This study evaluated the therapeutic efficacy of Rb1 in a rodent streptozotocin-induced DMED model. Thirty-two rats were randomly assigned to three groups: control group, DMED group, and DMED + Rb1 group. DMED was induced in male rats via an intraperitoneal injection of streptozotocin. After 8 weeks of Rb1 gavage, erectile function was assessed by the electrical stimulation of the cavernous nerve. In addition, western blot, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, immunofluorescence, terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) staining, and Masson’s trichrome staining were performed to verify the relevant factors and protein expression. Rb1 effectively improved the erectile function of the corpus cavernosum, decreased collagen content, and increased smooth muscle content in rats with diabetes. Rb1 decreased the levels of the pro-inflammatory factors (interleukin [IL]-6, tumor necrosis factor alpha [TNF-α], and IL-1β), and increased the levels of the anti-inflammatory factors (IL-10 and IL-4). Moreover, the activities of superoxide dismutase and catalase and levels of nitric oxide (NO) were increased, whereas malondialdehyde activity was decreased. Additionally, Rb1 activated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/endothelial nitric oxide synthase (eNOS) signaling pathway and inhibited cell apoptosis. Rb1 can improve erectile function in rats with DMED by increasing the activity of the PI3K/AKT/eNOS pathway, reducing oxidative stress, inhibiting inflammation and apoptosis, and alleviating corpus cavernosum fibrosis.

Keywords: diabetes mellitus; erectile dysfunction; ginsenoside Rb1; oxidative stress; PI3K/AKT/eNOS