Guilingji capsules enhances erectile function by promoting testosterone-dependent angiogenesis in the corpus cavernosum

Guilingji capsules (GLJC) have the effect of treating erectile dysfunction (ED). This study aims to explore the potential mechanisms of GLJC in treating ED. We conducted network pharmacology analysis of ED-related targets with GLJC components reported in the TCMSP database and GLJC components reported in the literature, respectively. Molecular docking was employed to validate the binding affinity of these molecular targets. Animal experiments were conducted to validate the aforementioned results. The mechanism of GLJC in treating ED was studied using d-galactose-induced aging rats, and orchiectomized rats were used to investigate further whether the mechanism of GLJC in treating ED is related to androgen. Two network pharmacology analyses indicated that Androgen receptor (AR) and fibroblast growth factor 2 (FGF2) are the candidate targets, suggesting that the mechanism of ED treatment by GLJC may be related to androgens and angiogenesis. Molecular docking further validated the effective binding of GLJC components to these two targets. In animal experiments, GLJC significantly increased the frequency of erections and elevated serum free testosterone levels and penile tissue AR expression in aged rats. GLJC also promoted angiogenesis and inhibited penile tissue fibrosis in aged rats by regulating the expression of FGF2, RICTOR/P-AKT/P-FOXO1. However, such regulation was not observed in orchiectomized rats. Therefore, GLJC increased testosterone utilization in d-galactose-induced aging rats and regulated FGF2, RICTOR/P-AKT/P-FOXO1 signaling pathway in a T-dependent manner, promoting corpus cavernosum survival and angiogenesis. This mechanism led to the inhibition of penile fibrosis.