Guanxinning Tablet Ameliorates Erectile Dysfunction in Diabetes Mellitus Rats with Involvement of PI3K/Akt/FOXO1 Signaling Pathway Modulation

Background/Objectives: Diabetes mellitus-induced erectile dysfunction (DMED) is characterized by severe endothelial and smooth-muscle dysfunction and reduced responsiveness to conventional therapy. Guanxinning tablet (GXN), a traditional Chinese medicine compound containing Salvia miltiorrhiza (Danshen) and Ligusticum stratum (Chuanxiong), has vascular-protective and anti-oxidative properties, but its effect on DMED remains unclear. This study evaluated whether GXN improves erectile function in a streptozotocin (STZ)-induced type 1 diabetic rat model and explored the possible involvement of PI3K/Akt/FOXO1 signaling. Methods: STZ-induced diabetic rats with ED were treated with GXN. Artery pressure (AP) and intracavernous pressure (ICP) were measured to evaluate erectile dysfunction. Western blots, immunohistochemistry, immunofluorescence, biochemical assays, TUNEL staining, RNA-seq, and in vitro HCMEC assays were performed to evaluate erectile effector cell function, oxidative stress, fibrosis, apoptosis, and PI3K/Akt/FOXO1-associated changes. Results: GXN improved erectile function in DMED rats and was associated with improved endothelial and smooth-muscle-related markers, reduced oxidative stress, attenuated fibrosis, and decreased apoptosis. RNA-seq and protein validation suggested that GXN treatment was associated with activation of PI3K/Akt/FOXO1-related signaling. In HCMECs, LY294002 (a PI3K inhibitor) partially reversed the GXN-associated improvement in cell viability and apoptosis-related markers. Conclusions: GXN ameliorated erectile dysfunction and tissue injury in STZ-induced type 1 diabetic rats, which were associated with PI3K/Akt/FOXO1 signaling. These findings support the potential of GXN as a traditional Chinese medicine compound for treating DMED.