Guipi Decoction Attenuates Fibrosis and Oxidative Stress to Ameliorate Diabetic Erectile Dysfunction in Rats via the RhoA/ROCK Signaling Pathway

Introduction: This study aimed to investigate whether Guipi Decoction ameliorates Diabetic Erectile Dysfunction (DMED) in rats by regulating the RhoA/ROCK signaling pathway. Methods: 36 SD rats were utilized: 6 served as controls, and 30 were induced into DMED models using STZ, confirmed by blood glucose >16.7 mmol/L and a failed erection test. Successfully modeled DMED rats were divided into five groups (n=6/group): Model (saline), Sildenafil (5 mg/kg), and GD Low (0.5 g/mL), Medium (1 g/mL), and High (2 g/mL) dose groups. All groups received corresponding treatments for 4 weeks. Assessments included: body weight, FBG, lipids (TC, TG), erectile function (ICP/MAP ratio), penile NO levels, renal function (BUN, SCr), oxidative stress markers (SOD activity, MDA content), penile histopathology (HE and Masson staining), and mRNA/protein expression levels of RhoA, ROCK1, ROCK2, Caspase-3, p-LIMK2, and p-MYPT1, analyzed via qPCR, Western blot, and IHC. Results: Compared with controls, DMED model rats showed significantly elevated FBG, TG, TC, BUN, SCr, and MDA levels, as well as upregulated expression of RhoA/ROCK pathway-related proteins and Caspase-3 (all P< 0.01). In contrast, their body weight, ICP/MAP ratio, NO levels, SOD activity, and penile smooth muscle/collagen ratio were significantly reduced (all P< 0.01). GD treatment exerted significant dose-dependent effects: relative to the Model group, GD increased the ICP/MAP ratio, NO levels, and SOD activity (all P< 0.01); decreased FBG, weight loss, TC, TG, BUN, SCr, and MDA levels (P< 0.05 or P< 0.01); improved erectile function; alleviated penile fibrosis and pathological damage; and downregulated the mRNA and protein expression of RhoA, ROCK1, ROCK2, Caspase-3, p-LIMK2, and p-MYPT1 (P< 0.05 or P< 0.01). Higher GD doses showed stronger therapeutic efficacy. Discussion: The therapeutic effects of GD on DMED may be attributed to its ability to inhibit the RhoA/ROCK signaling pathway, which in turn enhances NO bioavailability, mitigates oxidative stress (as reflected by increased SOD activity and decreased MDA content), and suppresses apoptosis (via reduced Caspase-3 expression). conclusion: Guipi Decoction may improve the erectile function of diabetic erectile dysfunction rats by regulating the RhoA/Rock signaling pathway, alleviate the pathological changes and fibrosis degree of the penile corpus cavernosum, and its mechanism may be related to increasing NO levels, antioxidative stress, and inhibiting apoptosis, etc. Conclusion: Guipi Decoction effectively improves erectile function and ameliorates penile histopathological lesions in DMED rats, suggesting its potential as a therapeutic agent for DMED through modulation of the RhoA/ROCK signaling pathway.