Endocrine, metabolic & immune disorders drug targets · 2026
Guipi Decoction Attenuates Fibrosis and Oxidative Stress to Ameliorate Diabetic Erectile Dysfunction in Rats via the RhoA/ROCK Signaling Pathway.
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Longhao Sun, Jiayun Li, Yuexin Ma, Xu Wang, Zhuo Zhao, Zhanmin Li
Аннотация
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: he 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 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.
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: he 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 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.