Leech-Centipede Granules Suppress EndMT to Improve Erectile Dysfunction in Rats with Diabetes Mellitus Via TGF-β/Smad Pathway

Objective To investigate whether Leech-Centipede (LC) Granules can improve erectile function in rats with diabetes mellitus-associated erectile dysfunction (DMED) through endothelial-to-mesenchymal transition (EndMT) inhibition. Methods Components of LC Granules were identified via ultra-high-performance liquid chromatography. Thirty male Sprague Dawley rats were injected with streptozotocin and fed continuously for 8 weeks to establish the DMED rat model. Rats with erectile dysfunction symptoms diagnosed using apomorphine were divided into DMED and low-, medium-, and high-doses LC groups ( n =6 in each). The negative control (NC, n =6) and DMED groups were given 5 mL of deionized water via intragastric gavage, and the low-, medium- and the high-doses LC groups were administered LC at 1.6, 3.2, and 6.4 g/kg, respectively, via intragastric gavage for 4 weeks. The intracavernous pressure (ICP), mean arterial pressure (MAP), and nitric oxide (NO) levels in cavernous tissue were measured for each group. Quantitative reverse transcription-polymerase chain reaction and Western blot were used to detect mRNA and protein expressions of endothelial and mesenchymal markers. Immunofluorescence staining was used to observe α-SMA, and Masson’s trichrome staining was performed to determine the myofiber/collagen ratio. Results A total of 474 active components were identified. After treatment, the ICP/MAP value and NO level were significantly higher in the medium- and high-dose LC groups than in the DMED group ( P <0.05). Compared with the DMED groups, the medium- and high-dose groups LC significantly increased and decreased endothelial and mesenchymal markers expression, respectively ( P <0.05). Tumor growth factor (TGF)β R II, p-Smad2, and p-Smad3 levels were considerably higher following diabetes onset but reduced following LC intervention ( P <0.05), except for TGF β 1 ( P >0.05). α-SMA expression was significantly higher in the DMED group and was reduced in all LC intervention groups ( P >0.05). The myofiber/collagen ratio in the LC groups was higher than that in the DMED group but lower than that in the NC group (all P <0.05). Conclusions LC Granules may improve the erectile function of DMED rats by suppressing TGF-β/Smad pathway to reverse EndMT.