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

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Abstract

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.

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Authors and Affiliations

Authors

Contributions

Zhang H and Feng CH contributed equally to this work. Liu H conceived and designed the experiments; Zhang H, Feng CH, He S, Deng MX and Meng H performed the experiments; Feng CH and Zhang H contributed to the statistical data analysis; Zhang H and Feng CH wrote the manuscript. All authors have read and approved the manuscript for publication.

Corresponding author

Correspondence to Hong Liu.

Ethics declarations

The authors declare that they have no competing interests.

Additional information

Supported by the Scientific Research Project of the Traditional Chinese Medicine Bureau of Guangdong Province, China (Nos. 20211136 and 20221086)

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11655_2022_3728_MOESM1_ESM.pdf

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

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Zhang, H., Feng, Ch., He, S. et al. Leech-Centipede Granules Suppress EndMT to Improve Erectile Dysfunction in Rats with Diabetes Mellitus via TGF-β/Smad Pathway. Chin. J. Integr. Med. 29, 28–36 (2023). https://doi.org/10.1007/s11655-022-3728-z

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  • DOI: https://doi.org/10.1007/s11655-022-3728-z

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