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Evaluation of 20(S)-ginsenoside Rg3 loaded hydrogel for the treatment of perianal ulcer in a rat model

  • Jin, Longhai (Department of Radiology, The Second Hospital of Jilin University) ;
  • Liu, Jinping (Research Center of Natural Drug, School of Pharmaceutical Sciences, Jilin University) ;
  • Wang, Shu (Department of Radiotherapy, The Second Hospital of Jilin University) ;
  • Zhao, Linxian (Department of General Surgery, The Second Hospital of Jilin University) ;
  • Li, Jiannan (Department of General Surgery, The Second Hospital of Jilin University)
  • Received : 2021.10.02
  • Accepted : 2022.03.08
  • Published : 2022.11.01

Abstract

Background: As a kind of common complication of the surgery of perianal diseases, perianal ulcer is known as a nuisance. This study aims to develop a kind of 20(S)-ginsenoside Rg3 (Rg3)-loaded hydrogel to treat perianal ulcers in a rat model. Methods: The copolymers PLGA1600-PEG1000-PLGA1600 were synthesized by ring-opening polymerization process and Rg3-loaded hydrogel was then developed. The perianal ulcer rat model was established to analyze the treatment efficacy of Rg3-loaded hydrogel for ulceration healing for 15 days. The animals were divided into control group, hydrogel group, free Rg3 group, Rg3-loaded hydrogel group, and Lidocaine Gel® group. The residual wound area rate was calculated and the blood concentrations of interleukin-1 (IL-1), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF) were recorded. Hematoxylin and eosin (H&E) staining, Masson's Trichrome (MT) staining, and tumor necrosis factor α (TNF-α), Ki-67, CD31, ERK1/2, and NF-κB immunohistochemical staining were performed. Results: The biodegradable and biocompatible hydrogel carries a homogenous interactive porous structure with 10 ㎛ pore size and five weeks in vivo degradation time. The loaded Rg3 can be released sustainably. The in vitro cytotoxicity study showed that the hydrogel had no effect on survival rate of murine skin fibroblasts L929. The Rg3-loaded hydrogel can facilitate perianal ulcer healing by inhibiting local and systematic inflammatory responses, swelling the proliferation of nuclear cells, collagen deposition, and vascularization, and activating ERK signal pathway. Conclusion: The Rg3-loaded hydrogel shows the best treatment efficacy of perianal ulcer and may be a candidate for perianal ulcer treatment.

Keywords

Acknowledgement

This study was supported by Youth Program of the National Natural Science Foundation of China (#32000953), Department of Finance of Jilin Province (#3D5197434429), Health Commission of Jilin Province (2021LC019), and the Education Project of Jilin University (#419070600046 and 45121031D024). We thank Prof. Peng Zhao for helping us revise this study.

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