Effects of Moist Exposed Burn Therapy and Ointment (MEBT/MEBO) on the autophagy mTOR signalling pathway in diabetic ulcer wounds

Pharm Biol. 2020 Dec;58(1):124-130. doi: 10.1080/13880209.2019.1711430.

Abstract

Context: Burn therapy (MEBT)/moist exposed burn ointment (MEBO) is an effective traditional Chinese medicine method to treat diabetic wound, but the mechanism is unclear. Autophagy has been proved to be closely related with wound healing, so MEBO/MEBT is hypothesized to promote diabetic wound healing by regulating autophagy.Objective: To explore the mechanism of moist exposed MEBT/MEBO promoting diabetic wound repair.Materials and methods: Eighty male Wistar rats were randomly assigned to control (n = 20) and diabetic group induced by intraperitoneal injection of STZ (n = 60), which were further randomly assigned to MEBO, Kangfuxin and model groups (n = 20 each). All rats underwent full-thickness skin resection in the back. Wound healing was dynamically observed and wound tissues were collected at five time points for pathological examination, autophagosome and the expression of PI3K, Akt and mTOR.Results: The healing time in the control group was the shortest, no statistically significant difference was found between the MEBO and the Kangfuxin group (p = 0.76). The morphology of autophagosomes ranged large to small, which was the most obvious in the MEBO group. The mRNA and protein expression of PI3K, Akt and mTOR in each group reached the peak on Day 5, the levels in the MEBO group were the highest (F = 18.43, 19.97, 15.36, p < 0.05). On Day 11, the expression levels in each group began to decline.Discussion and conclusions: In this study, we discussed the molecular mechanism of MEBT/MEBO promoting the repair of diabetic ulcer wounds through autophagy and PI3K-Akt-mTOR signalling pathway, which provides a new way for drug design in the future.

Keywords: Diabetes; PI3K–Akt–mTOR; fibroblasts; traditional Chinese medicine; wound healing rate.

MeSH terms

  • Animals
  • Autophagy / drug effects
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy*
  • Male
  • Phosphatidylinositol 3-Kinase / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Sitosterols / administration & dosage*
  • Sitosterols / pharmacology
  • Skin Ulcer / drug therapy*
  • Skin Ulcer / etiology
  • TOR Serine-Threonine Kinases / metabolism
  • Wound Healing / drug effects*

Substances

  • Sitosterols
  • moist exposed burn ointment
  • mTOR protein, rat
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases

Grants and funding

This work was supported by the National Natural Science Foundation of China [81660797]: The mechanism of MEBT/MEBO promoting wound repair of diabetic foot based on the PI3K-Akt-mTOR signalling pathway regulated by autophagy. Guangxi Natural Science Foundation [2018GXNSFAA281124]: Dynamic changes of the BMP/Smad signalling pathway in diabetic chronic wound and the regulatory effect of MEBT/MEBO.