Danggui Buxue Extract-Loaded Liposomes in Thermosensitive Gel Enhance In Vivo Dermal Wound Healing via Activation of the VEGF/PI3K/Akt and TGF-β/Smads Signaling Pathway.

Meng-Di Cui,Li-Qun Pan,Zi-Hao Pan

doi:10.1155/2017/8407249

Abstract

Danggui Buxue extract-loaded liposomes in thermosensitive gel (DBLTG) are a sustained-release local drug delivery system derived from Danggui Buxue decoction, a well-known Chinese herb formula with wound healing potential. In the present study, we investigated the therapeutic effects of DBLTG on dorsal full-thickness excisional wounds in rats by measuring the percentage of wound contraction and hydroxyproline content, as well as conducting histological observations and immunohistochemical analysis. We also assessed involvement of the vascular endothelial growth factor (VEGF)/phosphatidylinositol 3-kinase (PI3K)/Akt and transforming growth factor beta (TGF-β)/Smads signaling pathways in the wound healing process upon DBLTG treatment via western blot. The results show that DBLTG treatment remarkably accelerates wound closure, enhances hydroxyproline content in wound granulation tissue, promotes cutaneous wound healing by reducing the inflammatory response and improving fresh granulation tissue formation, and significantly increases the density of blood vessels, cells proliferation, and expression of type I and type III collagen. Moreover, DBLTG markedly upregulates the relative protein expression of VEGFA and TGF-β1 and notably stimulates the phosphorylation of Akt and Smad2/3. In conclusion, DBLTG significantly improved dermal wound healing in rats by stimulating angiogenesis and collagen synthesis; these effects are likely mediated via the VEGF/PI3K/Akt and TGF-β/Smads signaling pathways, respectively.

Highlights

Dermal wounds remain a major health problem worldwide
Fewer fibroblasts and more edema and inflammatory cells were found in both control groups. These results demonstrate that the AS and AR components of Danggui Buxue extract-loaded liposomes in thermosensitive gel (DBLTG) are responsible for the increased aggregation and proliferation of fibroblasts in rat excisional wounds
We found that secretion of type I and type III collagen is gradually enhanced as rat excisional wound healing progresses, an effect that is remarkably increased by DBLTG administration (Figures 4(c) and 4(d))

Summary

Introduction

Wound dressings consisting of biocompatible and biodegradable materials have been developed to improve the wound healing process [1, 2]. Thermosensitive gels are suitable as local drug delivery systems for dermal wound healing [3]. Thermosensitive gels provide an ideal semiobliterative moist environment for wound healing [4, 5], which is very important for cell proliferation and collagen synthesis. Thermosensitive gels are free-flowing at room temperature and, when injected into the wound bed, quickly transform into semisolid gels that fill the entire wound area, protecting the wound and absorbing wound secretions [6, 7]. Because of the porous structure, thermosensitive gels gradually deliver encapsulated drug into the dermal wound

Objectives

Methods

Results

Conclusion