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

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-beta)/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-beta 1 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-beta/Smads signaling pathways, respectively.