Research Article: Vaccarin hastens wound healing by promoting angiogenesis via activation of MAPK/ERK and PI3K/AKT signaling pathways in vivo1

Date Published: February 7, 2020

Publisher: Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia

Author(s): Bao Hou, Weiwei Cai, Ting Chen, Zhixuan Zhang, Haifeng Gong, Wei Yang, Liying Qiu.

http://doi.org/10.1590/s0102-865020190120000002

Abstract

To explore the potential role and unclear molecular mechanisms of vaccarin in wound healing.

Rats’ skin excision model to study the effects of vaccarin on wound healing in vivo . Hematoxylin and eosin staining was performed to evaluate Histopathologic characteristics. Immunohistochemistry was employed to assess the effects of vaccarin in accelerating angiogenesis. Western blot was used to evaluate relative protein expressed levels.

Vaccarin could significantly promote wound healing and endothelial cells and fibroblasts proliferation in the wound site. Immunohistochemistry and Western blot studies showed that the nodal proteins and receptor (bFGFR) related to angiogenesis signaling pathway were activated, and the microvascular density in the wound site was markedly higher than that in the control group.

The present study was the first to demonstrate that vaccarin is able to induce angiogenesis and accelerate wound healing in vivo by increasing expressions of p-Akt, p-Erk and p-bFGFR. This process is mediated by MAPK/ERK and PI3K/AKT signaling pathways.

Partial Text

The skin is the largest organ in the human body, accounting for 15% of body weight approximately1 , 2 {Mulholland, 2017 #122;Tobin, 2006 #191;Tobin, 2006 #225}. It plays an important role in protecting our body against the external environment. Convincing evidence showed that wound healing is still a problem that needs to be solved urgently, especially the chronic ulcers and diabetic wounds healing3 . A 2009 study had demonstrated that nearly 6.5 million patients suffer from the disturb of chronic wounds every year4 . Wound healing is not only a normal physical response, but also a multifaceted process involving orchestrated cellular signaling events and biochemical cascades5 , 6 . Wound healing mainly consists of four overlapped phases, including homeostasis, inflammation, proliferation and reorganization6 . Any defects at these stages will contribute to a negative impact on the healing process, resulting in wound healing becoming a major social problem. Although some research has been carried out on wound healing, no better means have been found to treat it.

Wound healing is a worldwide issue, which causes heavy economic and healthcare burden28 . This issue has attracted the attention of an increasing number of researchers. In previous reports, traditional Chinese medicines such as curcumin, bromelain29 , aloe vera30 , aeschynomene indica L. leaves31 , verbascum speciosum and astragaloside IV have been tried for the treatment of wounds. In addition, these drugs act on different stages of wound healing and achieve different healing effects. The results of this study showed that vaccarin could promote wound healing by inducing angiogenesis in vivo . The most interesting finding was that in the vaccarin treatment group, there was a large proliferation of fibroblasts during wound healing. Although Sun et al report that vaccarin can activate fgf-2-mediated FGFR1 signaling pathway in human microvascular endothelial cells16 , , we still cannot determine in vivo that vaccarin results in fibroblast proliferation, or that wound healing results in the proliferation of fibroblasts and endothelial.

Taken all results together, the present study is the first to demonstrate that vaccarin is able to induce angiogenesis and accelerate wound healing in vivo by increasing expressions of p-Akt, p-Erk and p-bFGFR. This process is mediated by MAPK/ERK and PI3K/AKT signaling pathways. Vaccarin has definitely shown to be a promising agent with great potential for wound healing.

 

Source:

http://doi.org/10.1590/s0102-865020190120000002

 

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