Cinnamaldehyde accelerates wound healing by promoting angiogenesis via up-regulation of PI3K and MAPK signaling pathways

Abstract

The bark of Cinnamomum cassia (C. cassia) has been used for the management of coronary heart disease (CHD) and diabetes mellitus. C. cassia may target the vasculature, as it stimulates angiogenesis, promotes blood circulation and wound healing. However, the active components and working mechanisms of C. cassia are not fully elucidated. The Shexiang Baoxin pill (SBP), which consists of seven medicinal materials, including C. cassia etc., is widely used as a traditional Chinese patent medicine for the treatment of CHD. Here, 22 single effective components of SBP were evaluated against the human umbilical vein endothelial cells (HUVECs). We demonstrated that in HUVECs, cinnamaldehyde (CA) stimulated proliferation, migration, and tube formation. CA also activated the phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways. Furthermore, the secretion of vascular endothelial growth factor (VEGF) from HUVECs was increased by CA. In vivo, CA partially restored intersegmental vessels in zebrafish pretreated with PTK787, which is a selective inhibitor for vascular endothelial growth factor receptor (VEGFR). CA also showed pro-angiogenic efficacy in the Matrigel plug assay. Additionally, CA attenuated wound sizes in a cutaneous wound model, and elevated VEGF protein and CD31-positive vascular density at the margin of these wounds. These results illustrate that CA accelerates wound healing by inducing angiogenesis in the wound area. The potential mechanism involves activation of the PI3K/AKT and MAPK signaling pathways. Such a small non-peptide molecule may have clinical applications for promoting therapeutic angiogenesis in chronic diabetic wounds and myocardial infarction.

Comparison of Proangiogenic Effects of Adipose-Derived Stem Cells and Foreskin Fibroblast Exosomes on Artificial Dermis Prefabricated Flaps

“…9 Stem Cells International (Figure 7(b)) and mitogen-activated protein kinase (MAPK) (Figure 7(c)) showed the greatest difference between ADSC-Exo and HFF-Exo in promoting the survival of prefabricated skin flaps. Several studies [32,33] have reported that the PI3K-Akt and MAPK signaling pathways are closely related to wound vascularization. The differential miRNAs may thus enhance endothelial cell proliferation and motility and promote angiogenesis by activating the PI3K-Akt and MAPK signaling pathways.…”

“…According to KEGG analysis results, the target genes of the differential miRNAs were mainly enriched in the PI3K-Akt and MAPK pathways, and also in focal adhesion, Ras signaling, and vascular smooth muscle contraction pathways, which are closely related to cell proliferation and migration. Many studies [32,33] have shown that the activation of these pathways can significantly promote angiogenesis and promote wound repair. We therefore suggest that ADSC-Exo are affected by the ischemic environment, leading to the enrichment and activation of the differential miRNAs in the above pathways, and thus promoting vascularization of the prefabricated flaps.…”

Immunomodulatory properties of graphene oxide for osteogenesis and angiogenesis

“…A number of studies have shown that a combination of VEGFR and PDGFR with corresponding ligands can promote the proliferation and angiogenesis of vascular ECs by activating multiple signaling pathways, such as PI3K/ Akt, MAPK, and PLC-γ. 34,35 Therefore, GO can be used to stimulate the development of an immune microenvironment that is suitable for bone regeneration.…”

Screening and preliminary validation of T lymphocyte immunoregulation‑associated long non‑coding RNAs in diabetic foot ulcers

“…Among the various signaling pathways involved in the regulation of DFUs, the MAPK signal transduction pathway is particularly important (24). The extracellular signal-related kinase (ERK) pathway is also considered to be an important MAPK signaling pathway, and has been revealed to have a crucial role in the inflammatory response induced by T cells by regulating the expression of inflammatory factors.…”