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.

Psoralen toxicity is an issue of wide concern. However, an assay for psoralen-induced developmental toxicity has not been reported to date. Moreover, the underlying mechanism of psoralen-induced developmental toxicity is unclear. Therefore, this study attempted to develop a psoralen-induced developmental toxicity assay in zebrafish embryos/larvae. Psoralen treatment caused a decrease in the hatching rate and body length and a significant increase in the malformation rate of zebrafish. Yolk retention, pericardial edema, swim-bladder deficiency, and curved body shape were also observed after psoralen treatment. Yolk retention might have been caused by an abnormality in lipid metabolism. Further experiments indicated that psoralen exerted toxic effects on the developing heart, liver, phagocytes, and nervous system. Increased generation of reactive oxygen species, inhibition of total superoxide dismutase activity, and increased malondialdehyde concentrations indicated inhibition of antioxidant capacity and the presence of oxidative stress. A greater number of apoptotic cells were observed after psoralen exposure, relative to the control. Furthermore, the results of gene-expression analysis showed that psoralen induced developmental toxicity by means of oxidative stress, apoptosis, and energy metabolism abnormalities. These findings will be helpful in understanding psoralen-induced toxicity.

No abstract