Preclinical and clinical studies have demonstrated that a free radical scavenger edaravone has neuroprotective effects on ischemic stroke but the underlying mechanism is not fully understood. The aim of this research is to explore the effect of edaravone on the apoptotic process involving the Fas/FasL signaling pathway. Transient focal ischemia in rats was induced for 2 hours by middle cerebral artery occlusion (MCAO). After reperfusion rats were treated i.v. with either edaravone or physiological saline. The expression of Fas-associated death domain protein (FADD), death-associated protein (Daxx) and caspase-8 was examined by immunohistochemistry. The mRNA levels for FADD and Daxx by reverse-transcriptase PCR (RT-PCR) and apoptosis was assessed by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL). Neurological scores and infarction volumes were also evaluated. Edaravone significantly improved the neurological outcome (p<0.05) and reduced the total infarct volumes (p<0.05), compared with saline control. In addition, edaravone-treatment significantly reduced the number of TUNEL-positive cells (p<0.01), reduced expression levels of FADD, Daxx and caspase-8 immunoreactivity (p <0.05 approximately 0.01), and decreased mRNA levels of FADD and Daxx (p<0.05 approximately 0.01) within the peri-infarct area. We conclude that edaravone may protect ischemic neurons from apoptosis via suppressing the gene expression of the Fas/FasL signaling pathway.

Burn injury is a gigantic challenge in public health which brings multiple negative effects to patients both in physical and spiritual aspects. Inflammation plays vital roles in the progression of burn injury, and our study investigated whether notoginsenoside R1 (NGR1) alleviated lipopolysaccharide (LPS)-induced human keratinocyte HaCaT cell inflammatory injury. Inflammatory injury was induced by LPS in HaCaT cells. Stimulated cells were then treated by NGR1 in different concentrations. Cell viability and cell apoptosis were detected by Cell Counting Kit-8 and flow cytometry, respectively. The concentration of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) was measured by enzyme-linked immunosorbent assay (ELISA). The accumulated levels of apoptosis-related proteins (caspase-3 and caspase-9), nuclear factor κB (NF-κB), p38 mitogen-activated protein kinase (p38MAPK) signal pathways–related proteins (p65, IκBα, and p38MAPK), and myeloid differentiation primary response 88 (MyD88) were examined by western blot. Transfection was used to alter the expression of MyD88. We found that LPS stimulated HaCaT cells and induced cell inflammation, evidenced by decreasing cell viability, increasing cell apoptosis, and elevating TNF-α and IL-6 expressions. Then, we found that NGR1 reversed the results by enhancing cell viability, inhibiting cell apoptosis, and reducing TNF-α and IL-6 expressions. In addition, NGR1 decreased the phosphorylation of p65, IκBα, and p38MAPK, which increased by LPS. Moreover, NGR1 negatively regulated the expression of MyD88, and transfection with pMyD88 led to the opposite results with what showed by NGR1 in LPS-stimulated HaCaT cells. To sum up, NGR1 alleviates LPS-induced HaCaT cell inflammatory injury by downregulation of MyD88, as well as inactivation of NF-κB and p38MAPK signal pathways.

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