Edaravone was originally developed as a potent free radical scavenger, and has been widely used to treat acute ischemic stroke in Japan since 2001. Free radicals play an important role in the pathogenesis of a variety of diseases, such as cardiovascular diseases and stroke. Therefore, free radicals may be targets for therapeutic intervention in these diseases. Edaravone shows protective effects on ischemic insults and inflammation in the heart, vessel, and brain in experimental studies. As well as scavenging free radicals, edaravone has anti-apoptotic, anti-necrotic, and anti-cytokine effects in cardiovascular diseases and stroke. Edaravone has preventive effects on myocardial injury following ischemia and reperfusion in patients with acute myocardial infarction. Edaravone may represent a new therapeutic intervention for endothelial dysfunction in the setting of atherosclerosis, heart failure, diabetes, or hypertension, because these diseases result from oxidative stress and/or cytokine-induced apoptosis. This review evaluates the potential of edaravone for treatment of cardiovascular disease, and covers clinical and experimental studies conducted between 1984 and 2013. We propose that edaravone, which scavenges free radicals, may offer a novel option for treatment of cardiovascular diseases. However, additional clinical studies are necessary to verify the efficacy of edaravone.

Vascular endothelial growth factor A (VEGF-A) is a prominent growth factor for both angiogenesis and lymphangiogenesis. Recent studies have shown the importance of VEGF-A in enhancing the growth of lymphatic endothelial cells in lymph nodes (LNs) and the migration of dendritic cells into LNs. VEGF-A is produced in inflamed tissues and/or in draining LNs, where B cells are a possible source of this growth factor. To study the effect of B cell-derived VEGF-A, we created transgenic mice (CD19^Cre/hVEGF-A^fl) that express human VEGF-A specifically in B cells. We found that the human VEGF-A produced by B cells not only induced lymphangiogenesis in LNs, but also induced the expansion of LNs and the development of high endothelial venules. Contrary to our expectation, we observed a significant decrease in the Ag-specific Ab production postimmunization with OVA and in the proinflammatory cytokine production postinoculation with LPS in these mice. Our findings suggest immunomodulatory effects of VEGF-A: B cell-derived VEGF-A promotes both lymphangiogenesis and angiogenesis within LNs, but then suppresses certain aspects of the ensuing immune responses.

Flavonoids are naturally active substances that form a large class of phenolic compounds abundant in certain foods. Black rice (Oryza sativa L.) contains high levels of anthocyanin polyphenols, which have beneficial effects on health owing to their antioxidant properties. The breakdown of collagenous networks with aging or skin deterioration results in the impairment of wound healing in the skin. Accordingly, reviving stagnant collagen synthesis can help maintain dermal homeostasis during wound healing. This study presents an assessment of the cellular activity of anthocyanins (ANT) extracted from Oryza sativa L., providing information necessary for the development of new products that support natural healing processes. The relative composition of ANT from Oryza sativa L. was determined by high-performance liquid chromatography/diode array detection. ANT promoted the migration of rat dermal fibroblasts (RDFs) and demonstrated antioxidant properties. ANT increased the mRNA expression of collagen type I alpha 2 (COL1A2) and upregulated type I collagen protein levels in H₂O₂-stimulated RDFs without cytotoxicity. Compared with the untreated group, treatment of RDFs with ANT in the presence of H₂O₂ led to the activation of signaling pathways, including the extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and Akt, whereas it significantly (p<0.001) inhibited the phosphorylation of IκBα and suppressed the activation of the nuclear factor-kappa B (NF-κB) subunits, p50 and p65, which are transcription factors responsible for inflammation. Taken together, our findings suggest that ANT from Oryza sativa L. have anti-inflammatory properties and antiaging potential by modulating type I collagen gene expression and suppressing H₂O₂-induced NF-κB activation in skin fibroblasts.

Free radicals play an important role in the pathogenesis of a variety of diseases; thus, they are an attractive target for therapeutic intervention in these diseases. Compounds capable of scavenging free radicals have been developed for this purpose and some, developed for the treatment of cerebral ischemic stroke, have progressed to clinical trials. One such scavenger, edaravone, is used to treat patients within 24 h of stroke. Edaravone, which can diffuse into many disease‑affected organs, also shows protective effects in the heart, lung, intestine, liver, pancreas, kidney, bladder and testis. As well as scavenging free radicals, edaravone has anti-apoptotic, anti-necrotic and anti-cytokine effects in various diseases. Here, we critically review the literature on its clinical efficacy and examine whether edaravone should be considered a candidate for worldwide development, focusing on its effects on diseases other than cerebral infarction. Edaravone has been safely used as a free radical scavenger for more than 10 years; we propose that edaravone may offer a novel treatment option for several diseases.

Edaravone, a potent free radical scavenger, is clinically used for the treatment of cerebral infarction in Japan. Here, we examined the effects of edaravone on the dynamics of high-mobility group box-1 (HMGB1), which is a key mediator of ischemic-induced brain damage, during a 48-h postischemia/reperfusion period in rats and in oxygen-glucose-deprived (OGD) PC12 cells. HMGB1 immunoreactivity was observed in both the cytoplasm and the periphery of cells in the cerebral infarction area 2 h after reperfusion. Intravenous administration of 3 and 6 mg/kg edaravone significantly inhibited nuclear translocation and HMGB1 release in the penumbra area and caused a 26.5 ± 10.4 and 43.8 ± 0.5% reduction, respectively, of the total infarct area at 24 h after reperfusion. Moreover, edaravone also decreased plasma HMGB1 levels. In vitro, edaravone dose-dependently (1–10 μM) suppressed OGD- and H₂O₂-induced HMGB1 release in PC12 cells. Furthermore, edaravone (3–30 μM) blocked HMGB1-triggered apoptosis in PC12 cells. Our findings suggest a novel neuroprotective mechanism for edaravone that abrogates the release of HMGB1.