shikonin and Brain-Ischemia

Inflammatory damage plays an important role in cerebral ischemic pathogenesis and represents a new target for treatment of stroke. Shikonin has gained attention for its prominent anti-inflammatory property, but up to now little is known about shikonin treatment in acute ischemic stroke. The aim of this study was to evaluate the potential neuroprotective role of shikonin in cerebral ischemic injury, and investigate whether shikonin modulated inflammatory responses after stroke. Focal cerebral ischemia in male ICR mice was induced by transient middle cerebral artery occlusion. Shikonin (10 and 25 mg/kg) was administered by gavage once a day for 3 days before surgery and another dosage after operation. Neurological deficit, infarct volume, brain edema, blood-brain barrier (BBB) dysfunction, and inflammatory mediators were evaluated at 24 and 72 h after stroke. Compared with vehicle group, 25 mg/kg shikonin significantly improved neurological deficit, decreased infarct volume and edema both at 24 and 72 h after transient ischemic stroke, our data also showed that shikonin inhibited the pro-inflammatory mediators, including TLR4, TNF-α, NF-κB, and phosphorylation of p38MAPK in ischemic cortex. In addition, shikonin effectively alleviated brain leakage of Evans blue, up-regulated claudin-5 expression, and inhibited the over-expressed MMP-9 in ischemic brain. These results suggested that shikonin effectively protected brain against ischemic damage by regulating inflammatory responses and ameliorating BBB permeability.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood-Brain Barrier; Brain Ischemia; Claudin-5; Down-Regulation; Infarction, Middle Cerebral Artery; Male; Matrix Metalloproteinase 9; Mice; Mice, Inbred ICR; Naphthoquinones; Neuroprotective Agents; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Stroke; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha; Up-Regulation

The aim of our study was to investigate the neuroprotective properties of shikonin, a naphthoquinone pigment isolated from the roots of the traditional Chinese herb Lithospermum erythrorhizon. In the present study, mice were divided randomly into sham, model, shikonin and edaravone-treated groups. Shikonin (50, 25, and 12.5mg/kg, i.g.) or maize oil was administered three times before ischemia and once at 2h after the onset of ischemia. Mice were anesthetized with chloral hydrate and subjected to middle cerebral artery 2h of occlusion and then 22h of reperfusion. Different antioxidant assays were employed in order to evaluate the antioxidant activities of shikonin in vitro. Neurological deficit, infarct size, histopathology changes and oxidative stress markers were evaluated after 22h of reperfusion. In comparison with the model group, treatment with shikonin significantly decreased neurological deficit scores, infarct size, the levels of malondialdehyde(MDA), carbonyl and reactive oxygen species, and attenuated neuronal damage, up-regulated superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px) activities and reduced glutathione (GSH)/glutathione disulfide (GSSG) ratio. Taken together, these results suggested that the neuroprotective effects of shikonin against cerebral ischemia/reperfusion injury may be attributed to its antioxidant effects.

Topics: Animals; Antioxidants; Biomarkers; Brain Ischemia; Dose-Response Relationship, Drug; Glutathione; Infarction, Middle Cerebral Artery; Male; Malondialdehyde; Mice; Mitochondria; Naphthoquinones; Neuroprotective Agents; Oxidative Stress; Oxidoreductases; Protein Carbonylation; Random Allocation; Reactive Oxygen Species; Reperfusion Injury; Up-Regulation