Protective effect of shikonin in experimental ischemic stroke: attenuated TLR4, p-p38MAPK, NF-κB, TNF-α and MMP-9 expression, up-regulated claudin-5 expression, ameliorated BBB permeability.

Abstract

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.

• Authors: Lina Wang, Zhenzhong Li, Xiangjian Zhang, Sheng Wang, Chunhua Zhu, Jiangyong Miao, Linyu Chen, Lili Cui, Huimin Qiao
• Journal: Neurochemical research (Neurochem Res) Vol. 39 Issue 1 Pg. 97-106 (Jan 2014) ISSN: 1573-6903 [Electronic] United States
• PMID: 24248858 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Claudin-5
• NF-kappa B
• Naphthoquinones
• Neuroprotective Agents
• Tlr4 protein, mouse
• Toll-Like Receptor 4
• Tumor Necrosis Factor-alpha
• shikonin
• p38 Mitogen-Activated Protein Kinases
• Matrix Metalloproteinase 9

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (therapeutic use)
• Blood-Brain Barrier (drug effects)
• Brain Ischemia (drug therapy, pathology)
• Claudin-5 (biosynthesis)
• Down-Regulation
• Infarction, Middle Cerebral Artery (pathology, physiopathology)
• Male
• Matrix Metalloproteinase 9 (biosynthesis)
• Mice
• Mice, Inbred ICR
• NF-kappa B (biosynthesis)
• Naphthoquinones (therapeutic use)
• Neuroprotective Agents (therapeutic use)
• Stroke (drug therapy)
• Toll-Like Receptor 4 (biosynthesis)
• Tumor Necrosis Factor-alpha (biosynthesis)
• Up-Regulation
• p38 Mitogen-Activated Protein Kinases (metabolism)