BackgroundIschemic brain injury is associated with neuroinflammatory response, which essentially involves glial activation and neutrophil infiltration. Transcription factors nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) contribute to ischemic neuroinflammatory processes and secondary brain injury by releasing proinflammatory mediators. Kaempferol-3-O-rutinoside (KRS) and kaempferol-3-O- glucoside (KGS) are primary flavonoids found in Carthamus tinctorius L. Recent studies demonstrated that KRS protected against ischemic brain injury. However, little is known about the underlying mechanisms. Flavonoids have been reported to have antiinflammatory properties. Herein, we explored the effects of KRS and KGS in a transient focal stroke model.Methodology/Principal FindingsRats were subjected to middle cerebral artery occlusion for 2 hours followed by 22 h reperfusion. An equimolar dose of KRS or KGS was administered i.v. at the beginning of reperfusion. The results showed that KRS or KGS significantly attenuated the neurological deficits, brain infarct volume, and neuron and axon injury, reflected by the upregulation of neuronal nuclear antigen-positive neurons and downregulation of amyloid precursor protein immunoreactivity in the ipsilateral ischemic hemisphere. Moreover, KRS and KGS inhibited the expression of OX-42, glial fibrillary acidic protein, phosphorylated STAT3 and NF-κB p65, and the nuclear content of NF-κB p65. Subsequently, these flavonoids inhibited the expression of tumor necrosis factor α, interleukin 1β, intercellular adhesion molecule 1, matrix metallopeptidase 9, inducible nitric oxide synthase, and myeloperoxidase.Conclusion/SignificanceOur findings suggest that postischemic treatment with KRS or KGS prevents ischemic brain injury and neuroinflammation by inhibition of STAT3 and NF-κB activation and has the therapeutic potential for the neuroinflammation-related diseases, such as ischemic stroke.
Increased MPV is an independent risk factor for both strokes. Elevated PLT count increases the risk for ischemic stroke, but decreases the risk for hemorrhagic stroke. However, neither MPV nor PLT count has significant association with the prognosis of either stroke.
Z-ligustilide (Z-LIG) is the primary lipophilic compound of the Chinese medicine Danggui (Radix Angelica sinensis). Previous studies demonstrated that Z-LIG had significant neuroprotective potential in both transient and permanent cerebral ischemia, possibly through antioxidant and anti-apoptotic mechanisms. The present study examined the mechanisms of Z-LIG on hydrogen peroxide (H(2)O(2))-induced injury in PC12 cells. Following exposure of the cells to H(2)O(2 )(500 microM), a significant reduction in cell survival and total antioxidant capacity (TAC), as well as increased intracellular reactive oxygen species (ROS), were observed. In addition, H(2)O(2 )treatment significantly upregulated Bax expression, cleaved-caspase 3, and cytosolic cytochrome-c, and decreased Bcl-2 protein levels. Pretreatment of the cells with Z-LIG (0.1, 1.0, 2.5, or 5.0 microg/ml) significantly attenuated H(2)O(2)-induced cell death, attenuated increased intracellular ROS levels, and decreased Bax expression, cleaved-caspase 3, and cytochrome-c. Further, Z-LIG improved cellular TAC and concentration-dependently upregulated Bcl-2 expression. These results demonstrate that Z-LIG has a pronounced protective effect against H(2)O(2)-induced cytotoxicity, at least partly through improving cellular antioxidant defense and inhibiting the mitochondrial apoptotic pathway. These findings suggest that Z-LIG may be useful in the treatment of neurodegenerative disorders in which oxidative stress and apoptosis are mainly implicated.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.