Safflower Yellow B Protects Brain against Cerebral Ischemia Reperfusion Injury through AMPK/NF-kB Pathway

• Published in: Evidence-based complementary and alternative medicine 2019-01, Vol.2019 (2019), p.1-11
• Main Authors: Sun, Yanyan, Yuan, Hongjie, Deng, Youliang, Du, Shibin
• Format: Article
• Language: English
• Subjects: Apoptosis; Brain; Brain injury; Cerebral blood flow; Cerebral infarction; Chinese medicine; Cyclooxygenase-2; Cytoplasm; Enzyme-linked immunosorbent assay; Infarction; Inflammation; Inhibition; Interleukin 1; Interleukin 6; Ischemia; Kinases; Neuroprotection; NF-κB protein; Nuclear transport; Occlusion; Oxidative stress; Pheochromocytoma cells; Phosphorylation; Reperfusion; Rodents; Signal transduction; siRNA; Translocation; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Viability; Western blotting
• ISSN: 1741-427X; 1741-4288
• DOI: 10.1155/2019/7219740

Inflammation had showed its important role in the pathogenesis of cerebral ischemia and secondary damage. Safflower yellow B (SYB) had neuroprotective effects against oxidative stress-induced brain injuries, but the mechanisms were still largely unknown to us. In this study, we tried to investigate the anti-inflammation effects of SYB and the possible roles of AMPK/NF-κB signaling pathway on these protective effects. In vivo, brain ischemia/reperfusion (I/R) was induced by transient middle cerebral artery occlusion for 2 h and reperfusion for 20 h. Neurofunctional evaluation, infarction area, and brain water contents were measured. Brain injury markers and inflammatory cytokines levels were measured by ELISA kits. In vitro, cell viability, apoptosis, and LDH leakage were measured after I/R in PC12 cells. The expression and phosphorylation levels of AMPK, NF-κB p65, and P-IκB-α in cytoplasm and nuclear were measured by Western blotting. SiRNA experiment was performed to certify the role of AMPK. The results showed SYB reduced infarct size, improved neurological outcomes, and inhibited brain injury after I/R. In vitro test, SYB treatment alleviated PC12 cells injury and apoptosis and inhibited the inflammatory cytokines (IL-1, IL-6, TNF-α, and COX-2) in a dose-dependent manner. SYB treatment induced AMPK phosphorylation and inhibited NF-κB p65 nuclear translocation both in brain and in PC12 cells. Further studies also showed that the inhibition of NF-κB activity of SYB was through AMPK. In conclusion, SYB protected brain I/R injury through reducing expression of inflammatory cytokines and this effect might be partly due to the inhibition of NF-κB mediated by AMPK.