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

Abstract

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.

miR-137 targets the inhibition of TCF4 to reverse the progression of osteoarthritis through the AMPK/NF-κB signaling pathway

“…The phosphorylation levels of AMPK and p65 are respectively related to the activation of AMPK and NF-κB. The activation of inflammatory signals of NF-κB needs to respond to the activation of AMPK pathway and the triggering of IκB-α [33,34]. In the present study, the activation performance of AMPK/NF-κB pathway marker is consistent with the previous research results [33][34][35].…”

“…The activation of inflammatory signals of NF-κB needs to respond to the activation of AMPK pathway and the triggering of IκB-α [33,34]. In the present study, the activation performance of AMPK/NF-κB pathway marker is consistent with the previous research results [33][34][35]. In addition, the relatively high apoptosis level of chondrocytes induced by LPS was also significantly reduced under the above intervention, which suggested that miR-137 could prevent chondrocyte apoptosis by targeting down-regulating TCF4 and inhibiting the activation of AMPK/NF-κB pathway, thus inhibiting the progress of OA.…”

Neuroprotective Effect of Danhong Injection on Cerebral Ischemia-Reperfusion Injury in Rats by Activation of the PI3K-Akt Pathway

“…In a study of the protective effect of Danshensu and Hydroxysafflor Yellow on ischemic reperfusion injury in mice, Xu et al showed that the drug combination had a better protective effect on nerve cells in mice than the individual drugs alone (Xu et al, 2017). Du et al found that Safflower Yellow B protected the brain ischemic reperfusion damage by inhibiting AMPK-mediated NF-κB activation and reducing the expression of inflammatory cytokines (Du et al, 2019). The evidence provided in this study confirm the reliable neuroprotection against ischemiareperfusion injury provided by DHI, which is a combination of two TCM active components.…”

A Metabolic Perspective and Opportunities in Pharmacologically Important Safflower

“…The flower extract, carthamin yellow (CY), reduced ischemia/reperfusion (I/R) injury in rats, aided by a reduced reactive oxygen species (ROS) release and inflammatory response [60]. The hydroxysafflor yellow B (HSYB) protected brain I/R injury through reducing the expression of inflammatory cytokines in rats [61]. HSYA attenuated lipopolysaccharide (LPS)-induced neurotoxicity and neuro-inflammation in primary mesencephalic cultures.…”