DOI: 10.1177/09731296231215158 ISSN: 0973-1296

Calycosin Protects against Focal Cerebral Ischemia/Reperfusion Injury via Inhibiting the HMGB1/TLR4/NF-κB Signaling Pathway

Yong Wang, Shifeng Wang, Peng Zhang, Shengjun Xiao, Huizhong Shi, Zihan Chen
  • Drug Discovery
  • Pharmaceutical Science

Background: The rate of disability and mortality associated with cerebral ischemia/reperfusion injury (CIRI) is high due to limited treatment options, making it a major challenge to clinical management. Calycosin is a biologically active compound hostile to inflammatory, neuroprotective, and tumor effects. Whether calycosin has an ischemia/reperfusion effect or mechanism is unclear.

Materials and Methods: For in vivo experiments, we randomly divided rats into five groups: blank control group, middle cerebral artery occlusion/reperfusion (MCAO/R) surgical group, calycosin + MCAO/R group (5 mg/kg), calycosin + MCAO/R group (10 mg/kg), and calycosin + MCAO/R group (20 mg/kg). Molding of the middle cerebral artery was performed. Calycosin’s neuroprotective effects were evaluated using the neurological deficit score, brain edema rate, and cerebral infarct volume. For in vitro experiments, we divided PC12 cells into five groups: blank control group, oxygen and glucose deprivation/reperfusion (OGD/R) group, calycosin + OGD/R group (1 × 10−6 mol/L), calycosin + OGD/R group (4 × 10−6 mol/L), and calycosin + OGD/R group (16 × 10−6 mol/L). The optimal concentration of calycosin on PC12 cells was determined using the cell counting kit-8 (CCK-8) cell activity assay. The expression of nuclear factor kappa-B (NF-κB)-related factors was detected using real-time quantitative polymerase chain reaction and Western blotting.

Results: In rats, the MCAO/R model resulted in elevated neurological deficit scores, increased brain infarct volumes, and increased brain edema rates. The OGD/R model decreased rat adrenal pheochromocytoma (PC12) cell activity, and calycosin had a significant cerebral protective effect on PC12 cells under OGD/R conditions. In addition, calycosin can inhibit the activation of the NF-κB pathway, and its neuroprotective effect may be related to the NF-κB pathway.

Conclusion: Calycosin can reduce focal CIRI, and the neuroprotective effect of calycosin may be related to the inhibition of the high mobility group protein 1/toll-like receptor 4 (TLR4)/NF-κB signaling pathways.

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