Neuroprotective mechanism of salvianolic acid B against cerebral ischemia–reperfusion injury in mice through downregulation of TLR4, p‐p38MAPK, p‐JNK, NF‐κB, and IL‐1β

Abstract

Abstract Objective Tissue injury and inflammation are two potential outcomes of cerebral ischemia–reperfusion (I/R) injury. Salvianolic acid B (Sal B), isolated from the roots of Salvia miltiorrhiza, is one of the major water‐soluble compounds with a wide range of pharmacological effects including antioxidant, anti‐inflammatory, antiproliferative, and neuroprotective effects. In the present study, we explored the neuroprotective effects and potential mechanisms of Sal B after I/R injury. Methods We induced cerebral ischemia in male CD‐1 mice through transient (60 min) middle cerebral artery occlusion (tMCAO), and then injected Sal B (30 mg/kg) intraperitoneally. Neurological deficits, infarct volumes, and brain edema were assessed at 24 and 72 h after tMCAO. We detected the expression of Toll‐like receptor 4 (TLR4), phosphorylated‐p38 mitogen‐activated protein kinase (P‐p38 MAPK), phosphorylated c‐Jun amino (N)‐terminal kinases (p‐JNK), nuclear factor‐κB (NF‐κB), and interleukin‐1β (IL‐1β) in the brain tissue. Results Compared with the tMCAO group, Sal B significantly improved neurological deficits, reduced infarct size, attenuated cerebral edema, and downregulated the expression of pro‐inflammatory mediators TLR4, p‐p38MAPK, p‐JNK, nuclear NF‐κB, and IL‐1β in brain tissue after I/R injury. Conclusion We found that Sal B protects brain tissues from I/R injury by activating its anti‐inflammatory properties.

Keywords

• cerebral ischemia–reperfusion
• inflammation
• neuroprotection
• salvianolic acid B