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

ObjectiveTissue 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.MethodsWe 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.ResultsCompared 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.ConclusionWe found that Sal B protects brain tissues from I/R injury by activating its anti‐inflammatory properties.

Novel Multi-Antioxidant Approach for Ischemic Stroke Therapy Targeting the Role of Oxidative Stress

“…In animal models, several other substances have proven to be effective, for instance, the following: Salvianolic acid B (Sal B), a hydrophilic caffeic acid derived from Salvia miltiorrhiza, has been widely studied due to its antioxidative, anti-inflammatory, and neuroprotective properties, probably mediated by blocking the TLR4, p-p38 MAPK, p-JNK, IL-1β, and NF-κB pathways [ 83 ]. Rhein, an anthraquinone, exerts neuroprotective effects by regulating the NRF2/SLC7A11/GPX4 pathway, inhibiting ferroptosis during IRI following a stroke in murine models [ 84 ].…”

“…Salvianolic acid B (Sal B), a hydrophilic caffeic acid derived from Salvia miltiorrhiza, has been widely studied due to its antioxidative, anti-inflammatory, and neuroprotective properties, probably mediated by blocking the TLR4, p-p38 MAPK, p-JNK, IL-1β, and NF-κB pathways [ 83 ].…”

Exosomes-Mediated Signaling Pathway: A New Direction for Treatment of Organ Ischemia-Reperfusion Injury

“…The different separation protocols may result in different subpopulations of exosomes with different miRNAs, proteins, functions, and non-vesicular macromolecules [140], making it difficult to recognize which molecules in exosomes are responsible for the observed effects. In addition, the complexity of signal transduction and the cross-talk between different pathways also increase the difficulty in understanding the precise mechanism of exosomes in treating diseases [141]. Therefore, prospective studies should focus on the standardization of these isolation and purification processes and a detailed exploration of different subgroups of exosomes, so as to clarify their exact mechanism and pave the way for the efficient clinical application.…”