Clematichinenoside protects blood brain barrier against ischemic stroke superimposed on systemic inflammatory challenges through up-regulating A20

Suppression of excessive inflammation can ameliorate blood brain barrier （BBB） injury, which shows therapeutic potential for clinical treatment of brain injury induced by stroke superimposed on systemic inflammatory diseases. In this study, we investigated whether and how clematichinenoside （AR）, an anti-inflammatory triter- pene saponin, protects brain injury from stroke superimposed on systemic inflammation. Lipopolysaccharide （LPS） was intraperitoneally injected immediately after middle cerebral artery occlusion （MCAO） in rats. Rat microvessel endothelial cells （rBMECs） were exposed to hypoxia/reoxygenation （H/R） coexisting with LPS. The results re- vealed that AR suppressed the excessive inflammation, restored BBB dysfunction, alleviated brain edema, de- lessened neurological dysfunction, and decreased infarct rate. Further study demon- creased neutrophil infiltration, inducible nitric oxide synthase （iNOS） , strated that the expression of nucleus nuclear factor kappa B （NF-KB）, intercellular adhesion molecule-1 （ ICAM-1 ）, tumor necrosis factor-α （TNF-α） and interlukin-1β （ IL-1β） were suppressed by AR via zinc finger protein A20. Besides, AR increased in vitro BBB integrity through A20. In con- clusion, AR alleviated cerebral inflammatory injury through A20-NF-KB signal pathway, offering an alternative medication for stroke associated with systemic inflammatory diseases.