Neuroprotective effects of andrographolide derivative CX-10 in transient focal ischemia in rat: Involvement of Nrf2/AE and TLR/NF-κB signaling.

摘要: Abstract Ischemic stroke is a major cause of mortality and disability worldwide. To date there no ideal effective treatment. 3, 14, 19-triacetyl andrographolide (CX-10) new molecule entity derived from andrographolide. The aim the present study was to evaluate neuroprotection CX-10 against experimental cerebral ischemia. anti-inflammation screened using LPS-induced inflammation in vitro vivo. Rats were subjected 1.5 h middle occlusion (MCAO) then reperfusion for 72 h. infarct size evaluated by TTC staining, behavioral disturbance evaluated, inflammatory cytokines anti-oxidant enzymes brain tissues examined. Western blot used analyze expression proteins. results showed that exerted potent anti-inflammatory anti-oxidation activities, which significantly inhibited TNF-α NO release, lowered IL-1β levels brain, meanwhile increased activities SOD, CAT GSH-P × . effect equivalent dexamethasone, obviously superior exhibited neuroprotective effects, manifested as reducing size, improving neurological function motor impairments. Furthermore, western analysis revealed treatment with down-regulated TLR4, NF-κB, iNOS, induced Nrf2 HO-1 expression. Overall, CX-10 has favorable ischemic injury. mechanism may involve inhibition TLR4/NF-κB signaling pathway upregulation Nrf2/ARE pathway. All these indicated likely be promising agent stroke.