Deoxysappanone B, a homoisoflavone from the Chinese medicinal plant Caesalpinia sappan L., protects neurons from microglia-mediated inflammatory injuries via inhibition of IκB kinase (IKK)-NF-κB and p38/ERK MAPK pathways

Caesalpinia sappan L. (Lignum Sappan) is a Chinese medicinal plant for treating ischemic cerebral apoplexy. Deoxysappanone B (DSB), a homoisoflavone compound isolated from C. sappan L. (Lignum Sappan), was studied for anti-neuroinflammatory and neuroprotective properties using lipopolysaccharide (LPS)-induced BV-2 microglia neuroinflammation model and LPS-induced microglia-neuron co-culture system. Our findings showed that DSB effectively inhibited BV-2 microglia-mediated neuroinflammatory mediators' release including NO, PGE(2), TNE-alpha, IL-G and reactive oxygen species. Moreover, DSB markedly protected neurons against inflammatory microglia-mediated neurotoxicity in a microglia-neuron co-culture system. Mechanism study revealed that DSB blocked two major neuroinflammation related signaling pathways including IKK-I kappa B-nuclear factor kappaB (NE-kappa B) and p38/ERK mitogen-activated protein kinase (MAPK) cascades, further leading to the inhibition of neuroinflammatory mediators' production. The present study provides evidence that the anti-neuroinflammatory and neuroprotective effect of DSB are clue to the suppression of neuroinflammatory mediators' production as well as inflammation-induced neurotoxicity through regulation of multi-targets. Therefore, DSB may serve as a neuroprotective agent for the treatment of neuroinflammatory disorders and inflammation related neuronal injury. (C) 2014 Elsevier B.V. All rights reserved.