Ephedra-cinnamomi attenuates cerebral ischemia-induced memory deficits via TLR4/MyD88/p38 MAPK pathway

Background: Cerebral ischemia is a common and serious neurological disease. Ephedra-cinnamomi composed of Ephedra and cinnamomi is a famous herb-pair in Traditional Chinese Medicine. The aim of present study was to investigate the effect of Ephedra-cinnamomi on cerebral ischemia injury in rats. Material and methods: Four-Vessel Occlusion (4-VO) method was applied to induce global cerebral ischemia injury. Rats were treated with Ephedra-cinnamomi (3, 6 and 12 g/kg, i.g.) while the untreated rates were regarded as the negative control. Then memory capacity was measured by Step through Passive Avoidance (STPA) test and Morris Water Maze (MWM) test. Pro-inflammatory cytokines levels were detected by Enzyme Linked Immunosorbent Assay (ELISA). Additionally, the protein expression levels of Toll-Like Receptor (TLR) 4, myeloid differentiation factor 88 (MyD88) and phosphorylated p38 mitogen-activated protein kinases (p-p38MAPKs) were detected by Western blot. Results: The results revealed that Ephedra-cinnamomi attenuated the cerebral ischemia-induced memory deficits and ameliorated histopathological changes. In addition, Ephedra-cinnamomi was able to reduce the pro-inflammatory cytokines production and inhibit the activation of TLR4/MyD88/p38 MAPK pathway in 4-VO induced rats model. Conclusion: The results indicated that Ephedra-cinnamomi significantly ameliorates the ischemic brain injury in rats. Furthermore, the molecular mechanism of improved ischemic brain by Ephedracinnamomi is associated with the inhibition of TLR4/p38 MAPK pathway and the suppression of proinflammatory cytokines production.