Caffeic Acid Ester Fraction from Erigeron Breviscapus Inhibits Microglial Activation and Provides Neuroprotection

Objective: To investigate the effects of caffeic acid ester fraction (Caf) from Erigeron breviscapus, mainly composed of dicaffeoylquinic acids (diCQAs), on microglial activation in vitro and focal cerebral ischemia in vivo. Methods: The production of nitric oxide (NO), tumor necrosis factor a (TNF-alpha), and interleukin-1 beta (IL-1 beta) induced by lipopolysaccharide (LPS) treatment in rat primary cultured microglia were measured by Griess reaction or enzyme-linked immunosorbent assay. Cell viability of cortical neurons was measured using AlamarBlue reagent. The behavioral tests and the infarct area of brain were used to evaluate the damage to central nervous system in rat middle cerebral artery occlusion (MCAO) model of cerebral ischemia. Real time polymerase chain reaction was used to determine the expression of inducible nitric oxide synthase (iNOS), TNF-alpha and IL-1 beta mRNA in ischemic cerebral tissues. Results: Caf inhibited the production of NO, TNF-alpha and IL-1 beta induced by LPS treatment in primary microglia in a dose-dependent manner. Exposure of cortical neurons to conditioned medium from Caf-treated microglia increased neuronal cell viability (P<0.01) compared with conditioned medium from LPS-treated alone. In MCAO rat model of cerebral ischemia, Cat could significantly improve neurobehavioural performance and reduce percentage infarct volume compared with the vehicle group (P<0.05). Caf could also significantly inhibit the up-regulation of iNOS, TNF-alpha, and IL-1 beta gene expressions in ischemic cerebral tissues. Conclusion: Caf could suppress microglial activation, which may be one mechanism of its neuroprotective effect against ischemia.