Angelica keiskei extract inhibits LPS-induced activation of microglia and ameliorates acute cerebral ischemic injury in mice

Abstract

Angelica keiskei (Miq.) Koidz. [Apiaceae] is a botanical drug with dual-purpose as food and medicine and its improvement in acute cerebral ischemic injury has not been studied. In the present study, we investigated the anti-neuroinflammatory and protective effects of the ethyl acetate extract of Angelica keiskei (EEAK) on acute cerebral ischemic injury. EEAK dose-dependently suppressed the production of inflammatory cytokines in lipopolysaccharide-activated BV2 microglia, with IC₅₀ values of 21.8 μg/mL for TNF-α and 7.9 μg/mL for IL-6, and also reduced NO and ROS levels at non-cytotoxic concentrations. In addition, EEAK inhibited the activation of the NF-κB and MAPK signaling pathways. In vivo, preventive oral administration of EEAK (50 and 100 mg/kg) significantly reduced infarct volume and improved neurological deficits in mice subjected to MCAO/R. EEAK also suppressed the mRNA expression of TNF-α, IL-6, IL-1β, and iNOS, as well as microglial activation, in ischemic brain tissues. These findings suggest that EEAK may protect against acute ischemic brain injury by inhibiting microglial activation and neuroinflammatory responses. Notably, as the treatment was administered preventively prior to acute ischemic brain injury, the therapeutic potential of EEAK in acute ischemic brain injury remains to be determined.