Eupatilin exerts neuroprotective effects in mice with transient focal cerebral ischemia by reducing microglial activation

Abstract

Microglial activation and its-driven neuroinflammation are characteristic pathogenetic features of neurodiseases, including focal cerebral ischemia. The Artemisia asiatica (Asteraceae) extract and its active component, eupatilin, are well-known to reduce inflammatory responses. But the therapeutic potential of eupatilin against focal cerebral ischemia is not known, along with its anti-inflammatory activities on activated microglia. In this study, we investigated the neuroprotective effect of eupatilin on focal cerebral ischemia through its anti-inflammation, particularly on activated microglia, employing a transient middle cerebral artery occlusion/reperfusion (tMCAO), combined with lipopolysaccharide-stimulated BV2 microglia. Eupatilin exerted anti-inflammatory responses in activated BV2 microglia, in which it reduced secretion of well-known inflammatory markers, including nitrite, IL-6, TNF-α, and PGE2, in a concentration-dependent manner. These observed in vitro effects of eupatilin led to in vivo neuroprotection against focal cerebral ischemia. Oral administration of eupatilin (10 mg/kg) in a therapeutic paradigm significantly reduced brain infarction and improved neurological functions in tMCAO-challenged mice. The same benefit was also observed when eupatilin was given even within 5 hours after MCAO induction. In addition, the neuroprotective effects of a single administration of eupatilin (10 mg/kg) immediately after tMCAO challenge persisted up to 3 days after tMCAO. Eupatilin administration reduced the number of Iba1-immunopositive cells across ischemic brain and induced their morphological changes from amoeboid into ramified in the ischemic core, which was accompanied with reduced microglial proliferation in ischemic brain. Eupatilin suppressed NF-κB signaling activities in ischemic brain by reducing IKKα/β phosphorylation, IκBα phosphorylation, and IκBα degradation. Overall, these data indicate that eupatilin is a neuroprotective agent against focal cerebral ischemia through the reduction of microglial activation.

Effect of Low-Dose Alcohol Consumption on Inflammation Following Transient Focal Cerebral Ischemia in Rats

“…Activated microglia may contribute to cerebral I/R injury via phagocytosis and elaboration of neuroinflammatory mediators toxic to cells 29 . Studies have shown that decreased microglial activation in the ischemic hemisphere of the brain is associated with marked reduced cerebral I/R injury 30 , 31 . In the present study, post-ischemic microglia activation was significantly attenuated after chronic low-dose consumption of red wine and ethanol.…”

Sphingosine 1-phosphate receptor subtype 3 (S1P3) contributes to brain injury after transient focal cerebral ischemia via modulating microglial activation and their M1 polarization

“…was administered twice a day at 12-h intervals on the second and third day after tMCAO challenge. Brain sections were prepared for Iba1/BrdU immunofluorescence as described previously [ 18 , 21 ].…”

CoQ10 Augments Rosuvastatin Neuroprotective Effect in a Model of Global Ischemia via Inhibition of NF-κB/JNK3/Bax and Activation of Akt/FOXO3A/Bim Cues

“…This transcription factor empowers the generation of proinflammatory enzymes and cytokines, including tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), and intracellular adhesion molecule-1 (ICAM-1) ( Zhang et al, 2016 ). These events amplify the inflammatory cascade and trigger the recruitment of neutrophils, thereby exacerbating the ischemic insult ( Cheng and Lee, 2016 ; Sapkota et al, 2017 ).…”