3,5,6,7,8,3′,4′-Heptamethoxyflavone, a citrus flavonoid, on protection against memory impairment and neuronal cell death in a global cerebral ischemia mouse model

• HMF protected against ischemia-induced memory dysfunction.
• HMF restored neuronal cell death in the hippocampal CA1 region following ischemia.
• HMF induced increases in BDNF synthesis and CaMK2 phosphorylation in the hippocampus.
• HMF suppressed microglial activation.
• HMF had a neuroprotective effect against ischemic insults.

The present study evaluated the effects of treatment with the citrus flavonoid, 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF) on protection against memory impairment and neuronal death in a global cerebral ischemia mouse model. The results showed that HMF, administrated for three days immediately after ischemic surgery, protected against ischemia-induced memory dysfunction, rescued neuronal cell death in the CA1 cell layer, increased the production of BDNF, stimulated the autophosphorylation of CaMK II and suppressed microglial activation in the hippocampus. These results suggest that HMF has a neuroprotective effect after brain ischemia by inducing BDNF production and anti-inflammatory effects.