Neuroprotection of N-benzyl Eicosapentaenamide in Neonatal Mice Following Hypoxic-Ischemic Brain Injury

Maca (Lepidium meyenii) has emerged as a popular functional plant food because of its medicinal properties and nutritional value. Macamides, as the exclusively active ingredients found in maca, are a unique series of non-polar, long-chain fatty acid N-benzylamides with multiple bioactivities such as antifatigue characteristics and improving reproductive health. In this study, a new kind of macamide, N-benzyl eicosapentaenamide (NB-EPA), was identified from maca. We further explore its potential neuroprotective role in hypoxic-ischemic brain injury. Our findings indicated that treatment with biosynthesized NB-EPA significantly alleviates the size of cerebral infarction and improves neurobehavioral disorders after hypoxic-ischemic brain damage in neonatal mice. NB-EPA inhibited the apoptosis of neuronal cells after ischemic challenge. NB-EPA improved neuronal cell survival and proliferation through the activation of phosphorylated AKT signaling. Of note, the protective property of NB-EPA against ischemic neuronal damage was dependent on suppression of the p53-PUMA pathway. Taken together, these findings suggest that NB-EPA may represent a new neuroprotectant for newborns with hypoxic-ischemic encephalopathy.

Automated summary

The study identified a new type of macamide, N-benzyl eicosapentaenamide (NB-EPA), from maca which showed significant neuroprotective effects in neonatal mice with hypoxic-ischemic brain injury. NB-EPA treatment reduced cerebral infarction size, improved neurobehavioral disorders, prevented neuronal apoptosis, and enhanced neuronal cell survival and proliferation through the activation of phosphorylated AKT signaling. The protective properties of NB-EPA against ischemic neuronal damage were found to be dependent on the suppression of the p53-PUMA pathway.