Antidepressant effect of the peptide EIILEAGK from Apostichopus japonicus via inflammatory and mitochondrial regulations in a lipopolysaccharide mouse model

An increasing number of studies support the hypothesis of inflammation-induced depression, and several anti-inflammatory drugs are known to target tumour necrosis factor ɑ (TNF-ɑ) and interleukin 6 (IL-6) to show antidepressant potential. Here, a novel peptide derived from the sea cucumber Apostichopus japonicus was found to have an anti-inflammatory effect, as demonstrated by inhibiting the activation of NF-κB and reducing the levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in the brain tissue and blood of lipopolysaccharide (LPS)-treated mice. Interestingly, LPS-induced depressive symptoms in mice were significantly improved after peptide treatment. In addition, LPS-induced oxidative stress and senescence in microglia were also reduced by the peptide. Further studies have shown that this peptide maintains the levels of mitochondrial complex 4 (COX IV), the mitochondria-associated protein mitochondrial fusion protein 2 (Mfn-2), optic atrophy 1 (OPA 1), and dynamin-related protein 1 (Drp 1) in neuronal cells, which are essential for the regulation of mitochondrial function and the maintenance of mitochondrial dynamic homeostasis. The sea cucumber-derived peptide can ameliorate the depression-like symptoms of LPS through inflammatory and mitochondrial function regulation.