Background: Major depressive disorder (MDD) is a common psychological disorder worldwide.
However, one-third of patients with MDD are resistant to the present antidepressant medicine which
regulates monoamine contents in the brain. Thus, another drug target is strongly required. Much
evidence strongly suggests that sirtuin1, which is the key factor to regulate mitochondrial activity,
may be implicated in MDD.
Objective: Since it is suggested that royal jelly (RJ) ameliorated depressive-like behavior and
affected mitochondrial activity in mice, we hypothesized RJ could be an alternative medicine against
MDD which acts via sirtuin1 signaling to improve mitochondrial activity.
Methods: In the present study, we applied a mouse model of MDD to investigate the effect of RJ on
the depressive-like behavior and the sirtuin1 signaling on mitochondrial activity.
Results: Our results indicated that either the oral administration of RJ for 12 days or single
intracerebroventricular (i.c.v.) injection decreased the duration of immobility in the tail suspension
test, which suggested that RJ had an antidepressant-like effect. Moreover, sirtuin1 protein expression
increased in mice following RJ treatment in the amygdala region, but not in the other brain regions.
Similarly, the expressions of oxidative phosphorylation (OXPHOS) related proteins increased in the
amygdala regions, but not in the hippocampal regions.
Conclusion: The increase of sirtuin1 and OXPHOS protein expression may at least in part contribute
to the antidepressant-like effect of the RJ pathway, and RJ may have the potential to be a novel antidepressant drug.