Antidepressant‐Like Effect of Ferulic Acid via Promotion of Energy Metabolism Activity

SCOPE: Ferulic acid (FA), a natural phenolic phytochemical abundantly present in whole grains, herbs, and dried fruits, exhibits anti‐inflammatory, antioxidant, and neuroprotective effects. In the present study, the antidepressant‐like effects of FA in male ICR mice using tail suspension test (TST) are investigated and its molecular mechanisms are explored. METHODS AND RESULTS: Oral administration of FA at a dose of 5 mg kg(–1) for 7 days significantly reduces immobility of mice compared to vehicle‐administered control group. Microarray and real‐time PCR analyses reveal that FA upregulates the expression of several genes associated with cell survival and proliferation, energy metabolism, and dopamine synthesis in mice limbic system of brain. Interestingly, it is found that FA, unlike antidepressant drug bupropion, strongly promotes energy metabolism. Additionally, FA increases catecholamine (dopamine and noradrenaline), brain‐derived neurotrophic factor, and ATP levels, and decreases glycogen levels in the limbic system of the mice brain. CONCLUSION: The research provides the first evidence that FA enhances energy production, which can be the underlying mechanism of the antidepressant‐like effects of FA observed in this study.