Extract of Euryale ferox Salisb exerts antidepressant effects and regulates autophagy through the adenosine monophosphate-activated protein kinase-UNC-51-like kinase 1 pathway.

Positive regulation of autophagy by Euryale ferox Salisb (ES) leads to antidepressant effects. This study focused on the potential antidepressant mechanisms induced by the petroleum ether fraction of ES (ES-PE) in the chronically unpredictable mild stress (CUMS) mouse model. Deficits in the sucrose preference test, open field test, tail suspension test, and forced swim test were observed following CUMS, and were reversed following ES-PE administration. Contrary to the expression of mammalian target of rapamycin, autophagy was decreased after establishment of the CUMS model. We also observed trends for downregulation of adenosine mononphosphate-activated protein kinase (AMPK) and mammalian autophagy-initiating kinase (ULK1), which were differentially affected by ES-PE. HT22 cells and Compound C, an inhibitor of AMPK, were used to verify the results in mice. Gas chromatography-mass spectrometry analysis revealed high level of vitamin E acetate in ES-PE. Taken together, our data indicate that ES-PE activated autophagy by regulating the AMPK pathway.