Affiliation:
1. School of Medical Technology Xuzhou Medical University Xuzhou China
2. School of Pharmacy Xuzhou Medical University Xuzhou China
3. Laboratory Medicine, Guangdong Provincial People's Hospital Guangzhou China
4. School of Medical Informatics and Engineering Xuzhou Medical University Xuzhou China
5. Centre for Precision Health, School of Medical and Health Sciences Edith Cowan University Perth Western Australia Australia
6. Research Center for Biochemistry and Molecular Biology and Jiangsu Key Laboratory of Brain Disease Bioinformation Xuzhou Medical University Xuzhou China
7. Department of Laboratory Medicine Affiliated Hospital of Xuzhou Medical University Xuzhou China
Abstract
AbstractDepression is a common and debilitating condition for which effective treatments are needed. Lepidium meyenii Walp (Maca) is a plant with potential medicinal effects in treating depression. Recently, there has been growing interest in plant‐derived extracellular vesicles (EVs) due to their low toxicity and ability to transport to human cells. Targeting the gut–brain axis, a novel strategy for depression management, may be achieved through the use of Maca‐derived EVs (Maca‐EVs). In this study, we successfully isolated Maca‐EVs using gradient ultracentrifugation and characterized their shape, size, and markers (CD63 and TSG101). The in vivo imaging showed that the Dil‐labeled Maca‐EVs crossed the brain–blood barrier and accumulated in the brain. The behavioral tests revealed that Maca‐EVs dramatically recovered the depression‐like behaviors of unpredictable chronic mild stress (UCMS) mice. UCMS mice fecal were characterized by an elevated abundance of g_Enterococcus, g_Lactobacillus, and g_Escherichia_Shigella, which were significantly restored by administration of Maca‐EVs. The effects of Maca‐EVs on the altered microbial and fecal metabolites in UCMS mice were mapped to biotin, pyrimidine, and amino acid (tyrosine, alanine, aspartate, and glutamate) metabolisms, which were closely associated with the serotonin (5‐HT) production. Maca‐EVs were able to increase serum monoamine neurotransmitter levels in UCMS mice, with 5‐HT showing the most significant changes. We further demonstrated that 5‐HT improved the expression of brain‐derived neurotrophic factor, a key regulator of neuronal plasticity, and its subsequent activation of TrkB/p‐AKT signaling by regulating the GTP‐Cdc42/ERK pathway. These findings suggest that Maca‐EVs enhance 5‐HT release, possibly by modulating the gut–brain axis, to improve depression behavior. Our study sheds light on a novel approach to depression treatment using plant‐derived EVs.
Funder
Natural Science Foundation of Jiangsu Province
Subject
Microbiology,Biotechnology