ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Neuropharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1693106
Therapeutic Potential of Extracellular Vesicles derived from Platycladus Orientalis Leaf in Treating Anxiety, Depression, and Insomnia
Provisionally accepted
Hongwei Liang1*
Peiyu Liu2Guiyang He1Yaoxin Lu3Juanjuan He1Faliang Wu3Meng Jia4Shaochang Jia4Ruijie Fan3Bing Liu3
Min Li2- 1China Pharmaceutical University, Nanjing, China
- 2Army Medical University, Chongqing, China
- 3Lushan Rehabilitation and Sanatorium Center, Jiujiang, China
- 4Nanjing University, Nanjing, China
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Extracellular vesicles (EVs), which mediate intercellular communication by transferring bioactive molecules such as lipids, proteins, and RNAs, have become a focal point in biomedical research due to their roles in various physiological and pathological processes. While much of the focus has been on EVs derived from animal cells, plant-derived EVs (plant-EVs) are emerging as a novel class of bioactive nanocarriers with unique therapeutic potential. In this study, we investigate the therapeutic effects of Extracellular Vesicles derived from Platycladus Orientalis Leaf (EVs from P. orientalis leaf) on stress-induced psychiatric disorders, using various rodent models of anxiety, depression, and insomnia. EVs from P. orientalis leaf were isolated using differential ultracentrifugation and characterized through transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Active small molecular compounds were analyzed by UPLC-MS/MS, and EV uptake was confirmed in PC12 cells. Behavioral effects were assessed using the chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS) models for anxiety and depression, and the PCPA-induced insomnia model. The results show that EVs from P. orientalis leaf effectively alleviate anxiety, depression, and insomnia in rodent models. Treatment with these EVs led to significant improvements in behavioral outcomes, including increased social interaction, reduced immobility time, and improved memory and learning. Furthermore, EVs enhanced the expression of serotonin(5-HT) and GABA in both serum and brain tissue, underscoring their potential to modulate neurotransmitter systems. These findings highlight the therapeutic potential of plant-EVs as novel, bioactive nanocarriers for mental health management.
Keywords: Platycladus orientalis (L.) franco, extracellular vesicles, Anxiety, Depression, insomnia
Received: 26 Aug 2025; Accepted: 16 Sep 2025.
Copyright: © 2025 Liang, Liu, He, Lu, He, Wu, Jia, Jia, Fan, Liu and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Hongwei Liang, hwliang@nju.edu.cn
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.