REVIEW article
Front. Pharmacol.
Sec. Neuropharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1616322
This article is part of the Research TopicResearch on Precision Prevention and Treatment of Neurological and Neurodegenerative DiseasesView all 13 articles
Pharmacological mechanism of natural antidepressants: The role of Epigenetic Modifications
Provisionally accepted- 1First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
- 2College of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China
- 3Institute of Child and Adolescent Health, School of Public Health, Health Science Centre, Peking University, Beijing, Beijing Municipality, China
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MDD is a complex mental illness shaped by the interplay between genetic vulnerability and environmental triggers. Its underlying pathophysiological processes are now understood to be influenced by epigenetic mechanisms. Growing evidence points to critical roles for DNA methylation, histone modification, and ncRNAs in driving transcriptional dysregulation within key brain regions implicated in MDD.These epigenetic alterations may underlie the persistent impairments in neuroplasticity following environmental stress exposure. NPs, renowned for their multi-target properties, have demonstrated promise in modulating epigenetic processes. However, a systematic synthesis of their regulatory roles, mechanisms, and therapeutic potential remains incomplete. This review aims to bridge this gap by integrating evidence from PubMed, Web of Science, and Embase databases to elucidate the role of epigenetic modifications in the pathogenesis and progression of MDD, dissect the mechanisms through which NPs exert antidepressant effects via epigenetic regulation, and highlight current research limitations while proposing strategies for translational applications in both preclinical and clinical settings.
Keywords: epigenetic modifications, Depression, Natural Products, molecular mechanism, Antidepressant Abbreviation List MDD, Major depressive disorder, NPs, Natural products, SSRIs, Serotonin reuptake inhibitors, DNA, deoxyribonucleic acid
Received: 22 Apr 2025; Accepted: 05 Aug 2025.
Copyright: © 2025 Lu, Shang, Zhong, Shi, Zhang, Zhao and Teng. 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: Jing Teng, First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
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.