From single pathways to holistic networks: unraveling the multimechanistic actions of acupuncture in depression
- 1Department of Rehabilitation Medicine, The Affiliated Huizhou Hospital of Guangzhou Medical University
- 2Tianjin Key Laboratory of Modern Chinese Medicine Theory of Innovation and Application, School of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine
Abstract
Depression is a globally prevalent mental disorder; however, current pharmacological treatments are limited by a delayed onset of action and significant adverse effects. As a safe and effective non-pharmacological therapy, acupuncture demonstrates unique advantages in treating mild to moderate depression. Its antidepressant mechanisms are multifaceted. Primarily, acupuncture mitigates neuroinflammation by inhibiting classical signaling pathways (e.g., nuclear factor kappa B/NOD-like receptor family pyrin domain containing 3), modulating microglial polarization, and restoring cytokine homeostasis. Furthermore, it enhances neuroplasticity by upregulating brain-derived neurotrophic factor expression, improving synaptic plasticity, and promoting adult neurogenesis. At the cellular level, acupuncture exerts neuroprotective effects by suppressing apoptotic cascades associated with mitochondrial dysfunction and endoplasmic reticulum stress, regulating autophagic balance, and restoring neuronal excitability. Systemically, it ameliorates metabolic dysregulation by optimizing cerebral energy metabolism, modulating gut microbiota composition, and reinforcing intestinal barrier integrity. Additionally, acupuncture effectively alleviates comorbid pain by modulating peripheral nociceptive signaling and central pain-emotion feedback loops. These synergistic effects across multiple systems and targets may together ameliorate the pathophysiological alterations associated with depression. Despite these advances, current research faces challenges, including the translational gap between animal models and clinical pathology, as well as an insufficient investigation of multi-mechanism interactions. Future efforts should focus on developing clinically relevant models, integrating multi-omics technologies, conducting high-quality clinical trials, and exploring biomarker-guided personalized treatments to advance the scientific and standardized application of acupuncture for depression.
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BibTeX
@article{quan2026from,
title = {{From single pathways to holistic networks: unraveling the multimechanistic actions of acupuncture in depression}},
author = {Shaohao Quan and Wanyi Xu and Haofei Du and Zhifang Xu and Tianyi Zhao and Meidan Zhao and Xiaowei Lin and Xiaokai Chen},
journal = {Frontiers in Psychiatry},
year = {2026},
month = oct,
doi = {10.3389/fpsyt.2026.1936946},
url = {https://www.frontiersin.org/articles/10.3389/fpsyt.2026.1936946/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - From single pathways to holistic networks: unraveling the multimechanistic actions of acupuncture in depression
AU - Shaohao Quan
AU - Wanyi Xu
AU - Haofei Du
AU - Zhifang Xu
AU - Tianyi Zhao
AU - Meidan Zhao
AU - Xiaowei Lin
AU - Xiaokai Chen
PY - 2026
DA - 2026/10/23
JO - Frontiers in Psychiatry
DO - 10.3389/fpsyt.2026.1936946
UR - https://www.frontiersin.org/articles/10.3389/fpsyt.2026.1936946/full
AB - Depression is a globally prevalent mental disorder; however, current pharmacological treatments are limited by a delayed onset of action and significant adverse effects. As a safe and effective non-pharmacological therapy, acupuncture demonstrates unique advantages in treating mild to moderate depression. Its antidepressant mechanisms are multifaceted. Primarily, acupuncture mitigates neuroinflammation by inhibiting classical signaling pathways (e.g., nuclear factor kappa B/NOD-like receptor family pyrin domain containing 3), modulating microglial polarization, and restoring cytokine homeostasis. Furthermore, it enhances neuroplasticity by upregulating brain-derived neurotrophic factor expression, improving synaptic plasticity, and promoting adult neurogenesis. At the cellular level, acupuncture exerts neuroprotective effects by suppressing apoptotic cascades associated with mitochondrial dysfunction and endoplasmic reticulum stress, regulating autophagic balance, and restoring neuronal excitability. Systemically, it ameliorates metabolic dysregulation by optimizing cerebral energy metabolism, modulating gut microbiota composition, and reinforcing intestinal barrier integrity. Additionally, acupuncture effectively alleviates comorbid pain by modulating peripheral nociceptive signaling and central pain-emotion feedback loops. These synergistic effects across multiple systems and targets may together ameliorate the pathophysiological alterations associated with depression. Despite these advances, current research faces challenges, including the translational gap between animal models and clinical pathology, as well as an insufficient investigation of multi-mechanism interactions. Future efforts should focus on developing clinically relevant models, integrating multi-omics technologies, conducting high-quality clinical trials, and exploring biomarker-guided personalized treatments to advance the scientific and standardized application of acupuncture for depression.
SN - 1664-0640
ER -