Ito, N, Nagai, T, Yabe, T et al. · Phytomedicine : international journal of phytotherapy and phytopharmacology · 2006 · DOI
This study tested whether Koso-san, a traditional Japanese herbal medicine, could help reduce depression-like symptoms in mice exposed to stress. Mice given Koso-san showed improved behavior in stress tests, and the herb appeared to normalize stress hormone systems in their brains that were overactive due to the stress exposure.
Since ME/CFS patients often experience depression, autonomic dysfunction, and potential HPA axis abnormalities, understanding how herbal medicines modulate stress hormone systems is clinically relevant. This study provides mechanistic insight into a traditional medicine already used clinically for fatigue and autonomic imbalance, which could inform future research into neuroendocrine interventions for ME/CFS.
This study does not demonstrate that Koso-san is effective in humans with ME/CFS, depression, or any other condition—it is a rodent mechanistic study only. It does not prove the HPA axis is abnormal in ME/CFS patients or that normalizing it via this herb will improve human symptoms. Findings in stressed mice may not translate to the complex pathophysiology of ME/CFS.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Ito, N, Nagai, T, Yabe, T, Nunome, S, Hanawa, T, & Yamada, H (2006). Antidepressant-like activity of a Kampo (Japanese herbal) medicine, Koso-san (Xiang-Su-San), and its mode of action via the hypothalamic-pituitary-adrenal axis.. Phytomedicine : international journal of phytotherapy and phytopharmacology. https://doi.org/10.1016/j.phymed.2006.01.002
BibTeX
@article{mecfsatlas-ito-2006-antidepressant-like,
author = {Ito, N and Nagai, T and Yabe, T and Nunome, S and Hanawa, T and Yamada, H},
title = {Antidepressant-like activity of a Kampo (Japanese herbal) medicine, Koso-san (Xiang-Su-San), and its mode of action via the hypothalamic-pituitary-adrenal axis.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
year = {2006},
doi = {10.1016/j.phymed.2006.01.002},
note = {PubMed: 16516452},
url = {https://www.mecfsatlas.com/evidence/ito-2006-antidepressant-like},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-28. https://www.mecfsatlas.com/evidence/ito-2006-antidepressant-like
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