Japanese Herbal Medicine Relieves Anxiety in NPY-Deficient Animals via Schizandrin | Research

The takeaway

The Kampo medicine Ninjinyoeito suppressed severe anxiety behaviors in neuropeptide Y-knockout zebrafish, with Schisandra fruit's schizandrin identified as the key anxiolytic compound — reducing brain stress signaling.

Schizandrin: key compound
Among 12 herbal ingredients and 4 Schisandra lignans tested, schizandrin was identified as the single most potent anxiolytic compound in NPY-deficient animals

What the researchers found

NYT suppressed anxiety behaviors in NPY-KO zebrafish after 4-day dietary supplementation, with reduced tyrosine hydroxylase and ERK phosphorylation in brain. 9/12 component herbs reduced freezing. Schisandra fruit and its lignan schizandrin were the most potent anxiolytic components.

Why it matters

NPY deficiency contributes to anxiety disorders in humans. Identifying natural compounds that compensate for NPY-related anxiety could provide new treatment options, especially for patients who don't respond to conventional anxiolytics.

The numbers in context

3% NYT diet; 4-day treatment; 9/12 herbs reduced freezing; schizandrin identified as active lignan

How the study worked

Animal study. NPY-knockout zebrafish fed 3% NYT-supplemented or control diet for 4 days. Cold stress-induced anxiety behavioral tests. Brain tyrosine hydroxylase and ERK phosphorylation measured. Individual herbal components and Schisandra lignans tested for anxiolytic activity.

Who was studied

Adult NPY-knockout zebrafish

What this study cannot tell us

Zebrafish model — anxiety behavior may not fully translate to human psychiatric conditions. Short treatment period (4 days). NPY complete knockout is more extreme than human NPY variation. Schizandrin mechanism of action beyond NPY system not fully elucidated.

How to read the evidence

Low-to-moderate evidence: systematic identification of active compound through zebrafish behavioral model, but non-mammalian species with artificial NPY deletion.

When this study was published

Published 2021. Kampo medicine research and NPY-targeted anxiety treatments continue to be explored.

The bigger picture

Understanding how natural compounds interact with the neuropeptide Y system connects traditional medicine to modern neuroscience. Schizandrin's anxiolytic action in NPY-deficient animals could inform development of targeted anxiety treatments.

Questions still open

Does schizandrin directly modulate the NPY system or act through a parallel pathway?
Would Schisandra fruit supplementation reduce anxiety in humans with low NPY levels?
Can schizandrin or NYT be developed as a clinical anxiolytic?

Common questions

What is neuropeptide Y and why does it matter for anxiety?

NPY is one of the most abundant brain peptides and is crucial for stress resilience. People with lower NPY levels tend to be more anxious and vulnerable to stress-related disorders. This study shows that when NPY is completely absent, specific natural compounds can still provide anxiety relief.

Can Schisandra fruit help with anxiety?

This zebrafish study found that Schisandra fruit — specifically its compound schizandrin — reduced anxiety behaviors in NPY-deficient animals. Schisandra has been used in traditional Asian medicine for centuries for stress and mood support, and this study provides modern scientific evidence for that use.

Read the original research

Ninjinyoeito improves anxiety behavior in neuropeptide Y deficient zebrafish.

Neuropeptides, 87, 102136

View on PubMed ↗Publisher’s paper ↗

Citation

Kawabe, Momoko; Hayashi, Akito; Komatsu, Masaharu; Inui, Akio; Shiozaki, Kazuhiro. (2021). Ninjinyoeito improves anxiety behavior in neuropeptide Y deficient zebrafish.. Neuropeptides, 87, 102136. https://doi.org/10.1016/j.npep.2021.102136