Ninjinyoeito improves anxiety behavior in neuropeptide Y deficient zebrafish.

Publisher: Elsevier Country of Publication: Netherlands NLM ID: 8103156 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-2785 (Electronic) Linking ISSN: 01434179 NLM ISO Abbreviation: Neuropeptides Subsets: MEDLINE

Publication: 2002- : Amsterdam : Elsevier
Original Publication: Edinburgh ; New York : Churchill Livingstone, c1980-

Phytotherapy*; Anti-Anxiety Agents/*therapeutic use ; Anxiety/*drug therapy ; Drugs, Chinese Herbal/*therapeutic use ; Neuropeptide Y/*deficiency; Animals ; Anti-Anxiety Agents/chemistry ; Anxiety/genetics ; Brain/enzymology ; Cold-Shock Response ; Disease Models, Animal ; Drug Evaluation, Preclinical ; Drugs, Chinese Herbal/chemistry ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Freezing Reaction, Cataleptic ; Fruit ; Gene Expression Regulation/drug effects ; Gene Knockout Techniques ; Lignans/isolation & purification ; Lignans/pharmacology ; Lignans/therapeutic use ; Medicine, Kampo ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; RNA, Messenger/biosynthesis ; RNA, Messenger/genetics ; Schisandra ; Swimming ; Tyrosine 3-Monooxygenase/metabolism ; Zebrafish ; Zebrafish Proteins

Anxiety induced by excess mental or physical stress is deeply involved in the onset of human psychiatric diseases such as depression, bipolar disorder, and panic disorder. Recently, Kampo medicines have received focus as antidepressant drugs for clinical use because of their synergistic and additive effects. Thus, we evaluated the anxiolytic activity of Ninjinyoeito (NYT) using neuropeptide Y-knockout (NPY-KO) zebrafish that exhibit severe anxiety responses to acute stress. Adult NPY-KO zebrafish were fed either a 3% NYT-supplemented or normal diet (i.e., the control diet) for four days and were then examined via behavioral tests. After short-term cold stress (10 °C, 2 s) was applied, control-fed NPY-KO zebrafish exhibited anxiety behaviors such as freezing, erratic movement, and increased swimming time along the tank wall. On the other hand, NYT-fed NPY-KO zebrafish significantly suppressed these anxiety behaviors, accompanied by a downregulation of tyrosine hydroxylase levels and phosphorylation of extracellular signal-regulated kinases in the brain. To understand the responsible component(s) in NYT, twelve kinds of herbal medicines that composed NYT were tested in behavioral trials with the zebrafish. Among them, nine significantly reduced freezing behavior in NPY-KO zebrafish. In particular, Schisandra fruit induced the most potent effect on abnormal zebrafish behavior, even in the lower amount (0.3% equivalent to NYT), followed by Atractylodes rhizome and Cinnamon bark. Subsequently, four lignans uniquely found in Schisandra fruit (i.e., gomisin A, gomisin N, schizandrin, and schizandrin B) were investigated for their anxiolytic activity in NPY-KO zebrafish. As a result, schizandrin was identified as a responsible compound in the anxiolytic effect of NYT. These results suggest that NYT has a positive effect on mental stress-induced anxiety and may be a promising therapeutic for psychiatric diseases.
(Copyright © 2021 Elsevier Ltd. All rights reserved.)

Keywords: Anxiety; Behavior; Knockout; Neuropeptide Y; Ninjinyoeito; Schisandra fruit; Schizandrin; Zebrafish

0 (Anti-Anxiety Agents)
0 (Drugs, Chinese Herbal)
0 (Lignans)
0 (Nerve Tissue Proteins)
0 (Neuropeptide Y)
0 (RNA, Messenger)
0 (Zebrafish Proteins)
0 (ninjin'yoeito)
EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)

Date Created: 20210315 Date Completed: 20211203 Latest Revision: 20211214

20231215

10.1016/j.npep.2021.102136

33721592