Effects of Xiao Yao San on interferon-α-induced depression in mice

Brain Res Bull. 2018 May:139:197-202. doi: 10.1016/j.brainresbull.2017.12.001. Epub 2017 Dec 16.

Abstract

Background and objective: Xiao Yao San (XYS) is a traditional Chinese medicine used to treat depression; however, the mechanism underlying its antidepressant properties remains unclear. The objective of the present study was to investigate the effects and action mechanisms of XYS on interferon-α-induced depression in mice.

Method: Mice were divided into six groups: control; model; low-, medium-, and high-dose XYS; and escitalopram-treated group. Except for the control mice, all groups of mice were injected with interferon (IFN)-α to establish the depression model. XYS and escitalopram were then administered to the respective mice daily for 21 days. Sucrose preference test (SPT), forced swim test (FST), and tail suspension test (TST) were used to measure behavioral indices. High-performance liquid chromatography (HPLC) was used to measure serotonin (5-HT) concentrations, while western blots were used to examine indoleamine-2,3-dioxygenase 1 (IDO1) expression in the dorsal raphe nucleus (DRN). The number of microglia in the DRN was observed using immunofluorescence.

Results: Compared with that of the control group, the model group showed a significant decrease in sucrose consumption (P < 0.05) and significant increase in the duration of immobility in the FST and TST (P < 0.05). These parameters improved significantly after XYS or escitalopram treatment. There was also a significantly higher and lower expression of IDO1 protein and 5-HT in the mouse DRN, respectively, which were reversed by administering XYS and escitalopram (P < 0.05). Moreover, the number of microglia in the mouse DRN increased significantly and was reduced by XYS and escitalopram (P < 0.05).

Conclusion: XYS reduced the number of microglia and expression of IDO1, which increased the levels of 5-HT in the mouse DRN and, thereby, improved the depressive behavior of mice. This may explain, at least in part, the antidepressant properties of XYS in patients.

Keywords: 3-dioxygenase 1; Indoleamine-2; Interferon-α; Microglia; Serotonin; Xiao Yao San.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / therapeutic use*
  • Calcium-Binding Proteins / metabolism
  • Citalopram / pharmacology
  • Citalopram / therapeutic use
  • Depression / chemically induced
  • Depression / drug therapy*
  • Depression / pathology
  • Disease Models, Animal
  • Dorsal Raphe Nucleus / drug effects
  • Dorsal Raphe Nucleus / metabolism
  • Drugs, Chinese Herbal / therapeutic use*
  • Food Preferences / drug effects
  • Glial Fibrillary Acidic Protein / metabolism
  • Hindlimb Suspension / psychology
  • Immunologic Factors / toxicity
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Interferon-alpha / toxicity
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microfilament Proteins / metabolism
  • Microglia / drug effects
  • Microglia / pathology
  • Serotonin / metabolism
  • Sucrose / administration & dosage
  • Swimming / psychology

Substances

  • Aif1 protein, mouse
  • Antidepressive Agents
  • Calcium-Binding Proteins
  • Drugs, Chinese Herbal
  • Glial Fibrillary Acidic Protein
  • IDO1 protein, mouse
  • Immunologic Factors
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Interferon-alpha
  • Microfilament Proteins
  • Citalopram
  • Serotonin
  • Sucrose