Behavioral and Network Pharmacology-Based Analyses for the Traditional Mongolian Medicine Zadi-5 in a Rat Model of Depression

Summary

The present protocol describes a method for the behavioral test validation and bioinformatical prediction of the therapeutic efficacy of Zadi-5, a traditional Mongolian medicine, in depression.

Abstract

Zadi-5 is a traditional Mongolian medicine that is widely used for the treatment of depression and symptoms of irritation. Although the therapeutic effects of Zadi-5 against depression have been indicated in previously reported clinical studies, the identity and impact of the active pharmaceutical compounds present in the drug have not been fully elucidated. This study used network pharmacology to predict the drug composition and identify the therapeutically active compounds in Zadi-5 pills. Here, we established a rat model of chronic unpredicted mild stress (CUMS) and conducted an open field test (OFT), Morris water maze (MWM) analysis, and sucrose consumption test (SCT) to investigate the potential therapeutic efficacy of Zadi-5 in depression. This study aimed to demonstrate Zadi-5's therapeutic effects for depression and predict the critical pathway of the action of Zadi-5 against the disorder. The vertical and horizontal scores (OFT), SCT, and zone crossing numbers of the fluoxetine (positive control) and Zadi-5 groups were significantly higher (P < 0.05) than those of the CUMS group rats without treatment. According to the results of network pharmacology analysis, the PI3K-AKT pathway was found to be essential for the antidepressant effect of Zadi-5.

Introduction

Depression, also known as major depressive disorder (MDD), is a severe neuropsychiatric disease responsible for growing medical and economic burdens on society. Due to the associated complexity, morbidity, and mortality rates, a significant amount of research has been conducted to find remedies for the disorder^1,2. According to a mental health survey by the World Health Organization, around 350 million people currently suffer from depression and its associated symptoms worldwide. It is predicted that depression will overtake cancer and cardiovascular diseases as the leading cause of disease burden globally by ....

Protocol

All the experimental protocols were approved by the Ethics of Animal Experiment Care Committee of Inner Mongolia Medical University and followed the guidelines of the National Institutes of Health on animal care and ethics. Male Sprague Dawley (SD) rats aged 8 weeks old (200 g ± 20 g) were housed in a room with a controlled temperature (22 °C ± 2 °C) and humidity (55% ± 15%) under a 12 h/12 h regulated light/dark cycle for 1 week. See Figure 1 for the workflow of the network pharmacology analysis.

1. Behavioral test in rats

1. Establish a CUMS rat model
   ....

Results

Behavioral test in animals
Results of the behavioral tests in the CUMS-induced rat depression model
No significant differences between the tested groups were found for the OFT score, sucrose consumption, and MWM analysis before CUMS stimulation. After establishing the CUMS model, the MOD group's vertical and horizontal scores were lower than those of the CON group (P < 0.05). Compared with the MOD group, the vertical and horizontal scores of the POS and Zadi-5 groups .......

Discussion

Depression is a mental disease characterized by low mood, anhedonia, and a lack of energy. This disorder is accompanied by distraction, cognitive dysfunction, social withdrawal, insomnia, sexual dysfunction, and gastrointestinal diseases^18,19. In the study of depression, establishing an animal model is crucial for understanding the pathological mechanisms and effects of new drugs. In this study, a CUMS-induced rat depression model was established through the irri.......

Materials

Name	Company	Catalog Number	Comments
Cytoscape software		version 3.7.0
Fluoxetine	Lilly Suzhou Pharmaceutical Co., Ltd	J20160029
Morris water maze video trail analysing system	Tai Meng Tech Co., Ltd	WMT-200
Sprague Dawley rats	Beijing Biotechnology Co., Ltd, China	SCXK (JING) 2016-0002
video tracking system	Tai Meng Tech Co., Ltd	ZH-ZFT
Zadi-5 pill	Pharmaceutical Preparation Center of International Mongolian Hospital, Inner Mongolia, China	M1301006