Screening and Identification of Antidepressant Active Ingredients from Puerariae Radix Extract and Study on Its Mechanism

Author:

Wang Guoze12ORCID,Luo Peng12ORCID,Zhang Shuai13ORCID,Huang Qun12ORCID,Zhang Shuling12ORCID,Zeng Qibing1ORCID,Mao Jingxin14ORCID

Affiliation:

1. School of Public Health, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang 550025, China

2. State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China

3. Department of Interventional Radiology, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang 550000, China

4. College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China

Abstract

Objective. Depression is a common mental disease with long course and high recurrence rate. Previous studies showed that Puerariae Radix and its extracts have powerful antidepressant effects in recent years. The study proposed an integrated strategy, combining network pharmacology and molecular pharmacology experiment to investigate the mechanisms of the antidepressant active ingredients from Puerariae Radix. Methods. TCMSP database, GeneCards database, Venny 2.1, UniProt database, STRING database, Cytoscape 3.7.2, and Metascape database were used to screen the active chemical components, antidepressant-related genes, and core targets, convert the abbreviated gene names in batch, search and predict the interaction between proteins, and construct the PPI network of Puerariae Radix. KEGG pathway and GO biological process enrichment and biological annotation were used to select antidepressant core gene targets. The MTT method was used to detect the effect of puerarin on the damage of PC12 cells induced by corticosterone. The DCFH-DA probe and ROS assay kit were utilized to detect the production of ROS in PC12 cells. PI/Annexin V was used to detect the apoptotic rate of puerarin on PC12 cells. Western blotting was used to verify the regulation of puerarin on the key targets of AKT1, FOS, CASP3, STAT3, and TNF-α in PC12 cells. Results and Conclusion. Eight main active components, 64 potential antidepressant gene targets, and 15 core antidepressant gene targets were obtained. 35 signaling pathways and 52 biological processes related to antidepressant effect of Puerariae Radix were identified. Puerarin was the active ingredient derived from Puerariae Radix which exhibited the antidepression effect by improving the viability of cell, reducing cell apoptosis, regulating ROS production, increasing protein expressions of AKT1 and FOS, and reducing protein expressions of CASP3, STAT3, and TNF-α. The study revealed the pharmacodynamic material basis and possible antidepressant mechanism of Puerariae Radix and provided new theoretical basis and ideas for antidepressant research.

Funder

Guizhou Medical University

Publisher

Hindawi Limited

Subject

Cell Biology,Ageing,General Medicine,Biochemistry

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