Network Pharmacology Strategy to Investigate the Pharmacological Mechanism of Siwu Decoction on Primary Dysmenorrhea and Molecular Docking Verification

Dandan Jiang,Xiaoyan Wang,Yufeng Zhang,Lijun Tian,Linus R Shao

doi:10.1155/2021/6662247

Abstract

Objective. To study the pharmacological mechanisms of Siwu decoction (SWD) on primary dysmenorrhea (PDM) and verify with molecular docking. Methods. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was utilized to acquire the active compounds and their corresponding target genes. The GeneCards database was utilized in the search for target genes that were associated with PDM. The intersection genes from the active target genes of SWD and those associated with PDM represented the active target genes of SWD that act on PDM. The Gene Ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were both carried out by RGUI 3.6.1 and Cytoscape 3.6.0 software. Cytoscape was also utilized for creating a compound-target network, and a protein-protein interaction (PPI) network was created through the STRING database. Molecular docking simulations of the macromolecular protein target receptors and their corresponding compounds were performed using AutoDockTool 1.5.6 and AutoDock Vina software. Results. We identified 14 active compounds as well as 97 active target genes of SWD by using the TCMSP. We compared the 97 active target genes of SWD to the 299 target genes related to PDM, and 23 active target genes for SWD that act on PDM which correlated with 11 active compounds were detected. The compound-target network as well as the PPI network were created, in addition to selecting the most essential compounds and their targets in order to create a key compound-target network. The most essential compounds were kaempferol, beta-sitosterol, stigmasterol, and myricanone. The key targets were AKT1, PTGS2, ESR1, AHR, CASP3, and PGR. Lastly, molecular docking was used to confirm binding of the target with its corresponding compound. Conclusion. The pharmacological mechanisms of SWD that act on PDM were investigated, and the active compounds in the SWD for treating PDM were further verified.

Highlights

Primary dysmenorrhea (PDM) is defined as dysmenorrhea resulting from nonpelvic organic lesions [1]. e clinical manifestations of PDM include lower abdominal spasmodic pain during menstrual periods accompanied by headache, nausea, vomiting, and lumbar and leg pain [2].Oral contraceptives and nonsteroidal anti-inflammatory drugs (NSAIDs) have been prescribed as first choice of treatment in PDM [3, 4]
3.4. e Gene Ontology (GO) Function Enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Enrichment Analysis. e entrez IDs of the active target genes of Siwu decoction (SWD) that act on PDM were retrieved through RGUI as well as org.Hs.eg.db (Table 2). ereafter, we conducted the Radix Paeoniae Alba (RPA) RPA RPA RPA RPA RPA RPA Radix Angelicae Sinensis (RAS) RPA Rhizoma Chuanxiong (RC) Rehmanniae Preparata (RRP) RPA RPA RC RC RC RC RC RC RAS RRP
E GO function enrichment analysis of biological process (BP) indicated the following: active target genes of SWD that act on PDM have been enriched significantly as reaction to toxic substances, the cellular response to xenobiotic stimulus, the metabolic processes of long-chain fatty acids, fatty acids, and unsaturated fatty acids, the response to xenobiotic stimulus, the xenobiotic metabolic process, the maternal process related to female pregnancy, the long-chain fatty acid biosynthetic process, the response to osmotic stress, and other

Summary

Introduction

Oral contraceptives and nonsteroidal anti-inflammatory drugs (NSAIDs) have been prescribed as first choice of treatment in PDM [3, 4]. These drugs have adverse effects, and their long-term effects are less than optimal. There have been studies in which Chinese herbal medicine (CHM) was given as PDM therapy, and the results showed that certain curative effect was achieved [5,6,7]. A metaanalysis and systematic review reported the effects of SWD as treatment for PDM where beneficial and potentially safer in comparison to standard therapy [10]

Methods

Results

Discussion

Conclusion