Network Pharmacology to Explore the Molecular Mechanisms of Prunella vulgaris for Treating Hashimoto's Thyroiditis.

Xiao-Xiong Gan,Si-Jing Li,Bo Xu,Lin-Kun Zhong,Ya-Yi Li,Wen-Song Cai,Fei Shen,Jian-Hua Feng

doi:10.3389/fphar.2021.700896

Abstract

Purpose: Prunella vulgaris (PV), a traditional Chinese medicine, has been used to treat patients with thyroid disease for centuries in China. The purpose of the present study was to investigate its bioactive ingredients and mechanisms against Hashimoto’s thyroiditis (HT) using network pharmacology and molecular docking technology to provide some basis for experimental research. Methods: Ingredients of the PV formula were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Additionally, HT-related genes were retrieved from the UniProt and GeneCards databases. Cytoscape constructed networks for visualization. A protein–protein interaction (PPI) network analysis was constructed, and a PPI network was built using the Search Tool for the Retrieval of Interacting Genes (STRING) database. These key targets of PV were enriched and analyzed by molecular docking verification, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Results: The compound–target network included 11 compounds and 66 target genes. Key targets contained Jun proto-oncogene (JUN), hsp90aa1.1 (AKI), mitogen-activated protein kinase 1 (MAPK1), and tumor protein p53 (TP53). The main pathways included the AGE-RAGE signaling pathway, the TNF signaling pathway, the PI3K–Akt signaling pathway, and the mitogen-activated protein kinase signaling pathway. The molecular docking results revealed that the main compound identified in the Prunella vulgaris was luteolin, followed by kaempferol, which had a strong affinity for HT. Conclusion: Molecular docking studies indicated that luteolin and kaempferol were bioactive compounds of PV and might play an essential role in treating HT by regulating multiple signaling pathways.

Highlights

Prunella vulgaris (PV) is a perennial herbaceous plant in the genus Prunella1
The molecular docking assay showed that the AKI and mitogen-activated protein kinase 1 (MAPK1) proteins have a stronger affinity for Hashimoto’s thyroiditis (HT) disease molecules
The AKI and MAPK1 protein active pockets showed that the small molecules luteolin and kaempferol have a compact binding pattern (Figure 7)

Summary

Introduction

Prunella vulgaris (PV) is a perennial herbaceous plant in the genus Prunella. Prunella vulgaris (PV) is a perennial herbaceous plant in the genus Prunella1 It is a Chinese medicine widely used to treat inflammation, eye pain, and headaches (Wang et al, 2019; Chen et al, 2020). The anti-inflammatory effects of PV have been recognized during the long-term practice of traditional Chinese medicine (TCM) (hui ZRGwsbydwy, 2000). PV is combined with Western medicines, such as levothyroxine, indomethacin, or prednisone, in liquid or capsules and has been used to treat Hashimoto’s thyroiditis patients. It has been shown that PV significantly reduces the antibody titers of thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (TGAb) (Yang et al, 2007; Zhang, 2014). The potential underlying mechanisms by which PV might exert its antiinflammatory effects are poorly understood

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