The Active Compounds and Therapeutic Mechanisms of Pentaherbs Formula for Oral and Topical Treatment of Atopic Dermatitis Based on Network Pharmacology.

Man Chu,Chun Kwok Wong,Ru He,Christopher Wai-Kei Lam,Miranda Sin-Man Tsang,Zhi Bo Quan

doi:10.3390/plants9091166

Abstract

To examine the molecular targets and therapeutic mechanism of a clinically proven Chinese medicinal pentaherbs formula (PHF) in atopic dermatitis (AD), we analyzed the active compounds and core targets, performed network and molecular docking analysis, and investigated interacting pathways. Information on compounds in PHF was obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and target prediction was performed using the Drugbank database. AD-related genes were gathered using the GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. Network analysis was performed by Cytoscape software and protein-protein interaction was analyzed by the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). The Database for Annotation, Visualization and Integrated Discovery (DAVID) Bioinformatics Resources were applied for the enrichment analysis of the potential biological process and pathways associated with the intersection targets between PHF and AD. Autodock software was used to perform protein compound docking analysis. We identified 43 active compounds in PHF associated with 117 targets, and 57 active compounds associated with 107 targets that form the main pathways linked to oral and topical treatment of AD, respectively. Among them, quercetin, luteolin, and kaempferol are key chemicals targeting the core genes involved in the oral use of PHF against AD, while apigenin, ursolic acid, and rosmarinic acid could be used in topical treatment of PHF against AD. The compound–target–disease network constructed in the current study reveals close interactions between multiple components and multiple targets. Enrichment analysis further supports the biological processes and signaling pathways identified, indicating the involvement of IL-17 and tumor necrosis factor signaling pathways in the action of PHF on AD. Our data demonstrated the main compounds and potential pharmacological mechanisms of oral and topical application of PHF in AD.

Highlights

Atopic dermatitis (AD) is a common allergic skin disease affecting all ages of people in the world, especially children [1,2]
Two-dimensional (2D) structures of the compounds were obtained from NCBI PubChem structure files, and 3D structures were built using ChemBio 3D Ultra software (CambridgeSoft, version 14.0) after energy minimization with MM2
For all the docking studies, 20 docked conformations were generated for each pair of ligand and receptor, and the energy calculations were performed employing the genetic algorithms

Summary

Introduction

Atopic dermatitis (AD) is a common allergic skin disease affecting all ages of people in the world, especially children [1,2]. While AD is not directly life-threatening, the chronic disease causes a significant burden on daily lives, affecting quality of life for the individual, their families, and the communities they live in, both socially and financially. It is characterized by redness, cracking, dryness, itchiness, thickening, and inflammation of the skin, accompanying the apoptosis of keratinocytes that compromises the quality of life of patients [6]. The dysfunction of the epidermal barrier leads to the penetration of allergens that drives dendritic cells to initiate Th2 polarization and eosinophilic inflammation [8,9]

Methods

Results

Discussion

Conclusion