Title:Network Pharmacology, Molecular Docking and Experimental Verification
Revealing the Mechanism of Fule Cream against Childhood Atopic
Dermatitis
Volume: 20
Issue: 6
Author(s): Chang Liu, Yuxin Liu, Yi Liu, Jing Guan, Ying Gao, Ling Ou, Yuenan Qi, Xiaoxi Lv*Jianmin Zhang*
Affiliation:
- Immunology
and Cancer Pharmacology Group, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute
of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
- Drug Clinical Trial Institution, Children’s Hospital, Capital Institute of Pediatrics, Beijing, 100020, China
Keywords:
Atopic dermatitis mouse model, childhood atopic dermatitis, fule cream, molecular docking, network pharmacology, bioactive ingredients.
Abstract:
Background: The Fule Cream (FLC) is an herbal formula widely used for the treatment
of pediatric atopic dermatitis (AD), however, the main active components and functional
mechanisms of FLC remain unclear. This study performed an initial exploration of the potential
acting mechanisms of FLC in childhood AD treatment through analyses of an AD mouse model
using network pharmacology, molecular docking technology, and RNA-seq analysis.
Materials and Methods: The main bioactive ingredients and potential targets of FLC were collected
from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and
SwissTargetPrediction databases. An herb-compound-target network was built using Cytoscape
3.7.2. The disease targets of pediatric AD were searched in the DisGeNET, Therapeutic Target
Database (TTD), OMIM, DrugBank and GeneCards databases. The overlapping targets between
the active compounds and the disease were imported into the STRING database for the construction
of the protein-protein interaction (PPI) network. Gene Ontology (GO) enrichment and
Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the intersection targets
were performed, and molecular docking verification of the core compounds and targets was
then performed using AutoDock Vina 1.1.2. The AD mouse model for experimental verification
was induced by MC903.
Results: The herb-compound-target network included 415 nodes and 1990 edges. Quercetin,
luteolin, beta-sitosterol, wogonin, ursolic acid, apigenin, stigmasterol, kaempferol, sitogluside
and myricetin were key nodes. The targets with higher degree values were IL-4, IL-10, IL-1α,
IL-1β, TNFα, CXCL8, CCL2, CXCL10, CSF2, and IL-6. GO enrichment and KEGG analyses
illustrated that important biological functions involved response to extracellular stimulus, regulation
of cell adhesion and migration, inflammatory response, cellular response to cytokine
stimulus, and cytokine receptor binding. The signaling pathways in the FLC treatment of pediatric
AD mainly involve the PI3K-Akt signaling pathway, cytokine‒cytokine receptor interaction,
chemokine signaling pathway, TNF signaling pathway, and NF-κB signaling pathway. The
binding energy scores of the compounds and targets indicate a good binding activity. Luteolin,
quercetin, and kaempferol showed a strong binding activity with TNFα and IL-4.
Conclusion: This study illustrates the main bioactive components and potential mechanisms of
FLC in the treatment of childhood AD, and provides a basis and reference for subsequent exploration.
