Bioinformatics and Network Pharmacology Identify the Therapeutic Role and Potential Mechanism of Melatonin in AD and Rosacea

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2021 Dec 13

PMID 34899707

Citations 23

Authors

Huaxiong Zhang

Yiya Zhang

Yangfan Li

Yaling Wang

Sha Yan

San Xu

Zhili Deng

XinLing Yang

Hongfu Xie

Ji Li

Affiliations

Soon will be listed here.

Abstract

Rosacea is significantly associated with dementia, particularly Alzheimer's disease (AD). However, the common underlying molecular mechanism connecting these two diseases remains limited. This study aimed to reveal the common molecular regulatory networks and identify the potential therapeutic drugs for rosacea and AD. There were 747 overlapped DEGs (ol-DEGs) that were detected in AD and rosacea, enriched in inflammation-, metabolism-, and apoptosis-related pathways. Using the TF regulatory network analysis, 37 common TFs and target genes were identified as hub genes. They were used to predict the therapeutic drugs for rosacea and AD using the DGIdb/CMap database. Among the 113 predicted drugs, melatonin (MLT) was co-associated with both RORA and IFN-γ in AD and rosacea. Subsequently, network pharmacology analysis identified 19 pharmacological targets of MLT and demonstrated that MLT could help in treating AD/rosacea partly by modulating inflammatory and vascular signaling pathways. Finally, we verified the therapeutic role and mechanism of MLT on rosacea and . We found that MLT treatment significantly improved rosacea-like skin lesion by reducing keratinocyte-mediated inflammatory cytokine secretion and repressing the migration of HUVEC cells. In conclusion, this study contributes to common pathologies shared by rosacea and AD and identified MLT as an effective treatment strategy for rosacea and AD regulating inflammation and angiogenesis.

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