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

酒渣鼻 药理学 炎症 医学 机制(生物学) 血管生成 生物 生物信息学 免疫学 癌症研究 皮肤病科 认识论 哲学 痤疮
作者
Huaxiong Zhang,Yiya Zhang,Yangfan Li,Yaling Wang,Sha Yan,San Xu,Zhili Deng,Xinling Yang,Hongfu Xie,Ji Li
出处
期刊:Frontiers in Immunology [Frontiers Media SA]
卷期号:12 被引量:40
标识
DOI:10.3389/fimmu.2021.756550
摘要

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 in vivo and in vitro . 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 via regulating inflammation and angiogenesis.
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