Bioinformatics and Network Pharmacology Identify the Therapeutic Role and Potential Mechanism of Melatonin in AD and Rosacea
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...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:151de9b290e04633b669aa2b5d8732ee2021-12-01T02:59:45ZBioinformatics and Network Pharmacology Identify the Therapeutic Role and Potential Mechanism of Melatonin in AD and Rosacea1664-322410.3389/fimmu.2021.756550https://doaj.org/article/151de9b290e04633b669aa2b5d8732ee2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.756550/fullhttps://doaj.org/toc/1664-3224Rosacea 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.Huaxiong ZhangHuaxiong ZhangHuaxiong ZhangYiya ZhangYiya ZhangYiya ZhangYangfan LiYangfan LiYaling WangYaling WangSha YanSha YanSan XuSan XuSan XuZhili DengZhili DengZhili DengXinling YangHongfu XieHongfu XieHongfu XieJi LiJi LiJi LiJi LiFrontiers Media S.A.articlerosaceaADMLTnetwork pharmacologyinflammationangiogenesisImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
rosacea AD MLT network pharmacology inflammation angiogenesis Immunologic diseases. Allergy RC581-607 |
| spellingShingle |
rosacea AD MLT network pharmacology inflammation angiogenesis Immunologic diseases. Allergy RC581-607 Huaxiong Zhang Huaxiong Zhang Huaxiong Zhang Yiya Zhang Yiya Zhang Yiya Zhang Yangfan Li Yangfan Li Yaling Wang Yaling Wang Sha Yan Sha Yan San Xu San Xu San Xu Zhili Deng Zhili Deng Zhili Deng Xinling Yang Hongfu Xie Hongfu Xie Hongfu Xie Ji Li Ji Li Ji Li Ji Li Bioinformatics and Network Pharmacology Identify the Therapeutic Role and Potential Mechanism of Melatonin in AD and Rosacea |
| description |
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. |
| format |
article |
| author |
Huaxiong Zhang Huaxiong Zhang Huaxiong Zhang Yiya Zhang Yiya Zhang Yiya Zhang Yangfan Li Yangfan Li Yaling Wang Yaling Wang Sha Yan Sha Yan San Xu San Xu San Xu Zhili Deng Zhili Deng Zhili Deng Xinling Yang Hongfu Xie Hongfu Xie Hongfu Xie Ji Li Ji Li Ji Li Ji Li |
| author_facet |
Huaxiong Zhang Huaxiong Zhang Huaxiong Zhang Yiya Zhang Yiya Zhang Yiya Zhang Yangfan Li Yangfan Li Yaling Wang Yaling Wang Sha Yan Sha Yan San Xu San Xu San Xu Zhili Deng Zhili Deng Zhili Deng Xinling Yang Hongfu Xie Hongfu Xie Hongfu Xie Ji Li Ji Li Ji Li Ji Li |
| author_sort |
Huaxiong Zhang |
| title |
Bioinformatics and Network Pharmacology Identify the Therapeutic Role and Potential Mechanism of Melatonin in AD and Rosacea |
| title_short |
Bioinformatics and Network Pharmacology Identify the Therapeutic Role and Potential Mechanism of Melatonin in AD and Rosacea |
| title_full |
Bioinformatics and Network Pharmacology Identify the Therapeutic Role and Potential Mechanism of Melatonin in AD and Rosacea |
| title_fullStr |
Bioinformatics and Network Pharmacology Identify the Therapeutic Role and Potential Mechanism of Melatonin in AD and Rosacea |
| title_full_unstemmed |
Bioinformatics and Network Pharmacology Identify the Therapeutic Role and Potential Mechanism of Melatonin in AD and Rosacea |
| title_sort |
bioinformatics and network pharmacology identify the therapeutic role and potential mechanism of melatonin in ad and rosacea |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/151de9b290e04633b669aa2b5d8732ee |
| work_keys_str_mv |
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