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

Zhang, Huaxiong; Zhang, Yiya; Li, Yangfan; Wang, Yaling; Sha, Yan; Xu, San; Deng, Zhili; Yang, Xinling; Xie, Hongfu; Li, Ji

doi:10.3389/fimmu.2021.756550

Cited by 34 publications

(24 citation statements)

References 77 publications

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“…The expression of inflammatory factors, TNF-α and IL-1β, have been shown to upregulated in the skin of rosacea patients and increase in rosacea-like mice inflammation model. 17 In this model, immunofluorescence staining showed that thalidomide reduced the expression of inflammatory cytokine TNF-α in LL-37-induced skin ( Figure 4 ). The expression of TNF-α and IL-1β in skin protein induced by LL-37 were also upregulated, while thalidomide decreased the expression ( Figures 5 ).…”

Section: Resultsmentioning

confidence: 84%

Thalidomide Attenuates Skin Lesions and Inflammation in Rosacea-Like Mice Induced by Long-Term Exposure of LL-37

Kang¹,

Zhang²,

He³

et al. 2022

DDDT

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Purpose Most of the existing studies focus on the early inflammation of rosacea, with few interventions on the later development of fibrosis and the relationship between thalidomide and rosacea. The purpose of this study was to construct a long-term induction model and explore the effects of thalidomide on the later stage of inflammation and early stage of fibrosis in rosacea. Patients and Methods BALB/c male mice were randomly divided into four groups: control group, control plus thalidomide group, LL-37 group and LL-37 plus thalidomide group, Intradermal and intraperitoneal injections were given. After repeated induction, skin changes were recorded by taking photos. The animals were sacrificed, the back skin was used for HE staining and VG staining to detect histomorphological characteristics. Immunofluorescence staining and Western blot were used to detect the expression of inflammatory and fibrosis-related factors. Results The results were compared with the early stage of the model, wherein the skin inflammation of the 20-day mice was more obvious with a trend of fibrosis. Compared with the control group, histopathological examination showed that the inflammatory cell infiltration in the LL-37 group was significantly increased, and the skin was thickened with collagen deposition. LL-37 induction significantly increased the expression of inflammatory markers (eg, TNF-α and IL-1β) and fibrotic markers (eg, COL1, α-SMA, vimentin and N-Cadherin). Intervention with thalidomide significantly reduced erythema, inflammatory cell infiltration, collagen deposition, and down-regulate the expression of inflammation and fibrosis related factors in rosacea mice. Conclusion The long-term continuous induction of LL-37 in mice could simulate the occurrence and development of rosacea, and thalidomide could ameliorate the rosacea induced by long-term exposure to LL-37 by regulating inflammatory infiltration, collagen deposition and fibrosis-related processes.

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Section: Resultsmentioning

confidence: 84%

Thalidomide Attenuates Skin Lesions and Inflammation in Rosacea-Like Mice Induced by Long-Term Exposure of LL-37

Kang¹,

Zhang²,

He³

et al. 2022

DDDT

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“…All the retrieved targets were transformed into their o cial symbols using the UniProt Knowledgebase search function (http://www.uniprot.org/) in the Protein Database (UniProt). Gene Cards (https://www.genecards.org/) and OMIM (https://omim.org/) [17] were utilized to gather the AD-related genes. Then, promising therapeutic targets were submitted to STRING (https://string-db.org/) for protein-protein interaction (PPI) discovery, and Cytoscape 3.8.0 was used to form a PPI network.…”

Section: Gut Microbiota-metabolite Correlation Analysismentioning

confidence: 99%

Anti-Alzheimers molecular mechanism of icariin: Insights from gut microbiota and metabolome combined network pharmacology

Liu

Wang

et al. 2023

Preprint

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Background Icariin (ICA), an active ingredient extracted from a natural plant called Epimedii, has shown a broad application prospect in the treatment of Alzheimer's disease (AD). Nevertheless, its potential therapeutic mechanism remains largely unknown.The present study aims to investigate the therapeutic effect and the underlying mechanism of ICA on AD by an integrated analysis of gut microbiota and metabolomics. Methods The cognitive impairment of mice was measured using the Morris Water Maze. Hematoxylin and eosin staining was used to identify the AD-induced pathologic change. 16S rRNA sequencing and multi-metabolomics were performed to analyze the alterations in microbiota and serum/fecal metabolism. Results Our results demonstrated that ICA intervention could markedly improve cognitive dysfunction in APP/PS1 mice and typical AD pathologies in the hippocampus of APP/PS1 mice. Gut microbiota analysis showed that ICA administration could reverse the imbalance of gut microbes in APP/PS1 mice by elevating the proportion of Akkermansia and reducing the proportion of Alistipe. Metabolomic analysis revealed AD-induced metabolic disorder was improved by ICA via glycerophospholipid metabolism and sphingolipid metabolism. Correlation analysis suggested that these were closely related to the abundance of Alistipe and Akkermansia. Conclusion These findings indicated that ICA may serve as a promising therapeutic approach for AD, and that the ICA-mediated protective effects were associated with the amelioration of microbiota disturbance and metabolic disorder.

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“…The idea of network medicine is based on the hypothesis that diseases occur due to the disruption of biological networks responsible for homeostasis as a result of activation or deactivation of certain proteins or biochemical reactions, which eventually disturb the balance of normal physiology pathways [ 313 , 314 , 315 ]. Hence, disease networks are complex disease processes that are caused by irregular diverse genes, proteins, and signaling cascades [ 308 ].…”

Section: Exploiting Network Biology Approaches In Alzheimer’s Disease...mentioning

confidence: 99%

“…The design of MTDL hypothesizes that successful disease-modifying treatments of AD should target systems biology pathways rather than selectively targeting individual proteins or drug targets [ 321 , 322 ]. As such, MTDLs can be defined as drugs and/or technologies designed to interact with more than one target involved in the pathogenesis of a defined disease [ 322 , 323 , 324 , 325 , 326 , 327 , 328 ], surpassing the “one-molecule, one-target” model [ 313 , 319 ]. It has been theorized that potent MTDL should simultaneously target the typical signs of AD, such as the irregular accumulation of Aβ peptides [ 329 , 330 , 331 , 332 , 333 ], tauopathies [ 334 , 335 , 336 , 337 ], and the cholinergic insufficiency in CNS [ 106 , 338 , 339 ].…”

Section: Exploiting Network Biology Approaches In Alzheimer’s Disease...mentioning

confidence: 99%

A Review of the Recent Advances in Alzheimer’s Disease Research and the Utilization of Network Biology Approaches for Prioritizing Diagnostics and Therapeutics

et al. 2022

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Alzheimer’s disease (AD) is a polygenic multifactorial neurodegenerative disease that, after decades of research and development, is still without a cure. There are some symptomatic treatments to manage the psychological symptoms but none of these drugs can halt disease progression. Additionally, over the last few years, many anti-AD drugs failed in late stages of clinical trials and many hypotheses surfaced to explain these failures, including the lack of clear understanding of disease pathways and processes. Recently, different epigenetic factors have been implicated in AD pathogenesis; thus, they could serve as promising AD diagnostic biomarkers. Additionally, network biology approaches have been suggested as effective tools to study AD on the systems level and discover multi-target-directed ligands as novel treatments for AD. Herein, we provide a comprehensive review on Alzheimer’s disease pathophysiology to provide a better understanding of disease pathogenesis hypotheses and decipher the role of genetic and epigenetic factors in disease development and progression. We also provide an overview of disease biomarkers and drug targets and suggest network biology approaches as new tools for identifying novel biomarkers and drugs. We also posit that the application of machine learning and artificial intelligence to mining Alzheimer’s disease multi-omics data will facilitate drug and biomarker discovery efforts and lead to effective individualized anti-Alzheimer treatments.

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

Cited by 34 publications

References 77 publications

Thalidomide Attenuates Skin Lesions and Inflammation in Rosacea-Like Mice Induced by Long-Term Exposure of LL-37

Thalidomide Attenuates Skin Lesions and Inflammation in Rosacea-Like Mice Induced by Long-Term Exposure of LL-37

Anti-Alzheimers molecular mechanism of icariin: Insights from gut microbiota and metabolome combined network pharmacology

A Review of the Recent Advances in Alzheimer’s Disease Research and the Utilization of Network Biology Approaches for Prioritizing Diagnostics and Therapeutics

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