Network pharmacology and experimental validation to identify the potential mechanism of Hedyotis diffusa Willd against rheumatoid arthritis

Deng, Hui; Jiang, Jing; Zhang, Sisi; Wu, Lijuan; Zhang, Qinglian; Sun, Wenmin

doi:10.1038/s41598-022-25579-3

Cited by 10 publications

(5 citation statements)

References 66 publications

(69 reference statements)

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“…From the TF–mRNA–miRNA regulatory network we predicted, it can be seen that there are some common transcription factors (such as ESR1) and miRNAs (including hsa-miR-671-5p, hsa-miR-939-5p, hsa-miR-6752-5p, hsa-miR-6858-5p, hsa-miR-6824-5p, hsa-miR-6765-5p, and hsa-miR-6089) between FAM209B and PTGES. Among them, ESR1 was a hub gene in many autoimmune diseases ( 57 ), including type 1 diabetes ( 58 ), systemic lupus erythematosus ( 59 ), and rheumatoid arthritis ( 60 ). ESR1 was widely expressed in thymocytes, T cells, B lymphocytes, etc., which serve roles in the functioning of the immune system and reducing inflammation.…”

Section: Discussionmentioning

confidence: 99%

Identification of biomarkers associated with immune scores in diabetic retinopathy

Zhang,

Zhu,

Wang

et al. 2023

Front. Endocrinol.

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BackgroundDiabetic retinopathy (DR) causes irreversible visual impairment in diabetes mellitus (DM) patients. Immunity played a crucial role in DR. Nevertheless, the triggering mechanism of DR was not yet thorough enough. Herein, we aim to identify the immune-associated genes as biomarkers associated with immune scores that can distinguish early DR from DM without DR.MethodsIn this study, total RNA of peripheral blood mononuclear cell (PBMC) samples from 15 non-proliferative DR patients and 15 DM patients without DR were collected and the transcriptome sequencing data were extracted. Firstly, the target genes were obtained by intersecting the differentially expressed genes (DEGs), which were screened by “limma”, and the module genes (related to immune scores), which were screened by “WGCNA”. In order to screen for the crucial genes, three machine learning algorithms were implemented, and a receiver operating characteristic (ROC) curve was used to obtain the diagnostic genes. Moreover, the gene set enrichment analysis (GSEA) was performed to understand the function of diagnostic genes, and analysis of the proportions of immune cells and their association with diagnostic genes was performed to analyze the pathogenesis of DR. Furthermore, the regulatory network of TF–mRNA–miRNA was built to reveal the possible regulation of diagnostic genes. Finally, the quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the mRNA level of diagnostic genes.ResultsA total of three immune-associated diagnostic genes, namely, FAM209B, POM121L1P, and PTGES, were obtained, and their expression was increased in PBMC samples of DR, and qRT-PCR results confirmed these results. Moreover, the functions of these genes were associated with immune response. The expression of POM121L1P and PTGES was significantly negatively associated with naive B cells, and the expression of FAM209B was significantly negatively associated with immature dendritic cells. Moreover, ESR1 could regulate both FAM209B and PTGES.ConclusionThis study identified three immune-associated diagnostic genes, FAM209B, POM121L1P, and PTGES, as biomarkers associated with immune scores in DR for the first time. This finding might proffer a novel perspective of the triggering mechanism of DR, and help to understand the role of immune-associated genes in the molecular mechanism of DR more deeply.

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Section: Discussionmentioning

confidence: 99%

Identification of biomarkers associated with immune scores in diabetic retinopathy

Zhang,

Zhu,

Wang

et al. 2023

Front. Endocrinol.

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“…The layout and network options were selected. From the 552 enriched pathways, eight significant KEGG pathways [ 37 ] were filtered and visually represented as a split doughnut pie chart within the network using a different color palette ( Figure 1B ) [ 38 , 39 ]. The purpose of drug–target enrichment is to unveil significant therapeutic targets, offering intricate guidance for drug discovery and development, with a special emphasis on drug–target checkpoints.…”

Section: Software and Methodsmentioning

confidence: 99%

Integrating network pharmacology and in silico analysis deciphers Withaferin-A’s anti-breast cancer potential via hedgehog pathway and target network interplay

Srinivasan,

Gangurde,

Chandane

et al. 2024

Briefings in Bioinformatics

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This study examines the remarkable effectiveness of Withaferin-A (WA), a withanolide obtained from Withania somnifera (Ashwagandha), in encountering the mortiferous breast malignancy, a global peril. The predominant objective is to investigate WA’s intrinsic target proteins and hedgehog (Hh) pathway proteins in breast cancer targeting through the application of in silico computational techniques and network pharmacology predictions. The databases and webtools like Swiss target prediction, GeneCards, DisGeNet and Online Mendelian Inheritance in Man were exploited to identify the common target proteins. The culmination of the WA network and protein–protein interaction network were devised using Stitch and String web tools, through which the drug–target network of 30 common proteins was constructed employing Cytoscape-version 3.9. Enrichment analysis was performed by incorporating Gprofiler, Metascape and Cytoscape plugins. David compounded the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, and enrichment was computed through bioinformatics tools. The 20 pivotal proteins were docked harnessing Glide, Schrodinger Suite 2023-2. The investigation was governed by docking scores and affinity. The shared target proteins underscored the precise Hh and WA network roles with the affirmation enrichment P-value of <0.025. The implications for hedgehog and cancer pathways were profound with enrichment (P < 0.01). Further, the ADMET and drug-likeness assessments assisted the claim. Robust interactions were noticed with docking studies, authenticated through molecular dynamics, molecular mechanics generalized born surface area scores and bonds. The computational investigation emphasized WA’s credible anti-breast activity, specifically with Hh proteins, implying stem-cell-level checkpoint restraints. Rigorous testament is imperative through in vitro and in vivo studies.

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“…Hedyotis diffusa , belongs to the Rubiaceae plant family. This plant is renowned for its anti‐inflammatory, immune regulation, and antioxidant properties (Deng et al., 2023; He et al., 2018). Recent studies have demonstrated the potential inhibitory effects of certain components of H. diffusa on enzymes associated with Alzheimer's disease.…”

Section: Introductionmentioning

confidence: 99%

Network pharmacology and experimental verification to explore the effect of Hedyotis diffusa on Alzheimer's disease

Chen,

Rao,

et al. 2024

Chem Biol Drug Des

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This study aimed to explore the active components and the effect of Hedyotis diffusa (HD) against Alzheimer's disease (AD) via network pharmacology, molecular docking, and experimental evaluations. We conducted a comprehensive screening process using the TCMSP, Swiss Target Prediction, and PharmMapper databases to identify the active components and their related targets in HD. In addition, we collected potential therapeutic targets of AD from the Gene Cards, Drugbank, and OMIM databases. Afterward, we utilized Cytoscape to establish both protein–protein interaction (PPI) networks and compound‐target (C‐T) networks. To gain further insights into the functional aspect, we performed GO and KEGG pathway analyses using the David database. Next, we employed Autodock vina to estimate the binding force between the components and the hub genes. To validate our network pharmacology findings, we conducted relevant experiments on Caenorhabditis elegans, further confirming the reliability of our results. Then a total of six active compounds and 149 therapeutic targets were detected. Through the analysis of the association between active compounds, therapeutic targets, and signaling pathways, it was observed that the therapeutic effect of HD primarily encompassed the inhibition of Aβ, suppression of AChE activity, and mitigating oxidative stress. Additionally, our investigation revealed that the key active compounds in HD primarily consisted of iridoids, which exhibited resistance against AD by acting on the Alzheimer's disease pathway and the AGE‐RAGE signaling pathway in diabetic complications.

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Network pharmacology and experimental validation to identify the potential mechanism of Hedyotis diffusa Willd against rheumatoid arthritis

Cited by 10 publications

References 66 publications

Identification of biomarkers associated with immune scores in diabetic retinopathy

Identification of biomarkers associated with immune scores in diabetic retinopathy

Integrating network pharmacology and in silico analysis deciphers Withaferin-A’s anti-breast cancer potential via hedgehog pathway and target network interplay

Network pharmacology and experimental verification to explore the effect of Hedyotis diffusa on Alzheimer's disease

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