Research on the Potential Mechanism of Gypenosides on Treating Thyroid-Associated Ophthalmopathy Based on Network Pharmacology

Li, Kaijun; Li, Haoyu; Xu, Wenhua; Liu, Wei; Du, Yi; He, Jianfeng

doi:10.12659/msm.917299

Cited by 15 publications

(14 citation statements)

References 39 publications

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“…IL-29 is also an activator of Janus kinase/signal transduction and activator (JAK-STAT) through STAT1, STAT2, STAT3, and STAT5 [35]. What is essential, thyroid-associated orbitopathy is an effect of the activation of JAK-STAT [36]. Moreover, IL-29 is an inductor of mitogen-activated protein kinase (MAPK), and MAPK is possibly engaged in GD development [37,38].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of IL-29 in Euthyroid Patients with Graves’ Orbitopathy: A Preliminary Study

Falkowski

Szczepanek‐Parulska

Sawicka‐Gutaj

et al. 2020

Mediators of Inflammation

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Background. The most frequent cause of hyperthyroidism is Graves’ disease (GD). Orbitopathy is the most prevalent and recognizable extrathyroidal manifestation of Graves’ disease with unrevealed pathogenesis. Interleukin 29 (IL-29) is a relatively newly discovered inflammatory cytokine. Thus, the aim of this study was to evaluate the relationship between IL-29 and Graves’ orbitopathy (GO) in euthyroid patients. Methods. Thirty-one euthyroid patients with Graves’ disease and with active GO [clinical activity score CAS≥3/7], seventeen euthyroid patients with GD but without GO, and seventy-two healthy control subjects (CS) matched for age and gender were enrolled in the study. The following parameters were evaluated in every participant: thyroid-related hormones and autoantibodies and inflammatory markers (white blood cells, hsCRP). ELISA assay was applied to measure the concentration of IL-29. Results. We found higher level of IL-29 in GO group in comparison with CS [165 (133-747) vs. 62 (62-217) pg/mL, p<0.001]. Furthermore, participants in the subgroup with GD with GO as compared with GD without GO had higher concentration of IL-29 [165 (133-747) vs. 62 (62-558) pg/mL, p=0.031]. The ROC analysis for IL-29 revealed IL-29 cut-off of 105 pg/mL (sensitivity 1.000 and specificity 0.597) as the best value significantly indicating the presence of GO in GD [area under the ROC curve (AUC): 0.739, 95% confidence interval (CI): 0.646-0.833, p<0.001]. Conclusions. The present study revealed for the first time an elevated level of IL-29 in the serum of patients with GD and GO that might suggest its involvement in the pathogenesis of GD ocular complications.

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Section: Discussionmentioning

confidence: 99%

Evaluation of IL-29 in Euthyroid Patients with Graves’ Orbitopathy: A Preliminary Study

Falkowski

Szczepanek‐Parulska

Sawicka‐Gutaj

et al. 2020

Mediators of Inflammation

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“…GPs exert pharmacological effects, such as anti-inflammatory, anti-oxidative stress, etc. 11 , 20 Actually, inflammatory response plays a significant role in endotoxin induced ALI, and severe inflammatory response also leading to apoptosis of endothelial and epithelial cell during ALI, impairing the integrity of alveolar-capillary barrier and the microvascular endothelium and alveolar epithelium barrier. In the study, LPS induced severe injury of lung tissue, and serious expression of inflammatory cytokines in vivo, while GPs effectively alleviated lung injury and improved the survival ratio of ALI mice.…”

Section: Discussionmentioning

confidence: 99%

“…The protein-protein interaction (PPI) pairs were extracted with median confidence more than 0.4. 11 The PPI network was visualized by Cytoscape software (version 3.4.0, http://www.cytoscape.org/ ). Nodes with higher degree of connectivity tend to be more essential in maintaining the stability of the entire network.…”

Section: Methodsmentioning

confidence: 99%

“…A network pharmacology analysis revealed the anti-inflammatory effects of GPs were mainly enriched in the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathway and provided potential therapeutic targets of GPs on inflammatory response. 11 The progress of ALI is accompanied by various inflammatory pathways activated and constantly magnified, eventually leading to poor prognosis. Some studies have revealed GPs inhibited the apoptosis induced by oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

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Gypenosides Inhibit Inflammatory Response and Apoptosis of Endothelial and Epithelial Cells in LPS-Induced ALI: A Study Based on Bioinformatic Analysis and in vivo/vitro Experiments

Zhu

Yuan

et al. 2021

DDDT

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Introduction: Severe inflammatory response leads to poor prognosis of acute lung injury (ALI), the role of gypenosides (GPs) on ALI is not fully clear. The study aimed at investigating the effects of GPs on ALI. Methods: We firstly established LPS-induced ALI mice model. Then, we tested whether GPs contributed to alleviate inflammatory response and lung injury of ALI in vivo. In order to identify specific mechanisms of the phenomenon, we conducted a bioinformatic analysis of LPS-induced ALI mice based on GEO database to identify hub differentially expressed genes (DEGs). PPI network of the DEGs was used to find hub-genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted based on the DAVID database to identify which pathways the genes enriched. Then, we tested whether GPs inhibited lung injury and inflammatory response via the enriched pathways. We also tested whether GPs inhibited the apoptosis of endothelial and epithelial cells secondary to severe inflammation. Results: We found GPs significantly alleviated lung injury and improved the survival rate of LPS-induced ALI mice in vivo. Bioinformatic analysis identified 20 hub-genes from DEGs, they were mainly enriched in NF-κB and TNF-α pathways. GPs could reduce the lung injury and inflammatory response via inhibiting NF-κB and TNF-α pathways in vivo. Our results indicated that GPs also inhibited inflammatory response of epithelial and endothelial cells via NF-κB and TNF-α pathways in vitro. Severe inflammatory response could also lead to apoptosis of endothelial and epithelial cells. Our results indicated that GPs effectively inhibited the apoptosis of endothelial and epithelial cells. Conclusion:Our study suggested GPs contributed to alleviated lung injury in vivo and inhibited inflammation and apoptosis of endothelial and epithelial cells in vitro, providing novel strategies for the prevention and therapy for ALI.

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“…23 Simultaneously, thyroid-associated ophthalmopathy is closely associated with JAK-STAT pathway activation. 24 IL-29 also induces mitogen-activated protein kinase (MAPK) 25 and lipopolysaccharide (LPS)-induced nuclear factor-kappa B (NF-κB) signalling pathways, 26 which are possibly involved in GD development. 27 Furthermore, IL-29 enhances the expression of Toll-like receptor 3 (TLR3), most likely via the JAK-STAT pathway 28 and Toll-like receptor 2 (TLR2) 29 which expression is activated during autoimmune thyroid disease (AITD) development.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of interleukin‐29 in autoimmune and inflammatory thyroid diseases

Falkowski

Szczepanek‐Parulska

Krygier

et al. 2021

Clinical Endocrinology

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Interleukins play an important role in the development of autoimmune disorders. Interleukin-29, abbreviated IL-29, is also called interferon lambda 1, abbreviated IFN-λ1. This protein is quite a new member of the recently discovered interferon lambda (IFN-λ) family. IL-29 is known to play a strong antiviral role. 1 However, dendritic cells and macrophages produce IL-29 during a wide range of autoimmune disorders without any underlying viral infection during pathogenesis. 2 Elevated IL-29 concentrations were found in diseases with autoimmune aetiology, such as Sjögren's syndrome, rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus and psoriasis. [3][4][5][6][7] The concentration of IL-29 was also evaluated in atopic dermatitis and asthma, where elevated levels were detected. 8,9 Moreover, concentrations of IL-29 were

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Research on the Potential Mechanism of Gypenosides on Treating Thyroid-Associated Ophthalmopathy Based on Network Pharmacology

Cited by 15 publications

References 39 publications

Evaluation of IL-29 in Euthyroid Patients with Graves’ Orbitopathy: A Preliminary Study

Evaluation of IL-29 in Euthyroid Patients with Graves’ Orbitopathy: A Preliminary Study

Gypenosides Inhibit Inflammatory Response and Apoptosis of Endothelial and Epithelial Cells in LPS-Induced ALI: A Study Based on Bioinformatic Analysis and in vivo/vitro Experiments

Evaluation of interleukin‐29 in autoimmune and inflammatory thyroid diseases

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