scholarly journals Exploration of Anti-inflammatory Mechanism of Forsythiaside A and Forsythiaside B in CuSO4-Induced Inflammation in Zebrafish by Metabolomic and Proteomic Analyses

2019 ◽  
Author(s):  
Lihong Gong ◽  
Linyuan Yu ◽  
Xiaohong Gong ◽  
Cheng Wang ◽  
Naihua Hu ◽  
...  
Keyword(s):  
Sugar Metabolism ◽  
Amino Sugar ◽  
Zebrafish Model ◽  
Zebrafish Larvae ◽  
Chemically Induced ◽  
Inflammatory Mechanism ◽  
Forsythia Suspensa ◽  
Proteomic Analyses ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Abstract Background: Inflammation is a general pathological phenomenon that operates during severe disturbance of homeostasis. Forsythiaside A (FA) and Forsythiaside B (FB) are isolated from air-dried fruits of Forsythia suspensa, which show a significant effect against inflammation. However, the anti-inflammatory effect and therapeutic mechanism have not yet been clarified in zebrafish. Methods: In this study, the anti-inflammatory effects of FA and FB were investigated in CuSO4-induced zebrafish model. Intracellular ROS and NO generation in zebrafish were performed using fluorescent probe dyes. Metabolomics and proteomics using liquid chromatography mass spectrometry were carried out to identify the expression of metabolites and proteins associated with chemically induced inflammation in zebrafish larvae. Quantitative PCR was performed to detect the progressive changes in the genes.Results: FA and FB inhibited neutrophils migration to the damaged neuromasts and remarkably reduced CuSO4-induced ROS and NO generation in zebrafish. Metabolomics analyses indicated that the Nicotinate and nicotinamide metabolism, Amino sugar and nucleotide sugar metabolism, Pyrimidine metabolism and Purine metabolism were mainly involved. The proteomic analyses identified 146 differentially expressed proteins, among which, the expression of collagen (col2a1b, col9a2, col9a1b), nme3, wdr3, mrps7, srpx, gch2, ptpn11a, rcvrn2, nit2, scaf4a and zgc:162509 were all reversed both in FA and FB groups. FA and FB could reverse the abnormal expression of these metabolites and proteins to alleviate chemical damage to the neuromasts in the lateral line of zebrafish.Conclusions: FA and FB possess remarkable anti-inflammatory effect and could be used to protect chemically induced neuromasts damage in zebrafish larvae.

scholarly journals Exploration of Anti-inflammatory Mechanism of Forsythiaside A and Forsythiaside B in CuSO4-Induced Inflammation in Zebrafish by Metabolomic and Proteomic Analyses

2020 ◽  
Author(s):  
Lihong Gong ◽  
Linyuan Yu ◽  
Xiaohong Gong ◽  
Cheng Wang ◽  
Naihua Hu ◽  
...  
Keyword(s):  
Collagen Type ◽  
Quantitative Polymerase Chain Reaction ◽  
Nucleoside Diphosphate Kinase ◽  
Fluorescence Probes ◽  
Protein Biomarkers ◽  
Zebrafish Larvae ◽  
Inflammatory Mechanism ◽  
Forsythia Suspensa ◽  
Proteomic Analyses ◽  
Anti Inflammatory

Abstract Background: Inflammation is a general pathological phenomenon during severe disturbances to the homeostasis. Forsythiaside A (FA) and Forsythiaside B (FB), isolated from the dried fruit of Forsythia suspensa (Thunb.) Vahl, are phenylethanoid compounds that show a significant anti-inflammatory effect. However, the properties and therapeutic mechanisms of this effect have not yet been systematically elucidated.Methods: In this study, the anti-inflammatory effects of FA and FB were investigated in CuSO4-induced inflammation in zebrafish larvae. Intracellular generation of reactive oxygen species (ROS) and nitric oxide (NO) was investigated using fluorescence probes. Metabolomic and proteomic analyses using liquid chromatography-mass spectrometry were carried out to identify the expressions of metabolites and proteins associated with the anti-inflammatory mechanism of FA and FB. Quantitative polymerase chain reaction (PCR) was performed to detect the progressive changes in gene expression.Results: FA and FB inhibited neutrophils migration to the damaged neuromasts and remarkably reduced CuSO4-induced ROS and NO generation in zebrafish larvae. Metabolomic analysis pointed to the involvement of Nicotinate and nicotinamide metabolism, Energy metabolism, Pyrimidine metabolism, and Purine metabolism. Proteomic analysis identified 146 differentially-expressed proteins between the control and model groups. These included Collagen [collagen type II alpha 1b precursor (col2a1b), collagen alpha-2(IX) chain precursor (col9a2), collagen type IX alpha I precursor (col9a1b)], Nucleoside diphosphate kinase 3 isoform X1 (Nme3), WD repeat-containing protein 3 (Wdr3), and 28S ribosomal protein S7 mitochondrial precursor (Mrps7). FA and FB were shown to reverse the abnormal expressions of potential metabolite and protein biomarkers and alleviate CuSO4-induced damage to the neuromasts in the zebrafish lateral line.Conclusions: Our results indicate that FA and FB possess remarkable anti-inflammatory properties, protecting against CuSO4-induced neuromasts damage in zebrafish larvae. The results also suggest a multi-component and multi-regulatory therapeutic mechanism for FA and FB.

scholarly journals Exploration of Anti-inflammatory Mechanism of Forsythiaside A and Forsythiaside B in CuSO4-Induced Inflammation in Zebrafish by Metabolomic and Proteomic Analyses

2020 ◽  
Author(s):  
Lihong Gong ◽  
Linyuan Yu ◽  
Xiaohong Gong ◽  
Cheng Wang ◽  
Naihua Hu ◽  
...  
Keyword(s):  
Collagen Type ◽  
Quantitative Polymerase Chain Reaction ◽  
Nucleoside Diphosphate Kinase ◽  
Model Group ◽  
Protein Biomarkers ◽  
Zebrafish Larvae ◽  
Inflammatory Mechanism ◽  
Forsythia Suspensa ◽  
Therapeutic Mechanism ◽  
Anti Inflammatory

Abstract Background: Inflammation is a general pathological phenomenon during severe disturbance of homeostasis. Forsythiaside A (FA) and Forsythiaside B (FB) are phenylethanoid components isolated from dried fruits of Forsythia suspensa (Thunb.) Vahl., which show a significant effect against inflammation. However, the anti-inflammatory properties and therapeutic mechanisms of FA and FB have not yet been systematically clarified. Methods: In this study, the anti-inflammatory effects of FA and FB were investigated in CuSO4-induced inflammation in zebrafish. Intracellular ROS and NO generation in zebrafish were investigated using fluorescent probes. Metabolomics and proteomics analyses using liquid chromatography mass spectrometry were carried out to identify the expressions of metabolites and proteins associated with the treatment of FA and FB in CuSO4-induced inflammation in zebrafish larvae. Quantitative polymerase chain reaction (PCR) was performed to detect the progressive changes in genes. Results: FA and FB inhibited neutrophils migration to the damaged neuromasts and remarkably reduced CuSO4-induced ROS and NO generation in zebrafish. Metabolomic analysis indicated that Nicotinate and nicotinamide metabolism, Energy metabolism, Pyrimidine metabolism and Purine metabolism were mainly involved. Proteomic analysis identified 146 differentially expressed proteins between control and model group. The changed expressions of Collagen (collagen type II alpha 1b precursor (col2a1b), collagen alpha-2(IX) chain precursor (col9a2), collagen type IX alpha I precursor (col9a1b)), nucleoside diphosphate kinase 3 isoform X1 (Nme3), WD repeat-containing protein 3 (Wdr3), 28S ribosomal protein S7 mitochondrial precursor (Mrps7) in model group were all reversed after being treated by FA or FB. FA and FB could reverse the abnormal expressions of potential metabolite and protein biomarkers to alleviate CuSO4 damage to the neuromasts in the lateral line of zebrafish. Conclusions: Our results indicated that FA and FB possessed remarkable anti-inflammatory activities against CuSO4-induced neuromasts damage in zebrafish larvae, and suggested a multi-component and multi-regulatory therapeutic mechanism of FA and FB.

scholarly journals Protective Effect of Phillyrin on Lethal LPS-Induced Neutrophil Inflammation in Zebrafish

2017 ◽  
Vol 43 (5) ◽  
pp. 2074-2087 ◽  
Author(s):  
Liling Yang ◽  
Xiangjun Zhou ◽  
Weijuan Huang ◽  
Qin Fang ◽  
Jianlan Hu ◽  
...  
Keyword(s):  
Signalling Pathway ◽  
Dependent Manner ◽  
Zebrafish Model ◽  
Lps Challenge ◽  
Cell Counts ◽  
Tnf Α ◽  
Forsythia Suspensa ◽  
Anti Inflammatory

Background/Aims: Forsythia suspensa Vahl. (Oleaceae) fruits are widely used in traditional Chinese medicine to treat pneumonia, typhoid, dysentery, ulcers and oedema. Antibacterial and anti-inflammatory activities have been reported for phillyrin (PHN), the main ingredient in Forsythia suspensa Vahl fruits, in vitro. However, the underlying mechanisms in vivo remain poorly defined. In this study, we discovered that PHN exerted potent anti-inflammatory effects in lethal LPS-induced neutrophil inflammation by suppressing the MyD88-dependent signalling pathway in zebrafish. Methods: LPS-yolk microinjection was used to induce a lethal LPS-infected zebrafish model. The effect of PHN on the survival of zebrafish challenged with lethal LPS was evaluated using survival analysis. The effect of PHN on neutrophil inflammation grading in vivo was assessed by tracking neutrophils with a transgenic line. The effects of PHN on neutrophil production and migration were analysed by SB+ cell counts during consecutive hours after modelling. Additionally, key cytokines and members of the MyD88 signalling pathway that are involved in inflammatory response were detected using quantitative RT-PCR. To assess gene expression changes during consecutive hours after modelling, the IL-1β, IL-6, TNF-α, MyD88, TRIF, ERK1/2, JNK, IκBa and NF-κB expression levels were measured. Results: PHN could protect zebrafish against a lethal LPS challenge in a dose-dependent manner, as indicated by decreased neutrophil infltration, reduced tissue necrosis and increased survival rates. Up-regulated IL-1β, IL-6 and TNF-α expression also showed the same tendencies of depression by PHN. Critically, PHN significantly inhibited the LPS-induced activation of MyD88, IκBa, and NF-κB but did not affect the expression of ERK1/2 MAPKs or JNK MAPKs in LPS-stimulated zebrafish. Additionally, PHN regulated the MyD88/IκBα/NF-κB signalling pathway by controlling IκBα, IL-1β, IL-6, and TNF-α expression. Conclusion: This study provides a rationale for the clinical application of PHN as an anti-inflammatory agent.

Antinociceptive and Anti-Inflammatory Activities ofCuscuta chinensisSeeds in Mice

2014 ◽  
Vol 42 (01) ◽  
pp. 223-242 ◽  
Author(s):  
Jung-Chun Liao ◽  
Wen-Te Chang ◽  
Meng-Shiou Lee ◽  
Yung-Jia Chiu ◽  
Wei-Kai Chao ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Inflammatory Diseases ◽  
Antinociceptive Effect ◽  
Inflammatory Mechanism ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Highly Correlated ◽  
Cuscuta Chinensis ◽  
Inflammatory Effect

The seeds of Cuscuta chinensis, Cuscutae Semen, are commonly used as a medicinal material for treating the aching and weakness of the loins and knees, tonifying the defects of the liver and the kidney, and treating the diarrhea due to hypofunction of the kidney and the spleen. Since aching and inflammation are highly correlated with such diseases, the aim of this study is to investigate the possible antinociceptive and anti-inflammatory mechanisms of the seeds of C. chinensis. The antinociceptive effect of the seeds of C. chinensis was evaluated via the acetic acid-induced writhing response and formalin-induced paw licking methods. The anti-inflammatory effect was evaluated via the λ-carrageenan induced mouse paw edema method. The results found that 100 and 500 mg/kg of the methanol extract of the seeds of C. chinensis( CCMeOH) significantly decreased (p < 0.01 and p < 0.001, respectively) the writhing response in the acetic acid assay. Additionally, 20–500 mg/kg of CCMeOHsignificantly decreased licking time at the early (20 and 100 mg/kg, p < 0.001) and late phases (100 mg/kg, p < 0.01; 500 mg/kg, p < 0.001) of the formalin test, respectively. Furthermore, CCMeOH(100 and 500 mg/kg) significantly decreased (p < 0.01 and p < 0.001, respectively) edema paw volume four hours after λ-carrageenan had been injected. The results in the following study also revealed that the anti-inflammatory mechanism of CCMeOHmay be due to declined levels of NO and MDA in the edema paw by increasing the activities of SOD, GPx and GRd in the liver. In addition, CCMeOHalso decreased IL-1β, IL-6, NF-κB, TNF-α, and COX-2 levels. This is the first study to demonstrate the possible mechanisms for the antinociceptive and anti-inflammatory effects of CCMeOHin vivo. Thus, it provides evidence for the treatment of Cuscutae Semen in inflammatory diseases.

scholarly journals Anti-inflammatory effect of lipophilic grape seed proanthocyanidin in RAW 264.7 cells and a zebrafish model

2020 ◽  
Vol 75 ◽  
pp. 104217
Author(s):  
Linli Zhang ◽  
Jun Chen ◽  
Hejing Liao ◽  
Changhong Li ◽  
Mingshun Chen
Keyword(s):  
Grape Seed ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Zebrafish Model ◽  
Grape Seed Proanthocyanidin ◽  
Anti Inflammatory ◽  
Inflammatory Effect

scholarly journals Low Molecular Weight Heparin Improves the Inflammatory State of Acute Sinusitis Rats Through Inhibiting the TLR4-MyD88-NF-κB Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Tong Wu ◽  
Sihan He ◽  
Zan Jiao ◽  
Xiang Liang ◽  
Yu Chen ◽  
...  
Keyword(s):  
Nasal Mucosa ◽  
Acute Sinusitis ◽  
Low Molecular Weight ◽  
Upper Respiratory Tract ◽  
Inflammatory Mechanism ◽  
Upper Respiratory ◽  
Anti Inflammatory ◽  
Experimental Group ◽  
Inflammatory Effect ◽  
Respiratory Tract Inflammation

Introduction: Low molecular weight heparin (LMWH), a natural sulfated glycosaminoglycan with an affinity for proangiogenic factors, is produced by chemical or enzymatic depolymerization of unfractionated heparin (UFH). Known for its anticoagulant effects, LMWH has recently been reported to have a strong anti-inflammatory effect on colitis, myocarditis, and airway inflammation. However, as a newly-developed drug, its anti-inflammatory mechanism in upper respiratory tract inflammation has not been well-studied.Methods: SD rats were randomly divided into control and experimental groups. The experimental group was established by building an acute nasal sinusitis model with expansion sponges mixed with Streptococcus pneumoniae. Then the experimental group rats were subcutaneously injected with different concentrations of LMWH. After seven consecutive days of injection, some rats were sacrificed, and blood and nasal mucosa samples were taken to determine their inflammation status. The remaining acute sinusitis rats were randomly selected for a week of nasal irrigation with normal saline or saline mixed with different concentrations of LMWH. One week later, rats were sacrificed, and samples of blood and nasal mucosa were taken to determine the inflammation status.Results: Rat nasal mucosa in the model group had obvious inflammation. The degree of nasal mucosa inflammation damage in the experimental group was lower than in the experimental control group, proving that LMWH has a protective effect on the nasal mucosa and that the effect correlates with dosage. Irrigation of the nose with saline mixed with LMWH can improve the anti-inflammatory effect. Protein related to the TLR4-MyD88-NF-κB signaling pathway was activated in the acute sinusitis rat model, and LMWH can significantly inhibit its expression.Conclusion: This is the first report of the anti-inflammatory effect of LMWH in acute upper respiratory tract inflammation, together with an explanation of its anti-inflammatory mechanism. The findings contribute a theoretical basis for its potential anti-tumor effect.

Anti-inflammatory effect of fucoidan extracted from Ecklonia cava in zebrafish model

2013 ◽  
Vol 92 (1) ◽  
pp. 84-89 ◽  
Author(s):  
Seung-Hong Lee ◽  
Chang-Ik Ko ◽  
Youngheun Jee ◽  
Yoonhwa Jeong ◽  
Misook Kim ◽  
...  
Keyword(s):  
Ecklonia Cava ◽  
Zebrafish Model ◽  
Anti Inflammatory ◽  
Inflammatory Effect

scholarly journals Soft Coral Dendronephthya puetteri Extract Ameliorates Inflammations by Suppressing Inflammatory Mediators and Oxidative Stress in LPS-Stimulated Zebrafish

2018 ◽  
Vol 19 (9) ◽  
pp. 2695 ◽  
Author(s):  
Eun-A Kim ◽  
Yuling Ding ◽  
Hye-Won Yang ◽  
Soo-Jin Heo ◽  
Seung-Hong Lee
Keyword(s):  
Cell Death ◽  
Soft Coral ◽  
In Vivo Model ◽  
Dependent Manner ◽  
Soft Corals ◽  
Zebrafish Model ◽  
Inflammatory Agent ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Marine-derived extract and/or bioactive compounds have attracted increasing demand due to their unique and potential uses as cures for various inflammation-based diseases. Several studies revealed anti-inflammatory candidates found in soft corals. However, the effects of soft corals on inflammation in an in vivo model remain to be determined. Therefore, the extract of soft coral Dendronephthya puetteri (DPE) was investigated for an in vivo anti-inflammatory effect in a lipopolysaccharide (LPS)-stimulated zebrafish model to determine its potential use as a natural anti-inflammatory agent. We also investigated whether DPE has toxic effects in a zebrafish model. No significant changes were observed in terms of survival, heart beat rate, or developmental abnormalities in the zebrafish embryos exposed to a concentration below 100 µg/mL of DPE. Treating the zebrafish model with LPS-treatment significantly increased the ROS, NO generation, and cell death. However, DPE inhibited this LPS-stimulated ROS, NO generation, and cell death in a dose-dependent manner. In addition, DPE significantly reduced the mRNA expression of both iNOS and COX-2 and markedly suppressed the expression levels of the proinflammatory cytokines, TNF-α and IL-6, in an LPS-stimulated zebrafish model. These findings demonstrate that DPE has profound anti-inflammatory effect in vivo, suggesting that DPE might be a strong natural anti-inflammatory agent.

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