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 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.

SLPI suppresses ATP-mediated release of IL-1β from human monocytes – evidence for a novel anti-inflammatory mechanism

Pneumologie ◽  
2015 ◽  
Vol 69 (07) ◽  
Author(s):  
A Zakrzewicz ◽  
S Wilker ◽  
S Janciauskiene ◽  
R Tikkanen ◽  
W Padberg ◽  
...  
Keyword(s):  
Human Monocytes ◽  
Inflammatory Mechanism ◽  
Anti Inflammatory

scholarly journals Anti-Inflammatory and Immunomodulatory Effects of the Grifola frondosa Natural Compound o-Orsellinaldehyde on LPS-Challenged Murine Primary Glial Cells. Roles of NF-κβ and MAPK

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 806
Author(s):  
Sarah Tomas-Hernandez ◽  
Jordi Blanco ◽  
Santiago Garcia-Vallvé ◽  
Gerard Pujadas ◽  
María José Ojeda-Montes ◽  
...  
Keyword(s):  
Natural Compound ◽  
Underlying Disease ◽  
Grifola Frondosa ◽  
Beneficial Effects ◽  
Inflammatory Conditions ◽  
Inflammatory Mechanism ◽  
Inflammatory Phenotype ◽  
Mice Brain ◽  
Anti Inflammatory

In response to foreign or endogenous stimuli, both microglia and astrocytes adopt an activated phenotype that promotes the release of pro-inflammatory mediators. This inflammatory mechanism, known as neuroinflammation, is essential in the defense against foreign invasion and in normal tissue repair; nevertheless, when constantly activated, this process can become detrimental through the release of neurotoxic factors that amplify underlying disease. In consequence, this study presents the anti-inflammatory and immunomodulatory properties of o-orsellinaldehyde, a natural compound found by an in silico approach in the Grifola frondosa mushroom, in astrocytes and microglia cells. For this purpose, primary microglia and astrocytes were isolated from mice brain and cultured in vitro. Subsequently, cells were exposed to LPS in the absence or presence of increasing concentrations of this natural compound. Specifically, the results shown that o-orsellinaldehyde strongly inhibits the LPS-induced inflammatory response in astrocytes and microglia by decreasing nitrite formation and downregulating iNOS and HO-1 expression. Furthermore, in microglia cells o-orsellinaldehyde inhibits NF-κB activation; and potently counteracts LPS-mediated p38 kinase and JNK phosphorylation (MAPK). In this regard, o-orsellinaldehyde treatment also induces a significant cell immunomodulation by repolarizing microglia toward the M2 anti-inflammatory phenotype. Altogether, these results could partially explain the reported beneficial effects of G. frondosa extracts on inflammatory conditions.

scholarly journals Fisetin inhibits lipopolysaccharide-induced inflammatory response by activating β-catenin, leading to a decrease in endotoxic shock

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ilandarage Menu Neelaka Molagoda ◽  
Jayasingha Arachchige Chathuranga C Jayasingha ◽  
Yung Hyun Choi ◽  
Rajapaksha Gedara Prasad Tharanga Jayasooriya ◽  
Chang-Hee Kang ◽  
...  
Keyword(s):  
Glycogen Synthase ◽  
Endotoxic Shock ◽  
Inflammatory Activity ◽  
Prostaglandin E ◽  
Necrosis Factor Alpha ◽  
Zebrafish Larvae ◽  
Proinflammatory Mediators ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Gsk 3Β

AbstractFisetin is a naturally occurring flavonoid that possesses several pharmacological benefits including anti-inflammatory activity. However, its precise anti-inflammatory mechanism is not clear. In the present study, we found that fisetin significantly inhibited the expression of proinflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE2), and cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Additionally, fisetin attenuated LPS-induced mortality and abnormalities in zebrafish larvae and normalized the heart rate. Fisetin decreased the recruitment of macrophages and neutrophils to the LPS-microinjected inflammatory site in zebrafish larvae, concomitant with a significant downregulation of proinflammatory genes, such as inducible NO synthase (iNOS), cyclooxygenase-2a (COX-2a), IL-6, and TNF-α. Fisetin inhibited the nuclear localization of nuclear factor-kappa B (NF-κB), which reduced the expression of pro-inflammatory genes. Further, fisetin inactivated glycogen synthase kinase 3β (GSK-3β) via phosphorylation at Ser9, and inhibited the degradation of β-catenin, which consequently promoted the localization of β-catenin into the nucleus. The pharmacological inhibition of β-catenin with FH535 reversed the fisetin-induced anti-inflammatory activity and restored NF-κB activity, which indicated that fisetin-mediated activation of β-catenin results in the inhibition of LPS-induced NF-κB activity. In LPS-microinjected zebrafish larvae, FH535 promoted the migration of macrophages to the yolk sac and decreased resident neutrophil counts in the posterior blood island and induced high expression of iNOS and COX-2a, which was accompanied by the inhibition of fisetin-induced anti-inflammatory activity. Altogether, the current study confirmed that the dietary flavonoid, fisetin, inhibited LPS-induced inflammation and endotoxic shock through crosstalk between GSK-3β/β-catenin and the NF-κB signaling pathways.

Anti-inflammatory Effects ofScoparia dulcisL. and Betulinic Acid

2011 ◽  
Vol 39 (05) ◽  
pp. 943-956 ◽  
Author(s):  
Jen-Chieh Tsai ◽  
Wen-Huang Peng ◽  
Tai-Hui Chiu ◽  
Shang-Chih Lai ◽  
Chao-Ying Lee
Keyword(s):  
Betulinic Acid ◽  
High Performance ◽  
Ethanol Extract ◽  
Paw Edema ◽  
Scoparia Dulcis ◽  
Inflammatory Mechanism ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Analytical Result

The aims of this study intended to investigate the anti-inflammatory activity of the 70% ethanol extract from Scoparia dulcis (SDE) and betulinic acid on λ-carrageenan-induced paw edema in mice. The anti-inflammatory mechanism of SDE and betulinic acid was examined by detecting the levels of cyclooxygenase-2 (COX-2), nitric oxide (NO), tumor necrosis factor (TNF-α), interleukin-1β (IL-1β) and malondialdehyde (MDA) in the edema paw tissue and the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRd) in the liver. The betulinic acid content in SDE was detected by high performance liquid chromatography (HPLC). In the anti-inflammatory model, the results showed that SDE (0.5 and 1.0 g/kg) and betulinic acid (20 and 40 mg/kg) reduced the paw edema at 3, 4 and 5 h after λ-carrageenan administration. Moreover, SDE and betulinic acid affected the levels of COX-2, NO, TNF-α and IL1-β in the λ-carrageenan-induced edema paws. The activities of SOD, GPx and GRd in the liver tissue were increased and the MDA levels in the edema paws were decreased. It is suggested that SDE and betulinic acid possessed anti-inflammatory activities and the anti-inflammatory mechanisms appear to be related to the reduction of the levels of COX-2, NO, TNF-α and IL1-β in inflamed tissues, as well as the inhibition of MDA level via increasing the activities of SOD, GPx and GRd. The analytical result showed that the content of betulinic acid in SDE was 6.25 mg/g extract.

Anti-inflammatory mechanism of lonchocarpine in LPS- or poly(I:C)-induced neuroinflammation

2017 ◽  
Vol 119 ◽  
pp. 431-442 ◽  
Author(s):  
Yeon-Hui Jeong ◽  
Jin-Sun Park ◽  
Dong-Hyun Kim ◽  
Jihee Lee Kang ◽  
Hee-Sun Kim
Keyword(s):  
Poly I:C ◽  
Inflammatory Mechanism ◽  
Anti Inflammatory
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