Exploration of anti-inflammatory mechanism of forsythiaside A and forsythiaside B in CuSO4-induced inflammation in zebrafish by metabolomic and proteomic analyses

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.

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

10.21203/rs.2.19758/v3 ◽

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.

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

Pneumologie ◽

10.1055/s-0035-1556628 ◽

2015 ◽

Vol 69 (07) ◽

Author(s):

A Zakrzewicz ◽

S Wilker ◽

S Janciauskiene ◽

R Tikkanen ◽

W Padberg ◽

...

Keyword(s):

Human Monocytes ◽

Inflammatory Mechanism ◽

Anti Inflammatory

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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 ◽

10.3390/pharmaceutics13060806 ◽

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.

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Predicting the Anti-Inflammatory Mechanism of Polygonum perfoliatum L based on Network Pharmacology

IOP Conference Series Earth and Environmental Science ◽

10.1088/1755-1315/632/5/052012 ◽

2021 ◽

Vol 632 ◽

pp. 052012

Author(s):

Mei Zhang ◽

Xulong Huang ◽

Feng Xu ◽

Ping Qin ◽

Qin Din ◽

...

Keyword(s):

Network Pharmacology ◽

Inflammatory Mechanism ◽

Polygonum Perfoliatum ◽

Anti Inflammatory

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High-throughput RNA sequencing reveals the anti-inflammatory mechanism of baicalin on Propionibacterium acnes-induced acne in rabbits

Journal of Traditional Chinese Medical Sciences ◽

10.1016/j.jtcms.2019.09.001 ◽

2019 ◽

Vol 6 (3) ◽

pp. 201-210

Author(s):

Xingzhe Yang ◽

Guangrui Huang ◽

Leiming You ◽

Honghao Sheng ◽

Yuxiu Sun ◽

...

Keyword(s):

Rna Sequencing ◽

High Throughput ◽

Propionibacterium Acnes ◽

Inflammatory Mechanism ◽

Anti Inflammatory

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Anti-inflammatory Effects ofScoparia dulcisL. and Betulinic Acid

The American Journal of Chinese Medicine ◽

10.1142/s0192415x11009329 ◽

2011 ◽

Vol 39 (05) ◽

pp. 943-956 ◽

Cited By ~ 38

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.

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