scholarly journals Study on Anti-Inflammatory Effect and Major Anti-Inflammatory Components of PSORI-CM02 by Zebrafish Model

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Xiaohong Yuan ◽  
Leyu Huang ◽  
Jiaqi Lei ◽  
Yingxin Long ◽  
Cong Li
Keyword(s):  
Chinese Medicine ◽  
Herbal Medicine ◽  
Critical Role ◽  
Transgenic Zebrafish ◽  
Zebrafish Model ◽  
Macrophage Phagocytosis ◽  
The Common ◽  
Multiple Component ◽  
Anti Inflammatory

PSORI-CM02 is an optimization formula of PSORI-CM01, which is a clinical herbal formula for the treatment for psoriasis in the Guangdong Provincial Hospital of Chinese Medicine. Previous research indicates that it plays a critical role in anti-inflammation and immunoregulation. Rhizoma smilacis glabrae (RSG) is one herbal medicine of PSORI-CM02, whose effective anti-inflammatory component is astilbin. This study aims to test the anti-inflammatory and immunoregulation effects of astilbin as well as RSG in PSORI-CM02, and we, respectively, used the CuSO4-induced neutrophil-specific transgenic zebrafish model Tg(mpx: EGFP) and the melanin allele mutated Albino strain zebrafish model to visualize the effects of neutrophil recruitment and macrophage phagocytosis. Our data indicated that both PSORI-CM02 and astilbin had anti-inflammatory effects, leading to a reduction in the recruitment of neutrophils and promotion in macrophage phagocytosis. Nevertheless, the negative liquor of Rhizoma smilacis glabrae (PSORI-CM02 without RSG) also had anti-inflammatory and promoting macrophage phagocytosis effects. The results revealed the formula excluding RSG also had anti-inflammatory and immunoregulation effects, which demonstrated that RSG was not the major anti-inflammatory herbal medicine in PSORI-CM02. Similarly, astilbin was not the major anti-inflammatory active ingredient in the formula. The anti-inflammatory and the promotion of macrophage phagocytosis effect of PSORI-CM02 in vivo zebrafish were the results of multiple component interaction, which was the common characteristic of the Chinese medicine compound.

scholarly journals Evaluation of the anti-inflammatory effects of synthesised tanshinone I and isotanshinone I analogues in zebrafish

2019 ◽  
Author(s):  
Matthew J. Foulkes ◽  
Katherine M. Henry ◽  
Stephen A. Renshaw ◽  
Simon Jones
Keyword(s):  
Inflammatory Diseases ◽  
Neutrophil Recruitment ◽  
Chronic Obstructive ◽  
Transgenic Zebrafish ◽  
Zebrafish Model ◽  
General Group ◽  
Obstructive Pulmonary Disease ◽  
Anti Inflammatory ◽  
Antiinflammatory Effects

AbstractDuring inflammation, dysregulated neutrophil behaviour can play a major role in chronic inflammatory diseases such as chronic obstructive pulmonary disease, for which current treatments are generally ineffective. Recently, tanshinones have shown promising antiinflammatory effects by targeting neutrophils in vivo, yet are still an underexplored general group of compounds. Here, an existing six step synthetic route was optimised and used to prepare a small family of substituted tanshinone and isomeric isotanshinone analogues, together with the synthesis of other structurally similar molecules. Evaluation of these using a transgenic zebrafish model of inflammation revealed that many of these compounds exhibit promising anti-inflammatory effects in vivo. Several compounds affect neutrophil recruitment and/or resolution of neutrophilic inflammation, and broad structure-activity relationships were constructed. In particular, the methoxy-substituted tanshinone 39 specifically accelerates resolution of inflammation without affecting organism host defence, making this a particularly attractive candidate for potential pro-resolution therapeutics. On the other hand, β-lapachones exhibit effects on neutrophil recruitment yet not on resolution. Notable differences in toxicity profiles between compound classes were also observed.

scholarly journals Anti-Inflammatory Activity of Exopolysaccharides from Phormidium sp. ETS05, the Most Abundant Cyanobacterium of the Therapeutic Euganean Thermal Muds, Using the Zebrafish Model

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 582 ◽  
Author(s):  
Raffaella Margherita Zampieri ◽  
Alessandra Adessi ◽  
Fabrizio Caldara ◽  
Alessia Codato ◽  
Mattia Furlan ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Chronic Inflammatory Disease ◽  
Bioactive Molecules ◽  
In Vitro Tests ◽  
Transgenic Zebrafish ◽  
Zebrafish Model ◽  
Beneficial Effects ◽  
Anti Inflammatory

The Euganean Thermal District (Italy) represents the oldest and largest thermal center in Europe, and its therapeutic mud is considered a unique product whose beneficial effects have been documented since Ancient Roman times. Mud properties depend on the heat and electrolytes of the thermal water, as well as on the bioactive molecules produced by its biotic component, mainly represented by cyanobacteria. The investigation of the healing effects of compounds produced by the Euganean cyanobacteria represents an important goal for scientific validation of Euganean mud therapies and for the discovering of new health beneficial biomolecules. In this work, we evaluated the therapeutic potential of exopolysaccharides (EPS) produced by Phormidium sp. ETS05, the most abundant cyanobacterium of the Euganean mud. Specifically, Phormidium EPS resulted in exerting anti-inflammatory and pro-resolution activities in chemical and injury-induced zebrafish inflammation models as demonstrated using specific transgenic zebrafish lines and morphometric and expression analyses. Moreover, in vivo and in vitro tests showed no toxicity at all for the EPS concentrations tested. The results suggest that these EPS, with their combined anti-inflammatory and pro-resolution activities, could be one of the most important therapeutic molecules present in the Euganean mud and confirm the potential of these treatments for chronic inflammatory disease recovery.

scholarly journals Development of BCR-ABL1 Transgenic Zebrafish Model Reproducing Chronic Myeloid Leukemia (CML) Like-Disease and Providing a New Insight into CML Mechanisms

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 445
Author(s):  
Daniela Zizioli ◽  
Simona Bernardi ◽  
Marco Varinelli ◽  
Mirko Farina ◽  
Luca Mignani ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Fusion Gene ◽  
Philadelphia Chromosome ◽  
Leukemic Cells ◽  
Transgenic Zebrafish ◽  
Hematopoietic Tissue ◽  
Zebrafish Model ◽  
Altered Expression

Zebrafish has proven to be a versatile and reliable experimental in vivo tool to study human hematopoiesis and model hematological malignancies. Transgenic technologies enable the generation of specific leukemia types by the expression of human oncogenes under specific promoters. Using this technology, a variety of myeloid and lymphoid malignancies zebrafish models have been described. Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasia characterized by the BCR-ABL1 fusion gene, derived from the t (9;22) translocation causing the Philadelphia Chromosome (Ph). The BCR-ABL1 protein is a constitutively activated tyrosine kinas inducing the leukemogenesis and resulting in an accumulation of immature leukemic cells into bone marrow and peripheral blood. To model Ph+ CML, a transgenic zebrafish line expressing the human BCR-ABL1 was generated by the Gal4/UAS system, and then crossed with the hsp70-Gal4 transgenic line. The new line named (BCR-ABL1pUAS:CFP/hsp70-Gal4), presented altered expression of hematopoietic markers during embryonic development compared to controls and transgenic larvae showed proliferating hematopoietic cells in the caudal hematopoietic tissue (CHT). The present transgenic zebrafish would be a robust CML model and a high-throughput drug screening tool.

scholarly journals In Vitro and in Vivo Imaging of Nitroxyl with Copper Fluorescent Probe in Living Cells and Zebrafish

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2551 ◽  
Author(s):  
Sathyadevi Palanisamy ◽  
Yu-Liang Wang ◽  
Yu-Jen Chen ◽  
Chiao-Yun Chen ◽  
Fu-Te Tsai ◽  
...  
Keyword(s):  
Critical Role ◽  
Model Organism ◽  
Living Cells ◽  
Biological Species ◽  
Zebrafish Model ◽  
Physiological Processes ◽  
Collective Data ◽  
Angeli's Salt

Nitroxyl (HNO) plays a critical role in many physiological processes which includes vasorelaxation in heart failure, neuroregulation, and myocardial contractility. Powerful imaging tools are required to obtain information for understanding the mechanisms involved in these in vivo processes. In order to develop a rapid and high sensitive probe for HNO detection in living cells and the zebrafish model organism, 2-((2-(benzothiazole-2yl)benzylidene) amino)benzoic acid (AbTCA) as a ligand, and its corresponding copper(II) complex Cu(II)-AbTCA were synthesized. The reaction results of Cu(II)-AbTCA with Angeli’s salt showed that Cu(II)-AbTCA could detect HNO quantitatively in a range of 40–360 µM with a detection limit of 9.05 µM. Furthermore, Cu(II)-AbTCA is more selective towards HNO over other biological species including thiols, reactive nitrogen, and reactive oxygen species. Importantly, Cu(II)-AbTCA was successfully applied to detect HNO in living cells and zebrafish. The collective data reveals that Cu(II)-AbTCA could be used as a potential probe for HNO detection in living systems.

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.

scholarly journals The Anti-Neuroinflammatory Effect of Fuzi and Ganjiang Extraction on LPS-Induced BV2 Microglia and Its Intervention Function on Depression-Like Behavior of Cancer-Related Fatigue Model Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Songwei Yang ◽  
Yantao Yang ◽  
Cong Chen ◽  
Huiqin Wang ◽  
Qidi Ai ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Inflammatory Mediators ◽  
Critical Role ◽  
Chinese Herb ◽  
Experimental Studies ◽  
Research Results ◽  
Cancer Related Fatigue

The Chinese herb couple Fuzi and Ganjiang (FG) has been a classic combination of traditional Chinese medicine that is commonly used clinically in China for nearly 2000 years. Traditional Chinese medicine suggests that FG can treat various ailments, including heart failure, fatigue, gastrointestinal upset, and depression. Neuroinflammation is one of the main pathogenesis of many neurodegenerative diseases in which microglia cells play a critical role in the occurrence and development of neuroinflammation. FG has been clinically proven to have an efficient therapeutic effect on depression and other neurological disorders, but its mechanism remains unknown. Cancer-related fatigue (CRF) is a serious threat to the quality of life of cancer patients and is characterized by both physical and psychological fatigue. Recent studies have found that neuroinflammation is a key inducement leading to the occurrence and development of CRF. Traditional Chinese medicine theory believes that extreme fatigue and depressive symptoms of CRF are related to Yang deficiency, and the application of Yang tonic drugs such as Fuzi and Ganjiang can relieve CRF symptoms, but the underlying mechanisms remain unknown. In order to define whether FG can inhibit CRF depression-like behavior by suppressing neuroinflammation, we conducted a series of experimental studies in vitro and in vivo. According to the UPLC-Q-TOF/MSE results, we speculated that there were 49 compounds in the FG extraction, among which 30 compounds were derived from Fuzi and 19 compounds were derived from Ganjiang. Our research data showed that FG can effectively reduce the production of pro-inflammatory mediators IL-6, TNF-α, ROS, NO, and PGE2 and suppress the expression of iNOS and COX2, which were related to the inhibition of NF-κB/activation of Nrf2/HO-1 signaling pathways. In addition, our research results revealed that FG can improve the depression-like behavior performance of CRF model mice in the tail suspension test, open field test, elevated plus maze test, and forced swimming test, which were associated with the inhibition of the expression of inflammatory mediators iNOS and COX2 in the prefrontal cortex and hippocampus of CRF model mice. Those research results suggested that FG has a satisfactory effect on depression-like behavior of CRF, which was related to the inhibition of neuroinflammation.

scholarly journals Perturbations of BMP/TGF-β and VEGF/VEGFR signalling pathways in non-syndromic sporadic brain arteriovenous malformations (BAVM)

2018 ◽  
Vol 55 (10) ◽  
pp. 675-684 ◽  
Author(s):  
Kun Wang ◽  
Sen Zhao ◽  
Bowen Liu ◽  
Qianqian Zhang ◽  
Yaqi Li ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Arteriovenous Malformations ◽  
Transforming Growth Factor ◽  
Transgenic Zebrafish ◽  
Zebrafish Model ◽  
Brain Arteriovenous Malformations ◽  
Pathogenic Variants ◽  
Uncertain Significance

BackgroundBrain arteriovenous malformations (BAVM) represent a congenital anomaly of the cerebral vessels with a prevalence of 10–18/100 000. BAVM is the leading aetiology of intracranial haemorrhage in children. Our objective was to identify gene variants potentially contributing to disease and to better define the molecular aetiology underlying non-syndromic sporadic BAVM.MethodsWe performed whole-exome trio sequencing of 100 unrelated families with a clinically uniform BAVM phenotype. Pathogenic variants were then studied in vivo using a transgenic zebrafish model.ResultsWe identified four pathogenic heterozygous variants in four patients, including one in the established BAVM-related gene, ENG, and three damaging variants in novel candidate genes: PITPNM3, SARS and LEMD3, which we then functionally validated in zebrafish. In addition, eight likely pathogenic heterozygous variants (TIMP3, SCUBE2, MAP4K4, CDH2, IL17RD, PREX2, ZFYVE16 and EGFR) were identified in eight patients, and 16 patients carried one or more variants of uncertain significance. Potential oligogenic inheritance (MAP4K4 with ENG, RASA1 with TIMP3 and SCUBE2 with ENG) was identified in three patients. Regulation of sma- and mad-related proteins (SMADs) (involved in bone morphogenic protein (BMP)/transforming growth factor beta (TGF-β) signalling) and vascular endothelial growth factor (VEGF)/vascular endotheliual growth factor recepter 2 (VEGFR2) binding and activity (affecting the VEGF signalling pathway) were the most significantly affected biological process involved in the pathogenesis of BAVM.ConclusionsOur study highlights the specific role of BMP/TGF-β and VEGF/VEGFR signalling in the aetiology of BAVM and the efficiency of intensive parallel sequencing in the challenging context of genetically heterogeneous paradigm.

scholarly journals Live imaging of neutrophil motility in a zebrafish model of WHIM syndrome

Blood ◽  
2010 ◽  
Vol 116 (15) ◽  
pp. 2803-2811 ◽  
Author(s):  
Kevin B. Walters ◽  
Julie M. Green ◽  
Jill C. Surfus ◽  
Sa Kan Yoo ◽  
Anna Huttenlocher
Keyword(s):  
Primary Immunodeficiency ◽  
Transgenic Zebrafish ◽  
Hematopoietic Tissue ◽  
Primary Immunodeficiency Disorder ◽  
Zebrafish Model ◽  
Whim Syndrome ◽  
Stromal Cell Derived Factor ◽  
Morpholino Oligonucleotides ◽  
Guanosine Triphosphatase

Abstract CXCR4 is a G protein–coupled chemokine receptor that has been implicated in the pathogenesis of primary immunodeficiency disorders and cancer. Autosomal dominant gain-of-function truncations of CXCR4 are associated with warts, hypo-gammaglobulinemia, infections, and myelokathexis (WHIM) syndrome, a primary immunodeficiency disorder characterized by neutropenia and recurrent infections. Recent progress has implicated CXCR4-SDF1 (stromal cell-derived factor 1) signaling in regulating neutrophil homeostasis, but the precise role of CXCR4-SDF1 interactions in regulating neutrophil motility in vivo is not known. Here, we use the optical transparency of zebrafish to visualize neutrophil trafficking in vivo in a zebrafish model of WHIM syndrome. We demonstrate that expression of WHIM mutations in zebrafish neutrophils induces neutrophil retention in hematopoietic tissue, impairing neutrophil motility and wound recruitment. The neutrophil retention signal induced by WHIM truncation mutations is SDF1 dependent, because depletion of SDF1 with the use of morpholino oligonucleotides restores neutrophil chemotaxis to wounds. Moreover, localized activation of a genetically encoded, photoactivatable Rac guanosine triphosphatase is sufficient to direct migration of neutrophils that express the WHIM mutation. The findings suggest that this transgenic zebrafish model of WHIM syndrome may provide a valuable tool to screen for agents that modify CXCR4-SDF1 retention signals.

scholarly journals Evidences of Herbal Medicine-Derived Natural Products Effects in Inflammatory Lung Diseases

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Fernanda Paula R. Santana ◽  
Nathalia M. Pinheiro ◽  
Márcia Isabel B. Mernak ◽  
Renato F. Righetti ◽  
Mílton A. Martins ◽  
...  
Keyword(s):  
Natural Products ◽  
Herbal Medicine ◽  
Biological Activities ◽  
Biological Effects ◽  
Pulmonary Inflammation ◽  
Experimental Models ◽  
Chronic Obstructive ◽  
Anti Inflammatory

Pulmonary inflammation is a hallmark of many respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and acute respiratory syndrome distress (ARDS). Most of these diseases are treated with anti-inflammatory therapy in order to prevent or to reduce the pulmonary inflammation. Herbal medicine-derived natural products have been used in folk medicine and scientific studies to evaluate the value of these compounds have grown in recent years. Many substances derived from plants have the biological effectsin vitroandin vivo, such as flavonoids, alkaloids, and terpenoids. Among the biological activities of natural products derived from plants can be pointed out the anti-inflammatory, antiviral, antiplatelet, antitumor anti-allergic activities, and antioxidant. Although many reports have evaluated the effects of these compounds in experimental models, studies evaluating clinical trials are scarce in the literature. This review aims to emphasize the effects of these different natural products in pulmonary diseases in experimental models and in humans and pointing out some possible mechanisms of action.

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