Protective Effect of Phillyrin on Lethal LPS-Induced Neutrophil Inflammation in Zebrafish
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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2017-10-01
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| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | https://www.karger.com/Article/FullText/484192 |
| _version_ | 1818966064278536192 |
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| author | Liling Yang Xiangjun Zhou Weijuan Huang Qin Fang Jianlan Hu Linzhong Yu Ning Ma Wenqing Zhang |
| author_facet | Liling Yang Xiangjun Zhou Weijuan Huang Qin Fang Jianlan Hu Linzhong Yu Ning Ma Wenqing Zhang |
| author_sort | Liling Yang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T13:26:57Z |
| format | Article |
| id | doaj.art-1766d705a3be43119dee2aecca8e7863 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-20T13:26:57Z |
| publishDate | 2017-10-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-1766d705a3be43119dee2aecca8e78632022-12-21T19:39:14ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782017-10-014352074208710.1159/000484192484192Protective Effect of Phillyrin on Lethal LPS-Induced Neutrophil Inflammation in ZebrafishLiling YangXiangjun ZhouWeijuan HuangQin FangJianlan HuLinzhong YuNing MaWenqing ZhangBackground/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.https://www.karger.com/Article/FullText/484192LpsPhillyrinNeutrophilsInflammationZebrafishMyD88NF-κB |
| spellingShingle | Liling Yang Xiangjun Zhou Weijuan Huang Qin Fang Jianlan Hu Linzhong Yu Ning Ma Wenqing Zhang Protective Effect of Phillyrin on Lethal LPS-Induced Neutrophil Inflammation in Zebrafish Cellular Physiology and Biochemistry Lps Phillyrin Neutrophils Inflammation Zebrafish MyD88 NF-κB |
| title | Protective Effect of Phillyrin on Lethal LPS-Induced Neutrophil Inflammation in Zebrafish |
| title_full | Protective Effect of Phillyrin on Lethal LPS-Induced Neutrophil Inflammation in Zebrafish |
| title_fullStr | Protective Effect of Phillyrin on Lethal LPS-Induced Neutrophil Inflammation in Zebrafish |
| title_full_unstemmed | Protective Effect of Phillyrin on Lethal LPS-Induced Neutrophil Inflammation in Zebrafish |
| title_short | Protective Effect of Phillyrin on Lethal LPS-Induced Neutrophil Inflammation in Zebrafish |
| title_sort | protective effect of phillyrin on lethal lps induced neutrophil inflammation in zebrafish |
| topic | Lps Phillyrin Neutrophils Inflammation Zebrafish MyD88 NF-κB |
| url | https://www.karger.com/Article/FullText/484192 |
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