N ew C9‐monoterpenoid Alkaloids Featuring a Rare Skeleton with Anti‐inflammatory and Anti‐viral Activities from Forsythia suspensa

Author(s):  
Wei Li ◽  
Li-Tong Sun ◽  
Lin Zhao ◽  
Xi-Dian Yue ◽  
Sheng-Jun Dai
2017 ◽  
Vol 43 (5) ◽  
pp. 2074-2087 ◽  
Author(s):  
Liling Yang ◽  
Xiangjun Zhou ◽  
Weijuan Huang ◽  
Qin Fang ◽  
Jianlan Hu ◽  
...  

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.


2017 ◽  
Vol 206 ◽  
pp. 73-77 ◽  
Author(s):  
Youn-Hwan Hwang ◽  
Dong-Gun Kim ◽  
Wei Li ◽  
Hye Jin Yang ◽  
Nam-Hui Yim ◽  
...  

2018 ◽  
Vol 227 ◽  
pp. 97-104 ◽  
Author(s):  
Jung Ju Lee ◽  
Kyun Ha Kim ◽  
Eun Jeong Kim ◽  
Jun-Yong Choi ◽  
Sang-Jun Kim ◽  
...  

2019 ◽  
Author(s):  
Lihong Gong ◽  
Linyuan Yu ◽  
Xiaohong Gong ◽  
Cheng Wang ◽  
Naihua Hu ◽  
...  

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.


2020 ◽  
Vol 96 ◽  
pp. 103651 ◽  
Author(s):  
Lin Zhao ◽  
Kang-Lin Xiang ◽  
Rong-Xia Liu ◽  
Ze-Ping Xie ◽  
Shu-Min Zhang ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Chang-Liang Chen ◽  
Dan-Dan Zhang

Inducible nitrogen oxide synthase (iNOS) is the primary contributor of the overproduction of nitric oxide and its inhibitors have been actively sought as effective anti-inflammatory agents. In this study, we prepared 70% ethanol extracts from 81 Chinese herbs. These extracts were subsequently evaluated for their effect on nitrogen oxide (NO) production and cell growth in LPS/IFNγ-costimulated and unstimulated murine macrophage RAW264.7 cells by Griess reaction and MTT assay. Extracts ofDaphne genkwaSieb.et Zucc,Caesalpinia sappanL.,Iles pubescensHook.et Arn,Forsythia suspensa(Thunb.) Vahl,Zingiber officinaleRosc,Inula japonicaThunb., andLigusticum chuanxiongHort markedly inhibited NO production (inhibition > 90% at 100 μg/mL). Among active extracts (inhibition > 50% at 100 μg/mL),Rubia cordifoliaL.,Glycyrrhiza glabraL.,Iles pubescensHook.et Arn,Nigella glanduliferaFreyn et Sint,Pueraria lobata(Willd.) Ohwi, andScutellaria barbataD. Don displayed no cytotoxicity to unstimulated RAW246.7 cells while increasing the growth of LPS/IFNγ-costimulated cells. By analyzing the correlation between their activities and their Traditional Chinese Medicine (TCM) characteristics, herbs with pungent flavor displayed potent anti-inflammatory capability. Our study provides a series of potential anti-inflammatory herbs and suggests that herbs with pungent flavor are candidates of effective anti-inflammatory agents.


2019 ◽  
Vol 29 (19) ◽  
pp. 126635
Author(s):  
Si-Yuan Shao ◽  
Ya-Nan Yang ◽  
Zi-Ming Feng ◽  
Jian-Shuang Jiang ◽  
Pei-Cheng Zhang

2020 ◽  
Author(s):  
Lihong Gong ◽  
Linyuan Yu ◽  
Xiaohong Gong ◽  
Cheng Wang ◽  
Naihua Hu ◽  
...  

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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