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.
Anti-inflammatory effect of lipophilic grape seed proanthocyanidin in RAW 264.7 cells and a zebrafish model