Abstract
BackgroundInflammation 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.MethodsIn 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.ResultsFA 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.ConclusionsOur 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.
Highlights
Inflammation is a general pathological phenomenon during severe disturbances to the homeostasis
Most of the neutrophils were assembled in the posterior blood island or caudal hematopoietic tissue, in which most leukocytes were distributed in this development stage (Fig. 2b)
Zebrafish larvae exposed to CuSO4 for 40 min formed a typical neutrophils cluster in the horizontal muscles, which indicated that neutrophils could migrate to the lateral line neuromasts, with the induction of CuSO4
Summary
Inflammation is a general pathological phenomenon during severe disturbances to the homeostasis. Excessive and uncontrolled inflammation can cause chronic diseases such as cancer and neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease [1, 2]. During this process, over-activation of the macrophages and neutrophils can induce the secretion of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), which are significant mediators of the inflammatory response [3]. Forsythiaside A (FA, Fig. 1a) and forsythiaside B (FB, Fig. 1b) are the major bioactive components extracted from Forsythiae Fructus They were reported to possess anti-inflammatory and anti-bacterial properties [5, 6]. Few studies have been conducted to systematically investigate their anti-inflammatory properties and therapeutic mechanisms
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