Lignans From Forsythia x Intermedia Leaves and Flowers Attenuate the Pro-inflammatory Function of Leukocytes and Their Interaction With Endothelial Cells

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ID: 18369
2018
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Overall Quality Improving Quality
82.1 /100
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AI Quality Assessment 🥈 High Quality
83.1 /100
Academic Rigor 88.0%
Novelty 78.0%
Clarity 85.0%
Key Strengths
  • Identification and isolation of active lignans
  • Comprehensive investigation of pro- and anti-inflammatory functions
  • Use of multiple experimental techniques (HPLC-DAD-MSn, ELISA, flow cytometry, western blots)
Areas for Improvement
  • Limited information on the specific source and cultivation of Forsythia x intermedia
  • Lack of in vivo validation of the findings
  • Potential for further investigation into the specific mechanisms of action of the identified lignans
AI Recommendations

Future studies could benefit from exploring the in vivo effects of the identified lignans and investigating their potential synergistic effects with other anti-inflammatory compounds. Further research into the specific mechanisms of action would also strengthen the findings.

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Abstract
Aim of the study: Taking into account that overactivated leukocytes are an important factor in the development of many chronic diseases, we investigated the activity of phytochemically characterized (HPLC-DAD-MSn) extracts from forsythia leaves and flowers on the pro- and anti-inflammatory functions of leukocytes (effects on IL-1β, IL-8, TNF-α, and TGFβ release) and their adherence to endothelial cells. Using bio-guided fractionation, we isolated the active compounds and determined their biological activity, and we included the positive control quercetin.Methods: The effect on IL-1β, TNF-α, IL-8, and TGF-α production by leukocytes was measured by enzyme-linked immunosorbent assay (ELISA). The surface expression of adhesion molecules was analyzed with flow cytometry, and the neutrophil attachment to the endothelial cells was assessed fluorimetrically. The effects on p38MAPK, ERK1/2 and JNK phosphorylation were determined using western blots.Results: Leaf extracts had the effect of decreasing TNF-α production in neutrophils and monocyte/macrophage cells. The bio-guided fractionation led to the isolation of the following lignan aglycones: (+)-pinoresinol, (+)-epipinoresinol, (−)-matairesinol, (+)-phillygenin, and (−)-arctigenin. Only phillygenin was able to stimulate the anti-inflammatory function of macrophages by inducing TGF-β release and IL-10 receptor surface expression. Arctigenin, phillygenin, and a metabolite produced by the gut microbiota, enterolactone, decreased TNF-α and IL-1β production and neutrophil adhesion to endothelial cells, probably by attenuating the p38 and ERK kinase pathways.Conclusion:Forsythia x intermedia is a valuable source of active lignans, which may be potential candidates for treating inflammatory diseases that are associated with the excessive production of cytokines such as TNF-α and IL-1β.
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michalak2018lignansfrontiers Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Michalak, Barbara;Filipek, Agnieszka;Chomicki, Piotr;Pyza, Małgorzata;Woźniak, Marta;Żyżyńska-Granica, Barbara;Piwowarski, Jakub P.;Kicel, Agnieszka;Olszewska, Monika A.;Kiss, Anna K.;
Journal Frontiers in pharmacology
Year 2018
DOI
10.3389/fphar.2018.00401
URL
http://journal.frontiersin.org/article/10.3389/fphar.2018.00401/full
Keywords
Forsythia x intermedia lignans Inflammation leukocytes endothelial cells cytokines HPLC-DAD-MSn ELISA mapk signaling

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