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Polydatin inhibits mast cell-mediated allergic inflammation by targeting PI3K/Akt, MAPK, NF-κB and Nrf2/HO-1 pathways
- Source :
- Scientific Reports, Vol 7, Iss 1, Pp 1-13 (2017), Scientific Reports
- Publication Year :
- 2017
- Publisher :
- Nature Publishing Group, 2017.
-
Abstract
- Polydatin(PD) shows anti-allergic inflammatory effect, and this study investigated its underlying mechanisms in in vitro and in vivo models. IgE-mediated passive cutaneous anaphylaxis (PCA) and passive systemic anaphylaxis (PSA) models were used to confirm PD effect in vivo. Various signaling pathway proteins in mast cell were examined. RT-PCR, ELISA and western blotting were applied when appropriate. Activity of Lyn and Fyn kinases in vitro was measured using the Kinase Enzyme System. PD dose-dependently reduced the pigmentation of Evans blue in the PCA model and decreased the concentration of serum histamine in PSA model, and attenuated the degranulation of mast cells without generating cytotoxicity. PD decreased pro-inflammatory cytokine expression (TNF-α, IL-4, IL-1β, and IL-8). PD directly inhibited activity of Lyn and Syk kinases and down-regulated downstream signaling pathway including MAPK, PI3K/AKT and NF-kB. In addition, PD also targets Nrf2/HO-1 pathway to inhibit mast cell-derived allergic inflammatory reactions. In conclusion, the study demonstrates that PD is a possible therapeutic candidate for allergic inflammatory diseases. It directly inhibited activity of Lyn and Syk kinases and down-regulates the signaling pathway of MAPK, PI3K/AKT and NF-κB, and up-regulates the signaling pathway of Nrf2/HO-1 to inhibit the degranulation of mast cells.
- Subjects :
- 0301 basic medicine
MAPK/ERK pathway
Male
MAP Kinase Signaling System
NF-E2-Related Factor 2
Syk
lcsh:Medicine
Cell Degranulation
Article
Allergic inflammation
Dermatitis, Atopic
03 medical and health sciences
Mice
Phosphatidylinositol 3-Kinases
0302 clinical medicine
Glucosides
LYN
Stilbenes
medicine
Animals
Mast Cells
Extracellular Signal-Regulated MAP Kinases
lcsh:Science
Protein kinase B
Anaphylaxis
PI3K/AKT/mTOR pathway
Inflammation
Mice, Inbred BALB C
Multidisciplinary
Chemistry
lcsh:R
Degranulation
Membrane Proteins
Mast cell
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
Cancer research
Cytokines
lcsh:Q
Proto-Oncogene Proteins c-akt
Heme Oxygenase-1
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 7
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....98c305d1f340a03a8edd959271d25d4e