Identification of Pinosylvin in Pinus nigra subsp. laricio : A Naturally Occurring Stilbenoid Suppressing LPS-Induced Expression of Pro-Inflammatory Cytokines and Mediators and Inhibiting the JAK/STAT Signaling Pathway.
Maria Rosaria PerriMichele PellegrinoMariangela MarrelliStefano AquaroFabiola CavaliereFedora GrandeMaria Antonietta OcchiuzziCarmine LupiaClaudia-Crina TomaFilomena ConfortiGiancarlo StattiPublished in: Pharmaceuticals (Basel, Switzerland) (2023)
Stilbenoids, a group of phytoalexin polyphenols produced by plants as a defence mechanism in response to stress conditions, are known for their anti-inflammatory potential. Pinosylvin, a naturally occurring molecule traditionally found in pinus trees, was here identified in Pinus nigra subsp. laricio var. calabrica from Southern Italy through HPLC analysis. Both this molecule and its well-known analogue resveratrol, the most famous wine polyphenol, were compared for their in vitro potential anti-inflammatory activity. Pinosylvin significantly inhibited the release of pro-inflammatory cytokines (TNF-α and IL-6) and NO mediator in LPS-stimulated RAW 264.7 cells. Moreover, its ability to inhibit the JAK/STAT signaling pathway was assessed: Western blot analyses showed a downregulation of both phosphorylated JAK2 and STAT3 proteins. Finally, in order to verify whether this biological activity could be attributed to a direct interaction of pinosylvin with JAK2, a molecular docking study was performed, confirming the capability of pinosylvin to bind the active site of the protein.
Keyphrases
- signaling pathway
- anti inflammatory
- induced apoptosis
- molecular docking
- lps induced
- pi k akt
- inflammatory response
- cell cycle arrest
- epithelial mesenchymal transition
- ms ms
- poor prognosis
- cell proliferation
- rheumatoid arthritis
- molecular dynamics simulations
- binding protein
- simultaneous determination
- oxidative stress
- cell death
- protein protein
- long non coding rna
- heat stress