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

鉴定黑松亚种落叶松中的松醇:一种天然存在的芪类化合物,可抑制 LPS 诱导的促炎细胞因子和介质表达并抑制 JAK/STAT 信号通路

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作者:Maria Rosaria Perri, Michele Pellegrino, Mariangela Marrelli, Stefano Aquaro, Fabiola Cavaliere, Fedora Grande, Maria Antonietta Occhiuzzi, Carmine Lupia, Claudia-Crina Toma, Filomena Conforti, Giancarlo Statti

Abstract

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.

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