Identification of Pinosylvin in <i>Pinus nigra</i> subsp. <i>laricio</i>: A Naturally Occurring Stilbenoid Suppressing LPS-Induced Expression of Pro-Inflammatory Cytokines and Mediators and Inhibiting the JAK/STAT Signaling Pathway
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 <i>Pinus nigra</...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-05-01
|
| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/16/5/718 |
| _version_ | 1797598715739897856 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Maria Rosaria Perri |
| collection | DOAJ |
| description | 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 <i>Pinus nigra</i> subsp. <i>laricio</i> var. <i>calabrica</i> 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. |
| first_indexed | 2024-03-11T03:25:36Z |
| format | Article |
| id | doaj.art-8e685358aa964a888c410972e8680174 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-11T03:25:36Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-8e685358aa964a888c410972e86801742023-11-18T02:48:55ZengMDPI AGPharmaceuticals1424-82472023-05-0116571810.3390/ph16050718Identification of Pinosylvin in <i>Pinus nigra</i> subsp. <i>laricio</i>: A Naturally Occurring Stilbenoid Suppressing LPS-Induced Expression of Pro-Inflammatory Cytokines and Mediators and Inhibiting the JAK/STAT Signaling PathwayMaria Rosaria Perri0Michele Pellegrino1Mariangela Marrelli2Stefano Aquaro3Fabiola Cavaliere4Fedora Grande5Maria Antonietta Occhiuzzi6Carmine Lupia7Claudia-Crina Toma8Filomena Conforti9Giancarlo Statti10Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, ItalyDepartment of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, ItalyDepartment of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, ItalyDepartment of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, ItalyDepartment of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, ItalyDepartment of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, ItalyDepartment of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, ItalyMediterranean Ethnobotanical Conservatory, 88054 Sersale, ItalyPharmacognosy Department, Faculty of Pharmacy, Vasile Goldis Western University of Arad, 87 L. Rebreanu Str., 310045 Arad, RomaniaDepartment of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, ItalyDepartment of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, ItalyStilbenoids, 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 <i>Pinus nigra</i> subsp. <i>laricio</i> var. <i>calabrica</i> 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.https://www.mdpi.com/1424-8247/16/5/718HPLCIL-6inflammationmolecular docking<i>Pinus</i> extractRAW 264.7 |
| spellingShingle | 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 Identification of Pinosylvin in <i>Pinus nigra</i> subsp. <i>laricio</i>: A Naturally Occurring Stilbenoid Suppressing LPS-Induced Expression of Pro-Inflammatory Cytokines and Mediators and Inhibiting the JAK/STAT Signaling Pathway Pharmaceuticals HPLC IL-6 inflammation molecular docking <i>Pinus</i> extract RAW 264.7 |
| title | Identification of Pinosylvin in <i>Pinus nigra</i> subsp. <i>laricio</i>: A Naturally Occurring Stilbenoid Suppressing LPS-Induced Expression of Pro-Inflammatory Cytokines and Mediators and Inhibiting the JAK/STAT Signaling Pathway |
| title_full | Identification of Pinosylvin in <i>Pinus nigra</i> subsp. <i>laricio</i>: A Naturally Occurring Stilbenoid Suppressing LPS-Induced Expression of Pro-Inflammatory Cytokines and Mediators and Inhibiting the JAK/STAT Signaling Pathway |
| title_fullStr | Identification of Pinosylvin in <i>Pinus nigra</i> subsp. <i>laricio</i>: A Naturally Occurring Stilbenoid Suppressing LPS-Induced Expression of Pro-Inflammatory Cytokines and Mediators and Inhibiting the JAK/STAT Signaling Pathway |
| title_full_unstemmed | Identification of Pinosylvin in <i>Pinus nigra</i> subsp. <i>laricio</i>: A Naturally Occurring Stilbenoid Suppressing LPS-Induced Expression of Pro-Inflammatory Cytokines and Mediators and Inhibiting the JAK/STAT Signaling Pathway |
| title_short | Identification of Pinosylvin in <i>Pinus nigra</i> subsp. <i>laricio</i>: A Naturally Occurring Stilbenoid Suppressing LPS-Induced Expression of Pro-Inflammatory Cytokines and Mediators and Inhibiting the JAK/STAT Signaling Pathway |
| title_sort | identification of pinosylvin in i pinus nigra i subsp i laricio i a naturally occurring stilbenoid suppressing lps induced expression of pro inflammatory cytokines and mediators and inhibiting the jak stat signaling pathway |
| topic | HPLC IL-6 inflammation molecular docking <i>Pinus</i> extract RAW 264.7 |
| url | https://www.mdpi.com/1424-8247/16/5/718 |
| work_keys_str_mv | AT mariarosariaperri identificationofpinosylvininipinusnigraisubspilaricioianaturallyoccurringstilbenoidsuppressinglpsinducedexpressionofproinflammatorycytokinesandmediatorsandinhibitingthejakstatsignalingpathway AT michelepellegrino identificationofpinosylvininipinusnigraisubspilaricioianaturallyoccurringstilbenoidsuppressinglpsinducedexpressionofproinflammatorycytokinesandmediatorsandinhibitingthejakstatsignalingpathway AT mariangelamarrelli identificationofpinosylvininipinusnigraisubspilaricioianaturallyoccurringstilbenoidsuppressinglpsinducedexpressionofproinflammatorycytokinesandmediatorsandinhibitingthejakstatsignalingpathway AT stefanoaquaro identificationofpinosylvininipinusnigraisubspilaricioianaturallyoccurringstilbenoidsuppressinglpsinducedexpressionofproinflammatorycytokinesandmediatorsandinhibitingthejakstatsignalingpathway AT fabiolacavaliere identificationofpinosylvininipinusnigraisubspilaricioianaturallyoccurringstilbenoidsuppressinglpsinducedexpressionofproinflammatorycytokinesandmediatorsandinhibitingthejakstatsignalingpathway AT fedoragrande identificationofpinosylvininipinusnigraisubspilaricioianaturallyoccurringstilbenoidsuppressinglpsinducedexpressionofproinflammatorycytokinesandmediatorsandinhibitingthejakstatsignalingpathway AT mariaantoniettaocchiuzzi identificationofpinosylvininipinusnigraisubspilaricioianaturallyoccurringstilbenoidsuppressinglpsinducedexpressionofproinflammatorycytokinesandmediatorsandinhibitingthejakstatsignalingpathway AT carminelupia identificationofpinosylvininipinusnigraisubspilaricioianaturallyoccurringstilbenoidsuppressinglpsinducedexpressionofproinflammatorycytokinesandmediatorsandinhibitingthejakstatsignalingpathway AT claudiacrinatoma identificationofpinosylvininipinusnigraisubspilaricioianaturallyoccurringstilbenoidsuppressinglpsinducedexpressionofproinflammatorycytokinesandmediatorsandinhibitingthejakstatsignalingpathway AT filomenaconforti identificationofpinosylvininipinusnigraisubspilaricioianaturallyoccurringstilbenoidsuppressinglpsinducedexpressionofproinflammatorycytokinesandmediatorsandinhibitingthejakstatsignalingpathway AT giancarlostatti identificationofpinosylvininipinusnigraisubspilaricioianaturallyoccurringstilbenoidsuppressinglpsinducedexpressionofproinflammatorycytokinesandmediatorsandinhibitingthejakstatsignalingpathway |