Direct Interaction of Garcinol and Related Polyisoprenylated Benzophenones of Garcinia cambogia Fruits with the Transcription Factor STAT‑1 as a Likely Mechanism of Their Inhibitory Effect on Cytokine Signaling Pathways
Garcinol (1), a polyisoprenylated benzophenone occurring in Garcinia species, has been reported to exert anti-inflammatory activity in LPS-stimulated macrophages, through inhibition of NF-κB and/or JAK/STAT-1 activation. In order to provide deeper insight into its effects on the cytokine signaling p...
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| Veröffentlicht in: | Journal of natural products (Washington, D.C.) D.C.), 2014-03, Vol.77 (3), p.543-549 |
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| container_title | Journal of natural products (Washington, D.C.) |
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| creator | Masullo, Milena Menegazzi, Marta Di Micco, Simone Beffy, Pascale Bifulco, Giuseppe Dal Bosco, Martina Novelli, Michela Pizza, Cosimo Masiello, Pellegrino Piacente, Sonia |
| description | Garcinol (1), a polyisoprenylated benzophenone occurring in Garcinia species, has been reported to exert anti-inflammatory activity in LPS-stimulated macrophages, through inhibition of NF-κB and/or JAK/STAT-1 activation. In order to provide deeper insight into its effects on the cytokine signaling pathway and to clarify the underlying molecular mechanisms, 1 was isolated from the fruits of Garcinia cambogia along with two other polyisoprenylated benzophenones, guttiferones K (2) and guttiferone M (3), differing from each other in their isoprenyl moieties and their positions on the benzophenone core. The affinities of 1–3 for the STAT-1 protein have been evaluated by surface plasmon resonance and molecular docking studies and resulted in K D values in the micromolar range. Consistent with the observed high affinity toward the STAT-1 protein, garcinol and guttiferones K and M were able to modulate cytokine signaling in different cultured cell lines, mainly by inhibiting STAT-1 nuclear transfer and DNA binding, as assessed by an electrophorectic mobility shift assay. |
| doi_str_mv | 10.1021/np400804y |
| format | Article |
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In order to provide deeper insight into its effects on the cytokine signaling pathway and to clarify the underlying molecular mechanisms, 1 was isolated from the fruits of Garcinia cambogia along with two other polyisoprenylated benzophenones, guttiferones K (2) and guttiferone M (3), differing from each other in their isoprenyl moieties and their positions on the benzophenone core. The affinities of 1–3 for the STAT-1 protein have been evaluated by surface plasmon resonance and molecular docking studies and resulted in K D values in the micromolar range. Consistent with the observed high affinity toward the STAT-1 protein, garcinol and guttiferones K and M were able to modulate cytokine signaling in different cultured cell lines, mainly by inhibiting STAT-1 nuclear transfer and DNA binding, as assessed by an electrophorectic mobility shift assay.</description><identifier>ISSN: 0163-3864</identifier><identifier>EISSN: 1520-6025</identifier><identifier>DOI: 10.1021/np400804y</identifier><identifier>PMID: 24417609</identifier><language>eng</language><publisher>United States: American Chemical Society and American Society of Pharmacognosy</publisher><subject>Benzophenones - chemistry ; Benzophenones - isolation & purification ; Benzophenones - pharmacology ; Blotting, Northern ; Female ; Fruit - chemistry ; Garcinia ; Garcinia cambogia ; Garcinia cambogia - chemistry ; Humans ; Lipopolysaccharides - pharmacology ; Macrophages - drug effects ; Methicillin-Resistant Staphylococcus aureus - drug effects ; Molecular Conformation ; Molecular Structure ; NF-kappa B - antagonists & inhibitors ; NF-kappa B - drug effects ; Signal Transduction - drug effects ; Sri Lanka ; STAT1 Transcription Factor - drug effects ; Terpenes - chemistry ; Terpenes - isolation & purification ; Terpenes - pharmacology</subject><ispartof>Journal of natural products (Washington, D.C.), 2014-03, Vol.77 (3), p.543-549</ispartof><rights>Copyright © 2014 American Chemical Society and American Society of Pharmacognosy</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a348t-9d8141de0725b76656fbf69fd94d10afcdfd556b23b25b1d182c9d3bd4b1f77e3</citedby><cites>FETCH-LOGICAL-a348t-9d8141de0725b76656fbf69fd94d10afcdfd556b23b25b1d182c9d3bd4b1f77e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/np400804y$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/np400804y$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24417609$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Masullo, Milena</creatorcontrib><creatorcontrib>Menegazzi, Marta</creatorcontrib><creatorcontrib>Di Micco, Simone</creatorcontrib><creatorcontrib>Beffy, Pascale</creatorcontrib><creatorcontrib>Bifulco, Giuseppe</creatorcontrib><creatorcontrib>Dal Bosco, Martina</creatorcontrib><creatorcontrib>Novelli, Michela</creatorcontrib><creatorcontrib>Pizza, Cosimo</creatorcontrib><creatorcontrib>Masiello, Pellegrino</creatorcontrib><creatorcontrib>Piacente, Sonia</creatorcontrib><title>Direct Interaction of Garcinol and Related Polyisoprenylated Benzophenones of Garcinia cambogia Fruits with the Transcription Factor STAT‑1 as a Likely Mechanism of Their Inhibitory Effect on Cytokine Signaling Pathways</title><title>Journal of natural products (Washington, D.C.)</title><addtitle>J. Nat. Prod</addtitle><description>Garcinol (1), a polyisoprenylated benzophenone occurring in Garcinia species, has been reported to exert anti-inflammatory activity in LPS-stimulated macrophages, through inhibition of NF-κB and/or JAK/STAT-1 activation. In order to provide deeper insight into its effects on the cytokine signaling pathway and to clarify the underlying molecular mechanisms, 1 was isolated from the fruits of Garcinia cambogia along with two other polyisoprenylated benzophenones, guttiferones K (2) and guttiferone M (3), differing from each other in their isoprenyl moieties and their positions on the benzophenone core. The affinities of 1–3 for the STAT-1 protein have been evaluated by surface plasmon resonance and molecular docking studies and resulted in K D values in the micromolar range. Consistent with the observed high affinity toward the STAT-1 protein, garcinol and guttiferones K and M were able to modulate cytokine signaling in different cultured cell lines, mainly by inhibiting STAT-1 nuclear transfer and DNA binding, as assessed by an electrophorectic mobility shift assay.</description><subject>Benzophenones - chemistry</subject><subject>Benzophenones - isolation & purification</subject><subject>Benzophenones - pharmacology</subject><subject>Blotting, Northern</subject><subject>Female</subject><subject>Fruit - chemistry</subject><subject>Garcinia</subject><subject>Garcinia cambogia</subject><subject>Garcinia cambogia - chemistry</subject><subject>Humans</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>Macrophages - drug effects</subject><subject>Methicillin-Resistant Staphylococcus aureus - drug effects</subject><subject>Molecular Conformation</subject><subject>Molecular Structure</subject><subject>NF-kappa B - antagonists & inhibitors</subject><subject>NF-kappa B - drug effects</subject><subject>Signal Transduction - drug effects</subject><subject>Sri Lanka</subject><subject>STAT1 Transcription Factor - drug effects</subject><subject>Terpenes - chemistry</subject><subject>Terpenes - isolation & purification</subject><subject>Terpenes - pharmacology</subject><issn>0163-3864</issn><issn>1520-6025</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc1u1DAURiMEokNhwQsgb5BgEbBj529Zhk6pNIiKhnXk2NcTt4md2o6qsOIVeEA2PAkeppQNC1a2rHPPd-UvSZ4T_IbgjLw1E8O4wmx5kKxInuG0wFn-MFlhUtCUVgU7Sp54f4UxprjOHydHGWOkLHC9Sn681w5EQOcmgOMiaGuQVeiMO6GNHRA3En2GgQeQ6MIOi_Z2cmCWw8s7MF_t1IOxBvzfOc2R4GNnd_GycbMOHt3q0KPQA2ocN144Pf2O2sRI69Blc9L8_PadIO4RR1t9DcOCPoLoudF-3IubHrSLW_a603FiQadK7feOjvUS7LU2gC71zvBBmx264KG_5Yt_mjxSfPDw7O48Tr5sTpv1h3T76ex8fbJNOWVVSGtZEUYk4DLLu7Io8kJ1qqiVrJkkmCshlczzostoFwEiSZWJWtJOso6osgR6nLw6eCdnb2bwoR21FzAM3ICdfUvymEPzKqP_hcZSacUi-vqACme9d6DayemRu6UluN0X394XH9kXd9q5G0Hek3-ajsDLA8CFb6_s7OJX-X-IfgGFNbom</recordid><startdate>20140328</startdate><enddate>20140328</enddate><creator>Masullo, Milena</creator><creator>Menegazzi, Marta</creator><creator>Di Micco, Simone</creator><creator>Beffy, Pascale</creator><creator>Bifulco, Giuseppe</creator><creator>Dal Bosco, Martina</creator><creator>Novelli, Michela</creator><creator>Pizza, Cosimo</creator><creator>Masiello, Pellegrino</creator><creator>Piacente, Sonia</creator><general>American Chemical Society and American Society of Pharmacognosy</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7T5</scope><scope>7TM</scope><scope>H94</scope></search><sort><creationdate>20140328</creationdate><title>Direct Interaction of Garcinol and Related Polyisoprenylated Benzophenones of Garcinia cambogia Fruits with the Transcription Factor STAT‑1 as a Likely Mechanism of Their Inhibitory Effect on Cytokine Signaling Pathways</title><author>Masullo, Milena ; Menegazzi, Marta ; Di Micco, Simone ; Beffy, Pascale ; Bifulco, Giuseppe ; Dal Bosco, Martina ; Novelli, Michela ; Pizza, Cosimo ; Masiello, Pellegrino ; Piacente, Sonia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a348t-9d8141de0725b76656fbf69fd94d10afcdfd556b23b25b1d182c9d3bd4b1f77e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Benzophenones - chemistry</topic><topic>Benzophenones - isolation & purification</topic><topic>Benzophenones - pharmacology</topic><topic>Blotting, Northern</topic><topic>Female</topic><topic>Fruit - chemistry</topic><topic>Garcinia</topic><topic>Garcinia cambogia</topic><topic>Garcinia cambogia - chemistry</topic><topic>Humans</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>Macrophages - drug effects</topic><topic>Methicillin-Resistant Staphylococcus aureus - drug effects</topic><topic>Molecular Conformation</topic><topic>Molecular Structure</topic><topic>NF-kappa B - antagonists & inhibitors</topic><topic>NF-kappa B - drug effects</topic><topic>Signal Transduction - drug effects</topic><topic>Sri Lanka</topic><topic>STAT1 Transcription Factor - drug effects</topic><topic>Terpenes - chemistry</topic><topic>Terpenes - isolation & purification</topic><topic>Terpenes - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Masullo, Milena</creatorcontrib><creatorcontrib>Menegazzi, Marta</creatorcontrib><creatorcontrib>Di Micco, Simone</creatorcontrib><creatorcontrib>Beffy, Pascale</creatorcontrib><creatorcontrib>Bifulco, Giuseppe</creatorcontrib><creatorcontrib>Dal Bosco, Martina</creatorcontrib><creatorcontrib>Novelli, Michela</creatorcontrib><creatorcontrib>Pizza, Cosimo</creatorcontrib><creatorcontrib>Masiello, Pellegrino</creatorcontrib><creatorcontrib>Piacente, Sonia</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Journal of natural products (Washington, D.C.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Masullo, Milena</au><au>Menegazzi, Marta</au><au>Di Micco, Simone</au><au>Beffy, Pascale</au><au>Bifulco, Giuseppe</au><au>Dal Bosco, Martina</au><au>Novelli, Michela</au><au>Pizza, Cosimo</au><au>Masiello, Pellegrino</au><au>Piacente, Sonia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Direct Interaction of Garcinol and Related Polyisoprenylated Benzophenones of Garcinia cambogia Fruits with the Transcription Factor STAT‑1 as a Likely Mechanism of Their Inhibitory Effect on Cytokine Signaling Pathways</atitle><jtitle>Journal of natural products (Washington, D.C.)</jtitle><addtitle>J. Nat. Prod</addtitle><date>2014-03-28</date><risdate>2014</risdate><volume>77</volume><issue>3</issue><spage>543</spage><epage>549</epage><pages>543-549</pages><issn>0163-3864</issn><eissn>1520-6025</eissn><abstract>Garcinol (1), a polyisoprenylated benzophenone occurring in Garcinia species, has been reported to exert anti-inflammatory activity in LPS-stimulated macrophages, through inhibition of NF-κB and/or JAK/STAT-1 activation. In order to provide deeper insight into its effects on the cytokine signaling pathway and to clarify the underlying molecular mechanisms, 1 was isolated from the fruits of Garcinia cambogia along with two other polyisoprenylated benzophenones, guttiferones K (2) and guttiferone M (3), differing from each other in their isoprenyl moieties and their positions on the benzophenone core. The affinities of 1–3 for the STAT-1 protein have been evaluated by surface plasmon resonance and molecular docking studies and resulted in K D values in the micromolar range. Consistent with the observed high affinity toward the STAT-1 protein, garcinol and guttiferones K and M were able to modulate cytokine signaling in different cultured cell lines, mainly by inhibiting STAT-1 nuclear transfer and DNA binding, as assessed by an electrophorectic mobility shift assay.</abstract><cop>United States</cop><pub>American Chemical Society and American Society of Pharmacognosy</pub><pmid>24417609</pmid><doi>10.1021/np400804y</doi><tpages>7</tpages></addata></record> |
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| identifier | ISSN: 0163-3864 |
| ispartof | Journal of natural products (Washington, D.C.), 2014-03, Vol.77 (3), p.543-549 |
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| source | MEDLINE; American Chemical Society Journals |
| subjects | Benzophenones - chemistry Benzophenones - isolation & purification Benzophenones - pharmacology Blotting, Northern Female Fruit - chemistry Garcinia Garcinia cambogia Garcinia cambogia - chemistry Humans Lipopolysaccharides - pharmacology Macrophages - drug effects Methicillin-Resistant Staphylococcus aureus - drug effects Molecular Conformation Molecular Structure NF-kappa B - antagonists & inhibitors NF-kappa B - drug effects Signal Transduction - drug effects Sri Lanka STAT1 Transcription Factor - drug effects Terpenes - chemistry Terpenes - isolation & purification Terpenes - pharmacology |
| title | Direct Interaction of Garcinol and Related Polyisoprenylated Benzophenones of Garcinia cambogia Fruits with the Transcription Factor STAT‑1 as a Likely Mechanism of Their Inhibitory Effect on Cytokine Signaling Pathways |
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