Natural chromones as potential anti-inflammatory agents: Pharmacological properties and related mechanisms
Chromones are a group of natural substances with a diversity of biological activities. Herein we assessed the pharmacological potential of three chromones (1, 2 and 3) isolated from Dictyoloma vandellianum as anti-inflammatory agents using in vitro and in vivo approaches. During in vitro screening,...
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creator | Opretzka, Luiza Carolina França Espírito-Santo, Renan Fernandes do Nascimento, Olívia Azevedo Abreu, Lucas Silva Alves, Iura Muniz Döring, Eva Soares, Milena Botelho Pereira Velozo, Eudes da Silva Laufer, Stefan A. Villarreal, Cristiane Flora |
description | Chromones are a group of natural substances with a diversity of biological activities. Herein we assessed the pharmacological potential of three chromones (1, 2 and 3) isolated from Dictyoloma vandellianum as anti-inflammatory agents using in vitro and in vivo approaches. During in vitro screening, the production of NO and cytokines by macrophages stimulated with LPS and IFN-γ was inhibited by all chromones at concentrations (5–20 μM) that did not induce cytotoxicity. Analysis of pharmacokinetic parameters (in vitro half-life and intrinsic clearance) using human liver microsomes revealed that 3 has a superior pharmacokinetic profile, compared to 1 and 2. Treatment with 3 (100 mg/kg, ip) did not affect the mice motor performance, while 1 and 2 induced motor deficit. Taking into account the pharmacokinetic profile and absence of motor impairment, 3 was selected for further pharmacological characterization. Corroborating the data from in vitro screening, treatment of cell cultures with 3 (5–20 μM) reduced TNF-α, IL-6 and IL-1β production by stimulated macrophages. In the complete Freund's adjuvant-induced paw inflammation model in mice, 3 (25 and 50 mg/kg, ip) inhibited mechanical hyperalgesia, edema and cytokine production/release (IL-1β, IL-6 and TNF-α). 3 (5–20 μM) also reduced the transcriptional activity of NF-κB in stimulated macrophages. Furthermore, treatment with RU486, a glucocorticoid receptor (GR) antagonist, partially prevented the inhibitory effect of 3 on macrophages, indicating that this chromone exerts its anti-inflammatory effects in part through the activation of GR. The results presented herein demonstrate the pharmacological potential of natural chromones, highlighting 3 as a possible candidate for the drug discovery process targeting new anti-inflammatory drugs.
•Chromones from Dictyoloma vandellianum have consistent anti-inflammatory properties.•Natural chromones have favorable in vitro pharmacokinetic profile.•Anti-inflammatory effects of chromones involve glucocorticoid receptors activation.•Inhibition of NF-κB may contribute to the anti-inflammatory effects of chromones. |
doi_str_mv | 10.1016/j.intimp.2019.03.044 |
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•Chromones from Dictyoloma vandellianum have consistent anti-inflammatory properties.•Natural chromones have favorable in vitro pharmacokinetic profile.•Anti-inflammatory effects of chromones involve glucocorticoid receptors activation.•Inhibition of NF-κB may contribute to the anti-inflammatory effects of chromones.</description><identifier>ISSN: 1567-5769</identifier><identifier>EISSN: 1878-1705</identifier><identifier>DOI: 10.1016/j.intimp.2019.03.044</identifier><identifier>PMID: 30959369</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Anti-inflammatory ; Anti-inflammatory agents ; Antinociception ; Biocompatibility ; Biodiversity ; Chromones ; Cytokines ; Cytotoxicity ; Drug delivery ; Drug development ; Drug discovery ; Edema ; Freund's adjuvant ; Glucocorticoid receptor ; Glucocorticoids ; IL-1β ; Inflammation ; Interleukin 6 ; Lipopolysaccharides ; Macrophages ; Mice ; Microsomes ; Motor task performance ; NF-κB ; NF-κB protein ; Pain perception ; Pharmacology ; Screening ; Toxicity ; Transcription ; Tumor necrosis factor-α ; γ-Interferon</subject><ispartof>International immunopharmacology, 2019-07, Vol.72, p.31-39</ispartof><rights>2019 Elsevier B.V.</rights><rights>Copyright © 2019 Elsevier B.V. All rights reserved.</rights><rights>Copyright Elsevier BV Jul 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c436t-7c050aa997eb32c4167fd8759479494d99cf52b1c50091ce05c286f3f15b85673</citedby><cites>FETCH-LOGICAL-c436t-7c050aa997eb32c4167fd8759479494d99cf52b1c50091ce05c286f3f15b85673</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.intimp.2019.03.044$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,782,786,3552,27931,27932,46002</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30959369$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Opretzka, Luiza Carolina França</creatorcontrib><creatorcontrib>Espírito-Santo, Renan Fernandes do</creatorcontrib><creatorcontrib>Nascimento, Olívia Azevedo</creatorcontrib><creatorcontrib>Abreu, Lucas Silva</creatorcontrib><creatorcontrib>Alves, Iura Muniz</creatorcontrib><creatorcontrib>Döring, Eva</creatorcontrib><creatorcontrib>Soares, Milena Botelho Pereira</creatorcontrib><creatorcontrib>Velozo, Eudes da Silva</creatorcontrib><creatorcontrib>Laufer, Stefan A.</creatorcontrib><creatorcontrib>Villarreal, Cristiane Flora</creatorcontrib><title>Natural chromones as potential anti-inflammatory agents: Pharmacological properties and related mechanisms</title><title>International immunopharmacology</title><addtitle>Int Immunopharmacol</addtitle><description>Chromones are a group of natural substances with a diversity of biological activities. Herein we assessed the pharmacological potential of three chromones (1, 2 and 3) isolated from Dictyoloma vandellianum as anti-inflammatory agents using in vitro and in vivo approaches. During in vitro screening, the production of NO and cytokines by macrophages stimulated with LPS and IFN-γ was inhibited by all chromones at concentrations (5–20 μM) that did not induce cytotoxicity. Analysis of pharmacokinetic parameters (in vitro half-life and intrinsic clearance) using human liver microsomes revealed that 3 has a superior pharmacokinetic profile, compared to 1 and 2. Treatment with 3 (100 mg/kg, ip) did not affect the mice motor performance, while 1 and 2 induced motor deficit. Taking into account the pharmacokinetic profile and absence of motor impairment, 3 was selected for further pharmacological characterization. Corroborating the data from in vitro screening, treatment of cell cultures with 3 (5–20 μM) reduced TNF-α, IL-6 and IL-1β production by stimulated macrophages. In the complete Freund's adjuvant-induced paw inflammation model in mice, 3 (25 and 50 mg/kg, ip) inhibited mechanical hyperalgesia, edema and cytokine production/release (IL-1β, IL-6 and TNF-α). 3 (5–20 μM) also reduced the transcriptional activity of NF-κB in stimulated macrophages. Furthermore, treatment with RU486, a glucocorticoid receptor (GR) antagonist, partially prevented the inhibitory effect of 3 on macrophages, indicating that this chromone exerts its anti-inflammatory effects in part through the activation of GR. The results presented herein demonstrate the pharmacological potential of natural chromones, highlighting 3 as a possible candidate for the drug discovery process targeting new anti-inflammatory drugs.
•Chromones from Dictyoloma vandellianum have consistent anti-inflammatory properties.•Natural chromones have favorable in vitro pharmacokinetic profile.•Anti-inflammatory effects of chromones involve glucocorticoid receptors activation.•Inhibition of NF-κB may contribute to the anti-inflammatory effects of chromones.</description><subject>Anti-inflammatory</subject><subject>Anti-inflammatory agents</subject><subject>Antinociception</subject><subject>Biocompatibility</subject><subject>Biodiversity</subject><subject>Chromones</subject><subject>Cytokines</subject><subject>Cytotoxicity</subject><subject>Drug delivery</subject><subject>Drug development</subject><subject>Drug discovery</subject><subject>Edema</subject><subject>Freund's adjuvant</subject><subject>Glucocorticoid receptor</subject><subject>Glucocorticoids</subject><subject>IL-1β</subject><subject>Inflammation</subject><subject>Interleukin 6</subject><subject>Lipopolysaccharides</subject><subject>Macrophages</subject><subject>Mice</subject><subject>Microsomes</subject><subject>Motor task performance</subject><subject>NF-κB</subject><subject>NF-κB protein</subject><subject>Pain perception</subject><subject>Pharmacology</subject><subject>Screening</subject><subject>Toxicity</subject><subject>Transcription</subject><subject>Tumor necrosis factor-α</subject><subject>γ-Interferon</subject><issn>1567-5769</issn><issn>1878-1705</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kc1u1TAQhS0EoqXwBqiKxIZNgh3bcdxFpariT6qgi7K2fJ1Jr6M4DrZTqW_PXN2WBQtWMxp_czwzh5D3jDaMsu7T1Pil-LA2LWW6obyhQrwgp6xXfc0UlS8xl52qper0CXmT80Qp1gV7TU441VLzTp-S6YctW7Jz5fYphrhArmyu1lgAxbFsMdR-GWcbgi0xPVb2Hp_yRXW7tylYF-d47x2Sa4orpOIPCstQJZhtgaEK4PZ28Tnkt-TVaOcM757iGfn15fPd9bf65ufX79dXN7UTvCu1clRSa7VWsOOtE6xT49ArqYXSQotBazfKdsecpFQzB1S6tu9GPjK563FhfkY-HnVxot8b5GKCzw7m2S4Qt2zalnYtZ0JoRD_8g05xSwtOh5RoldKSMaTEkXIp5pxgNGvywaZHw6g5eGEmc_TCHLwwlBv0AtvOn8S3XYDhb9Pz8RG4PAKA13jwkEx2HhYHg0_gihmi__8PfwBJKp1K</recordid><startdate>20190701</startdate><enddate>20190701</enddate><creator>Opretzka, Luiza Carolina França</creator><creator>Espírito-Santo, Renan Fernandes do</creator><creator>Nascimento, Olívia Azevedo</creator><creator>Abreu, Lucas Silva</creator><creator>Alves, Iura Muniz</creator><creator>Döring, Eva</creator><creator>Soares, Milena Botelho Pereira</creator><creator>Velozo, Eudes da Silva</creator><creator>Laufer, Stefan A.</creator><creator>Villarreal, Cristiane Flora</creator><general>Elsevier B.V</general><general>Elsevier BV</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7T5</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20190701</creationdate><title>Natural chromones as potential anti-inflammatory agents: Pharmacological properties and related mechanisms</title><author>Opretzka, Luiza Carolina França ; Espírito-Santo, Renan Fernandes do ; Nascimento, Olívia Azevedo ; Abreu, Lucas Silva ; Alves, Iura Muniz ; Döring, Eva ; Soares, Milena Botelho Pereira ; Velozo, Eudes da Silva ; Laufer, Stefan A. ; Villarreal, Cristiane Flora</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c436t-7c050aa997eb32c4167fd8759479494d99cf52b1c50091ce05c286f3f15b85673</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Anti-inflammatory</topic><topic>Anti-inflammatory agents</topic><topic>Antinociception</topic><topic>Biocompatibility</topic><topic>Biodiversity</topic><topic>Chromones</topic><topic>Cytokines</topic><topic>Cytotoxicity</topic><topic>Drug delivery</topic><topic>Drug development</topic><topic>Drug discovery</topic><topic>Edema</topic><topic>Freund's adjuvant</topic><topic>Glucocorticoid receptor</topic><topic>Glucocorticoids</topic><topic>IL-1β</topic><topic>Inflammation</topic><topic>Interleukin 6</topic><topic>Lipopolysaccharides</topic><topic>Macrophages</topic><topic>Mice</topic><topic>Microsomes</topic><topic>Motor task performance</topic><topic>NF-κB</topic><topic>NF-κB protein</topic><topic>Pain perception</topic><topic>Pharmacology</topic><topic>Screening</topic><topic>Toxicity</topic><topic>Transcription</topic><topic>Tumor necrosis factor-α</topic><topic>γ-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Opretzka, Luiza Carolina França</creatorcontrib><creatorcontrib>Espírito-Santo, Renan Fernandes do</creatorcontrib><creatorcontrib>Nascimento, Olívia Azevedo</creatorcontrib><creatorcontrib>Abreu, Lucas Silva</creatorcontrib><creatorcontrib>Alves, Iura Muniz</creatorcontrib><creatorcontrib>Döring, Eva</creatorcontrib><creatorcontrib>Soares, Milena Botelho Pereira</creatorcontrib><creatorcontrib>Velozo, Eudes da Silva</creatorcontrib><creatorcontrib>Laufer, Stefan A.</creatorcontrib><creatorcontrib>Villarreal, Cristiane Flora</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>International immunopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Opretzka, Luiza Carolina França</au><au>Espírito-Santo, Renan Fernandes do</au><au>Nascimento, Olívia Azevedo</au><au>Abreu, Lucas Silva</au><au>Alves, Iura Muniz</au><au>Döring, Eva</au><au>Soares, Milena Botelho Pereira</au><au>Velozo, Eudes da Silva</au><au>Laufer, Stefan A.</au><au>Villarreal, Cristiane Flora</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Natural chromones as potential anti-inflammatory agents: Pharmacological properties and related mechanisms</atitle><jtitle>International immunopharmacology</jtitle><addtitle>Int Immunopharmacol</addtitle><date>2019-07-01</date><risdate>2019</risdate><volume>72</volume><spage>31</spage><epage>39</epage><pages>31-39</pages><issn>1567-5769</issn><eissn>1878-1705</eissn><abstract>Chromones are a group of natural substances with a diversity of biological activities. Herein we assessed the pharmacological potential of three chromones (1, 2 and 3) isolated from Dictyoloma vandellianum as anti-inflammatory agents using in vitro and in vivo approaches. During in vitro screening, the production of NO and cytokines by macrophages stimulated with LPS and IFN-γ was inhibited by all chromones at concentrations (5–20 μM) that did not induce cytotoxicity. Analysis of pharmacokinetic parameters (in vitro half-life and intrinsic clearance) using human liver microsomes revealed that 3 has a superior pharmacokinetic profile, compared to 1 and 2. Treatment with 3 (100 mg/kg, ip) did not affect the mice motor performance, while 1 and 2 induced motor deficit. Taking into account the pharmacokinetic profile and absence of motor impairment, 3 was selected for further pharmacological characterization. Corroborating the data from in vitro screening, treatment of cell cultures with 3 (5–20 μM) reduced TNF-α, IL-6 and IL-1β production by stimulated macrophages. In the complete Freund's adjuvant-induced paw inflammation model in mice, 3 (25 and 50 mg/kg, ip) inhibited mechanical hyperalgesia, edema and cytokine production/release (IL-1β, IL-6 and TNF-α). 3 (5–20 μM) also reduced the transcriptional activity of NF-κB in stimulated macrophages. Furthermore, treatment with RU486, a glucocorticoid receptor (GR) antagonist, partially prevented the inhibitory effect of 3 on macrophages, indicating that this chromone exerts its anti-inflammatory effects in part through the activation of GR. The results presented herein demonstrate the pharmacological potential of natural chromones, highlighting 3 as a possible candidate for the drug discovery process targeting new anti-inflammatory drugs.
•Chromones from Dictyoloma vandellianum have consistent anti-inflammatory properties.•Natural chromones have favorable in vitro pharmacokinetic profile.•Anti-inflammatory effects of chromones involve glucocorticoid receptors activation.•Inhibition of NF-κB may contribute to the anti-inflammatory effects of chromones.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>30959369</pmid><doi>10.1016/j.intimp.2019.03.044</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Anti-inflammatory Anti-inflammatory agents Antinociception Biocompatibility Biodiversity Chromones Cytokines Cytotoxicity Drug delivery Drug development Drug discovery Edema Freund's adjuvant Glucocorticoid receptor Glucocorticoids IL-1β Inflammation Interleukin 6 Lipopolysaccharides Macrophages Mice Microsomes Motor task performance NF-κB NF-κB protein Pain perception Pharmacology Screening Toxicity Transcription Tumor necrosis factor-α γ-Interferon |
title | Natural chromones as potential anti-inflammatory agents: Pharmacological properties and related mechanisms |
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