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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Veröffentlicht in:International immunopharmacology 2019-07, Vol.72, p.31-39
Hauptverfasser: 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
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container_start_page 31
container_title International immunopharmacology
container_volume 72
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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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. 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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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