RESUMO
This study aims to explore the anti-inflammatory mechanisms of sargachromenol in both RAW 264.7 cells and lipopolysaccharide (LPS)-treated mice, as previous reports have suggested that sargachromenol possesses anti-aging, anti-inflammatory, antioxidant, and neuroprotective properties. Although the precise mechanism behind its anti-inflammatory activity remains unclear, pretreatment with sargachromenol effectively reduced the production of nitric oxide, prostaglandin E2, and interleukin (IL)-1ß in LPS-stimulated RAW 264.7 cells by inhibiting cyclooxygenase-2. Moreover, sargachromenol inhibited the activation of nuclear factor-κB (NF-κB) by preventing the degradation of the inhibitor of κB-α (IκB-α) and inhibiting protein kinase B (Akt) phosphorylation in LPS-stimulated cells. We also found that sargachromenol induced the production of heme oxygenase-1 (HO-1) by activating the nuclear transcription factor erythroid-2-related factor 2 (Nrf2). In LPS-treated mice, oral administration of sargachromenol effectively reduced the levels of IL-1ß, IL-6, and tumor necrosis factor-α (TNF-α) in the serum, suggesting its ability to suppress the production of inflammatory mediators by inhibiting the Akt/NF-κB pathway and upregulating the Nrf2/HO-1 pathway.
Assuntos
Lipopolissacarídeos , NF-kappa B , Animais , Camundongos , NF-kappa B/metabolismo , Células RAW 264.7 , Lipopolissacarídeos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Anti-Inflamatórios/farmacologia , Heme Oxigenase-1/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Ciclo-Oxigenase 2/metabolismoRESUMO
Sargassum species have been reported to be a source of phytochemicals, with a wide range of biological activities. In this study, we evaluated the hepatoprotective effect of a meroterpenoid-rich fraction of the ethanolic extract from Sargassum serratifolium (MES) against tert-butyl hydroperoxide (t-BHP)-treated HepG2 cells. Treatment with MES recovered the cell viability from the t-BHP-induced oxidative damage in a dose-dependent manner. It suppressed the reactive oxygen species production, lipid peroxidation, and glutathione depletion in the t-BHP-treated HepG2 cells. The activity of the antioxidants induced by t-BHP, including superoxide dismutase (SOD) and catalase, was reduced by the MES treatment. Moreover, it increased the nuclear translocation of nuclear factor erythroid 2-related factor 2, leading to the enhanced activity of glutathione S transferase, and the increased production of heme oxygenase-1 and NAD(P)H:quinine oxidoreductase 1 in t-BHP-treated HepG2 cells. These results demonstrate that the antioxidant activity of MES substituted the activity of the SOD and catalase, and induced the production of detoxifying enzymes, indicating that MES might be used as a hepatoprotectant against t-BHP-induced oxidative stress.
Assuntos
Etanol/química , Estresse Oxidativo/efeitos dos fármacos , Sargassum/química , Terpenos/química , Terpenos/farmacologia , terc-Butil Hidroperóxido/farmacologia , Antioxidantes/metabolismo , Catalase/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Glutationa/metabolismo , Heme Oxigenase-1/metabolismo , Células Hep G2 , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , NADP/metabolismo , Oxirredução/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismoRESUMO
OBJECTIVE: Microglial activation has been implicated in many neurological disorders for its inflammatory and neurotrophic effects. In this study, we investigated the pharmaceutical properties of 6,6'-bieckol on the regulation of nuclear factor-κB (NF-κB) activation responsible to the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 using lipopolysaccharide (LPS)-stimulated BV2 and murine primary microglial cells. Meterials and methods: The levels of nitric oxide (NO), prostaglandin E2 (PGE)2, and pro-inflammatory cytokines were measured by Griess assay and enzyme-linked immunosorbent assay. The levels of iNOS, COX-2, mitogen-activated protein kinases (MAPKs), and Akt were measured using Western blot. Nuclear translocation and transcriptional activation of NF-κB were determined by immunofluorescence and reporter gene assay, respectively. RESULTS: We found that 6,6'-bieckol decreased the expression of iNOS and COX-2 as well as pro-inflammatory cytokines in LPS-stimulated BV2 and primary microglial cells in a dose-dependent manner. 6,6'-Bieckol inhibited activation of NF-κB by preventing the degradation of inhibitor κB (IκB)-α and led to prevent the nuclear translocation of NF-κB/p65 subunit. Moreover, 6,6'-bieckol inhibited the phosphorylation of Akt, JNK, and p38 MAPK. DISCUSSION AND CONCLUSION: These results indicate that the anti-inflammatory effect of 6,6'-bieckol on LPS-stimulated microglial cells is mainly regulated by the inhibition of IκB-α/NF-κB and JNK/p38 MAPK/Akt pathways, supporting biochemical characteristics of the compound for therapeutic agent against neuroinflammatory diseases caused by microglial activation.
Assuntos
Anti-Inflamatórios/farmacologia , Regulação para Baixo/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , MAP Quinase Quinase 4/imunologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Microglia/imunologia , NF-kappa B/imunologia , Proteínas Proto-Oncogênicas c-akt/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno/imunologia , Animais , Anti-Inflamatórios/química , Regulação para Baixo/imunologia , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/imunologia , Sistema de Sinalização das MAP Quinases/imunologia , Camundongos , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Excessive pro-inflammatory cytokine production from activated microglia contributes to neurodegenerative diseases, thus, microglial inactivation may delay the progress of neurodegeneration by attenuating the neuroinflammation. Among 5 selected brown algae, we found the highest antioxidant and anti-neuroinflammatory activities from Myagropsis myagroides ethanolic extract (MME) in lipopolysaccharide (LPS)-stimulated BV-2 cells. METHODS: The levels of nitric oxide (NO), prostaglandin E2 (PGE2), and pro-inflammatory cytokines were measured by Griess assay and enzyme linked immunesorbent assay. The levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), mitogen-activated protein kinases (MAPKs), and Akt were measured using Western blot. Nuclear translocation and transcriptional activation of nuclear factor-κB (NF-κB) were determined by immunefluorescence and reporter gene assay, respectively. RESULTS: MME inhibited the expression of iNOS and COX-2 at mRNA and protein levels, resulting in reduction of NO and PGE2 production. As a result, pro-inflammatory cytokines were reduced by MME. MME also inhibited the activation and translocation of NF-κB by preventing inhibitor κB-α (IκB-α) degradation. Moreover, MME inhibited the phosphorylation of extracellular signal regulated kinases (ERKs) and c-Jun N-terminal kinases (JNKs). Main anti-inflammatory compound in MME was identified as sargachromenol by NMR spectroscopy. CONCLUSIONS: These results indicate that the anti-inflammatory effect of sargachromenol-rich MME on LPS-stimulated microglia is mainly regulated by the inhibition of IκB-α/NF-κB and ERK/JNK pathways.
Assuntos
Anti-Inflamatórios/farmacologia , Benzopiranos/farmacologia , Phaeophyceae/química , Análise de Variância , Animais , Anti-Inflamatórios/química , Benzopiranos/química , Linhagem Celular , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Microglia/efeitos dos fármacos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: This study aims to investigate anti-inflammatory effect of ethanolic extract of Myagropsis myagroides (EMM) in the lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and the phorbol 12-myristate 13-acetate (PMA)-induced ear edema in mice, and to clarify its underlying molecular mechanisms. METHODS: The levels of nitric oxide (NO), prostaglandin E2 (PGE2), and pro-inflammatory cytokines were measured by Griess assay and enzyme linked immunosorbent assay. The expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), mitogen-activated protein kinases (MAPKs), and Akt were measured using Western blotting. Nuclear translocation and transcriptional activation of nuclear factor-κB (NF-κB) were determined by immunocytochemistry and reporter gene assay, respectively. PMA-induced mouse ear edema was used as the animal model of inflammation. Anti-inflammatory compounds in EMM were isolated using high-performance liquid chromatography and identified by nuclear magnetic resonance. RESULTS: EMM significantly inhibited the production of NO, PGE2, and pro-inflammatory cytokines in a dose-dependent manner and suppressed the expression of iNOS and COX-2 in LPS-stimulated RAW 264.7 cells. EMM strongly suppressed nuclear translocation of NF-κB by preventing degradation of inhibitor of κB-α as well as by inhibiting phosphorylation of Akt and MAPKs. EMM reduced ear edema in PMA-induced mice. One of the anti-inflammatory compounds in EMM was identified as 6,6'-bieckol. CONCLUSIONS: These results suggest that the anti-inflammatory properties of EMM are associated with the down-regulation of iNOS, COX-2, and pro-inflammatory cytokines through the inhibition of NF-κB pathway in LPS-stimulated macrophages.
Assuntos
Anti-Inflamatórios/uso terapêutico , Edema/tratamento farmacológico , Mediadores da Inflamação/metabolismo , Inflamação/prevenção & controle , Phaeophyceae/química , Fitoterapia , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/análise , Anti-Inflamatórios/farmacologia , Transporte Biológico , Dioxinas/análise , Dioxinas/farmacologia , Dioxinas/uso terapêutico , Orelha , Inflamação/induzido quimicamente , Inflamação/metabolismo , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais/química , Extratos Vegetais/farmacologiaRESUMO
Colitis is a colon mucosal disorder characterized by intestinal damage and inflammation. This current study aimed to evaluate the effect of meroterpenoid-rich ethanoic extract of a brown algae, Sargassum macrocarpum (MES) on dextran sulfate sodium (DSS)-induced colitis in mice and explore the possible mechanisms. Mice were given 4% DSS in drinking water for 7 days to induce colitis, followed by 3 days of regular water. MES (12 mg/kg body weight) or celecoxib (10 mg/kg body weight) was administrated orally to mice on a daily basis during these 10 days. Both MES and celecoxib supplementations significantly attenuated DSS-induced weight loss, shortening of colon length, elevated myeloperoxidase activity as well as histomorphological changes of colon. MES and celecoxib reduced the inflammation level of colon tissue, as indicated by its suppression on a panel of pro-inflammatory cytokines, including interleukin (IL)-1ß, IL-17, tumor necrosis factor α, and interferon γ, and a group of inflammatory proteins, including intracellular adhesion molecule 1, vascular adhesion molecule 1, matrix metalloproteinase (MMP)-2, MMP-9, MMP-13, and inducible nitric oxidase. In addition, their administration down-regulated pro-inflammatory cytokines in serum. Moreover, the supplementation of MES suppressed the DSS-induced hyperactivation of Akt, JNK, and NF-κB signaling pathways. Taken together, our results demonstrate that MES ameliorates DSS-induced colitis in mice, suggesting that MES may have therapeutic implications for the treatment of colitis.
RESUMO
Sargahydroquinoic acid (SHQA) is a major plastoquinone in Sargassum macrocarpum and has shown the capacity to prevent inflammation and oxidative stress. However, the protective mechanisms were unclear. The molecular mechanisms of SHQA on ameliorating inflammation and oxidative stress have been investigated, using lipopolysaccharide (LPS)-stimulated macrophages. SHQA was isolated and purified from S. macrocarpum and the anti-inflammatory mechanisms were explored using LPS-stimulated murine macrophage RAW 264.7 cells. SHQA did not change the expression of cyclooxygenase-2 (COX-2) but inhibited the activity of COX-2. As a result, SHQA significantly diminished the secretions of nitric oxide (NO), prostaglandin E2 (PGE2), and multiple pro-inflammatory cytokines. LPS-induced activation of nuclear factor-κB (NF-κB) was inhibited by SHQA by preventing the degradation of inhibitor κB-α (IκBα). NF-κB activation was also downregulated by the inhibition of Akt phosphorylation in LPS-stimulated cells. Furthermore, SHQA induced the expression of heme oxygenase 1 via Nrf2 activation. These results indicated that SHQA inhibited LPS-induced expressions of inflammatory mediators via suppressing the Akt-mediated NF-κB pathway as well as upregulating the Nrf2/HO-1 pathway. Our findings suggest that SHQA might be a potential therapeutic agent in various inflammatory diseases.
Assuntos
Alcenos/farmacologia , Anti-Inflamatórios/farmacologia , Benzoquinonas/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Lipopolissacarídeos/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/antagonistas & inibidores , Alcenos/isolamento & purificação , Animais , Anti-Inflamatórios/isolamento & purificação , Benzoquinonas/isolamento & purificação , Inibidores de Ciclo-Oxigenase 2/isolamento & purificação , Relação Dose-Resposta a Droga , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Camundongos , NF-kappa B/metabolismo , Células RAW 264.7 , SargassumRESUMO
SCOPE: Rheumatoid arthritis (RA) is an autoimmune disorder related to the inflammation of cartilage due to the infiltration of inflammatory cells. Sargassum serratifolium, a brown alga, possesses strong anti-inflammatory activities. METHODS AND RESULTS: The effect of meroterpenoid-rich fraction from the ethanol extract of S. serratifolium (MES) on RA and its underlying mechanisms on the inhibition of RA using a collagen-induced arthritis (CIA) mouse model are examined. The results show that MES ameliorates paw swelling and reduces the arthritis score. MES considerably decreases the secretion of pro-inflammatory cytokines in the serum and joint tissue of mice. Histopathological analysis demonstrates that MES strongly inhibited bone damage and inflammatory cell intrusion in the joint tissue. The expression of inflammatory enzymes and adhesion molecules is significantly inhibited in the serum and joint tissue of MES-fed mice. In addition, MES downregulates the nuclear factor κB (NF-κB) signaling pathway by suppressing the phosphorylation of protein kinase B, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinases. CONCLUSIONS: MES supplementation remarkably reduces inflammatory response in CIA mouse model. These results indicate that MES can be used as a pharmaceutical agent against RA.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Sargassum/química , Terpenos/farmacologia , Alcenos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Benzopiranos/farmacologia , Benzoquinonas/farmacologia , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Condrócitos/patologia , Ciclo-Oxigenase 2/metabolismo , Citocinas/sangue , Citocinas/metabolismo , Etanol/química , Interleucina-6/metabolismo , Articulações/efeitos dos fármacos , Articulações/patologia , Masculino , Camundongos Endogâmicos DBA , NF-kappa B/metabolismo , Terpenos/químicaRESUMO
Sargassum serratifolium has been known to contain a high level of meroterpenoids as antioxidant components. We investigated antioxidant activities and active components in various solvent extracts from S. serratifolium. Ethyl acetate, ethanol, and methanol extracts showed relatively strong DPPH, ABTs, and superoxide radical scavenging activities. Hexane and ethyl acetate extract showed the strongest hydroxyl radical and reactive oxygen species (ROS), respectively, scavenging activities. Sargahydroquinoic acid (SHQA), sargachromanol (SCM) and sargaquinoic acid (SQA) were main antioxidant components in S. serratifolium. Ethanol extract showed the highest levels of SHQA, SCM, and SQA which comprised to be 227⯱â¯6.31â¯mg/g. SHQA and SCM exhibited stronger antioxidant capacities than SQA based on lower IC50 values in ROS, DPPH, ABTs, and superoxide radical scavenging assays. The result showed that ethanol is the most efficient extracting solvent for the active components from S. serratifolium and the plant has the potential as a natural antioxidant.
Assuntos
Antioxidantes/análise , Antioxidantes/metabolismo , Sargassum/química , Acetatos/química , Alcenos/análise , Alcenos/metabolismo , Animais , Antioxidantes/farmacologia , Benzoquinonas/análise , Benzoquinonas/metabolismo , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Hexanos/química , Metanol/química , Camundongos , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Alga Marinha/química , Solventes/químicaRESUMO
Vascular inflammation is a key factor in the pathogenesis of atherosclerosis. The purpose of this study was to investigate the protective effects of sargachromenol (SCM) against tumor necrosis factor (TNF)-α-induced vascular inflammation. SCM decreased the expression of cell adhesion molecules, including intracellular adhesion molecule-1 and vascular cell adhesion molecule-1, in TNF-α-stimulated human umbilical vein endothelial cells (HUVECs), resulted in reduced adhesion of monocytes to HUVECs. SCM also decreased the production of monocyte chemoattractant protein-1 and matrix metalloproteinase-9 in TNF-α-induced HUVECs. Additionally, SCM inhibited activation of nuclear factor kappa B (NF-κB) induced by TNF-α through preventing the degradation of inhibitor kappa B. Moreover, SCM reduced the production of reactive oxygen species in TNF-α-treated HUVECs. Overall, SCM alleviated vascular inflammation through the regulation of NF-κB activation and through its intrinsic antioxidant activity in TNF-α-induced HUVECs. These results indicate that SCM may have potential application as a therapeutic agent against vascular inflammation.
Assuntos
Anti-Inflamatórios/farmacologia , Benzopiranos/farmacologia , Endotélio Vascular/efeitos dos fármacos , Monócitos/efeitos dos fármacos , NF-kappa B/metabolismo , Sargassum/imunologia , Adesão Celular/efeitos dos fármacos , Quimiocina CCL2/metabolismo , Endotélio Vascular/fisiologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Monócitos/imunologia , Cultura Primária de Células , Espécies Reativas de Oxigênio , Transdução de Sinais/efeitos dos fármacos , Ativação Transcricional/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Milk thistle leaves and flowers have been traditionally used as herbal remedy to alleviate liver diseases for decades. Korean milk thistle, Cirsium japonicum var. maackii (Maxim.) Matsum has been employed in traditional folk medicine as diuretic, antiphlogistic, hemostatic, and detoxifying agents. AIM OF THE STUDY: The aim of current investigation was to evaluate hepatoprotective properties of the MeOH extract of the roots, stems, leaves and flowers of Korean milk thistle as well as four isolated flavonoids, luteolin, luteolin 5-O-glucoside, apigenin and apigenin 7-O-glucuronide during t-BHP-induced oxidative stress in HepG2 cells. MATERIALS AND METHODS: Hepatoprotective potential of the MeOH extracts and flavonoids derived from Korean milk thistle against t-BHP-induced oxidative stress in HepG2 cells were evaluated following MTT method. Incubating HepG2 cells with t-BHP markedly decreased the cell viability and increased the intracellular ROS generation accompanied by depleted GSH levels. Protein expression of heme oxygenase (HO-1) and nuclear factor-E2-related factor 2 (Nrf-2) was determined by Western blot. RESULTS: Our findings revealed that pretreating HepG2 cells with MeOH extracts and bioactive flavonoids significantly attenuated the t-BHP-induced oxidative damage, followed by increased cell viability in a dose-dependent manner. The results illustrate that excess ROS generation was reduced and GSH levels increased dose-dependently when HepG2 cells were pretreated with four flavonoids. Moreover, Western blotting analysis demonstrated that protein expressions of Nrf-2 and HO-1 were also up-regulated by flavonoids treatment. CONCLUSIONS: These results clearly demonstrate that the MeOH extracts and flavonoids from Korean milk thistle protected HepG2 cells against oxidative damage triggered by t-BHP principally by modulating ROS generation and restoring depleted GSH levels in addition to the increased Nrf-2/HO-1 signaling cascade. These flavonoids are potential natural antioxidative biomarkers against oxidative stress-induced hepatotoxicity.
Assuntos
Cirsium/química , Flavonoides/farmacologia , Extratos Vegetais/farmacologia , terc-Butil Hidroperóxido/toxicidade , Flavonoides/química , Glutationa/metabolismo , Células Hep G2 , Humanos , Estrutura Molecular , Extratos Vegetais/química , Espécies Reativas de Oxigênio , República da CoreiaRESUMO
Sargassum serratifolium was found to contain high concentrations of meroterpenoids, having strong antioxidant, anti-inflammatory, and neuroprotective activities. This study aims to investigate the anti-inflammatory mechanisms of an ethanolic extract of S. serratifolium (ESS) using lipopolysaccharide (LPS)-stimulated BV2 microglial cells and to identify the anti-inflammatory components in ESS. The level of proinflammatory cytokines was measured by enzyme-linked immunosorbent assay. The expression of inflammation-related proteins and mRNA was evaluated by Western blot and reverse transcription-polymerase chain reaction analysis, respectively. Anti-inflammatory activities of isolated components from ESS were analyzed in LPS-stimulated BV2 cells. ESS inhibited LPS-induced nitric oxide (NO) and prostaglandin E2 and the expression of inducible NO synthase and cyclooxygenase-2. ESS also decreased the release of proinflammatory cytokines in a dose-dependent manner. LPS-induced nuclear factor-kappa B (κB) transcriptional activity and translocation into the nucleus were remarkably suppressed by ESS through the prevention of inhibitor κB-α degradation. The main anti-inflammatory components in ESS were identified as sargahydroquinoic acid, sargachromenol, and sargaquinoic acid based on the inhibition of NO production using LPS-stimulated BV2 cells. Furthermore, treatment with ESS significantly reduced levels of tumor necrosis factor-α and interleukin-1ß stimulated with LPS in mouse hippocampus. Our results indicate that ESS can be used as a functional food or therapeutic agent for the treatment of neuroinflammatory diseases.
Assuntos
Anti-Inflamatórios/farmacologia , Lipopolissacarídeos/farmacologia , Microglia/efeitos dos fármacos , Extratos Vegetais/farmacologia , Sargassum/química , Alcenos/farmacologia , Animais , Anti-Inflamatórios/química , Benzopiranos/farmacologia , Benzoquinonas/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Microglia/citologia , Microglia/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , RNA Mensageiro/biossíntese , RNA Mensageiro/efeitos dos fármacos , Distribuição Aleatória , Transdução de Sinais/efeitos dos fármacosRESUMO
Sargaquinoic acid (SQA) has been known for its antioxidant and anti-inflammatory properties. This study investigated the effects of SQA isolated from Sargassum serratifolium on the inhibition of tumor necrosis factor (TNF)-α-induced monocyte adhesion to human umbilical vein endothelial cells (HUVECs). SQA decreased the expression of cell adhesion molecules such as intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 as well as chemotactic cytokines such as interleukin-8 and monocyte chemoattractant protein-1 in TNF-α-treated HUVECs. As a result, SQA prevented monocyte adhesion to TNF-α-induced adhesion. SQA also inhibited TNF-α-induced nuclear factor kappa B (NF-κB) translocation into the nucleus by preventing proteolytic degradation of inhibitor κB-α. Overall, SQA protects against TNF-α-induced vascular inflammation through inhibition of the NF-κB pathway in HUVECs. These data suggest that SQA may be used as a therapeutic agent for vascular inflammatory diseases such as atherosclerosis.
Assuntos
Alcenos/farmacologia , Benzoquinonas/farmacologia , Adesão Celular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/citologia , Monócitos/citologia , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Sargassum/química , Fator de Necrose Tumoral alfa/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Molécula 1 de Adesão de Célula Vascular/metabolismoRESUMO
Myagropsis myagroides, a brown alga, showed strong anti-inflammatory activities in the previous studies. In this study, we isolated a strong anti-inflammatory compound, sargaquinoic acid (SQA), from M. myagroides and investigated the anti-inflammatory action using lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. SQA suppressed the production of inducible nitric oxide synthase and cyclooxygenase-2 in LPS-stimulated cells as well as that of reactive oxygen species. As a result, SQA inhibited the production of NO, prostaglandin E2, and pro-inflammatory cytokines. LPS-induced transcriptional activation of nuclear factor-κB (NF-κB) was remarkably inhibited by SQA treatment through the prevention of inhibitor κB-α degradation. The regulation of NF-κB activation was also mediated by the phosphorylation of ERK and Akt in LPS-stimulated RAW 264.7 cells. Moreover, SQA induced the production of heme oxygenase 1 via activation of transcription factor Nrf2. These results indicate that SQA inhibits the LPS-induced expression of inflammatory mediators via suppression of ERK and Akt-mediated NF-κB pathway as well as up-regulation of Nrf2/HO-1 pathway, indicating that SQA has a potential therapeutic and preventive application in various inflammatory diseases.
Assuntos
Alcenos/farmacologia , Benzoquinonas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/tratamento farmacológico , Lipopolissacarídeos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Alcenos/química , Animais , Benzoquinonas/química , Linhagem Celular , Ciclo-Oxigenase 2/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/genética , NF-kappa B/genética , Óxido Nítrico Sintase Tipo II/metabolismo , PhaeophyceaeRESUMO
Myagropsis myagroides has been used as a Chinese medicine and its extract has shown various biological activities, however, its anti-inflammatory mechanism remains unknown. In this study, we investigated the inhibitory effects of the ethyl acetate fraction of M. myagroides (EFM) on the production of inflammatory mediators and pro-inflammatory cytokines in lipopolysaccharides (LPS)-stimulated RAW 264.7 cells. EFM significantly inhibited LPS-induced production of nitric oxide (NO), prostaglandin E(2), and pro-inflammatory cytokines in a dose-dependent manner and suppressed the production of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 in RAW 264.7 cells. Inhibitory effect of EFM on iNOS expression and NO production was further confirmed using LPS-activated mouse peritoneal macrophages. EFM treatment strongly suppressed the activation of nuclear factor-kappa B (NF-κB) by suppressing phosphorylation of Akt and extracellular signal-regulated kinases (ERKs). EFM as well as phlorofucofuroeckol B (PFF-B), a major compound isolated from EFM, reduced ear edema induced by phorbol 12-myristate 13-acetate in mice. These results indicate that the anti-inflammatory effect of EFM, rich in PFF-B, on LPS-stimulated macrophages is regulated by the inhibition of NF-κB pathway through the inhibition of ERKs and Akt phosphorylation in LPS-stimulated macrophage cells.