Wi-Gyeong Gwon

Anti-inflammatory effects of sargachromenol-rich ethanolic extract of Myagropsis myagroides on lipopolysaccharide-stimulated BV-2 cells

BackgroundExcessive 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.MethodsThe 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.ResultsMME 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.ConclusionsThese 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.

Sargaquinoic acid attenuates inflammatory responses by regulating NF-κB and Nrf2 pathways in lipopolysaccharide-stimulated RAW 264.7 cells

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.

Anti-inflammatory action of the ethanolic extract from Sargassum serratifolium on lipopolysaccharide-stimulated mouse peritoneal macrophages and identification of active components

Sargassum, a genus of brown algae (Phaeophyceae) in the Sargassaceae family, comprises approximately 400 species in the world. Among them, Sargassum serratifolium has been reported to have high level of meroterpenoids, which have antioxidant, anti-inflammatory, and neuroprotective activities. This study investigated the anti-inflammatory mechanism of ethanolic extract of S. serratifolium (ESS) in lipopolysaccharide (LPS)-stimulated peritoneal macrophages and identified anti-inflammatory compounds in ESS. ESS inhibited LPS-induced nitric oxide (NO) and prostaglandin E2 and the expression of inducible nitric oxide synthase and cyclooxygenase-2. ESS also reduced the release of pro-inflammatory cytokines in a dose-dependent manner. LPS-induced nuclear factor-κB transcriptional activity and translocation into the nucleus were significantly inhibited by ESS treatment through the prevention of the degradation of inhibitor κB-α. Furthermore, ESS inhibited the production of pro-inflammatory cytokines in mouse serum. The main anti-inflammatory components in ESS were identified as sargahydroquinoic acid, sargachromenol, and sargaquinoic acid based on the inhibition of NO production. Our results indicate that ESS can be used as a potential source of therapeutic agents for the treatment of inflammatory diseases.

Hexane Fraction from Sargassum fulvellum Inhibits Lipopolysaccharide-Induced Inducible Nitric Oxide Synthase Expression in RAW 264.7 Cells via NF-κB Pathways

Sargassum fulvellum (Turner) C. Agardh has been used to treat various inflammatory diseases, including lump, dropsy, swollen and painful scrotum, and urination problems for several centuries with no side effects. This study aims to investigate the anti-inflammatory effect of the hexane fraction of S. fulvellum (HFS) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and phorbol 12-myristate 13-acetate (PMA)-induced mouse-ear edema. The anti-inflammatory activity of HFS in LPS-stimulated RAW 264.7 cells was investigated by assessing the inhibition of nitric oxide (NO) and pro-inflammatory cytokine production during Griess reaction and enzyme-linked immunosorbent assay (ELISA), respectively. The molecular mechanisms that underlie the anti-inflammatory action of HFS were investigated by analyzing the activation of transcription factor and its upstream signaling proteins. Additionally, an in vivo study of the anti-inflammatory effect of HFS was carried out using PMA-induced mouse-ear edema. HFS inhibited LPS-induced NO production in a dose-dependent manner and suppressed the expression of inducible NO synthase (iNOS) in the RAW 264.7 cells. Further, HFS reduced the production of pro-inflammatory cytokines in the LPS-stimulated RAW 264.7 cells. HFS significantly inhibited LPS-induced nuclear factor kappa B (NF-κB) transcriptional activity and NF-κB translocation into the nucleus by preventing degradation of inhibitor κB-α. Moreover, HFS inhibited the activation of Akt and mitogen-activated protein kinases (MAPKs) in the LPS-stimulated RAW 264.7 cells. Furthermore, HFS suppressed PMA-induced mouse-ear edema. The above data indicate that the anti-inflammatory effects of HFS on LPS-stimulated cells are associated with the suppression of NF-κB through the inhibition of MAPKs and Akt phosphorylation.

6,6′-Bieckol suppresses inflammatory responses by down-regulating nuclear factor-κB activation via Akt, JNK, and p38 MAPK in LPS-stimulated microglial cells

Abstract 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.

Sargachromenol protects against vascular inflammation by preventing TNF-α-induced monocyte adhesion to primary endothelial cells via inhibition of NF-κB activation

Abstract 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)‐&agr;‐induced vascular inflammation. SCM decreased the expression of cell adhesion molecules, including intracellular adhesion molecule‐1 and vascular cell adhesion molecule‐1, in TNF‐&agr;‐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‐&agr;‐induced HUVECs. Additionally, SCM inhibited activation of nuclear factor kappa B (NF‐&kgr;B) induced by TNF‐&agr; through preventing the degradation of inhibitor kappa B. Moreover, SCM reduced the production of reactive oxygen species in TNF‐&agr;‐treated HUVECs. Overall, SCM alleviated vascular inflammation through the regulation of NF‐&kgr;B activation and through its intrinsic antioxidant activity in TNF‐&agr;‐induced HUVECs. These results indicate that SCM may have potential application as a therapeutic agent against vascular inflammation. HighlightsSargachromenol (SCM) was isolated from Sargassum serratifolium.SCM inhibited the adhesion of THP‐1 to TNF‐&agr;‐stimulated endothelium.SCM inhibited the expression of ICAM‐1, VCAM‐1, and MCP‐1 via NF‐&kgr;B pathway.SCM could be a novel therapeutic agent to treat vascular inflammatory diseases.

Correction to Sargaquinoic Acid Inhibits TNF-α-Induced NF-κB Signaling, Thereby Contributing to Decreased Monocyte Adhesion to Human Umbilical Vein Endothelial Cells (HUVECs)

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.

Protective effects of flavonoids isolated from Korean milk thistle Cirsium japonicum var. maackii (Maxim.) Matsum on tert-butyl hydroperoxide-induced hepatotoxicity in HepG2 cells

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.