• The Korean Journal of Physiology and Pharmacology
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• v.18 no.1
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• pp.79-86
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• 2014

Hydroxycinnamic acids have been reported to possess numerous pharmacological activities such as antioxidant, anti-inflammatory, and anti-tumor properties. However, the biological activity of 1-p-coumaroyl ${\beta}$-D-glucoside (CG), a glucose ester derivative of p-coumaric acid, has not been clearly examined. The objective of this study is to elucidate the anti-inflammatory action of CG in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. In the present study, CG significantly suppressed LPS-induced excessive production of pro-inflammatory mediators such as nitric oxide (NO) and $PGE_2$ and the protein expression of iNOS and COX-2. CG also inhibited LPS-induced secretion of pro-inflammatory cytokines, IL-$1{\beta}$ and TNF-${\alpha}$. In addition, CG significantly suppressed LPS-induced degradation of $I{\kappa}B$. To elucidate the underlying mechanism by which CG exerts its anti-inflammatory action, involvement of various signaling pathways were examined. CG exhibited significantly increased Akt phosphorylation in a concentration-dependent manner, although MAPKs such as Erk, JNK, and p38 appeared not to be involved. Furthermore, inhibition of Akt/PI3K signaling pathway with wortmannin significantly, albeit not completely, abolished CG-induced Akt phosphorylation and anti-inflammatory actions. Taken together, the present study demonstrates that Akt signaling pathway might play a major role in CG-mediated anti-inflammatory activity in LPS-stimulated RAW264.7 macrophage cells.

• Nutrition Research and Practice
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• v.11 no.5
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• pp.357-364
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• 2017

BACKGROUND/OBJECTIVES: Oxidative stress is closely related with inflammation and development of many diseases. Black soybean seed coat contains high amount of anthocyanins, which are well-known for free radical scavenging activities. This study investigated inflammatory response and action mechanism of black soybean anthocyanins with regard to antioxidant activity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. MATERIALS/METHODS: RAW 264.7 cells were treated with anthocyanins extracted from black soybean seed coats in a concentration range of 12.5 to $100{\mu}g/mL$. The production of reactive oxygen species (ROS), secretion of pro-inflammatory mediators and cytokines, and the signaling in the mitogen activated protein kinases (MAPKs) pathway were examined. RESULTS: Black soybean anthocyanins significantly decreased LPS-stimulated production of ROS, inflammatory mediators such as nitric oxide (NO) and prostaglandin $E_2$, and pro-inflammatory cytokines, including tumor necrosis factor ${\alpha}$ and interleukin-6, in a dose-dependent manner without cytotoxicity (P < 0.001). Black soybean anthocyanins downregulated the expression of inducible NO synthase and cyclooxygenase-2 in LPS-stimulated RAW 264.7 cells (P < 0.001). Moreover, black soybean anthocyanins inhibited LPS-induced phosphorylation of MAPKs, including extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 (P < 0.001). CONCLUSION: These results suggest that black soybean anthocyanins exert anti-inflammatory activity by inhibiting ROS generation and subsequent MAPKs signaling, thereby inhibiting inflammatory responses.

• Korean Journal of Veterinary Research
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• v.57 no.2
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• pp.97-104
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• 2017

Solanum lycopersicum, commonly known as tomato, is widely used in raw, cooked, or liquid forms because it contains nutritional compounds that are beneficial for human health, including carotenoids, lycopene, ascorbic acid, vitamins, and minerals. The tomato is perhaps the most widely studied fruit, especially with respect to its cardioprotective effects. In this study, we aimed to identify the anti-inflammatory mechanisms by which the tomato elicits its anti-inflammatory properties. We treated murine macrophage RAW 264.7 cells with a tomato ethanol extract and performed various biochemical assays including nitric oxide inhibition, cell viability, RNA extraction, expression of pro-inflammatory mediators and cytokines, and immunoblotting, as well we assessed cell survival rates. Our results have shown for the first time that a tomato ethanol extract treatment can suppress nitric oxide production in a dose-dependent manner without cytotoxicity. Moreover, it inhibits the expression of pro-inflammatory mediators and cytokines and elicits its anti-inflammatory effects via the nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$) and mitogen-activated protein kinase (MAPK) pathways. In addition, administration of tomato syrup potently rescued mice from septic shock induced by lipopolysaccharide injection. Collectively, our results elucidate details regarding the anti-inflammatory mechanisms of tomato.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.10a
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• pp.96-96
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• 2018

Although the roots of Heracleum moellendorffii (HM-R) have been long treated for inflammatory human diseases, scientific evidence for the anti-inflammatory activity of HM-R is not sufficient. In this study, we investigated anti-inflammatory activity and mechanism of action of HM-R in LPS-stimulated RAW264.7 cells. HM-R blocked LPS-induced NO and PGE2 production, but not HM-L. HM-R inhibited LPS-induced overexpression of iNOS, COX-2, $IL-1{\beta}$ and IL-6 in RAW264.7 cells. HM-R inhibited LPS-induced $NF-{\kappa}B$ signaling activation through blocking $I{\kappa}B-{\alpha}$ degradation and p65 nuclear accumulation. In addition, HM-R inhibited MAPK signaling activation by attenuating the phosphorylation of ERK1/2, p38 and JNK. Furthermore, HM-R inhibited attenuated LPS-mediated overexpression of the osteoclast-specific factors such as NFATc1, cathepsin K, MCP-1 and TRAP. These results indicate that HM-R may exert anti-inflammatory activity by inhibiting $NF-{\kappa}B$ and MAPK signaling activation. From these findings, HM-R has potential to be a candidate for the development of chemopreventive or therapeutic agents for the inflammation and inflammatory diseases.

• ALGAE
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• v.32 no.3
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• pp.261-273
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• 2017

Fine dust (FD) particles have become a major contributor to air pollution causing detrimental effects on the respiratory system and skin. Although some studies have investigated the effects of FD on the respiratory system, their possible effects on the skin remain under-explored. We investigated the FD mediated inflammatory responses in keratinocytes, present in the outer layers of skin tissues and the transfer of inflammatory potential to macrophages. We further evaluated the anti-inflammatory effects of the polyphenolic derivative, diphlorethohydroxycarmalol (DPHC) isolated from Ishige okamurae against FD-induced inflammation. Size distribution of FD particles was analyzed by scanning electron microscopy. FD particles induced the production of cyclooxygenase-2, prostaglandin E2 ($PGE_2$), interleukin (IL)-$1{\beta}$, and IL-6 in HaCaT keratinocytes and the expression of nitric oxide (NO), inducible nitric oxide synthases (iNOS), $PGE_2$, tumor necrosis factor-${\alpha}$ expression in RAW 264.7 macrophages. Further, we evaluated the inflammatory potential of the culture medium of inflammation-induced HaCaT cells in RAW 264.7 macrophages and observed a marked increase in the expression of NO, iNOS, $PGE_2$, and proinflammatory cytokines. DPHC treatment markedly attenuated the inflammatory responses, indicating its effectiveness in suppressing a broad range of inflammatory responses. It also showed anti-inflammatory potential in in-vivo experiments using FD-stimulated zebrafish embryos by decreasing NO and reactive oxygen species production, while eventing cell death caused by inflammation.

• Fisheries and Aquatic Sciences
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• v.21 no.6
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• pp.15.1-15.9
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• 2018

Background: Inflammation has been known to associate with many human diseases. The objective of this study was to evaluate an anti-inflammatory effect of ozonated krill (Euphausia superba) oil, which was prepared by the treatment of krill oil using ozone gas. The anti-inflammatory activity was evaluated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Results: Ozonated krill oil significantly inhibited nitric oxide (NO) production and suppressed the mRNA and protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW 264.7 macrophages. Ozonated krill oil also reduced the mRNA expression of inflammatory cytokines such as interleukin (IL)-$1{\beta}$, IL-6, and tumor necrosis factor (TNF)-${\alpha}$ in LPS-stimulated RAW 264.7 macrophages. To elucidate the mechanism underlying the anti-inflammatory activity of ozonated krill oil, we evaluated the effects of ozonated krill oil on the activation of mitogen-activated protein kinases (MAPKs) pathway. Ozonated krill oil suppressed the LPS-stimulated phosphorylation of p38 MAPK and c-Jun N-terminal kinases (JNK). Conclusion: This study revealed that the ozonated krill oil exhibited an anti-inflammatory effect in LPS-stimulated RAW 264.7 macrophages. To the best of our knowledge, this is the first report that ozonated krill oil suppressed pro-inflammatory mediator and cytokine expression in LPS-stimulated RAW 264.7 macrophages by inhibiting the phosphorylation of p38 MAPK and JNK.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.3
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• pp.503-509
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• 2011

Jakyaktang(芍藥湯; JYT) exhibits potent anti-inflammatory activity in widely intestinal disease, but its mechanism was undisclosed. To elucidate the molecular mechanisms of JYT on pharmacological and biochemical actions in inflammation, we examined the effect of JYT on pro-inflammatory mediators in phorbol 12-myristate 13-acetate (PMA) plus A23187-induced mast cell and lipopolysaccharide (LPS)-stimulated macrophages. The investigation focused on whether JYT inhibited pro-inflammatory cytokines such as interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) in PMA plus A23187- induced HMC-1 cells and inflammatory madiators such as nitric oxide (NO), TNF-${\alpha}$, IL-6, iNOS, COX-2 in LPS-stimulated RAW 264.7 cells. We found that JYT inhibited LPS-induced NO, TNF-${\alpha}$ and IL-6 productions as well as the expressions of iNOS and COX-2. These results suggest that JYT has inhibitory effects on mast cell-mediated and macropage-mediated inflammation.

• Biomolecules & Therapeutics
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• v.21 no.1
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• pp.60-65
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• 2013

3,4,5-Trihydroxycinnamic acid (THC) is a derivative of hydroxycinnamic acids, which have been reported to possess a variety of biological properties such as anti-inflammatory, anti-tumor, and neuroprotective activities. However, biological activity of THC has not been extensively examined. Recently, we reported that THC possesses anti-inflammatory activity in LPS-stimulated BV2 microglial cells. However, its precise mechanism by which THC exerts anti-inflammatory action has not been clearly identified. Therefore, the present study was carried out to understand the anti-inflammatory mechanism of THC in BV2 microglial cells. THC effectively suppressed the LPS-induced induction of pro-inflammatory mediators such as NO, TNF-${\alpha}$, and IL-$1{\beta}$. THC also suppressed expression of MCP-1, which plays a key role in the migration of activated microglia. To understand the underlying mechanism by which THC exerts these anti-inflammatory properties, involvement of Nrf2, which is a cytoprotective transcription factor, was examined. THC resulted in increased phosphorylation of Nrf2 with consequent expression of HO-1 in a concentration-dependent manner. THC-induced phosphorylation of Nrf2 was blocked with SB203580, a p38 MAPK inhibitor, indicating that p38 MAPK is the responsible kinase for the phosphorylation of Nrf2. Taken together, the present study for the first time demonstrates that THC exerts anti-inflammatory properties through the activation of Nrf2 in BV2 microglial cells, suggesting that THC might be a valuable therapeutic adjuvant for the treatment of inflammation-related disorders in the CNS.

• Biomolecules & Therapeutics
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• v.25 no.6
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• pp.641-647
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• 2017

Galangin (3,5,7-trihydroxyflavone) is a polyphenolic compound abundant in honey and medicinal herbs, such as Alpinia officinarum. In this study, we investigated the anti-inflammatory effects of galangin under in vitro and in vivo neuroinflammatory conditions caused by polyinosinic-polycytidylic acid (poly(I:C)), a viral mimic dsRNA analog. Galangin suppressed the production of nitric oxide, reactive oxygen species, and pro-inflammatory cytokines in poly(I:C)-stimulated BV2 microglia. On the other hand, galangin enhanced anti-inflammatory interleukin (IL)-10 production. Galangin also suppressed the expression of pro-inflammatory markers in poly(I:C)-injected mouse brains. Further mechanistic studies showed that galangin inhibited poly(I:C)-induced nuclear factor (NF)-${\kappa}B$ activity and phosphorylation of Akt without affecting MAP kinases. Interestingly, galangin increased the expression and transcriptional activity of peroxisome proliferator-activated receptor (PPAR)-${\gamma}$, known to play an anti-inflammatory role. To investigate whether PPAR-${\gamma}$ is involved in the anti-inflammatory function of galangin, BV2 cells were pre-treated with PPAR-${\gamma}$ antagonist before treatment of galangin. We found that PPAR-${\gamma}$ antagonist significantly blocked galangin-mediated upregulation of IL-10 and attenuated the inhibition of tumor necrosis factor (TNF)-${\alpha}$ and IL-6 in poly(I:C)-stimulated microglia. In conclusion, our data suggest that PI3K/Akt, NF-${\kappa}B$, and PPAR-${\gamma}$ play a pivotal role in mediating the anti-inflammatory effects of galangin in poly(I:C)-stimulated microglia.

• Korean Journal of Pharmacognosy
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• v.43 no.3
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• pp.231-238
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• 2012

Menthae herba (MH) extracts exhibit anti-inflammatory effects. The purpose of this study was to determine whether the anti-inflammatory effects of MH extracts vary according to the cultivation regions. We performed a comparative analysis of MH extracts by evaluating the production of inflammatory mediators in RAW 264.7 murine macrophage cells and HaCaT human keratinocyte cells. MH extracts obtained from different cultivation regions in Korea and China significantly reduced the production of nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$), and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) in RAW 264.7 cells stimulated with lipopolysaccharide (LPS). No differences in these inhibitory activities were observed between MH extracts. In HaCaT cells stimulated with TNF-${\alpha}$ and interferon-${\gamma}$ (IFN-${\gamma}$), MH extracts did not inhibit the production of macrophage-derived chemokine (MDC/CCL22), but most extracts reduced the production of the regulated on activation normal T-cell expression and secreted (RANTES/CCL5). We used clustering tree analysis of the MH extracts according to the chromatographic pattern and anti-inflammatory potency of MH extracts. We observed differences in the chromatographic pattern of MH extracts but no difference in anti-inflammatory potency. Our findings suggest that MH extracts from different regions do not show any differences in their pharmacological potency in that MH extracts are used as therapeutic agents to treat inflammatory disorders.