• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.4
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• pp.916-920
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• 2007

Flowers of Magnolia denudata has been reported to possess a variety of pharmacological activities. In this study, we investigated the anti-inflammatory effects and mechanism of the water extract of Flowers of Magnolia denudata(MD) in lipopolysacchride (LPS)-mediated inflammatory mediators in murine peritoneal macrophages. MD itself does not have any toxic effects in murine peritoneal macrophages. MD inhibits LPS-induced nitric oxide (NO), tumor necrosis factor $(TNF)-{\alpha}$, IL-6 and IL-12 production in murine peritoneal macrophages. Furthermore, we have found that MD inhibited LPS-induced $NF-{\kappa}B$ but not c-Jun N-terminal kinase (JNK), p38 and extracellular signal-ragulated kinase (ERK) activation. These results suggested that MD inhibit LPS-induced production of $TNF-{\alpha}$, IL-6 and IL-12 via suppression of the $NF-{\kappa}B$ activation.

• Natural Product Sciences
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• v.13 no.4
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• pp.283-288
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• 2007

Acanthopanacis Cortex (AC) has been popularly used as an herbal medicine for medical treatment of rheumatoid arthritis, insomnia, impotence and diabetes. Here, we investigated immunostimulating effects of the aqueous extract of AC on macrophage. We studied nitric oxide (NO) and tumor necrosis factor (TNF)-${\alpha}$ release in response to AC treatment, as they are important secretory products of macrophage. AC alone induce the NO and TNF-${\alpha}$ production. AC increase c-Jun NH2-terminal kinase 1/2 (JNK) and extracellular signal-regulated kinase (ERK) phosphorylation but does not p38 activation in RAW 264.7 cells. Also AC resulted in the enhanced cell-surface expression of CD80 and CD14. In addition, AC resulted in enhanced T cell-stimulatory capacity and increased T cell secretion of interferon (IFN)-gamma. After feeding with AC to mouse for 10 days, the change of $CD28^+$ and $CD40^+$ population was analyzed. AC increased $CD28^+$ population in splenocytes in vivo. These studies indicate that AC induces macrophage activation and suggest the possible use of AC in macrophage-based immunotherapies.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.35 no.2
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• pp.1-12
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• 2022

Objectives : This study was conducted to verify the anti-inflammatory effects of Aster glehni water extracts in HaCaT keratinocytes. Methods : In this study, cell viability was confirmed by MTT assay. Production of TNF-α and IL-6 was determined by ELISA. mRNA expression of TARC and MDC were measusred by qRT-PCR. Also, expressions of p-JNK, JNK, p-ERK, ERK, p-p38, and p-38 were investigated by using western blot assay. Results : Aster glehni water extracts were not shown any significant cytotoxicity at 15.625-500㎍/㎖ in HaCaT keratinocytes. Aster glehni extracts inhibited the TNF-α and IL-6 production in HaCaT keratinocytes treated with TNF-α and IFN-γ. Also, expression of TARC, MDC, p-ERK, and p-STAT1 was decreased. Conclusions : These results suggest that Aster glehni water extracts have anti-inflammatory effects in HaCaT keratinocytes and can be applied to the development of anti-inflammatory treatment substances.

• The Korea Journal of Herbology
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• v.27 no.1
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• pp.59-64
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• 2012

Objective : This study was performed to evaluate the effect of Forsythiae Fructus (FF) ethanol extract on inflammatory cytokine production and its underlying mechanisms in mouse macrophages. Methods : Peritoneal macrophages from thioglycollate medium-injected mice were cultured and stimulated with lipopolysaccharide(LPS) or LPS/interferon(IFN)-${\gamma}$ for cytokine measurement and cellular signaling molecule analysis. Results : FF ethanol extract decreased the levels of secreted tumor necrosis factor(TNF)-${\alpha}$ and interleukin(IL)-6 in IFN-${\gamma}$/LPS-stimulated cells in a concentration-dependent manner. FF extract reduced IFN-${\gamma}$/LPS-induced STAT1 phosphorylation and LPS-induced p38 and JNK activation, but not ERK1/2 activity. The extract also inhibited LPS-induced $I{\kappa}B{\alpha}$ degradation through suppression of $I{\kappa}B{\alpha}$ kinase. Conclusions : These results suggest that FF ethanol extract affects the production of TNF-${\alpha}$ and IL-6 through inhibition of activation of STAT-1, $I{\kappa}B{\alpha}$, p38, and JNK.

• Journal of Life Science
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• v.23 no.5
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• pp.650-656
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• 2013

Endothelial protein C receptor (EPCR) plays a pivotal role in augmenting Protein C activation through the thrombin-thrombomodulin complex. EPCR activity is markedly changed by ectodomain cleavage and released as the soluble protein (sEPCR). EPCR shedding is mediated by tumor necrosis factor-${\alpha}$ converting enzyme (TACE). Lycopene found in tomatoes and tomato products has anti-oxidant, anti- cancer and anti-inflammatory effects. However, little is known about the effects of lycopene on EPCR shedding. We investigated this issue by monitoring the effects of lycopene on the phorbol-12-myristate 13-acetate (PMA), tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$ and on the cecal ligation and puncture (CLP)-mediated EPCR shedding. Data showed that lycopene potently inhibited the PMA, TNF-${\alpha}$, IL-$1{\beta}$ and CLP-induced EPCR shedding by suppressing TACE expression. Furthermore, lycopene reduced PMA-stimulated phosphorylation of p38, extracellular regulated kinases (ERK) 1/2 and c-Jun N-terminal kinase (JNK). Given these results, lycopene should be viewed as a candidate therapeutic agent for the treatment of various severe vascular inflammatory diseases via inhibition of the EPCR shedding.

• Korean Journal of Plant Resources
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• v.31 no.2
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• pp.117-123
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• 2018

In this study, we evaluated anti-inflammatory effect of biji in LPS-stimulated RAW264.7 cells. Biji inhibited the generation of NO and $PGE_2$ through the suppression of iNOS and COX-2 expression. In addition, biji attenuated the expression of TNF-${\alpha}$ and IL-$1{\beta}$ induced by LPS. Biji blocked LPS-mediated $I{\kappa}B-{\alpha}$ degradation and subsequently inhibited p65 nucleus accumulation in RAW264.7 cells, which indicates that biji inhibits NF-${\kappa}B$ signaling. In addition, biji suppressed p38 phosphorylation induced by LPS. Our results suggests that biji may exert anti-inflammatory activity through blocking the generation of the inflammatory mediators such as NO, $PGE_2$, iNOS, COX-2, TNF-${\alpha}$ and IL-$1{\beta}$ via the inhibiting the activation of NF-${\kappa}B$ and p38. From these findings, biji has potential to be a candidate for the development of chemoprevention or therapeutic agents for inflammatory diseases.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.10
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• pp.1439-1449
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• 2015

Prunus persica Flos (PPF) were investigated for their antioxidant and anti-inflammatory activities to find a natural functional food resource preventing degenerative diseases associated with excessive oxidative stress and chronic inflammation. PPF was extracted using ethanol (EtOH) and then sequentially fractioned by hexane (Hx), dichloromethane (DM), ethyl acetate (EA), n-butanol (BtOH), and water (DW). Contents of total phenolics and flavonoids, as well as 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activities were measured. Anti-inflammatory effects in terms of nitric oxide (NO), prostaglandin (PG) E2, and pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-${\alpha}$ production were also measured using LPS-treated RAW 264.7 macrophages. EtOH extract showed relatively high antioxidant activity with high total phenolic (78.1 mg tannic acid/g) and flavonoid contents (55.3 mg rutin/g). EA fraction contained the highest total phenolic and flavonoid contents (394.6 mg tannic acid/g, 253.7 mg rutin/g), followed by BtOH (128.3 mg tannic acid/g, 93.1 mg rutin/g). EA and BtOH fractions and EtOH extract showed higher DPPH radical and ABTS radical scavenging activities than the others (P<0.05). In LPS-treated RAW 264.7 macrophages, EtOH extract ($200{\mu}g/mL$) showed significantly reduced (P<0.05) NO, PGE2, and TNF-${\alpha}$ production levels to 38.5%, 32.3%, and 48.9% of the control, respectively, as well as reduced iNOS and COX-2 protein expression. DM fraction ($50{\mu}g/mL$) showed significantly reduced (P<0.05) NO, PGE2, IL-6, and TNF-${\alpha}$ production levels to 43.5%, 13.3%, 38.7%, and 41.3% of the control, respectively, and EA fraction ($50{\mu}g/mL$) showed significantly reduced NO, PGE2, IL-6, and TNF-${\alpha}$ production levels to 44.8%, 22.4%, 45.7%, and 62.0% of the control, respectively. Taken together, EtOH extract of PPF showed potent antioxidant and anti-inflammatory activities, and EA and BtOH fractions showed comparatively stronger antioxidant activities while DM and EA fractions showed stronger anti-inflammatory activities. It can be concluded that EtOH extract of PPF and its fractions are good candidates as natural resources for the development of anti-oxidative and anti-inflammatory functional food products.

• Journal of Life Science
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• v.30 no.1
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• pp.106-112
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• 2020

Aminoacyl tRNA synthetase complex interacting multifunctional protein 2 (AIMP2) is a scaffolding protein required for the assembly of multi-tRNA synthetase, and it can exert pro-apoptotic activity in response to DNA damage. In the presence of DNA damage, AIMP2 binds to mouse double minute 2 homolog (MDM2) to protect p53 from MDM2 attack. TGF-β signaling results in the nuclear translocation of AIMP2, whereby AIMP2 interacts with FUSE-binding protein, and, thus, suppresses c-myc. TNF receptor-associated factor 2 (TRAF2) is an important mediator between TNF-receptors 1 and 2 which are involved in the signaling of c-Jun N-terminal kinase (JNK), nuclear factor κB (NF-κB), and p38 mitogen-activated protein kinases (MAPKs). TRAF2 is required for the activations of JNK and NF-κB via TNF-α and the mediation of anti-apoptosis signaling. AIMP2 can also enhance pro-apoptosis in the TNF-α signaling. During this signaling, AIMP2 assists the association of E3 ubiquitin ligase, the cellular inhibitor of apoptosis protein 1 (c-IAP1) which is well known and responsible for the degradation of TRAF2. The formation of a complex among AIMP2, TRAF2, and c-IAP1 results in proteasome-mediated TRAF2 degradation. AIMP2 can induce apoptosis via downregulation of TRAF2 to interact directly in TNF-α signaling. This review provides new insight into the molecular mechanism responsible for AIMP2 and TRAF2 complex formation and treatments for TNFα-associated diseases.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.10a
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• pp.65-65
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• 2019

In this study, we evaluated the anti-inflammatory effect of extracts of leaves (LCLE) and branches (LCBE) from L. caerulea in LPS-stimulated RAW264.7 cells. Inhibitory effect of LCLE and LCBE against LPS-induced overproduction of NO, iNOS and $IL-1{\beta}$ was higher than LCFE. Furthermore, LCLE and LCBE significantly inhibited the overexpression of COX-2, IL-6 and $TNF-{\alpha}$ in LPS-stimulated RAW264.7 cells. LCLE and LCBE did not inhibited LPS-induced degradation of $I{\kappa}B-{\alpha}$, but blocked the nuclear accumulation of p65. LCLE did not inhibited LPS-induced phosphorylation of ERK1/2 and p38, while LCBE significantly attenuated phosphorylation level of p38. LCLE and LCBE increased HO-1 protein level and decrease of iNOS and $IL-1{\beta}$ expression by LCLE and LCBE was inhibited by HO-1 knockdown. The inhibition of p38 by SB203580 and ROS by NAC blocked HO-1 expression by LCLE and LCBE. LCLE and LCBE increased p38 phosphorylation and the inhibition of ROS by NAC blocked p38 phosphorylation LCLE and LCBE. LCLE and LCBE induced nuclear accumulation of Nrf2, but this was significantly reversed by the inhibition of p38 and ROS. In addition, LCLE and LCBE increased ATF3 expression and decrease of iNOS and $IL-1{\beta}$ expression by LCLE and LCBE was inhibited by ATF3 knockdown. Collectively, LCLE and LCBE inhibited LPS-induced $NF-{\kappa}B$ activation by blocking p65 nuclear accumulation, increased HO-1 expression by ROS/p38/Nrf2 activation, and increased ATF3 expression. Furthermore, LCBE inhibited LPS-induced p38 phosphorylation.

• Biomolecules & Therapeutics
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• v.20 no.1
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• pp.43-49
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• 2012

Stimulation of mast cells through the high affinity IgE receptor (Fc${\varepsilon}$RI) induces degranulation, lipid mediator release, and cytokine secretion leading to allergic reactions. Although various signaling pathways have been characterized to be involved in the Fc${\varepsilon}$RI-mediated responses, little is known about the precious mechanism for the expression of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) in mast cells. Here, we report that rapamycin, a specific inhibitor of mammalian target of rapamycin (mTOR), reduces the expression of TNF-${\alpha}$ in rat basophilic leukemia (RBL-2H3) cells. IgE or specific antigen stimulation of RBL-2H3 cells increases the expression of TNF-${\alpha}$ and activates various signaling molecules including S6K1, Akt and p38 MAPK. Rapamycin specifically inhibits antigeninduced TNF-${\alpha}$ mRNA level, while other kinase inhibitors have no effect on TNF-${\alpha}$ mRNA level. These data indicate that mTOR signaling pathway is the main regulation mechanism for antigen-induced TNF-${\alpha}$ expression. TNF-${\alpha}$ mRNA stability analysis using reporter construct containing TNF-${\alpha}$ adenylate/uridylate-rich elements (AREs) shows that rapamycin destabilizes TNF-${\alpha}$ mRNA via regulating the AU-rich element of TNF-${\alpha}$ mRNA. The antigen-induced activation of S6K1 is inhibited by specific kinase inhibitors including mTOR, PI3K, PKC and $Ca^{2+}$chelator inhibitor, while TNF-${\alpha}$ mRNA level is reduced only by rapamycin treatment. These data suggest that the effects of rapamycin on the expression of TNF-${\alpha}$ mRNA are not mediated by S6K1 but regulated by mTOR. Taken together, our results reveal that mTOR signaling pathway is a novel regulation mechanism for antigen-induced TNF-${\alpha}$ expression in RBL-2H3 cells.