• The Journal of Korean Obstetrics and Gynecology
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• v.34 no.4
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• pp.12-29
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• 2021

Objective: This study was performed to investigate the inhibitory effect of Cheongpochukeo-tang (CCT) on lipopolysaccharide (LPS)-induced inflammation model. Methods: RAW 264.7 cells were pre-treated with CCT and incubated with LPS (500 ng/ml) after 1 hour. Cell viability was measured by MTT assay to figure out cytotoxicity of CCT. The production of nitric oxide and mRNA expression of pro-inflammatory cytokine were measured. And the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) were examined to figure out molecular mechanisms of CCT's anti-inflammatory effects. In addition, mice survival rate and cytokine levels of serum were observed after treated with CCT. And mice liver tissues were observed and their cytokines levels in liver tissue were measured. Results: CCT did not have cytotoxic effect in RAW 264.7 cells. It inhibited LPS-induced nitric oxide (NO) production, but showed an increase in NO by itself at 2 mg/ml concentration. CCT inhibited mRNA expression of IL-1β, IL-6, TNF-α in a dose dependant and the activaton of MAPKs and NF-κB. In addition, CCT reduced mortality in the LPS-induced mouse model and inhibited production of cytokines in mouse serum and liver tissue. Conclusion: The results suggest that CCT could reduce LPS-induced inflammation by inhibiting MAPKs and NF-κB activaton, NO production, and pro-inflammatory cytokines secretion. Thereby, CCT could be effective medicine for the inflammatory disease.

• Natural Product Sciences
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• v.23 no.2
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• pp.103-107
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• 2017

Angelica koreana is an important medicinal plant for some locals in East Asia including Korea. A few reports have shown the efficacy of its phytochemical constituents. We have isolated and purified one compound falcarindiol (FAL) from the methanolic extract of A. koreana roots. At concentrations from to $1{\mu}M$ to $25{\mu}M$, the FAL isolated from the roots of A. koreana exerted no significant cytotoxicity and down-regulated LPS-stimulated pro-inflammatory cytokine IL-8 in colon epithelial cells, while up-regulating anti-inflammatory cytokine IL-10. In addition, the FAL decreased the expression of LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 protein by Western blot analysis. Colon epithelial cells play pivotal roles in regulating the colon immune system and thus FAL is expected to be candidate agent as therapeutic potential for the treatment of inflammatory bowel disease (IBD) by modulating LPS-induced inflammation in colon epithelial cells.

• Journal of Pharmacopuncture
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• v.15 no.1
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• pp.7-11
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• 2012

Aim: Historically, mineral compound herbal medicines have long been used in treatments of immune-related diseases in Korea, China and other Asian countries. In this study, we investigated the anti-inflammatory effect of egg white combined with chalcanthite (IS4) on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Methods: RAW 264.7 cells cultured with LPS and various concentrations of IS4 were analyzed to determine the production of pro-inflammatory cytokines and mediators by using enzyme-linked immune sorbent assays (ELISAs). Results: IS4 concentration inhibited the production of interleukin-1beta (IL-$1{\beta}$), interleukin-6 (IL-6), and granulocyte-macrophage colony-stimulating factor (GM-CSF) induced by LPS. IS4 at high concentrations (25 and 50 ${\mu}g/ml$) inhibited, in concentration-dependent manner, the expression of tumor necrosis factor-alpha (TNF-${\alpha}$) stimulated by LPS. Conclusion: IS4 has shown an anti-inflammatory effect in RAW 264.7 cells.

• Journal of Mushroom
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• v.19 no.3
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• pp.225-233
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• 2021

In this study, we evaluated the anti-inflammatory effect of extract from Cudrania tricuspidata twig sawdust fermented with Ganoderma lucidum mycelium. Fermented Cudrania tricuspidata twig sawdust extracted with 70% ethanol and elucidated the potential signaling pathway in lipopolysaccharide (LPS)-induced RAW264.7 cells. Fermented Cudrania tricuspidata twig sawdust inhibits LPS-stimulated nitric oxide (NO) production without affecting cell viability in a dose-dependent manner and production of LPS-induced pro-inflammatory cytokines such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α and prostaglandin2 (PGE₂). Fermented Cudrania tricuspidata twig sawdust also suppressed the expression of the pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW264.7 cells. Moreover, Fermented Cudrania tricuspidata twig sawdust significantly attenuated LPS-induced IkappaB (IκB) degradation and suppressed nuclear factor kappa B (NF-κB) nuclear translocation. These results suggest that fermented Cudrania tricuspidata twig sawdust may have great potential for the development of anti-inflammatory agent.

• The Korea Journal of Herbology
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• v.28 no.1
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• pp.83-90
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• 2013

Objectives : Tetramethylpyrazine (TMP) is an active ingredient in Ligusticum wallichii and has a wide range of neuroprotection effects. This study investigated anti-neuroinflammatory effect of TMP on brain regions in intracerebroventricular (i.c.v.) lipopolysaccharide (LPS)-treated C57BL/6 mice. Methods : TMP was administered intraperitoneally at doses of 10, 20, and 30 mg/kg at 1 h prior to LPS (3 mg/kg) i.c.v. injection. mRNA level of pro-inflammatory cytokines, including tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin (IL)-$1{\beta}$ and IL-6, was measured in the cerebral cortex, hippocampus, and hypothalamus tissue using real-time polymerase chain reaction at 24 h after the LPS injection. Cyclooxygenase-2 (COX-2) positive cells in the hypothalamus was also observed using immunohistochemistry at 24 h after the LPS injection. Results : At a dose of 30 mg/kg TMP significantly attenuated up-regulation of TNF-${\alpha}$ and IL-$1{\beta}$ mRNA in the cerebral cortex and IL-$1{\beta}$ mRNA in the hippocampus. In the hypothalamus, doses of 20 mg/kg and 30 mg/kg TMP significantly attenuated up-regulation of TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 mRNA induced by the LPS injection. In addition, TMP (30 mg/kg) significantly reduced the number of COX-2 positive cells in the hypothalamus. Conclusion : These results indicate that TMP has an anti-inflammatory effect on neuroinflammation, especially in the hypothalamus, induced by LPS i.c.v. injection and suggest that TMP-containing Ligusticum wallichii may play a modulatory role on the systemic responses following hypothalamic inflammation.

• Herbal Formula Science
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• v.20 no.2
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• pp.83-92
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• 2012

Objectives : The aim of this study was to evaluate the efficacy of Hwangryunhaedok-tang (HHT) and Gungangbuja-tang (GBT) on lipopolysaccharide (LPS)-induced mouse model of inflammation. HHT and GBT are one of the representative prescriptions of cold drug and one of the representative prescriptions of hot drug, respectively. For experimental evaluation of their efficacy, we investigated the anti-inflammatory effects of HHT and GBT on LPS-induced inflammation and the mechanisms of their action. Methods : ICR mice were given a HHT (50, 500 mg/kg), GBT (100, 1000 mg/kg) extract orally on three consecutive days. On the third day, they were administered LPS intraperitoneally (35 mg/kg), 1 h after the last sample administration. Blood and liver samples were taken 6 h after the LPS challenge. Cytokine expression and inflammation-related protein factor analyses were performed by Western blotting. Results : Oral administration of HHT significantly reduced pro-inflammatory cytokines, including interleukin (IL)-6, and interferon (IFN)-${\gamma}$ in the serum. While GBT inhibited an increase of IL-6, IFN-${\gamma}$ was not affected. Immunoblot analysis showed that LPS-induced NF-${\kappa}b$ activation was inhibited by GBT, meanwhile HHT only inhibited NF-${\kappa}b$ expression at high does (500 mg/kg). In addition, HHT and GBT inhibited LPS-induced phosphorylation of Erk1/2, Jnk and p38 MAPKs. GBT also significantly inhibited i-Nos and Cox-2 expression, and HHT inhibited only i-Nos expression. Conclusions : Both of HHT and GBT showed anti-inflammatory effects against LPS-induced endotoxemia. However, HHT significantly decreased inflammatory cytokine levels, such as IL-6 and IFN-${\gamma}$ more than GBT, while GBT significantly inhibited inflammatory proteins, including NF-${\kappa}b$, MAP Kinases, i-Nos and Cox-2, more than HHT. These results suggest that HHT and GBT regulate the different mechanisms of action and pathways, presumably by regulating cytokine levels (IL-6, IFN-${\gamma}$), NF-${\kappa}b$ activation, and several pro-inflammatory gene expression, although both of HHT and GBT have anti-inflammatory effects.

• Molecules and Cells
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• v.37 no.6
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• pp.441-448
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• 2014

Inflammasomes are specialized signaling platforms critical for the regulation of innate immune and inflammatory responses. Various NLR family members (i.e., NLRP1, NLRP3, and IPAF) as well as the PYHIN family member AIM2 can form inflammasome complexes. These multiprotein complexes activate inflammatory caspases (i.e., caspase-1) which in turn catalyze the maturation of select pro-inflammatory cytokines, including interleukin (IL)-$1{\beta}$ and IL-18. Activation of the NLRP3 inflammasome typically requires two initiating signals. Toll-like receptor (TLR) and NOD-like receptor (NLR) agonists activate the transcription of pro-inflammatory cytokine genes through an NF-${\kappa}B$-dependent priming signal. Following exposure to extracellular ATP, stimulation of the P2X purinoreceptor-7 ($P2X_7R$), which results in $K^+$ efflux, is required as a second signal for NLRP3 inflammasome formation. Alternative models for NLRP3 activation involve lysosomal destabilization and phagocytic NADPH oxidase and /or mitochondria-dependent reactive oxygen species (ROS) production. In this review we examine regulatory mechanisms that activate the NLRP3 inflammasome pathway. Furthermore, we discuss the potential roles of NLRP3 in metabolic and cognitive diseases, including obesity, type 2 diabetes mellitus, Alzheimer's disease, and major depressive disorder. Novel therapeutics involving inflammasome activation may result in possible clinical applications in the near future.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.04a
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• pp.106-106
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• 2018

Cyanidin 3 - rutinoside chloride (CRC) is major anthocyanin, found in Schisandra chinensis, is known to have antioxidant, anticancer, anti-inflammatory, tonic, and anti-aging effects in Korea, China and Japan. In the present study, the human mast cell line (HMC-1) was used to investigate the effects on the production of pro-inflammatory mediators. In this study, CRC showed no cytotoxicity in HMC-1. CRC significantly inhibited the secretion of inflammatory cytokines such as tumor necrosis factor $(TNF)-{\alpha}$ and interleukin (IL)-6 in PMA plus A23187 cacium ionophore (PMACI)-stimulated HMC-1 cells. In addition, CRC suppressed the serum levels of IgE. Furthermore, CRC decreased the PMACI- stimulated phosphorylation of mitogen activated protein kinases (MAPKs) such as p-ERK, p- JNK and p-P38. These results indicate that the pharmacological actions of CRC suggest their potential activity for treatment of allergic inflammation through the down-regulation of mast cell activation.

• Archives of Pharmacal Research
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• v.29 no.1
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• pp.1-15
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• 2006

Vascular endothelial cell injury or dysfunction has been implicated in the onset and' progression of cardiovascular diseases including atherosclerosis. A number of previous studies have demonstrated that the pro-oxidative and pro-inflammatory pathways within vascular endothelium play an important role in the initiation and progression of atherosclerosis, Recent evidence has provided compelling evidence to indicate that interleukin-4 (IL-4) can induce proc inflammatory environment via oxidative stress-mediated up-regulation of inflammatory mediators such as cytokine, chemokine, and adhesion molecules in vascular endothelial cells. In addition, apoptotic cell death within vascular endothelium has been hypothesized to be involved in the development of atherosclerosis. Emerging evidence has demonstrated that IL-4 can induce apoptosis of human vascular endothelial cells through the caspase-3-dependent pathway, suggesting that IL-4 can increase endothelial cell turnover by accelerated apoptosis, the event which may cause the dysfunction of the vascular endothelium. These studies will have a high probability of revealing new directions that lead to the development of clinical strategies toward the prevention and/or treatment for individuals with inflammatory vascular diseases including atherosclerosis.

• YAKHAK HOEJI
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• v.59 no.6
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• pp.251-258
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• 2015

Aim of the present study was to investigate whether methanol extract from the leaves of Staphylea bumalda could be used to suppress lipopolysaccharide (LPS)-induced inflammatory responses in murine macrophage cell lines, Raw 264.7 cells. The extract reduced nitric oxide (NO), cyclooxigenase-2 (COX-2) and pro-inflammatory cytokines production from LPS-stimulated Raw 264.7 cells. These inhibitory effects were associated with decreases in the phosphorylation of MAP kinases and the activity of $NF{\kappa}B$ signal pathways. Our results indicate that Staphylea bumalda significantly inhibits the inflammatory activity of activated macrophages, suggesting that Staphylea bumalda could be a potential candidate for the treatment of inflammatory disease.