• Korean Journal of Plant Resources
• /
• v.32 no.6
• /
• pp.669-676
• /
• 2019

Zanthoxylum piperitum D.C. (ZP) peels has been used as a natural spice and herb medicine for hypertension reduction, for strokes, and for its anti-bacterial and anti-oxidant activity. However, the anti-inflammatory mechanisms employed by ZP have yet to be completely understood. In this study, we elucidate the anti-inflammatory mechanism of ZP in lipopolysaccharide (LPS)-induced RAW264.7 cells. We evaluated the effects of ZP in LPS-induced levels of inflammatory cytokines, prostaglandin E₂ (PGE₂), and caspase-1 using ELISA. The expression levels of inflammatory-related genes, including cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS), were assayed by Western blot analysis. We elucidated the effect of ZP on nuclear factor (NF)-κB activation by means of a luciferase activity assay. The findings of this study demonstrated that ZP inhibited the production of inflammatory cytokine and PGE₂ and inhibited the increased levels of COX-2 and iNOS caused by LPS. Additionally, we showed that the anti-inflammatory effect of ZP arises by suppressing the activation of NF-κB and caspase-1 in LPS- induced RAW264.7 cells. These results provide novel insights into the pharmacological actions of ZP as a potential candidate for development of new drugs to treat inflammatory diseases.

• The Korean Journal of Physiology and Pharmacology
• /
• v.21 no.4
• /
• pp.449-456
• /
• 2017

Beauvericin (BEA), a cyclic hexadepsipeptide produced by the fungus Beauveria bassiana, is known to have anti-cancer, anti-inflammatory, and anti-microbial actions. However, how BEA suppresses macrophage-induced inflammatory responses has not been fully elucidated. In this study, we explored the anti-inflammatory properties of BEA and the underlying molecular mechanisms using lipopolysaccharide (LPS)-treated macrophage-like RAW264.7 cells. Levels of nitric oxide (NO), mRNA levels of transcription factors and the inflammatory genes inducible NO synthase (iNOS) and interleukin (IL)-1, and protein levels of activated intracellular signaling molecules were determined by Griess assay, semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), luciferase reporter gene assay, and immunoblotting analysis. BEA dose-dependently blocked the production of NO in LPS-treated RAW264.7 cells without inducing cell cytotoxicity. BEA also prevented LPS-triggered morphological changes. This compound significantly inhibited nuclear translocation of the $NF-{\kappa}B$ subunits p65 and p50. Luciferase reporter gene assays demonstrated that BEA suppresses MyD88-dependent NF-${\kappa}B$ activation. By analyzing upstream signaling events for $NF-{\kappa}B$ activation and overexpressing Src and Syk, these two enzymes were revealed to be targets of BEA. Together, these results suggest that BEA suppresses $NF-{\kappa}B$-dependent inflammatory responses by suppressing both Src and Syk.

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

• Biomolecules & Therapeutics
• /
• v.13 no.4
• /
• pp.214-219
• /
• 2005

Chunghyuldan (Qingxuedan in Chinese) (CHD) has been used for patients with atherosclerosis and brain ischemia in Korea. To evaluate antiischemic activity of CHD, its antiinflammatory effect in lipopolysaccharide-induced BV-2 cells was investigated. CHD potently inhibited nitric oxide (NO) production in LPS-induced BV-2 cells with an $IC_{50}$ value of 4.8${\mu}g/ml$. CHD did not only inhibit mRNA and protein expression levels of inducible NO synthase and cyclooxygenase-2 in LPS-induced BV-2 cells, but also repressed mRNA expression levels of proinflammatory cytokines IL-l$\beta$ and TNF-$\alpha$. CHD also downregulated the activation of NF-kB and AP-l transcription factors induced by LPS. These results suggest that CHD may improve inflammatory brain ischemia by the downregulation the activation of NF-kB and AP-l transcription factors.

• Biomolecules & Therapeutics
• /
• v.23 no.2
• /
• pp.110-118
• /
• 2015

According to the expansion of lifespan, neuronal disorder based on inflammation has been social problem. Therefore, we isolated shikonin from Lithospermum erythrorhizon and evaluated anti-inflammatory effects of shikonin in lipopolysaccharide (LSP)-stimulated BV2 microglial cells. Shikonin dose-dependently inhibits the expression of the proinflammatory mediators, nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$), and tumor necrosis factor-${\kappa}B$ (TNF-${\alpha}$) as well as their main regulatory genes and products such as inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-${\alpha}$ in LPS-stimulated BV2 microglial cells. Additionally, shikonin suppressed the LPS-induced DNA-binding activity of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) to regulate the key regulatory genes of the proinflammatory mediators, such as iNOS, COX-2, and TNF-${\alpha}$, accompanied with downregulation of reactive oxygen species (ROS) generation. The results indicate that shikonin may downregulate the expression of proinflammatory genes involved in the synthesis of NO, $PGE_2$, and TNF-${\alpha}$ in LPS-treated BV2 microglial cells by suppressing ROS and NF-${\kappa}B$. Taken together, our results revealed that shikonin exerts downregulation of proinflammatory mediators by interference the ROS and NF-${\kappa}B$ signaling pathway.

• Biomolecules & Therapeutics
• /
• v.19 no.3
• /
• pp.324-330
• /
• 2011

Broussonetia papyrifera and Lonicera japonica have long been used in the treatment of inflammatory disorders, especially respiratory inflammation, in Chinese medicine. Previously, phytoformula (BL) containing B. papyrifera and L. japonica was found to exert strong anti-inflammatory activity in vitro and in vivo. In this study, the effects of BL on lung inflammation including bronchitis were examined in vitro and in vivo. BL (10-100 ${\mu}g$/ml) inhibited nitric oxide (NO) production of lipopolysaccharide (LPS)-treated alveolar macrophages, MH-S cells, primarily by down-regulating inducible NO synthase. BL also inhibited production of the proinflammatory cytokines, TNF-${\alpha}$ and IL-6. Against an animal model of pleural cavity inflammation, BL (200-400 mg/kg) significantly inhibited 5 h and 24 h carrageenan-induced pleurisy in rats when administered orally. Additionally, BL inhibited experimental bronchitis induced by intratracheal instillation of LPS to rats. Taken together, these results indicate that BL may be effective for the treatment of human lung inflammation as well as bronchitis.

• Herbal Formula Science
• /
• v.18 no.1
• /
• pp.121-132
• /
• 2010

Inflammatory reaction is characterized by over-production of inflammatory mediators due to an up-regulation of inflammatory pathways, which produce pro-inflammatory mediators, such as interleukin-1beta (IL-$1{\beta}$), IL-6, tumour necrosis factor alpha (TNF-$\alpha$), prostaglantin $E_2$ ($PGE_2$), and nitric oxide (NO) in U937 cells. We investigate the anti-inflammatory effects of water extracts from Lonicerae Flos and Scutellariae Radix in lipopolysaccharide (LPS)-stimulated U937 cells. Each extract suppressed the production of inflammatory mediators (NO, IL-$1{\beta}$, TNF-$\alpha$, and $PGE_2$) and the expression of inducible NO synthase and cyclooxygenase-2 in LPS- stimulated U937 cells in a dose-dependent manner. These suppressive effects were synergistically increased by their combination. Their combination extract also inhibited NF-${\kappa}B$-DNA complex of NF-${\kappa}B$ binding activity and translocation of NF-${\kappa}B$ from cytosol to nucleus. These results suggest that the combination of water-extractable components of Lonicerae Flos and Scutellariae Radix may be useful for therapeutic drugs against inflammatory immune diseases, probably by suppressing the production of inflammatory mediators.

• Journal of Microbiology and Biotechnology
• /
• v.30 no.1
• /
• pp.71-78
• /
• 2020

Lactobacillus sakei S1 strongly inhibits the expression of interleukin (IL)-6 and IL-1β in lipopolysaccharide-induced peritoneal macrophages by a mechanism for which lactic acid bacteria from kimchi that inhibit tumor necrosis factor-alpha (TNF-α) were isolated. Therefore, we further evaluated the protective effect of this strain on the colitis mouse model induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). TNBS significantly elevated myeloperoxidase (MPO) expression, macroscopic scores, and colon shortening. Oral L. sakei S1 administration resulted in reduction of TNBS-induced loss in body weight, colon shortening, MPO activity, expression of cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB). L. sakei S1 inhibited the expression of inflammatory cytokines IL-1β, IL-6 and TNF-α, induced by TNBS, but enhanced IL-10 expression. L. sakei S1 showed resistance to artificial digestive juices and adherence to intestinal epithelial Caco-2 cells. Thus, L. sakei S1 may inhibit the NF-κB pathway and be used in functional food to treat colitis.

• The Korean Journal of Physiology and Pharmacology
• /
• v.18 no.1
• /
• pp.33-39
• /
• 2014

Shepherd's purse, Capsella bursa-pastoris (L.) Medik., has been considered a health food for centuries in Asia and is known to contain the isothiocyanate compound sulforaphane. In this study, we evaluated the anti-inflammatory and antibacterial properties of a sulforaphane-containing solution (SCS) isolated from shepherd's purse. SCS had significant anti-inflammatory activity indicated by the decreased levels of nitric oxide (NO), cytokines (interleukin $1{\beta}$ [IL-$1{\beta}$], IL-6, and IL-10), and prostaglandin $E_2$ ($PGE_2$) in lipopolysaccharide-stimulated RAW 264.7 murine macrophages. In addition, SCS decreased the inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2) levels, which confirmed the anti- inflammatory activity of SCS. Further, SCS inhibited vancomycin-resistant enterococci (VRE) and Bacillus anthracis. The minimal inhibitory concentration was $250{\mu}g/ml$ for VRE and $1,000{\mu}g/ml$ for B. anthracis. Taken together, these data indicate that SCS has potential anti-inflammatory and anti-superbacterial properties, and thus it can be used as a functional food or pharmaceutical.

• Journal of Ginseng Research
• /
• v.37 no.1
• /
• pp.74-79
• /
• 2013

In continuation of our research to find biological components from Panax stipuleanatus, four oleanane-type triterpenes (12 to 15) were isolated successively. Fifteen oleanane-type saponins (1 to 15) were evaluated for nuclear factor (NF)-${\kappa}B$ activity using a luciferase reporter gene assay in HepG2 cells. Compounds 6 to 11 inhibited NF-${\kappa}B$, with $IC_{50}$ values between 3.1 to 18.9 ${\mu}M$. The effects on inducible nitric oxide synthase and cyclooxygenase-2 by compounds 8, 10, and 11 were also examined using reverse transcription-polymerase chain reaction. Three compounds (8, 10, and 11) inhibited NF-${\kappa}B$ activity by reducing the concentration of inflammatory factors in HepG2 cells.