• YAKHAK HOEJI
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• v.52 no.5
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• pp.402-406
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• 2008

Previously, we have shown that 1-furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) has an anti-inflammatory activity in a rat paw-edema model. In the present study, we investigated an inhibitory effect of FPP-3 on the tumor necrosis factor (TNF)-${\apha}$-induced inflammatory cytokine response in HT-29 human colon epithelial cells. Treatment with FPP-3 significantly prevented the TNF-${\apha}$-induced attachment of leukocytes to HT-29 colon epithelial cells, which is one of the pathologic hallmarks in colon inflammation. The effect of FPP-3 was markedly superior than that of 5-aminosalicylic acid (5-ASA), a commonly used drug for the treatment of inflammatory bowel disease (IBD). The pretreatment with FPP-3 inhibited TNF-${\apha}$- induced monocyte chemoattractant protein (MCP)-1, interleukin (IL)-8 mRNA expressions. In addition, FPP-3 significantly suppressed TNF-${\apha}$-induced nuclear factor (NF)-${\kappa}B$ transcription activity. These results demonstrate that FPP-3 modulates intestinal inflammation via suppressing the NF-${\kappa}B$ dependent expressions of MCP-1 and IL-8, and suggest that FPP-3 may be a valuable agent for the treatment of IBD.

• Korean Journal of Medicinal Crop Science
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• v.19 no.4
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• pp.217-226
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• 2011

The study was conducted to investigate candidate materials as anti-inflammation agent from plant resources. Activities of 33 plant parts extracts with the final concentration of 5${\mu}g/ml$ were evaluated on the several inflammation-related markers such as the release of proinflammatoty cytokine [tumor necrosis factor-alpha (TNF-${\alpha}$) & interleukin-6 (IL-6)], nitric oxide (NO), the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and inhibitor of nuclear factor kappa-B alpha ($I{\kappa}-B{\alpha}$) in lipopolysaccharide (LPS)-treated RAW 264.7 cells. The extracts in the final concentration of 10 ${\mu}g/ml$ were also screened on peroxynitrite (ONOO$^-$) scavenging activity. Eleven extracts selected from the screening assay were verified on the inhibition activity on peroxynitrite and total reactive species oxygen (ROS) in the several concentrations. As results, Alpinia officinarum Hance (rhizome), Inula britannica var. chinensis Regel (flower), Ulmus arvifolia Jacq (trunk peel) and Aster scaber Thunb. (aerial part) showed comparatively potent anti-inflammatory activities in vitro cells or chemical level systems, and then these four plant parts should be studied on the antiinflammatory mechanism by further studies.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.1
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• pp.1-7
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• 2015

Our previous study has shown berberine prevents damage to the intestinal mucosal barrier during early phase of sepsis in rat through mechanisms independent of the NOD-like receptors signaling pathway. In this study, we explored the regulatory effects of berberine on Toll-like receptors during the intestinal mucosal damaging process in rats. Male Sprague-Dawlay (SD) rats were treated with berberine for 5 d before undergoing cecal ligation and puncture (CLP) to induce polymicrobial sepsis. The expression of Toll-like receptor 2 (TLR 2), TLR 4, TLR 9, the activity of nuclear factor-kappa B ($NF-{\kappa}B$), the levels of selected cytokines and chemokines, percentage of cell death in intestinal epithelial cells, and mucosal permeability were investigated at 0, 2, 6, 12 and 24 h after CLP. Results showed that the tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-6 (IL-6) level were significantly lower in berberine-treated rats compared to the control animals. Conversely, the expression level of tight junction proteins, percentage of cell death in intestinal epithelial cells and the mucosal permeability were significantly higher in berberine-treated rats. The mRNA expression of TLR 2, TLR 4, and TLR 9 were significantly affected by berberine treatment. Our results indicate that pretreatment with berberine attenuates tissue injury and protects the intestinal mucosal barrier in early phase of sepsis and this may possibly have been mediated through the TLRs pathway.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.2
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• pp.270-274
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• 2011

The prevalence of atopic dermatitis has markedly increased in recent years but the mechanism has not been clearly revealed. Recent study exhibited that atopic dermatitis was exacerbated by the increase of proteinase-activated receptor (PAR)-2 expression, which activated $I{\kappa}B$ kinase --> nuclear factor kappa B. Therefore, we determined whether the allergens of dust mites induced the expression of PAR-2, intercellular adhesion molecule-1 (ICAM-1, adehision molecule), interleukins (IL)-6 in HaCaT keratocytes and which herbal 1,3-butylene glycol extracts (Mori Cortex Radicis, Sanguisorba officinalis L., Arctium lappa Linne, Torilis japonica DC, Melia azedarach Linne var. japoinca Makino) suppressed their expression. Dust mite allergen increased PAR-2, ICAM-1 and IL-6 expression in HaCaT cells in a dose-dependent manner up to $3{\mu}g/mL$ but their expression reached the plateau over the dosages. The allergen ($3{\mu}g/mL$) also secreted more cytokines such as tumor necrosis factor (TNF)-${\alpha}$ and IL-6 into the media. Among five different herbal extracts ($50{\mu}g/mL$), Mori Cortex Radicis and Sanguisorba officinalis L. suppressed the PAR-2, ICAM-1 and IL-6 expression in HaCaT cells, which was activated by dust mite allergen ($3{\mu}g/mL$) and they also reduced the secretion of TNF-${\alpha}$ and IL-6 into the media. In conclusion, Mori Cortex Radicis and Sanguisorba officinalis L. can effectively reduce the prevalence and progression of atopic dermatitis by dute mite allergen.

• The Korea Journal of Herbology
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• v.31 no.6
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• pp.37-44
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• 2016

Objective : This study aimed to evaluate the protective effect of Artemisiae Capillaris Herba (AC) in reflux esophagitis (RE) rats. Methods : The AC was measured antioxidant activity through in vitro experiments, such as total polyphenol and flavonoid contents, 1, 1-diphenyl-2-picrylhydrazyl (DPPH) and 2, 2'-azinobis-3-ethyl-benzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity. Base on the results, we had conducted in vivo experiments. Rats were divided normal, control, AC treatment 50 mg/kg BW (AC50), and AC treatment 100 mg/kg BW (AC100) groups. AC were orally administered 2 h before the induction of RE. RE was induced by tie the pylorus and the transitional junction between the forestomach and the corpus in Sprague-Dawley rats. The rats were sacrificed 5 h after the surgery. We analyzed the expression of inflammatory related markers by western blot and observed the production of reactive oxygen species (ROS) and hematoxylin-eosin staining, Results : The $IC_{50}$ of AC for DPPH and ABTS were showed 12.60 and $33.32{\mu}g/m{\ell}$ respectively. In the RE rat, AC decreased inflammatory related markers, such as phosphorylated inhibitor of ${\kappa}B{\alpha}$, nuclear factor-kappa B, cyclooxygenase-2, inducible nitric oxide synthase, and tumor necrosis factor alpha. Also, AC reduced the increased reactive oxygen species in serum. The anti-inflammatory effect of AC appeared to be partially mediated through the inhibition of ROS. Also, AC markedly ameliorated esophageal mucosa damage via the inhibition of protein expression related to inflammation. Conclusions : Therefore, these results suggest that AC would be used as a therapeutic material in protection and/or treatment for reflux esophagitis.

• Journal of Applied Biological Chemistry
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• v.62 no.2
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• pp.111-122
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• 2019

The mulberry tree (Morus alba L.) has been traditionally used in Chinese medicine to treat inflammatory diseases. We investigated the effects of bioconversion on different components of the mulberry tree, and determined changes in the physiological activities. Ethyl acetate-soluble fractions of five different segments (fruit, Mori Fructus; leaf, Mori Folium; twig, Mori Ramulus; root, Mori Cortex; and mistletoe, Loranthi Ramulus) of the mulberry tree show enhanced anti-oxidant effects in the 2,2-diphenyl-1-picrylhydrazyl, and 2,2'-azinobis-(3-ethylvenzothiazoline-6-sulfonic acid) assays, and enhanced anti-inflammatory effects of lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production in RAW 264.7 macrophages, after being treated with a crude enzyme extract from Aspergillus kawachii, in the following order of activity: Mori Folium>Mori Cortex>Mori Ramulus>Mori Fructus>Loranthi Ramulus. Ethyl acetate- soluble fraction of mulberry leaves (Mori Folium) that underwent bioconversion was most effective, and was devoid of any cytotoxicity. The fraction was also effective against mRNA expression of LPS-induced pro-inflammatory cytokines, such as inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis $factor-{\alpha}$, $interleukin-1{\beta}$, and interleukin-6. In addition, the fraction was effective in LPS-induced phosphorylation of mitogen-activated protein kinases and IKK, and $I{\kappa}B$ degradation, followed by translocation of the nuclear $factor-{\kappa}B$ from the cytoplasm to the nucleus. Thus, bioconversion increased the anti-oxidative and anti-inflammatory activities of the mulberry leaf.

• The Korean Journal of Pain
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• v.33 no.1
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• pp.30-39
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• 2020

Background: This study examined the effects of gabexate mesilate on spinal nerve ligation (SNL)-induced neuropathic pain. To confirm the involvement of gabexate mesilate on neuroinflammation, we focused on the activation of nuclear factor-κB (NF-κB) and consequent the expression of proinflammatory cytokines and inducible nitric oxide synthase (iNOS). Methods: Male Sprague-Dawley rats were used for the study. After randomization into three groups: the sham-operation group, vehicle-treated group (administered normal saline as a control), and the gabexate group (administered gabexate mesilate 20 mg/kg), SNL was performed. At the 3rd day, mechanical allodynia was confirmed using von Frey filaments, and drugs were administered intraperitoneally daily according to the group. The paw withdrawal threshold (PWT) was examined on the 3rd, 7th, and 14th day. The expressions of p65 subunit of NF-κB, interleukin (IL)-1, IL-6, tumor necrosis factor-α, and iNOS were evaluated on the 7th and 14th day following SNL. Results: The PWT was significantly higher in the gabexate group compared with the vehicle-treated group (P < 0.05). The expressions of p65, proinflammatory cytokines, and iNOS significantly decreased in the gabexate group compared with the vehicle-treated group (P < 0.05) on the 7th day. On the 14th day, the expressions of p65 and iNOS showed lower levels, but those of the proinflammatory cytokines showed no significant differences. Conclusions: Gabexate mesilate increased PWT after SNL and attenuate the progress of mechanical allodynia. These results seem to be involved with the antiinflammatory effect of gabexate mesilate via inhibition of NF-κB, proinflammatory cytokines, and nitric oxide.

• The Journal of Internal Korean Medicine
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• v.33 no.3
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• pp.272-283
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• 2012

Objectives : The purpose of this study was to investigate the mechanism of protective effect of Jinmu-tang (JMT, Zhenwu-tang) extract on $H_2O_2$-induced cell death in C6 glial cells. Methods : Cultured C6 glial cells of white mice were pretreated with JMT extract and exposed to $H_2O_2$ for inducing cell death. We measure the cell viability by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and investigate the cell morphology using a light microscope after crystal violet (CV) staining. Reactive oxygen species (ROS) formation was analyzed using a flow cytometer and a fluorescent microscope after staining with 2'7'-dichlorofluorescein diacetate (DCF-DA). DNA fragmentation was analyzed using a flow cytometer after propidium iodide (PI) staining and nuclei morphology was investigated using a fluorescent microscope after 2-[4-amidinophenyl]-6-indo-lecarbamidine dihydrochloride (DAPI) staining. We analyzed expression of Bax, processing of procaspase-3 and poly (ADP-ribose) polymerase (PARP), and activation of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) by western blot method. Tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) secretion was analyzed using Quantikine kit. Results : We determined the elevated cell viability by JMT extract on $H_2O_2$-induced C6 glial cell death. ROS formation, DNA fragmentation, $I{\kappa}B{\alpha}$ phosphorylation, NF-${\kappa}B$ activation, and secretion of TNF-${\alpha}$ induced by $H_2O_2$ are inhibited by JMT extract pre-treatment. JMT extract inhibits Bax expression, processing of caspase-3 and PARP that are critical biochemical markers of apoptotic cell death. Conclusions : These results suggest that JMT extract has a protective effect on $H_2O_2$-induced C6 glial cell death in various pathways.

• Journal of Applied Biological Chemistry
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• v.61 no.3
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• pp.275-281
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• 2018

Pinus densiflora root (PDR) is used as a medicinal plant. In this study, we investigated whether the PDR extract has anti-inflammatory activities. Cell viability assays showed that the extract was not toxic toward RAW 264.7 cells at concentrations up to $10{\mu}g/mL$. At $10{\mu}g/mL$, the extract decreased nitric oxide (NO) content to 40% of the control level. The protein expression of inducible nitric oxide synthase (iNOS), which generates NO, decreased with increasing concentrations of the extract. Prostaglandin $E_2$ ($PGE_2$) levels were significantly inhibited by over 50% in the presence of $10{\mu}g/mL$ of the extract. The protein expression of cyclooxygenase-2 (COX-2), which generates $PGE_2$, decreased with increasing concentrations of the extract. Proinflammatory cytokines, such as tumor necrosis factor-alpha ($TNF-{\alpha}$), interleukin-6 (IL-6), and $IL-1{\beta}$, were detected in RAW 264.7 cells after lipopolysaccharide (LPS) treatment. The extract did not affect the levels of $TNF-{\alpha}$ and IL-6, but it significantly inhibited the level of $IL-1{\beta}$. It also completely inhibited the transcription of nuclear factor-kappaB ($NF-{\kappa}B$). These results indicate that the PDR extract reduces inflammatory response-related proteins, such as NO, $PGE_2$, iNOS, and COX-2, in LPS-induced RAW 264.7 cells via the regulation of $NF-{\kappa}B$. Consequently, we have provided a mechanism to explain the anti-inflammatory effect of the PDR extract; that is, it exerts such an effect by regulating $NF-{\kappa}B$. The PDR extract can therefore be considered as an effective anti-inflammatory agent.

• Tuberculosis and Respiratory Diseases
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• v.73 no.1
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• pp.22-31
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• 2012

Background: Oxidation plays an important role in acute lung injury. This study was conducted in order to elucidate the effect of repetitive post-treatment of N-acetylcysteine (NAC) in lipopolysaccaride (LPS)-induced acute lung injury (ALI) of rats. Methods: Six-week-old male Sprague-Dawley rats were divided into 4 groups. LPS (Escherichia coli 5 mg/kg) was administered intravenously via the tail vein. NAC (20 mg/kg) was injected intraperitoneally 3, 6, and 12 hours after LPS injection. Broncho-alveolar lavage fluid (BALF) and lung tissues were obtained to evaluate the ALI at 24 hours after LPS injection. The concentration of tumor necrosis factor ${\alpha}$ (TNF-${\alpha}$) and interleukin $1{\beta}$ (IL-$1{\beta}$) were measured in BALF. Nuclear factor ${\kappa}B$ (NF-${\kappa}B$), lipid peroxidation (LPO), and myeloperoxidase (MPO) were measured using lung tissues. Micro-computed tomography (micro-CT) images were examined in each group at 72 hours apart from the main experiments in order to observe the delayed effects of NAC. Results: TNF-${\alpha}$ and IL-$1{\beta}$ concentration in BALF were not different between LPS and NAC treatment groups. The concentration of LPO in NAC treatment group was significantly lower than that of LPS group ($5.5{\pm}2.8$ nmol/mL vs. $16.5{\pm}1.6$ nmol/mL) (p=0.001). The activity of MPO in NAC treatment group was significantly lower than that of LPS group ($6.4{\pm}1.8$ unit/g vs. $11.2{\pm}6.3$ unit/g, tissue) (p<0.048). The concentration of NF-${\kappa}B$ in NAC treatment group was significantly lower than that of LPS group ($0.3{\pm}0.1\;ng/{\mu}L$ vs. $0.4{\pm}0.2\;ng/{\mu}L$) (p=0.0001). Micro-CT showed less extent of lung injury in NAC treatment than LPS group. Conclusion: After induction of ALI with lipopolysaccharide, the therapeutic administration of NAC partially attenuated the extent of ALI through the inhibition of NF-${\kappa}B$ activation.