• Journal of Physiology & Pathology in Korean Medicine
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• v.30 no.5
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• pp.338-346
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• 2016

Signal transducer and activator of transcription 3 (STAT3) is associated with various human diseases, such as cancer, auto-immune disease, and intestinal inflammation. The limited and inadequate effect of standard approaches for treating inflammatory bowel disease (IBD) has prompted to develop alternative anti-colitis agents through inhibition of STAT3. Here, we show that gallic acid (GA), a 3,4,5-trihydroxybenzoic acid, markedly reduced phosphorylation of STAT3. Among the derivatives of benzoic acids, GA showed significant inhibition on STAT3 phosphorylation. In addition, GA ameliorated the dextran sodium sulfate (DSS)-induced acute colitis as determined by the measurement of symptomatic and histological indices. The suppression of DSS-induced acute colitis by GA treatment may be related to the regulation of cytokines and growth factors. Furthermore, GA inhibited phosphorylation of STAT3 in the colon tissue of DSS-treated mice. These findings may be useful in comprehending the molecular action of GA on STAT3 phosphorylation and provide novel insights into the potential application of GA in the treatment of STAT3-related inflammatory disease, such as IBD.

• Journal of Life Science
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• v.15 no.2 s.69
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• pp.279-286
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• 2005

The Opuntia ficus-indica var. saboten Makino (Cactus) is a tropical or subtropical plant, which is cultivated or grows naturally in Jeju island. It has been widely used as folk medicine for burned wound, edema and indigestion. In addition, its extract has been claimed to have several biological activities including anti-inflammation in oriental medicine. In this study, we examined the antimicrobial activities of the methanol extract of Opuntia ficus-indica var. saboten Makino. The extract showed a broad spectrum of antimicrobial activity against pathogenic bacteria, including antibiotics resistant bacteria (MRSA, R-P. aeruginosa, VRE) and Propionibacterium acnes, yeast, and fungi. The extract retained the activity after heat treatment for 15 min at $100^{\circ}C$ and $121^{\circ}C$ and after extended storage, up to 10 weeks storage period at $4^{\circ}C$ and $25^{\circ}C$, also stably retained its activity. It showed a better inhibitoring effect to the growth of E. coli than sodium benzoate did it at the same concentration. Addition of various salts or metal ions did not affect on its antimicrobial activity. Therefore, the antimicrobial characteristics of the extract can be applicable as a natural preservative and an antimicrobial agent for bacterial disease.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.3
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• pp.603-608
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• 2006

In activated macrophage, large amounts of nitric oxide (NO) are generated by inducible nitric oxide synthase (iNOS), resulting in acute or chronic inflammatory disorders. In Raw 264.7 cells stimulated with lipopolysaccharide (LPS) to mimic inflammation, water extracts from the fruit of Chaenomeles sinensis, the root of Polygonum cuspidatum and Boswellia carterii inhibited the LPS-induced NO production in a parallel dose-dependent manner. To investigate the mechanism by which those extracts inhibits NO production, we examined the expression of iNOS and COX-2 in both mRNA and protein levels. We observed a significant change in the iNOS expression between LPS alone and LPS plus those extracts-treated cells. However, water extracts from Chaenomeles sinensis, Polygonum cuspidatum and Boswellia carterii did not inhibit COX-2 expression which was induced by LPS treatment in Raw 264.7 cells. These data suggest that water extracts from Chaenomeles sinensis, Polygonum cuspidatum and Boswellia carterii can modulate anti-inflammatory immune response, which may be in part associated with the regulation of NO synthesis through the regulation of iNOS expression in mouse macrophage cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.2
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• pp.385-389
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• 2008

Nitric oxide (NO) has been suggested to play an important role in endotoxin-mediated shock and inflammation. In this study, we investigated the effect of Rosa laevigata Michx. (Rosaceae) on the production of NO and the molecular mechanism of its action. Rosa laevigata inhibited NO generation and iNOS expression in LPS-stimulated murine macrophages. Activity of nuclear $factor{-\kappa}B\;(NF{-\kappa}B)$ and the degradation of $I{\kappa}B-{\alpha}$ were suppressed by Rosa laevigata. Furthermore, extracellular signal-stimulated kinase (ERK), which is known to be involved in $NF{-\kappa}B$ activation, is inhibited by Rosa laevigata. These results suggest that Rosa laevigata could exert its anti-inflammatory actions by suppressing the synthesis of NO through inhibition of $NF{-\kappa}B$ activity.

• Biomolecules & Therapeutics
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• v.23 no.5
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• pp.421-427
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• 2015

Imperatorin has been known to exert many biological functions including anti-inflammatory activity. In this study, we investigated the inhibitory effects of imperatorin on the production of inflammatory mediators in mouse bone marrow-derived mast cells (BMMC). Imperatorin inhibited degranulation and the generation of eicosanoids (leukotriene $C_4$ ($LTC_4$) and prostaglandin $D_2$ ($PGD_2$) in IgE/antigen (Ag)-stimulated BMMC. To elucidate the molecular mechanism involved in this process, we investigated the effect of imperatorin on intracellular signaling in BMMC. Biochemical analyses of the IgE/Ag-mediated signaling pathway demonstrated that imperatorin dramatically attenuated degranulation and the production of 5-lipoxygenase-dependent $LTC_4$ and cyclooxygenase-2-dependent $PGD_2$ through the inhibition of intracellular calcium influx/phospholipase $C{\gamma}1$, cytosolic phospholipase $A_2$/mitogen-activated protein kinases and/or nuclear factor-${\kappa}B$ pathways in BMMC. These results suggest that the effects of imperatorin on inhibition of degranulation and eicosanoid generation through the suppression of multiple steps of IgE/Ag-mediated signaling pathways would be beneficial for the prevention of allergic inflammation.

• Biomolecules & Therapeutics
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• v.23 no.5
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• pp.465-470
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• 2015

Chrysin is a 5,7-dihydroxyflavone and was recently shown to potently inhibit enterovirus 71 (EV71) by suppressing viral 3C protease ($3C^{pro}$ activity. In the current study, we investigated whether chrysin also shows antiviral activity against coxsackievirus B3 (CVB3), which belongs to the same genus (Enterovirus) as EV71, and assessed its ability to prevent the resulting acute pancreatitis and myocarditis. We found that chrysin showed antiviral activity against CVB3 at $10{\mu}M$, but exhibited mild cellular cytotoxicity at $50{\mu}M$, prompting us to synthesize derivatives of chrysin to increase the antiviral activity and reduce its cytotoxicity. Among four 4-substituted benzyl derivatives derived from C(5) benzyl-protected derivatives 7, 9-11 had significant antiviral activity and showed the most potent activity against CVB3 with low cytotoxicity in Vero cells. Intraperitoneal injection of CVB3 in BALB/c mice with $1{\times}10^6TCID_{50}$ (50% tissue culture infective dose) of CVB3 induced acute pancreatitis with ablation of acinar cells and increased serum CXCL1 levels, whereas the daily administration of 9 for 5 days significantly alleviated the pancreatic inflammation and reduced the elevation in serum CXCL1 levels. Collectively, we assessed the anti-CVB3 activities of chrysin and its derivatives, and found that among 4-substituted benzyl derivatives, 9 exhibited the highest activity against CVB3 in vivo, and protected mice from CVB3-induced pancreatic damage, simultaneously lowering serum CXCL1 levels.

• Biomolecules & Therapeutics
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• v.26 no.2
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• pp.157-166
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• 2018

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a common clinical syndrome of diffuse lung inflammation with high mortality rates and limited therapeutic methods. Diosmetin, an active component from Chinese herbs, has long been noticed because of its antioxidant and anti-inflammatory activities. The aim of this study was to evaluate the effects of diosmetin on LPS-induced ALI model and unveil the possible mechanisms. Our results revealed that pretreatment with diosmetin effectively alleviated lung histopathological changes, which were further evaluated by lung injury scores. Diosmetin also decreased lung wet/dry ratios, as well as total protein levels, inflammatory cell infiltration and proinflammatory cytokine (eg. $TNF-{\alpha}$, $IL-1{\beta}$ and IL-6) overproduction in bronchoalveolar lavage fluid (BALF). Additionally, increased MPO, MDA and ROS levels induced by LPS were also markly suppressed by diosmetin. Furthermore, diosmetin significantly increased the expression of Nrf2 along with its target gene HO-1 and blocked the activation of NLRP3 inflammasome in the lung tissues, which might be central to the protective effects of diosmetin. Further supporting these results, in vitro experiments also showed that diosmetin activated Nrf2 and HO-1, as well as inhibited the NLRP3 inflammasome in both RAW264.7 and A549 cells. The present study highlights the protective effects of diosmetin on LPS-induced ALI via activation of Nrf2 and inhibition of NLRP3 inflammasome, bringing up the hope of its application as a therapeutic drug towards LPS-induced ALI.

• Journal of Animal Science and Technology
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• v.60 no.6
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• pp.10.1-10.6
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• 2018

Background: Stress causes inflammation that impairs intestinal barrier function. Dietary spray-dried plasma (SDP) has recognized anti-inflammatory effects and improvement of gut barrier function. Therefore, the purpose of this study was to investigate the effects of dietary SDP on intestinal morphology of mated female mice under stress condition. Results: Villus height, width, and area of small intestines were low on gestation day (GD) 3 or 4 under stress conditions, and higher later (Time, P < 0.05). Crypt depth of colon was low on GD 4 and higher later (Time, P < 0.05). Meanwhile, the SDP treatments improved (P < 0.05) intestinal morphology, indicated by increased villus height, villus width, villus area, and ratio between villus height and crypt depth of small intestines and crypt depth of colon, and by decreased crypt depth of small intestines, compared with the control diet. The SDP treatments also increased (P < 0.05) the number of goblet cells in intestines compared with the control diet. There were no differences between different levels of SDP. Conclusion: Dietary SDP improves intestinal morphology of mated female mice under stress condition.

• Nutrition Research and Practice
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• v.7 no.6
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• pp.460-465
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• 2013

The hepatoprotective activity of Acanthopanax koreanum Nakai extract (AE) was investigated against D-Galactosamine/Lipopolysaccharide (D-GalN/LPS)-induced liver failure rats compared with that of acanthoic acid (AA) isolated from AE. Although D-GalN/LPS (250 mg/kg body weight/$10{\mu}g/kg$ body weight, i.p.) induced hepatic damage, pretreatments with AE (1 and 3% AE/g day) and AA (0.037% AA, equivalent to 3% AE/g day) alleviated the hepatic damage. This effect was the result of a significant decrease in the activity of alanine transaminase. Concomitantly, both the nitric oxide and IL-6 levels in the plasma were significantly decreased by high-dose AE (AE3) treatment compared to the GalN/LPS control (AE0). This response resulted from the regulation of pro-inflammatory signaling via a decrease in TLR4 and CD14 mRNA levels in the liver. While a high degree of necrosis and hemorrhage were observed in the AE0, pretreatment with AE3 and AA reduced the extent of hepatocyte degeneration, necrosis, hemorrhage and inflammatory cell infiltrates compared to the AE0. In conclusion, these results suggest that especially high-dose AE are capable of alleviating D-GalN/LPS-induced hepatic injury by decreasing hepatic toxicity, thereby mitigating the TLR 4-dependent cytokine release. The anti-inflammatory effect of AE could be contributing to that of AA and AE is better than AA.

• Food Science and Biotechnology
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• v.18 no.5
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• pp.1063-1070
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• 2009

Dangyuja (Citrus grandis Osbeck) is a native plant growing only on Jeju Island in Korea. In this study, antiinflammatory effect of dangyuja leaves on a murine macrophage cell line was investigated. RAW 264.7 murine macrophage cells were stimulated with lipopolysaccharide (LPS, $1{\mu}g/mL$) to induce expression of pro-inflammatory markers [interleukin (IL)-6 and inducible nitric oxide synthase (iNOS)]. The crude extract (80% MeOH Ex.) and solvent fractions (hexane, $CHCl_3$, EtOAc, BuOH, and $H_2O$ Ex.) were obtained from dangyuja leaves. The $CHCl_3$ fraction inhibited the nitric oxide (NO) and IL-6 production in a dose-dependent manner. Also, the $CHCl_3$ fraction inhibited mRNA expression and protein levels of iNOS in a dose-dependent manner. Furthermore, the $CHCl_3$ fraction inhibited LPS-induced nuclear factor (NF)-${\kappa}B$ activation and phosphorylation of mitogen-activated protein kinases (MAPKs: ERK, JNK, and p38). These results suggest that dangyuja leaves may inhibit LPS-induced production of inflammatory markers by blocking NF-${\kappa}B$ and MAPKs signaling in RAW 264.7 cells.