• Korean Journal of Food Science and Technology
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• v.44 no.3
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• pp.331-336
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• 2012

In this study, we selected Gardeniae fructus (GF) as an anti-inflammatory functional material and improved the biological activity of GF through the treatment of ${\beta}$-glucosidase. For the simple evaluation of anti-inflammatory activity, the inhibitory activity of GF extract (GFE) on the production of NO by RAW264.7 cells in the presence of LPS was examined. ${\beta}$-glucosidase originating from Aspergillus niger or Aspergillus fumigatus has effectively improved the anti-inflammatory activity of GFE. The enzyme treatment raised the activity of GFE by more than 10 times. The optimum conditions for the enzyme reaction were at pH 4.6, $45^{\circ}C$, and 20 U/mL for 24 h with agitation. In addition, in vitro production of cytokines (IL-$1{\beta}$, IL-6, TNF-${\alpha}$), COX-2, and the NF-${\kappa}B$ activation of RAW264.7 cells decreased more in the presence of GFE treated with ${\beta}$-glucosidase originating from Aspergillus niger (GFAN) than in the presence of GFE. These results suggest that enzyme-treated GFE might be a potential candidate for natural anti-inflammatory food materials.

• Korean Journal of Food Science and Technology
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• v.47 no.4
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• pp.511-516
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• 2015

In the present study, we investigated changes in the nutritional components of pre- and post-germinated barley seeds and also investigated their immune-enhancing effects such as production of nitric oxide (NO), interleukin (IL)-6, and tumor necrosis factor (TNF)-${\alpha}$ on the RAW 264.7 macrophage cell line. Protein and total sugar contents increased slightly with increase in germination time. The major neutral sugars of germinated balrey seeds were arabinose, glucose, and xylose. Glucose content decreased during germination, whereas arabinose and xylose contents increased during germination. Amino acid contents of barley germinated for 24 and 48 hours increased 1.03-fold and 1.24-fold, respectively, compared to that of pre-germinated barley. Moreover, RAW 264.7 macrophages stimulated with barley germinated for 24 and 48 hours showed higher production of NO, IL-6, and TNF-${\alpha}$ compared to that observed in pre-germinated barley. The results of the present study indicate that germinated barley may have immune-enhancing effects derived from its ability to activate RAW 264.7 macrophages, which play a major role in innate immunity.

• Journal of Life Science
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• v.30 no.7
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• pp.634-639
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• 2020

Starfish are a potential source of marine materials, but their unique odor can limit application. Our previous work suggested that brittle star Ophioplocus japonicus extract could be more effective as a cosmetic material by reducing its odor through a roasting process. However, the biological properties of heat-treated Ophioplocus japonicus extract (HOJE) remain poorly understood. We here examined the anti-inflammatory potential of HOJE in lipopolysaccharide (LPS)-induced RAW 264.7 cells. HOJE significantly inhibits LPS-stimulated nitric oxide (NO) production without affecting cell viability in a dose-dependent manner and suppresses LPS-induced expression of inducible nitric oxide synthases (iNOS) and pro-inflammatory cytokines such as interleukin-6 and -1β. Furthermore, treatment of pyrrolidine dithiocarbamate to inhibit nuclear factor kappa B (NF-κB) signaling accelerated the inhibitory effect of HOJE on NO production, and the translocation of NF-κB p65 from the cytosol to the nucleus was attenuated by HOJE. These results show that HOJE ameliorates inflammation partly through NF-κB signaling which consequently suggests that it has anti-inflammatory potential.

• Journal of Acupuncture Research
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• v.22 no.2
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• pp.93-101
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• 2005

Objective: We have evaluated UDHA into the joint for its effectiveness on immune responses to CII in the rat CIA. In an attempt to gain further insight into the mode of action of UDHA, we also investigated the effects of UDHA on the incidence and development of arthritis in rat CIA with 2 different regimens: (1) started prior to a primary immunization, (2) started on the day of a primary immunization. Methods : Male rats were immunized with an emulsion of $200\;{\mu}g/100g$ of CII and complete Freund's adjuvant (CFA). The rats were then given intraperitoneal(i.p) stimulation of Ulmus davidiana Planch herbal acupuncture(UDHA) or saline during the experiment. Lymph node cells were obtained from rats 14 days after immunization and cultured in vitro with CII. When compared with rats treated with saline as control, UDHA at doses of more than $20\;{\mu}g/100\;g$ rat once a day for 7 days inhibited the ability of inguinal lymph node cells to produce T cell cytokines interleukin-$1{\beta}$, tumor necrosis $factor-{\alpha}$ $(TNF-{\alpha})$. When rats were injected intraperitoneally with SRBC, hemaglutination titers in UD-treated and control rats did not differ significantly when low doses of UD was given to rats. However, i.p injection of UD at doses of more than $10\;{\mu}g/100\;g/day$ for 7 days slightly suppressed antibody production. Results : The present results show that treatment with UDHA can inhibit the onset and development of arthritis and the immune responses to collagen. Conclusion: Therapeutic i.p injection with UD affect the clinical course of the disease and the immune responses to CII.

• Biomolecules & Therapeutics
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• v.19 no.4
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• pp.431-437
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• 2011

Aberrant activation of microglia has been reported to cause neuronal damages by releasing a variety of pro-inflammatory cytokines. Besides where microglia become active, damages have been also observed in remote places, which is considered due to the migration of activated microglia. Therefore, an agent that could suppress abnormal activation of microglia and their subsequent migration might be valuable in activated microglia-related brain pathologies. The objective of the present study was to evaluate anti-inflammatory effects of betulinic acid on lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Pretreatment of betulinic acid significantly attenuated LPS-induced NO production and protein expression of iNOS. Betulinic acid also significantly suppressed LPS-induced release and expression of cytokines such as TNF-${\alpha}$ and IL-$1{\beta}$. Furthermore, betulinic acid significantly uppressed LPS-induced MMP-9 expression, which has been suggested to play an important role in the migration of activated microglia. In order to understand the possible mechanism by which betulinic acid suppresses LPS-induced cytokine production and migration of microglia, the role of NF-kB, a major pro-inflammatory transcription factor, was examined. Betulinic acid significantly suppressed LPS-induced degradation of IKB, which retains NF-kB in the cytoplasm. Therefore, nuclear translocation of NF-kB upon LPS stimulation was significantly suppressed with betulinic acid. Taken together, the present study for the first time demonstrates that betulinic acid possesses anti-inflammatory activity through the suppression of nuclear translocation of NF-kB in BV2 microglial cells.

• Herbal Formula Science
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• v.27 no.2
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• pp.101-120
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• 2019

PURPOSE : Euonymi Lignum Suberalatum (EL) is the stem fin of Euonymi alatus. In traditional Korean medicine, EL is used for treatment of uterine bleeding, metritis and static blood. Recently, many studies have reported several pharmacological effects of EL including anticancer, antimicrobial, antidiabetic activity, and anti-oxidative stress. However, the mechanisms underlying anti-inflammatory effects by the EL is not established. METHODS : To investigate anti-inflammatory effects of Euonymi Lignum Suberalatum Water (ELWE), Raw 264.7 cells were pre-treated with $10-300{\mu}g/mL$ of ELWE, and then exposed to $1{\mu}g/mL$ of LPS. Levels of NO, IL-6, $IL-1{\beta}$ and $TNF-{\alpha}$ were detected by ELISA kit. Expression of pro-inflammatory proteins were determined by immunoblot analysis. To evaluate the anti-inflammatory effect in vivo, rat paw edema volume, and expressions of COX-2 and iNOS proteins in carrageenan (CA)-induced rat paw edema model. RESULTS : NO production activated by LPS, was decreased by $30-300{\mu}g/mL$ of ELWE. Production of inflammatory mediators such as $TNF-{\alpha}$, ILs, $PGE_2$ were decreased by ELWE 100 and $300{\mu}g/mL$. In addition, ELWE reduced LPS-mediated iNOS and COX-2 expression. Moreover, ELWE increased $I-{\kappa}B{\alpha}$ expression in cytoplasm and decreased $NF-{\kappa}B$ expression in nucleus. In vivo study, ELWE reduced the increases of paw swelling, and expression of iNOS and COX-2 proteins in paw edema induced by CA injection. CONCLUSION : The results indicate that ELWE could inhibit the acute inflammatory response, via modulation of $NF-{\kappa}B$ activation. Furthermore, inhibition of rat paw edema induced by CA is considered as clear evidence that ELWE may be a useful source to treat acute inflammation.

• BMB Reports
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• v.55 no.2
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• pp.81-86
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• 2022

Macrophages are a major cellular component of innate immunity and are mainly known to have phagocytic activity. In the tumor microenvironment (TME), they can be differentiated into tumor-associated macrophages (TAMs). As the most abundant immune cells in the TME, TAMs promote tumor progression by enhancing angiogenesis, suppressing T cells and increasing immunosuppressive cytokine production. N-myc downstream-regulated gene 2 (NDRG2) is a tumor suppressor gene, whose expression is down-regulated in various cancers. However, the effect of NDRG2 on the differentiation of macrophages into TAMs in breast cancer remains elusive. In this study, we investigated the effect of NDRG2 expression in breast cancer cells on the differentiation of macrophages into TAMs. Compared to tumor cell-conditioned medium (TCCM) from 4T1-mock cells, TCCM from NDRG2-over-expressing 4T1 mouse breast cancer cells did not significantly change the morphology of RAW 264.7 cells. However, TCCM from 4T1-NDRG2 cells reduced the mRNA levels of TAM-related genes, including MR1, IL-10, ARG1 and iNOS, in RAW 264.7 cells. In addition, TCCM from 4T1-NDRG2 cells reduced the expression of TAM-related surface markers, such as CD206, in peritoneal macrophages (PEM). The mRNA expression of TAM-related genes, including IL-10, YM1, FIZZ1, MR1, ARG1 and iNOS, was also downregulated by TCCM from 4T1-NDRG2 cells. Remarkably, TCCM from 4T1-NDRG2 cells reduced the expression of PD-L1 and Fra-1 as well as the production of GM-CSF, IL-10 and ROS, leading to the attenuation of T cell-inhibitory activity of PEM. These data showed that compared with TCCM from 4T1-mock cells, TCCM from 4T1-NDRG2 cells suppressed the TAM differentiation and activation. Collectively, these results suggest that NDRG2 expression in breast cancer may reduce the differentiation of macrophages into TAMs in the TME.

• The Korea Journal of Herbology
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• v.28 no.5
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• pp.7-11
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• 2013

Objectives : Seungmagalgeun-tang (SMGGT) is traditional medicine widely used for inflammatory disease and flu. But SMGGT exhibits potent anti-inflammatory activity with an unknown mechanism. To elucidate the molecular mechanisms of SMGGT water extract on pharmacological and biochemical actions in inflammation, we examined the effect of SMGGT on pro-inflammatory mediators in Phorbol-12-myristate-13-acetate (PMA)+A23187-stimulated mast cells. Methods : In the present study, pro-inflammatory cytokine production was determined by performing enzyme-linked immunosorbent assay (ELISA), reverse transcription polymerase chain reaction (RT-PCR), and western blot analysis to measure the activation of MAPKs. Cells were treated with SMGGT 1 h prior to the addition of 50 nM of PMA and $1{\mu}M$ of A23187. Cell viability was measured by MTS assay. The investigation focused on whether SMGGT inhibited the expressions of interleukin-6 (IL-6), interleukin-8 (IL-8) and mitogen-activated protein kinases (MAPKs) in PMA+A23187-stimulated mast cells. Results : SMGGT has no cytotoxicity at examined concentration (100, 250, and $500{\mu}g/ml$). Also, gene expression of IL-6 and IL-8 in HMC-1 cells stimulated by PMA+A23187 was down regulated by SMGGT. Furthermore, SMGGT suppressed the PMA+A23187-induced phosphorylation of extracellular signal-regulated kinase (ERK) and c-jun N-terminal Kinase(JNK). But, SMGGT could not regulate phosphorylation of p38 MAPK. Conclusions : These results suggest that SMGGT has inhibitory effects on PMA+A23187-induced IL-6 and IL-8 production. These inhibitory effects occur through blockades on the phosphorylation of ERK and JNK.

• Journal of fish pathology
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• v.35 no.1
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• pp.103-111
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• 2022

This study has been performed to investigate the potential effects of by-product discarded after probiotics production (BPPP) on growth performance, immune gene expression, innate-immunity status, and disease resistance of carp, Cyprinus carpio. For 3 weeks, carp were fed four diets containing different levels of BPPP at 0, 0.1, 0.2 and 0.5% per kg of normal diet. Every 7 days of feeding, immune-related gene expression, serum lysozyme activity and ACH₅₀ were analyzed. Growth rates and challenge test with E. tarda were conducted after 3 weeks of BPPP feeding. Both lysozyme activity and ACH₅₀ were significantly (p<0.05) increased in all BPPP supplemented groups compared to the control at every 7 day for 3 weeks of feeding trial. The gene expression of pro-inflammatory cytokines, IL-1β and TNF-α was significantly (p<0.05) up-regulated until 21 days of feeding in all groups except for 0.2% group on day 7 post feeding. The anti-inflammatory cytokine IL-10 gene expression was only significantly (p<0.05) increased in 0.1% group on day 7 and decreased (p<0.05) on day 14 in all BPPP supplemented groups. On day 21, the IL-10 gene expression was augmented (p<0.05) in all groups. SOD gene expression was significantly (p<0.05) increased compared to the control on day 14 and 21 post feeding, whereas no significant difference was observed on day 7. In challenging test, 0.2%, 0.1%, 0.5% and control group showed 80%, 70%, 60% and 40% of survival rate, respectively. Feed conversion rate was only improved in 0.5% group. In conclusion, the present study indicates that dietary BPPP suplementation improved growth performance, innate immune response and bactericidal activity in carp.

• Journal of Korean Medicine Rehabilitation
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• v.32 no.4
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• pp.9-18
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• 2022

Objectives This study was conducted to confirm the anti-inflammatory effect of Naetakbaekryeom-san (NTB), and whether it could be another treatment for inflammatory diseases. Methods The NTB water extract was extracted with hot water at 100℃ for 2 hours, concentrated at 80℃ under reduced pressure, and used. After 2 hours of pretreatment with NTB and positive control Bay11-7082, nitric oxide (NO), inducible NO synthase (iNOS), interleukin (IL)-6, IL-1𝛽, tumor necrosis factor alpha (TNF-𝛼) were measured in RAW264.7 cells activated with lipopolysaccharides (LPS) 500 ng/mL. After 2 hours of pretreatment with NTB, the anti-inflammatory effect of NTB was evaluated by measuring nuclear factor kappa-light-chain-enhancer of activated B cells (NF-𝜅B) in RAW264.7 cells and 293T cells activated with phorbol 12-myristate 13-acetic acid (PMA) 30 ng/mL. Results In RAW264.7 cells activated with LPS, NTB at concentrations of 0.1, 0.3, and 1.0 mg/mL showed no cytotoxicity, significantly inhibited NO production and inhibition of iNOS expression. TNF-𝛼 cytokine levels was not regulated, but NTB at each concentration inhibited the production of IL-1𝛽 and IL-6, and the effect was higher than that of the positive control Bay11-7082 (20 𝜇M). In PMA-activated RAW264.7 cells and 293T cells, each concentration of NBT decreased the NF-𝜅B transcriptional activity, with the greatest decrease at 1 mg/mL. Conclusions These results demonstrated the anti-inflammatory effect of NTB water extracts, but further studies such as comparison of anti-inflammatory effects and antioxidant effects by NTB component, comparison of effects according to extraction solvents, and clinical studies are needed.