• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.10
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• pp.1439-1449
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• 2015

Prunus persica Flos (PPF) were investigated for their antioxidant and anti-inflammatory activities to find a natural functional food resource preventing degenerative diseases associated with excessive oxidative stress and chronic inflammation. PPF was extracted using ethanol (EtOH) and then sequentially fractioned by hexane (Hx), dichloromethane (DM), ethyl acetate (EA), n-butanol (BtOH), and water (DW). Contents of total phenolics and flavonoids, as well as 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activities were measured. Anti-inflammatory effects in terms of nitric oxide (NO), prostaglandin (PG) E2, and pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-${\alpha}$ production were also measured using LPS-treated RAW 264.7 macrophages. EtOH extract showed relatively high antioxidant activity with high total phenolic (78.1 mg tannic acid/g) and flavonoid contents (55.3 mg rutin/g). EA fraction contained the highest total phenolic and flavonoid contents (394.6 mg tannic acid/g, 253.7 mg rutin/g), followed by BtOH (128.3 mg tannic acid/g, 93.1 mg rutin/g). EA and BtOH fractions and EtOH extract showed higher DPPH radical and ABTS radical scavenging activities than the others (P<0.05). In LPS-treated RAW 264.7 macrophages, EtOH extract ($200{\mu}g/mL$) showed significantly reduced (P<0.05) NO, PGE2, and TNF-${\alpha}$ production levels to 38.5%, 32.3%, and 48.9% of the control, respectively, as well as reduced iNOS and COX-2 protein expression. DM fraction ($50{\mu}g/mL$) showed significantly reduced (P<0.05) NO, PGE2, IL-6, and TNF-${\alpha}$ production levels to 43.5%, 13.3%, 38.7%, and 41.3% of the control, respectively, and EA fraction ($50{\mu}g/mL$) showed significantly reduced NO, PGE2, IL-6, and TNF-${\alpha}$ production levels to 44.8%, 22.4%, 45.7%, and 62.0% of the control, respectively. Taken together, EtOH extract of PPF showed potent antioxidant and anti-inflammatory activities, and EA and BtOH fractions showed comparatively stronger antioxidant activities while DM and EA fractions showed stronger anti-inflammatory activities. It can be concluded that EtOH extract of PPF and its fractions are good candidates as natural resources for the development of anti-oxidative and anti-inflammatory functional food products.

• Journal of Gastric Cancer
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• v.6 no.3
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• pp.154-160
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• 2006

Purpose: According to the 2nd English Edition of the Japanese Gastric Cancer Association (JGCA) in 1998, in case of distal gastric cancer, the 14v (superior mesenteric vein) lymph node (LN) is included in the N2 group. However, in Korea, a modified radical gastrectomy is performed, and a 14v LN dissection is not done as a routine procedure. Thus, we investigated the rate of metastatic 14v LNs, evaluated the necessity of dissection of the 14v LN, and searched for indications of 14v LN dissection. Materials and Methods: From April 2004 to August 2005, we enrolled the patients who were diagnosed as having advanced gastric cancer in the distal third portion of the stomach. We peformed a distal gastrectomy with D2 lymph node dissection as defined in the 2nd English edition of the JGCA classification. We calculated the positive rate of metastatic LNs of each station and analyzed the relationship between the positive rates of No.6 LNs and 14v LNs. We also compared the positive 14v LN group with the negative 14v LN group. Results: The total number of patients was 50, the mean age was 56 (range $30{\sim}80$) years, and sex ratio (Male/Female) was 1.63 : 1. In 47 (94%) cases, distal a gastrectomy with gastroduodenostomy was done, and in the remaining 3 (6%) cases, a distal gastrectomy with gastrojejunostomy was done. The most frequently metastatic LNs were nos. 3 and 6 (54%). The metastatic rate of the f4v LN was 10%, which was similar to that of LN no. 9. In the comparison of the 14v positive group with the 14v negative group, there were significant differences in the numbers of metastatic LNs (mean 25.4 vs 4.91, P<0.001) and the numbers of metastatic no. 6 LNs, (mean 6.8 vs 1.42, P<0.001), and if no. 6 LNs were metastatic, the possibility of metastasis to the 14v LN was 19.2%. In the 14v positive group, all cases were more than stage 3 by the UICC 6th edition. Conclusion: In cases of advanced cancer with metastasis to the no. 6 IN, there was a good chance of metastasis to the 14v LN. Thus, in the operative field, if the tumor is advanced to more than stage 3 by the UICC classification and the no. 6 LN is metastatic, a 14v LN dissection is necessary. However, the usefulness of a 14v LN dissection should be evaluated prospectively through an analysis of tumor recurrence and long-term survival.

• Microbiology and Biotechnology Letters
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• v.44 no.3
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• pp.268-277
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• 2016

This study aimed to investigate the anti-inflammatory effect of the ethanol extract from Chondrus ocellatus Holmes (COHEE) in RAW 264.7 cells and in a mouse ear edema model, by measuring the production of lipopolysaccharide-induced inflammatory response mediators. There were no cytotoxic effects on the proliferation of macrophages treated with COHEE compared with the control. COHEE inhibited the production of nitric oxide and pro-inflammatory cytokines [interleukin (IL)-6, tumor necrosis factor-α, and IL-1β]. The extract also reduced the expression of inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-κB p65, and phosphorylated mitogen-activated protein kinase in a dose-dependent manner. In the croton-oil-induced ear edema model, COHEE decreased the formation of mouse ear edema at the highest dose compared with the control, and histological analysis revealed that the epidermal/dermal tissue thickness and mast cell numbers were reduced. Therefore, these results suggest that COHEE may be a promising topical anti-inflammatory therapeutic material through its action of modulating NF-κB and the MAPK signaling pathway.

• Journal of Applied Biological Chemistry
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• v.61 no.2
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• pp.205-211
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• 2018

Rebaudioside A is a natural sweetener isolated from Stevia rebaudiana Bertoni, one of the glycosides based on steviol. Recent studies have shown that rebaudioside A inhibits the inflammatory response by inhibiting cytokines secretion such as interleukin-$1{\alpha}/1{\beta}$ in activated RAW264.7 mouse macrophage cells by LPS. However, the inhibitory mechanism of inflammation by rebaudioside A in the presence of LPS has not been fully elucidated. Therefore, in this study, we tried to investigate the anti-inflammatory activity of rebaudioside A at the protein level when RAW264.7 cells were stimulated by LPS. The inducible nitric oxide synthase protein expression level was reduced in the group treated with $250{\mu}M$ rebaudioside A compared to the LPS-treated group. In addition, the mRNA expression level of $NF-{\kappa}B$, which is a representative nuclear transcription factor by inflammatory signal, was also decreased as compared with that of LPS-treated group. In addition, $NF-{\kappa}B$ and inhibitor-${\kappa}B$ ($I-{\kappa}B$) complexes that are known to be dissociated by $I-{\kappa}B$ phosphorylation and ubiquitination were less phosphorylated than LPS treated group in the presence rebaudioside A. Finally, we could find that rebaudioside A was involved in the $NF-{\kappa}B$ pathway through reducing extracellular signal-regulated kinase1/2 phosphorylation in a concentration-dependent manner. These results suggest that rebaudioside A might suppress inflammatory reaction through MAPK and $NF-{\kappa}B$ regulation in LPS-stimulated RAW264.7.

• Microbiology and Biotechnology Letters
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• v.45 no.2
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• pp.101-109
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• 2017

This study investigated the effect of the dichloromethane fraction form Katsuwonus pelamis heart on anti-inflammatory responses in lipopolysaccharide-stimulated RAW 264.7 cells and mouse models. Ethanol extract was partitioned with dichloromethane, ethyl acetate, butanol, and water. Among the fractions, the dichloromethane fraction showed a significant decrease in nitric oxide (NO) and pro-inflammatory cytokines [interleukin (IL)-6, $IL-1{\beta}$, and tumor necrosis $factor-{\alpha}$] production compared to ethanol extract. The dichloromethane fraction attenuated the expression of inducible nitric oxide synthase and nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) p65 proteins in a dose-dependent manner. In addition, the expression of phosphorylation of mitogen-activated protein kinases (MAPKs) was also inhibited by the dichloromethane fraction. Moreover, the administration of 10, 50, and 250 mg/kg body weight-dose dependently inhibited the formation of edema by croton-oil and the application of dichloromethane (2 mg/ear) significantly reduced epidermal and dermal thickness and the infiltrated mast cell numbers. Therefore, the dichloromethane fraction exhibited an anti-inflammation effect by inhibiting $NF-{\kappa}B$ and MAPK signaling activation in macrophages.

• Microbiology and Biotechnology Letters
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• v.45 no.2
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• pp.110-117
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• 2017

The anti-inflammatory effect of Sargassum patens C. Agardh ethanol extract (SPEE) was examined based on the lipopolysaccharide (LPS)-induced inflammatory response in this study. SPEE treatment was not cytotoxic to macrophages compared to the control. The production of NO was suppressed by SPEE by approximately 28% at $100{\mu}g/ml$, and levels of interleukin-6, tumor necrosis $factor-{\alpha}$, and $interleukin-1{\beta}$ decreased in a dose-dependent manner. In addition, the expression of inducible nitric oxide synthase, cyclooxygenase-2, and nuclear $factor-{\kappa}B$ was suppressed by SPEE treatment. In vivo, croton oil-induced mouse ear edema was attenuated by SPEE and the infiltration of mast cells into the tissue decreased. Based on these results, SPEE inhibits the release of LPS-induced pro-inflammatory cytokines and mediators, suggesting that SPEE is a potential agent for anti-inflammatory therapies.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.05b
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• pp.106.2-132
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• 2002

형질전환 (유전자 결핍; Knockout) Min 마우스를 이용하여 대장암 발생에서 배추, 양배추 주성분인 indole-3-carbinol (I3C)의 대장암 예방효과를 규명하고자 하였다. 실험동물로는 C57BL/6J-Apc$^{min/+}$(Min 마우스)계의 5내지 6주령의 수컷 이형접합체 형질전환 마우스 70마리와 C57BL/6J계의 동일 산자, 동일 주령의 수컷 wildtype 비형질전환 마우스 10kfl를 The Jackson Laboratory 사 (Bar harber, ME, USA)로부터 직접 구입하였다. C57BL/6J-Apc$^{min/+}$계 수컷 이형접합체 형질전환 (Min)마우스 70마리를 각 군 20내지 25마리씩 세군으로 나누었다. Group 1에는 20마리, Group 2에는 25마리, Group 3에는 25마리를 배치하고, I3C 투여 실험군 (Group 1과 2)에는 실험시작시에 AIN-76A 분말사료에 I3C가 각각 100 및 300ppm이 함유되도록 조제하여 공급하였다. 그리고 실험군(Group 3)에는 실험시작부터 종료시까지 AIN-76A 정제고형사료(Teklad사, WI, USA)를 자유로이 급이하였다. 각군간의 체중, 사료 및 음수소비량을 매 2주마다 측정하였고, 10주간 (16주령)의 실험종료시에는 최종체중과 간장, 신장, 비장 등의 장기무게를 측정하여 상대장기 무게비를 산출하였다. 대조군으로서 C57BL/6J계의 동일 산자, 동일 주령의 수컷 wildtype 비형질전환 마우스 10마리는 같은 조건의 사육실에서 AIN-76A 정제고형사료를 33주간 자유로이 급이하였다. 실험동물은 부검전에 하룻밤 동안 절식하고 이산화탄소 흡입 마취하에서 흉대동맥을 절단하여 방혈하고 각 장기(심장, 폐, 위)를 적출하여 생리심염수에 넣어 장기무게를 측정하고 포르말린에 고정하였다. 소장과 대장의 검사를 위하여 위의 식도부위와 직장을 실로 결찰하여 적출하고 생리심염수를 주입하여 팽창시켜, 십이지장, 공장, 및 회장, 그리고 대장으로 나누어 여과지에 펼친 후 포르말린에 고정하였다. 소장과 대장은 육안 및 자동 영상분석길ㄹ 이용한 분석이 끝난 후에 각 부위별로 4-6개의 절편을 작제하여 포르말린에 재고정하고, 통상적인 조직처리과정, 파리핀 포매 및 3-4$\mu$m 두께의 조직절편을 제작하여 H&E 염색을 실시하여 현미경으로 검경하였다. 약 1주일간의 포르말린 고정이 끝난 소장 및 대장을 부위별, 별 종양개수 및 분포를 자동영상분석기(Kontron Co. Ltd., Germany)로 분석하였다. 체의 변화, 장기무게, 사료소비량 및 마리당 종양의 개수에 대한 통계학적 유의성 검증을 위하여 Duncan's t-test로 통계처리 하였고, 종양 발생빈도에 대하여는 Likelihood ration Chi-square test로 유의성을 검증하였다. C57BL/6J-Apc$^{min/+}$계 수컷 이형접합체 형질전환 마우스에 AIN-76A 정제사료만을 투여한 대조군의 대장선종의 발생률은 84%(Group 3; 21/25례)로써 I3C 100ppm 및 300ppm을 투여한 경우에 있어서는 각군 모두 60%(Group 1; 12/20 례, Group 2; 15/25 례)로 감소하는 경향을 나타내었다. 대장선종의 마리당 발생개수에 있어서는 C57BL/6J-Apc$^{min/+}$계 수컷 이형접합체 형질전환 마우스에 AIN-76A 정제사료만을 투여한 대조군은 1.40$\pm$0.24(100%)에 비하여 I3C 저농도 투여 실험군(Group 1; 0.85$\pm$0.23; 61%, P<0.01), 그리고 I3C 고농도 투여 실험군(Group 2 ; 1.32$\pm$0.29 ; 94%)의 순으로 감소하였다. 선종의 크기별 종양의 발생개수의 분포에 있어서 I3C 저농도 투여 실험군에 있어서는 선종의 크기가 3mm이하의 수가 현저하게 감소하였다. C57BL/6J-Apc$^{min/+}$계 수컷 이형접합체 형질전환 마우스에 AIN-76A 정제사료만을 투여한 대조군의 부위별 소장선종의 발생수는 십이지장부위를 제외하고 각 군에서 유의한 변화는 관찰되지 않았다. 십이지장 종양의 발생개수에서만 I3C 저농도 투여 실험군(Group 1 ; 3.11$\pm$0.85)이 대조군 (Group 3: 1.48$\pm$0.35) 및 I3C 고농도 투여 실험군(Group 2: 1.56$\pm$0.47)에 비하여 유의성 있게 증가하였다. (P<0.05). 따라서 I3C은 소장에서는 암예방 효과가 뚜렷하지 않으나, 대장에 대한 암에방 효과가 있을 것으로 생각된다. 소장 및 대장을 제외한 간장, 신장, 비장, 심장, 폐 그리고 위 등의 기타 장기에서의 조직병리학적 변화는 관찰되지 않았다. 소장 및 대장의 종양은 선종(polyps)으로 관찰되었다. 지난 10여년간 형질전환 및 유전자 결핍 실험동물의 종류가 기하 급수적으로 증가하여 이용되고 있다. 가족성 대장 선종성 용종증(FAP)의 대표적인 모델로 이용되고 있는 C57BL/6J-Apc$^{min/+}$계 수컷 이형접합체 형질전환 마우스를 사용하여 배추나 양배추의 주요성분인 Indole-3-carbinol(I3C)의 대장암 예방효과가 있는지를 검색하여 본 결과 AIN-76A정제사료만을 투여한 대조군의 대장선종의 발생률 84%에 비하여 I3C 100 및 300ppm을 투여한 실험군에 있어서 각군 모두 60%로서 감소하는 경향을 나타내었으며, 대장선종의 마리당 발생개수에 있어서는 대조군의 1.40$\pm$1.041를 100%로 환산하였을 경우 I3C 저농도 및 고농도 투여 실험군에서는 각각 약 61%와 94%를 나타내여 감소하였다. 특히 대장선종의 크기별 분포에 있어서 선종의 크기가 3mm이하의 수가 현저하게 감소하였다. 따라서 저농도 I3C의 투여는 실험적 유전성 가족성 대장 선종성 용종증 모델에 있어서 어느정도 암 예방효과가 있는 것으로 생각된다. 그러나 소장 선종의 발생에는 별 영향이 없는 것으로 생각된다. 그러나 본 실험에 사용된 C57BL/6J-Apc$^{min/+}$계 수컷 이형접합체 형질전환 마우스는 실험개시 시점이 7내지 8주령이 경과하여 이미 태생기부터 소장 및 대장의 선종 발생이 진행되어 온 것을 감안하고 특히 비스테로이드계 항염증 소염제(NSAIDS)와 같은 강력한 COX-2억제제가 아님을 고려하면, 상당한 선종의 발생을 억제할 수 있는 가능성이 매우 높다고 생각한다. 또한 이제까지 배추나 양배추 성분의 복합성분들에 대한 실험적 대장암 모델에서의 촉진효과 등에 대한 보고들이 있어 온 점을 고려할 때 위암(Kim 등, 1994) 간암(Kim 등, 1994), 유방암(Grubbs, 등, 1995; Bradlow 등, 1995)에 대한 예방효과가 있을 것으로 생각된다. 앞으로 이러한 종양조직내에서의 COX-2 및 iNOS mRNA와 단백질의 발현정도를 분자병리학적으로 연구중에 있으며, 향후 십자화과식물 성분인 indole-3-carbinol이 마우스뿐 만 아니라 랫드의 화학발암물질에 의한 대장종양에 대한 억제효과 있는지 연구 필요가 있다. Min 마우스와 같은 형질 전환(유전자결핍;knockout) 실험동물을 이용한 새로운 중기 발암성 시험범의 확립을 통한 각종 환경 유해물질의 발암성 유무 및 COX-2 억제작용이 있는 식품인자의 암예방 후보물질을 체계적으로 검색하는데 유용하게 활용될 수 있을 것으로 생각한다.

• Journal of Life Science
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• v.30 no.9
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• pp.804-812
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• 2020

The giant mealworm beetle, Zophobas atratus (Coleoptera: Tenebrionidae) has been used as a protein source for small pets and mammals. Recently, it was temporarily registered in the list of the Food Code. We previously performed an in silico analysis of the Zophobas atratus transcriptome to identify putative antimicrobial peptides and identified several antimicrobial peptide candidates. Among them, we assessed the antimicrobial and anti-inflammatory activities of zophobacin 1 that was selected bio-informatically based on its physicochemical properties against microorganisms and mouse macrophage Raw264.7 cells. Zophobacin 1 showed antimicrobial activities against microorganisms without inducing hemolysis and decreased the nitric oxide production of the lipopolysaccharide-induced Raw264.7 cells. Moreover, ELISA and Western blot analysis revealed that zophobacin 1 reduced expression levels of pro-inflammatory enzymes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). We also investigated expression of pro-inflammatory cytokines (interleukin-6 and interleukin-1β) production through quantitative real time-PCR and ELISA. Zophobacin 1 markedly reduced the expression level of cytokines through the regulation of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) signaling. We confirmed that zophobacin 1 bound to bacterial cell membranes via a specific interaction with lipopolysaccharides. These data suggest that zophobacin 1 could be promising molecules for development as antimicrobial and anti-inflammatory therapeutic agents.

• Food Science and Preservation
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• v.22 no.5
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• pp.735-743
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• 2015

This study investigated the anti-inflammatory activity of barley leaf extract in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and hairless mice. Pre-treatment with barley leaf extract significantly inhibited the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-II (COX-II) in a dose-dependent manner in LPS-stimulated RAW264.7 cells. Barley leaf extract also significantly inhibited the secretion of inflammatory cytokines, such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$), and interleukin-6 (IL-6). Moreover, phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear translocation of nuclear factor-kappa B (NF-${\kappa}B$) were strongly suppressed by barley leaf extract in LPS-stimulated cells. In hairless mice, barley extract significantly decreased the pathological phenotypes of contact dermatitis, such as erythema, edema, and scabs. These results indicate that barley leaf extract has an anti-inflammatory effect and therefore a possible role in the treatment of inflammatory diseases or in functional cosmetics.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.5
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• pp.682-689
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• 2013

This study determined the effects of cabbage juice and cabbage-mixed juices on the growth of AGS human gastric cancer cells and their anti-gastritic effects on HCl-ethanol induced gastritis in SD rats. Cabbage juice showed the highest growth inhibition on AGS gastric cancer cells in vitro (42%), compared with chlorella (20%) and kale juice (21%). However, cabbage-chlorella and cabbage-kale juice mixtures (at a 7:3 ratio) showed synergistic effects (57% and 65% inhibitory effects, respectively) on the gastric cancer cells. Inflammatory genes (iNOS, COX-2, TNF-${\alpha}$ and IL-$1{\beta}$) were significantly down-regulated in the mixed juices. Tests of DPPH radical scavenging activity and acid-neutralizing capacity with the mixed juices also showed this trend, as cabbage-chlorella and cabbage-kale mixed juices showed synergistic effects compared to cabbage juice alone. The inhibition rate of acute gastritis induced by HCl-ethanol in rats was 46% with high amounts of cabbage (CH; 800 mg/kg), 71% with high amounts of cabbage and chlorella (CChH; 800 mg/kg), 74% with high amounts of cabbage and kale (CKH; 800 mg/kg), and 75% with cimetidine (positive control) compared with the control. In addition, rates with CChH and CKH showed decreasing gastric secretions with increasing pH. These results show that cabbage juice and cabbage-mixed juices, especially with chlorella or kale, exhibit remarkable anti-gastritic effects and can be administered for a long period for the prevention and treatment of gastric cancer and gastritis.