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Anti-Inflammatory Effect of Wheat Germ Oil on Lipopolysaccharide-stimulated RAW 264.7 Cells and Mouse Ear Edema (LPS로 유도한 RAW 264.7 세포 및 귀부종 동물 모델에 대한 밀배아유의 항염증 효과)

  • Kang, Bo-Kyeong;Kim, Min-Ji;Jeong, Da-Hyun;Kim, Koth-Bong-Woo-Ri;Bae, Nan-Young;Park, Ji-Hye;Park, Sun-Hee;Ahn, Dong-Hyun
    • Microbiology and Biotechnology Letters
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    • v.44 no.3
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    • pp.236-245
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    • 2016
  • This study investigated the anti-inflammatory effects of wheat germ oil (WGO) on RAW 264.7 cells. It was shown that WGO had no cytotoxicity against the treated cells or negative effect on their proliferation. WGO suppressed nitric oxide (NO) secretion considerably and had inhibitory effects on the production of LPS-induced NO and pro-inflammatory cytokines (IL-6, TNF-α, and IL-1β). In particular, the IL-6 and TNF-α inhibition activities were over 90% at 100 μg/ml concentration of the oil. WGO also inhibited the LPS-induced expression of cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor-kappa B (NF-κB), and reduced the expression of phosphorylated ERK and JNK. Moreover, the croton-oil-induced edema in mouse ears was reduced by WGO, and no mortalities occurred in mice administered 5,000 mg/kg body weight of WGO over a 2-week observation period. In conclusion, these results provide evidence for the anti-inflammatory effect of WGO that likely occurs via modulation of NF-κB and the JNK/ERK MAPK signaling pathway.

Prototypes of Panaxadiol and Panaxatriol Saponins Suppress LPS-mediated iNOS/NO Production in RAW264.7 Murine Macrophage Cells (RAW264.7 대식세포에서 LPS 매개 iNOS/NO 생성에 대한 protopanaxadiol saponin 및 protopanaxatriol saponin의 억제효과)

  • Kim, Jin-Ik;Narantuya, Nandintsetseg;Choi, Yong-Won;Kang, Dae-Ook;Kim, Dong-Wan;Lee, Kyoung;Ko, Sung-Ryong;Moon, Ja-Young
    • Journal of Life Science
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    • v.26 no.12
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    • pp.1422-1430
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    • 2016
  • This study was performed to investigate the modulatory effects of two prototypes of Panax ginseng saponin fractions, 20(S)-protopanaxadiol saponins (PDS) and 20(S)-protopanaxatriol saponins (PTS), on the induction of inflammatory mediators in lipopolysaccharide (LPS)-treated RAW264.7 murine macrophage cells. For this purpose, RAW264.7 cells were treated with LPS ($10{\mu}g/ml$) before, after, or simultaneously with PDS or PTS ($150{\mu}g/ml$), and the released level of nitric oxide (NO) and expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were evaluated. When RAW264.7 cells were treated with LPS and ginseng saponin fractions simultaneously for 24 hr, PTS, compared to PDS, more strongly attenuated the NO production induced by LPS treatment. When the cells were pretreated with LPS for 2 hr followed by PDS or PTS treatment for 24 hr, both ginseng saponins strongly reduced NO release. The pretreatment of RAW264.7 cells with PDS or PTS for 2 hr followed by LPS treatment for 24 hr significantly attenuated the LPS-induced production of NO. PTS showed stronger inhibitory potency to NO generation than PDS. Our western blot experiment showed that both PDS and PTS ($150{\mu}g/ml$) also significantly down-regulated the expressions of iNOS and COX-2 induced by LPS treatment. Our results suggest that both PDS and PTS possess strong protective effects against LPS-stimulated inflammation and that their protective effects are mediated by the suppression of NO synthesis via down-regulation of pro-inflammatory enzymes, iNOS, and COX-2 in the RAW264.7 cells.

Anti-inflammatory effects of Ishige sinicola ethanol extract in LPS-induced RAW 264.7 cell and mouse model (LPS로 유도된 RAW 264.7 Cell과 마우스 모델에 대한 넓패(Ishige sinicola) 에탄올 추출물의 항염증 효과)

  • Kim, Ji-Hye;Kim, Min-Ji;Kim, Koth-Bong-Woo-Ri;Park, Sun-Hee;Cho, Kwang-Su;Kim, Go-Eun;XU, Xiaotong;Lee, Da-Hye;Park, Ga-Ryeong;Ahn, Dong-Hyun
    • Food Science and Preservation
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    • v.24 no.8
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    • pp.1149-1157
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    • 2017
  • Inflammation is the first response of the immune system to infection or irritation in our body. The use of medicinal plants has been widely applied as an alternative source for drug development. One of marine natural resources, the anti-inflammatory effect of Ishige sinicola ethanol extract (ISEE), was evaluated by using LPS-induced RAW 264.7 cell and mice model. As a result, the production of nitric oxide (NO) and pro-inflammatory cytokines (IL-6, IL-$1{\beta}$, TNF-${\alpha}$) were inhibited with increasing concentration of ISEE without any cytotoxicity. Furthermore, ISEE suppressed the expression of not only inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-kappa B (NF-${\kappa}B$) p65, and mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK) 1/2, p38, and c-Jun N-terminal kinase (JNK) in a dose-dependent manner. In mice ear edema test, the formation of edema was reduced at the highest dosage of ISEE and the reduction of the number of infiltrated mast cells was observed in histological analysis. These results indicate that ISEE has a potent anti-inflammatory activity and can be used as a pharmaceutical material for many kinds of inflammatory disease.

Transcriptome Analyses for the Anti-Adipogenic Mechanism of an Herbal Composition (생약복합물의 지방세포형성억제 기전규명을 위한 전사체 분석)

  • Lee, Hae-Yong;Kang, Ryun-Hwa;Bae, Sung-Min;Chae, Soo-Ahn;Lee, Jung-Ju;Oh, Dong-Jin;Park, Suk-Won;Cho, Soo-Hyun;Shim, Yae-Jie;Yoon, Yoo-Sik
    • Journal of Life Science
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    • v.20 no.7
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    • pp.1054-1065
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    • 2010
  • SH21B is a natural composition composed of seven herbs: Scutellaria baicalensis Georgi, Prunus armeniaca Maxim, Ephedra sinica Stapf, Acorus gramineus Soland, Typha orientalis Presl, Polygala tenuifolia Willd and Nelumbo nucifera Gaertner (Ratio 3:3:3:3:3:2:2). In our previous study, we reported that SH21B inhibited adipogenesis and fat accumulation in 3T3-L1 cells through modulation of various regulators in the adipogenesis pathway. The aim of this study was to analyze the transcriptome profiles for the anti-adipogenic effects of SH21B in 3T3-L1 cells. Total RNAs from SH21B-treated 3T3-L1 cells were reverse-transcribed into cDNAs and hybridized to Affymetrix Mouse Gene 1.0 ST array. From microarray analyses, we identified 2,568 genes of which expressions were changed more than two-fold by SH21B, and the clustering analyses of these genes resulted in 9 clusters. Three clusters among the 9 showed down-regulation by SH21B (cluster 4, cluster 6 and cluster 9), and two clusters showed up-regulation by SH21B (cluster 7 and cluster 8) during the adipogenesis of 3T3-L1 cells. It was found that many genes related to cell proliferation and adipogenesis were included in these clusters. Clusters 4, 6 and 9 included genes which were related with adipogenesis induction and cell cycle arrest. Clusters 7 and 8 included genes related to cell proliferation as well as adipogenesis inhibition. These results suggest that the mechanisms of the anti-adipogenic effects of SH21B may be the modulation of genes involved in cell proliferation and adipogenesis.

A Study of the Anti-inflammatory Effect of Protein Derived from Tenebrio molitor Larvae (알칼리 법으로 추출한 갈색거저리 유충 단백질의 항염증 효능)

  • Seo, Minchul;Lee, Hwa Jeong;Lee, Joon Ha;Baek, Minhee;Kim, In-Woo;Kim, Sun Young;Hwang, Jae-Sam;Kim, Mi-Ae
    • Journal of Life Science
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    • v.29 no.8
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    • pp.854-860
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    • 2019
  • This study investigated the optimum pH conditions for efficient extraction of protein from defatted Tenebrio molitor (TM) larvae. We examined the anti-inflammatory effect of protein derived from defatted TM larvae obtained by an alkaline extraction method. Six extraction pH values (7, 8, 9, 10, 11, and 12) and three precipitation pH values (2, 4, and 6) were used. The protein content, browning degree, and recovery yield of the protein obtained under each pH condition were determined. For efficient extraction of protein from defatted TM larvae, a combination of an extraction pH of 9 and precipitation pH of 4 resulted in a 32.4% recovery yield based on the extraction value and degree of browning. To determine whether the protein ameliorated inflammation by inhibition of macrophage activation by lipopolysaccharides (LPS), we measured nitric oxide (NO), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) expression in LPS-stimulated raw 264.7 macrophage cells. The protein markedly inhibited the production of NO without cytotoxicity and reduced the expression level of COX-2 and iNOS protein through the regulation of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B ($NF-{\kappa}B$) signaling. These results suggested that protein derived from TM larvae could have potential applications in anti-inflammatory therapeutic agents and protein supplements.

Extract of Fructus Corni Ameliorates Testosterone-induced Benign Prostatic Hypertrophy in Sprague Dawley Rats (산수유 추출물에 의한 testosterone으로 유발된 양성 전립선 비대증의 개선)

  • Ji, Seon Yeong;Kim, Min Yeong;Hwangbo, Hyun;Lee, Hyesook;Hong, Su Hyun;Kim, Tae Hee;Yoon, Seonhye;Kim, Hyun Jin;Jung, Ha Eun;Kim, Sung Yeon;Kim, Tae Jung;Kim, Min Ji;Kim, Sung Ok;Choi, Yung Hyun
    • Journal of Life Science
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    • v.31 no.6
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    • pp.550-558
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    • 2021
  • Fructus Corni, the fruit of Cornus officinalis, has long been used for the prevention and treatment of various diseases. We recently suggested that it was effective against benign prostatic hyperplasia (BPH). In this study, we investigated the inhibitory effect of Corni Fructus (CF) water extract on BPH induced by testosterone propionate (TP) in noncastrated and castrated animal models. BPH was induced in Sprague Dawley rats by an intramuscular injection of TP in castrated or noncastrated rats. Finasteride (FINA) treatment was used as a positive control for inhibition of BPH. According to our results, CF administration inhibited excessive enlargement of development of the prostate in both the noncastrated and castrated groups compared to the control and FINA-treated groups. The inhibitory effect of CF on BPH was associated with inhibition of expression of hypoxia-inducible factor-1α, 5α-reductase type 2, steroid receptor coactivator-1, androgen receptor (AR), and prostate-specific antigen. Serum levels of the stress hormone cortisol increased during BPH induction by TP in both the noncastrated and castrated groups, but they were attenuated significantly by CF administration. However, insulin and IGF-1 levels were not increased in the BPH-induced groups and CF, and no effective results were found by CF administration. These results point to a beneficial effect of CF on BPH through inhibition of AR signaling pathway activity and imply that CF shows excellent potential as a therapeutic agent for the prevention and treatment of BPH.

Anti-inflammatory Activity of Antimicrobial Peptide Zophobacin 1 Derived from the Zophobas atratus (아메리카왕거저리 유래 항균 펩타이드 조포바신 1의 항염증활성)

  • Shin, Yong Pyo;Lee, Joon Ha;Kim, In-Woo;Seo, Minchul;Kim, Mi-Ae;Lee, Hwa Jeong;Baek, Minhee;Kim, Seong Hyun;Hwang, Jae Sam
    • 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.

Protective effects of Gastrodia rhizoma and steamed & fermented Gastrodiae rhizoma with anti-oxidant efficacy and suppression of NFκB signaling pathway on LPS-induced liver injury (LPS로 유발한 간손상 마우스에서 항산화 및 항염증 효능을 통한 천마와 증숙 발효 천마의 간보호 효과)

  • Kim, Hyoung-Jin;Kwon, O Jun;Lee, Ah Reum;Roh, Seong-Soo;Seo, Young-Bae
    • Journal of Applied Biological Chemistry
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    • v.59 no.3
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    • pp.179-188
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    • 2016
  • This study is aimed to evaluate the protective effect of Gastrodiae rhizoma and steamed, dried & fermented Gastrodiae rhizoma on Lipopolysaccharide (LPS)-induced hepatic injury in the mice model. Sample was selected to GR0F0 (not processed gastrodia rhizome) and GR6F4 (fermented with Saccharomyces cerevisiae before steamed and dried 6 times) based on 1,1-diphenyl-2-picrylhydrazyl, 2,2'-azinobis-3-ethyl-benzothiazoline-6-sulfonic acid, and High-performance liquid chromatography analysis. Mice were randomly divided into 4 groups - Normal group, vehicle group (LPS treated), GR0F0 group (fed GR0F0 before LPS treated) and GR6F4 group (fed GR6F4 before LPS treated) with 6 mice in each group. GR0F0 group and GR6F4 group were fed each extract 200 mg/kg/day during 8 days. LPS 20 mg/kg injected to the experimental groups as abdominal injection. We measured aspartate aminotransferase, alanine amino-transferase in serum. GR0F0 and GR6F4 showed a significant decrease compared to the vehicle group. As a result of measuring the ROS, GR6F4 group showed a significant reduction in both the serum and liver tissues compared to the vehicle group. GR0F0 group showed a significant reduction only in the liver tissues. Activator protein-1, cyclooxygenase-2, and Inducible nitric oxide synthase were significantly decreased GR0F0 group and GR6F4 group. But tumor necrosis factor alpha only showed a significant reduction in GR6F4 group. GR0F0 and GR6F4 groups against liver damage in mice with LPS. That showed significant effects on anti-oxidant and anti-inflammatory action. The effects of GR6F4 group showed superior results compared to GR0F0 group. Therefore, Steamed, dried & fermented Gastrodia rhizoma was might have a protective effect on liver injury.

Protective effects of quality certified traditional Doenjang in Korea on TNF-α-induced vascular inflammation in human umbilical vein endothelial cells (혈관내피세포에서 TNF-α 자극에 의해 유도되는 혈관염증에 대한 전통식품 품질인증 된장의 효능 평가)

  • Kim, Eun-Ju;Jang, Yeon-Jeong;Kim, So-Young;Choi, Hye-Sun;Park, Shin-Young
    • Food Science and Preservation
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    • v.23 no.3
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    • pp.378-386
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    • 2016
  • Anti-atherogenic effects in tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)-stimulated human umbilical vein endothelial cells (HUVEC) are involved in the suppression of oxidative stress, cell adhesion molecules, and pro-inflammatory factors. This study investigated the vascular inflammation inhibitory activity of traditional Doenjang plays a key role in the pathogenesis and progression of atherosclerosis. The protective effects of Korean Deonjang was investigated on the expression of cell adhesion molecules (CAMs) in tumor necrosis factor (TNF)-${\alpha}$-induced human umbilical vascular endothelial cells (HUVECs). Deonjang extracts (20, 50, $100{\mu}g/mL$) decreased the expression of 20 ng/mL TNF-${\alpha}$-induced vascular cell adhesion molecule (VCAM)-1 intracellular adhesion molecule (ICAM)-1 proteins, and their corresponding mRNA levels. Nitric oxides (NO) produced by endothlial nitric oxides synthase (eNOS) dilated blood vessels, which had protective effects against platelet and leukocyte adhesion. While TNF-${\alpha}$-induced suppressed the production of nitric oxide in HUVECs, Doenjang restored NO production in HUVECs. In addition, Deonjang reduced the TNF-${\alpha}$-induced expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 mRNA levels. These results suggested that Doenjang can inhibited the production of cell adhesion molecules and inflammatory mediators, which could be a potential candidate for preventing atherosclerosis.

Anti-inflammatory Activity of Antimicrobial Peptide Papiliocin 3 Derived from the Swallowtail Butterfly, Papilio xuthus (호랑나비 유래 항균 펩타이드 파필리오신 3의 항염증 활성)

  • Shin, Yong Pyo;Lee, Joon Ha;Kim, In-Woo;Seo, Minchul;Kim, Mi-Ae;Lee, Hwa Jeong;Baek, Minhee;Kim, Seong Hyun;Hwang, Jae Sam
    • Journal of Life Science
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    • v.30 no.10
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    • pp.886-895
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    • 2020
  • The development of novel peptide antibiotics with potent antimicrobial activity and anti-inflammatory activity is urgently needed. In a previous work, we performed an in-silico analysis of the Papilio xuthus transcriptome to identify putative antimicrobial peptides and identified several candidates. In this study, we investigated the antibacterial and anti-inflammatory activities of papiliocin 3, which was selected bioinformatically based on its physicochemical properties against bacteria and mouse macrophage Raw264.7 cells. Papiliocin 3 showed antibacterial activities against E. coli and S. aureus without inducing hemolysis and decreased the nitric oxide production of the lipopolysaccharide-induced Raw264.7 cells. Moreover, ELISA and Western blot analysis revealed that papiliocin 3 reduced the expression levels of pro-inflammatory enzymes, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2). In addition, we examined whether papiliocin 3 could inhibit the expression of pro-inflammatory cytokines (interleukin-6 and interleukin-1β) in LPS-induced Raw264.7 cells. We found that papiliocin 3 markedly reduced the expression level of cytokines through the regulation of mitogen-activated protein kinases (MAPK) and nuclear factor kappa B (NF-κB) signaling. We also confirmed that papiliocin 3 binds to bacterial cell membranes via a specific interaction with lipopolysaccharides. Collectively, these findings suggest that papiliocin 3 could be a promising molecule for development as a novel peptide antibiotic.