• Clinical and Experimental Reproductive Medicine
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• v.37 no.3
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• pp.231-237
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• 2010

Objective: To evaluate whether T helper 1 (Th1) immune response is predominant in women with reproductive failures (recurrent spontaneous abortion and recurrent implantation failure) and the activation of T cell is related to Th1 propensity. Methods: Women with a history of recurrent implantation failure or recurrent spontaneous abortion comprise the study group (n=37). Controls are normal fertile women without a history of infertility or pregnancy losses (n=11). Th1/Th2 ratios of interferon (INF)-$\gamma$/interleukin (IL)-10 and tumor necrosis factor (TNF)-$\alpha$/IL-10 expression on $CD3^+/4^+$ cells, CD154, and CD69 expression on T cells are measured by flow cytometric analysis. Results: The ratios of TNF-$\alpha$ to IL-10 expressing on $CD3^+/4^+$ cells (Th1/Th2 cell ratios) are significantly higher in study group ($42.1{\pm}2.3$) as compared with that of controls ($28.7{\pm}2.7$) (p=0.002). The overall trend of CD154 and CD69 expression on T cells are elevated in study group than those of controls. The proportion (%) of $CD3^+/4^+/154^+$ cells ($1.7{\pm}0.5$ vs. $0.3{\pm}0.2$, p=0.038) and the % of $CD3^+/8^+/154^+$ cells ($0.6{\pm}0.2$ vs. $0.1{\pm}0.0$, p=0.024) are significantly higher in study group. The % of $CD3^+/69^+$ cells ($5.6{\pm}1.9$ vs. $1.3{\pm}5.4$, p=0.046) and % of $CD3^+/8^+/69^+$ cells ($4.8{\pm}1.3$ vs. $1.8{\pm}0.2$, p=0.035) among $CD3^+/8^+$ cells are significantly increased in study group. Conclusion: Women with reproductive failures have Th1 propensity with increased T cell activation. These finding means that activated T cell has a harmful effect on early pregnancy and implantation by induction of Th1 immunity.

• Journal of Life Science
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• v.24 no.6
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• pp.664-670
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• 2014

In the present study, we investigate the role of V. vulnificus in promoting the inflammation of mouse ileal ephitelium and its related signaling pathways. ICR mice were infected orally with V. vulnificus ($1{\times}10^9CFU$) for 16 h as a representative model of food-borne infection. To find the major portal of entry of V. vulnificus in mouse intestine, we have measured the levels of bacterial colonization in small intestine, colon, spleen, and liver. V. vulnificus appeared to colonize in intestine and colon in the order of ileum >> jejunum> colon, but lack in the duodenum, spleen, and liver. V. vulnificus in ileum caused severe necrotizing enteritis and showed shortened villi heights accompanied by an expanded width and inflammation, compared with the control mice. V. vulnificus induced ileal epithelium inflammation by activating phosphorylation of PKC and membrane translocation of $PKC{\alpha}$. V. vulnificus induced the phosphorylation of ERK and JNK, but did not affect p38 MAPK phosphorylation. Notably, V. vulnificus stimulated the I-${\kappa}B$-dependent phosphorylation of NF-${\kappa}B$ in mouse ileal epithelium. Finally, the ileal infection of V. vulnificus resulted in a significant increase in expression of proinflammatory cytokines and Toll-like receptors, respectively, compared to the control. Collectively, our results indicate that V. vulnificus induces ileal epithelium inflammation by increasing NF-${\kappa}B$ phosphorylation via activation of PKC, ERK, and JNK, which is critical for host defense mechanism in food-borne infection by V. vulnificus.

• Korean Journal of Medicinal Crop Science
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• v.11 no.1
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• pp.5-12
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• 2003

The biological activities of extracts from Rubus coreanus Miq. were compared. About 70% of the growth of human hepatocarcinoma and 79% of human gastric cancer cell was inhibited in adding 1.0 mg/ml of the extracts of Rubus coreanus Miq. respectively. The growth of human breast cancer cells was also inhibited in adding 1.0 mg/ml of the extracts as well as 78% of the human cancer cells. It was proved that the growth of human normal lung cell, scored as 15% for the extracts. Overall selectivity of the extracts on several human cancer cell line was over 5, which is higher than those from the Rubus coreanus Miq. The growth of both human immune B and T cells was enhanced up to 1.4 to 1.8 times by adding the extracts, compared to the controls. The secretion of tumor necrosis $factor-alpha(TNF-{\alpha})$ from T cell was also increased up to 78.8 pg/ml in adding the ethanol extract (0.5 mg/ml). Ethanol extract also increased up to about 70 pg/ml of interleukin-6(IL-6) from B cell. For screening regulate function of blood pressure, angiotensin converting enzyme(ACE) activity was inhibited up to 25% by adding the ethanol extract (1.0 mg/ml). In testing the hypoglycemic activity, 20% of ${\alpha}-glucosidase$ activity was inhibited for the extracts (0.5 mg/ml). GST activity was increased in the range of 1.2 to 1.6 times by adding extracts.

• Korean Journal of Medicinal Crop Science
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• v.11 no.1
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• pp.13-18
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• 2003

The biological activities of extracts from Rosa rugosae Radix were compared. About 78% of the growth of human hepato- carcinoma and 68% of human gastric cancer cell was inhibited in adding 0.5 mg/ml of the extracts of Rosa rugosae Radix respectively. The growth of human breast cancer cells was also inhibited in adding 0.5 mg/ml of the extracts as well as 66% of the human cancer cells. It was proved that the growth of human normal lung cell, scored as 20% for the extracts. Overall selectivity of the extracts on several human cancer cell line was over 4, which is higher than those from the Rosa rugosae Radix. The growth of both human immune B and T cells was enhanced up to 1.2 to 1.5 times by adding the extracts, compared to the controls. The secretion of tumor necrosis factor-alpha$(TNF-{\alpha})$ from T cell was also increased up to 61.9 pg/ml in adding the ethanol extract (0.5 mg/ml). Ethanol extract also increased up to about 61.3 pg/ml of interleukin-6(IL-6) from B cell.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.1
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• pp.20-28
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• 2011

Crude polysaccharide (CP) was fractionated from the submerged culture (containing both mycelia and culture broth, SC) with Phellinus linteus (PL) in mushroom complete medium (MCM) supplemented with ginseng extract ($65^{\circ}$Bx, GE) to enhance the immune activity. PL-GE-15-CP from SC cultivated in MCM supplemented with GE-15% (v/v, a ratio of MCM volume to GE) showed significantly higher macrophage stimulation (1.45 fold of the saline control at $100{\mu}g$/mL) than PL-GE-5 and 10-CP with GE-5 and 10%, or PL-CP from SC without GE. The potent intestinal immune system modulating activity through Peyer's patch was also obtained by PL-GE-15-CP (1.46 fold). When PL-GE-15-CP further fractionated on DEAE-Sepharose CL-6B (Cl- form), PL-GE-15-CP-II was the significantly higher than others from PL-GE-15-CP or PL-CP on macrophage stimulation, interleukin (IL)-12 production and intestinal immune system modulation (1.54, 3.96 and 1.56 fold, respectively). PL-GE-15-CP-II also had higher anti-metastatic activity against colon 26-M3.1 carcinoma cell (57.3% inhibition of tumor control, $200{\mu}g$/mouse) rather than PL-CP-II. This active fraction (PL-GE-15-CP-II) mainly contained neutral sugar (82.45%) and uronic acid (12.99%), and component sugar analysis showed that PL-GE-15-CP-II consisted mainly of uronic acid, Ara, Man, Gal and Glc (molar ratio of 0.52:0.97:0.63:1.00:0.54). Furthermore, the activity of GE culture was higher compared with culture without GE, indicating that GE helped to enhance the immune activity of P. linteus; also, it is assumed that the polysaccharide plays an important role in immune enhancement.

• Korean Journal of Poultry Science
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• v.42 no.3
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• pp.231-238
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• 2015

The present study aimed to investigate the effects of lycopene on hepatic metabolic- and immune-related gene expression in laying hens. A total of 48 25-week-old White Leghorn hens were randomly allocated into four groups consisting of four replicates of three birds: control (basal diet), T1 (basal diet + 10 mg/kg of tomato powder-containing lycopene), T2 (basal diet + 10 mg/kg of micelles of tomato powder-containing lycopene), and T3 (basal diet + 10 mg/kg of purified lycopene). Chickens were fed ad libitum for 5 weeks, and then total RNA was extracted from the livers for quantitative RT-PCR analysis. Peroxisome proliferator-activated receptor ${\gamma}$ (PPAR${\gamma}$) expression was decreased in the liver of chickens after lycopene supplementation (P<0.05). Micellar lycopene supplementation decreased the expression of PPAR${\gamma}$ target genes including fatty acid binding protein 4 (FABP4) and fatty acids synthase (FASN) in the T2 group (P<0.05). Sterol regulatory element-binding protein 2 (SREBP2) and C/EBP-${\alpha}$ were also downregulated in hens fed with micellar lycopene (P<0.05). Glucose transporter 8 (GLUT-8) was upregulated in the T2 and T3 groups (P<0.05). However, the expression of carnitine palmitoyltransferase 1 (CPT-1) was not changed by lycopene supplementation. Pro-inflammatory cytokines such as tumor necrosis factor ${\alpha}$ (TNF-${\alpha}$) and interleukin 6 (IL-6) were downregulated by lycopene supplementation (P<0.05). These data suggest that the type of lycopene supplementation is critical and that micelles of tomato powder-containing lycopene may play an important role in the modulation of lipid metabolism and immunity in chickens.

• Proceedings of the Korean Society of Life Science Conference
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• 2002.05a
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• pp.17-22
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• 2002

지구상에는 수천종의 버섯류가 자생하고 있어 유전자원으로서의 중요성이 지대할 뿐만 아니라 기능성 식품소재 및 각종 약리 활성을 나타내는 신약개발 소재로도 크게 주목을 받고 있다. 이들 버섯은 균사체의 영양대사로 얻어지는 대사산물이 축적된 자실체의 형태로 나타나는데, 최근에 와서 자실체 및 균사체의 추출물이나 균사체 배양물이 체질개선이나 각종 병의 예방과 치료에 효과가 있는 것으로 밝혀져 건강식품이나 의약품으로서의 용도가 크게 증가하고 있는 실정이다. 특히, 담자균이 생산하는 특정 구조를 갖는 다당류는 오래전부터 종래의 화학요법제와는 달리 숙주내의 면역 기능을 부활하여 소위 면역요법제로서의 항암효과를 나타냄이 알려져왔었다. 현재까지 제약 및 의학적인 방법이 질병의 주된 치료방법으로 이용되어 왔지만 최근에 특정식품의 섭취가 만성질환의 발생을 억제 또는 지연시킨다는 연구 보고가 나오면서부터 만성질환의 치료방법으로서 식이요법을 중요하게 생각하게 되었다. 따라서 새로운 식품소재 및 가공식품의 개발을 통한 성인병 등의 각종 질병예방이 국민보건문제 해결에 필수적이다. 현재 일본 등에서는 표고버섯, 구름버섯 및 치마버섯 유래의 다당체 또는 단백다당체인 lentinan, krestin 또는 PS-K, schizophyllan 및 PSP 등이 실용화되어 높은 가격에 판매되고 있다. 국내에서도 야생 구름버섯 자실체로부터 추출한 단백 다당체인 Copolang(광동제약)이 개발되어 PS-K와 유사하게 암의 치료에 병행 사용되고 있고, 또 강력한 항암활성이 보고된 상황버섯의 균사체 추출물인 단백 다당체가 Mesima-Ex FK(한국신약)라는 상품명으로 암의 치료에 병행 사용되고 있는 것으로 알려지고 있다. 담자균류와 아울러 미생물 유래 다당체는 그 구조와 특성에 있어서 매우 다양함을 지니고 있다. 이러한 미생물 유래 다당류의 공업적 생산과 이용에 대한 연구로서는 Leuconostoc mesenteroides가 생산하는 dextran이 혈장증량제로 개발된 이래 Xanthomonas campestris가 생산하는 pullulan, Zoogloea rgmigera가 생산하는zooglan둥이 대표적인 예로 보고되고 있다. 한편, 미생물 유래 다당류는 구성당, 분자량, 화학적 구조 등과 같은 특성의 차이에 의해 많은 종류가 존재하고 있으며, 다양한 물성 및 유화제, 응고제, gel 형성제, 필름 형성제, 흡착제, 안정제, 접착제 등과 같은 용도로 광범위하게 이용되고 있다. 또한 근래에 들어서는 미생물 유래 다당체가 지니는 항암활성이 확인되어 새로운 의약품으로서의 개발 가능성이 기대된다. 그 밖에도 기존에 알려져 있는 식물 및 해조류 유래의 다당체와는 달리, 발효조를 이용한 연속배양에 의해 공업적 대량 생산이 가능하며, 더욱이 생산된 다당체의 분리 및 회수가 용이하다는 이점을 지니고 있다. 최근에 들어서는 유전공학적 기법을이용한 고생산성 변이균주 및 새로운 기능을 지닌 다당체의 개발에 관한 연구가 보고되고 있는 등 고부가가치를 지닌 새로운 바이오 소재로서의 기능 및 용도 개발에 관한 연구가 활발히 진행되고 있다. 이러한 항암 활성을 나타내는 여러 가지 담자균류중 Agaricus blazei로부터 생산되는 다당체는 고형암 이외에 S형 결장암, 난소암, 유방암, 폐암, 간암 등에 효과가 입증되었고, 천연물질에 의한 암 면역요법으로 각광을 받고 있으며, 항암 및 항virus의 완치율과 저지율에서 현재 여러가지 약효가 있는 버섯중에서도 탁원한 효과가 있는 것으로 증명되고 있다. 이들 다당체는 사이토카인을 생산시켜서 T임파구와 B임파구의 항원 특이적인 면역반응을 활성화시키고, 세포장해성 T세포와 활성화 대식세포의 세포장해 기능을 충진시켜서 암세포를 파괴시킨다. 또한 콜로니 자극인자인 사이토카인을 생산시켜서 면역담당세포의 신생을 촉진시키기도 하며, 암의 화학요법과 방사선 요법으로 저하된 백혈구를 회복시키는 역할을 한다. 따라서 최근의 연구동향은 생산된 다당체의 항암활성을 향상시키고자 하여 배양기간중에 interleukin을 의도적으로 첨가하는 경향이 있다. 이러한 항암 활성을 나타내는 담자균체 유래 다당체는 버섯의 기원에 따라 그 형태에 약간의 차이를 나타내기는 하나 그 기본 형태는 ${\beta}-(1,6)-glucosyl$ 분지를 가진 ${\beta}-(1,3)-glucan$이며, 평균 분자량은 50 ${\sim}$ 200만 정도이다. Agaricus blazei의 원산지인 브라질의 피에다데(Piedade) 지방의 환경조건(산지의 습도는 80%, 낮 기온 $35^{\circ)C$, 밤 기온 $20{\sim}25^{\circ}C$로 대단히 높으며, 정기적으로 열대지방 특유의 소나기가 내리는 지역)에서 볼 수 있듯이 Agaricus blazei의 성장 환경은 매우 까다로운 편이며, 날것으로는 보관이 잘 안되기 때문에 그 재배에 큰 어려움이 있다. 또한, 고체배양에 의해 생산된 버섯 자실체로부터 유기용매 및 열수추출 방법으로 다당체를 생산하는 방법은 균일한 형태의 버섯 자실체를 공급받기가 어렵기 때문에 다당체의 생산 수율이 낮고, 많은 노동력이 요구되는 어려움이 있다. 그러나 액체배양에 의한 다당체 생산의 경우는 고체배양에 의한 다당체 생산에 비해 일정한 조건하에서 배양이 가능하다는 장점이 있으며, 항상 균일한 균사체 및 배양액을 얻을 수 있다. 따라서 원하는 유용물질을 쉽게 획득할 수 있는 장점이 있다.

• Journal of Nutrition and Health
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• v.52 no.6
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• pp.515-528
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• 2019

Purpose: This study examined the immunological activity and optimized the mixture conditions of Sargassum horneri (S. horneri) extracts in vitro and in vivo models. Methods: S. horneri was extracted using three different methods: hot water extraction (HWE), 50% ethanol extraction (EE), and supercritical fluid extraction (SFE). Splenocyte proliferation and cytokine production (Interleukin-2 and Interferon-γ) were measured using a WST-1 assay and enzyme-linked immunosorbent assay, respectively. The levels of nitric oxide and T cell activation production were measured using a Griess assay and flow cytometry, respectively. The natural killer (NK) cell activity was determined using an EZ-LDH kit. Results: Among the three different types of extracts, HWE showed the highest levels of splenocyte proliferation and cytokine production in vitro. In the animal model, three different types of extracts were administrated for 14 days (once/day) at 50 and 100 mg/kg body weight. HWE and SFE showed a high level of splenocyte proliferation and cytokine production in the with and without mitogen-treated groups, whereas EE administration did not induce the splenocyte activation. When RAW264.7 macrophage cells were treated with different mixtures (HWE with 5, 10, 15, 20% of SFE) to determine the optimal mixture ratio of HWE and SFE, the levels of nitric oxide and cytokine production increased strongly in the HWE with 5% and 10% of SFE containing group. In the animal model, HWE with 5% and 10% of SFE mixture administration increased the levels of splenocyte proliferation, cytokine production, and activated CD4⁺ cell population significantly, with the highest level observed in the HWE with 5% of SFE group. Moreover, the NK cell activity was increased significantly in the HWE with 5% of SFE mixture-treated group compared to the control group. Conclusion: The optimal mixture condition of S. horneri with immune-enhancing activity is the HWE with 5% of SFE mixture. These results confirmed that the extracts of S. horneri and its mixtures are potential candidate materials for immune enhancement.

• The Journal of Korean Obstetrics and Gynecology
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• v.27 no.1
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• pp.81-100
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• 2014

Objectives: The object of this study was to observe the in vitro anti-bacterial and anti-inflammatory effects of six single aqueous herbal extracts-Quisqualis Fructus (QuF), Meliae Cortex (MeC), Arecae Semen (ArS), Crassirhizomae Rhizoma (CrR), Ulmi Pasta Semen(UlS), Torreyae Semen(ToS)- against Staphylococcus aureus (S. aureus) and Lipopolysaccharide(LPS)-activated Raw 264.7 cells. Methods: Anti-bacterial activities against S. aureus of aqueous extracts of QuF, MeC, ArS, CrR, UlS and ToS were detected using standard agar microdilution methods. In addition, the effects on the cell viability, prostaglandin $E_2$ ($PGE_2$), nitric oxide (NO), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin (IL)-$1{\beta}$ and IL-6 productions of LPS activated Raw 264.7 cells were detected. The anti-bacterial and anti-inflammatory effects were respectively compared with lincomycin and piroxicam. Results: Minimal Inhibition Concentration (MIC) of aqueous extracts of QuF, MeC, ArS, CrR, UlS and ToS against S. aureus was respectively detected $5.625{\pm}4.075$ (3.125~12.500), $0.332{\pm}0.273$ (0.098~0.782), $1.094{\pm}0.428$ (0.782~1.563), $2.969{\pm}2.096$ (0.782~6.250), $9.375{\pm}4.419$ (3.125~12.500)>25 mg/ml. MIC of lincomycin was detected as $0.469{\pm}0.297$ (0.195~0.782) ${\mu}g/ml$ at same conditions. In addition, $ED_{50}$ against LPS-induced cell viabilities and cytokine releases of QuF, MeC, ArS, CrR, UlS and ToS was as follows - Cell viability: 66.370, 2.908, 1.747, 259.553, 18.150 and 34.160 mg/ml; NO production: 389.486, 0.294, 0.138, 523.060, 45.363 and 49.327 mg/ml; $PGE_2$ production: 114.271, 0.223, 0.046, 243.078, 8.829 and 28.947 mg/ml; TNF-${\alpha}$ production: 406.288, 0.343, 0.123, 9404.227, 125.406 and 140.775 mg/ml; IL-$1{\beta}$ production: 117.178, 0.135, 0.019, 237.451, 7.923 and 19.418 mg/ml; IL-6 production: 31.261, 0.105, 0.055, 128.434, 2.290 and 3.745 mg/ml. ED50 of piroxicam against LPS-induced cell viabilities, NO, $PGE_2$, TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 were detected as 35.179, 6.552, 1.162, 7.273, 7.101 and $5.044{\mu}g/ml$, respectively at same conditions. Conclusions: All six single aqueous herbal extracts showed anti-bacterial effects against S. aureus, in the order of MeC, ArS, CrR, QuF and UlS aqueous extracts except for ToS; they did not showed any anti-bacterial effects (MIC>25 mg/ml). They also showed anti-inflammatory effects against LPS-activated Raw 264.7 cells in the order of ArS, MeC, UlS, ToS, QuF and CrR aqueous extracts. It means that the ArS and MeC will be showed favorable potent anti-bacterial and related anti-inflammatory effects.

• Journal of Mushroom
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• v.19 no.3
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• pp.225-233
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• 2021

In this study, we evaluated the anti-inflammatory effect of extract from Cudrania tricuspidata twig sawdust fermented with Ganoderma lucidum mycelium. Fermented Cudrania tricuspidata twig sawdust extracted with 70% ethanol and elucidated the potential signaling pathway in lipopolysaccharide (LPS)-induced RAW264.7 cells. Fermented Cudrania tricuspidata twig sawdust inhibits LPS-stimulated nitric oxide (NO) production without affecting cell viability in a dose-dependent manner and production of LPS-induced pro-inflammatory cytokines such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α and prostaglandin2 (PGE₂). Fermented Cudrania tricuspidata twig sawdust also suppressed the expression of the pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW264.7 cells. Moreover, Fermented Cudrania tricuspidata twig sawdust significantly attenuated LPS-induced IkappaB (IκB) degradation and suppressed nuclear factor kappa B (NF-κB) nuclear translocation. These results suggest that fermented Cudrania tricuspidata twig sawdust may have great potential for the development of anti-inflammatory agent.