• Journal of Ginseng Research
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• 제42권1호
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• pp.68-74
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• 2018

Background: Ginsenosides have been reported to have many health benefits, including anti-inflammatory effects, and the resolution of inflammation is now considered to be an active process driven by M2-type macrophages. In order to determine whether ginsenosides modulate macrophage phenotypes to reduce inflammation, 11 ginsenosides were studied with respect to macrophage polarization and the resolution of inflammation. Methods: Mouse peritoneal macrophages were polarized into M1 or M2 phenotypes. Reverse transcription-polymerase chain reaction, Western blotting, and measurement of nitric oxide (NO) and prostaglandin $E_2$ levels were performed in vitro and in a zymosan-induced peritonitis C57BL/6 mouse model. Results: Ginsenoside $Rg_3$ was identified as a proresolving ginseng compound based on the induction of M2 macrophage polarization. Ginsenoside $Rg_3$ not only induced the expression of arginase-1 (a representative M2 marker gene), but also suppressed M1 marker genes, such as inducible NO synthase, and NO levels. The proresolving activity of ginsenoside $Rg_3$ was also observed in vivo in a zymosan-induced peritonitis model. Ginsenoside $Rg_3$ accelerated the resolution process when administered at peak inflammatory response into the peritoneal cavity. Conclusion: These results suggest that ginsenoside $Rg_3$ induces the M2 polarization of macrophages and accelerates the resolution of inflammation. This finding opens a new avenue in ginseng pharmacology.

• 한국식품영양학회지
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• 제31권2호
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• pp.236-241
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• 2018

Flammulina velutipes is an edible mushroom and contains a lot of fiber, vitamin $B_1$, $B_2$, niacin and folic acid. This study was conducted to explore the effects of the Flammulina velutipes mushroom on immune cells and immunity. Th1 cytokine productions as $IFN-{\gamma}$, $TNF-{\alpha}$, and IL-2 were measured in an activated macrophage by Flammulina velutipes water extract in seven concentrations (0, 5, 10, 50, 100, 250, 500, and $1,000{\mu}g/mL$). Also, the splenocyte proliferation index was measured at 48 hours after treatment of the Flammulina velutipes water extract in seven concentrations or mitogen, LPS and ConA. The $IFN-{\gamma}$ and $TNF-{\alpha}$ productions were increased by treatment of the Flammulina velutipes water extract. The $TNF-{\alpha}$ production was significantly higher in the $50{\sim}1,000{\mu}g/mL$ Flammulina velutipes water extract treated macrophages. The $IFN-{\gamma}$ production of macrophages treated with the Flammulina velutipes water extract increased significantly in all groups, and the highest $1000{\mu}g/mL$ concentration. The splenocyte proliferation index was enhanced when the $10{\sim}1,000{\mu}g/mL$ Flammulina velutipes water extracts were treated compared to the control. These primary results suggest that Flammulina velutipes may enhance the immune function by activation of the macrophage and spleen cell.

• Archives of Pharmacal Research
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• 제26권12호
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• pp.1087-1095
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• 2003

Betulinic acid (BA), a pentacyclic triterpene isolated from Lycopus lucidus, has been reported to be a selective inducer of apoptosis in various human cancer and shown anti-inflammatory and immunomodulatory properties. We postulated that BA modulates the immunomodulatory properties at least two groups of protein mediators of inflammation, interlukin-1$\beta$ (IL-1$\beta$) and the tumor necrosis factor- $\alpha$ (TNF-$\alpha$) on the basis of the critical role of the monocytes and tissue macrophages in inflammatory and immune responses. TNF-$\alpha$ and IL-1$\beta$ were produced by BA in a dose dependent manner at concentration of 0.625 and 10 $\mu$g/mL. The production of NO associated with iNOS was inhibited when treated with LPS at the concentration of 2.5 to 20 $\mu$g/mL of BA whereas COX-2 expression was decreased at 2.5 to 20 $\mu$g/mL. These modulations of inflammatory mediators were examined in LPS-stimulated RAW 264.7 cells and peritoneal macrophages. The morphology of macrophage was also examined and enhanced surface CD 40 molecule was expressed when treated BA at 0.625∼5 $\mu$g/mL with or without LPS. Furthermore, BA (20 $\mu$g/mL) enhanced apoptosis by producing DNA ladder in the RAW 264.7 cells. Our results indicated that BA induced activation of macrophage and pro-inflammatory cytokines. This may provide a molecular basis for the ability of BA to mediate macrophage, suppress inflammation, and modulate the immune response.

• 한국식품영양과학회지
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• 제27권5호
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• pp.952-959
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• 1998

To investigate the effect of sea tangle on macrophage activity in normal and diabetic states, 10week old ICR mice were fed control(C) and sea tangle(S) diet containing 5%(w/w) cellulose and 13.6%(w/w) dry sea tangle for four weeks, after which two thirds of mice(CD and SD) were made diabetic by intramuscular injection of streptozotocin(150mg/kg bw). At 4th day after diabetes was apparent by urinary glucose, one half of diabetic mice(CDM and SDM) were treated with metformin(500mg/kg bw) orally. Peritoneal macrophages obtained from 3%-thioglycollate treated mice were cultured in the presence of lipopolysaccaride from Salmonella abortus equi(10$\mu\textrm{g}$/ml) for 24 hrs and tumor necrosis factor-$\alpha$(TNF$\alpha$), interleukin-1$\beta$(1L-1$\beta$)and prostaglandin E2(PGE2) were measured in culture media. Release of IL-1$\beta$and PGE2 from macrophage were increased in normal mice by sea tangle diet and had the same tedency in diabetic mice with or without metformin treatment although not statistically significant. Release of TNF$\alpha$ tended to be reduced by diabetes but were not changed significantly by sea tangle diet. Fatty acid compositions of macrophage and liver phospholipids showed that diabetes reduced arachidonic acid/linoleic acid ratio and sea tangle diet appeared to increase contentsof polyunsaturated fatty acids.

• 약학회지
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• 제44권2호
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• pp.182-188
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• 2000

High soy consumption leading to high exposures of soy isoflavones has been associated with a reduced risk of cancers at many sites. As part of a study focusing on the chemopreventive mechanisms, we have investigated the modulating effects of daidzein and genistein, a prominent and more bioavailable isoflavone in soy foods, on murine immune function. Daidzein (50 mg/kg) or genistein (50 mg/kg) was administered p.o. once a day for 7 days in BALB/c mice. Daidzein decreased the mitogen-stimulated proliferation of murine splenocyte, but genistein increased it. Daidzein stimulated the secretion of interleukin-4, but inhibited the secretion of ${\gamma}$-interferon, interleukin-2 and tumor necrosis factor-$\alpha$. Genistein stimulated the secretion of ${\gamma}$-interferon, interleukin-2 and tumor necrosis factor-$\alpha$, but inhibited the secretion of interleukin-4. Daidzein and geiustein inhibited the production of nitric oxide and enhanced the phagocytic activity in peritoneal macrophage. These results suggest that cancer preventive effects of daidzein is partly concerned with the secretion of $T_{H}$2 cells cytokine and the activation of macrophage phagocytosis, and genistein is partly concerned with the secretion of $T_{H}$l cells cytokine, tumor necrosis factor-$\alpha$ and the activation of macrophage phagocytosis.sis.

• 한국축산식품학회지
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• 제43권4호
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• pp.703-711
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• 2023

As an initial study to elucidate the molecular mechanism of how probiotics modulate macrophage activity, we monitored mRNA expression patterns in peritoneal macrophages (PMs) treated with two different strains of probiotics. After treatment with either Weissella cibaria WIKIM28 or Latilactobacillus sakei WIKIM50, total RNAs from PMs were isolated and subjected into gene chip analyses. As controls, mRNAs from vehicle (phosphate-buffered saline, PBS)-treated PMs were also subjected to gene chip analysis. Compared to vehicle (PBS)-treated PMs, WIKIM28-treated and WIKIM50-treated PMs exhibited a total of 889 and 432 differentially expressed genes with expression differences of at least 4 folds, respectively. Compared to WIKIM28-treated PMs, WIKIM50-treated PMs showed 25 up-regulated genes and 21 down-regulated genes with expression differences of more than 2 folds. Interestingly, mRNA transcripts of M2 macrophage polarization marker such as anxa1, mafb, and sepp1 were increased in WIKIM50-treated PMs comparing to those in WIKIM28-treated PMs. Reversely, mRNA transcripts of M1 macrophage polarization marker such as hdac9, ptgs2, and socs3 were decreased in WIKIM50-treated PMs comparing to those in WIKIM28-treated PMs. In agreement with these observations, mRNA expression levels of tumor necrosis factor-α and interleukin-1α were significantly reduced in WIKIM50-treated macrophages compared to those in WIKIM28-treated macrophages. These results may indicate that probiotics can be classified as two different types depending on their ability to convert macrophages into M1 or M2 polarization.

• 한국식품과학회지
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• 제30권3호
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• pp.709-716
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• 1998

양송이의 알칼리 추출물에서 면역계의 주요인자인보체계와 macrophage를 활성화시키는 다당들을 분리, 정제하고 구조적 특성을 비교하였다. AB-20-IVa-2는 항보체 활성과 macrophage 활성능을 동시에 나타내는 단백다당으로 주요 구성당은 glucose > galactose > mannose 순으로 함유되어 있고 주요 구성아미노산은 phenylalanine (34.72%)과 valine (27.84%)이었다. AB-20-Ia와 AB-20-IIa-2a는 macrophage 활성을 갖고 있는 순수다당으로 AB-20-Ia의 주요 구성당은 glucose > xylose > mannose이고 AB-20-IIa-2a는 xylose > glucose > mannose이었다. AB-20-Ia, AB-20-IIa-2a, AB-20-IVa-2의 분자량은 각각 84만, 75만, 65만 정도로 추정되었다. AB-20-Ia, AB-20-IIa-2a, AB-20-IVa-2의 구조적 특성을 비교하기 위하여 NMR 분석, methyl화 분석을 통해 anomer 배위 양식과 당쇄 결합 양식을 조사하였다. AB-20-Ia는 ${\beta}-anomer$ 형태로 존재하는데 비해서 AB-20-IIa-2a는 ${\alpha}-$와 ${\beta}-anomer$ 모두 확인되었으며 ${\beta}-$의 비율이 좀 더 높았다. 또, AB-20-Ia와 AB-20-IIa-2a 모두 구성당 잔기에 acetyl기가 존재하였으며 특히, macrophage 활성능이 더 강한 AB-20-IIa-2a에 더 높은 비율로 함유되어 있었다. 이 정제 다당들의 당쇄 결합양식은 AB-20-Ia는 주로 ${\beta}-1,6-linked\;glucofuranosyl$ 잔기가 주쇄를 구성하고 있고, AB-20-IIa-2a는 1,6-linked glucopyranosyl 잔기가 주쇄를 이루고 여기에 측쇄들이 1,4 결합으로 연결된 다당으로 추정되었다. 또, AB-20-IVa-2는 1,2-linked xylofuranosyl 잔기와 1,6-linked glucopyranosyl 잔기가 주쇄를 이루고 이 xylofuranosyl 잔기에 측쇄들이 1,3 결합으로 연결된 다당으로 추정되었다.

• 한국식품영양과학회지
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• 제44권9호
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• pp.1256-1263
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• 2015

본 연구에서는 유자가 선천성 면역력에 미치는 효과를 알아보기 위하여 유자 30% 주정추출물(CJE)을 사용하였으며 선천성 면역에 중요한 역할을 하는 대식세포를 이용해 실험하였다. CJE는 마우스 대식세포인 RAW264.7에서 $1,000{\mu}g/mL$의 최고 농도까지 세포독성을 보이지 않았고, 전사인자 $NF-{\kappa}B$와 염증성 매개물질인 COX-2, PGE2의 활성 및 발 현 증강에 영향을 미치며, 특히 $300{\mu}g/mL$의 농도에서부터 유의적 차이를 보이는 것으로 확인되었다. 산화질소 생성능과 대식세포에서 분비되는 사이토카인인 $TNF-{\alpha}$, $IL-1{\beta}$의 발현을 대조군에 비해 농도 의존적으로 증가시킨다는 결과를 얻었으나, IL-6에서는 통계적으로 약간의 유의성이 있는 증가를 보였고 IL-10은 정상대조군에 비해 거의 유의적인 차이를 보이지 않았다. CJE는 또한 NK 세포의 활성을 농도 의존적으로 증가시키고 비장세포의 증식능도 농도 의존적으로 증가시킨다는 것을 확인하였다. 이러한 결과로 미루어 보아 CJE는 인체의 대식세포 활성의 증가를 통해 선천성 면역력을 증가시킬 것으로 판단된다.

• 생명과학회지
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• 제30권4호
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• pp.352-358
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• 2020

홍국은 한국에서 오랫동안 음식과 전통의학 소재로 사용되어 왔다. Monascus sp.의 생장과 2차 대사과정을 통해 Monascus 색소, monacolins, γ-aminobutyric acid 등을 생산할 수 있다. Monascus 종의 대사산물인 monacolin K, γ-aminobutyric acid과 dimerumic acid는 특정 항산화 효과로 인해 콜레스테롤과 혈압을 낮춘다고 알려져 있다. 이 연구는 Monascus sp.로 발효된 홍국쌀 에탄올 추출물의 항염증 활성을 조사하였다. 홍국 에탄올 추출물의 총 폴리페놀 함량을 측정하였고, 항염증 효과는 LPS가 유도된 Raw 264.7 cell에서 NO 생성, iNOS 및 사이클로옥시게나아제-2(cyclooxygenase-2 (COX-2)) 단백질 활성을 측정하였다. 총 폴리페놀 함량은 발효되지 않은 일반쌀보다 높은 함량을 나타내었다. NO 생성 저해활성 평가는 400 ㎍/ml 농도에서 LPS를 처리하지 않은 음성대조군의 NO 생성량과 유사한 결과를 나타내었다. iNOS 및 COX-2 단백질 발현 저해활성은 400 및 800 ㎍/ml에서 iNOS의 발현을 상당부분 억제하였다. 홍국 에탄올 추출물은 높은 항염증 효과를 확인하였으며, 기능성화장품 및 항염증소재로서 활용 가능할 것으로 사료된다.

• 한국식품저장유통학회지
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• 제23권6호
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• pp.906-912
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• 2016

${\beta}$-Glucan은 효모나 버섯의 세포벽이나 곡물의 섬유에 들어있는 천연 화합물이며, 면역 시스템을 활성화 한다고 알려져 있다. Aureobasidium pullulans 수용성의 ${\beta}$-1,3/1,6-glucan을 생성한다. 본 연구에서는 A. pullulans 로부터 생성된 ${\beta}$-1,3/1,6-glucan의 면역활성에 관한 효과를 조사하기 위하여, 면역활성에 관여하는 NK 세로의 활성과 대식세포에 미치는 영향을 관찰하였다. NK 세포에 의한 Yac-1 세포의 사멸율은 ${\beta}$-1,3/1,6-glucan을 처리한 군은 처리하지 않은 대조군에 비하여 63-39% 증가하는 것으로 나타났고, 대식세포의 탐식작용은 zymosan을 처리한 군보다 15-21% 증가함을 보였다. LP-BM5 바이러스 복제 억제능을 확인하기 위하여 SC-1/LP-BM5 세포주에 ${\beta}$-1,3/1,6-glucan을 처리한 결과 $200{\mu}g/mL$ 처리에서 LP-BM5 바이러스 복제능이 최대 74% 유의적으로 감소하였다. 이 결과는 ${\beta}$-1,3/1,6-glucan이 면역활성에 관여하는 NK 세포와 대식세포를 활성화하여 면역체계가 민감하게 반응할 수 있도록 만들고, LP-BM5 바이러스 복제를 억제하여 면역력을 증진할 수 있다는 것을 보여준다.