• Journal of Microbiology and Biotechnology
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• 제34권2호
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• pp.476-483
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• 2024

Fractionated lipids of Halocynthia aurantium (Pyuridae) have been demonstrated to possess anti-inflammatory properties. However, their modulatory properties have not been reported yet. Thus, the objective of this study was to determine immune enhancing effects of fractionated lipids from H. aurantium tunic on macrophage cells. The tunic of H. aurantium was used to isolate total lipids, which were then subsequently separated into neutral lipids, glycolipids, and phospholipids. RAW264.7 cells were stimulated with different concentrations (0.5, 1.0, 2.0, and 4.0%) of each fractionated lipid. Cytotoxicity, production of NO, expression levels of immune-associated genes, and signaling pathways were then determined. Neutral lipids and glycolipids significantly stimulated NO and PGE₂ production and expression levels of IL-1β, IL-6, TNF-α, and COX-2 in a dose-dependent manner, while phospholipids ineffectively induced NO production and mRNA expression. Furthermore, it was found that both neutral lipids and glycolipids increased NF-κB p-65, p38, ERK1/2, and JNK phosphorylation, suggesting that these lipids might enhance immunity by activating NF-κB and MAPK signaling pathways. In addition, H. aurantium lipids-induced TNF-α expression was decreased by blocking MAPK or NF-κB signaling pathways. Phagocytic activity of RAW 264.7 cells was also significantly enhanced by neutral lipids and glycolipids. These results suggest that neutral lipids and glycolipids from H. aurantium tunic have potential as immune-enhancing materials.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 2006년도 춘계학술대회
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• pp.3-12
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• 2006

1 The present work was performed to investigate the effects of ginsenoside Rh2 on proliferation, cell cycle-regulation and differentiation of human leukemia HL-60 cells as well as the underlying mechanisms for these effects. 2 Ginsenoside Rh2 potently inhibited the proliferation of HL-60 cells in both a dose- and time-dependent manner with an $IC_{50}$, $20{\mu}M$. 3 DNA flow-cytometry indicated that ginsenoside Rh2 markedly induced a $G_1$ phase arrest of HL-60 cells. 4 Among the $G_1$ phase cell cycle-related proteins, the levels of cyclin-dependent kinase(CDK)4, 6 and cyclin D1, cyclin D2, cyclin D3 were reduced by ginsenoside Rh2, whereas the steadystate levels of CDK2 and cyclin E were unaffected. 5 The protein levels of a CDK inhibitor p16, $p21^{CIP1/WAF1}$ and $p27^{KIP1}$ were markedly increased by ginsenoside Rh2. 6 Ginsenoside Rh2 markedly enhanced the binding of $p21^{CIP1/WAF1}$ and $p27^{KIP1}$ with CDK2 and CDK6, resulting in the reduced activity of both kinases and the hypophosphorylation of Rb protein. 7 We furthermore suggest that ginsenoside Rh2 is a potent inducer of the differentiation of HL-60 cells, based on observations such as a reduction of the nitroblue tetrazolium level, an increase in the esterase activities and phagocytic activity, morphology changes, and the expression of CD11b, CD14, CD64 and CD66b surface antigens. 8 In conclusion, the onset of ginsenoside Rh2-induced the $G_0/G_1$ arrest of HL-60 cells prior to the differentiation is linked to a sharp up-regulation of the $p21^{CIP1/WAF1}$ level and a decrease in the CDK2, CDK4 and CDK6 activities. This is the first report demonstrating that ginsenoside Rh2 potently inhibits the proliferation of human promyelocytic HL-60 cells via the $G_1$ phase cell cycle arrest and differentiation induction.

• 수산해양교육연구
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• 제27권6호
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• pp.1656-1664
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• 2015

고삼 뿌리 열수 추출물을 농도별로 넙치 사료에 흡습시켜 12주 동안 어류에 급여 후 비특이적 면역 및 질병저항성에 대한 효과를 조사하였다. 고삼 추출물의 첨가는 어류 성장에는 아무런 영향을 미치지 않았다. 혈액화학적인 조사 결과에서도 고삼 첨가로 인한 넙치의 생리에는 아무런 영향을 나타내지 않았다. 라이소자임 활성은 0.05%의 고삼 추출물 농도로 흡습시킨 사료 그룹에서 라이소자임 활성이 증가됨을 알 수 있었다. 백혈구의 식세포 활성은 0.05%의 고삼 추출물로 흡습시킨 사료 그룹에서 유의적으로 증가되었다. 병리학적 결과를 통하여 고삼 추출물을 농도별로 넙치에 투여하였을때 병리조직학적 영향이 없음을 알 수 있었다. 에드와드균의 인위감염에 의한 질병저항성은 0.05%의 고삼 추출물로 흡습시킨 사료 그룹에서만 상대생존율이 높게 나타났다. 이상의 결과를 종합하여 볼 때 고삼뿌리 열수 추출물은 넙치에 대한 비특이적 면역력 증강 및 질병 저항성 증강에 효과가 있는 것으로 사료되었다.

• 대한한의학방제학회지
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• 제5권1호
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• pp.184-202
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• 1997

The results of immune response and antiallergic reaction were as follows. 1. Hemagglutinin titer and hemolysin titer were increased in case of AMR, AR, SNH. But the results were not recognized as having significance. 2. PFC was increased in case of AMR, AR. But the results were not recognized as having significance. 3. RFC was increased in all groups, and the results in the AR, SNH were significant. 4. In experimentation of phagocytic activity in peritoneal exudate cells, AR and SNH showed significant increase. In spleen cells AR and SNH showed significant increase. In monolymphocytus cells AMR, AR and SNH were increased, but result of AMR was of no significance. 5. I examined promotion on spleen cells transformation. As these results, AMR showed increase in $50{\mu}g/m{\ell}$, $5000{\mu}g/m{\ell}$ in comparison with control group. And in $500{\mu}g/m{\ell}$ AMR showed increase in case of 24 hours, 72 hours incubation, but showed decrease in case of 48 hours incubation. AR showed increase in all. In $50{\mu}g/m{\ell}$ SNH showed increase in comparison with control group. And in $500{\mu}g/m{\ell}$, $5000{\mu}g/m{\ell}$ SNH showed increase in case of 24 hours, 48 hours incubation, but showed decrease in case of 72 hours incubation. 6. I examined proliferation of spleen cells. As these results AMR and SNH showed the highest increase in $50{\mu}g/m{\ell}$, but showed the lowest increase in $5000{\mu}g/m{\ell}$. AR showed the highest increase in $500{\mu}g/m{\ell}$, but this result was the almost same in $50{\mu}g/m{\ell}$, $5000{\mu}g/m{\ell}$. And AMR, AR, SNH showed higher activity in Lipopolysaccharide than Concanavalin A. 7. In all groups results of PCA were decreased in 2 week. In 4 week AR and SNH showed decrease, but AMR didn't show change. In 6 week AR and SNH showed decrease, but on the contrary AMR showed increase. 8. In experimentation on histamine contents, AMR showed significant increase at first agent contact. And AR, SNH showed decrease at first agent contact, but these results were of no importance. At second agent contact AMR showed decrease, but was of no importance. AR, SNH showed significant decrease. At third agent contact, AMR showed significant increase. AR, SNH showed decrease, but these results were of no importance. From above these results, AR and SNH showed good effects on immunoreaction. And all the herb medicines in this examination showed good effects in promotion on spleen cells transformation and proliferation of spleen cells, especially activated B-cells. AR, SNH showed good effects on anti-allergic reaction, but AMR was almost inefficient. Accordingly I think that AR shall be used in disease bringing about a lowering of immunity, that is, AR shall be used in strengthening the body resistance. And I think that SNH shall be used in eliminating pathogenic factors with strengthening the body resistance. It is necessary to a deep study in future.

• 대한한방종양학회지
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• 제8권1호
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• pp.103-125
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• 2002

This experimental study was carried out to evaluate the anti-tumor and the immunomodulatory effects of Jiaweicitaowan(加未慈桃丸) against cancer. The in vitro anti-tumor effects were evaluated by MTT assay. The cytotoxicity, extension of survival days, the effect of inhibition solid tumor which was induced sarcoma 180, and the changes of body weight were evaluated for in vivo effects of anti-tumor. To evaluate the immunomodulatory effects of Jiawei- citaowan(加未慈桃丸), delayed type hypersensitivity, hemagglutinin, hemolysin titers for humoral immune response, rosette forming cells for cell-mediated immune response, natural killer cell activity, proliferation of lymphocyte, productivty of Interleukin-2, and carbon clearance were measured with methotrexate treated mice. The results were as follows; 1. In the case of existence ability of tumor cell, IC50 had an anti-tumor ativity resulted 2.52mg/ml to SNU-C4. 0.41mg/ml to SNU-396, resulted to 0.09mg/mlSNU-1. 2. The groups of Jiaweicitaowan(加未慈桃丸) 10mg/ml, 20mg/kg had no body weight loss. reduction in intake of water and feed, so these had no toxicity. 3. In the case of the effect of extention of existence. the group of 20mg/kg Jiaweicitaowan(加未慈桃丸) extract treated group was showed 250% in ILS. 4. The effect of inhibition solid tumor was significantly decreased in both 10mg/kg, 20mg/kg of Jiaweicitaowan(加未慈桃丸) extract treated groups as compared with control group S. The groups of 10mg/kg, 20mg/kg Jiaweicitaowan(加未慈桃丸) had significant effect of body weight change compared to control group. 6. Delayed type hypersensitivity was not significant in both Jiaweicitaowan(加未慈桃丸) extract treated groups as compared with control group. 7. Hemagglutinin and Hemolysin titers were significantly increased by dose-dependent. so these results showed that the humoral immume respose was activated. 8. For the effect of rosette formimg cells was not significant in hoth Jiaweicitaowan(加未慈桃丸) extract treated groups as compared with control group. 9. Natural killer cell activity was significantly increased in both Jiaweicitaowan(加未慈桃丸) extract treated groups as compared with control group in the ratio of 100: 1, 50: 1 of effector and target cells, but in the ratio of 10:1, the Jiaweicitaowan(加未慈桃丸) extract treated groups were not significant. 10. The proliferation of lymphocyte and productivty of Interleukin-2 were significantly increased by dose-dependent in both 10mg/ kg, 20mg/ kg of Jiaweicitaowan(加未慈桃丸) extract treated groups as compared with control group. 11. In the phagocytic effect, the 20mg/kg of Jiaweicitaowan(加未慈桃丸) extract treated group showed the increasing effect with significance as compared with control group. According to the results, we can suggest that Jiaweicitaowan(加未慈桃丸) has the antitumor and the immunomodulatory effects.

• Journal of Ginseng Research
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• 제40권4호
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• pp.437-444
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• 2016

Background: Although Korean Red Ginseng (KRG) has been traditionally used for a long time, its anti-inflammatory role and underlying molecular and cellular mechanisms have been poorly understood. In this study, the anti-inflammatory roles of KRG-derived components, namely, water extract (KRG-WE), saponin fraction (KRG-SF), and nonsaponin fraction (KRG-NSF), were investigated. Methods: To check saponin levels in the test fractions, KRG-WE, KRG-NSF, and KRG-SF were analyzed using high-performance liquid chromatography. The anti-inflammatory roles and underlying cellular and molecular mechanisms of these components were investigated using a macrophage-like cell line (RAW264.7 cells) and an acute gastritis model in mice. Results: Of the tested fractions, KGR-SF (but not KRG-NSF and KRG-WE) markedly inhibited the viability of RAW264.7 cells, and splenocytes at more than 500 mg/mL significantly suppressed NO production at $100{\mu}g/mL$, diminished mRNA expression of inflammatory genes such as inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-${\alpha}$, and interferon-${\beta}$ at $200{\mu}g/mL$, and completely blocked phagocytic uptake by RAW264.7 cells. All three fractions suppressed luciferase activity triggered by interferon regulatory factor 3 (IRF3), but not that triggered by activator protein-1 and nuclear factor-kappa B. Phospho-IRF3 and phospho-TBK1 were simultaneously decreased in KRG-SF. Interestingly, all these fractions, when orally administered, clearly ameliorated the symptoms of gastric ulcer in HCl/ethanol-induced gastritis mice. Conclusion: These results suggest that KRG-WE, KRG-NSF, and KRG-SF might have anti-inflammatory properties, mostly because of the suppression of the IRF3 pathway.

• 혜화의학회지
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• 제4권2호
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• pp.335-336
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• 1996

Artemisinin, a new antimalarial to treat patients infected with strains of Plasmodium jalciparum, derived from the plant Artemisia annua Linn, has immunopharmacologic actions such as enhence the PHA -induced lymphocyte transformation rate, increased the weight of spleen but reduced the weight of thymus, reduced phagocytic function of peritoneal macrophage, remarkably reduced the level of serum IgG and hemolysin fonning capacity (sentitized with SRBC), inhibited the activity of Ts cells of donor mice by supraoptimal immunuization(SOI), but enhenced activity of Ts cells of recipient mice by SOI. These results suggested that Ts cells may be the target cells of artemisinin. To the serum complement C3 level of plasmodium berghei-infeted mice, artemisinin (i. m,) could remarkly increase it. The artemisinin also obviously reduced the prostaglandin E(PGE) in the mouse hind paw swelling induced by carrageenin. Numerous studies have demonstrated that pharmacologic doses of PGE attenuate the development of immunocomplex nephritis. Some autologous immune mechanisms may be invoolved In the pathogensis of some types of glomurulonephritis. Glomerular abnormalities can be induced in animals by variety of immunological manipulations. The resulting disorder has many clinical and pathogical similarities to the disease in human. Our purpose was therefore to test the ability of the artemisinin to lessen the severity of rabbit IgG accelerated nephrotoxic serum glomerulonephritis in mice model. Mice which had treated with rabbit IgG and NTS, administrated with saline, showed Significant inceases of urinary protein, cholesterol level, and decrease of serum albumin in NS group. On the contrary, By i.g. adminstration of artemisinin at dose of 12.5, 25 and 50 mg/kg for 14 days after NTS injection, shown that artemisinin inhibited the nephritic changes in some parameters by means of urinary protein(p<0.05, p<0.01) and serum choleterol(p<0.05, p<0.01) and albumin (p<0.05, p<0.01), blood urea nitrogen (p<0.05, p<0.01), serum albumin(p<0.05, p<0.01); Cyclophosphamide(i.p. 10mg/kg for 14d) had almost same effect as the artemisinin had. Morphological studies shown that The picture of kidney from the mouse with NTS-nephritis accerated with rabbit IgG, treated with i.g. saline as the control, the mesangiocapillary were enlarged and proliferated; There were inflammatory cells infiltrating around the glomeruli; The ethelial cell were proliferated in the wall of Bowman's capsule. Histopatholological picture of kidney from the NTS-nephritis accerated with rabbit IgG mouse treated with i.p. 10mg/kg cyclophosphamide as the positive control. No siginicant histopathological evidence were found. Treaded with i.p. 12.5mg/kg artemisinine, the picture shown that mesangiocapillary were lightly proliferated; There were inflammatory cells infiltrating around the glomeruli; Treaded with i.p. 25mg/kg artemisinine, The picture shown that the mesangiocapillary were lightly proliferated; Treaded with i.p. 50mg/kg artemisinine, The picture shown that both the mesangiocapillary proliferated and the inflammatory cells infiltrating around the glomeruli are less than treated with saline, 12.5 and 25 mg/kg artemisinine. On the basis of these studies we conclude that the artemisinin can relieve pathological change caused by NTS-nephritis aacerated with rabbit IgG.

• BMB Reports
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• 제55권2호
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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.

• 한국식품영양과학회지
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• 제44권5호
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• pp.664-672
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• 2015

녹차 성숙잎으로부터 새로운 면역 활성 다당 소재를 개발할 목적으로 녹차잎을 pectinase로 처리하여 조다당 GTE-0을 분리하고 이들의 면역증진 활성과 화학적 특성에 대해 조사하였다. GTE-0은 중성당 54.9%, 산성당 45.1%로 이루어져 있었으며, 구성당 분석 결과 주로 glucose(14.2%), arabinose(12.2%), rhamnose(11.1%) 및 galactose(7.3%)로 구성되어 있었다. 한편 GTE-0은 비특이적 면역계에 있어 중요한 역할을 담당하고 있는 보체계에 대하여 양성대조군 PSK에 준하는 우수한 활성이 농도 의존적으로 나타났다. 또한 GTE-0을 처리하고 검경 시 형태적으로 구분이 가능한 활성화된 대식세포의 숫자가 증가되는 경향을 보였다. 대식세포의 NO, ROS 및 $H_2O_2$ 생산에 미치는 GTE-0의 효과를 검토한 결과 ROS와 $H_2O_2$는 모두 농도 의존적으로 생산량을 증가시키는 우수한 활성을 나타낸 반면, NO의 생산능은 1,000 mg/mL의 고농도에서보다 오히려 100 mg/mL의 저농도에서 더 우수한 활성을 나타내었다. 또한 GTE-0으로 자극한 대식세포는 무처리 대조군에 비해 IL-6, IL-12 및 TNF-${\alpha}$와 같은 다양한 cytokine들의 생산이 농도 의존적으로 증가되는 경향을 보였다. 대식세포의 식작용 활성을 측정한 결과 무처리 대조군에 비해 GTE-0 100 mg/mL 농도이상 처리하였을 때 우수한 활성을 나타내었다. 또한 활성화된 대식세포의 YAC-1 종양세포주에 대한 치사 활성을 ex vivo로 측정한 결과 100 mg/mL의 농도에서 무처리군 대비 유의적으로 높은 치사 활성을 보였다. 이상의 결과로부터 녹차 성숙잎으로부터 분리된 효소 처리 조다당 GTE-0은 강력한 면역 활성 증진 효과를 갖고 있음을 결론지을 수 있었다.

• 한국식품영양과학회지
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• 제45권11호
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• pp.1564-1570
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• 2016

본 연구에서는 고순도 ${\beta}$-1.3/1.6-glucan이 선천면역계에 중요한 역할을 하는 대식세포와 자연살해세포의 활성화와 적응면역계에서 중요한 역할을 하는 T 세포 면역계에 대한 면역조절 효과를 살펴보고자 대식세포의 활성능, 자연살해 세포의 활성능, 그리고 T 세포 면역계에 조절작용을 하는 사이토카인, CD4+/CD8+ T 세포에 미치는 영향을 관찰하였다. 마우스 복강에서 불리한 대식세포를 이용하여 세포독성을 확인한 결과 고순도 ${\beta}$-1.3/1.6-glucan $10{\sim}200{\mu}g/mL$의 농도에서 독성이 나타나지 않았다. 또한, 고순도 ${\beta}$-1.3/1.6-glucan은 대식세포의 활성능, 자연살해세포의 활성능에 도움을 주어 활성능을 증가시켜 외부로부터 침입한 미생물, 감염된 세포나 종양세포 등을 효과적으로 제거할 수 있을 것이라 예상할 수 있었다. 마지막으로 T 세포 면역계에 조절작용을 하는 사이토카인과 CD4+/CD8+를 확인한 결과 고순도 ${\beta}$-1.3/1.6-glucan이 사이토카인들의 분비량 및 CD4+/CD8+를 증가시켜 T 세포 면역계에 조절뿐아니라 B 세포 면역계의 조절에 도움을 줄 것이라 예상할 수 있었다. 결론적으로 고순도 ${\beta}$-1.3/1.6-glucan은 선천면역뿐 아니라 적응면역에서 영향을 미칠 것이라 생각하며 면역조절에 긍정적인 변화를 보였으므로 추후 면역 조절제로서 기능성 식품의 상업화에 기초 자료가 되어 국내 기능성 소재로서의 개발 가능성을 기대할 수 있다.