• 생약학회지
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• 제41권2호
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• pp.122-129
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• 2010

Mistletoe (Viscum album) is a common name for many species of semi-parasitic plants which grow on deciduous trees all over the world. In this study, the immunomodulatory activity of the water-extract of Korean mistletoe fruits (KMFWE), was investigated on murine peritoneal macrophages. The culture supernatants of KMF-WE-stimulated murine peritoneal macrophages showed the increased production of IFN-$\gamma$, IL-$1{\beta}$ and TNF-$\alpha$, in a dose-dependent manner. KMF-WE also induced chemokine production from murine peritoneal macrophages such as RANTES, MCP-1, MIP-$1{\alpha}$ and MIP-$1{\beta}$, as well as nitric oxide (NO) production, in a dose-dependent manner. The gel filtration fraction revealed F-1, which is the early-eluted and high molecular weight product, is the major fraction of KMF-WE to activate the murine peritoneal macrophage to induce cytokines, chemokines and NO. The nature of F-1 fraction needs to be examined in detail in further studies to define the regulatory mechanisms of cytokine or chemokine induction by KMF-WE on macrophages. These results suggest that KMF-WE possess a potent immunostimulant activity and can be a promising candidate available for development of immunomodulators.

• 생약학회지
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• 제41권4호
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• pp.275-281
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• 2010

To evaluate the immunomodulatory activity of a water extract (KMF-WE) of Korean mistletoe (Viscum album var. coloratum) fruit, we examined its ability to induce humoral and cellular immune response against keyhole limpet hemocyanine (KLH). Immunized mice with KLH admixed with KMF-WE (KLH/KMF-WE) showed significant induction of KLH-specific antibodies compared to mice immunized with KLH alone. The assay for determining isotypes of antibodies revealed that KMFWE augmented KLH-specific-IgG1 and -IgG2a production. In vitro T lymphocyte proliferation analysis against KLH revealed that the splenocytes of mice immunized with KLH/KMF-WE showed a significantly higher proliferative ability than those from mice immunized with KLH alone. The culture supernatants of splenocytes, which were harvested from mice immunized with KLH/KMF-WE, showed higher levels of both Th-1 type (IL-2, IFN-${\gamma}$) and Th-2 type (IL-4) cytokines in response to KLH stimulation compared to those from mice immunized with KLH alone. Also, in delayed-type hypersensitivity (DTH) assay, mice immunized with KLH/KMF-WE showed a significantly higher reaction to KLH than mice treated with KLH alone. These results suggest that KMF-WE possess immunoadjuvant activity to enhance both antigen-specific humoral and cellular immune responses against protein antigens (KLH).

• 대한한방종양학회지
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• 제6권1호
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• pp.47-65
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• 2000

In order to investigate antitumor and immune response effect by Hyangsapyungwisan after Sarcoma-180 cells and methotrexate were treatred each other, the extract of Hyangsapyungwisan was orally administered to ICR mice for 14 days. To evaluate the effects of the Hyangsapyungwisan, 50% inhibition concentration($IC_{50}$), mean survival days, tumor weight for antitumor effects, hemagglutinin titer, hemolysin titer, rosette forming cells, natural killer cell activity and productivity of interleukin-2 for immune responses measured in ICR mice. The results were summarized as follows: 1. Mean survival time in Hyangsapyungwisan-treated group was slightly prolonged, as compared with control group(13.46%). 2. On the MTT assay, cell viability was significantly inhibited by $5{\mu}g/well,\;2.5{\mu}g/well,\;1.25{\mu}g/well,\;and\;0.625{\mu}g/well$ of Hyangsapyung-wisan concentration inhibited cell viability significantly. $IC_{50}$ for cell viability was $11.59{\mu}g/well$. 3. Tumor weight in Hyangsapyungwisan treated group was depressed, as compared with the control group(p<0.05). 4. Hemagglutinin titer in Hyangsapyungwisan-treated group was slightly increased with no significance, as compared with the control group. 5. Hemolysin titer in Hyangsapyungwisan-treated group was silightly increased, as compared with the control group(p<0.05). 6. Rosette forming cells in Hyangsapyungwisan-treated group was silightly increased, as compared with the control group(p<0.05). 7. Naural killer cell activity in Hyangsapyungwisan-treated group was significantly increased(p<0.05). 8. Production of interleukin-2 was significantly increased(p<0.05). According to the above results, Hyangsapygwisan had prominent antitumor effects, and enhance both cellular and humoral immunity in mice.

• 대한한의학회지
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• 제28권4호
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• pp.27-41
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• 2007

Aim : This study aimed at elucidating the effects of Inonotus obliquus on anti-tumor effects in vivo and immune-based characterization of the mushroom as a potential candidate for cancer remedy. Methods : To investigate the immunomodulatory effects of Inonotus obliquus, we investigated macrophage functions and NK cell activities through the measurement of NO production of macrophage, NK cell cytotoxicity and expressions of cytokines and genes regulating immune responses, in addition to pulmonary metastasis model in vivo. Results : Inonotus obliquus showed general cytotoxicity at high concentrations over the 100 ${\mu}g/m{\ell}$ on the both of normal and cancer cell lines. Inonotus obliquus showed both inhibitory and promotive effects on pulmonary colonization of CT-26 cell depending on period or route of administration in vivo. Conclusion : From these results, it cannot be concluded that Inonotus obliquus has cancer-specific activity. Furthermore, Inonotus obliquus has the provability to show adverse effects differently according to the concentration and the method of administration.

• Biomolecules & Therapeutics
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• 제19권1호
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• pp.77-83
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• 2011

Sulforaphane is an isothiocyanate found in cruciferous vegetables that has been reported to be an effective cancer preventive agent inducing growth arrest and/or cell death in cancer cells of various organs. This paper reports that sulforaphane exerts immunomodulatory activity on the MHC-restricted antigen presenting function. Sulforaphane efficiently increased the class II-restricted presentation of an exogenous antigen, ovalbumin (OVA), in both dendritic cells (DCs) and peritoneal macrophages in vitro. The class II-restricted OVA presentation-enhancing activity of sulforaphane was also confirmed using mice that had been injected with sulforaphane followed by soluble OVA. On the other hand, sulforaphane did not affect the class I-restricted presentation of exogenous OVA at concentrations that increase the class II-restricted antigen presentation. At a high concentration ($20\;{\mu}M$), sulforaphane inhibited the class I-restricted presentation of exogenous OVA. Sulforaphane did not affect the phagocytic activity of the DCs, and the cell surface expression of total H-$2K^b$, B7-1, B7-2 and CD54 molecules, even though it increased the expression of I-$A^b$ molecules to a barely discernable level. These results show that sulforaphane increases the class II-restricted antigen presenting function preferentially, and might provide a novel insight into the mechanisms of the anti-cancer effects of sulforaphane.

• 한국식품영양과학회지
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• 제32권1호
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• pp.149-154
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• 2003

백작약은 한의학에서 보기ㆍ보혈을 위한 탕제에 이용되는 구성 생약재 중의 하나로서 본 연구에서는 백작약이 면역세포를 활성화시켜 암세포의 생장을 억제할 수 있는 능력이 있는지를 확인하고자 하였다. 그 결과 백작약 조다당분획(PJ-P)는 대식 세포를 활성화시켜 그 고유기능인 탐식 기능을 항진시켰다. 또한 암세포를 저해하는데 중요한 작용을 하는 NO와 TNF-$\alpha$, IL-1 그리고 IL-6의 분비를 향상시켰다. 이렇게 PJ-P에 의해 활성화된 대식 세포는 cytokine들과 NO를 생산함으로써 시험관 내에서 암세포를 살해하였으며, 또한 PJ-P는 암세포를 이식한 마우스의 생존기간을 연장시켰다 이같은 실험결과는 백작약의 조다당분획이 항암보조제 및 면역반응조절제로 활용될 가능성이 있음을 시사한다.

• Parasites, Hosts and Diseases
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• 제60권2호
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• pp.117-126
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• 2022

Cystatin, a cysteine protease inhibitor found in many parasites, plays important roles in immune evasion. This study analyzed the molecular characteristics of a cystatin from Fasciola hepatica (FhCystatin) and expressed recombinant FhCystatin (rFhcystatin) to investigate the immune modulatory effects on lipopolysaccharide-induced proliferation, migration, cytokine secretion, nitric oxide (NO) production, and apoptosis in mouse macrophages. The FhCystatin gene encoded 116 amino acids and contained a conserved cystatin-like domain. rFhCystatin significantly inhibited the activity of cathepsin B. rFhCystatin bound to the surface of mouse RAW264.7 cells, significantly inhibited cell proliferation and promoted apoptosis. Moreover, rFhCystatin inhibited the expression of cellular nitric oxide, interleukin-6, and tumor necrosis factor-α, and promoted the expression of transforming growth factor-β and interleukin-10. These results showed that FhCystatin played an important role in regulating the activity of mouse macrophages. Our findings provide new insights into mechanisms underlying the immune evasion and contribute to the exploration of potential targets for the development of new drug to control F. hepatica infection.

• 대한본초학회지
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• 제37권5호
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• pp.83-88
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• 2022

Objectives : Jakyakgamcho-tang (JGT) has been traditionally used to treat muscular convulsion and pain in South Korea. According to recent studies, JGT has been reported to have anti-depression, anti-inflammation, anti-oxidative, anti-diabetics, anti-spasm and analgesic effects, but studies on its anti-neuroinflammatory and neuroprotective effect have not been deeply conducted. Thus, we investigated the anti-neuroinflammatory activity of JGT on lipopolysaccharide (LPS)-stimulated mouse microglia cells. Methods : To investigate the anti-neuroinflammatory effects of JGT on BV2 microglial cells, we examined the production of nitric oxide (NO) using griess assay, and mRNA expressions of pro-inflammatory cytokines such as interleukin (IL)-1𝛽, IL-6, and tumor necrosis factor (TNF)-𝛼 using real time RT-PCR. Furthermore, to determine the regulating mechanisms of JGT, we investigated the heme oxygenase (HO)-1 by real time RT-PCR. Results : Pre-treatment of JGT effectively decreased NO production in LPS-stimulated BV2 cells at concentrations without cytotoxicity. Additionally, JGT significantly suppressed the production of IL-1𝛽, IL-6, and TNF-𝛼 in LPS-stimulated BV2 cells. Furthermore, JGT activated the HO-1 expression, which is one of the immunomodulatory signaling molecules. And the abolishment of HO-1 by tin protoporphyrin IX (SnPP, the HO-1 inhibitor) reversed the anti- inflammatory activity of JGT in LPS-stimulated BV2 cells. Conclusions : Our results suggest that the JGT has anti-neuroinflammatory effect through the activation of HO-1 in LPS-stimulated BV2 cells. Thereby, JGT could expected to be used for the prevention and treatment of neurodegenerative disease related to neuroinflammation.

• Parasites, Hosts and Diseases
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• 제62권2호
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• pp.205-216
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• 2024

Sigma-class glutathione transferase (GST) proteins with dual GST and prostaglandin synthase (PGS) activities play a crucial role in the establishment of Clonorchis sinensis infection. Herein, we analyzed the structural and enzymatic properties of sigma-class GST (CsGST-σ) proteins to obtain insight into their antioxidant and immunomodulatory functions in comparison with mu-class GST (CsGST-µ) proteins. CsGST-σ proteins conserved characteristic structures, which had been described in mammalian hematopoietic prostaglandin D₂ synthases. Recombinant forms of these CsGST-σ and CsGST-µ proteins expressed in Escherichia coli exhibited considerable degrees of GST and PGS activities with substantially different specific activities. All recombinant proteins displayed higher affinities toward prostaglandin H₂ (PGS substrate; average K_m of 30.7 and 3.0 ㎛ for prostaglandin D₂ [PGDS] and E₂ synthase [PGES], respectively) than those toward CDNB (GST substrate; average K_m of 1,205.1 ㎛). Furthermore, the catalytic efficiency (K_cat/K_m) of the PGDS/PGES activity was higher than that of GST activity (average K_cat/K_m of 3.1, 0.7, and 7.0×10^-3 s^-1㎛^-1 for PGDS, PGES, and GST, respectively). Our data strongly suggest that the C. sinensis sigma- and mu-class GST proteins are deeply involved in regulating host immune responses by generating PGD₂ and PGE₂ in addition to their roles in general detoxification.

• 한국자원식물학회지
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• 제25권5호
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• pp.561-567
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• 2012

본 연구는 EA에 의한 대식세포의 활성화를 매개로 한 항암효과와 항암작용과 관련된 대식세포의 면역조절효과를 확인하였다. 연구 결과 EA에 의해 RAW264.7세포 및 peritoneal macrophage 모두에서 항암효과가 증가하였으며, 증가된 대식세포의 항암효과는 TLR4 signaling을 blocking하는 CLI-095을 함께 처리하였을 때 일부 감소되었다. 이는 EA에 의한 항암 효과가 부분적으로 TLR4를 경유하는 기전으로 나타나는 것을 의미한다. 또한, EA에 대한 대식세포의 NO 분비조절효과를 측정하였으며, EA는 대식세포의 NO 생성을 증가시켰으나, 인위적으로 염증을 유발시켜 NO를 과도하게 분비한 상태에서는 NO 분비를 오히려 억제시키는 결과를 나타내었다. 이와 같이 EA에 의한 NO조절에 대한 이중 효과는 인체에 면역증강과 항염증 효과라는 긍정적인 효과를 나타내는 방향으로 조절하고 있으므로 EA를 이용한 항암요법의 보조제 및 면역보조제로써의 활용에 유익할 것으로 사료된다. 향후 EA에 대한 항암 작용 및 NO 조절에서 세포내 신호전달 작용기전에 대한 심도 있는 연구가 진행되어야 할 것으로 보인다.