• Biomolecules & Therapeutics
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• 제23권4호
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• pp.345-349
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• 2015

Betulinic acid, a pentacyclic triterpene isolated from Jujube tree (Zizyphus jujuba Mill), has been known for a wide range of biological and medicinal properties such as antibacterial, antimalarial, anti-inflammatory, antihelmintic, antinociceptive, and anticancer activities. In the study, we investigated the antiviral activity on influenza A/PR/8 virus infected A549 human lung adenocarcinoma epithelial cell line and C57BL/6 mice. Betulinic acid showed the anti-influenza viral activity at a concentration of $50{\mu}M$ without a significant cytotoxicity in influenza A/PR/8 virus infected A549 cells. Also, betulinic acid significantly attenuated pulmonary pathology including increased necrosis, numbers of inflammatory cells and pulmonary edema induced by influenza A/PR/8 virus infection compared with vehicle- or oseltamivir-treated mice in vivo model. The down-regulation of IFN-${\gamma}$ level, which is critical for innate and adaptive immunity in viral infection, after treating of betulinic acid in mouse lung. Based on the obtained results, it is suggested that betulinic acid can be the potential therapeutic agent for virus infection via anti-inflammatory activity.

• 생명과학회지
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• 제23권1호
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• pp.63-68
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• 2013

생리활성물질을 다량함유하고 있는 마늘의 발효산물인 흑마늘의 면역활성을 검증하기 위하여 C57BL6 마우스 비장세포를 이용하여 흑마늘이 비장세포의 활성화에 미치는 영향을 확인하였다. 흑마늘 추출물은 시판되는 남해 흑마늘 액기스를 농축하여 사용하였다. 그 결과 IL-2에서 흑마늘 추출물만 처리한 군에서 생성이 증가하였으며, LPS와 흑마늘 추출물을 함께 처리하였을 때 IL-2와 TNF-${\alpha}$, IFN-${\gamma}$의 생성이 LPS만 처리한 군보다 증가하여 대식세포나 T림프구의 발현에 의해 일어나는 세포성 매개 면역을 활성화를 유도하는 Th1 세포의 발현을 활성화 하였다. 그리고 IL-6는 흑마늘 추출물만 처리하였을 때 후기생성이 증가하였으며, LPS와 흑마늘 추출물을 함께 처리한 경우 LPS만 처리한 군보다 IL-4와 IL-6의 생성이 증가하였다. IL-10은 LPS와 흑마늘 추출물을 함께 처리하였을 때 후기 생성이 감소하였는데, 이는 B 림프구의 활성화에 따른 항체생성 면역을 활성화하며 Th1 세포로부터 유도되는 세포성 면역반응을 억제함으로서 항체유도 체액성 면역반응으로 전환을 효과적으로 조절하는 것을 확인하였다. 따라서 흑마늘 추출물은 마우스 비장세포에서 T 림프구의 활성화에 따른 Th1 세포와 Th2 세포가 활성화되어 면역계의 세포성 면역과 체액성 면역반응을 활성화하여 면역조절에 효과를 나타내는 것으로 사료된다.

• 대한한방내과학회지
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• 제33권4호
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• pp.387-404
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• 2012

Objectives : This study was to observe anticancer and related immunomodulatory effects of Kwibi-tang extracts (KBTe) on non-small cell lung carcinoma (squamous epithelial carcinoma), NCI-H520, xenograft Balb/c nu-nu nude mice. Methods : Three different dosages of KBTe, 50, 100 and 200 mg/kg were orally administered once a day for 42 days from 11 days after tumor cell inoculation. Six groups, each of 8 mice per group were used in the present study. Changes in body weight, tumor volume and weight, lymphatic organs (spleen and popliteal lymph node), serum interferon (IFN)-${\gamma}$ levels, splenocytes NK cell activity and peritoneal macrophage activities, splenic tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$ and IL-10 contents were observed with tumor mass and lymphatic organ histopathology to detect anticancer and immunomodulatory effects. The results were compared with a potent cytotoxic anticancer agent, 5-FU (5-Fluorouracil) 30 mg/kg, intraperitoneal treatment (3-day intervals for 42 days, the optimal effective treatment regimes already confirmed). Results & Conclusions : This study suggest that over 50 mg/kg of KBTe showed favorable anticancer effects on the NCI-H520 cell xenograft with immunomodulatory effects. Although relatively lower anticancer effects were observed in KBTe 200 mg/kg treated mice as compared with 5-FU 30 mg/kg treated mice, no meaningful favorable immunomodulatory effects were observed after 5-FU treatment in the present study.

• IMMUNE NETWORK
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• 제13권3호
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• pp.86-93
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• 2013

In the present study, we investigated if priming of autoreactive $CD8^+T$ cells would be inhibited by competitive peptides for major histocompatibility complex (MHC) class I binding. We used a mouse model of vitiligo which is induced by immunization of $K^b$-binding tyrosinase-related protein 2 (TRP2)-180 peptide. Competitive peptides for $K^b$ binding inhibited IFN-${\gamma}$production and proliferation of TRP2-180-specific $CD8^+T$ cells upon ex vivo peptide restimulation, while other MHC class I-binding peptides did not. In mice, the capability of inhibition was influenced by T-cell immunogenicity of the competitive peptides. The competitive peptide with a high T-cell immunogenicity efficiently inhibited priming of TRP2-180-specific $CD8^+T$ cells in vivo, whereas the competitive peptide with a low T-cell immunogenicity did not. Taken together, the inhibition of priming of autoreactive $CD8^+T$ cells depends on not only competition of peptides for MHC class I binding but also competitive peptide-specific $CD8^+T$ cells, suggesting that clonal expansion of autoreactive T cells would be affected by expansion of competitive peptide-specific T cells. This result provides new insights into the development of competitive peptides-based therapy for the treatment of autoimmune diseases.

• Biomolecules & Therapeutics
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• 제16권4호
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• pp.351-355
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• 2008

Prodigiosin was isolated from marine bacteria Hahella chejuensis which has been recently discovered from Marado, Cheju Island, Republic of Korea. Immunosuppressive properties have been reported for prodigiosin members such as undecylprodigiosin, metacycloprodigiosin, prodigiosin, and its synthetic analogue PNU156804 (PNU). However, the effect of this agent on the function of macrophage and splenocyte has not been characterized in detail. In the present study, we examined the effects of prodigiosin for its ability to alter the function of murine macrophage and NK cell, and the proliferation of splenocytes. When thioglycollate-elicited macrophages pre-exposed to prodigiosin (1-50 ng/ml) were stimulated with LPS/IFN-$\gamma$, pretreatment with prodigiosin resulted in the inhibition of tumoricidal activity of macrophage in a concentration-dependent manner. Tumoricidal activity of NK cell was also inhibited by prodigiosin. Moreover, we found that prodigiosin was able to cause a dose-dependent inhibition of murine lymphocyte responsiveness to Con A and LPS although T-mitogenic response was the more sensitive one. Taken together, the present results point out that prodigiosin has a suppressive effect on the mitogen-induced proliferation of murine lymphocytes and the function of macrophage and NK cell.

• 대한한방내과학회지
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• 제40권3호
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• pp.425-442
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• 2019

Objectives: This study aimed to reveal the pharmacological properties of the newly prescribed herbal mixture, Chenmadansamgamibokhap-tang(CDBT), against hypoxia-induced neuronal cell injury (especially mouse hippocampal neuronal cell line, HT-22 cells) and their corresponding mechanisms. Methods: A cell-based in vitro experiment, in which a hypoxia condition induced neuronal cell death, was performed. Various concentrations of the CDBT were pre-treated to the HT-22 cells for 4 h before 18 h in the hypoxia chamber. The glial cell BV-2 cells were stimulated with $IFN{\gamma}$ and LSP to produce inflammatory cytokines and reactive oxygen species. When the neuronal HT-22 cells were treated with this culture solution, the drug efficacy against neuronal cell death was examined. Results: CDBT showed cytotoxicity in the normal condition of HT-22 cells at a dose of $125{\mu}g/mL$ and showed a protective effect against hypoxia-induced neuronal cell death at a dose of $31.3{\mu}g/mL$. CDBT prevented hypoxia-induced neuronal cell death in a dose-dependent manner in the HT-22 cells by regulating $HIF1{\alpha}$ and cell death signaling. CDBT prevented neuronal cell death signals and DNA fragmentation due to the hypoxia condition. CDBT significantly reduced cellular oxidation, cell death signals, and caspase-3 activities due to microglial cell activations. Moreover, CDBT significantly ameliorated LPS-induced BV-2 cell activation and evoked cellular oxidation through the recovery of redox homeostasis. Conclusions: CDBT cam be considered as a vital therapeutic agent against neuronal cell deaths. Further studies are required to reveal the other functions of CDBT in vivo or in the clinical field.

• 대한본초학회지
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• 제24권1호
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• pp.79-88
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• 2009

Objectives : It has been recently shown that Piperis Longi Fructus (PLF) is involved in the reduction of eosinophil recruitment and production of Th2 cytokines in vivo. However, the main therapeutic mechanisms of PLF remains a matter of considerable debate. To investigate the therapeutic mechanisms of PLF, we examined the influence of PLF on regulatory T cells number, IgE, histamine production in vivo and Th1/Th2 cytokine balance in vitro. Methods : All mice were immunized on two different days (21 days and 7 days before inhalational exposure) by i.p. injections of 0.2 $m\ell$ alum-precipitated Ag containing 100 ${\mu}g$ of OVA bound to 4 mg of aluminum hydroxide in PBS. Seven days after the second sensitization, mice were exposed to aerosolized ovalbumin for 30 min/day on 3 days/week for 12 weeks(at a flow rate of 250 L/min, 2.5％ ovalbumin in normal saline) and PLF (150 mg/kg) were orally administered 3 times a week for 8 weeks. Splenocytes from C57BL/6 mice at 8 weeks of age were stimulated with anti-CD3 (1 mg/ml) plus anti-CD28 (1 mg/ml) antibody for 48hrs. IL-4 and IFN-$\gamma$ in the culture supernatants were measured by ELISA Results : The suppressive effects of PLF on asthma model were demonstrated by the increase the number of regulatory T cells and by reducing IgE, histamine production in vivo and modulation of Th1/Th2 cytokine balance. Conclusions : These results indicate that PLF has a deep inhibitory effects on asthma model mice by increase the number of regulatory T cells, and by reducing IgE, histamine production.

• 대한한방내과학회지
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• 제39권4호
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• pp.471-479
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• 2018

Objectives: This study was aimed to analyze the correlation of clinical characteristics of cancer patients treated with Korean Medicine and their natural killer cell activity (NKA). Methods: The medical records of 52 cancer patients who conducted NKA test at Cheonan Korean Medicine Hospital of Daejeon University from March 2016 to May 2018 were reviewed. NKA was determined at Seegene Medical institute using NK Vue Gold(R) kit, evaluating activated $IFN-{\gamma}$ by enzyme immunoassay after incubation of whole blood. Careful investigations were conducted by categorizing the patients by their sex, origin, stage, ECOG scale, and conventional treatment type. We used data from the medical records and statistical analysis using SPSS 25.0 V. Results: The average NKA of all patients was $623.1{\pm}722.0pg/mL$. The NKA value was higher for females than for males. No correlation was evident between age and NKA, but patients aged over 70 years had the lowest NKA average result. Stage III and IV patients showed clearly lower NKA values when compared to stage I and II patients. NKA and ECOG scale values showed no evident relationship. Conclusions: This study presented the characteristics of NKA in cancer patients treated with Korean medicine. The NKA result differed by gender and stage. Based on these findings, further study is needed regarding the clinical meaning of NKA.

• 대한의생명과학회지
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• 제20권3호
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• pp.173-179
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• 2014

Asian sand dust is known to promote various respiratory symptoms or disorders. For the prevention of harmful health effects by Asian sand dust, the best strategy is known to avoid or reduce exposure to the Asian sand dust. Several studies have shown that Korean red ginseng (RG) has anti-inflammatory and anti-allergic effects. The study aimed to clarify the effect of Korean red ginseng intake on lung inflammation responses to artificial sand dust (ASD) similar to Asian sand dust. BALB/c mice were divided into five groups (n=12) of control (saline), ovalbumin (OVA), OVA with ASD, OVA plus RG with ASD, and OVA plus dexamethasone (DEXA) with ASD. Histopathologic evaluation of lung was conducted. Interleukin (IL)-5, IL-12, interferon (IFN)-${\gamma}$, IL-13, monocyte chemotactic protein (MCP)-1, and eotaxin within bronchoalveolar lavage (BAL) fluid were measured by ELISA. OVA+ASD group significantly increased concentrations of IL-5, IL-13, MCP-1, and eotaxin (P<0.01) compared to the control. OVA+ASD+RG group showed significant decreased levels of IL-2, IL-13, MCP-1 and eotaxin (P<0.01) compared with OVA+ASD. Between RG and DEXA treatment groups, there was no significant difference in all cytokines and chemokines. The inflammatory cells were significantly decreased in treatment groups with RG or DEXA compared to OVA+ASD group. This study suggests a beneficial effect of Korean RG administration in preventing inflammation of lung resulting from Asian sand dust.

• 한국약용작물학회지
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• 제19권1호
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• pp.16-23
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• 2011

This study was conducted to investigate the anti-inflammatory effects of Pruns mume, Schisandra chinensis, Chaenomeles sinensis-- Prunus mume mixtrue (PM) treatment on colitis induced in mice by dextran sodium sulfate (DSS) treatment. A total of 25 male BALB/c mice (average weight $20.7\;{\pm}\; 1.6 \;g$) were divided into 5 treatment groups and fed a commercial diet (A), PM administration (B), commercial diet + induced colitis by DSS (C), PM administration + induced colitis by DSS (D) and sulfasalazine + induced colitis by DSS (E). We found that PM treatment (D) and sulfasalazine (E) decreased the expression of $TNF-{\alpha}$ and COX-2 compared to the DSS-induced colitis group (C). The expression of IL-4, STAT6, $IFN-{\gamma}$, STAT1 was decreased in group D and group E compared to the colitis group (C), COX-2 and STAT1 were more decreased in group D. The serum IgE levels decreased in the PM treatment groups (C and D) compared to the non-PM treatment groups (A and B) although there was no significant difference between the PM treatment groups. It is notable that a therapeutic application of the PM extracts ameliorated DSS-induced colitis in mice.