• 대한본초학회지
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• 제32권5호
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• pp.27-38
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• 2017

Objective : In the present study, we examined whether Canavalia gladiata D.C. (CG) and Arctium lappa L., Redix (AL) mixture (CGAL), their components, lupeol and chicoric acid, regulate immune system and suppress the tumor in vitro and in vivo. Methods : LPS-induced reactive oxygen species (ROS) and nitric oxide (NO) were measured after treatment with CG extract (CGE), CGAL, lupeol, chicoric acid and lupeol and chicoric acid mixture (lupeol+CA) in Raw264.7 cell. To determine the effect of CGE on immune responses, immune cell population and IgG production were assessed in mice. To investigate the effect of CGAL and their component on anti-tumor activity, tumor volume and weight were measured, cell cycles and immune cell population were analyzed in MC38 injected tumor bearing mice. Also, NK cell activity was determined in splenocyte isolated from tumor bearing mice. Results : CGE, CGAL, lupeol, chicoric acid and lupeol+CA decreased the LPS-induced ROS and NO production without cell toxicity in RAW264.7 cells. CGE increased the immune cell populations of $CD4^+T$, $CD8^+T$ and macrophages in various immune organ of mice. In tumor bearing mice, CGAL, lupeol, chicoric acid and lupeol+CA suppressed tumor volume and weight. In cell cycle analysis, they decreased the percentages of S phase. In addition, CGAL, lupeol, chicoric acid and lupeol+CA immune cell populations of $CD4^+T$, $CD8^+Tcell$, NK cell and macrophage in tumor as well as NK cell activity. Conclusion : CGAL and its compounds may enhance immune responses and suppress tumor growth, and may be capable of developing health functional foods.

• 대한본초학회지
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• 제31권4호
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• pp.1-10
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• 2016

Objectives: In Korean medicine, Curculiginis Rhizoma was treated for arthritis in remedy. But efficacy of Curculiginis Rhizoma on collagen induced arthritis was not revealed.Methods: Anti inflammatory effect of Curculiginis Rhizoma was researched in vitro with RAW264.7 cell and cell toxicity, levels of proinflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-12) and PGE2 were analyzed by ELISA assay. Inflammatory protein were analyzed by western blotting assay (JNK, ERK, COX-2, TNF-α and IL-1β). In vivo, collagen induced arthritis mice model was used to evaluate anti-inflammation effect through arthritis index, immune cell number and cytokine levels (TNF-α, IL-6 and IL-1β) in serum.Results: ECR(Extract of Curculiginis Rhizoma) has not shown cell toxicity in 200 ㎍/㎖ on RAW264.7 cell. ECR suppressed releases of NO, TNF-α, IL-1β, IL-6, IL-12 and PGE2 on RAW264.7 cell treated with lipopolysacharide (1 ㎍/㎖). And ECR inhibited regulation of TNF-α, IL-1β and IL-6 mRNA, reduced protein release of JNK, ERK, iNOS, COX-2, IL-1β and TNF-α. AI of group treated with ECR 200 ㎎/㎏ and 100 ㎎/㎏ were significantly decreased compared to vihicle arthritis mice, the number of immune cell in foot joint was increased on control mice but those of group treated with ECR 200 ㎎/㎏ and 100 ㎎/㎏ were significantly reduced. This results correspond with contens of cytokines (TNF-α, IL-1β and IL-6) in serum.Conclusions: Curculiginis Rhizoma has anti-inflammation effect on RAW264.7 cell in vitro and collagen induced arthritis in vivo. So it is necessary to research more mechanism for cascade imfact.

• Molecular & Cellular Toxicology
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• 제1권4호
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• pp.230-236
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• 2005

Formaldehyde is a common environmental contaminant found in tobacco smoke, paint, garments, diesel and exhaust, and medical and industrial products. Formaldehyde has been considered to be potentially carcinogenic, making it a subject of major environmental concern. However, only a little information on the mechanism of immunological sensitization and asthma by this compound has been known. So, we performed with Jurkat cell line, a human T lymphocyte, to assess the induction of DNA damage and to identify the DEGs related to immune response or toxicity by formaldehyde. In this study, we investigated the induction of DNA single strand breaks by formaldehyde using single cell gel electrophoresis assay (comet assay). And we compared gene expression between control and formaldehyde treatment to identify genes that are specifically or predominantly expressed by employing annealing control primer (ACP)-based $GeneFishing^{TM}$ method. The cytotoxicity ($IC_{30}$) of formaldehyde was determined above the 0.65 mM in Jurkat cell in 48 h treatment. Based on the $IC_{30}$ value from cytotoxicity test, we performed the comet assay in this concentration. From these results, 0.65 mM of formaldehyde was not revealed significant DNA damages in the absence of S-9 metabolic activation system. And the one differentially expressed gene (DEG) of formaldehyde was identified to zinc finger protein 292 using $GeneFishing^{TM}$ method. Through further investigation, we will identify more meaningful and useful DEGs on formaldehyde, and then can get the information on the associated mechanism and pathway with immune response or other toxicity by formaldehyde exposure.

• 혜화의학회지
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• 제22권2호
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• pp.67-79
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• 2014

In order to investigate the efficacy of BJBB on atopic dermatitis, various immune related factors were studied. The results and conclusions are as follows. Atopic dermatitis symptoms were improved in BJBB treated group and significant decrease in dermatitis index were observed in 13 weeks. ALT, AST and BUN, Cr levels were all with in the normal ranges in BJBB treated group, indicating no induced toxicity. BJBB treated group showed significant decrease in CD4+, CD11b+/Gr-1+ immune cell ratio in dorsal skin by 33% and 62% respectively. BJBB treated group showed significant decrease in the expression of IL-4, IL-5, IL-13 and histamine by 83%, 62%, 53% and 61% respectively. Also the group showed decrease in the transcription of IL-4, IL-5 and IL-13 mRNA in spleen by 41%, 52% and 50% respectively. BJBB treated group showed decrease in the expression of IgE by 57% respectively. The results above indicated that treatment of BJBB improved atopic dermatitis symptoms by immune modulation activity a clinical evidence. thus, BJBB has a potential use as a composition of medicinal plants for treatment against inflammation related disease.

• 한국임상약학회지
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• 제28권1호
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• pp.65-75
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• 2018

Objective: Over the last several years, immunotherapy has become one of the most promising therapeutic options for cancer. This study aims to summarize the updates on cancer immunotherapy focusing on immune checkpoint inhibitors, such as programmed cell death-1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors, which have received attention as new anticancer therapeutic agents. Methods: A literature survey was carried out on PubMed to identify high-impact papers on cancer immunotherapy from 2010. The most recent data on clinical efficacy and safety have been included highlighting the response characteristics to recently approved immunotherapeutic agents. Results: In various cancers, immune checkpoints are a means for cancer cells to evade the immune system. Furthermore, CTLA-4 and PD-L1 can be overexpressed, allowing malignant cells to evade T-cells. Numerous clinical trials have been performed to seek appropriate indication of these products in various cancer types. Among them, the most conspicuous types are melanoma, non-small-cell lung cancer, and head and neck cancer. The approval of ipilimumab by Food and Drug Administration (FDA) commenced a new era of cancer immunotherapy. This was followed by the approval of nivolumab and pembrolizumab. Currently, combination therapies are being investigated for various cancer types. Conclusion: In this study, we reviewed recently reported scientific and clinical evidence for currently approved immune checkpoint inhibitors. Although these novel checkpoint inhibitors are ever evolving for cancer therapies, there exist limitations that need to be overcome, indicating the necessity for further studies aiming to improve their efficacy, toxicity, and cost.

• KSBB Journal
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• 제29권1호
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• pp.36-41
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• 2014

Skin disease is one of the most common diseases and its incidence is increasing dramatically in modern society. Specially, many attempts have been made to treat chronic skin inflammation diseases, such as psoriasis and atopic dermatitis, but effective therapies for the immune cell-mediated skin diseases, including psoriasis and atopic dermatitis have not been developed. Until recently, several drug candidates which were claimed to be effective for skin diseases have been reported, but most of them are not used to treat chronic skin disease. Especially, Psoriasis is characterized by excessive growth and aberrant differentiation of keratinocytes, but is fully reversible with appropriate therapy. The trigger of the keratinocyte response is thought to be activation of the cellular immune system, with T cells and various immune-related cytokines. Formation of new blood vessels starts with early psoriatic changes and disappears with disease clearance. Several angiogenic mediators are up-regulated in psoriasis development. Contact- and mediator-dependent factors derived from keratinocytes, mast cells and immune cells may contribute to the strong blood vessel formation of psoriasis. New technologies and experimental models provide new insights into the role of angiogenesis in psoriasis pathogenesis. TMP and its derivatives themselves effectively inhibited in vitro cell migration, tube formation, and the expression of angiogenic factors. However, TMP and its derivatives induced side effects including hemolysis and local side effects. Therefore, in an attempt to reduce the toxicity and the undesirable side effects of TMP and derivatives, a liposomal formulation was prepared and tested for its effectiveness. TMP and derivatives liposomes retained the effectiveness of TMP in vitro while side effects were reduced. These results support the conclusion that TMP effectively inhibits in vitro angiogenesis, with the possibility that use as a psoriasis relief agent.

• 동의생리병리학회지
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• 제23권6호
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• pp.1282-1291
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• 2009

A combined prescription of GGB and CHS (G&C prescription group) was used to investigate its effects on immune related factors and histological changes in atopic dermatitis(AD) induced mice. Significant decrease of atopic dermatitis clinical index in G&C prescription group. In DLN, G&C prescription group significantly modulated the immune cells. G&C prescription group also showed significant effect on the immune cells of the dorsal skin as well as DLN. The group indicated significant decrease of the biosynthesis of IL-4, IL-5, IL-13, GM-CSF, cytokines in serum. On the other hand, the biosynthesis of TNF-$\alpha$ was decreased. G&C prescription group significantly decreased the immunoglobulin IgE levels in serum. The results suggest that G&C prescription significantly improves atopic dermatitis through regulation of immune cells and cytokines. Comparative studies with Protopic ointment also showed that G&C prescription showed significant effect in AD patients, and active application of the prescription in clinicals is anticipated. However, the reason for the results that oppose to those of previous studies should be investigated. Also, therapeutic effects of both internal and external applications should be studied individually as well as for any synergistic effects. Safety, toxicity, as well as stability studies should follow to develop G&C prescription into long-term external clinical product.

• Toxicological Research
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• 제22권4호
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• pp.431-438
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• 2006

The object of this study was to obtain acute toxicity information (single oral dose toxicity) of lyophilized water extract of Puerariae Radix (PR) in both male and female mice. In order to investigate the 50% lethal dose $(LD_{50})$, approximate lethal dosage (ALD), test substances were once orally administered to female and male ICR mice at dose levels of 2000 and 0 (control) mg/kg (body wt.) according to the recommendation of KFDA Guidelines [2005-60, 2005]. The mortality and body weight changes, clinical signs and gross observation were monitored during 14 days after dosing. Organ weight and histopathology of 12 principal organs were measured. As the results, we could not find any mortality, clinical signs, body weight changes and gross findings except for PR extracts unrelated sporadic findings. In addition, no abnormal changes related PR extracts treatment on the organ weight and histopathology of principal organs were detected except for some sporadic findings including hyperplasia of lymphoid follicles in the popliteal lymph nodes and spleen as pharmacological effects of PR extracts. The results obtained in this study suggest that the PR extracts does not cause any toxicological signs except for pharmacological effects of enhancement of Immune system. The $LD_{50}$ and ALD of PR extracts in both female and male mice were considered as over 2000 mg/kg because no mortalities were detected up to 2000mg/kg that was the highest dose recommended by KFDA and Organization for Economic Co-Operation and Development.

• Toxicological Research
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• 제29권4호
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• pp.285-292
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• 2013

Ginseng is a well-known traditional medicine used in Asian countries for several thousand years, and it is currently applied to medicine, cosmetics, and nutritional supplements due to its many healing and energygiving properties. It is well demonstrated that ginsenosides, the main ingredient of ginseng, produce a variety of pharmacological and therapeutic effects on central nerve system (CNS) disorders, cardiovascular disease, endocrine secretions, aging, and immune function. Korean red ginseng extract is a dietary supplement containing ginsenoside Rb1 and ginsenoside Rg1 extracted from Panax ginseng. While the pharmacokinetics and bioavailability of the extract have been well established, its toxicological properties remain obscure. Thus, four-week oral toxicity studies in rats were conducted to investigate whether Korean red ginseng extract could have a potential toxicity to humans. The test article was administered once daily by oral gavage to four groups of male and female Sprague-Dawley (SD) rats at dose levels of 0, 500, 1,000, and 2,000 mg/kg/day for four weeks. Neither deaths nor clinical symptoms were observed in any group during the experiment. Furthermore, no abnormalities in body weight, food consumption, ophthalmology, urinalysis, hematology, serum biochemistry, gross findings, organ weights, or histopathology were revealed related to the administration of the test article in either sex of any dosed group. Therefore, a target organ was not determined in this study, and the no observed adverse effect level (NOAEL) of Korean red ginseng extract was established to be 2,000 mg/kg/day.

• 생명과학회지
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• 제23권11호
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• pp.1388-1396
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• 2013

본 연구는 인공재배 상황버섯 자실체 추출물인 금사목질진흙버섯 자실체 추출물의 mouse sarcoma cells인 S-180 세포에 대한 정맥 투여 시 항암 효과와 급성독성 및 4주 아 급성 독성에 대한 보고이다. 금사목질진흙버섯 자실체 추출물의 항암효과는 250 mg/kg에서 대조군 대비 42.7%의 크기로 가장 높은 효과를 나타내었으며, 농도 의존적인 경향을 나타내었다. 급성 독성에서는 $LD_{50}$치가 632.84 mg/kg (♂)과 814.48 mg/kg (♀)로 나타났으며, 이자와 장기의 무게비가 증가하는 현상이 나타나, 영향이 있는 것으로 추측되었다. 4주 아 급성 독성 시험에서 $LD_{50}$치는 355.41 mg/kg (♂)과 383.53 mg/kg (♀)로 나타났으며, 특히 250 mg/kg 투여군에서는 간의 무게 비가 2배 정도 증가하는 현상과 황색 반점이 나타났다. 특히 125 mg/kg 이상 투여군에서는 점프 능력과 민첩성 등의 운동 능력이 현저히 증가되는 현상이 관찰되었으며, 이에 대한 정확한 메카니즘은 확인할 수 없었다. 이상의 결과를 바탕으로 금사목질진흙버섯 자실체 추출물에 대한 표준물질 정제 과정을 통한 작용기전과 운동능력 향상에 대한 실험 등이 추가된다면 유효 농도에서 독성이 낮으면서도 암을 제어할 수 있는 새로운 천연물 신약의 후보 물질로 이용될 가능성이 있는 것으로 판단된다.