• The Korea Journal of Herbology
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• v.31 no.4
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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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• v.1 no.4
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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.

• Journal of Haehwa Medicine
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• v.22 no.2
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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.

• Korean Journal of Clinical Pharmacy
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• v.28 no.1
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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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• v.29 no.1
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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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.6
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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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• v.22 no.4
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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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• v.29 no.4
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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.

• Journal of Life Science
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• v.23 no.11
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• pp.1388-1396
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• 2013

This study used an S-180 cell-injected mouse model to evaluate the antitumor effects of the acute and subacute toxicity of Keumsa (Phellinus linteus) extract intravenously administrated in ICR mice. When administered intravenously (31.3-250 mg/kg body weight), Keumsa (Phellinus linteus) extract significantly inhibited the growth of the solid tumor cell. The antitumor activity of Keumsa (Phellinus linteus) extract increased in a dose-dependent manner. The highest dose (250 mg/kg body weight) was highly effective, reducing tumor formation by 42.7% compared with the control group. In the acute toxicity test, $LD_{50}$ of the Keumsa (Phellinus linteus) extract showed 632.84 mg/kg (♂) and 814.48 mg/kg (♀) after intravenous administration. In addition, liver and spleen weight were increased in a dose-dependent manner. In the subacute toxicity test, the mice were intravenously administered over the course of 28 days. The $LD_{50}$ of the Keumsa (Phellinus linteus) extract showed 355.41 mg/kg (♂) and 383.53 mg/kg (♀) after intravenous administration. The liver and spleen weight also increased in a dose-dependent manner. In the case of the group that received more than 125 mg/kg of intravenous administration, exercise capacity, such as jumping ability and agility, were significantly increased. These results suggest that Keumsa (Phellinus linteus) extract can be regarded as a potent enhancer of the innate immune response, and it can be considered as a new natural product with low toxicity that may be used as a candidate for antitumor action.

• The Journal of Internal Korean Medicine
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• v.30 no.3
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• pp.465-480
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• 2009

Objective : Lonicerae Flos has detoxifying properties and been used as antipyretic, antibacterial and antitumor. Fermentation of herbal medicine is known to increase the absorption, enhance effectiveness, decrease herbal toxicity and reduce side-effects. This study was performed to measure the effects of fermented Lonicerae Flos on influenza A/WSN (H1N1) virus replication. Material and Methods : Lonicerae Flos was fermented by Lactobacillus casei PM1. Fermented Lonicerae Flos was treated for 12 hours to MDCK (Mardin Darby canine kidney) cells, then cell-virulence was observed by MTT assay for 12 hours, 24 hours, and 36 hours after treatment. Following cases were conducted for 0, 10, 100, and $1000{\mu}g/ml$ concentrations of fermented Lonicerae Flos under the same time-frame; the fermented Lonicerae Flos was treated to MDCK cells before and after contamination by A-type influenza virus. The fermented Lonicerae Flos and the virus were mixed directly. The influence was observed by MTT assay and plaque assay. Results : These findings suggest that the fermented Lonicerae Flos inhibited the virulence of influenza A virus in MDCK cells and suppressed the plaque forming colonies induced by influenza A virus. Furthermore, pretreatment with fermented Lonicerae Flos was more effective than post-treatment. The titer of influenza virus was reduced for all before and after influenza A virus inoculation.