• 제목/요약/키워드: cellular toxicity

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N,N,N-Trimethylphytosphingosine (TMP)의 염증성 피부질환 치료제 가능성에 관한 연구 (Study for Possibility of N,N,N-Trimethylphytosphingosine (TMP) for Management of Chronic Skin Diseases)

  • 서원상;오한나;박우정;엄상용;강상모
    • 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.

계혈등 물추출물의 항산화 및 간보호효과 (Antioxidant Effect and Liver Protection Effect of Spatholobi Caulis Water Extract)

  • 이재준;최홍식;김승모
    • 대한본초학회지
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    • 제26권3호
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    • pp.47-56
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    • 2011
  • Objectives : This study investigated whether the water extract of Spatholobi Caulis (SCE) has the ability to protect hepatocyte against oxidative stress induced by tert-butylhydroperoxide (tBHP) in vitro and $CCl_4$ in vivo. Methods : In vitro, HepG2 cells pre-treated with Spatholobi Caulis water extract (1, 3, 10, $30{\mu}g$/ml) for 12h and further incubated with tBHP ($100{\mu}M$) for the next 12h. Cell viability was assessed by MTT assay. In vivo, rats were orally administrated with the aqueous extract of Spatholobi Caulis (SCE; 50, 100 mg/kg) for 4 days and then, injected with $CCl_4$ 1 mg/kg body weight to induce acute liver damage. Results : Treatment with SCE inhibited cell death induced by tBHP, as evidenced by alterations in the levels of the proteins associated with apoptosis:SCE prevented a decrease in $Bcl_2$, and cleavage of poly(ADP-ribose)polymerase and pro-caspase-3. Moreover, SCE inhibited the ability of tBHP to generate $H_2O_2$ production, thereby restoring GSH content. Moreover, SCE treatments in rats effectively decreased liver injuries induced by a single dose of $CCl_4$, as evidenced by decreases in hepatic degeneration and inflammation as well as plasma alanine aminotransferase and lactate dehydrogenase activities. Consistently, treatments of SCE also protected liver in rats stimulated by $CCl_4$, as indicated by restoration GSH and prevention of MDA in the liver. Conclusions : SCE has the ability 1) to protect hepatocyte against oxidative stress induced by tBHP and 2) to prevent $CCl_4$-inducible acute liver toxicity. Present findings may be informative not only in elucidating the pharmacological mechanism of Spatholobi Caulis, but in determining its potential application for oxidative cellular damage in the liver.

효율적인 약물 방출 스텐트 제조를 위한 고분자 코팅물질 개발 (Development of Polymeric Coating Material for Effective Drug-eluting Stent)

  • 박태현;조은애;나건
    • 폴리머
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    • 제35권5호
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    • pp.483-487
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    • 2011
  • 효율적 비혈관용 약물방출 스텐트 제조를 위해 풀루란 아세테이트(pullulan acetate, PA)가 테프론(poly-tetrafluorethylene; PTFE)으로 피막된 스텐트(PTFE-stent)의 코팅재료로 연구되었다. 파크리탁셀 함유 PA가 코팅된 PTFE-stent의 표면, 약물 방출 거동, 세포독성이 측정되었으며, 동물실험을 통해 이의 가능성이 검토되었다. 전자현미경으로 표면을 관찰한 결과 표면이 PTFE 피막에 비해 훨씬 매끄러웠고, 약물은 80일 동안 서방적 방출 거동을 보였다. PA와 함께 코팅된 파크리탁셀의 안정성을 annexin V 결합 염색법을 통하여 측정한 결과 apoptosis의 비율이 천연 파크리탁셀과 유사한 것으로 보아 봉입된 파크리탁셀의 변성이 없음을 알 수 있었다. 소동물 실험에서는 파크리탁셀이 봉입된 PA-PTFE가 고형암의 성장을 억제하였다. 위의 결과로 보아 PA는 효율적 비혈관계 약물방출 스텐트 개발에 매우 유용한 물질이라고 기대된다.

삼잎국화 추출물의 피부세포 생리활성 효과 (Effect of Rudbeckia laciniata Extract on Physiological Activity of HaCaT Cells)

  • 김준섭
    • 한국식품영양학회지
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    • 제29권3호
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    • pp.335-340
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    • 2016
  • The objective of the present investigation was to obtain vitamin, mineral, flavonoid, and polyphenol profiles of Rudbeckia laciniata (RL), and to examine the effects of extract of RL (RLE) on various physiological activities of HaCaT keratinocyte for the utilization of RL as natural raw materials to develop functional food. To accomplish this purpose, we checked the contents of the general nutrients of RL. The contents of vitamin A, vitamin $B_1$ and vitamin $B_2$ were $7.49{\mu}g/g$, $51.96{\mu}g/g$, and $132{\mu}g/g$ respectively, while vitamin C and vitamin $D_3$ were not detected. The contents of mineral such as Ca, K and Fe were 2.01 mg/g, 6.06 mg/g and 0.03 mg/g respectively. Total flavonoid contents of RLE were 0.25 mg/g, and total polyphenol were estimated as 1.43 mg/g. Because RL contains high levels of vitamin A which is associated with skin aging, we investigated the effect of RLE on physiological function of keratinocytes with respect to skin aging. We found that RLE significantly increased the growth rate of HaCaT cells and reduced ultraviolet radiation B (UVB)-induced cellular toxicity. Also, the extract of Rudbeckia laciniata attenuated the UVB-induced reactive oxygen species (ROS) generation in a dose-dependent manner in HaCaT cells. In addition, treatment with the extract dose-dependently increased migration activity of HaCaT cells. Thus, these findings indicated that RLE could regulate the physiological activity of keratinocytes, and may be used to develop functional foods.

Cry 독소단백질 혼합과 면역억제제 첨가를 통한 Bacillus thuringiensis 살충제 적용범위 및 방제력 증진 기술 (A Technique to Enhance Bacillus thuringiensis Spectrum and Control Efficacy Using Cry Toxin Mixture and Immunosuppressant)

  • 엄성현;박영진;김용균
    • 농약과학회지
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    • 제18권3호
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    • pp.181-190
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    • 2014
  • 곤충병원세균인 Bacillus thuringiensis (비티)는 포자 형성과 더불어 살충성 Cry 독소단백질을 생산한다. Cry 독소단백질은 대상 곤충의 중장에 위치한 수용체와 특이적으로 결합하며 살충작용을 발휘하기에 비티의 적용해 충범위가 비교적 좁다. 본 연구는 비티의 적용해충범위와 살충력을 증가시키기 위한 일환으로 실시되었다. 서로 다른 네 가지 비티 균주에서 분리된 Cry 독소단백질은 각각 좁은 적용해충범위를 나타냈다. 이들 Cry 독소단백질을 혼합한 결과 적용범위가 현격하게 증가했다. 벡큘로바이러스가 비티의 적용범위를 증가시키는 지 알아보기 위해 Cry1Ac 또는 Cry1Ca 독소단백질을 각각 발현시키는 재조합바이러스로 검정한 결과 벡큘로바이러스는 Cry 독소단백질의 적용범위를 증가시키는 데 유효하지 않았다. Xenorhabdus nematophila (Xn) 세균 배양액은 조사된 모든 곤충의 세포성 면역을 억제하고 Cry 독소단백질의 살충력을 증가시켰다. 이 Xn 세균배양액을 혼합 Cry 독소단백질에 추가한 결과 적용해충범위와 살충력을 모두 증가시켰다.

청황산(靑黃散)의 백혈병(白血病)에 대(對)한 항종양효능(抗腫瘍效能) 연구(硏究) (A literal study of anti-tumor effects of chunghwangsan for leukemia)

  • 박종학;손창규;조종관
    • 혜화의학회지
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    • 제10권2호
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    • pp.83-89
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    • 2002
  • In the literatual study of anti-tumor effects of chunghwangsan for leukemia, the results were as follows. 1. Chunghwangsan is composed of Indigo naturalis and Realgar. The composing rate is 9 : 1 and it is made into capsule or piece. The basic administration is 0.3g per day and could increase the quantity each day. 2. The effects of Chunghwangsan is expelling toxin and colling, colling blood to detumescence, drying wetness and anticancer are. So it can be used to treat AML, CML and lymphoma. 3. The anticancer component of Indigo naturalis is indirubin which has the effects of suppression the transplanted tumor, activating the phagocyte of macrophage, promoting the maturation of myeloblast to improve cure rate of CML. The anticancer component of Realgar is $As_2O_3$ which has the direct cellular toxicity for leukemia cell. 4. In viewpoints of oriental medicine, leukemia is malignant myeloid neoplasia in which pathogen invade to shaoyin(少陰). So Chunghwangsan which is expelling toxin and colling, colling blood to detumescence, drying wetness and anticancer is effective to leukemia. 5. In clinical reports, Chunghwangsan is often used in CML, and also used in AML, lymphoma and so on. 6. Chunghwangsan is cool-natured, so we must carefully pay attention to pregnant women and hematsdthenic patients. The main side effects are nausea, bone marrow pain, diarrhea, polydefecation, hematokezia and purpora. We sometimes take invigorating stomach medicine to prevent the side effects. 7. If we continuously develop Chunghwangsan and therapy for leukemia with syndrome differentiation. we can improve the response and cure rate for leukemia in the future.

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Effects of Kojic acid, Arbutin and Vitamin C on cell viability and melanin synthesis in B16BL6 cells

  • Park, Yumi;Lee, Jongsung;Park, Junho;Park, Deokhoon
    • 대한화장품학회지
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    • 제29권1호
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    • pp.151-167
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    • 2003
  • Melanin biosynthesis is a human defense mechanism to protect skin from UV irradiation and also determines colors of hair and skin. However, as a interest on skin-whitening increases, researches to prevent pigmentation and hypersynthesis of melanin in skin are being actively in progress. Active components used as a whitening agent in cosmeceuticals are kojic acid, arbutin, vitamin C and hydroquinone. However, until now, because comparison researches among them in the aspect of both melanin formation and cellular toxicity have not been performed, we can't exactly estimate merits and defects of them as a whitening agent. To this end, we performed experiments to compare their effects on cell viability and melanin formation. As a first step, in vitro tyrosinase inhibition assay was done. While kojic acid and hydroquinone showed strong inhibition activities(their IC$\_$50/s are all < 100uM), arbutin and vitamin C showed weak activities. IC$\_$50/s of arbutin and vitamin C are 100uM and 400∼500uM, respectively. In B16BL6 melanoma cells, like in vitro tyrosinase inhibition assay, arbutin and kojic acid showed more strong inhibition effect on melanin synthesis than vitamin C. And unlike arbutin, vitamin C and kojic acid induced cell death at high concentration. Although arbutin showed no cytotoxicity, it has side effect to induce morphological change at high concentration.. In this paper, we suggest both kojic acid and arbutin have stronger ability to inhibit melanogenesis than vitamin C. And they also have side effect, that is, kojic acid induces cell death like vitamin C and arbutin changes cell morphology respectively.

In vitro Transport of Fexofenadine.HCl in Deformable Liposomes Across the Human Nasal Epithelial Cell Monolayers

  • Lin, Hong-Xia;Lee, Chi-Ho;Shim, Chang-Koo;Chung, Suk-Jae;Kim, Dae-Duk
    • Journal of Pharmaceutical Investigation
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    • 제34권6호
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    • pp.483-489
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    • 2004
  • Fexofenadine HCl is non-sedating histamine H1 receptor antagonist that can be used for the treatment of seasonal allergic rhinitis. The objective of this study was to investigate whether the carriers of deformable liposomes can enhance the transepithelial permeability of fexofenadine HCl across the in vitro ALI human nasal monolayer model. Characterization of this model was achieved by bioelectric measurements and morphological studies. The passage 2 and 3 of cell monolayers exhibited the TEER value of $2852\;{\pm}\;482\;ohm\;{\times}\;cm^2$ on 11 days of seeding and maintained high TEER value for 5 days. The deformable liposome of fexofenadine HCl was prepared with phosphatidylcholine (PC) and cholic acid using extruder method. The mean particle size was about 200 nm and the maximum entrapment efficiency of 33.0% was obtained in the formulation of 1% PC and $100\;{\mu}g/ml$ fexofenadine HCl. The toxicity of the deformable liposome to human nasal monolayers was evaluated by MTT assay and TEER value change. MTT assay showed that it has no toxic effect on the nasal epithelial cells in 2-hour incubation when the PC concentration was below 1%. However, deformable liposome could not enhance the transepithelial permeability $(P_{app})$ and cellular uptake of fexofenadine HCl. In conclusion, the in vitro model could be used in nasal drug transport studies and evaluation of transepithelial permeability of formulations.

인간 배아 줄기세포의 OPS와 Grid를 이용한 유리화 동결법의 효율성 비교 (Modification of Efficient Vitrification Method by Using Open Pulled Straw (OPS) and EM Grid as Vehicles in Human Embryonic Stem Cell)

  • 박규형;최성준;김희선;오선경;문신용;차광렬;정형민
    • 한국수정란이식학회지
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    • 제18권3호
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    • pp.179-186
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    • 2003
  • Human embryonic stem (hES) cell lines have been derived from human blastocysts and are expected to have far-reaching applications in regenerative medicine. The objective of this study is to improve freezing method with less cryo-injuries and best survival rates in hES cells by comparing various vitrification conditions. For the vitrifications, ES cells are exposed to the 4 different cryoprotectants, ethylene glycol (EG), 1,2-propanediol (PROH), EG with dime-thylsulfoxide (DMSO) and EG with PROH. We compared to types of vehicles, such as open pulled straw (OPS) or electron microscopic cooper grids (EM grids). Thawed hES cells were dipped into sequentially holding media with 0.2 M sucrose for 1 min, 0.1 M sucrose for 5 min and holding media for 5 min twice and plated onto a fresh feeder layer. Survival rates of vitrified hES cells were assessed by counting of undifferentiated colonies. It shows high survival rates of hES cells frozen with EG and DMSO (60.8%), or EG and PROH(65.8%) on EM grids better than those of OPS, compared to those frozen with EG alone (2.4%) or PROH alone (0%) alone. The hES cells vitrified with EM grid showed relatively constant colony forming efficiency and survival rates, compared to those of unverified hES cells. The vitrified hES cells retained the normal morphology, alkaline phosphates activity, and the expression of SSEA-3 and 4. Through RT-PCR analysis showed Oct-4 gene expression was down-regulated and embryonic germ layer markers were up-regulated in the vitrified hES cells during spontaneous differentiation. These results show that vitrification method by using EM grid supplemented with EG and PROH in hES cells may be most efficient at present to minimize cyto-toxicity and cellular damage derived by ice crystal formation and furthermore may be employed for clinical application.

마치현 70% 에탄올 추출물의 Heme Oxygenase-1 발현을 통한 산화적 스트레스에 대한 사람각질형성세포 보호 효과 (The Cytoprotective Action of Portulaca oleracea 70% EtOH Extracts via the Heme Oxygenase-1 on Hydrogen Peroxide-induced Oxidative Stress in Human Keratinocyte HaCaT Cells)

  • 서승희;정길생
    • 생약학회지
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    • 제46권2호
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    • pp.116-122
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    • 2015
  • Keratinocytes are first barrier against outer challenges on skin. However, it is still largely unknown about effective protectors against ultraviolet B (UVB), and oxidative stress in human keratinocyte, HaCaT cells. Inducible heme oxygenase (HO)-1 acts against oxidants that are thought to play a role in the pathogenesis of skin disorders. Therefore, the purpose of this study was to evaluate the effect of Portulaca oleracea 70% EtOH extracts against hydrogen peroxide (H2O2)-induced oxidative stress in human keratinocytes, HaCaT cells. P. oleracea 70% EtOH extracts showed the potent protective effects on H2O2-induced toxicity by induced the expression of HO-1 in human keratinocyte, HaCaT cells. Furthermore, P. oleracea 70 % EtOH extracts caused the nuclear accumulation of nuclear factor E2-related factor 2 (Nrf2) in human keratinocytes, HaCaT cells. In addition, we found that treatment with c-Jun N-terminal kinase (JNK) inhibitor (SP600125) reduced P. oleracea 70% EtOH extracts-induced HO-1 expression, and JNK inhibitor (SP600125) also inhibited protective effects by P. oleracea 70% EtOH extracts. Therefore, these results suggest that P. oleracea 70 % EtOH extracts increases cellular resistance to H2O2-induced oxidative injury in human keratinocyte, HaCaT cells, presumably through JNK pathway-Nrf2-dependent HO-1 expression.