• 대한한의학회지
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• 제30권6호
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• pp.69-79
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• 2009

Objective: In this study, the immunomodulatory activity of a mixture of wild Panax ginseng and red-mold rice extracts (MPR) on RAW 264.7 macrophage cells in the presence and absence of methotrexate (MTX), an anti-cancer drug, was investigated. Methods and Results: In the cell viability, MPR showed a significant cell proliferation and inhibited cell regression by red-mold rice (RMR) alone or MTX alone. MPR induced moderate increase in nitric oxide (NO) production. NO production and inducible nitric oxide synthase (iNOS) mRNA expression by LPS decreased after MPR treatment. In addition, MPR slightly induced COX-2 mRNA expression, but it did not affect the expression of COX-2 mRNA by LPS treatment. In RT-PCR analyses, MPR induced IL-$1{\alpha}$, IL-$1{\beta}$, IL-6, and TNF-$\alpha$ mRNA expression, but had no effect on IL-10 and TGF-$\beta$, regardless of MTX treatment. Furthermore, MPR did not interfere with the cytotoxicity of MTX against MCF-7 human breast carcinoma cells. Conclusions: MPR is efficacious in protecting against MTX-induced cell regression as a result of macrophage activation, resulting in induction of cytokine expression, implying that MPR could be considered an adjuvant in MTX-chemotherapy.

• Molecules and Cells
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• 제40권1호
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• pp.66-72
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• 2017

Pathological hypertrophy of the heart is closely associated with endoplasmic reticulum stress (ERS), leading to maladaptations such as myocardial fibrosis, induction of apoptosis, and cardiac dysfunctions. Salubrinal is a known selective inhibitor of protein phosphatase 1 (PP1) complex involving dephosphorylation of phospho-eukaryotic translation initiation factor 2 subunit $(p-eIF2)-{\alpha}$, the key signaling process in the ERS pathway. In this study, the effects of salubrinal were examined on cardiac hypertrophy using the mouse model of transverse aortic constriction (TAC) and cell model of neonatal rat ventricular myocytes (NRVMs). Treatment of TAC-induced mice with salubrinal ($0.5mg{\cdot}kg^{-1}{\cdot}day^{-1}$) alleviated cardiac hypertrophy and tissue fibrosis. Salubrinal also alleviated hypertrophic growth in endothelin 1 (ET1)-treated NRVMs. Therefore, the present results suggest that salubrinal may be a potentially efficacious drug for treating pathological cardiac remodeling.

• 대한한방내과학회지
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• 제27권1호
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• pp.228-236
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• 2006

Objectives : Macrophage has an important innate defense role in the immune system. When we are infected with pathogens, macrophage ingests them through phagocytosis or endocytosis, and then secretes many cytokines, such as IL-1, IL-6 and $TGF{\alpha}$, which are regulators of immune responses. The aim of this study is to determine how Samjunghwan effects the expression of cytokine and other immune-related genes in macrophages. Methods : Cells were treated directly with Samjunghwan and/or LPS at regular intervals. Total RNA of cells was isolated using TRIzol reagent, and the changes in cytokine gene expressions were investigated using RT-PCR, western blot and ELISA. Results : $IL-1{\alpha},\;IL-1{\beta}$ and COX-2 genes were inducibly expressed specifically by Samjunghwan in macrophage. Especially, $IL-1{\beta}$ gene was induced most strongly by treatment with Samjunghwan. Over time, treatment with Samjunghwan showed that the expression levels of $IL-1{\alpha}\;and\;$IL-1{\beta}$ genes increased from 1 to 4h, and then decreased from 4 to ISh. However, the expression level of COX-2 gene increased continuously up to 11h. $IL-1{\alpha},\;IL-1{\beta}$ and COX-2 genes were expressed synergistically by a simultaneous treatment of both Samjunghwan and LPS in macrophages. Secretion levels of translated $IL-1{\beta}$ increased continuously up to 11h. Conclusions : Though this study is only a start in the investigation of the efficasy of Samjunghwan, these results suggest that Samjunghwan has positive effects on immune responses.

• 동의생리병리학회지
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• 제27권2호
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• pp.183-188
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• 2013

Ultraviolet (UV) B irradiation induces the production of matrix metalloproteinases (MMPs), which are responsible for the degradation or synthesis inhibition of collagenous extracellular matrix in connective tissues, causing skin photoaging. In this study, we examined the inhibitory effect of MMP-1 expression of yam extract in tumor necrosis factor-alpha (TNF-${\alpha}$)-stimulated human dermal fibroblast neonatal (HDFn) cell and preventive effect of UVB-induced damage in hairless mice skin. The synthesis of procollagen and the release of MMP-1 in HDFn cells were measured by EIA kit and MMP-1 assay kit, respectively. UVB radiation was applied to the backs of the mice three times a week for 8 weeks. Mice were randomly divided into three groups, and were topical application with the Dioscorea batatas (DB, 6%) or vehicle. Reduction of TNF-${\alpha}$-induced procollagen synthesis was increased by DB (50 ug/ml), which was higher than positive control group (TGF-${\beta}$). Also, pre-treatment of HDFn cells with DB inhibited TNF-${\alpha}$-induced release of MMP-1. In vivo study, we found that preventive effect of DB against UV-induced epidermal thickness. DB suppressed the expression of MMP-3 and MMP-13 induced by UVB irradiation. Our results show that DB have preventive effect of UV-induced skin damage in hairless mice.

• 한국연초학회지
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• 제32권1호
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• pp.19-27
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• 2010

The aim of this study is to compare the sensitivity of both two NCI-H292 and A549 cell types to acute inflammatory responses induced by cigarette smoke. For this, we treated two kinds of smoke fractions derived from 2R4F reference cigarettes: total particulate matter(TPM) collected onto a Cambridge filter pad and gas/vapor phase(GVP) prepared by bubbling through in buffer solution. When we measured cellular cytotoxicity by neutral red uptake assay after treatment for 24 hours, TPM and GVP induced cytotoxic effect in a dose-dependent manner in the range of 10-$100{\mu}g$/mL and 60-$300 {\mu}g$/mL., respectively, in both cell types without any cellular difference. Additionally, when we examined acute inflammatory responses by analyzing cytokines secreted into culture media including tumor necrosis factor-$\alpha$ (TNF-$\alpha$), interleukin-8(IL-8), and transforming growth factor-$\alpha$(TGF-$\alpha$) as well as matrix metalloproteinase-1(MMP-1), the treatment with smoke fractions increased those marker proteins in a dose-dependent manner in NCI-H292. Meanwhile, in A549 cells only MMP-1 was observed to be increased in a dose-dependent fashion. Collectively, our data indicate that NCI-H292 cell type is more sensitive to cigarette smoke-induced inflammatory response than A549 cells. This suggests that NCI-H292 could be useful as an in vitro evaluation tool to assess harmful effects of cigarette smoke.

• 생명과학회지
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• 제23권4호
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• pp.501-509
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• 2013

포름알데히드는 주로 산업용으로 사용되는 독성이 강한 물질로서 생체에 노출 시 염증, 산화적 스트레스, 알레르기 반응, 나아가서 암을 유발하게 된다. 불가사리에서 추출되는 saponin은 sulphated sterol glycosides 등으로서 인삼 saponin (ginsenoside)들과 화학적 구조가 비슷하여 항균 및 세포독성을 비롯한 미생물을 괴사시키는 기능을 가지고 있음이 보고되었다. 또한 손상된 불가사리의 조직에는 염증성 사이토카인이 발현되는데 TGF-${\beta}$의 증가로 손상 받은 부위를 빠르게 치료, 재생하게 된다. 본 실험은 조직손상 후 8일 된 불가사리 추출물과 포름알데히드를 IMR-90에 처리했을 때와 포름알데히드에 노출시킨 ICR 마우스에 불가사리 추출물을 흡입시켰을 때 염증성 폐 손상의 방어 및 치료에 미치는 효과를 알아보았다. 포름알데히드에 노출된 IMR-90에 조직손상 후 8일이 경과한 불가사리 추출물을 처리한 결과, 세포의 유의한 증식을 보였으며 염증 조절에 영향을 주는 TNF-${\alpha}$, NF-${\kappa}B$의 발현억제 및 $I{\kappa}-B{\alpha}$의 합성을 촉진시켰다. 포름알데히드에 노출된 ICR 마우스에 조직손상 후 8일이 경과한 불가사리 추출물을 처리한 군에서 체중의 증가, 항산화 효소의 증가, 지질과산화 작용의 감소, surfactant protein A의 증가, TNF-${\alpha}$ 및 NF-${\kappa}B$의 발현억제, $I{\kappa}-B{\alpha}$ 발현의 증가와 조직재생에 우수한 효과를 보였다. 이러한 결과는 포름알데히드로 인한 세포 및 폐 손상을 불가사리 추출물의 항염증 작용을 통하여 억제하거나 완화시킴을 확인할 수 있다.

• 대한본초학회지
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• 제25권4호
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• pp.121-128
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• 2010

Objectives : This study purposed to research the inhibitory effect of Berberidis Ramulus on the liver cancer. Methods : A total extract of Berberidis Ramulus decoction were prepared. Through the measurement of the cell proliferation, apoptosis, morphology and cytokine level from the extracts, the influence on HepG2 cell were compared. Results : Berberidis Ramulus extract significantly inhibited the proliferation, increased the apoptosis, decreased the TGF-${\beta}$ gene expression and the K-RAS gene expression, significantly increased the level of TNF-${\alpha}$ secretion and increased the rates of IFN-${\gamma}$ secretory cells. Conclusion : It is suggested that Berberidis Ramulus extract turned out to have anti-cancer effects on HepG2 cell.

• Mass Spectrometry Letters
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• 제1권1호
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• pp.5-8
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• 2010

In the present study, collisionally-activated dissociation (CAD) experiments were performed under low energy collision conditions in six peptides containing a disulfide bond. Fragments produced as a result of the cleavage of a disulfide bond were obtained after CAD in four peptides (bactenecin, TGF-$\alpha$, cortistantin, and linearly linked peptide, Scheme 1) with basic amino acid residues. In contrast, the CAD analysis of two peptides with no basic residue (oxytocin and tocinoic acid) rarely produced fragments indicative of cleavage of a disulfide bond. These results are consistent with the mobile proton model suggested by the McLuckey and O'air groups (ref. 22 and 23); nonmobile protons sequestered at basic amino acid residues appear to promote the cleavage of disulfide bonds.

• Asian-Australasian Journal of Animal Sciences
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• 제13권6호
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• pp.845-855
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• 2000

As high as 50% of pregnancies are known to fail and the majority of such losses occur during the peri-implantation period. For the establishment of pregnancy in mammalian species, therefore, implantation of the conceptus to the maternal endometrium must be completed successfully. Physiological events associated with implantation differ among mammals. In ruminant ungulates, an elongation of the trophohlast in early conceptus development is required before the attachment of the conceptus to the uterine endometrium. Moreover, implantation sites are restricted to each uterine caruncula where tissue remodeling, feto-maternal cell fusion and placentation take place in a coordinated manner. These unique events occur under strict conditions and are regulated by numerous factors from the uterine endometrium and trophoblast in a spatial manner. Interferon-tau (IFN-${\tau}$), a conceptus-derived anti-Iuteolytic factor, which rescues corpus luteum from its regression in ruminants, is particularly apt to play an important role as a local regulator in coordination with other factors, such as TGF-${\beta}$, Cox-2 and MMPs at the attachment and placentation sites.

• 대한한방내과학회지
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• 제34권2호
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• pp.134-146
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• 2013

Objectives : Auklandia Lappa (ALE) is one of the herbs used frequently to treat abdominal pain and diarrhea and reported anti-inflammatory activity by suppressing proinflammatory cytokines. This study was designed to investigate whether ALE could show protective activities on experimental colitis induced by dextran sulfate sodium (DSS) models. Methods : Colitis was induced by DSS in Balb/c mice. ALE 10, 30, 100 and 300 mg/kg were orally administered twice a day for 7 days in DSS model. Mice weight was measured daily. Scoring of clinical findings was measured every other day. Colon length, edema, fecal blood and histological damages were assessed at day 7 in DSS model. In histological analysis, we checked cryptal glands, surface epithelium, submucosa, transmural, stroma and scored degree of inflammatory cell damage by modified histological scoring. We also calculated cytokines concentrations including IFN-${\gamma}$, TNF-${\alpha}$, IL-6, IL-$1{\beta}$, IL-17, IL-23, IL-10 and TGF-${\beta}1$ by Biometric Multiplex Cytokine Profiling method. Results : ALE showed the protective effects on DSS-induced experimental colitis. ALE inhibited shortening of colon length and histological damages of colon does-dependently, but it did not inhibit weight loss. ALE also inhibited IFN-${\gamma}$ and IL-6 expression, and upregulated cytokines (IL-10, TGF-${\beta}1$) related to regulatory T cell differentiation and proliferation. Conclusions : The current results demonstrate the clinical utility of ALE in traditional medicine and indicate the possibility of potent drug development of inflammatory bowel diseases from natural products. Further investigations for exact mechanisms will be needed.