• 약학회지
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• 제41권3호
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• pp.365-369
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• 1997

Human chorionic gonadotropin (hCG) is a placental hormone and is involved in maintenance of the corpus luteum during pregnancy. In the present study, effect of hCG on nitiric ox ide (NO) generation from peritoneal macrophage was examined. hCG ahd no effect on NO generation by itself, whereas recombinant interferon- ${\gamma}$ (rIFN-${\gamma}$) alone had modest activity. When hCG was used in combination with rIFN-${\gamma}$, there was a marked cooperative induction of NO generation in a dose-dependent manner. The optimal effect of hCG on NO generation was shown at 6 hr after treatment with rIFN-${\gamma}$. Furthermore, northern blot analysis of showed that hCG increased the expression of inducible NO synthase(iNOS) gene. These results suggest that hCG induces NO generation from macrophages by increasing the expression of iNOS gene.

• Journal of Preventive Medicine and Public Health
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• 제31권2호
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• pp.265-274
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• 1998

To investigate the change of nitric oxide(NO), copper, and zinc in serum on smoking and alcohol ingestion in young adults, this study was performed in a cross-sectional study in 127 healthy men in Korea who had HBsAg(-), HCVAb(-), and no symptomatic liver, heart, gastrointestinal, chronic diseases, and inflammatory sign(lower than 10,000 white blood cell count in CBC). At the men's entry into the study, blood samples were drawn from each subject and immediately centrifuged for analysis of NO, copper, and zinc. Each man completed a questionnaire that provided information on smoking, alcohol intake and present and past medical history NO was analyzed by HPLC(Green et al., 1982), copper and zinc by atomic absorption spectrophotometer with air-acetylene flame and total cholesterol(TC) by Spectrum EPX. Smoking(number of cigarettes per day and pack-year) and alcohol intake was grouped fertile. Copper was adjusted for age and zinc and for age and TC. NO, copper, and zinc on smoking and alcohol ingestion were analyzed in general linear models, respectively. NO, copper and zinc in serum did not show statistical differences between non-smoking and high-smoking group and no-alcohol intake and high-alcohol intake group. This study suggested that copper, zinc, and NO was not. good biological marker for early effect by smoking and alcohol intake in young adults. However, selection bias should be considered in evaluation of this result. A large prospective study will be needed in advance on usefulness of copper, zinc, and NO as a marker for risk factors and early change of atherosclerosis.

• 대한한의학방제학회지
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• 제11권1호
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• pp.115-128
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• 2003

Bojungikgitang is the water extracts prepared from Ginseng Radix, Astragali Radix, Angelicae gigantis Radix, Astractylodis Rhizoma alba, Aurantii nobilis Pericarpium, Glycyrrhizae Radix, Bupleuri Radix, Cimicifugae Rhizoma, which has been used for the treatment of indigestion, and immunological disease in oriental countries. In this study, the effects of Bojungikgitang on the productions of nitiric oxide (NO) and prostaglandin $E_2\;(PGE_2)$, and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were examined using RAW 264.7 macrophages activated with $interferon-{\gamma}\;(IFN-{\gamma})$ plus lipopolysaccharide (LPS). Bojungikgitang (10-400 ${\mu}$g/ml) per se had no cytotoxic effect in unstimulated macrophages, but this compound dose-dependently reduced the release of NO and $PGE_2$ caused by stimulation of $LPS/IFN-{\gamma}$. The levels of iNOS and COX-2 protein were markedly suppressed by the treatment with Bojungikgitang in a concentration dependent manner. Moreover, Bojungikgitang also attenuated the production of tumor necrosis factor (TNF)-${\alpha}$, interleukin (1L)-1${\beta}$ and IL-6 in LPS-stimulated RAW 264.7 macrophages. These results suggest that Bojungikgitang decreases the NO and $PGE_2$ production in macrophages by inhibiting iNOS and COX-2 expression and these properties may contribute to the anti-inflammatory activity of Bojungikgitang.

• 약학회지
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• 제51권6호
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• pp.476-481
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• 2007

A polymorphic fungus, Candida albicans, causes various forms of infections such as disseminated candidiasis and vaginitis. Recent reports indicate that the fungus is a main etiological agent for the arthritis. In search of new sources for treatment of the fungal arthritis, we examined $18{\beta}$-glycyrrhetinic acid ($18{\beta}$-GA) against C. albicans-caused septic arthritis. The compound is isolated from Glycyrrhizae Radix that is known to have various immunomodulating activities and is one of the most popular herbal medicines. For induction of animal model of a septic arthritis, mice were given an emulsion form of C. albicans cell wall mixed with Complete Freund's Adjuvant (CFA) via footpad-injection. To determine prophylactic and therapeutic effects, the component was given to the animals before or after the induction of the arthritis, respectively. Data showed that intraperitoneal administration of $18{\beta}$-GA resulted in reduction of the inflammation, indicating the component had both prophylactic and therapeutic activities. For investigation of mechanism of the $18{\beta}$-GA, inhibitory effects on NO (nitiric oxide) and on T-lymphocyte proliferation were determined. Results demonstrated that $18{\beta}$-GA suppressed NO production from LPS (lipopolysaccharide)-treated macrophages and also inhibited proliferation of Con A (concanavalin A)activated T-cells. Taken together, $18{\beta}$-GA, a pentacyclic triterpene, has anti-arthritic activity against C. albicans-caused septic arthritis, possibly by blocking NO production and T-cell suppression.

• IMMUNE NETWORK
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• 제7권1호
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• pp.31-38
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• 2007

Background: Mizoribine (MZR) is an imidazole nucleoside isolated from Eupenicillium brefeldianum. MZR is currendy in clinical use for patients who have undergone renal transplantation. Therapeutic efficacy of MZR has also been demonstrated in rheumatoid arthritis and lupus nephritis. MZR has been shown to inhibit the proliferation or lymphocytes by interfering with inosine monophosphate dehydrogenase. Since the exact mechanism by which MZR benefits rheumatoid arthritis (RA) is not clear, we investigated the ability of MZR to direct its immunosuppressive influences on other antigen presenting cells, such as macrophages. Methods: Mouse macrophage RAW264.7 cells were stimulated with lipopolysaccharide in the presence of MZR. To elucidate the mechanism of the therapeutic efficacy in chronic inflammatory diseases, we examined the effects of MZR on the production of pro-inflammatory cytokines, nitric oxide (NO) and prostaglandin $E_2\;(PGE_2)$ in macrophages. Results: MZR dose-dependendy decreased the production of nitric oxide and pro- inflammatory cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukins $1{\beta}$ (IL-${\beta}$ and IL-6 $PGE_2$. Examination of gene expression levels showed that the anti-inflammatory effect correlated with the down-regulation of inducible nitiric oxide synthase expression, cycloxygenase-2 expression and TNF-${\alpha}$ gene expression. Conclusion: In this work, we resulted whether MZR $(1.25{\sim}10{\mu}g/ml)$ inhibited macrophage activation by inhibiting secretion of pro-inflammatory cytokines, NO and $PGE_2$. These findings provide an explanation for the therapeutic efficacy of MZR in chronic inflammation-associated diseases.

• 약학회지
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• 제49권5호
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• pp.422-427
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• 2005

Our previous data showed the protein isolated from Coptidis Rhizoma (CRP) had antifungal activity. In present study, we examined mode of action of the CRP and its activity against subcutaneous candidiasis due to C. albicans yeast cells. Results showed that the CRP blocked hyphal production from yeast form of C. albicans. The CRP also activated RAW 264.7 monocyte/macrophage cell line, which resulted in nitiric oxide (NO) production from the cells. This activation seemed to increase macrophage phagocytosis to destroy the invaders. Like other antimicrobial peptides, CRP was influenced by ionic strength, thus resulting in a decrease of antifungal activity. In murine model of a subcutaneous candidiasis, the sizes of infected areas of the nude mice given the CRP after subcutaneous injection of C. albicans yeast cells to the dorsal skin were $90\%$ less than those of the nude mice groups that received DPBS instead of the CRP. All data indicate that the CRP, which appeared to act like an antimicrobial peptide and to inhibit the morphological transition from blastoconidia, was effec­tive against the subcutaneous disease.

• KSBB Journal
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• 제30권4호
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• pp.182-190
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• 2015

The Zostera marina ethanolic extract (ZMEE) was tested in this study to investigate the anti-inflammatory activity in LPS-induced RAW 264.7 cells and mouse model. Nitric oxide production and inducible nitiric oxide synthase expression in cells treated with ZMEE was reduced significantly in a dose-dependent manner. Similarly, the secretion of pro-inflammatory cytokines such as interleukin (IL)-6, IL-$1{\beta}$, and TNF-${\alpha}$ was inhibited markedly. In addition, the expression of nuclear factor kappa B (NF-${\kappa}B$) and the phosphorylation of JNK, ERK, and p38 MAPKs was suppressed by ZMEE as well. In vivo test, ZMEE attenuated the croton oil-induced mouse ear edema and there were no mortalities in mice administered 5,000 mg/kg body weight of ZMEE during the observation periods. The results in photomicrograph of mice ear tissue showed the reduction of dermal thickness and the number of infiltrated mast cells. These results indicate that ZMEE inhibits the production of LPS-induced pro-inflammatory mediators, suggesting that ZMEE may be a potential material for anti-inflammatory therapies.

• 생명과학회지
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• 제16권7호
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• pp.1181-1187
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• 2006

본 연구는 염증 형성과정에 있어서, 해조류로부터 항염증 효과를 나타내는 물질을 분리하여 그 유도체인 HS-1580 series (HS-1580, HS-1581, HS-1582)를 합성하였다. Nitiric oxide (NO) 생성에 있어 Raw 264.7 cells에서 lipopolysaccharide(LPS) 단독으로 처리하였을 때는 대조군에서보다 4배 이상 NO 생성이 증가하였지만, HS-1580 series를 처리하고 LPS를 처리한 군에서는 농도 의존적으로 NO 생성이 억제되었다. HS-1580 series가 NO 생성 자체를 억제함으로서 NO 함량이 감소되었는지, inducible NOS (iNOS) 단백질 발현을 억제에 기인한 것인지 알아보기 위해서 Western blot으로 조사하였다. iNOS protein 발현이 HS-1580 series에 의해서 억제되었고 HS-1580 series가 cyclooxygenase-2 (COX-2), tumor necrosis factor-a $TNF-{\alpha}$ 와 $interluekin-1{\beta}\;(IL-1{\beta})$ 생성을 농도 의존적으로 억제시켰다. 이상의 결과로 HS-1580 series가 iNOS 단백질 발현 억제에 기인한 NO 생성억제, COX-2 발현 억제 및 pro-inflammatory cytokines인 $TNF-{\alpha}$ 와 $IL-1{\beta}$ 생성을 억제하는 항염증 효과를 가짐을 알 수 있다.

• 대한한의학방제학회지
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• 제5권1호
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• pp.169-178
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• 1997

동의학(東醫學)에서는 질병의 발생에 대하여 정기(正氣)의 강약(强弱)에 그 관건(關鍵)이 있다하였다. 그리하여 모든 질병의 치료에 있어서도 정기(正氣)의 회복에 중점을 두는 부정법(扶正法)이나 거사법(祛邪法)을 사용하면서도 정기(正氣)에 손상(損傷)을 입히지 않도록 많은 관심을 기우리고 있다. 암(癌)의 치료 또한 정기(正氣)가 얼마만큼 보충되는가에 따라 항병능력(抗病能力)이 항진(亢進)된다할 수 있을 것이다. 현재 국내외적(國內外的)으로 악성종양(惡性腫瘍)을 치료하기 위하여 다방면으로 연구를 하고 있으며, 또한 실제로 사용하고 있는 치료방법들로는 수술요법(手術療法) 방사선요법(放射線療法) 면역료법(免疫療法) 화학요법(化學療法)등이 있지만 아직까지는 미흡한 상태라 할 수 있을 것이다. 현재 일반적으로 항암제(抗癌劑)를 이용한 화학요법(化學療法) 등이 사용되고 있고, 면역료법(免疫療法)을 위한 많은 방법들이 연구되고 있어 본 저자(著者)들은 천문동(天門冬)이 면역세포(免疫細胞)의 증식(增殖)을 촉진시켜주면서 항암작용(抗癌作用)이 있을 것으로 사료(思料)되는 바 피부암세포(皮膚癌細胞)인 A431 cell line과 골수암세포(骨髓癌細胞)인 KHOS-NP cell line에 천문동(天門冬)을 투여(投與)하여 암세포(癌細胞)의 증식(增殖)을 살펴보고, 면역세포(免疫細胞)인 T cell과 B cell의 증식(增殖)을 살펴보았다. 또한 복강내(腹腔內) macrophage에서 분비되는 NO의 양(量)을 In vitro와 In vivo실험(實驗)을 통하여 살펴보았고, T cell의 apoptosis 및 subpopulation의 양(量)을 관찰하였다. 이 결과(結果) 천문동(天門冬)은 A431 cell 및 KHOS-NP cell에 항암작용(抗癌作用)을 보였고, T-cell의 증식(增殖)을 촉진시켰으며, 마우스 복강내(腹腔內) macrophage에서 분비(分泌)되는 NO의 양(量)을 감소시켜고, T cell의 apoptosis에 있어서는 대조군(對照群)에 비하여 유의성(有意性)있게 증가(增加)시켰으며, subpopulation에서는 $T_H$ cell을 증가(增加)시켰다. 그리하여 천문동(天門冬)은 항암작용(抗癌作用) 뿐만아니라 면역세포(免疫細胞)의 증식(增殖)에도 관여하는 약물(藥物)로 인정(認定)할 수 있을 것으로 사료(思料)된다.

• 동의생리병리학회지
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• 제30권3호
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• pp.164-176
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• 2016

This study was perfomed to investigate the effects of Chunghyul-plus(CHP) on oxidative damage and hyperlipidemia in db/db mouse. After treatment with CHP, safety in cytotoxicity, heavy metal toxicity, production of reactive oxygen species(ROS), nitric oxide (N0) and proinflammatory cytokine IL-Ib, TNF-a, IL-6 in RAW 264.7 cells. Serum total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, insulin, GLP-1, glucose, food intake, body weight, organ weight, AST, ALT, ALP, BUN, creatine and histologic change of liver and aorta were measured in db/db mouse after oral administration of CHP. CHP showed safety in cytotoxicity and toxicity of liver and kidney for logn time administration. CHP increased the DPPH and ABTS radical scavenging activity. CHP showed significant inhibitory effect on reactive oxygen species (ROS), and showed inhibitory effect on nitiric oxide(NO) compared to control group. CHP decreased cytokine IL-6 production significantly, and decreased IL-1β and TNF-α compared to control group. CHP decreased body and organ weitht, intake food, and glucose levels compared to control group. CHP decreased total cholesterol and triglyceride significantly, and decreased LDL-cholesterol levels and increased HDL-cholesterol levels compared to control group. CHP decreased atherogenic index and cardiac risk factor significantly. CHP increased serum insulin and GLP-1 compared to control group. In histologic examination, lipophagy in the liver and aorta decreased in CHP treated mice and the cell was regular and boundary of vessel wall was clear compared to control group. These results suggest that CHP is effective in antioxidation activity and treatment and prevention of hyperlipidemia, atherosclerosis, diabetes, ischemic heart disease, stroke and other cardiocerebrovascular disease.