• 대한본초학회지
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• 제23권3호
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• pp.127-134
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• 2008

Objectives : The present study was designed to investigate whether Ostericum koreanum (OK) could regulate lipopolysaccharide (LPS)-induced inflammatory response in vitro and in vivo. Methods : To evaluate of anti-inflammatory effect of OK, we examined Nitric oxide (NO), proinflammatory cytokines production in LPS-stimulated RAW264.7 cells. Furthermore, we checked molecular mechanism especially in the phosphorylation of mitogen-activated protein kinases (MAPKs) and the degradation of inhibitory kappa B a ($Ik-B{\alpha}$) using western blot and also investigated survival of mice in LPS-mediated endotoxin shock. Results : 1. Extract from OK itself have weak cytotoxic effect on RAW264.7 cells. Extract from OK inhibited LPS-induced NO, tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), interleukin $(IL)-1{\beta}$, IL-6 and IL-10 production in RAW264.7 cells. 2. OK inhibited the phosphorylation of MAPKs, such as p38, extracelluar signal-regulated kinase (ERK1/2) and c-Jun NH2-terminal kinase (JNK) and also the degradation of $I{\kappa}-B{\alpha}$ in the LPS-stimulated RAW264.7 cells 3. OK did not inhibit LPS-induced endotoxin shock. Conclusions : OK down-regulated LPS-induced NO and cytokines production through suppressing activation of MAPKs and degradation of $I{\kappa}-B{\alpha}$. Our results suggested that OK may be a beneficial drug against inflammatory diseases.

• 대한의생명과학회지
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• 제6권2호
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• pp.159-164
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• 2000

혈액 전해질 성분들에 대한 대장균 내독소의 영향을 조사하기 위해 토끼를 대상으로 한 동물실험을 실시하였다. 대장균 내독소 (혈청형 O55 : B5)를 토끼의 귀정맥을 통해 0.10 mg/kg 혹은 0.50 mg/kg 농도로 주입한 후 3, 6, 12, 24시간대에 채혈하여서 $Ca^{++}$, $Mg^{++}$, $Na^{+}$, $K^{+}$, Cl$^{-}$ 농도를 측정하였다. 대조군에 비해, 내독소투여 토끼의 $Ca^{++}$ 농도는 6시간대에 증가하였고, $Mg^{++}$ 농도는 3, 6, 12시간대에, $Na^{+}$과 $K^{+}$는 모든 채혈시간대에, 그리고 Cl$^{-}$ 농도는 3, 12, 24시간대에 각각 유의하게 높았다 (p<0.05). 흥미롭게도, 고 $Mg^{+}$ 혈증 (약 4.0 mg/dL)을 보인 내독소투여 토끼들은 심각한 임상징후들로 인식되는 분비물의 증가, 쇼크, 빈호흡, 경련, 혹은 설사와 같은 증세를 보였다. 본 연구의 결과들은 대장균 내독소가 혈액 전해질 농도의 항상성 혼란을 유도하며 이러한 생리적 불균형은 치명적 상황과 그로 인한 죽음을 야기할 수도 있음을 시사하고 있다.

• 약학회지
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• 제51권1호
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• pp.44-50
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• 2007

Acute septic shock is one of inflammatory diseases mediated by pro-inflammatory cytokines such as tumor necrosis factor (TNF)-${\alpha}$. In this study, we examined the pathological difference and mechanism of lipopolysaccharides isolated from E. coli (E-LPS) or S. abortus (S-LPS) on inducing acute septic shock in ICR mouse. All mice were died by intraperitoneal treatment of S-LPS with 0.75 mg/kg, whereas E-LPS treated with even 3 mg/kg only showed 30% of mice lethal, indicating that S-LPS may be more feasible in triggering a strong septic shock condition. The secretion pattern of TNF-${\alpha}$, a critical pro-inflammatory cytokine in septic shock condition, was also distinct between E-LPS- and S-LPS-treated groups. Thus, S-LPS strikingly increased serum level of TNF-${\alpha}$ (6 ng/ml) at 1 h, while E-LPS just displayed at 2 ng/ml level. However the interaction of S-LPS with LPS receptor toll like receptor (TLR)-4, was not stronger than that of E-LPS, according to experiments with macrophage cell line RAW264.7 cells. Thus, E-LPS rather than S-LPS strongly enhanced the production of TNF-${\alpha}$. Interestingly, S-LPS more strongly up-regulated splenocyte proliferation, compared to E-LPS group, whereas there was no difference between S- or E-LPS treated groups in proliferation of Balb/c- or C57BL/6-originated splenic lymphocytes. Therefore, our data suggest that S-LPS is a more active endotoxin and that the strong septic shock-inducing effect of S-LPS seems due to the enhancement of early TNF-${\alpha}$ production and S-LPS-sensitive lymphocyte proliferation.

• 대한본초학회지
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• 제26권3호
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• pp.23-29
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• 2011

Objective : The purpose of this study was to investigate the anti-inflammatory effects of aqueous extract from Scolopendrae Corpus (SC) on lipopolysaccharide (LPS)-induced inflammatory response. Methods : To evaluate the anti-inflammatory effects of SC, we examined the inflammatory mediators such as nitric oxide (NO) and pro-inflammatory cytokines (TNF-a, inteleukin (IL)-$1{\beta}$ and IL-6) on RAW 264.7 cells. We also examined molecular mechanisms such as mitogen-activated protein kinases (MAPKs) and inhibitory kappa B a ($I{\kappa}$-Ba) using western blot. Furthermore, we also investigated the effect of SC on LPS-induced endotoxin shock. Results : Extract from SC itself had not any cytotoxic effect in RAW 264.7 cells. Aqueous extract from SC inhibited LPS-induced NO production and iNOS expression. SC pre-treatment also inhibited IL-$1{\beta}$, IL-6 production in RAW 264.7 cells. To investigate inhibitory effects of SC on inflammatory mediators, activation of MAPKs was examined. SC inhibited the phosphorylation of p38 kinases (p38), c-Jun $NH_2$-terminal kinase (JNK) and also the degradation of $I{\kappa}$-$B{\alpha}$ in RAW 264.7 cells stimulated with LPS. Furthermore, SC administration reduced LPS-induced endotoxin shock. Conclusion : SC down-regulated LPS-induced production of inflammatory mediators through inhibition of activation of p38, JNK and degradation of $I{\kappa}$-$B{\alpha}$. Taken together, our results suggest that SC may be a beneficial drug against inflammatory diseases such as sepsis.

• 대한한방부인과학회지
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• 제21권4호
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• pp.17-35
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• 2008

Purpose: It is the purpose of this study to investigate the anti-inflammatory effects of water extract from Gagamsoyosan(GGSYS) on the peritoneal macrophage. Methods: To evaluate anti-inflammatory effects of GGSYS. inflammatory cytokines were measured in lipopolysaccharide(LPS) -stimulated macrophages. Furthermore. the western blot has been done to look into the molecular mechanism. Results: GGSYS did not have any cytotoxicity in the peritoneal macrophages and suppressed production of LPS-induced NO. tumor necrosis factor-alpha (TNF-$\alpha$). interleukin(IL)-1$\beta$. IL-6. IL-12. GGSYS inhibited the activation of extracelluar signal-regulated kinase (ERK1/2). c-Jun N-terminal kinase(JNK), p38 kinase and the degradation of inhibitory kappa B-alpha($I_{k}B-\alpha$) in the LPS-stimulated peritoneal macro phages. GGSYS inhibited LPS-induced endotoxin shock and the production of TNF-$\alpha$. IL-l$\beta$. IL-6 in serum from LPS-stimulated mice. Conclusion: These results suggest that GGSYS may have the anti-inflammatory effect which can inhibit the production of NO and inflammatory cytokines. GGSYS is expected to protect against inflammatory diseases.

• 동의생리병리학회지
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• 제16권5호
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• pp.921-927
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• 2002

Inflammation is localized response to foreign substance such as bacteria or in some instance to internally produced substances and has relation with immunity system. The macrophages plays a role in the development of the Iymphohaemopoietic system before and after birth, as well as in the natural and acquired immune responses of adult to immunogens, including infectious agents. NO have been suggested to play an important role in endotoxin-mediated shock and imflammation. In this study, we investigated the effect of Omisodok-eum on the production of NO. The Omisodok-eum inhibited the secretion of NO in LPS-stimulated mouse peritoneal macrophages, without affecting cell viability. The protein level of inducible nitric oxide synlhase(iNOS) in peritoneal macrophages was also decreased by Omisodok-eum. These results suggest that Omisodok-eum suppresses the endotoxin-induced inflammatory responses through inhibiting the production of NO

• 대한수의학회지
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• 제22권2호
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• pp.211-219
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• 1982

닭의 급성(急性) 가금(家禽) 콜레라의 폐사원인(斃死原因)과 기전(機轉)을 구명(究明)하고자 생후(生後) 10~32주령(週齡) 닭에 P. multocida균(菌)을 칠개(七個) 경로(經路)(정맥(靜脈), 근육(筋肉), 피하(皮下), 비강(鼻腔), 구강(口腔), 복강(腹腔) 및 귀)를 통해 주입(注入)해서 가금(家禽) 콜레라를 발병(發病)시키고 파종성(播種性) 혈관내(血管內) 응고(凝固)의 발현여부(發顯與否)와 그 분포(分布) 및 본(本) 질병(疾病) 진행(進行) 과정중(過程中) P. multocida의 endotoxin 역할(役割)에 대하여 연구(硏究)하였다. 파종성(播種性) 혈관내(血管內) 응고(凝固)의 병리조직학적(病理組織學的)인 진단(診斷)은 소동맥(小動脈), 소정맥(小靜脈), 모세혈관(毛細血管) 그리고 다소 큰 혈관내(血管內)에 섬유소성(纖維素性) 혈전(血栓)의 증명(證明)으로 이루어졌다. 각종(各種) 장기내(臟器內) 파종성(播種性) 혈관내(血管內) 응고(凝固)는 주(主)로 3일(日) 이내(以內)에 폐사(斃死)된 닭에서 쉽게 관찰(觀察)할 수 있었고, 장기중(臟器中) 폐(肺)는 혈전(血栓)의 발현빈도(發顯頻度)가 가장 높았으며(90%) 그 다음으로 간(肝)(70%), 신장(腎臟)(60%), 심장(心臟)(20%), 비장(脾臟), 뇌(腦), 췌장(膵臟), 흉선(胸線) 및 갑상선(甲狀腺)의 순(順)이었다. 섬유소성(纖維素性) 혈전(血栓)의 밀도(密度)(조직절편당(組織切片當) 혈전(血栓)의 수(數)) 역시 폐(肺)가 가장 높고 비장(脾臟), 신장(腎臟), 간(肝) 및 심장(心臟)의 순(順)이었다. 급성(急性) 가금(家禽) 콜레라 감염시(感染時) 범발성(汎發性) 출혈(出血)은 파종성(播種性) 혈관내(血管內) 응고(凝固)를 일으키는 P. multocida균(菌)의 endotoxin에 기인(基因)된 것으로 사료(思料)되며 닭의 급성(急性) 가금(家禽) 콜레라의 폐사원인(斃死原因)은 단순(單純)한 출혈성(出血性) 패혈증(敗血症)이 아니라 전신적(全身的)으로 발생(發生)되는 파종성(播種性) 혈관내(血管內) 응고(凝固)를 수반하는 endotoxin(septic) shock사(死)임이 밝혀졌다.

• Toxicological Research
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• 제12권2호
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• pp.195-201
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• 1996

Endotoxic shock causes death in humans and animals via extreme hypoperfusion of peripheral organs. A massive production of nitric oxide (NO) both from the endothelical cells and smooth muscle cells has been proposed as a possible mechanism in this process. Since NO attenuated the contractility to vasoconstricting agents such as norepinephrine (NE) by directly acting on the smooth muscle cells, this mechanism was considered mainly as a postsynaptic mechanism. In this research it was investigated whether NO, thus released, also participates in the presynaptic events for the regulation of vascular tone in endotoxic shock. The role of NO was studied by adding NO donors or NO synthase inhibitor $N^\omega $methyl-L-arginine (NMA) in stimulated sympathetic nerves of the mesenteric vascular bed and the Langendorff heart of rats. Sodium nitroprusside (SNP), an NO donor, reduced the pressor responses of isolated mesenteric artery either to electrical stimulation or exogenously administered phenylephrine (PE). In this mesentery, although neither agent influenced NE release, in the presence of the adrenergic $\alpha_2$-receptor antagonist yohimbine, elecrical stimulation-evoked NE release was augumented by SNP. In the heart SNP facilitated the NE release induced by electrical stimulation, while NMA had no effect. From these results it is proposed that there exists a local reflex phenomenon in the junction between the sympathetic nerve terminals and the smooth muscle of resistance blood vessels; by which sympathetic responses are reduced by NO at the postjunctional level while NO facilitates NE release contributing to augumentation of sympathetic tone. All these facts suggest that NO produced during endotoxic shock has dual effects: whereas NO blunts the vasoconstrictive activity of NE at the postsynaptic level, NO presynaptically facilitates the release of NE from sympathetic nerve terminals.

• Journal of Ginseng Research
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• 제32권4호
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• pp.315-323
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• 2008

In the previous studies, we isolated the compound K rich fractions (CKRF) and showed that CKRF inhibited Toll-like receptor (TLR) 4- or TLR9-induced inflammatory signaling. To extend our previous studies,1) we investigated the molecular mechanisms of CKRF in the TLR4-associated signaling via nuclear factor (NF)-${\kappa}B$, and in vivo role of CKRF for induction of tolerance in lipopolysaccharide (LPS)-induced septic shock. In murine bone marrow-dervied macrophages, CKRF significantly inhibited the induction of mRNA expression of proinflammatory mediators such as tumor necrosis factor-${\alpha}$, interleukin-6, cyclooxygenase-2, and inducible nitric oxide synthase. In addition, CKRF significantly attenuated the transcriptional activities of TLR4/LPS-induced NF-${\kappa}B$. Nuclear translocation of NF-${\kappa}B$ in response to LPS stimulation was significantly abrogated by pre-treatment with CKRF. Furthermore, CKRF inhibited the recruitment of p65 to the interferon-sensitive response element flanking region in response to LPS. Finally, oral administration of CKRF significantly protected mice from Gram-negative bacterial LPS-induced lethal shock and inhibited systemic inflammatory cytokine levels. Together, these results demonstrate that CKRF modulates the TLR4-dependent NF-${\kappa}B$ activation, and suggest a therapeutic role for Gram-negative septic shock.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.249-249
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• 1994

PAF (Platelet-activating factor: 혈소판 활성화인자)는 1972년 Benveniste등에 의해 토끼의 호중구 배양 상청액중에서 발견되어 1979년 그 구조가 1-alkyl-2-acethyl-sn glycero-3-phosphocholine의 구조를 갖는 에테르형 인 지질임이 밝혀졌다. 그후 혈소판 이외 과립구, 단구나 macrophage, 혈관내피세포등 조직의 염증담당세포가 다양한 자극에 응하여 PAF를 생성됨이 보고되었다. PAF가 나타내는 대표적 활성으로는 혈소판, 호중구, 단구들의 활성화, 호중구의 유주 활성, 혈관투과성 항진, 혈압강하작용. 기관지 수축 등이 알려졌으며. 또한 염증, 알러지, 천식 endotoxin shock 등 여러질병에 직·간접적으로 관여함이 알려졌다. 이와같은 여러 생리 현상은 PAF의 특이적수용체를 개재하여 일어난다는 것이 밝혀졌다. 따라서 PAF의 다양한 질병의 관여가 밝혀짐으로서, PAF길항제의 개발이 활발히 진행되어왔다. 지금까지 PAF길항제의 개발은 PAF 구조 유사체. benzodiazepam유도체, thiazole유도체 등과 같은 합성품과 ginkolide, kadsurenone과 같은 천연물 유리의 것이 알려져 in vivo model에서도 그 효능이 확인되었다. 본 연구는 이와 같은 배경에서 20여 종의 생약에서 PAF 길항제를 검색하던 중 5종류의 생약에서 PAF 길항작용을 갖는 분획을 찾았기에 이에 보고한다.