• The Korea Journal of Herbology
• /
• v.23 no.3
• /
• pp.127-134
• /
• 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.

• Biomedical Science Letters
• /
• v.6 no.2
• /
• pp.159-164
• /
• 2000

We studied the effects of Escherichia coli (E. coli) endotoxin on blood electrolytes levels in rabbits. Endotoxin (5. coli serotype O55 : B5) was injected via rabbits' ear vein : 0.10 mg/kg (Group A) or 0.50 mg/kg (Group B). Blood samples were taken at postendotoxemic 3, 6, 12 and 24 hrs and were analyzed for detections of the levels of blood electrolytes such as $Ca^{++}$, $Mg^{++}$, Na$^{+}$, $K^{+}$ and Cl$^{-}$. As compared to control group, in endotoxin-treated rabbits $Ca^{++}$ levels elevated at 6 hrs but decreased at 24 hrs, $Mg^{++}$ levels were high at 3, 6 and 12 hrs, Na$^{+}$ and $K^{+}$ levels increased at all sampling times and Cl$^{-}$ levels rose at 3, 12 and 24 hrs (p<0.05). Interestingly, endotoxic rabbits having hypermagnesemia (about 4.0 mg/dL) showed severe syndromes such as increased secretion, shock, tachypnea, seizure and/or diarrhea, suggesting that these may be clinical signs of imminent death in rabbits. These observations testify that bacterial endotoxin leads to dyshomeostasis of blood electrolytes and the physiological imbalances may cause fatal disorders and subsequent death.

• YAKHAK HOEJI
• /
• v.51 no.1
• /
• pp.44-50
• /
• 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.

• The Korea Journal of Herbology
• /
• v.26 no.3
• /
• pp.23-29
• /
• 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.

• The Journal of Korean Obstetrics and Gynecology
• /
• v.21 no.4
• /
• pp.17-35
• /
• 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.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.16 no.5
• /
• pp.921-927
• /
• 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

• Korean Journal of Veterinary Research
• /
• v.22 no.2
• /
• pp.211-219
• /
• 1982

Chickens from 10 to 32 weeks of age were inoculated with P. multocida via seven routs(intravenous, intramuscular, intraperitoneal, subcutaneous, into ear, intranasal, per oral). The development or distribution of disseminated intravascular coagulation (DIC) in multiple organs and the role of P. multocida endotoxins in disease process of fowl cholera were studied. The histological diagnosis of DIC was made by demonstration of fibrinous in arterioles, capillaries, venules and medium-sized blood vessels. The presence of fibrinous thrombi in blood vessels of multiple organs was observed in chickens which died within approximately 3 days post inoculation. Fibrinous thrombi were observed most frequently in the lung(90% of all cases with DIC) followed by liver (70%), kidney (60%), heart(20%), spleen, brain, pancreas, thymus and thyroid gland. The density of fibrinous thrombi (i.e. the number of thrombi per section) was greatest in the lung, followed by spleen, kidney, liver and heart. It is thought that the widespread hemorrhage of acute fowl cholera is also caused by P. multocida endotoxin which initiates DIC in variety of organs. The cause of death for the chickens after infection with acute fowl cholera is probably due to an endotoxin (septic) shock accompanied with DIC in multiple organs.

• Toxicological Research
• /
• v.12 no.2
• /
• pp.195-201
• /
• 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
• /
• v.32 no.4
• /
• pp.315-323
• /
• 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.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1994.04a
• /
• pp.249-249
• /
• 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.