• Bulletin of the Korean Chemical Society
• /
• 제29권3호
• /
• pp.647-655
• /
• 2008

Microsomal prostaglandin E2 synthase (mPGES-1) is a potent target for pain and inflammation. Various QSAR (quantitative structure activity relationship) analyses used to understand the factors affecting inhibitory potency for a series of MK886 analogues. We derived four QSAR models utilizing various quantum mechanical (QM) descriptors. These QM models indicate that steric, electrostatic and hydrophobic interaction can be important factors. Common pharmacophore hypotheses (CPHs) also have studied. The QSAR model derived by best-fitted CPHs considering hydrophobic, negative group and ring effect gave a reasonable result (q2 = 0.77, r2 = 0.97 and Rtestset = 0.90). The pharmacophore-derived molecular alignment subsequently used for 3D-QSAR. The CoMFA (Comparative Molecular Field Analysis) and CoMSIA (Comparative Molecular Similarity Indices Analysis) techniques employed on same series of mPGES-1 inhibitors which gives a statistically reasonable result (CoMFA; q2 = 0.90, r2 = 0.99. CoMSIA; q2 = 0.93, r2 = 1.00). All modeling results (QM-based QSAR, pharmacophore modeling and 3D-QSAR) imply steric, electrostatic and hydrophobic contribution to the inhibitory activity. CoMFA and CoMSIA models suggest the introduction of bulky group around ring B may enhance the inhibitory activity.

• Restorative Dentistry and Endodontics
• /
• 제24권3호
• /
• pp.437-446
• /
• 1999

Porphyromonas endodontalis(P. endodontalis) is one of the important causative bacteria of pulpal and periapical disease. P. endodontalis has lipopolysaccharide(LPS) and it plays a major role in stimulating the synthesis and release of cytokines from immune cells and prostaglandin $E_2$ from host cells. The purpose of this study is to prepare LPS from P. endodontalis and to evaluate the effect of LPS on membrane permeability of fibroblast. P. endodontalis ATCC 35406 was cultured in anaerobic condition, and LPS was extracted. LPS was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Human periodontal ligament cell, colon fibroblast(CCD-18Co, KCLB 21459) and skin fibroblast(Detroit 551, KCLB 10110) were perfused with 0.01% P. endodontalis LPS solution, high concentration of $K^+$ solution and $Ca^{2+}$-free solution, $Ca^{2+}$ concentration ratio was measured by microfluorometry. 1. Intracellular $Ca^{2+}$ concentration was not changed in human periodontal fibroblast and skin fibroblast(Detroit 551) stimulated by P. endodontalis LPS. 2. Intracellular $Ca^{2+}$ concentration was increased in colon fibroblast(CCD-18Co) stimulated by P. endodontalis LPS. 3. Colon fibroblast(CCD-18Co) has voltage dependent $Ca^{2+}$ channel activated by high concentration of $K^+$ solution. 4. P. endodontalis LPS has no effect on the increase of intracellular $Ca^{2+}$ concentration during perfusion of $Ca^{2+}$-free solution.

• 한국식품저장유통학회지
• /
• 제19권2호
• /
• pp.287-293
• /
• 2012

본 연구에서는 HMGB1 의해 증가되는 각종 염증관련물질에 대해 라이코펜이 가지는 저해 역할을 규명하고 하였다. 라이코펜은 HMGB1에 의해 증가되는 MCP-1, IL-8, sPLA2-IIA, PGE2의 발현을 NF-${\kappa}B$ 그리고 TNF-${\alpha}$의 활성를 저해함으로써 감소시켰다. 특히, 1 mM에서 그 효능이 통계적으로 유효하였다. 결론적으로 HMGB1에 의해서 발생하는 각종 혈관염증질환에서 라이코펜은 증가하는 각종 염증관련물질을 저해하였고, 결국 라이코펜이 패혈증을 포함하는 염증질환을 효과적으로 치료할 수 있는 방법에 있어 많은 방향성을 제시할 것으로 기대한다.

• 대한한방부인과학회지
• /
• 제19권1호
• /
• pp.139-154
• /
• 2006

Objective : This experimental study was carried out to investigate anti-coagulation effects and mechanism of Hongdeung-tang on the dissentimenated intravascular coagulation Methods : Each 10 rats were classified as normal gorup, control group and treated group. The control group was given a 0.5mg/ml endotoxin intra-vein injection and was occurred Disseminated Intravascular Coagulation(DIC). The treated group were orally administrated 1ml Hongdeung-tang concentration once a day for 6 days and then it was treated the same as the control group. We took the blood from heart and were investigated number of Platelet and white blood cell(WBC), fibrinogen concentration, prothrombin time(PT), activated partial thromboplastin time(APTT), interleukin-6(IL-6), Tumor Necrosis $Factor-{\alpha}(TNF-{\alpha})$, Prostaglandin $E2(PGE_2)$ from them. Results : There were a statistically significant increase of platelet and fibrinogen concentration in the treated group compared to the treated group. The PT was a significantly reduced in treated group compared to the control group. There was no significant change in numbers of WBC and APTT between control and treated group. On the contrary, the number of PT, IL-6, $TNF-{\alpha}$, $PGE_2$ were significantly decreased in treated group compared to the control group. Conclusion : DIC which was occurred by endotoxin intravenous injection seems to related to the increase of IL-6, $TNF-{\alpha}$, $PGE_2$ and Hongdeung-tang has an effect that supress those factors. we can assume Hongdeung-tang has an anti-coagulation effect by those supressing effect.

• 생명과학회지
• /
• 제18권1호
• /
• pp.96-102
• /
• 2008

이상의 연구 결과에 의하면 piceatannol의 처리에 의한 U937 세포의 증식억제는 세포주기 S기 arrest 및 apoptosis 유발과 뚜렷한 연관성이 있었다. 또한 piceatannol은 hTERT 및 TEP-1 유전자의 발현 저하와 연관된 telomerase 활성의 저하 효과도 나타내었으나, COXs의 발현 및 PGE2의 생성에는 큰 변화를 주지 못하였다. 따라서 본 연구의 결과는 암세포에서 높게 발현되는 telomerase 활성 조절제로서 piceatannol의 적용이 가능함을 보여주며, 이는 piceatannol의 항암작용을 이해하는데 매우 유용한 자료라 생각한다.

• 한방안이비인후피부과학회지
• /
• 제26권4호
• /
• pp.70-80
• /
• 2013

Objectives : Haliotidis Concha has been used to treat various human diseases such as liver dysfunction and inflammatory disorder. Although it has been shown the effects of Haliotidis Concha on the various diseases, it has almost not been studied about the anti-inflammatory effects of the Haliotidis Concha and its mechanisms. Methods : This research investigated the effects of the Haliotidis Concha ethanol extract (HCE) on the production of nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) as well as tumor necrosis factor-alpha (TNF-${\alpha}$). The protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were assayed by immunoblot analyses, and the productions of NO, $PGE_2$ and TNF-${\alpha}$ were assessed by ELISA. Results : Haliotidis Concha decreased the production of NO and $PGE_2$, and inhibited the expression iNOS and COX-2 proteins in a concentration-dependent manner in LPS-treated Raw 264.7 cells. HCE suppressed the ability of LPS to activate the signaling pathways of nuclear factor kappa B (NF-${\kappa}B$) as indicated by HCE inhibited nuclear NF-${\kappa}B$ level and I-${\kappa}B{\alpha}$ phosphorylation. Also, HCE inhibited mitogen-activated protein kinases (MAPKs). Conclusions : HCE repressed the production of LPS-inducible NO, $PGE_2$ and TNF-${\alpha}$, which may be mediated by inhibition of NF-${\kappa}B$ translocation. This study suggest the use for the treatment of acute inflammatory disorders.

• 한국자원식물학회:학술대회논문집
• /
• 한국자원식물학회 2010년도 정기총회 및 추계학술발표회
• /
• pp.13-13
• /
• 2010

In the present study, the chemical constituents of Artemisia fukudo essential oil (AFE) were investigated using GC-MS. The major constituents were ${\alpha}$-thujone (40.28%), ${\beta}$-thujone (12.69%), camphor (6.95%) and caryophyllene (6.01%). We also examined the effects of AFE on the production of nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-IL-$1{\beta}$ (IL-$1{\beta}$), and IL-6 in lipopolysaccharide (LPS)-activated RAW 264.7 cells. Western blotting and RT-PCR analyses indicated that AFE has potent dose-dependent inhibitory effects on pro-inflammatory cytokines and mediators. We investigated the mechanism by which AFE inhibits NO and $PGE_2$ by examining the level of nuclear factor-${\kappa}B$ (NF-${\kappa}B$: p50 and p65) activation within the mitogen-activated protein kinase (MAPK: ERK, JNK and p38) pathway, which is an inflammation induced signal pathway in RAW 264.7 cells. AFE inhibited LPS-induced ERK, JNK and p38 phosphorylation. Furthermore, AFE inhibited the LPS-induced phosphorylation and degradation of $I{\kappa}B-{\alpha}$, which is required for the nuclear translocations of the p50 and p65 NF-${\kappa}B$ subunits in RAW 264.7 cells. Our results suggest that AFE might exert an anti-inflammatory effect by inhibiting the expression of pro-inflammatory cytokines. Such an effect is mediated by a blocking of NF-${\kappa}B$ activation which consequently inhibits the generation of inflammatory mediators in RAW 264.7 cells. AFE may be useful for treating inflammatory diseases.

• 대한한의학회지
• /
• 제30권1호
• /
• pp.150-162
• /
• 2009

Objectives: Inflammatory mediators, such as nitric oxide (NO), prostaglandin E2 ($PGE_2$) and pro-inflammatory cytokines, TNF-${\alpha}$ and IL-$1{\beta}$ playa critical role in inflammatory immune response. Therefore, intervention of inflammatory mediator production promises therapeutic benefit for treatment of many chronic inflammatory diseases, such as allergic asthma, rheumatoid arthritis, multiple sclerosis, septic shock and neurodegenerative diseases. In this study, the pharmacological effects of the flower MeOH extract Panax notoginseng (Notoginseng Flos; NF) on inflammation were investigated to address potential therapeutic or toxic effects. Methods: RA W264.7 cells were treated with different concentrations of NF methanol (NF-M) extract in the presence or absence of LPS ($1{\mu}g/m{\ell}$). Results: NF-M extract significantly inhibited LPS-induced production of NO, $PGE_2$ and pro-inflammatory cytokines, TNF-${\alpha}$ and IL-$1{\beta}$ in a dose-dependent manner. In addition, NF-M extract suppressed mRNA expressions and protein levels of iNOS, COX-2 and pro-inflammatory cytokines in LPS-stimulated RA W264.7 cells. Conclusion: These results indicated that NF-M extract inhibits LPS-induced production of inflammatory mediators in macrophages and demonstrated that NF-M extract possesses anti-inflammatory properties in vitro.

• 대한한의학회지
• /
• 제31권3호
• /
• pp.47-54
• /
• 2010

Objective: To derive information on the efficacy of Sam-chul-kun-bi-tang (SKT), by evaluating its anti-inflammatory effect. SKT is a widely-used herbal formula in traditional Korean medicine. In man y studies, plant-derived anti-inflammatory efficacies have been investigated for their potential inhibitory effects on lipopolysaccharide (LPS)-stimulated macrophages. This study was performed to examine the anti-inflammatory effects of SKT extract on LPS-stimulated RAW 264.7 cells. Methods: The production of nitric oxide (NO), prostaglandin $(PG)E_2$, tumor necrosis factor (TNF)-$\alpha$ and interleukin (IL)-6 were examined in a macrophage cell line, RAW 264.7 cells, in the presence of SKT. RAW 264.7 cells were incubated with LPS 1 ${\mu}g/mL$ and SKT for 18 hrs. The anti-inflammatory activity of SKT was investigated by carrageenan-induced paw edema in rats. The paw volume was measured at 2 and 4 hrs following carrageenan-induced paw edema in rats. Results: SKT showed inhibitory effect on $PGE_2$, TNF-$\alpha$ and IL-6 in LPS-stimulated RAW 264.7 cells. But SKT was not inhibitory effect on NO by LPS-stimulated RAW 264.7 cells. Administration of SKT (1 g/kg) also showed a reduction in carrageenan-induced paw edema on rats. Conclusion: These results suggest that SKT has anti-inflammatory activities in both in vitro and in vivo models.

• Clinical and Experimental Pediatrics
• /
• 제55권10호
• /
• pp.377-382
• /
• 2012

Purpose: This single-center study aimed to assess the clinical features and surgical approaches and outcomes of complete transposition of the great arteries (TGA). Methods: TGA patients who had undergone surgical correction at the Kyungpook National University Hospital from January 2000 to December 2010, were retrospectively evaluated for patient characteristics, clinical manifestation, preoperative management, intraoperative findings, postoperative progress, and follow-up status. Results: Twenty-eight patients (17 boys and 11 girls, mean age=$10.6{\pm}21.5$ days) were included and were categorized as follows: group I, TGA with intact ventricular septum (n=13); group II, TGA with ventricular septal defect (VSD, n=12); and group III, TGA/VSD with pulmonary stenosis (n=3). Group I underwent the most intensive preoperative management (balloon atrial septostomy and prostaglandin E1 medication). Group II showed the highest incidence of heart failure (P<0.05). Usual and unusual coronary anatomy patterns were observed in 20 (71%) and 8 patients, respectively. Arterial and half-turned truncal switch operations were performed in 25 and 3 patients (Group III), respectively. Postoperative complications included cardiac arrhythmias (8 patients), central nervous system complications (3 patients), acute renal failure (1 patient), infections (3 patients), and cardiac tamponade (1 patient), and no statistically significant difference was observed between the groups. Group II showed the mildest aortic regurgitation on follow-up echocardiograms (P<0.05). One patient underwent reoperation, and 1 died. The overall mortality rate was 4%. Conclusion: Our study showed favorable results in all the groups and no significant difference in postoperative complication, reoperation, and mortality among the groups. However, our results were inadequate to evaluate the risk factors for reoperation and mortality owing to the small number of patients and short follow-up duration.