• Biomolecules & Therapeutics
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• 제22권1호
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• pp.27-34
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• 2014

Curcumin is naturally occurring polyphenolic compound found in turmeric and has many pharmacological activities. The present study was undertaken to evaluate anti-allergic inflammatory activity of curcumin, and to investigate its inhibitory mechanisms in immunoglobulin E (IgE)/Ag-induced mouse bone marrow-derived mast cells (BMMCs) and in a mouse model of IgE/Ag-mediated passive systemic anaphylaxis (PSA). Curcumin inhibited cyclooxygenase-2 (COX-2) dependent prostaglandin $D_2$ ($PGD_2$) and 5-lipoxygenase (5-LO) dependent leukotriene $C_4$ ($LTC_4$) generation dose-dependently in BMMCs. To probe the mechanism involved, we assessed the effects of curcumin on the phosphorylation of Syk and its downstream signal molecules. Curcumin inhibited intracellular $Ca^{2+}$ influx via phospholipase $C{\gamma}1$ ($PLC{\gamma}1$) activation and the phosphorylation of mitogen-activated protein kinases (MAPKs) and the nuclear factor-${\kappa}B$ (NF-${\kappa}B$) pathway. Furthermore, the oral administration of curcumin significantly attenuated IgE/Ag-induced PSA, as determined by serum $LTC_4$, $PGD_2$, and histamine levels. Taken together, this study shows that curcumin offers a basis for drug development for the treatment of allergic inflammatory diseases.

• Molecules and Cells
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• 제44권12호
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• pp.893-899
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• 2021

BLT2 is a low-affinity receptor for leukotriene B₄, a potent lipid mediator of inflammation generated from arachidonic acid via the 5-lipoxygenase pathway. The aim of this study was to investigate whether BLT2 plays any role in sepsis, a systemic inflammatory response syndrome caused by infection. A murine model of cecal ligation and puncture (CLP)-induced sepsis was used to evaluate the role of BLT2 in septic inflammation. In the present study, we observed that the levels of ligands for BLT2 (LTB₄ [leukotriene B₄] and 12(S)-HETE [12(S)-hydroxyeicosatetraenoic acid]) were significantly increased in the peritoneal lavage fluid and serum from mice with CLP-induced sepsis. We also observed that the levels of BLT2 as well as 5-lipoxygenase (5-LO) and 12-LO, which are synthesizing enzymes for LTB₄ and 12(S)-HETE, were significantly increased in lung and liver tissues in the CLP mouse model. Blockade of BLT2 markedly suppressed the production of sepsis-associated cytokines (IL-6 [interleukin-6], TNF-α [tumor necrosis factor alpha], and IL-1β [interleukin-β] as well as IL-17 [interleukin-17]) and alleviated lung inflammation in the CLP group. Taken together, our results suggest that BLT2 cascade contributes to lung inflammation in CLP-induced sepsis by mediating the production of inflammatory cytokines. These findings suggest that BLT2 may be a potential therapeutic target for sepsis patients.

• 대한한방부인과학회지
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• 제34권3호
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• pp.29-48
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• 2021

Objectives: Banchong-san (BCS) is a herbal formula composed of 13 korean medicinal herbs and is traditionally used to treat inflammatory diseases and pain. The object of this study was to research the antioxidant, anti-inflammatory, antipruritic and antimicrobial effects of the BCS in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Methods: In this experiment, effects of BCS on the following four were measured as follows: (1) Anti-oxidative effects were evaluated by 1,1-diphenyl-2-picryl-hydrazyl (DPPH) Radical scavenging activity, 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) Radical scavenging activity. (2) Anti-inflammatory effects were evaluated by the production amount of Reactive oxygen species (ROS), Nitric oxide (NO), Interleukin-1β (IL-1β), Interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), Prostaglandin E2 (PGE₂), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2)(the previous two are "mRNA"), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinases (p38), inhibitor of nuclear factor kappa B (IκBα), nuclear factor kappa B (NF-κB) (the previous five are "Protein") in LPS-Stimulated RAW 264.7 cells. (3)Antipruritic effects were evaluated by the production amount of histamine, Leukotriene B4 (LTB4), LeukotrieneC4 (LTC4) Levels in phorbol 12-myristate 13-acetate(PMA)/ionomycin-stimulated MC/9 mast cell. (4) Anti-microbial effects were evaluated by the growth suppression of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Aspergillus niger. Results: The following results were obtained through each measurement: (1) DPPH Radical Scavenging Activity, ABTS Radical Scavenging Activity evoked a significant concentration-dependent increase. (2) ROS, NO, IL-1β, IL-6, TNF-α, PGE₂ production amount, iNOS, COX-2 mRNA expression were significantly reduced in the BCS extraction group compared with the control group and significantly decreased the amount of ERK, JNK, p38, NF-κB Protein expression. The amount of IκB-α Protein Expression have increased significantly. (3) The amounts of histamine, LTB4, LTC4 were significantly decreased. (4) The antibacterial efficacy, BCS inhibited the growth of Escherichia coli, Pseudomonas aeruginosa at concentrations of 5 ㎍/ml, but did not suppress the growth of staphylococcus aureus and aspergillus niger. Conclusions: The experimental results show that BCS has anti-oxidant, anti-inflammatory, antipruritic and antimicrobial properties.

• The Korean Journal of Pain
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• 제32권3호
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• pp.168-177
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• 2019

Background: Brennan's rodent paw incision model has been extensively used for understanding mechanisms underlying postoperative pain in humans. However, alterations of physiological parameters like blood pressure and heart rate, or even feeding and drinking patterns after the incision have not been documented as yet. Moreover, though eicosanoids like prostaglandins and leukotrienes contribute to inflammation, tissue levels of these inflammatory mediators have never been studied. This work further investigates the antinociceptive effect of protein C after intra-wound administration. Methods: Separate groups of Sprague-Dawley rats were used for quantitation of cyclooxygenase (COX) activity and leukotriene B4 level by enzyme-linked immunosorbent assay, as well as estimation of cardiovascular parameters and feeding and drinking behavior after paw incision. In the next part, rats were subjected to incision and $10{\mu}g$ of protein C was locally administered by a micropipette. Both evoked and non-evoked pain parameters were then estimated. Results: COX, particularly COX-2 activity and leukotriene B4 levels increased after incision. Hemodynamic parameters were normal. Feeding and drinking were affected on days 1 and 3, and on day 1, respectively. Protein C attenuated non-evoked pain behavior alone up to day 2. Conclusions: Based upon current observations, Brennan's rodent paw incision model appears to exhibit a prolonged period of nociception similar to that after surgery, with minimal interference of physiological parameters. Protein C, which is likely converted to activated protein C in the wound, attenuated the guarding score, which probably represents pain at rest after surgery in humans.

• Biomolecules & Therapeutics
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• 제23권5호
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• pp.421-427
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• 2015

Imperatorin has been known to exert many biological functions including anti-inflammatory activity. In this study, we investigated the inhibitory effects of imperatorin on the production of inflammatory mediators in mouse bone marrow-derived mast cells (BMMC). Imperatorin inhibited degranulation and the generation of eicosanoids (leukotriene $C_4$ ($LTC_4$) and prostaglandin $D_2$ ($PGD_2$) in IgE/antigen (Ag)-stimulated BMMC. To elucidate the molecular mechanism involved in this process, we investigated the effect of imperatorin on intracellular signaling in BMMC. Biochemical analyses of the IgE/Ag-mediated signaling pathway demonstrated that imperatorin dramatically attenuated degranulation and the production of 5-lipoxygenase-dependent $LTC_4$ and cyclooxygenase-2-dependent $PGD_2$ through the inhibition of intracellular calcium influx/phospholipase $C{\gamma}1$, cytosolic phospholipase $A_2$/mitogen-activated protein kinases and/or nuclear factor-${\kappa}B$ pathways in BMMC. These results suggest that the effects of imperatorin on inhibition of degranulation and eicosanoid generation through the suppression of multiple steps of IgE/Ag-mediated signaling pathways would be beneficial for the prevention of allergic inflammation.

• Journal of Microbiology and Biotechnology
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• 제32권9호
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• pp.1126-1133
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• 2022

This study investigated the contribution of lipoxygenase (LOX) inhibitors, nordihydroguaiaretic acid (NDGA), tetra-O-methyl nordihydroguaiaretic acid (M₄N) and zileuton (ZIL), and thromboxane A2 (TXA₂) inhibitor 4,5-diphenylimidazole (DPI) in the proliferation of Brucella abortus infection. None of the compounds affected the uptake of Brucella into the macrophages. We determined the effect of neutralizing leukotriene B4 (LTB4) receptor and showed that the uptake of the bacteria was inhibited at 30 min post-infection. M₄N treatment attenuated intracellular survival of Brucella at 2 h post-incubation but it was not observed in the succeeding time points. DPI treatment showed reduced survival of Brucella at 24 h post-incubation while blocking LTB4 receptor was observed to have a lower intracellular growth at 48 h post-incubation suggesting different action of the inhibitors in the course of the survival of Brucella within the cells. Reduced proliferation of the bacteria in the spleens of mice was observed in animals treated with ZIL or DPI. Increased serum cytokine level of TNF-α and MCP-1 was observed in mice treated with M₄N or ZIL while a lower IFN-γ level in ZIL-treated mice and a higher IL-12 serum level in DPI-treated mice were observed at 7 d post-infection. At 14 d post-infection, ZIL-treated mice displayed reduced serum level of IL-12 and IL-10. Overall, inhibition of 5-LOX or TXA₂ or a combination therapy promises a potential alternative therapy against B. abortus infection. Furthermore, strong ligands for LTB4 receptor could also be a good candidate for the control of Brucella infection.

• Journal of Nutrition and Health
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• 제40권7호
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• pp.606-615
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• 2007

본 연구에서는 in vitro에서 검색된 산초나무 잎의 용매분획의 항혈전 및 항염증작용을 in vivo에서 확인하고자 고지방식이를 섭취한 흰쥐에게 n-butanol 분획과 methylene chloride분획을 1일 50, 100, 150 mg을 4주간 경구투여 하였다. 혈장 APTT 및 TT는 정상식이군에 비해 고지방식이군에서 유의적으로 감소되었으며, 고지방식이군에 methylene chloride분획 50 mg 이상 공급군은 유의적으로 증가되어 100 mg 이상 공급군은 정상식이군 수준이었다. 다형핵 백혈구 5#-lipoxygenase 활성과 leukotriene $B_4$ 함량이 정상식이군에 비해 고지방식이군에서 증가되었으며, 5#-lipoxygenase 활성은 두 용매 분획을 100 mg 이상 공급한 군들이 모두 감소하였다. 백혈구의 leukotriene $B_4$ 함량은 n-butanol 분획에 의하여 역시 100 mg 이상 공급으로 감소하였으나 methylene chloride 분획에 의하여는 150 mg 공급군에서만 감소하였다. 간 조직 마이크로솜의 cytochrome $P_{450}$ 함량은 정상식이군에 비해 고지방식이군에서 유의적으로 증가되었으며, 두 용매분획의 투여로 감소하는 경향이었으나 butanol 분획 150mg 투여군에서만 유의적으로 감소하였다. 간 조직 $O_2^-$M의 함량과 $H_2O_2$ 함량도 정상식이군에 비해 고지방식이군에서 증가되었으며, butanol 분획 100 mg 이상투여로 $O_2^-$의 함량이 감소하고 methylene chloride분획 100 mg이상에서 $H_2O_2$ 함량이 감소하였고 두 용매 분획을 150 gm 이상 투여하였을 때는 $O_2^-$와 $H_2O_2$함량이 모두 감소하였다. 간 조직 GST 활성과 GSH 함량 및 GSG/GSSG 비율은 정상식이군에 비해 고지방식이군에서 감소되었으며, 두 용매 분획 150 mg 투여로 유의적으로 증가되었으나 GSG/GSSG 비율은 100 mg이상 투여로 증가하였다. 결론적으로, 산초나무 잎의 methylene chloride분획은 고지방식이 흰쥐에서 혈행 장애와 염증 반응을 완화시키고, 간 조직에서의 자유라디칼 생성계를 약화시킬 뿐만 아니라, glutathione계의 환원상태를 유지시킴으로서 신체를 보호하는 효과가 있으며 butanol 분획은 항혈전 효과를 제외한 항염증 및 항산화작용에 의한 신체 보호 작용은 기대된다. 이러한 활성을 이용하면 날로 증가되는 지방섭취량에 의한 만성퇴행성질환을 억제하는데 우수한 기능성식품 소재로써 활용할 수 있다고 생각된다.

• Restorative Dentistry and Endodontics
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• 제21권2호
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• pp.451-469
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• 1996

The purpose of this study was to investigate the effect of calcium hydroxide and glass ionomer cement fillings on the levels of $LTB_4$ and $LTC_4$ in experimentally inflamed rat dental pulp. The dental pulp in the mandibular incisor of wistar rat was irritated by cutting a 5mm deep hole in the dentin with a twist drill bur of 0.5mm diameter, without cooling. The cavities were filled with calcium hydroxide(light-cured) and glass ionomer cement(light cured). The untreated pulp served as control tissue specimen. After cavity preparations, the rat with or without various treatment were sacrificed in various time by decapitation. The dental pulp tissue were carefully removed and the concentrations of $LTB_4$ and $LTC_4$ were determined by radioimmunoassay. And pulps were examined histologically to observe inflammatory feature. The result were obtained as follows : 1. The inflammatory features of pulps were observed microscopically in all experimental groups. And degree of inflammation was decreased with time. 2. The concentrations of $LTB_4$ and $LTC_4$ for all experimental groups were significantly higher than those for control group 6 hours after cavity preparation(p<0.05). 3. The group filled with calcium hydroxide was the lowest, and the group filled with glass ionomer cement, the group of irritation in that order showed increased concentrations of $LTB_4$ and $LTC_4$ 6 hours after cavity preparation. In the concentrations of $LTB_4$, significant differences among 3 groups were noted(p<0.05). 4. The group filled with calcium hydroxide was the lowest, and the group filled with glass ionomer cement, the group of irritation in that order showed increased concentrations of $LTB_4$ and $LTC_4$ 24 hours after cavity preparation. And there were statistically significant difference in concentrations of $LTB_4$ between the group of irritation and the group filled with calcium hydroxide(p<0.05). 5. The group filled with calcium hydroxide was the lowest, and the group filled with glass ionomer cement, the group of irritation in that order showed increased concentrations of $LTB_4$ and $LTC_4$ 48 hours after cavity preparation. But no statistically difference was found (p>0.05). 6. The concentrations of $LTB_4$ and $LTC_4$ in all experimental groups were highest level at 6 hour after experiment and decreased as time progresses(correlation coefficient>0.8).

• 한국식품영양과학회지
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• 제26권4호
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• pp.697-703
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• 1997

본 연구는 급원이 다른 n-3 지방산 섭취가 휜쥐에서 면역반응과 PGE$_2$ 및 LTB$_4$ 생성에 미치는 영항을 알아보기 위해 시도되었다. 실험동물은 생후 4주 정도의 Sp-rague-Dawley종 수컷을 사용하였으며 실험식 이를 4 주간 섭취 시 킨 후 희생하여 면역 실험을 행하였다. 실험 군간의 식이 섭취량, 체중 증가량, 식이 효율, 비장무게는 유의적인 차이가 없었다. 비장세포의 ConA와 PWM에 대한 증식능력 실험 결과는 ConA의 경우, 대조군과 FO군의 증식비율은 비슷하였고 PO군이 약간 높게 나타났으나 유의적인 차이는 없었다. PW의 경우는 대조군 보다 FO군과 PO군이 높게 나타나 n-3 지방산을 섭취한 군들이 증식 능력이 높은 유의적인 차이를 보였다. 그리고 PGE$_2$의 농도는 대조군이 FO군과 PO군에 비해 유의적으로 높았으며, LTB$_4$의 농도는 실험군간의 차이가 나타나지 않았다. 그러므로 비장세포의 PWM에 대한 증식능력이 n-3 지방산을 섭취한 경우에 대조군보다 높았던 것이 PGE$_2$ 농도와 관련이 있는 것으로 보이며 들기름과 어유는 같은 정도의 효과를 가지는 것으로 나타났다.

• 대한치과교정학회지
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• 제24권4호
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• pp.871-883
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• 1994

This experiment was designed to study possible roles of $interleukin-1\beta$, interleukin-6 and tumor necrosis $factor-\alpha$ in bone remodeling by measuring their effects on $PGE_2,\; LTB_4$ and collagenase production when they were administered to human periodontal ligament fibroblasts. Human periodontal ligament fibroblasts were collected from first premolars extracted for orthodontic treatment. They were incubated in the environment of $37^{\circ}C,\;5\%\;Co^2,\;and\;100\%$ humidity. They were treated with $0.25\%$ trypsin-EDTA solution and centrifuged. PDL cells in the fifth to seventh passage were used for the experiment. Cells were seeded onto the culture dishes and when they were successfully attached, human recombinant $interleukin-1\beta$, interleukin-6, and tumor necrosis $factor-\alpha$ were administered, alone or in combination. They were incubated for 4, 8 and 24 hours and the levels of $PGE_2,\;LTB_4$ and collagenase released into the culture media were assessed by enzymeimmunoassay and collagenase activity assay. The conclusions are as follows: 1. $IL-1\beta\;and\;TNF-\alpha$ were very active in stimulating the production of $PGE_2$ and collagenase by human periodontal ligament fibroblasts, while IL-6 increased $LTB_4$ production. 2. $IL-1\beta$ significantly increased $PGE_2$, but $LTB_4$ Production was not increased. $IL-1\beta$ is thought to act mainly via the cyclooxygenase pathway of arachidonic acid metabolism. 3. IL-6 tended to inhibit $IL-1\beta$ in the production of $PGE_2$ and collagense whereas IL-6 and $TNF-\alpha$ showed auditive effect in the level of $PGE_2$. The above cytokines increased the release of at least one of $PGE_2,\;LTB_4$ and collagenase. It suggests that cytokines are involved in bone remodeling process by stimulating PDL fibroblasts to produce various bone-resorptive agents. The roles of cytokines in bone remodeling as a whole would need further study.