• 동의생리병리학회지
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• 제26권6호
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• pp.874-885
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• 2012

In the present study, the possibility of whether the pharmacological effects of Scutellariae Radix Aqueous Extracts(SR) were favorably changed by report that lipopolysaccharide(LPS)-induced rat acute lung injury was treated with Red-Koji(Monascus purpureus 12002) fermentation. Three different dosages of Red-Koji fermented SR extract(fSR), 125, 250 and 500 mg/kg were orally administered once a day for 28 days before LPS(Escherichia coli 0111:B4) treatments, and then 5 hours after LPS treatment(500 ${\mu}g$/head, intra trachea instillation), all rats were sacrificed. Changes in the body weights, lung weights, pulmonary transcapillary albumin transit, arterial gas parameters(pH, $PaO_2$ and $PaCO_2$) bronchoalveolar lavage fluid(BALF) protein, lactate dehydrogenase(LDH) and proinflammatory cytokine tumor necrosis factor-${\alpha}$(TNF-${\alpha}$), interleukin-$1{\beta}$(IL-$1{\beta}$) contents, total cell numbers, neutrophil and alveolar macrophage ratios, lung malondialdehyde(MDA), myeloperoxidase(MPO), proinflammatory cytokine TNF-${\alpha}$ and IL-$1{\beta}$ contents were observed with histopathology of the lung, changes on luminal surface of alveolus(LSA), thickness of alveolar septum, number of polymorphonuclear neutrophils(PMNs). As results of LPS-injection, dramatical increases in lung weights, pulmonary transcapillary albumin transit increases in $PaCO_2$, decreases in pH of arterial blood and $PaO_2$, increases of BALF protein, LDH, TNF-${\alpha}$ and IL-$1{\beta}$ contents, total cells, neutrophil and alveolar macrophage ratios, lung MDA, MPO, TNF-${\alpha}$ and IL-$1{\beta}$ contents increases were detected with decreases in LSA and increases of alveolar septum and PMNs numbers, respectively as compared with intact control. Especially fSR 125 mg/kg showed quite similar favorable effects on the LPS-induced acute lung injuries as compared with 60 mg/kg of ${\alpha}$-lipoic acid and 250 mg/kg of SR. The results suggest that over 125 mg/kg of fSR extracts showed favorable effects on the LPS-induced acute lung injury mediated by their antioxidant and anti-inflammatory effects. Moreover, increases of the pharmacological effects of SR on LPS-induced acute lung injury were observed by Red-Koji fermentation in this study, at least 2-fold higher.

• 한국수정란이식학회지
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• 제21권3호
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• pp.241-245
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• 2006

본 연구는 젖소에 있어서 lipopolysaccharide의 처리가 번식 성적에 미치는 영향을 구명하기 위하여 2003년부터 2005년까지 3년간에 걸쳐 축산연구소 개방형 깔짚우사에서 사육중인 홀스타인 착유우 50두를 대상으로 처리구 및 대조구 각각 25두씩을 공시하였고 분만후 20일째에 1회에 한하여 Bacteroids helcogenes와 Fusobacterium varium으로부터 분리한 LPS $100{\mu}g$을 PBS 용액 35 ml에 희석하여 수정란 이식용 카테타로 자궁내에 주입한 후 발정 발현시 인공 수정을 실시하여 다음과 같은 결과를 얻었다. 1. LPS 처리후 첫 수정에 의한 수태율은 대조구 및 처리구가 각각 20.0% 및 56.0%로 처리구가 대조구에 비하여 높은 경향을 나타내었다. 2. LPS 처리후 2회 이상 수정에 의한 수태율은 대조구 및 처리구가 각각 40.0% 및 64.0%로 처리구가 대조구에 비하여 높은 경향을 나타내었다. 3. 수태된 개체들의 수태당 종부횟수는 대조구 및 처리구가 각각 $2.0{\pm}0.1$회 및 $1.2{\pm}0.4$회로 처리구가 대조구에 비하여 유의적으로 낮았다(p<0.05).

• International Journal of Oral Biology
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• 제35권3호
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• pp.113-119
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• 2010

Porphyromonas (P.) gingivalis lipopolysaccharide (Pg LPS) is the major pathogenic component of periodontal disease. In this study, we have attempted to determine the expression profiles of the signal transduction pathway genes induced by Pg LPS in comparison with Escherichia (E.) coli LPS (Ec LPS). DC2.4 cells were treated for two hours with $1\;{\mu}g/ml$ of Pg LPS or $0.5\;{\mu}g/ml$ of Ec LPS. The total RNA from these cells was then isolated and reverse-transcribed. Gene expression profiles were then analyzed with a signal transduction pathway finder GEArray Q series kit and significant changes in expression were confirmed by real-time PCR. The microarray results indicated that several genes, including Tnfrsf10b, Vcam1, Scyb9, Trim25, Klk6, and Stra6 were upregulated in the DC2.4 cells in response to Pg LPS treatment, but were downregulated or unaffected by Ec LPS. Realtime PCR revealed that the expression of Trim25, Scyb9 and Tnfrsf10b was increased over the untreated control. Notably, Trim25 and Tnfrsf10b were more strongly induced by Pg LPS than by Ec LPS. These results provide greater insight into the signal transduction pathways that are altered by P. gingivalis LPS.

• Toxicological Research
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• 제22권3호
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• pp.245-251
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• 2006

Nitric oxide(nitrogen monoxide, NO) plays important physiological roles, but excessive generation can be toxic. NO is present in cigarette smoke at up to 1,000 ppm, and probably represents one of the greatest exogenous sources of NO to which humans are exposed. We investigated whether cigarette smoking reduces the production of endogenous NO and whether it influences the action of lipopolysaccharide(LPS) to induce nitric oxide synthase activity in mouse brain. Mice(C57BL6/J) were exposed to cigarette smoke for 8 weeks. LPS was injected intraperitoneally in single or combination with the exposure to cigarette smoke. Six hours after the injection of LPS, mice were sacrificed and sera and brains were collected. Serum concentrations of nitrate and nitrite were not charged by 4-week smoke exposure, but were significantly increased by 6 and 8 weeks of smoke exposure. Interestingly, cigarette smoke reduced the elevation in serum nitrate and nitrite concentrations produced by LPS after 4-week smoking exposure. NO synthase(NOS) activity in brain was upregulated by LPS-administration. However, cigarette smoke exposure remarkably and consistently decreased the LPS-induced activity in mouse brain. This result suggests that cigarette smoking may affect against overproduction of the endogenous NO by LPS through the inhibition of NOS activity induced by LPS in brain or by modulation of the LPS action for the induction of NOS activity. We also suggest the possibility that the exogenous NO evolved in cigarette smoke enables feedback inhibition of NOS activity or other possibility that it attenuates the toxicity of endotoxin LPS in vivo by unknown mechanisms, which should be further studied.

• 동의신경정신과학회지
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• 제33권3호
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• pp.277-285
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• 2022

Objectives: Gastrodia elata (GE) has been used to treat cognition impairment, including Alzheimer's disease (AD) in Korea. The purpose of this study was to investigate the effects of GE water extracts (GEE) on the lipopolysaccharide (LPS)-induced AD model in mice. (Aβ). Methods: We classified six groups as follow; group 1: control (CON), group 2: LPS (0.5 mg/kg/day, four times), group 3: 4 mg/kg donepezil (DP), group 4: 100 mg/kg GEE+LPS, group 5: 200 mg/kg GEE+LPS, group 6: 500 mg/kg GEE+LPS. Results: We found that GEE has an effect that inhibits decrease of discrimination index in object recognition test, as well as spontaneous alteration in the Y-maze test by LPS. Treatment with LPS increased amlyloid-β (Aβ) concentration, and decreased brain-derived neurotrophic factor (BDNF) in cerebral cortex of mice. However, GEE significantly protected against LPS-induced Aβ and BDNF changes. Our findings also showed that the inflammatory cytokines [tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β)] mRNA and protein were up-regulated by the LPS injection. But GEE significantly suppressed LPS-induced inflammatory cytokines increase in a dose-dependent manner. Conclusions: This study suggests that the GEE may be an effective AD therapeutic agent, in treating neurodegenerative diseases including AD.

• Animal Bioscience
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• 제37권1호
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• pp.131-141
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• 2024

Objective: This experiment aimed to explore the protective action of dietary supplementation with isoquinoline alkaloids (IA) from Macleaya cordata on lipopolysaccharide (LPS)-induced liver injury in broilers. Methods: Total 216 healthy broilers were selected in a 21-d trial and assigned randomly to the following 3 treatments: control (CON) group, LPS group, and LPS+IA group. The CON and LPS groups were provided with a basal diet, whereas the LPS+IA group received the basal diet supplemented with 0.6 mg/kg Macleaya cordata IA. Broilers in LPS and LPS+IA groups were intraperitoneally injected with LPS (1 mg/kg body weight) at 17, 19, and 21 days of age, while those in CON group were injected with equivalent amount of saline solution. Results: Results showed LPS injection caused systemic and liver inflammation in broilers, inhibited immune function, and ultimately lead to liver injury. By contrast, supplementation of IA ameliorated LPS-induced adverse change in serum parameters, boosted immunity in LPS+IA group. Furthermore, IA suppressed the elevation of hepatic inflammatory cytokines and caspases levels induced by LPS, as well as the expressions of genes related to the toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88)/nuclear factor-kappa B (NF-κB) pathway. Conclusion: Dietary inclusion of 0.6 mg/kg Macleaya cordata IA could enhance immune function of body and inhibit liver damage via inactivating TLR4/MyD88/NF-κB signaling pathway in broilers.

• Animal Bioscience
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• 제37권2호
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• pp.303-314
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• 2024

Objective: Rutin, also called vitamin P, is a flavonoids from plants. Previous studies have indicated that rutin can alleviate the injury of tissues and cells by inhibiting oxidative stress and ameliorating inflammation. There is no report on the protective effects of rutin on goat rumen epithelial cells (GRECs) at present. Hence, we investigated whether rutin can alleviate lipopolysaccharide (LPS)-induced damage in GRECs. Methods: GRECs were cultured in basal medium or basal medium containing 1 ㎍/mL LPS, or 1 ㎍/mL LPS and 20 ㎍/mL rutin. Six replicates were performed for each group. After 3-h culture, the GRECs were harvested to detect the relevant parameters. Results: Rutin significantly enhanced the cell activity (p<0.05) and transepithelial electrical resistance (TEER) (p<0.01) and significantly reduced the apoptosis rate (p<0.05) of LPS-induced GRECs. Rutin significantly increased superoxide dismutase, glutathione peroxidase, and catalase activity (p<0.01) and significantly decreased lactate dehydrogenase activity and reactive oxygen species and malondialdehyde (MDA) levels in LPS-induced GRECs (p<0.01). The mRNA and protein levels of interleukin 6 (IL-6), IL-1β, and C-X-C motif chemokine ligand 8 (CXCL8) and the mRNA level of tumor necrosis factor-α (TNF-α) and chemokine C-C motif ligand 5 (CCL5) were significantly increased in LPS-induced GRECs (p<0.05 or p<0.01), while rutin supplementation significantly decreased the mRNA and protein levels of IL-6, TNF-α, and CXCL8 in LPS-induced GRECs (p<0.05 or p<0.01). The mRNA level of toll-like receptor 2 (TLR2), and the mRNA and protein levels of TLR4 and nuclear factor κB (NF-κB) was significantly improved in LPS-induced GRECs (p<0.05 or p<0.01), whereas rutin supplementation could significantly reduce the mRNA and protein levels of TLR4 (p<0.05 or p<0.01). In addition, rutin had a tendency of decreasing the protein levels of CXCL6, NF-κB, and inhibitor of nuclear factor kappa-B alpha (0.05

• The Korean Journal of Physiology and Pharmacology
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• 제17권2호
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• pp.133-137
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• 2013

Vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), P- and E-selectin play a pivotal role for initiation of atherosclerosis. Ginsenoside, a class of steroid glycosides, is abundant in Panax ginseng root, which has been used for prevention of illness in Korea. In this study, we investigated the mechanism(s) by which ginsenoside Rg2 may inhibit VCAM-1 and ICAM-1 expressions stimulated with lipopolysaccharide (LPS) in human umbilical vein endothelial cell (HUVEC). LPS increased VCAM-1 and ICAM-1 expression. Ginsenoside Rg2 prevented LPS-mediated increase of VCAM-1 and ICAM-1 expression. On the other hand, JSH, a nuclear factor kappa B (NF-${\kappa}B$) inhibitor, reduced both VCAM-1 and ICAM-1 expression stimulated with LPS. SB202190, inhibitor of p38 mitogen-activated protein kinase (p38 MAPK), and wortmannin, phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, reduced LPS-mediated VCAM-1 but not ICAM-1 expression. PD98059, inhibitor of mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) did not affect VCAM-1 and ICAM-1 expression stimulated with LPS. SP600125, inhibitor of c-Jun N-terminal kinase (JNK), reduced LPS-mediated ICAM-1 but not VCAM-1 expression. LPS reduced IkappaB${\alpha}$ ($I{\kappa}B{\alpha}$) expression, in a time-dependent manner within 1 hr. Ginsenoside Rg2 prevented the decrease of $I{\kappa}B{\alpha}$ expression stimulated with LPS. Moreover, ginsenoside Rg2 reduced LPS-mediated THP-1 monocyte adhesion to HUVEC, in a concentration-dependent manner. These data provide a novel mechanism where the ginsenoside Rg2 may provide direct vascular benefits with inhibition of leukocyte adhesion into vascular wall thereby providing protection against vascular inflammatory disease.

• Journal of Acupuncture Research
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• 제24권1호
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• pp.151-163
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• 2007

Objectives : Juglandis Semen herbal acupuncture solution(JSS) has a broad array of clinical applications in oriental medicine, including treatment of chronic musculoskeletal diseases such as arthritis. This study was performed to investigate the global gene expression profiles using microarray assay in RAW 264.7 cell line treated with JSS and to advance our understanding of the pharmacologic effect of JSS. Methods : Change of the gene expression profile in RAW cell line following treatment with lipopolysaccharide(LPS) alone, or with LPS plus JSS was investigated with a cut-off level of 2 fold change in the expression. Especially, Change of the gene expression by treatment with LPS alone was compared with that by treatment with LPS plus JSS with a cut-off level of 1/2 fold change in the expression. Results: Of the 8170 genes profiled in this study, 51 were upragulated and 21 downregulated following LPS treatment, and 88 were upregulated and 69 downregulated following costimulation of JSS and LPS. Of the 51 genes upregulated following LPS treatment, 10 were downregulated following costimulation of JSS and LPS. Of the 21 genes downregulated following LPS treatment, 3 were upregulated following costimulation of JSS and LPS. Conclusion : JSS treatment induced upregulation of some genes including IL-10 and downregulation of that including MMP13 with its possible implication in an antiinflammatory action of JSS. However, further research on expression profile changes induced by JSS treatment is expected.

• Toxicological Research
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• 제20권3호
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• pp.233-239
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• 2004

The present study was designed to determine the impact of mercury on endotoxin-induced inflammatory cytokine expression and corresponding signal transduction in mouse kidney. Male BALB/c mice were exposed continuously to 0, 0.3, 1.5, 7.5, or 37.5 ppm of mercury in drink-ing water for 14 days and at the end of the treatment period, lipopolysaccharide (LPS, 0.5 mg/kg) was injected intraperitoneally 2 h prior to euthanasia. The doses of mercury and LPS did not cause hepatotoxicity or renal toxicity as indicated by unaltered plasma alanine aminotransferase and aspartate aminotransferase levels, and terminal UTP nucleotide end-labeling assay from kidney, respectively. Mercury decreased kidney glutathione (GSH) and with LPS, it additively decreased GSH. Mercury activated p38 mitogen-activated protein kinase (MAPK) and additively increased LPS-induced p38 MAPK phosphorylation. In contrast, mercury inhibited LPS-induced activation of extra-cellular signal-regulated kinase (ERK) but had no effect alone. Mercury increased the gene expression of tumor necrosis factor $\alpha$ (TN F$\alpha$) and potentiated LPS-induced TNF$\alpha$ expression. Mercury did not affect LPS-induced interleukin-1$\beta$ (IL-1$\beta$) expression but decreased LPS-induced IL-6 expression. These results suggest that low levels of mercury might augment LPS-induced TNF$\alpha$ expression by altering GSH and p38 MAPK. Mercury modulates LPS-induced p38 and ERK activation, and downstream TNF$\alpha$ and IL-6 expression in kidney, respectively.