• Journal of Sasang Constitutional Medicine
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• v.14 no.3
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• pp.114-131
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• 2002

1. PURPOSE : The purpose of this study is to investigate the effect of Chungpyesagantang on LPS induced Arthritis in Mice. 2. METHOD : All the BALB/C Mice used in this study were 4wks of age at the start of the experiment. The experimental model of Arthritis was induced by injectection of $300{\mu}g/kg$ LPS in mice knee joint. The experiment was compare daily CS treatment group after Arthritis elicitation with Arthritis elicitated group at day 4, 7, 14 after Arthritis elicitation. 3. RESULTS 1) The hyperplasia of synoviocytes of CS treatment group after Arthritis elicitation is soften than Arthritis elicitated group. 2) The aggregation of collagen fibers CS treatment group after Arthritis elicitation is decreased than Arthritis elicitated group. 3) The distribution of TUNEL positive cells(apoptotic cell) of CS treatment group was remarkably increased than Arthritis elicitated group. 4) The distribution of $TNF-{\alpha}$, $NF-{\kappa}B\;p50$, COX-2 positive cells of CS treatment group after Arthritis elicitation in synovial membrane was decreased than Arthritis elicitated group. 5) The distribution of $IL-2R-{\alpha}$, ICAM-1 positive cells of CS treatment group after Arthritis elicitation in apical surface of synovial membrane was decreased than Arthritis elicitated group. 6) The distribution of $NF-{\kappa}B\;p50$, $IL-2R-{\alpha}$ in common iliac lymph node of CS treatment group after Arthritis elicitation positive cells was decreased than Arthritis elicitated group. 4. CONCLUSION : As a result of these experimental results, it may be concluded that Chungpyesagantang used for treatment of LPS induced Arthritis in Mice. Inflamation activity in CS treatment group after Arthritis elicitation was decreased than Arthritis elicitated group.

• BMB Reports
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• v.52 no.8
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• pp.508-513
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• 2019

In this study, the anti-inflammatory effects of ${\alpha}-lipoic$ acid (LA) and decursinol (Dec) hybrid compound LA-Dec were evaluated and compared with its prodrugs, LA and Dec. LA-Dec dose-dependently inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) generation in BV2 mouse microglial cells. On the other hand, no or mild inhibitory effect was shown by the Dec and LA, respectively. LA-Dec demonstrated dose-dependent protection from activation-induced cell death in BV2 cells. LA-Dec, but not LA or Dec individually, inhibited LPS-induced increased expressions of induced NO synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins in a dose-dependent manner in both BV2 and mouse macrophage, RAW264.7 cells. Furthermore, LA-Dec inhibited LPS-induced expressions of iNOS, COX-2, interleukin-6, tumor necrosis $factor-{\alpha}$, and $interleukin-1{\beta}$ mRNA in BV2 cells, whereas the same concentration of LA or Dec was ineffective. Signaling studies demonstrated that LA-Dec inhibited LPS-activated signal transducer and activator of transcription 3 and protein kinase B activation, but not nuclear factor-kappa B or mitogen-activated protein kinase signaling. The data implicate LA-Dec hybrid compound as a potential therapeutic agent for inflammatory diseases of the peripheral and central nervous systems.

• Journal of Microbiology and Biotechnology
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• v.31 no.1
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• pp.51-62
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• 2021

Here, we investigated the prebiotic and antioxidant effects of Actinidia arguta sprout water extract (AASWE) on lipopolysaccharide (LPS)-induced cognitive deficit mice. AASWE increased viable cell count, titratable acidity, and acetic acid production in Lactobacillus reuteri strain and showed a cytoprotective effect on LPS-induced inflammation in HT-29 cells. We assessed the behavior of LPS-induced cognitive deficit mice using Y-maze, passive avoidance and Morris water maze tests and found that administration of AASWE significantly improved learning and memory function. The AASWE group showed antioxidant activity through downregulation of malondialdehyde levels and upregulation of superoxide dismutase levels in brain tissue. In addition, the AASWE group exhibited activation of the cholinergic system with decreased acetylcholinesterase activity in brain tissue. Furthermore, AASWE effectively downregulated inflammatory mediators such as phosphorylated-JNK, phosphorylated-NF-κB, TNF-α and interleukin-6. The major bioactive compounds of AASWE were identified as quercetin-3-O-arabinopyranosyl(1→2)-rhamnopyranosyl(1→6)-glucopyranose, quercetin-3-O-apiosyl(1 → 2)-galactoside, rutin, and 3-caffeoylquinic acid. Based on these results, we suggest that AASWE not only increases the growth of beneficial bacteria in the intestines, but also shows an ameliorating effect on LPS-induced cognitive impairment.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.4
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• pp.447-454
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• 1999

The production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) are known to be modulated by a variety of factors. Recent study showed that endotoxin-induced NO synthesis and iNOS expression were greatly enhanced by elevation of extracellular glucose concentration in murine macrophages. Although this was suggested to be due to the activation of protein kinase C (PKC) via sorbitol pathway, there was lack of evidence for this speculation. This study was performed to delineate the underlying intracellular mechanisms of glucose-enhancing effect on endotoxin-induced NO production in Raw264.7 macrophages. The levels of NO release induced by lipopolysaccharide (LPS) significantly increased by the treatment of glucose in a concentration dependent manner and also, this effect was observed in LPS-preprimed cells. Concurrent incubation of cells with PKC inhibitors, H-7 or chelerythrine, and LPS resulted in the diminution of NO production regardless of glucose concentration but this was not in the case of LPS-prepriming, that is, chelerythrine showed a minimal effect on the glucose- enhancing effect. PMA, a PKC activator, did not show any significant effect on glucose-associated NO production. Modulation of sorbitol pathway with zopolrestat, an aldose reductase inhibitor, did not affect LPS-induced NO production and iNOS expression under high glucose condition. And also, sodium pyruvate, which is expected to normalize cytosolic $NADH/NAD^+$ ratio, did not show any significant effect at concentrations of up to 10 mM. Glucosamine marginally increased the endotoxin-induced nitrite release in both control and high glucose treated group. 6-diazo-5-oxonorleucine (L-DON) and azaserine, glutamine: fructose- 6-phosphate amidotransferase (GFAT) inhibitors, significantly diminished the augmentation effect of high glucose on endotoxin-induced NO production. On the other hand, negative modulation of GFAT inhibitors was not reversed by the treatment of glucosamine, suggesting the minimal involvement, if any, of glucosamine pathway in glucose-enhancing effect. In summary, these results strongly suggest that the hexosamine biosynthesis pathway and the activation of PKC via sorbitol pathway do not contribute to the augmenting effect of high glucose on endotoxin induced NO production in macrophage-like Raw264.7 cells.

• Journal of Yeungnam Medical Science
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• v.14 no.2
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• pp.337-349
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• 1997

This study was undertaken to examine the intensity of involvement of inducible nitric oxide synthase (iNOS) and cyclic GMP signal transduction pathway as one of the mechanisms of vaso-relaxative action of bacterial lipopolysaccharide (LPS) on the canine femoral artery strips. Canine femoral arteries were isolated and spiral strips of 10 mm long and 2 mm wide were made in the Tyrode solution of $0-4^{\circ}C$. The strips were prepared for isometric myography in Biancani's isolated muscle chamber containing 1 ml of Tyrode solution, which was maintained with pH 7.4 by aeration with 95% $O_2$/5% $CO_2$ at $37^{\circ}C$ and nitric oxide (NO) production was measured simulltaneously with isolated nitric oxide meter. LPS induced NO production, suppressed the phenylephrine (PE) induced contraction and enhanced the acetylcholine (ACh) induced relaxation. $N^G$-nitro-L-arginine methyl ester (L-NAME), an NOS inhibitor, methylene blue, a guanylyl cyclase inhibitor, potentiated PE induced contraction and suppressed ACh induced relaxation on the LPS treated strips. The inhibitory potency of methylene blue for LPS induced vascular hyporesponsiveness was stronger than that of L-NAME. These results suggest that in canine femoral artery, both iNOS and cyclic GMP signal trnasduction pathway are related with LPS induced vascular hyporeponsiveness, but in minor with iNOS and in major with cyclic GMP signal trnasduction pathway.

• Journal of Animal Science and Technology
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• v.63 no.1
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• pp.114-124
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• 2021

The objective of this study was to characterize the enzymatic hydrolysis of lipopolysaccharide (LPS) by wheat phytase and to investigate the effects of wheat phytase-treated LPS on in vitro toxicity, cell viability and release of a pro-inflammatory cytokine, interleukin (IL)-8 by target cells compared with the intact LPS. The phosphatase activity of wheat phytase towards LPS was investigated in the presence or absence of inhibitors such as L-phenylalanine and L-homoarginine. In vitro toxicity of LPS hydrolyzed with wheat phytase in comparison to intact LPS was assessed. Cell viability in human aortic endothelial (HAE) cells exposed to LPS treated with wheat phytase in comparison to intact LPS was measured. The release of IL-8 in human intestinal epithelial cell line, HT-29 cells applied to LPS treated with wheat phytase in comparison to intact LPS was assayed. Wheat phytase hydrolyzed LPS, resulting in a significant release of inorganic phosphate for 1 h (p < 0.05). Furthermore, the degradation of LPS by wheat phytase was nearly unaffected by the addition of L-phenylalanine, the inhibitor of tissue-specific alkaline phosphatase or L-homoarginine, the inhibitor of tissue-non-specific alkaline phosphatase. Wheat phytase effectively reduced the in vitro toxicity of LPS, resulting in a retention of 63% and 54% of its initial toxicity after 1-3 h of the enzyme reaction, respectively (p < 0.05). Intact LPS decreased the cell viability of HAE cells. However, LPS dephosphorylated by wheat phytase counteracted the inhibitory effect on cell viability. LPS treated with wheat phytase decreased IL-8 secretion from intestinal epithelial cell line, HT-29 cell to 14% (p < 0.05) when compared with intact LPS. In conclusion, wheat phytase is a potential therapeutic candidate and prophylactic agent for control of infections induced by pathogenic Gram-negative bacteria and associated LPS-mediated inflammatory diseases in animal husbandry.

• Biomedical Science Letters
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• v.24 no.1
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• pp.50-54
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• 2018

N-nitroso-N-methylurea (NMU) and N-nitroso-N-ethylurea (NEU), direct alkylating chemical mutagens and carcinogens, are shown to be the upregulators of cellular $NF-{\kappa}B$, regulating various genes that mediate tumorigenesis and carcinogenesis. Nitric oxide (NO), a toxic reactive radical gas, has been known to induce programmed cell death or apoptosis in various cells. Therefore, the assessment of NO production was examined to elucidate the possible contribution of NO release to the chemical carcinogenic potency of NMU and NEU in human skin cells. NMU and NEU did not alter the NO production, but they caused a significant downregulation of the NO generation on lipopolysaccharide (LPS)-induced NO production at concentrations ranging from $2{\sim}5{\mu}M$. The degree of downregulation of NO by NMU and NEU decreased up to 15% and 20%, respectively, compared to the control. These results demonstrate that the LPS-inducible keratinocytes NO synthase is involved in modulating carcinogenic potency by NMU and NEU, and the regulation of the cellular $NF-{\kappa}B$ activity by NMU and NEU is negatively correlated with the level of LPS-induced NO production in human skin cells. The findings of this study suggest the hypothesis that NMU and NEU-induced carcinogenesis may be associated with the downregulation of NO production, and the inducible NO may play an important role in NMU and NEU-induced carcinogenicity in human epidermal keratinocytes.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.1
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• pp.63-68
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• 2014

The fruit of Tribulus terrestris L. (Zygophyllaceae) is an important source of traditional Korean and Chinese medicines. In this study, NNMBS223, consisting of the ethanol extract of T. terrestris, showed potent anti-inflammatory activities in RAW264.7 macrophages. We investigated the effect of NNMBS223 in suppressing the protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and production of iNOS-derived nitric oxide (NO), COX-2-derived prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-stimulated macrophages. In addition, NNMBS223 induced expression of heme oxygenase (HO)-1 through nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) in macrophages. The effects of NNMBS223 on LPS-induced production of NO and PGE2 were partially reversed by the HO activity inhibitor tin protoporphyrin (SnPP). These findings suggest that Nrf2-dependent increases in expression of HO-1 induced by NNMBS223 conferred anti-inflammatory activities in LPS stimulated RAW264.7 macrophages.

• Archives of Pharmacal Research
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• v.27 no.7
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• pp.751-756
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• 2004

Flavonoids have been demonstrated to exhibit a wide range of biological activities including anti-inflammatory and neuroprotective actions. Although a significant amount of flavonoids has been identified to be present as glycosides in medicinal plants, determinations of the biological activities of flavonoids were mainly carried out with aglycones of flavonoids. Therefore, the exact role of the glycosidation of flavonoid aglycones needs to be established. In an attempt to understand the possible role of glycosidation on the modulation of the biological activities of flavonoids, diverse glycosides of kaempferol, quercetin, and aromadendrin were examined in terms of their anti-inflammatory activity determined with the suppression of lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV2 microglial cells. The results indicated that glycosidation of aglycones attenuated the suppressive activity of aglycones on LPS-induced NO production. Although attenuated, some of glycosides, depending on the position and degree of glycosidation, maintained the inhibitory capability of LPS-induced NO production. These findings suggest that glycosidation of flavonoid aglycones should be considered as an important modulator of the biological activities of flavonoids.

• BMB Reports
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• v.55 no.3
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• pp.136-141
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• 2022

Inflammation is one of the body's natural responses to injury and illness as part of the healing process. However, persistent inflammation can lead to chronic inflammatory diseases and multi-organ failure. Altered mitochondrial function has been implicated in several acute and chronic inflammatory diseases by inducing an abnormal inflammatory response. Therefore, treating inflammatory diseases by recovering mitochondrial function may be a potential therapeutic approach. Recently, mitochondrial transplantation has been proven to be beneficial in hyperinflammatory animal models. However, it is unclear how mitochondrial transplantation attenuates inflammatory responses induced by external stimuli. Here, we isolated mitochondria from umbilical cord-derived mesenchymal stem cells, referred as to PN-101. We found that PN-101 could significantly reduce LPS-induced mortality in mice. In addition, in phorbol 12-myristate 13-acetate (PMA)-treated THP-1 macrophages, PN-101 attenuated LPS-induced increase production of pro-inflammatory cytokines. Furthermore, the anti-inflammatory effect of PN-101 was mediated by blockade of phosphorylation, nuclear translocation, and trans-activity of NFκB. Taken together, our results demonstrate that PN-101 has therapeutic potential to attenuate pathological inflammatory responses.