• Natural Product Sciences
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• v.26 no.2
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• pp.176-181
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• 2020

Two new compounds, 3-methyl-but-2-en-1-yl-1-O-β-xylopyranosyl-(1"→2')-O-β-glucopyranoside (1) and 1-O-β-glucopyranosyl-6-hydroxy-2-methyl-hep-2-enoic acid (2), along with sixteen known terpenoids were isolated from the peels of Citrus unshiu Markov. Their structures were elucidated based on extensive NMR analyses (¹H NMR, ¹³C NMR, DEPT, COSY, HMQC, and HMBC) and high-resolution mass spectrometry. In addition, all isolates (1 - 18) were tested their effects on nitric oxide (NO) production in RAW264.7 cells. Limonin (15) showed to inhibit LPS-induced NO production in a concentration-dependent manner without cytotoxicity.

• YAKHAK HOEJI
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• v.45 no.4
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• pp.413-418
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• 2001

To investigate action of ATP on ischemia-induced brain injury, we measured phospholipase $A_2$activity and nitric oxide (NO) production in C6 cells. ATP alone did not have any influence on phospholipase $A_2$activity but increased NO production. Glutamate (1 mM) significantly increased phospholipase $A_2$activity whereas did not increased NO production. ATP significantly inhibited phospholipase $A_2$activation induced by 0.1 $\mu$M A23187, 1 mM glutamate and 1 mM $H_2O$$_2$, but did not inhibited 1 $\mu$M PMA-induced phospholipase $A_2$activation. From the above results, it is suggested that the action of ATP in C6 cells has dual actions, such as the inhibition of agonist-induced phospholipase $A_2$activation and the increase of NO production.

• Bulletin of the Korean Chemical Society
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• v.31 no.1
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• pp.27-30
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• 2010

A series of thioureas were synthesized as inhibitors of NO production in lipopolysaccharide-activated macrophages. We investigated the effect of lipophilic moiety and N-substituents of the thioureas on the activity. Phenoxazine and carbazole-containing derivatives revealed higher activity than indole-containing thioureas. The appropriate spacer between lipophilic tail and thiourea head and methyl substituent at N3 position of thiourea brought beneficial effect on the inhibition of NO production. Among prepared compounds, phenoxazine-containing derivative 2a was the most potent with $2.32 {\mu}M$ of $IC_{50}$ value. RT-PCR analysis suggested that the prepared thioureas inhibited NO production through the suppression of iNOS mRNA expression.

• Bulletin of the Korean Chemical Society
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• v.30 no.1
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• pp.119-123
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• 2009

Structural modifications were performed on the C-3 and C-28 positions of ursolic acid and oleanolic acid and the NO production inhibitory activities of the resulting derivatives were evaluated. The SAR revealed that the ursolic acid and oleanolic acid derivatives 3a and 4a, which possessing methoxy group at C-3 position exhibit improved NO production inhibitory activity on LPS-induced RAW247 cells while showing less cytotoxicity than the parent compounds.

• Natural Product Sciences
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• v.18 no.3
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• pp.141-146
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• 2012

Veronica peregrina (Scrophylariaceae) has been widely used as a Korean traditional medicine for the treatment of various pathological conditions including infection, hemorrhage and gastric ulcer. In the current study, we investigated the inhibitory effect of methanolic extracts of V. Peregrina (VPM) on the LPS-mediated nitric oxide (NO) production in mouse (C57BL/6) peritoneal macrophages. NO production was significantly down-regulated by the treatment of VPM dose dependently. To evaluate the mechanism of the inhibitory action of VPM on NO production, we performed iNOS enzyme activity assay and checked the change of inducible nitric oxide synthase (iNOS) levels by Western blotting. Although VPM did not affect iNOS enzyme activity, iNOS protein expression was attenuated by VPM indicating VPM inhibits NO production via suppression of iNOS enzyme expression. In addition, VPM attenuated the expression of another pro-inflammatory mediator such as cyclooxygenase-2 (COX-2) in a dose dependent manner. We also found that VPM can reduce trypsin-induced paw edema in mice. Based on this study, we suggest that V. peregrina may be beneficial in diseases which related to macrophage-mediated inflammatory disorders.

• YAKHAK HOEJI
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• v.50 no.6
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• pp.367-371
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• 2006

Phellinus pini (Hymenocaetaceae) has been used for the immunomodulating activity hypolipidemic effect, gastric cancer non-insulin dependant diabetes, diarrhea, and menstrual irregularity. From the screening of each fraction for the inhibitory activity of NO production in lipopolysaccaride (LPS) activated RAW 264.7 cells, methanol extract of Phellinus pini and hexane soluble fraction exhibited inhibition of NO production compared with LPS control without toxicity. The hexane soluble fraction showed dose dependent inhibition of NO production. According to activity guided fractionation, the active hexane fr. was repeatedly chromatographed over silica gel, ergosta-4,6,8(14),22- tetraen-3-one was isolated. The compound inhibited NOS activation (IC$_{50}$ = 29.7 uM) and NO production of activated macrophage at 30 uM.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.151.3-152
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• 2003

Aromatic diamine JSH-21 showed an IC50 value of 9.2 uM with 74.5% inhibition at 30 uM, 53.5% at 10 uM and 24.5% at 3 uM on LPS-induced NO production in murine macrophages Raw 264.7. To examine whether inhibitory effect on NO production by JSH-21 was attributed to influence on iNOS expression, iNOS transcript and protein were analyzed by sequantitative RT-PCR and immunoblot analysis. Consistent with previous result on NO production, treatment of the Raw 264.7 cells with JSH-21 decreased the LPS-induced expression of iNOS transcript and protein in a dose-dependent manner with IC50 values of about 10 uM. (omitted)

• 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 Physiology & Pathology in Korean Medicine
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• v.22 no.5
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• pp.1210-1214
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• 2008

The purpose of this study is to investigate the effect of water extract from Artemisiae Argi Folium (WAAF) on hepatotoxicity caused by acetaminophen (AAP) and acetaldehyde which are regarded as hepatotoxin. Artemisiae Argi Folium was known to have the antibacterial, immune-enhancing, and anticoagulative properties. In Korean Medicine, Artemisiae Argi Folium is supposed to be related with 'liver meridian' according to traditional medical theory. AAP and acetaldehyde reduce the intracellular production of hydrogen peroxide ($H_2O_2$) and nitric oxide (NO) production of human hepatocyte HepG2. The intracellular production of hydrogen peroxide ($H_2O_2$) was measured by dihydrorhodamine 123 (DHR) assay. NO production was measured with Griess test. WAAF increased the production of $H_2O_2$ and NO reduced by AAP and acetaldehyde in HepG2 cells. Therefore, It could be suggested that WAAF has the hepatoprotective activity against AAP and acetaldehyde.

• CELLMED
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• v.8 no.2
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• pp.8.1-8.5
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• 2018

Nitric oxide (NO) is a small diffusible molecule which plays an important role in various physiological activities. NO is a notable molecule, functioning as a cytotoxic agent and cellular messenger. There has been considerable interest in NO production by activated macrophages because this gaseous metabolite plays a fundamental role in the cytotoxic and cytostatic effects of macrophages towards invasive micro-organisms and tumour cells. No is a bioactive free radical that has been implicated in many physiological functions, plays a critical role during inflammation and therefore constitutes a potential target for developing therapeutics for inflammatory diseases. The use of medicinal plants by the population has been an important alternative the resource in the treatment of various diseases. Its growing acceptance in the medical community has been due to the fact that several plants with biological activities have been scientifically investigated and their efficacy and safety have been proven. In this review, discussed suppressive effects of No production by traditional medicines in RAW 264.7 and THP-1 macrophages.