• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.145-145
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• 1998

In the present study, we have demonstrated that taurine could stimulate the production of nitric oxide and the activity of ERK2 (extracellular signal regulated protein kinase or pp42 MAP kinase). Nitric oxide(NO), the product of inducible nitric oxide synthase(iNOS), is known to be implicated in the metabolism of bone. ERK cascade plays a key role in the gene expression of iNOS in osteoblastic cell. We investigated whether taurine (l-20mM) could stimulate ERK2 activity, nitric oxide production, and inducible nitric oxide synthase in osteoblast-like UMR-106 cells. Nitric oxide was measured spectophotometrically as nitrite and the activation of ERK2 and iNOS was studied using Western 145 blot analysis. Taurine increased the production of nitric oxide in a dose-dependent manner and the effect was reached to a maximum at 10 mM. The activation of iNOS were consistent with NO levels. The tyrosine phosphorylation of ERK2 was increased by taurine in a time-dependent manner. The these result suggest that taurine might stimulate the production of nitric oxide in osteoblast-like cells by the activation of ERK2 and could regulate the metabolism of bone via nitric oxide.

• Archives of Pharmacal Research
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• v.27 no.9
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• pp.937-943
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• 2004

Recent investigations have shown that certain flavonoids, especially flavone derivatives, inhibit nitric oxide (NO) production by inducible NO synthase (iNOS) in macrophages, which contrib-ute their anti-inflammatory action. For the purpose of finding the optimized chemical structures of flavonoids that inhibit NO production, various A- and B-ring substituted flavones were syn-thesized and evaluated for their inhibitory activity using lipopolysaccharide-treated RAW 264.7 cells. It was found that the optimal chemical structures were A-ring 5,7-dihydroxyflavones hav-ing the B-ring 2＇,3＇-dihydroxy or 3＇,4＇-dihydroxy or 3＇,4＇-hydroxy/methoxy (methoxy/hydroxy) groups. These structurally optimized compounds were revealed to be down-regulators of iNOS induction, but not direct iNOS inhibitors. Of these derivatives that were evaluated, 2＇,3＇,5,7-tet-rahydroxyflavone and 3＇,4＇,5,7-tetrahydroxyflavone (Iuteolin) showed the strongest inhibition. The $IC_{50}$/ values for these compounds were 19.7 and 17.1 11M, respectively. Therefore, these compounds may have a potential as new anti-inflammatory agents.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.6
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• pp.665-672
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• 1997

This study aimed to investigate the mechanism of cerebroprotection of platelet-activating factor(PAF) antagonists in transient cerebral ischemia of rat. Right middle cerebral artery(MCA) of Sprague-Dawley rat was occluded for 2 hours using an intraluminal filament technique. After 22 hours of reperfusion, morphometrically detectable infarct was developed in the cortex and striatum identical to the territory of MCA. The infarct size was significantly reduced by PAF antagonists, BN 52021 and CV-6209, as well as an inducible nitric oxide synthase(iNOS) inhibitor aminoguanidine(1 mg/kg, i.p., respectively) administered 5 min after MCA occlusion. PAF antagonists significantly inhibited the enzymatic activities of both myeloperoxidase and iNOS in the cerebral hemisphere ipsilateral to ischemia, whereas aminoguanidine did not inhibit myeloperoxidase activity but significantly inhibited the iNOS activity. These results suggest that PAF antagonists exert a cerebroprotective effect against ischemic brain damage through inhibition of leukocyte infiltration and iNOS activity in the postischemic brain.

• The Journal of Korean Medicine
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• v.29 no.1
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• pp.47-59
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• 2008

Objective : Anti-inflammatory effects of the extract of Lycii Fructus on lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophage cells were investigated. Method : In order to assess the cytotoxic effect of Lycii Fructus on the raw 264.7 macrophages 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay was performed. Reverse transcription-polymerase chain reaction(RT-PCR) analysis of the mRNA levels of tumor necrosis factor-$\alpha$(TNF-$\alpha$) and inducible nitric oxide synthase(iNOS) was performed in order to provide an estimate of the relative level of expression of these genes. The protein level of the inhibitor of nuclear factor-${\kappa}B(I{\kappa}B)$ and nuclear factor-${\kappa}B$(NF-${\kappa}B$) activity was investigated by Western blot assay. NO production was investigated by NO detection. Result : Lycii Fructus suppressed NO production by inhibiting the LPS-induced expressions of iNOS and TNF-$^-\alpha$ mRNA and iNOS protein in RAW 264.7 macrophage cells. Also, Lycii Fructus suppressed activation of NF-${\kappa}B$ in the nucleus. Conclusion : These results show that the extract of Lycii Fructus has anti-inflammatory effect probably by suppressing iNOS expressions through the down-regulation of NF-${\kappa}B$ binding activity.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.4
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• pp.315-320
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• 2013

Here, we show that radicicol, a fungal antibiotic, resulted in marked inhibition of inducible nitric oxide synthase (iNOS) transcription by the pancreatic beta cell line MIN6N8a in response to cytokine mixture (CM: TNF-${\alpha}$, IFN-${\gamma}$, and IL-$1{\beta}$). Treatment of MIN6N8a cells with radicicol inhibited CM-stimulated activation of NF-${\kappa}B$/Rel, which plays a critical role in iNOS transcription, in a dose-related manner. Nitrite production in the presence of PD98059, a specific inhibitor of the extracellular signal-regulated protein kinase-1 and 2 (ERK1/2) pathway, was dramatically diminished, suggesting that the ERK1/2 pathway is involved in CM-induced iNOS expression. In contrast, SB203580, a specific inhibitor of p38, had no effect on nitrite generation. Collectively, this series of experiments indicates that radicicol inhibits iNOS gene expression by blocking ERK1/2 signaling. Due to the critical role that NO release plays in mediating destruction of pancreatic beta cells, the inhibitory effects of radicicol on iNOS expression suggest that radicicol may represent a useful anti-diabetic activity.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.3
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• pp.785-791
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• 2005

Corydalis Tuber has traditionally been used for the treatment of water retention in the body. Administration of the aqueous extract of Corydalis Tuber has been known to be effective for the control of pain and treatment of arthritis. It was reported that Corydalis Tuber possesses anti-inflammatory activity and modulates the intestinal immune system. The effect of Corydalis Tuber against LPS-stimulated expressions of COX-2, iNOS, and $IL-1{\beta}$ in cells of the murine RAW 264.7 macrophages was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, reverse transcription-polymerase chain reaction (RT-PCR), $PGE_2$ immunoassay, and NO detection. The aqueous extract of Corydalis Tuber was shown to suppress $PGE_2$ production by inhibition on the LPS-stimulated enhancement of COX-2 enzyme activity, $IL-1{\beta}$, and iNOS expression in the RAW 264.7 macrophages. Present results suggest that Corydalis Tuber exerts anti-inflammatory and analgesic effects probably by suppressing of COX-2, iNOS, and $IL-1{\beta}$ expressions, resulting in inhibition of $PGE_2$ synthesis. Corydalis Tuber has anti-inflammatory and analgesic effects probably by suppressing of COX-2, iNOS, and $IL-1{\beta}$ mRNA expressions, resulting in inhibition of $PGE_2$ and NO synthesis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.6
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• pp.1449-1453
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• 2008

Galla Rhois is a nest of parasitic bug, has been traditionally used for the treatment of the therapy of diarrhea, peptic ulcer, hemauria, etc., that showed various anti-inflammatory activity, and other biological properties. We studied the effect of Galla Rhois ethanol extract. we investigated whether compounds isolated from the ethanol extract of Galla Rhois, could modulate iNOS and COX-2 expression in RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS). We found compounds that suppressed LPS-induced iNOS and COX-2 expression. Suppression of the expression of iNOS and COX-2 was in parallel with the comparable inhibition of the production of nitric oxide (NO) and prostaglandin E2 (PGE2). Our results suggest that compounds can inhibit NO and PGE2 productions through suppression of LPS-induced iNOS and COX-2 expression. Because COX-2- or iNOS-dependent mechanisms are involved in inflammation and tumor progression, our findings provide a new uncovering mechanism responsible for anti-inflammatory and antitumor effects of Galla Rhois.

• Natural Product Sciences
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• v.18 no.3
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• pp.183-189
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• 2012

It is well known that inflammation is associated with neurodegenerative disorders, including Alzheimer' disease, Parkinson's disease and ischemia. Nitric oxide (NO), a pro-inflammatory mediator, is produced by inducible NO synthase (iNOS) in microglia as well as macrophages and appears to account for neurodegeneration. In this study, we aimed to isolate NO inhibitors from Pyrus pyrifolia by activity guided purification. As a result, we identified daucosterol and ${\beta}$-sitosterol, which have not been isolated from this plant before. This article also describes NO inhibitory activities of the methanol extract of Pyrus pyrifolia fruit and the isolated compounds from this, which are lupeol, betulin, betulinic acid, ${\beta}$-sitosterol and daucosterol, in LPS-activated RAW 264.7 and BV2 cell lines. Western blot analysis was performed to clarify the underlying mechanism of NO inhibition in the two cell lines.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.53 no.2
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• pp.233-238
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• 2008

This experiment was conducted to enhance the colored potatoes utilization and to determine the biological activity of colored potato extracts. In order to understand the factors responsible for the potent anti-oxidant ability of colored potatoes, it has been evaluated for anti-oxidative activity using oxygen radical absorbance capacity (ORAC) assay. 'Hongyoung' extract was significant anti-oxidant activities in ORAC assay. About two-fold higher radical absorbance capacity was found in 'Hongyoung' compared to that in 'Jayoung'. The ability of 80% ethanol extracts from colored potatoes to influence the inhibitory activity of nitric oxide (NO) and nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) has also been investigated. The various therapeutic benefit claims in the new functional medicinal usage of colored potatoes ascribed to the phenolic compounds and anthocyanin. This result revealed that the extracts of colored potatoes are expected to be good candidate for development into sources of free radical scavenger or COX-2 inhibiting agents.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.5
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• pp.443-449
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• 2001

Previously we reported that THI 52 inhibits tumor necrosis factor $(TNF)-{\alpha}$ mRNA expression in mouse peritoneal macrophages exposed to LPS plus $IFN-{\gamma}.$ In the present study, the effects of THI 52 on vascular reactivity ex vivo, and iNOS protein expression (rat lung) were investigated in LPS-treated rats. Treatment of THI 52 concentration-dependently reduced not only serum nitrite production but also the expression of iNOS protein in rat lung tissues. Thoracic aorta taken from LPS injected rat for 8 h ex vivo resulted in suppression of vasoconstrictor effects to phenylephrine (PE), which was restored by THI 52 (20 mg/kg) 30 min prior to LPS. When measured iNOS activity, treatment of THI 52 concentration-dependently reduced the enzyme activity in RAW 264.7 cells activated with LPS plus $IFN-{\gamma}.$ Likewise, iNOS activity was significantly reduced in lung tissues taken those rats that were injected THI 52 prior to LPS injection compared with LPS injection alone. These results strongly suggest that THI 52 can suppress iNOS gene expression induced by LPS, and restore the vascular contractility to PE. Thus, THI 52, a new synthetic isoquinoline alkaloid, may be beneficial in inflammatory disorders where production of NO is excessed by iNOS expression.