• Food Science of Animal Resources
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• v.40 no.2
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• pp.274-285
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• 2020

In this study, ovalbumin (OVA) hydrolysates were prepared using various proteolytic enzymes and the anti-inflammatory activities of the hydrolysates were determined. Also, the potential application of OVA as a functional food material was discussed. The effect of OVA hydrolysates on the inhibition of nitric oxide (NO) production was evaluated via the Griess reaction, and their effects on the expression of inducible NO synthase (inducible nitric oxide synthase, iNOS) were assessed using the quantitative real-time PCR and Western blotting. To determine the mechanism by which OVA hydrolysates activate macrophages, pathways associated with the mitogen-activated protein kinase (MAPK) signaling were evaluated. When the OVA hydrolysates were added to RAW 264.7 cells without lipopolysaccharide (LPS) stimulation, they did not affect the production of NO. However, both the OVA-Protex 6L hydrolysate (OHPT) and OVA-trypsin hydrolysate (OHT) inhibited NO production dose-dependently in LPS-stimulated RAW 264.7 cells. Especially, OHT showed a strong NO-inhibitory activity (62.35% at 2 mg/mL) and suppressed iNOS production and the mRNA expression for iNOS (p<0.05). Also, OHT treatment decreased the phosphorylation levels of Jun amino-terminal kinases (JNK) and extracellular signal-regulated kinases (ERK) in the MAPK signaling pathway. These findings suggested that OVA hydrolysates could be used as an anti-inflammatory agent that prevent the overproduction of NO.

• 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.

• Korean Journal of Food Science and Technology
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• v.48 no.6
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• pp.618-621
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• 2016

Geranium thunbergii is a perennial plant commonly used as an oriental medicine for prevention of diarrhea, constipation, and gastrointestinal disorders. However, its anti-inflammatory effect has not been evaluated thus far. Therefore, the present study aimed to investigate the anti-inflammatory effect of G. thunbergii. In this study, G. thunbergii extracted with methanol; this methanol extract was further partitioned using various solvents, and G. thunbergii ethyl acetate fraction (GTEF) was obtained. To determine the anti-inflammatory activity of G. thunbergii, the effects of GTEF on nitric oxide (NO) production in lipopolysaccharide-stimulated RAW 264.7 cells were evaluated. GTEF suppressed NO production in a dose-dependent manner without any toxic effects. In addition, western blotting was performed to examine the effect of GTEF on expression of inducible nitric oxide synthase and cyclooxygenase-2. These results suggest that GTEF as a phytoextract may be useful for the prevention or treatment of inflammation.

• BMB Reports
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• v.43 no.9
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• pp.584-592
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• 2010

Tetrahydrobiopterin (BH4) is a multifunctional cofactor of aromatic amino acid hydroxylases and nitric oxide synthase (NOS) as well as an intracellular antioxidant in animals. Through regulation of NOS activity BH4 plays a pivotal role not only in a variety of normal cellular functions but also in the pathogenesis of cardiovascular and neurodegenerative diseases, which develop under oxidative stress conditions. It appears that a balanced interplay between BH4 and NOS is crucial for cellular fate. If cellular BH4 homeostasis maintained by BH4 synthesis and regeneration fails to cope with increased oxidative stress, NOS is uncoupled to generate superoxide rather than NO and, in turn, exacerbates impaired BH4 homeostasis, thereby leading to cell death. The fundamental biochemical events involved in the BH4-NOS interplay are essentially the same, as revealed in mammalian endothelial, cardiac, and neuronal cells. This review summarizes information on the cellular BH4 homeostasis in mammals, focusing on its regulation under normal and oxidative stress conditions.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.31-32
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• 2001

A wide array of phenolic substances, particularly those present in dietary and medicinal plants, have been reported to possess substantial anticarcinogenic and antimutagenic activities. The majority of naturally occurring phenolics retain antioxidative and anti-inflammatory properties which appear to contribute to their chemopreventive or chemoprotective activity. Inducible cyclooxygenase (COX-2) and nitric oxide synthase (iNOS) are important enzymes that mediate inflammatory processes.(omitted)

• YAKHAK HOEJI
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• v.48 no.2
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• pp.159-164
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• 2004

Primary pro-inflammatory cytokines are a trio: tumor necrosis- $\alpha$ (TNF-$\alpha$), interleukine-$\beta$ (IL-$\beta$), and interleukine-6 (IL-6). These cytokines initiate and regulate the acute-phase inflammatory response during infection, trauma, or stress and appear to play an important role in the immune process. Nitric oxide (NO) is a multi-functional mediator, which plays an important role in regulating various biological functions in vivo. NO production by inducible nitric oxide synthase (iNOS) in macrophages is essential for the defense mechanisms against microorganisms and tumor cells. However, over-expression of iNOS by various stimuli, resulting in over-production of NO, contributes to the pathogenesis of septic shock and some inflammatory and auto-immune disease. Solvent fractions of sage ( Salvia officinalis L.), which is cultivated in Jeju-Do, was assayed for their effects on TNF-$\alpha$ and IL-6 production in LPS-stimulated RAW 264.7 macrophages. Hexane and ethylacetate (EtOAc) fraction of sage inhibited the protein and mRNA expression of TNF-$\alpha$ and IL-6 in LPS stimulated RAW 264.7 cells at the concentration of 100 $\mu\textrm{g}$/$m\ell$. Also, incubation of RAW 264.7 cells with the fraction of hexane or EtOAc (50 $\mu\textrm{g}$/$m\ell$) inhibited the LPS induced nitrite accumulation and the LPS/IFN-${\gamma}$ induced iNOS protein. And this inhibition of iNOS protein is concordant with the inhibition of iNOS mRNA expression. Above results suggest that extract of sage may have anti-inflammatory activity through the inhibition of pro-inflammatory cytokines (TNF-$\alpha$, IL-1$\beta$, IL-6), iNOS and NO.

• Korean Journal of Plant Resources
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• v.32 no.4
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• pp.264-269
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• 2019

This research was performed to identify the anti-inflammatory constituent from the herb of Lycorus lucidus (Lamiaceae). The MeOH extract of this plant material and its two fractions, the lipophilic- ($CHCl_3$ fraction) and the hydrophilic fraction (BuOH fraction), were prepared to test anti-inflammatory activity. For this purpose, the inhibition rate on inducible nitric oxide synthase (iNOS) activity was assessed by determining nitric oxide (NO) formation in lipopolysaccharide (LPS)-induced macrophage 264.7 cells. The $CHCl_3$ fraction that greatly inhibited nitric NO formation was chromatographed to lead the isolation of ursolic acid. Since ursolic acid inhibited NO formation dose dependently in this study, this compound was considered as one of the active constituent responsible for anti-inflammation. However, the activity of rosmarinic acid isolated from the BuOH fraction was weak.

• Biomolecules & Therapeutics
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• v.16 no.1
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• pp.9-13
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• 2008

Some pharmacological activities of Ulmus davidiana var. japonica were evaluated using its methanol extract (UDE). An acute anti-inflammatory activity of UDE was assessed using carrageenan-induced hind paw edema in rats. UDE exhibited an antioxidant activity when assayed by a stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH). Dose-dependent anti-nociceptive activity of UDE was assessed using the acetic acid-induced writhing test in mice. UDE was able to diminish the reactive oxygen species (ROS) level in the lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. UDE also suppressed production of nitric oxide and induction of inducible nitric oxide synthase and cyclooxygenase-2 in the stimulated macrophages cells. collectively, the results imply that U. davidiana var. japonica has antioxidant and anti-nociceptive activities in addition to anti-inflammatory activity.

• Biomolecules & Therapeutics
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• v.16 no.2
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• pp.82-86
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• 2008

The fruits of Gardenia jasminoides Ellis have been previously reported to possess anti-inflammatory activity. In this study, the constituents including geniposide, geniposidic acid, genipin and crocin were evaluated for their effects on prostaglandin and NO production in an attempt to establish anti-inflammatory cellular mechanisms. Among the constituents tested, only genipin significantly inhibited cyclooxygenase-2-mediated $PGE_2$ and inducible nitric oxide synthase-mediated NO production from lipopolysaccharide-treated RAW 264.7 cells at 10-100 ${\mu}$M. Genipin also inhibited nuclear transcription factor-${\kappa}B$ activation. Moreover, genipin showed in vivo antiinflammatory activity on ${\lambda}$-carrageenan-induced paw edema in mice (10.4-29.9% inhibition at 20-100 mg/kg, i.p.). All of these results suggest that genipin may contribute to anti-inflammatory activity of the fruits of G. jasminoides and an inhibitory action on prostaglandin and NO production is, at least, the part of anti-inflammatory mechanism of genipin.

• Biomedical Science Letters
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• v.11 no.2
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• pp.211-219
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• 2005

Trigeminovascular system plays an important role for the cerebral memodynamics. The aim of this study was to investigate the alterations in cerebrovascular reactivity by trigeminovascular system injury in rats. Trigeminovascular system of male Sprague-Dawley rats was injured by either denervation of nasocilliary nerve or neonatal capsaicin treatment. Trigeminovascular system was stimulated by controlled hemorrhagic hypotension or somatosensory (whisker) stimulation. Changes in regional cerebral blood flow (rCBF) and pial arterial diameter were continuously measured by laser-Doppler flowmetry and videomicroscopy, respectively. Nitric oxide synthase (NOS) activity in cerebral cortex was determined by measuring the conversion of $L-^3H-arginine\;to\;L-^3H-citrulline$. Cyclic GMP levels in cerebral cortex and pial artery were determined using the cyclic GMP $^{125}I$ scintillation proximity assay system. rCBF autoregulation was impaired or almost abolished by trigeminovascular system injury. rCBF response to whisker stimulation was significantly attenuated by trigeminovascular system injury. NOS activity as well as cyclic GMP level in cerebral cortex and pial artery were significantly reduced in the group of trigeminovascular system injury. These results suggest that trigeminovascular system injury causes prominent alterations in cerebrovascular reactivity, and that NO, which is generated by neuronal NOS in the trigeminovascular system, is implicated in the regulation of rCBF.