• Biomedical Science Letters
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• v.16 no.2
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• pp.91-95
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• 2010

Meso-dihydroguaiaretic acid (MDGA) is a medicinal herbal product isolated from the bark of Machilus thunbergii Sieb. et Zucc. (Lauraceae). It exhibits a neuroprotective effect and also exerts cytotoxicity to certain cancer cells. In the present study, we investigated whether or not MDGA inhibits inflammatory reaction through the inhibition of nitric oxide (NO) generation. The results showed that MDGA (5~$25 {\mu}M$) inhibited 100 ng/ml lipopolysaccharide (LPS)- induced NO generation in macrophage Raw 264.7 cells in a concentration-dependent manner. We also measured the cytotoxic effects of MDGA on Raw 264.7 cells and found no evidence of cytotoxicity. The inhibition of NO generation by MDGA was consistent with the inhibitory effect on the expression of inducible nitric oxide synthase (iNOS). In addition, MDGA inhibited the LPS-induced gene expression of $interleukin-1{\beta}$ $(IL-1{\beta})$ as well as tumor necrosis $factor-{\alpha}$ $(TNF-{\alpha})$. The present results may provide that MDGA has anti-inflammatory properties through inhibition of the toll-like receptors (TLRs) pathway, and suggest that MDGA can be used as an anti-inflammatory agent.

• The Journal of the Society of Korean Medicine Diagnostics
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• v.17 no.3
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• pp.263-273
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• 2013

Objectives This study was designed to investigate the anti-inflammatory effect of extracts from Ligustrum obtusifolium S. fruits(LOF) in RAW 264.7 Macrophages stimulated with lipopolysaccharide(LPS). Methods We examined productions of nitric oxide(NO), reactive oxygen species(ROS), inducible isoforms of NO synthase(iNOS), cyclooxygenase-2(COX-2) to investigate the anti-inflammatory effect of LOF extracts. In addition, we measured generation of pro-inflammatory cytokines(TNF-${\alpha}$, IL-6). Results Cell viability showed that LOF extracts had no cytotoxicity in Raw 264.7 cells. The treatment with LOF extracts significantly decreased the generation of NO and pro-inflammatory cytokines(TNF-${\alpha}$, IL-6) in LPS-stimulated macrophage cells. Furthermore LOF extracts inhibited intracellular ROS generation dose dependently and reduced the expression of iNOS, COX-2 proteins. Conclusions These results showed that the LOF extracts had an anti-inflammatory effect on LPS-stimulated Raw 264.7 cells. These findings provide scientific support for the use of this Ligustrum obtusifolium S. for inflammatory-related diseases.

• Journal of Ginseng Research
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• v.37 no.1
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• pp.64-73
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• 2013

Korean red ginseng water extract (KG-WE) has known beneficial effects on the cardiovascular system via inducting nitric oxide (NO) production in endothelium. Endothelial arginase inhibits the activity of endothelial nitric oxide synthase (eNOS) by substrate depletion, thereby reducing NO bioavailability and contributing to vascular diseases including hypertension, aging, and atherosclerosis. In the present study, we demonstrate that KG-WE inhibits arginase activity and negatively regulates NO production and reactive oxygen species generation in endothelium. This is associated with increased dimerization of eNOS without affecting the protein expression levels of either arginase or eNOS. In a vascular tension assay, when aortas isolated from wild type mice were incubated with KG-WE, NO-dependent enhanced vasorelaxation was observed. Furthermore, KG-WE administered via by drinking water to atherogenic model mice being fed high cholesterol diet improved impaired vascular function. Taken together, these results suggest that KG-WE may exert vasoprotective effects through augmentation of NO signaling by inhibiting arginase. Therefore, KG-WE may be useful in the treatment of vascular diseases derived from endothelial dysfunction, such as atherosclerosis.

• Archives of Pharmacal Research
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• v.27 no.1
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• pp.94-98
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• 2004

Effects of dopaminergic drugs on the degranulation of mast cells (RBL-2H3 cells) and the nitric oxide production from macrophage cells (RAW 264.7) were studied. Among the dopaminergic agonists and antagonists tested, bromocriptine, 7-OH-DPAT, haloperidol, and clozapine showed potent inhibitions of mast cell degranualtion ($IC_{50} value, 5 \mu$ M). However, these dopaminergic agents did not affect the tyrosine phosphorylations of the signaling components of the high affinity IgE receptor ($Fc\varepsilonRI$), such as Syk, $PLC\gamma1$, and $PLC\gamma2$.; This suggested that these signaling components were not involved in the inhibition of the mast cell degranulation by these compounds. On the other hand, dopamine, bromocriptine, 7-OH-DAPT, and haloperidol markedly inhibited the nitric oxide production from RAW 264.7 cells ($IC_{50}$ values, 10-20$\mu$M). Bromocriptine, a dopamine agonist that is routinely used for the treatment of Parkinsons disease, inhibited the expression of the inducible nitric oxide synthase at an early stage of the LPS-induced protein expression in a dose-dependent manner. The results suggested that these dopaminergic agents, when used for the treatment of dopamine receptors-related diseases, such as Schizophrenia or Parkinsons disease, might have additional beneficial effects.

• Biomolecules & Therapeutics
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• v.3 no.1
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• pp.58-62
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• 1995

We investigated whether nitric oxide (NO) may serve a role in bladder function by immunohistochemical analysis of the distribution of intrinsic NADPH-diaphorase and functional study of isometric tension recordings via a photo-induced adequate nitric oxide (PIANO) generating system using rat bladder. Results suggest that a small number of NADPH-diaphorase-positive perikarya are present within the bladder wall and within adjacent small ganglia. Furthermore, NADPH-diaphorase-positive nerve fibers were observed in the adventitial and muscular layers, subjacent to the urothelium and perivascular fibers. Rat bladder strips precontracted with 3$\mu$M carbachol were reversibly relaxed upon NO generation by UV irradiation. PIANO-mediated relaxation was sensitive to oxygen free radicals. In addition, tissue cGMP levels were increased by the PIANO generating system and elevated cGMP levels were decreased by pretreatment of guanylate cyclase inhibitor, methylene blue. These results indicate that NO may serve a role in modulating bladder tone in the rat.

• Bulletin of the Korean Chemical Society
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• v.19 no.5
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• pp.506-507
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• 1998

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.83-90
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• 2017

Advanced age is one of the risk factors for vascular diseases that are mainly caused by impaired nitric oxide (NO) production. It has been demonstrated that endothelial arginase constrains the activity of endothelial nitric oxide synthase (eNOS) and limits NO generation. Hence, arginase inhibition is suggested to be vasoprotective in aging. In this study, we examined the effects of intravenous injection of Piceatannol, an arginase inhibitor, on aged mice. Our results show that Piceatannol administration reduced the blood pressure in aged mice by inhibiting arginase activity, which was associated with NO production and reactive oxygen species generation. In addition, Piceatannol administration recovered $Ca^{2+}$/calmodulin-dependent protein kinase II phosphorylation, eNOS phosphorylation and eNOS dimer stability in the aged mice. The improved NO signaling was shown to be effective in attenuating the phenylephrine-dependent contractile response and in enhancing the acetylcholine-dependent vasorelaxation response in aortic rings from the aged mice. These data suggest Piceatannol as a potential treatment for vascular disease.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.5
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• pp.1512-1515
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• 2004

In this study, we investigated in vitro nitric oxide (NO) scavenging effect on nine herbal extracts using an NO donor S-nitroso-N-acetylpenicillamine (SNAP) compared with vitamin C. All herbal extracts effectively reduced the generation of NO radicals in a dose-dependant manner and over 65% in 10h. Especially, Ephedrae herba, Carthami flos and Lonicerae flos declined over 75% of NO scavenging effect, suggested that the herbal extracts are the powerful free radical scavengers and may be effective in clinical applications.

• Archives of Pharmacal Research
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• v.27 no.3
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• pp.314-318
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• 2004

Microglia are the major inflammatory cells in the central nervous system and become activated in response to brain injuries such as ischemia, trauma, and neurodegenerative diseases including Alzheimer's disease (AD). Moreover, activated microglia are known to release a variety of proinflammatory cytokines and oxidants such as nitric oxide (NO). Minocycline is a semi-synthetic second-generation tetracycline that exerts anti-inflammatory effects that are completely distinct form its antimicrobial action. In this study, the inhibitory effects of minocycline on NO and prostaglandin E$_2$ (PGE$_2$) release was examined in lipopolysaccharides (LPS)-challenged BV2 murine microglial cells. Further, effects of minocycline on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression levels were also determined. The results showed that minocycline significantly inhibited NO and PGE$_2$ production and iNOS and COX-2 expression in BV2 microglial cells. These findings suggest that minocycline should be evaluated as potential therapeutic agent for various pathological conditions due to the excessive activation of microglia.

• The korean journal of orthodontics
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• v.25 no.6 s.53
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• pp.715-722
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• 1995

Orthodontic tooth movement in response to orthodontic force results from actions of osteoclasts and osteeoblasts in the cell level. Convincing evidence has now been provided to support the view that osteoclasts are derived from mononuclear cells that originate in the bone marrow or other hematopoietic organs and they migrate to the bones via vascular routes. Nitric oxide(NO), which accounts for the biological properties of endothelium-derived relaxing factor(EDRF), is the endogenous stimulator of soluble guanylate cylase. The discovery of the formation of nitric oxide(NO) from L-arginine in mammalian tissues and its biological roles has, in the last 7 years, thrown new light onto many areas of research. Data from experiments in vitro showed that N-metyl-L-arginine(L-NMA) and L-nitro-L- arginine(L-NAME) are competitive inhibitors of nitric oxide synthase. This study suggest that the multinucleated cells in our culture have characteristics of osteoclasts and that the potential bone cell activity of nitric oxide in vitro may be mediated in part by stimulation of marrow mononuclear cells to form osteoclast-like cells. Bone marrow cells were obtaineed from tibia of 19-days old chick embryo. After sacrifice, tibia was quickly dissected and the bone were then split to expose the medullary bone. The cells were attached for 4 hours and the nonadherent cells were collected. Marrow cells weere cultured in 96-well plate in medium 199. To examine the number of TRAP-positive multinucleated cells(MNCs), $10^{-8}\;M\;Vit=D_3$ and various concentration of L-NMA and L-NAME weere added at the beginning of cultures and with each medium change. After 7 days of culture. tartrate-resistant acid phosphatase(TRAP) staining was performed for microscopic evaluation. Cells haying more than three nuclei per cell were counted as MNCs. The obsrved results were as follows;1. 1,25-dihydroxyvitamine $D_3$ stimulated the osteoclast-like multinucleated cells in cultures of chick embryo bone marrow. 2. Nitric oxide synthase inhibitors(NOSI ; N-NMA, N-NAME) stimulated the osteoclast-like cells in cultures of chick embry bone marrow. 3. 1,25-dihydroxyvitamine$D_3$ and nitric oxide synthase inhibitors did not appear to have additive effect on the generation of TRAP-positive MNCs. These results suggest that nitric oxide synthase inhibitors may stimulate the osteoclast-like multinucleated cell formation and fusion in cultures of chick bone marrow.