• Toxicological Research
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• 제24권3호
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• pp.169-174
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• 2008

This study examined the mechanisms underlying the effects of the vasorelaxation active substance(VAS), dimethyladenosine-5'-L-arabinose, and its partial purification fraction on nitric oxide synthase in improving erectile dysfunction with particular focus on the nitric oxide (NO)-cGMP pathways. Two rat models, 9-month-old SD rats and 11-month-old SD rats, were given VAS(40 mg/kg per day) for 4 days, The aqueous fraction of silworm male pupae extract; semi-purified VAS(100 mg/kg per day) for 10 days, respectively. The NOS activities of the following three enzymes were examined: neuronal NO synthase(nNOS), inducible NOS(iNOS), endothelial NOS(eNOS), vascular endothelial growth factor on endothelial cells(VEGF) and anti-inflammation effect of Tumor necrosis factor-$\alpha$. The results showed increases in the nitric oxide synthase activities. Western blotting of the tissue homogenate showed an increase in the nNOS level in the brain and tongue, and an increase in the endothelial NO synthase(eNOS) level in penis. However, there was little association with VEGF production in HUVEC endothelial cells and no relationship with TNF-$\alpha$ which showed low levels.

• 대한의생명과학회지
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• 제25권1호
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• pp.60-65
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• 2019

Toll-like receptors (TLRs) are one of the families of pattern recognition receptors (PRR) operating in the innate immunity. TLRs have the ability to recognize relatively conserved microbial components, which are generally referred to as pathogen-associated molecular patterns (PAMPs). The activation of TLRs signaling leads to the activation of $NF-{\kappa}B$ and the expression of pro-inflammatory gene products such as cytokines and inducible nitric oxide synthase (iNOS). To evaluate the therapeutic potential of pristimerin, which is a naturally occurring triterpenoid compound from Celastraceae plants, iNOS expression induced by MALP-2 (TLR2 and TLR6 agonist), Poly[I:C] (TLR3 agonist), or LPS (TLR4 agonist) were examined. Pristimerin suppressed the iNOS expression induced by MALP-2, Poly[I:C], or LPS. These results suggest that pristimerin can modulate TLRs signaling pathways leading to decreased inflammatory gene expression.

• 약학회지
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• 제48권2호
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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.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Dietary and Medicinal Antimutgens and Anticarcinogens
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• pp.131-131
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• 2001

Prostaglandins and nitric oxide produced by inducible cyclooygenase (COX-2) and nitric oxide synthase (iNOS), respectively, have been implicated as important mediators in the process of inflammation and carcinogenesis. On this line, the potential COX-2 or iNOS inhibitors have been considered as anti-inflammatory and cancer chemopreventive agents.(omitted)

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.171.1-171.1
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• 2003

In some tissues 17b-estradiol (E2) is known to increase endothelial NOS expression. In the present study we examined the effects of E2 on estrogen receptors (ERa and b) and inducible nitric oxide synthase (iNOS) expression and analyzed the mechanisms in rat peritoneal macrophages. (omitted)

• Preventive Nutrition and Food Science
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• 제13권4호
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• pp.362-365
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• 2008

Agaricus bisporus, also known as white button mushroom, is one of the most popular mushrooms consumed in Korea. This mushroom contains high concentrations of flavanoids and exhibits antioxidant activity. In this study, we examined the effects of Agaricus bisporus ethanol extract (ABE) on lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 cells. Nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) protein levels were assessed in cells treated with $100\;{\mu}M$ LPS in the presence or absence of ABE. 0.5 mg/mL of ABE suppressed NO production significantly. Moreover, ABE inhibited levels of iNOS protein. Taken together, these results suggest that ABE exerts anti-inflammatory activity in LPS-induced inflammation in RAW 264.7 cells.

• Natural Product Sciences
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• 제5권3호
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• pp.113-120
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• 1999

Nitric oxide (NO) is a free radical synthesized from L-arginine by nitric oxide synthase (NOS). It is believed that NO is an important mediator in numerous physiological and inflammatory responses. Particularly, a large amount of NO released from the inducible nitric oxide synthase (iNOS) is mostly associated with inflammatory processes. Overproduction of NO in these processes including sepsis and autoimmune diseases can have deleterious consequences and pathophysiologic relevance. Therefore, for the discovery of new inhibitory agents against iNOS activity, we have evaluated about 100 kinds of natural products after partition into three layers (n-hexane, ethyl acetate and aqueous) from 100% methanol extracts to study inhibitory effects on iNOS activity induced by lipopolysaccharide (LPS) in RAW264.7 cells culture system. As a positive control, curcumin, which is known as an anti-tumor promoter, anti-inflammatory agent as an iNOS inhibitor, was used and showed the dose-dependent inhibitory effect $(IC_{50},\;2.5\;{\mu}g/ml)$. Among tested fractions, the n-hexane fraction of Cimicifuga heracleifolia $(IC_{50}:\;9.65\;{\mu}g/ml)$, Forsythiae fructus $(IC_{50}:\;6.36\;{\mu}g/ml)$, Saposhnikovia divaricata $(IC_{50}:\;5.92\;{\mu}g/ml)$, and the ethyl acetate fraction of Chrysanthemum sibiricum $(IC_{50}:\;2.56\;{\mu}g/ml)$, Gastrodia elata $(IC_{50}:\;3.46\;{\mu}g/ml)$, and the aqueous fraction of Dianthus chinensis $(IC_{50}:\;6.73\;{\mu}g/ml)$, Euonymus alatus $(IC_{50}:\;6.78\;{\mu}g/ml)$, Mechania urticifoloria $(IC_{50}:\;8.01\;{\mu}g/ml)$ showed strong inhibitory activity against LPS-stimulated iNOS. Especially, the ethyl acetate fraction of Chrysanthemum sibiricum $(IC_{50}:\;2.56\;{\mu}g/ml)$, which exhibited the strongest inhibition against iNOS, was fractionated with silica-gel column chromatography. These subfractions exhibited dose-dependent inhibition against iNOS activity in the range of $2.59-5.6\;{\mu}g/ml$ except for fraction No. 3, 4, 5, 6, 8, 9, and 16. Our study shows that Chrysanthemum sibiricum has the strongest inhibitory effect against iNOS activity and has similar effect to curcumin. Therefore, further studies for the identification of active principles from Chrysanthemum sibiricum and investigation for the mechanism of the inhibition of iNOS by active principles will be performed.

• The Korean Journal of Physiology and Pharmacology
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• 제2권2호
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• pp.233-239
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• 1998

Stimulated alveolar macrophages and neutrophils produce nitric oxide, a free radical by an inducible nitric oxide synthase(iNOS), which reacts with superoxide anion to form peroxynitrite, a more highly reactive toxic species. The objectives of the present study were to evaluate acute inflammatory lung injury and to determine iNOS mRNA induction and nitric oxide production by rat broncho-alveolar lavage cells following intratracheal treatment of silica. After 4 h exposure to silica, differential counts of broncho-alveolar lavage cells and lactate dehydrogenase(LDH) activity as well as total protein in the broncho-alveolar lavage fluid were determined. Broncho-alveolar lavage cells were also assayed for iNOS mRNA and the productions of nitrite and nitrate measured in the cells cultured. Differential analysis of broncho-alveolar lavage cells showed that the number of alveolar macrophages slightly decreased following silica treatment; however, red blood cells, lymphocytes, and neutrophils significantly were increased by 9-, 14-, and 119-fold following silica treatment, respectively, compared with the saline control. It was also found significant increases in the LDH activity and total protein in the lavage fluid obtained from silica-treated rats, indicating silica-induced acute lung injury. Northern blot analysis demonstrated that the steady state levels of iNOS mRNA in broncho-alveolar lavage cells were increased following silica treatment. The productions of nitrite and nitrate in the cultured cells were significantly increased by 2-fold following silica treatment, respectively, which were attenuated by the NOS inhibitor $N{\omega}-nitro-L-arginine-methyl$ ester(L-NAME) and partially reversed by L-arginine. These findings suggest that nitric oxide production in alveolar macrophages and recruited neutrophils is increased in response to silica. Nitric oxide may contribute in part to acute inflammatory lung injury.

• Archives of Pharmacal Research
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• 제22권1호
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• pp.55-59
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• 1999

Nitric oxide synthesized by inducible nitric oxide synthase (iNOS) has been implicated as a mediator of inflammation in rheumatic and autoimmune diseases. The effects of higenamine, a tetrahydroisoquinoline compound, on induction of NOS by bacterial lipopolysaccaride (LPS) were examined in murine peritoneal macrophages. LPS-induced nitrite/nitrate production was markedly inhibited by higenamine which at 0.01 mM, decreased nitrite/nitrate levels by $48.7{\pm}4.4%$This was comparable to the inhibition of LPS-induced nitrite/nitrate production by tetrandrin ($49.51{\pm}2.02%$). at the same concentration. Northern and Western blot analysis of iNOS expression demonstrated that iNOS expression was significantly attenuated following co-incubation of peritoneal macrophages with LPS (10 $\mu\textrm{g}$/m;; 18hrs) and higenamine (0.001, 0.,01 mM; 18hrs). These results suggest that higenamine can inhibit LPS-induced expression of iNOS mRNA in murine peritoneal macrophages. The clinical implications of these findings remain to be established.

• 대한의생명과학회지
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• 제19권2호
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• pp.168-172
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• 2013

Toll-like receptors (TLRs) play an important role for host defense against invading pathogens. TLR4 has been identified as the receptor for lipopolysaccharide (LPS), which is a cell wall component of gram-negative bacteria. The activation of TLR4 signaling by LPS leads to the activation of NF-${\kappa}B$ and the expression of pro-inflammatory gene products such as cytokines, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). To evaluate the therapeutic potential of (E)-1-(2-(2-nitrovinyl)phenyl)pyrrolidine (NVPP), previously synthesized in our laboratory, NF-${\kappa}B$ activation and iNOS and COX-2 expression induced by LPS were examined. NVPP inhibited the activation of NF-${\kappa}B$ induced by LPS. NVPP also suppressed the iNOS expression induced by LPS but it did not suppress COX-2 expression induced by LPS. These results suggest that NVPP has the specific mechanism for anti-inflammatory responses.