• Biomedical Science Letters
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• v.25 no.2
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• pp.196-200
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• 2019

Effect of retinoids, i.e., all-trans retinoic acid and 13-cis retinoic acid, on the activity of nitric oxide synthase (NOS) was evaluated in human malignant keratinocytes to examine the possible correlation of retinoids with NOS activities. All-trans retinoic acid and 13-cis retinoic acid did not alter the nitric oxide (NO) production. However, in the presence of lipopolysaccharide (LPS, $1{\mu}g/mL$), they significantly increased NO release in a dose-dependent manner until 48 h at concentrations of $50{\sim}100{\mu}M$. The degree of upregulation of NO by all-trans retinoic acid and 13-cis retinoic acid increased up to 35% and 37%, respectively, compared to that by the control, which demonstrated the upregulation of LPS-inducible nitric oxide synthase (iNOS)-dependent generation of NO as well as showing a crucial link between retinoids-induced activity and NOS. Findings of this study now suggest that the upregulation of LPS-iNOS activity may be associated with modulation of retinoids-induced control of cellular developmental processes, which may produce new therapeutics of retinoids in the complexity of how NO affects human keratinocytes.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.176-176
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• 1998

An enhanced formation of nitric oxide (NO) is an important mediator of hypotention, peripheral vasodilation and vascular hyporeactivity to vasoconstrictor agents in endotoxaemia. And tumor necrosis factor (TNF${\alpha}$), as a primary mediator of circulatory shock has been known to induce inducible nitric oxide synthase (i-NOS), leading to excessive production of NO. We isolated two sesquiterpene lactone compounds from Saussurea lappa and their structures were elucidated as dehydrocostus lactone and costunolide. These compounds inhibit the production of both NO and TNF${\alpha}$ by LPS (1 $\mu\textrm{g}$/$m\ell$)-activated Raw 264.7 cells. NO was measured spectropho-tometrically as nitrite by the Griess reagent and TNF${\alpha}$ by ELISA. Dehydrocostus lactone (IC$\sub$50/ : 3.0 ${\mu}$M) and costunolide (IC$\sub$50/ : 4.5 ${\mu}$M) inhibited the production of NO in LPS-activated Raw 264.7 cells by suppressing inducible nitric oxide synthase enzyme expression. These compounds also decreased the TNF${\alpha}$ levels in LPS-activated system in vitro and in vivo.

• Korean Journal of Veterinary Research
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• v.51 no.3
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• pp.185-191
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• 2011

Trimethyltin chloride (TMT) has been used as a neurotoxin for inducing brain dysfunction and neuronal death. Neuronal death in the hippocampus by TMT may generate excessive nitric oxide, but there are few studies about nitric oxide synthase enzyme involved in the synthesis of nitric oxide. The purpose of present study is to analyze the TMT toxicity in each region of rat hippocampus. To evaluate the involvement of nitric oxide, we analyzed the effects of aminoguanidine known as a selective inhibitor for inducible nitric oxide synthase on behavioral changes and the hippocampus of rat by TMT toxicity. 6-week-old male Sprague-Dawley rats were administered with a single dose of TMT (8 mg/kg b.w., i.p.) and the control group was similarly administered with distilled water. TMT + aminoguanidine-treated groups were administered with aminoguanidine (10 mg/kg or 100 mg/kg b.w., i.p.) for 3 days prior to TMT injection. The rats were sacrificed 2 days after TMT administration. In the TMT-treated group, a number of cell losses were seen in CA1, CA3 and the dentate gyrus. In the TMT + aminoguanidine-treated group, neuronal death was seen in CA1 and CA3, but reduced in the dentate gyrus compared to the TMT-treated group. Western blot analysis showed that cleaved caspase-3 expression was increased in the TMT-treated group compared to the control group. However, the expression significantly declined in the TMT + aminoguanidine-treated group. The present findings suggest that inducible nitric oxide synthase is involved in neuronal death induced by TMT.

• Korean Journal of Food Science and Technology
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• v.43 no.1
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• pp.110-113
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• 2011

Egg allergies are the most prevalent food hypersensitivity in children. The major egg allergens are proteins, such as ovalbumin (OVA) and ovomucoid (OVM), which are mainly contained in egg whites. OVA is the major protein in egg white, comprising 54% of the total protein content. OVA has been widely used in experimental inhalant and dietary allergy animal models, but its mechanism has not been clearly identified. In this study, we showed that OVA induced nuclear factor-${\kappa}B$ activation. OVA also induced the expression of cyclooxygenase-2 and inducible nitric oxide synthase. These data suggest new approaches for developing efficient anti-allergic strategies.

• Advances in Traditional Medicine
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• v.7 no.5
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• pp.540-548
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• 2008

Paeonia radix is the root of Paeonia aliflora Pallas, which is a perennial plant classified in the family Paeoniaceae. Paeonia radix possesses several pharmacological effects such as analgesic, anti-inflammatory and anti-allergic, anti-oxidative, and anti-coagulant activities. In this study, we investigated the effect of the aqueous extract of Paeonia radix on the lipopolysaccharide-induced inflammation in mouse BV2 microglial cells. The aqueous extract of Paeonia radix at respective concentration was treated one hour before lipopolysaccharide treatment. In the present results, the aqueous extract of Paeonia radix suppressed prostaglandin $E_2$ synthesis and nitric oxide production by inhibiting the lipopolysaccharide-stimulated mRNA expressions of cyclooxygenase-2 and inducible nitric oxide synthase in mouse BV2 microglial cells. These results demonstrate that Paeonia radix exerts anti-inflammatory and analgesic effects probably by suppressing mRNA expressions of cyclooxygenase-2 and inducible nitric oxide synthesis. The present study demonstrates that Paeonia radix may offer a valuable mean of therapy for brain inflammatory diseases.

• Biomedical Science Letters
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• v.19 no.2
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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.

• Biomedical Science Letters
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• v.24 no.2
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• pp.102-107
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• 2018

Toll-like receptors (TLRs) play an important role for host defense against invading pathogens. 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 cardamonin, which is a naturally occurring chalcone from Alpinia species (zingiberaceous plant species), $NF-{\kappa}B$ activation and iNOS expression induced by MALP-2 (TLR2 and TLR6 agonist) or LPS (TLR4 agonist) were examined. Cardamonin inhibited the activation of $NF-{\kappa}B$ induced by MALP-2 or LPS. Cardamonin also suppressed the iNOS expression induced by MALP-2 or LPS. These results suggest that cardamonin has the specific mechanism for anti-inflammatory responses by regulating of TLRs signaling pathway.

• Biomedical Science Letters
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• v.23 no.2
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• pp.104-110
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• 2017

Inflammation is a pathophysiological process that is known to be involved in numerous diseases. Microbial infection or tissue injury activates inflammatory responses, resulting in the induction of proinflammatory proteins including inducible nitric oxide synthase (iNOS). Aster yomena is used in traditional Korean remedies. Here, we investigated the effects of ethanol extracts of Aster yomena (EAY) on the expression of iNOS induced by ovalbumin (OVA), one of the major egg allergens, or lipopolysaccharide (LPS), a Toll-like receptor 4 agonist. EAY inhibited OVA- or LPS-induced $NF-{\kappa}B$ activation. EAY also suppressed OVA- or LPS-induced iNOS expression and nitrite production. These results suggest that EAY has the specific mechanism for anti-inflammatory responses and the potential to be developed as a potent anti-inflammatory and anti-allergic drug.

• Biomedical Science Letters
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• v.25 no.1
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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.

• The Journal of Korean Medicine
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• v.26 no.4
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• pp.152-161
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• 2005

The excessive release of proinflammatory products by activated microglia causes neurotoxicity, and this has been implicated in the pathogenesis of neurodegenerative diseases. Harpagophytum procumbens (Pedaliaceae) has been widely used for the treatment of pain and arthritis in the clinical field. In this study, we investigated the effect of Harpagophytum procumbens against lipopolysaccharide-induced inflammation. From the present results, the aqueous extract of Harpagophytum procumbens was shown to suppress prostaglandin-E2 synthesis and nitric oxide production by inhibiting the lipopolysaccharide-stimulated enhancement of cyclooxygenase-2 and inducible nitric oxide synthase expressions in mouse BV2 microglial cells. These results suggest that Harpagophytum procumbens may offer a valuable means of therapy for the treatment of brain inflammatory diseases by attenuating lipopolysaccharide-induced prostaglandin-E2 synthesis and nitric oxide production.