• Biomolecules & Therapeutics
• /
• 제27권4호
• /
• pp.381-385
• /
• 2019

We attempted to examine anti-inflammatory and anti-oxidant effects of 4'-O-${\beta}$-D-glucosyl-5-O-methylvisamminol (GOMV), the first epigenetic inhibitor of histone phosphorylation at Ser10. While GOMV did not affect the viability of murine macrophage RAW 264.7 cells, it significantly suppressed lipopolysaccharide (LPS)-induced generation of prostaglandin $E_2$ ($PGE_2$) and nitric oxide (NO) through transcriptional inhibition of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). GOMV also scavenged free radicals in vitro, increased NF-E2-related factor 2 (NRF2), and activated antioxidant response element (ARE), thereby resulting in the induction of phase II cytoprotective enzymes in human keratinocyte HaCaT cells. Finally, GOMV significantly protected HaCaT cells against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced oxidative intracellular damages. Together, our results illustrate that GOMV possesses anti-inflammatory and anti-oxidant activity.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
• /
• pp.146.2-147
• /
• 2003

The benzoxathiol LYR-71 compound was discovered as an inhibitor of NF-kB transcriptional activity with an IC50 value of 5.4 uM. Furthermore, benzoxathiol LYR-71 compound inhibited the NF-kB binding activity to DNA in a dose-dependent manner, which was identified by EMSA with oligonucleotide corresponding to NF-kB consensus sequence. It is well known that NF-kB is an important transcription factor to regulate the expression of inflammatory enzymes (iNOS and COX-2) and cytokines (TNF, IL-1 and IL-6). (omitted)

• Nutrition Research and Practice
• /
• 제14권2호
• /
• pp.109-116
• /
• 2020

BACKGROUND/OBJECTIVES: Excessive intake of simple sugars induces obesity and increases the risk of inflammation. Thus, interest in alternative sweeteners as a sugar substitute is increasing. The purpose of this study was to determine the effect of saccharin on inflammation in 3T3-L1 adipocytes. MATERIALS/METHODS: 3T3-L1 preadipocytes were differentiated into adipocytes. The adipocytes were treated with saccharin (0, 50, 100, and 200 ㎍/mL) for 24 h. Inflammation was induced by exposure of treated adipocytes to lipopolysaccharide (LPS) for 18 h and cell proliferation was measured. The concentration of nitric oxide (NO) was measured by using Griess reagent. Protein expressions of nuclear factor kappa B (NF-κB) and inhibitor κB (IκB) were determined by western blot analysis. The mRNA expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin 1β (IL-1β), interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α) were determined by real-time PCR. RESULTS: Compared with the control group, the amount of NO and the mRNA expression of iNOS in the LPS-treated group were increased by about 17.6% and 46.9%, respectively, (P < 0.05), and those parameter levels were significantly decreased by saccharin treatment (P < 0.05). Protein expression of NF-κB was decreased and that of IκB was increased by saccharin treatment (P < 0.05). Saccharin decreased the mRNA expression of COX-2 and the inflammation cytokines (IL-1β, IL-6, MCP-1, and TNF-α) (P < 0.05). CONCLUSIONS: The results of this study suggest that saccharin can inhibit LPS-induced inflammatory responses in 3T3-L1 adipocytes via the NF-κB pathway.

• 한국약용작물학회지
• /
• 제16권5호
• /
• pp.326-331
• /
• 2008

To search for immunoactive natural products exerting anti-inflammatory activity, we have evaluated the effects on the water extracts of Artemisia princeps Pampanini (APP) on lipopolysaccharide-induced nitric oxide (NO), tumor necrosis factor-$\alpha$ (TNF-$\alpha$), and prostaglandin $E_2$ ($PGE_2$) production by RAW 264.7 macrophage cell line. Our data indicate that this extract is a potent inhibitor of NO production and it also significantly decreased PGE2 and TNF-$\alpha$ production. Consistent with these results, the protein and mRNA expression level of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) was inhibited by water extracts of APP in a dose-dependent manner. These results suggest that APP may exert anti-inflammatory and analgesic effects possibly by suppressing the inducible NO synthase and COX-2 expressions.

• 약학회지
• /
• 제45권1호
• /
• pp.116-124
• /
• 2001

Nitric oxide is a labile, gaseous, broad spectrum second messenger that used in various tissues and cells. If it is induced by endogenously and exogenously in the neuronal cells, it is able to mediate analgesia or hyperalgesia at the periphery and in the spinal level respectively. This dual role of nitric oxide in the sensory system is very intriguing but has not been fully understood yet. In this experiment, acetylcholine (300 $\mu$g/paw), sodium nitroprusside (600 $\mu$g/paw), and L-arginine (300 $\mu$g/paw) represented antinociceptive effect to noxious topical stimulus, but pronociceptive responses followed by spinally application (20$\mu$g/5$\mu$l, 10$\mu$g/3$\mu$l, 500$\mu$g/5$\mu$l respectively). Calcium ion is critical element which activates nitric oxide synthase, therefore verapamil (300 $\mu$g/paw) and NOS inhibitor (20 mg/kg, L-NAME or L-NOArg) are injected into right hind paw (i.pl.). When verapamil is combined with NOS inhibitors analgesic effects through NO-cGMP pathway are inhibited as compared with ACh alone. Diluted formalin (2.5%), when injected into rats'hind paw (0.05 ml), elicited a biphasic algesic responses and nitric oxide had an analgesic effect on both $A\delta$ and C sensory nerve fibers which manipulate the phases respective1y. Nitric oxides, which produced from constitutive nitric oxide synthase, activated cyclooxygenase-type I and then prostaglandins are produced from them. So, indomethacin and ibuprofen, inhibitors of COX$_1$enzyme, when pretreated intraperitoneally (100 mg/kg) could reduce the hyperalgesic state. From these results, it is possible to imagine that the intrathecally administered NO donors expressed hyperalgesia through both long-term potentiation mechanism and arachidonic acid-prostaglandin cascade.

• BMB Reports
• /
• 제52권12호
• /
• pp.695-699
• /
• 2019

Cytokine-induced apoptosis inhibitor 1 (CIAPIN1), known as an anti-apoptotic and signal-transduction protein, plays a pivotal role in a variety of biological processes. However, the role of CIAPIN1 in inflammation is unclear. We investigated the protective effects of CIAPIN1 in lipopolysaccharide (LPS)-exposed Raw 264.7 cells and against inflammatory damage induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in a mouse model using cell-permeable Tat-CIAPIN1. Transduced Tat-CIAPIN1 significantly reduced ROS production and DNA fragmentation in LPS-exposed Raw 264.7 cells. Also, Tat-CIAPIN1 inhibited MAPKs and NF-κB activation, reduced the expression of Bax, and cleaved caspase-3, COX-2, iNOS, IL-6, and TNF-α in LPS-exposed cells. In a TPA-induced animal model, transduced Tat-CIAPIN1 drastically decreased inflammation damage and inhibited COX-2, iNOS, IL-6, and TNF-α expression. Therefore, these findings suggest that Tat-CIAPIN1 might lead to a new strategy for the treatment of inflammatory skin disorders.

• Biomolecules & Therapeutics
• /
• 제19권4호
• /
• pp.419-424
• /
• 2011

Galla Rhois and its components are known to possess anti-infl ammatory properties. In the present study, we prepared equilibrium mixture of ethyl m-digallate and ethyl p-digallate isomers (EDG) from Galla Rhois and examined its effect on nitric oxide (NO) production in murine macrophage cell line. Treatment of RAW264.7 macrophages with EDG signifi cantly inhibited NO production and inducible nitric oxide synthase (iNOS) expression stimulated by LPS, as assessed by Western blot and quantitative RT-PCR analyses. We also demonstrated that EDG treatment led to an increase in heme oxygenase-1 (HO-1) mRNA and protein expression. EDG treatment also enhanced expression level of nuclear factor-erythroid 2-related factor 2 (Nrf2) in nucleus, which is critical for transcriptional induction of HO-1. Treatment with SnPP (tin protoporphyrin IX), a selective HO-1 inhibitor, reversed EDG-mediated inhibition of nitrite production, suggesting that HO-1 plays an important role in the suppression of NO production by EDG. Taken together, these results indicate that EDG isolated from Galla Rhois suppresses LPS-stimulated NO production in RAW 264.7 macrophages via HO-1 induction.

• 대한한방소아과학회지
• /
• 제35권4호
• /
• pp.48-55
• /
• 2021

Objective The purpose of this study was to confirm the effects of Galgeunhwanggeumhwangryeon-tang in reducing inflammation through the endocannabinoid system (ECS) control in atopic dermatitis. Methods 8-week-old Balb/C mice were divided into 4 groups: contorl group (Ctrl), lipid barrier elimination group (ADE), palmitoylethanolamide treated group after lipid barrier elimination (PEA), and Galgeunhwanggeumhwangryeon-tang applied group after lipid barrier elimination (GGRT). After inducing atopic dermatitis, cannabinoid receptor (CB) 1, CB2, CD68, phosphorylated inhibitor kappa B (p-IκB), inducible nitric oxide synthase (iNOS), substance P and serotonin were observed to confirm the regulation of the ECS, macrophage activity and mast cell activity. Results CB1 and CB2 showed higher positive reactions in the GGRT than in the LBE and PEA. CD68, p-IκB and iNOS showed higher positive reaction in the LBE, PEA and GGRT than in the Ctrl, but the increase in the positive reaction was lower in the GGRT compared to the LBE and PEA. Substance P and serotonin showed higher positive reaction in the LBE, PEA and GGRT than in the Ctrl, but the increase in the positive reaction was lower in the GGRT compared to the LBE and PEA. Conclusions The effects of Galgeunhwanggeumhwangryeon-tang were confirmed though the regulation of the ECS, macrophage activity and mast cell activity.

• 대한한방소아과학회지
• /
• 제36권3호
• /
• pp.87-96
• /
• 2022

Objective The purpose of this study was to confirm the effect of Sabaek-san extract on skin damage recovery and inflammation relief in atopic dermatitis-induced mice through Endocannabinoid system (ECS) control. Methods In this study, we used 6-week-old NC/Nga mice were divided into 4 group: control group (Ctrl), lipid barrier elimination group (LBEG), palmitoylethanolamide (PEA) treated group after lipid barrier elimination (PEAG), and Sabaek-san extract treatment group after lipid barrier elimination (SBSG). Each group was assigned 10 animals. After drug administration of three weeks duration following lipid barrier elimination, cannabinoid receptor (CB) 1, CB2, CD (Cluster of Differentiation) 68, phosphorylated inhibitor kappa B (p-IκB), inducible nitric oxide synthase (iNOS), Fc ε receptor, substance P and serotonin were observed to confirm the regulation of the ECS, macrophage activity and mast cell activity. Results We found that 8-hydroxydeoxyguanosine (8-OXdG) positive reaction was significantly lower in the SBST group than in LBET and PEAT groups. Both CB1 and CB2 showed higher positive reactions in the SBST group than in the LBET and PEAT. CD68, p-IκB, iNOS, Fc ε receptor, Substance P and serotonin showed lower positive reaction in the SBST compared to the LBET and PEAT. Conclusion It was confirmed that the Sabaek-san extract can reduce the inflammation of atopic dermatitis by restoring the structural damage of the skin lipid barrier through ECS activity.

• Parasites, Hosts and Diseases
• /
• 제62권1호
• /
• pp.30-41
• /
• 2024

The dense granule protein of Toxoplasma gondii, inhibitor of signal transducer and activator of transcription 1 (IST) is an inhibitor of signal transducer and activator of transcription 1 (STAT1) transcriptional activity that binds to STAT1 and regulates the expression of inflammatory molecules in host cells. A sterile inflammatory liver injury in pathological acute liver failures occurs when excessive innate immune function, such as the massive release of IFN-γ and TNF-α, is activated without infection. In relation to inflammatory liver injury, we hypothesized that Toxoplasma gondii inhibitor of STAT1 transcription (TgIST) can inhibit the inflammatory response induced by activating the STAT1/IRF-1 mechanism in liver inflammation. This study used IFN-γ and TNF-α as inflammatory inducers at the cellular level of murine hepatocytes (Hepa-1c1c7) to determine whether TgIST inhibits the STAT1/IRF-1 axis. In stable cells transfected with TgIST, STAT1 expression decreased with a decrease in interferon regulatory factor (IRF)-1 levels. Furthermore, STAT1 inhibition of TgIST resulted in lower levels of NF-κB and COX2, as well as significantly lower levels of class II transactivator (CIITA), iNOS, and chemokines (CLXCL9/10/11). TgIST also significantly reduced the expression of hepatocyte proapoptotic markers (Caspase3/8/9, P53, and BAX), which are linked to sterile inflammatory liver injury. TgIST also reduced the expression of adhesion (ICAM-1 and VCAM-1) and infiltration markers of programmed death-ligand 1 (PD-L1) induced by hepatocyte and tissue damage. TgIST restored the cell apoptosis induced by IFN-γ/TNF-α stimulation. These results suggest that TgIST can inhibit STAT1-mediated inflammatory and apoptotic responses in hepatocytes stimulated with proinflammatory cytokines.