• Journal of Physiology & Pathology in Korean Medicine
• /
• v.24 no.3
• /
• pp.463-469
• /
• 2010

This research is performed to obtain positive evidences of Mori cortex, a kind of oriental medicinal herbs, in the cellular levels. The extracts of M. cortex have shown anti-inflammatory effects against cutaneous inflammation and clinical effects on pulmonary asthma and congestion in oriental medicine. Thus BV2 cells were chosen because microglia are considered as the main immunocompetent cells in the central nervous system. Lipopolysaccharide (LPS)-induced microglial activation of cultured BV2 cells and subsequent release of nitric oxide (NO) and Prostaglandin E2 (PGE2) were effectively suppressed by methylene chloride extract of Morus alba L. (MEMA). From the inflammation-mediated mRNA and protein analyses, we showed that inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-$1{\beta}$ (IL-$1{\beta}$) and tumor necrosis alpha (TNF-${\alpha}$) induced by LPS were markedly decreased by MEMA treatment. From the observation of nuclear factor-kB (NF-${\kappa}B$) which is controlling and mediating inflammation through COX-2 and iNOS, there showed that p65, a subunit of NF-${\kappa}B$, was increased in nuclear and $I{\kappa}B$, a competitor of NF-${\kappa}B$, was recovered in cytosol after MEMA treatment. These are corresponding with results of iNOS, COX-2, IL-$1{\kappa}$ and TNF-${\alpha}$, and confirm some suppressive effect against transcriptional activation of NF-${\kappa}B$. In conclusion, the anti-inflammatory action of M. cortex against BV2 microglia cells is expected to protect nerve tissues through suppression of neuronal inflammation in various neurodegenerative diseases.

• Molecules and Cells
• /
• v.42 no.9
• /
• pp.628-636
• /
• 2019

Altered genetic features in cancer cells lead to a high rate of aerobic glycolysis and metabolic reprogramming that is essential for increased cancer cell viability and rapid proliferation. Pyruvate kinase muscle (PKM) is a rate-limiting enzyme in the final step of glycolysis. Herein, we report that PKM is a potential therapeutic target in triple-negative breast cancer (TNBC) cells. We found that PKM1 or PKM2 is highly expressed in TNBC tissues or cells. Knockdown of PKM significantly suppressed cell proliferation and migration, and strongly reduced S phase and induced G2 phase cell cycle arrest by reducing phosphorylation of the CDC2 protein in TNBC cells. Additionally, knockdown of PKM significantly suppressed $NF-{\kappa}B$ (nuclear factor kappa-light-chain-enhancer of activated B cells) activity by reducing the phosphorylation of p65 at serine 536, and also decreased the expression of $NF-{\kappa}B$ target genes. Taken together, PKM is a potential target that may have therapeutic implications for TNBC cells.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.6
• /
• pp.2277-2281
• /
• 2015

Objectives: To explore the expression of astrocyte elevated gene-1 (AEG-1) in cervical cancer and analyze its correlation with microvascular density (MVD), nuclear factor kappaB (NF-kB p65) and vascular endothelial growth factor (VEGF). Materials and Methods: Immunohistochemical MaxVision method was adopted to detect the expression level of AEG-1, NF-kB p65 and VEGF in 45 samples of invading cervical cancer and 12 samples of cervicitis from The First Affiliated Hospital of Wenzhou Medical University. Tumor microvascular endothelial marker CD34 combined with Weidner was used to determine the MVD in cervical cancer tissue. The positive expression and staining conditions of AEG-1, NF-kB p65 and VEGF in cervical cancer tissues were observed under a light microscope. Correlations between expression of AEG-1 protein and those of NF-Kb p65 and VEGF, as well as MVD, were analyzed using Pearson correlation. Results: The expression levels of AEG-1 were $0.186{\pm}0.043$ in cervical cancer and $0.051{\pm}0.002$ in chronic cervicitis (p<0.01). Moreover, expression of AEG-1 was related to vascular invasion and lymphatic metastasis of cervical cancer (p<0.01), but not with age of the patients, differentiation degree, tumour size, pathological type and parametrial infiltration (p>0.05). Pearson correlation analysis showed that the expression of AEG-1 was linked with NF-kB p65 (r=0.501, p=0.000), VEGF (r=0.718, p=0.000) as well as MVD in cervical cancer tissue (r=0.815, p=0.000). Conclusions: AEG-1 is highly expressed in cervical cancer and promotes angiogenesis, which might be related to the fact that AEG-1 activating the signal pathway of NF-kB could up-regulate the level of VEGF expression.

• The Korean Journal of Physiology and Pharmacology
• /
• v.18 no.4
• /
• pp.313-320
• /
• 2014

The study was conducted to investigate the role of vitamin E in the high altitude hypoxia-induced damage to the intestinal barrier in rats. Sprague-Dawley rats were divided into control (Control), high altitude hypoxia (HH), and high altitude hypoxia + vitamin E (250 mg/kg $BW^*d$) (HV) groups. After the third day, the HH and HV groups were placed in a hypobaric chamber at a stimulated elevation of 7000 m for 5 days. The rats in the HV group were given vitamin E by gavage daily for 8 days. The other rats were given equal volume saline. The results showed that high altitude hypoxia caused the enlargement of heart, liver, lung and kidney, and intestinal villi damage. Supplementation with vitamin E significantly alleviated hypoxia-caused damage to the main organs including intestine, increased the serum superoxide dismutase (SOD) (p< 0.05), diamino oxidase (DAO) (p< 0.01) levels, and decreased the serum levels of interleukin-2 (IL-2) (p< 0.01), interleukin-4 (IL-4) (p<0.001), interferon-gamma ($IFN-{\gamma}$) (p<0.01) and malondialdehyde (MDA) (p<0.001), and decreased the serum erythropoietin (EPO) activity (p<0.05). Administration of vitamin E significantly increased the S-IgA (p<0.001) in ileum and significantly improved the expression levels of occludin and $I{\kappa}B{\alpha}$, and decreased the expression levels of hypoxia-inducible factor 1 alpha and 2 alpha ($HIF-1{\alpha}$ and $HIF-2{\alpha}$), Toll-like receptors (TLR4), P-$I{\kappa}B{\alpha}$ and nuclear factor-${\kappa}B$ p65(NF-${\kappa}B$ P65) in ileum compared to the HH group. This study suggested that vitamin E protectis from intestinal injury caused by high altitude hypoxia environment. These effects may be related to the HIF and TLR4/NF-${\kappa}B$ signaling pathway.

• Biomolecules & Therapeutics
• /
• v.19 no.3
• /
• pp.331-335
• /
• 2011

In this study, we determined the anti-inflammatory activity and mechanism of action of a hexane fraction (hWRF) obtained from white Rosa hybrida flowers by employing various assays such as quantitative real-time PCR, Western blotting, and Electrophoretic-Mobility Shift Assay (EMSA). The results revealed that the hWRF had excellent anti-inflammatory potency by reducing inflammatory repertoires, such as inducible nitric oxide synthase (iNOS), interleukin-$1{\beta}$, and cyclooxygenase-2 (COX-2) in RAW264.7 cells when stimulated with lipopolysaccharide (LPS), a pro-inflammatory mediator. The reduction of nitric oxide (NO) release from RAW 264.7 cells supported the anti-inflammatory effect of hWRF. Interestingly, hWRF effectively inhibited LPS-mediated nuclear factor-${\kappa}B$ (NF-${\kappa}B$) p65 subunit translocation into the nucleus and extracellular signal-regulated kinase (ERK)1/2 phosphorylation, suggesting that hWRF anti-inflammatory activity may be based on inhibition of the NF-${\kappa}B$ and MAPK pathways. Based on the findings described in this study, hWRF holds promise for use as a potential anti-inflammatory agent for either therapeutic or functional adjuvant purposes.

• The Journal of Korean Obstetrics and Gynecology
• /
• v.32 no.3
• /
• pp.32-56
• /
• 2019

Objectives: The purpose of this study was to investigate the in vitro anti-inflammatory, anti-pruritic and antimicrobial effects of the three herbal prescription (EST, SCT, WDT), which has been traditionally used for treating leukorrhea induced by various infections in the female genital tract. Methods: In this experiment, the anti-inflammatory effects were evaluated by Nitric oxide (NO), $Interlukine-1{\beta}$ ($IL-1{\beta}$), Interlukine-2 (IL-2), Interlukine-6 (IL-6), Tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), Prostaglandin $E_2$ ($PGE_2$), Leukotriene $B_4$ ($LTB_4$) production amount and Inducible nitric oxide synthase (iNOS), Nuclear factor kappa B ($NF-{\kappa}B$), Cyclooxygenase-2 (COX-2) gene expression levels in RAW264.7 cells. And the anti-pruritic effects were evaluated by Histamine, Acetylcholine (ACh), Acetylcholinesterase (AChE), Substance P production amount in Mast cell/9 (MC/9) and Pheochromocytoma 12 (PC12) cells. The anti-microbial effect was measured by inhibition zone diameter on Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans and Aspergillus niger. Results: As a result of measuring anti-inflammatory efficacy, $IL-1{\beta}$, IL-2, IL-6, $TNF-{\alpha}$, $PGE_2$, and $LTB_4$ production amounts were significantly reduced in the EST, SCT, WDT extraction groups compared with the control group, and significantly decreased the amount of $NF-{\kappa}B$, iNOS, and COX-2 gene expression and the amount of Phospho-Inhibitor kappa B alpha ($p-I{\kappa}B-{\alpha}$)/Inhibitor kappa B alpha ($I{\kappa}B-{\alpha}$) and $NF-{\kappa}B$ p65 protein expression. In addition, As a result of measuring the anti-pruritic effect, the amounts of histamine, ACh and Substance P were significantly decreased, and AChE production was slightly decreased, but it's significance did not appear. Finally the anti-microbial effects of EST, SCT, WDT extraction groups against Pseudomonas aeruginosa, Candida albicans and Aspergillus niger was inhibited, however the growth of Escherichia coli and Staphylococcus aureus was not inhibited. Conclusions: These data suggest that EST, SCT, WDT can be used to treat patients with leukorrhea.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.45 no.2
• /
• pp.194-201
• /
• 2016

The anti-inflammatory activity of ethanol extract from Chondrus nipponicus Yendo (CNYEE) was investigated by measuring production of a lipopolysaccharide-induced inflammatory response mediator. CNYEE had no cytotoxic effects on proliferation of macrophages compared to the control. CNYEE significantly inhibited (over 50%) NO production at $50{\mu}g/mL$, with inhibitory effects on expression levels of cytokines such as interleukin (IL)-6, tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and IL-$1{\beta}$. In particular, IL-6 inhibitory activity of CNYEE was higher than 70% at $100{\mu}g/mL$. CNYEE also reduced protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor (NF)-${\kappa}B$ in a dose-dependent manner. CNYEE also significantly reduced phosphorylation of p38, extracellular signal-regulated kinase, and c-Jun N-terminal kinase. Therefore, these results suggest that CNYEE may have anti-inflammatory effects by modulating the NF-${\kappa}B$ and mitogen-activated protein kinases signaling pathways and may be used as an anti-inflammatory therapeutic material.

• The Korean Journal of Physiology and Pharmacology
• /
• v.13 no.6
• /
• pp.475-482
• /
• 2009

Rifampicin is a macrocyclic antibiotic which is used extensively for treatment against Mycobacterium tuberculosis and other mycobacterial infections. Recently, a number of studies have focused on the immune-regulatory effects of rifampicin. Therefore, we hypothesized that rifampicin may influence the TLR2 expression in LPS-activated RAW 264.7 cells. In this study, we determined that rifampicin suppresses LPS-induced TLR2 mRNA expression. The down-regulation of TLR2 expression coincided with decreased production of TNF-$\alpha$ Since NF-${\kappa}B$ is a major transcription factor that regulates genes for TLR2 and TNF-$\alpha$, we examined the effect of rifampicin on the LPS-induced NF-${\kappa}B$ activation. Rifampicin inhibited NF-${\kappa}B$ DNA-binding activity in LPS-activated RAW 264.7 cells, while it did not affect IKK$\alpha/\beta$ activity. However, rifampicin slightly inhibited the nuclear translocation of NF-${\kappa}B$ p65. In addition, rifampicin increased physical interaction between pregnane X receptor, a receptor for rifampicin, and NF-${\kappa}B$ p65, suggesting pregnane X receptor interferes with NF-${\kappa}B$ binding to DNA. Taken together, our results demonstrate that rifampicin inhibits LPS-induced TLR2 expression, at least in part, via the suppression of NF-${\kappa}B$ DNA-binding activity in RAW 264.7 cells. Thus, the present results suggest that the rifampicin-mediated inhibition of TLR2 via the suppression of NF-${\kappa}B$ DNA-binding activity may be a novel mechanism of the immune-suppressive effects of rifampicin.

• Biomolecules & Therapeutics
• /
• v.31 no.3
• /
• pp.306-311
• /
• 2023

The current study aimed to reveal the potential effect of meclofenamate, a nonsteroidal anti-inflammatory drug, on the gene expression of airway MUC5AC mucin. Human pulmonary mucoepidermoid NCI-H292 cells were pretreated with meclofenamate for 30 min and stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 h. Thereafter, the effect of meclofenamate on the PMA-induced nuclear factor kappa B (NF-kB) signaling pathway was assessed. Meclofenamate inhibited glycoprotein production and mRNA expression of MUC5AC mucins induced by PMA by inhibiting the degradation of inhibitory kappa Bα (IkBα) and NF-kB p65 nuclear translocation. These results suggest meclofenamate suppresses mucin gene expression by regulating NF-kB signaling pathway in human pulmonary epithelial cells.

• Nutrition Research and Practice
• /
• v.9 no.2
• /
• pp.123-128
• /
• 2015

BACKGROUND/OBJECTIVES: Natural products or active components with a protective effect against oxidative stress have attracted significant attention for prevention and treatment of degenerative disease. Oligonol is a low molecular weight polyphenol containing catechin-type monomers and oligomers derived from Litchi chinensis Sonn. We investigated the protective effect and its related mechanism of oligonol against oxidative stress. MATERIALS/METHODS: Oxidative stress in C6 glial cells was induced by hydrogen peroxide ($H_2O_2$) and the protective effects of oligonol on cell viability, nitric oxide (NO) and reactive oxygen species (ROS) synthesis, and mRNA expression related to oxidative stress were determined. RESULTS: Treatment with oligonol inhibited NO and ROS formation under cellular oxidative stress in C6 glial cells. In addition, it recovered cell viability in a dose dependent-manner. Treatment with oligonol also resulted in down-regulated mRNA expression related to oxidative stress, nuclear factor kappa-B (NF-${\kappa}B$) p65, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS), compared with the control group treated with $H_2O_2$. In particular, expression of NF-${\kappa}B$ p65, COX-2, and iNOS was effectively reduced to the normal level by treatment with $10{\mu}g/mL$ and $25{\mu}g/mL$ of oligonol. CONCLUSIONS: These results indicate that oligonol has protective activity against oxidative stress-induced inflammation. Oligonol might be a promising agent for treatment of degenerative diseases through inhibition of ROS formation and NF-${\kappa}B$ pathway gene expression.