• The Korean Journal of Physiology and Pharmacology
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• v.15 no.3
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• pp.143-147
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• 2011

Defensins, cysteine-rich cationic polypeptides released from neutrophils, are known to have powerful antimicrobial properties. In this study, we sacrificed 30 rats to investigate the effects of ${\alpha}$-defensin 1 on detrusor muscle contractions in isolated rat bladder. From the experiments we found relaxing effects of ${\alpha}$-defensin 1 on the contractions induced by phenylephrine (PE) but not by bethanechol (BCh) in the detrusor smooth muscles. To determine the mechanisms of the effects of ${\alpha}$-defensin 1, the changes of effects on PE-induced contraction by ${\alpha}$-defensin 1 pretreatment were observed after pretreatment of Rho kinase inhibitor (Y-27632), protein kinase C (PKC) inhibitor (Calphostin C), potent activator of PKC (PDBu; phorbol 12,13-dibutyrate), and NF-${\kappa}B$ inhibitors (PDTC; pyrrolidinedithiocarbamate and sulfasalazine). The contractile responses of PE ($10^{-9}{\sim}10^{-4}$ M) were significantly decreased in some concentrations of ${\alpha}$-defensin 1 ($5{\times}10^{-9}$ and $5{\times}10^{-8}$ M). When strips were pretreated with NF-kB inhibitors (PDTC and sulfasalazine; $10^{-7}{\sim}10^{-6}$ M), the relaxing responses by ${\alpha}$-defensin 1 pretreatment were disappeared. The present study demonstrated that ${\alpha}$-defensin 1 has relaxing effects on the contractions of rat detrusor muscles, through NF-${\kappa}B$ pathway. Further studies in vivo are required to clarify whether ${\alpha}$-defensin 1 might be clinically related with bladder dysfunction by inflammation process.

• Korean Journal of Plant Resources
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• v.31 no.3
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• pp.211-217
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• 2018

Hibiscus syriacus (H. syriacus) as the national flower of Korea has been used as the herbal medicine in Asia. In this study, we evaluated the anti-inflammatory effect of 70% ethanol extracts from the root of Hibiscus syriacus (RHS-E70) and elucidated the potential signaling pathway in LPS-stimulated RAW264.7 cells. RHS-E70 dose-dependently suppressed NO production by inhibiting iNOS and IL-${\beta}$ expression in LPS-stimulated RAW264.7 cells. RHS-E70 inhibited the phosphorylation and degradation of $I{\kappa}B-{\alpha}$, which contributed to the inhibition of p65 nuclear accumulation and NF-${\kappa}B$ activation. Furthermore, RHS-E70 suppressed the phosphorylation of ERK1/2 and p38, which results in the inhibition of ATF2 phosphorylation and subsequent nuclear accumulation. These results indicate that RHS-E70 may exert anti-inflammatory activity by inhibiting NF-${\kappa}B$ and MAPK/ATF2 signaling. From these findings, RHS-E70 has potential to be a candidate for the development of chemopreventive or therapeutic agents for the inflammatory diseases.

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

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3239-3245
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• 2012

Gliomas are a group of heterogeneous primary central nervous system tumors. Hyperthermia has proven to be a potential therapeutic tool for cancers in the clinic. However, the molecular mechanisms of hyperthermia remain unclear. The objective of this study was to investigate the effects of hyperthermia on the invasiveness in C6 glioma cells and related molecular pathways. Here our data show hyperthermia stimulated the release of tumor necrosis factor-alpha (TNF-${\alpha}$) and decreased C6 glioma cell migration and invasive capability at 30, 60, 120 and 180 min; with increased spontaneous apoptosis in C6 glioma cells at 120 min. We also found mitogen-activated protein kinase (P38 MAPK) protein expression to be increased and nuclear factor-kappa B (NF-${\kappa}B$) protein expression decreased. Based on the results, we conclude that hyperthermia alone reduced invasion of C6 glioma cells through stimulating TNF-${\alpha}$ signaling to activate apoptosis, enhancing P38 MAPK expression and inhibiting the NF-${\kappa}B$ pathway, a first report in C6 rat glioma cells.

• Molecules and Cells
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• v.22 no.1
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• pp.104-112
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• 2006

We previously reported that DA-9601, ethanol herbal extract of Artemisia asiatica, inhibited histamine and leukotriene releases in guinea pig lung mast cells activated with specific antigen/antibody reaction. This study aimed to evaluate the inhibitory effect of DA-9601 on the OVA-induced airway inflammation in allergic asthma mouse model. BALB/c mice were sensitized and challenged with OVA. DA-9601 was administered orally 1 h before every local OVA-challenge. OVA-specific serum IgE was measured by ELISA, recruitment of inflammatory cells in BAL fluids and lung tissues by Diff-Quik and H&E staining, respectively, the expressions of CD40, CD40L and VCAM-1 by immunohistochemistry, goblet cell hyperplasia by PAS staining, activities of MMPs by gelatin zymography, expressions of mRNA and proteins of cytokines by RT-PCR and ELISA, activities of MAP kinases by western blot, and activity of NF-${\kappa}B$ by EMSA. DA-9601 reduced IgE level, recruitment of inflammatory cells into the BAL fluid and lung tissues, expressions of CD40, CD40L and VCAM-1 molecules, goblet cell hyperplasia, MMPs activity, expressions of mRNA and productions of various cytokines, activities of MAP kinases and NK-${\kappa}B$ increased from OVA-challenged mice. These data suggest that DA-9601 may be developed as a clinical therapeutic agent in allergic diseases due to suppressing the airway allergic inflammation via regulation of various cellular molecules expressed by MAP kinases/NF-${\kappa}B$ pathway.

• Journal of Oriental Neuropsychiatry
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• v.25 no.4
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• pp.423-434
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• 2014

Objectives: Activated microglia cells play an important role in inflammatory responses in the central nervous system (CNS) which are involved in neurodegenerative diseases. We attempted to determine the anti-inflammatory effects of Cheongnoimyungshin-hwan (CNMSH) in microglia cells. Methods: We examined the effect of CNMSH on the inflammatory responses in BV2 microglia cells induced by lipopolysaccharide (LPS) and explored the mechanism underlying the action of CNMSH. Results: BV2 cells treated with LPS showed an up-regulation of nitric oxide (NO), prostaglandin $PGE_2(PGE_2)$ and interleukin $1{\beta}(IL-1{\beta})$ release, whereas CNMSH suppressed this up-regulation. CNMSH inhibited the induction of COX-2, iNOS and $IL-1{\beta}$ proteins in LPS-treated BV2 cells and blocked the LPS-induced phosphorylation and nuclear translocation of nuclear factor ${\kappa}B(NF-{\kappa}B$). Furthermore, CNMSH attenuated the LPS-induced phosphorylation of extracellular signal-regulated kinase and p38 mitogen activated protein kinase (MAPK), as well as the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, but did not inhibit the LPS-induced phosphorylation of c-Jun amino terminal kinase. Conclusions: These results suggest that the inhibitory effect of CNMSH on the LPS-induced production of inflammatory mediators and cytokines in BV2 cells is associated with the suppression of the $NF-{\kappa}B$ and PI3KAkt signaling pathways.

• Journal of Periodontal and Implant Science
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• v.52 no.2
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• pp.127-140
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• 2022

Purpose: In dental avulsion, delayed replantation usually has an uncertain prognosis. After tooth replantation, complex inflammatory responses promote a return to periodontal tissue homeostasis. Various types of cytokines are produced in the inflammatory microenvironment, and these cytokines determine the periodontal tissue response. This study aimed to identify the gene expression profiles of replanted teeth and evaluate the functional differences between immediate and delayed replantation. Methods: Maxillary molars from Sprague-Dawley rats were extracted, exposed to a dry environment, and then replanted. The animals were divided into 2 groups according to the extra-oral time: immediate replantation (dry for 5 minutes) and delayed replantation (dry for 60 minutes). Either 3 or 7 days after replantation, the animals were sacrificed. Periodontal soft tissues were harvested for mRNA sequencing. Hallmark gene set enrichment analysis was performed to predict the function of gene-gene interactions. The normalized enrichment score (NES) was calculated to determine functional differences. Results: The hallmark gene sets enriched in delayed replantation at 3 days were oxidative phosphorylation (NES=2.82, Q<0.001) and tumor necrosis factor-alpha (TNF-α) signaling via the nuclear factor kappa light chain enhancer of activated B cells (NF-κB) pathway (NES=1.52, Q=0.034). At 7 days after delayed replantation, TNF-α signaling via the NF-κB pathway (NES=-1.82, Q=0.002), angiogenesis (NES=-1.66, Q=0.01), and the transforming growth factor-beta signaling pathway (NES=-1.46, Q=0.051) were negatively highlighted. Conclusions: Differentially expressed gene profiles were significantly different between immediate and delayed replantation. TNF-α signaling via the NF-κB pathway was marked during the healing process. However, the enrichment score of this pathway changed in a time-dependent manner between immediate and delayed replantation.

• Journal of Ginseng Research
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• v.39 no.2
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• pp.116-124
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• 2015

Background: Ginseng, the root of Panax ginseng (PG), is used widely as a herbal medicine to prevent and treat various diseases. Panax ginseng has pharmacological effects on neurodegenerative diseases such as Alzheimer's disease (AD). The present study evaluated the neuroprotective effects of PG and its possible neuroprotective mechanisms in advanced glycation end product (AGE)-induced AD in a rat model. Methods: Advanced glycation end products were injected bilaterally into the CA3 region of the rats' brains. The Morris water maze test and step-down type passive avoidance test were performed to evaluate their memory and cognitive abilities. The oxidation indexes in the hippocampus were detected. Immunohistochemistry was conducted to visualize the receptors for advanced glycation end products (RAGEs) and nuclear factor-kappa-light-chain-enhancer of activated B cell (NF-${\kappa}B$). Results: Behavioral results showed that PG (1 g/kg, 0.5 g/kg, and 0.25 g/kg) significantly shortened the escape latency, remarkably increased the number of crossing times, significantly decreased the number of errors, and prolonged the latency in rats with AGE-induced AD. Panax ginseng also significantly reduced the malondialdehyde level, increased the glutathione content, and increased superoxide dismutase activity in the hippocampus. Panax ginseng significantly decreased the expression of RAGE and NF-${\kappa}B$. The blockade of anti-RAGE antibody could significantly reduce AGE-induced impairments and regulate these expressions. Conclusion: Our results demonstrated that PG significantly inhibits AGE-induced memory impairment and attenuates Alzheimer-like pathophysiological changes. These neuroprotective effects of PG may be associated with the RAGE/NF-${\kappa}B$ pathway. Our results provided the experimental basis for applying PG in preventing and treating AD.

• Journal of Periodontal and Implant Science
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• v.35 no.2
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• pp.427-436
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• 2005

Objective: MMP-8 is a neutrophil enzyme and its level increases in some inflammatory diseases, including periodontal disease. We knew that the lipopolysaccharide of E.coli(E-LPS) induced MMP-8 release from human neutrophils. E-LPS is known to induce the production and release of inflammatory cytokines through CD14, Toll-like receptor(TLR). In the present study, we investigated whether MMP-8 release by E-LPS is induced via CD14-TLR pathway and the cellular mechanism of MMP-8 release in human neutrophils. Material and methods: Human neutrophils were isolated from the peripheral blood of healthy donors and pre-incubated in medium containing antibodies against CD14, anti-TLR2 and anti-TLR4 or several inhibitors of microtubules and microfilaments and then incubated with E-LPS. The cells were treated TPCK and E-LPS simultaneously. The MMP-8amount in the culture medium was determined using ELISA. Results: E-LPS increased MMP-8release from neutrophils and its induction was inhibited by anti-CD14 and anti-TLR4 but not by anti-TLR2 antibodies. The inhibitors of microtubule and microfilament polymerization significantly decreased E-LPS-induced MMP-8release. TPCK inhibited E-LPS-induced MMP-8 release. Conclusion: These results suggest that MMP-8 release is induced by E-LPS via the CD14-TLR4 signal pathway in human neutrophils and may be depedent on microtubule and microfilament systems and $NF-{\kappa}B$ pathway.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.4
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• pp.261-272
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• 2021

Doxorubicin (Dox) is widely used to the treatment of cancer, however, it could cause damage to gastric mucosa. To investigate the protective effects and related mechanisms of coenzyme Q10 (CoQ10) and vitamin C (VC) on Dox-induced gastric mucosal injury, we presented the survey of the 4 groups of the rats with different conditions. The results showed Dox treatment significantly induced GES-1 apoptosis, but preconditioning in GES-1 cells with VC or CoQ10 significantly inhibited the Dox-induced decrease and other harm effects, including the expression and of IκKβ, IκBα, NF-κB/p65 and tumor necrosis factor (TNF-α) in GES-1 cells. Moreover, high-throughput sequencing results showed Dox treatment increased the number of harmful gut microbes, and CoQ10 and VC treatment inhibited this effect. CoQ10 and VC treatment inhibits Dox-induced gastric mucosal injury by inhibiting the activation of the IkKB/IκBα/NF-κB/p65/TNF-α pathway, promoting anti-inflammatory effects of gastric tissue and regulating the composition of the intestinal flora.