• Korean Journal of Plant Resources
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• v.33 no.5
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• pp.460-466
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• 2020

In this study, we evaluated the anti-cancer activity and potential molecular mechanism of 70% ethanol extracts of leaves from Rodgersia podophylla against human colorectal cancer cells, HCT116. RPL dose-dependently decreased the cell viability through RPL-induced apoptosis in HCT116 cells. RPL induced inactivation the nuclear factor κB(NF-κB) through blocking IκB-α degradtion and P65 nuclear accumulation. The inhibition of GSK3β by LiCl attenuated RP-L-mediated NF-κB signaling inactivation. In addition, RP-L induced GSK3β activation. Based on these findings, RPL may be a potential candidate for the development of chemopreventive or therapeutic agents for human colorectal cancer.

• Journal of Life Science
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• v.31 no.12
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• pp.1110-1119
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• 2021

The purpose of this study was to investigate whether the inflammatory response in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages could be promoted by particulate matter 2.5 (PM_2.5) stimulation. To this end, the levels of inflammatory parameters, reactive oxygen species (ROS) and inflammation-regulating genes were investigated in RAW 264.7 cells treated with PM_2.5 in the presence or absence of LPS. Our results showed that the production levels of pro-inflammatory mediators (nitric oxide and prostaglandin E₂) and cytokines (interleukin-6 and -1β) were significantly increased by PM_2.5 stimulation in LPS-treated RAW 264.7 cells, which was correlated with increased expression genes involved in their production. In addition, when LPS-treated RAW 264.7 cells were exposed to PM_2.5, nuclear factor-kappaB (NF-κB) expression was further increased in the nucleus, and the expression of inhibitor of NF-κB as well as NF-κB in the cytoplasm was decreased. These results suggest that the co-treatment of PM_2.5 and LPS further increases the activation of the NF-κB signaling pathway compared to each treatment alone, thereby contributing to the promotion of transcriptional activity of inflammatory genes. Furthermore, although the generation of ROS was greatly increased by PM_2.5 in LPS-treated RAW 264.7 cells, the NF-κB inhibitor did not reduce the generation of ROS. In addition, when the generation of ROS was artificially suppressed, the production of inflammatory mediators and the activation of NF-κB were both abolished. Therefore, our results suggest that the increase in the NF-κB-mediated inflammatory response induced by PM_2.5 in LPS-treated RAW 264.7 macrophages was a ROS generation-dependent phenomenon.

• Journal of Microbiology and Biotechnology
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• v.30 no.10
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• pp.1458-1466
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• 2020

Oligomeric proanthocyanidins (OPCs), classified as condensed tannins, have significant antioxidation, anti-inflammation and anti-cancer effects. This study was performed to investigate the anti-inflammatory effects of OPCs and the mechanism underlying these effects in lipopolysaccharide (LPS)-stimulated bovine mammary epithelial cells (MAC-T). Real-time PCR and ELISA assays indicated that OPC treatment at 1, 3 and 5 ㎍/ml significantly reduced the mRNA and protein, respectively, of oxidant indicators cyclooxygenase-2 (COX-2) (p < 0.05) and inducible nitric oxide synthase (iNOS) (p < 0.01) as well as inflammation cytokines interleukin (IL)-6 (p < 0.01), IL-1β (p < 0.01) and tumor necrosis factor-α (TNF-α) (p < 0.05) in LPS-induced MAC-T cells. Moreover, OPCs downregulated LPS-induced phosphorylation of p65 and inhibitor of nuclear factor kappa B (NF-κB) (IκB) in the NF-κB signaling pathway (p < 0.01), and they inhibited p65 translocation from the cytoplasm to the nucleus as revealed by immunofluorescence test and western blot. Additionally, OPCs decreased phosphorylation of p38, extracellular signal regulated kinase and c-jun NH₂-terminal kinase in the MAPK signaling pathway (p < 0.01). In conclusion, the anti-inflammatory and antioxidant activities of OPCs involve NF-κB and MAPK signaling pathways, thus inhibiting expression of pro-inflammatory factors and oxidation indicators. These findings provide novel experimental evidence for the further practical application of OPCs in prevention and treatment of bovine mastitis.

• Journal of Microbiology and Biotechnology
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• v.29 no.1
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• pp.11-20
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• 2019

Ecklonia cava, an edible marine brown alga (Laminariaceae), is a rich source of bioactive compounds such as fucoidan and phlorotannins. Ecklonia cava extract (ECE) was prepared using 70% ethanol extraction and ECE contained 67% and 10.6% of total phlorotannins and dieckol, respectively. ECE treatment significantly inhibited receptor activator of nuclear $factor-{\kappa}B$ ligand (RANKL)-induced osteoclast differentiation of RAW 264.7 cells and pit formation in bone resorption assay (p <0.05). Moreover, it suppressed RANKL-induced $NF-{\kappa}B$ and mitogen-activated protein kinase signaling in a dose dependent manner. Downregulated osteoclast-specific gene (tartrate-resistant acid phosphatase, cathepsin K, and matrix metalloproteinase-9) expression and osteoclast proliferative transcriptional factors (nuclear factor of activated T cells-1 and c-fos) confirmed ECE-mediated suppression of osteoclastogenesis. ECE treatment ($100{\mu}g/ml$) increased heme oxygenase-1 expression by 2.5-fold and decreased intercellular reactive oxygen species production during osteoclastogenesis. The effective inhibition of RANKL-stimulated osteoclast differentiation and oxidative stress by ECE suggest that ECE has therapeutic potential in alleviating osteoclast-associated disorders.

• Journal of Microbiology and Biotechnology
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• v.29 no.2
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• pp.297-303
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• 2019

Corticosteroids are commonly used for pain control in rotator cuff tear. Deregulated $NF-{\kappa}B$ activation is a hallmark of chronic inflammatory diseases and has been responsible for the pathogenesis of rotator cuff tear. The Dexamethasone(DEXA) is a synthetic corticosteroid. The purpose of this study was to examine the exact effect of dexamethasone on $NF-{\kappa}B$ signaling in rotator cuff tear. We measured $NF-{\kappa}B$ expression in four groups: control, $TNF-{\alpha}$-treated, DEXA-treated, and combined treatment with $TNF-{\alpha}$ and DEXA. Tenocytes were isolated from patients with rotator cuff tears and pre-incubated with $TNF-{\alpha}$ (10 ng/ml), DEXA ($1{\mu}M$), or both of them for 10 min, 1 h, and 2 h. Expression of p65, p50, and p52 in the nuclei and cytosol was analyzed by western blotting and immunofluorescence imaging using confocal microscopy. We also evaluated nucleus/cytosol (N/C) ratios of p65, p50, and p52. In our study, the combined treatment with DEXA and $TNF-{\alpha}$ showed increased N/C ratios of p65, p50, and p52 compared with those in the $TNF-{\alpha}$ group at all time points. Additionally, in the DEXA group, N/C ratios of p65, p50, and p52 gradually increased from 10 min to 2 h. In conclusion, DEXA promoted the nuclear localization of p65, p50, and p52, but was not effective in inhibiting the inflammatory response of $TNF-{\alpha}$-stimulated rotator cuff tear.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.2
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• pp.415-421
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• 2008

Pro-inflammatory mediators, such as prostaglandin $E_2$ (PGE2), nitric oxide (NO), and cyclooxygenases-2 (COX-2), play pivotal roles in normal as well as transformed cells. Previous studies have shown that Euphorbiae humifusae Wind exhibits anti-proliferative and antioxidant activities. However, the it's anti-inflammatory properties are unclear. In this study, we examine the effects of water extract of E. humifusae (WEEH) on the expression of COX-2 and the production of $PGE_2$ in human lymphatic U937 cells. Treatment of phorbol 12-myristate-13-acetate (PMA) significantly induced COX-2 expression and $PGE_2$ production in U937 cells. However, pretreatment WEEH markedly inhibited the PMA-induced COX-2 expression and $PGE_2$ production in a dose-dependent manner. Moreover, WEEH prevented the elevated early growth response gene-1 (Egr-1) expression and nuclear factor-kappaB ($NF{-\kappa}B\; p65$) nuclear translocation stimulated by PMA treatment. Taken together, the present data indicate that WEEH exhibits anti-inflammatory properties by suppressing the transcription of pro-inflammatory cytokine genes through the $NF{-\kappa}B$ and Egr-1 signaling pathway.

• IMMUNE NETWORK
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• v.13 no.4
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• pp.148-156
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• 2013

The $PrP^C$ is expressed in many types of immune cells including monocytes and macrophages, however, its function in immune regulation remains to be elucidated. In the present study, we examined a role for $PrP^C$ in regulation of monocyte function. Specifically, the effect of a soluble form of $PrP^C$ was studied in human monocytes. A recombinant fusion protein of soluble human $PrP^C$ fused with the Fc portion of human IgG1 (designated as soluble $PrP^C$-Fc) bound to the cell surface of monocytes, induced differentiation to macrophage-like cells, and enhanced adherence and phagocytic activity. In addition, soluble $PrP^C$-Fc stimulated monocytes to produce pro-inflammatory cytokines such as $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6. Both ERK and $NF-{\kappa}B$ signaling pathways were activated in soluble $PrP^C$-treated monocytes, and inhibitors of either pathway abrogated monocyte adherence and cytokine production. Taken together, we conclude that soluble $PrP^C$-Fc enhanced adherence, phagocytosis, and cytokine production of monocytes via activation of the ERK and $NF-{\kappa}B$ signaling pathways.

• The Korea Journal of Herbology
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• v.23 no.4
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• pp.81-89
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• 2008

Objectives: In this study, the pharmacological effects of the ethylacetate extract of Ostericum koreanum(North Kangwhal; NK) on allergic inflammation were investigated in activated human mast cells. Methods: North Kangwhal was extracted with 80% methanol for 24 h, and then fractionated with ethylacetate(NK-EtOAc extract). HMC-1 cells, an human mast line, were pre-incubated with different concentrations of NK-EtOAc extract for 30 min, and then stimulated with PMA(50 nM/ml) and A23187($1{\mu}M/ml$) at indicated times. The cell toxicity was determined by MTT assay. The concentrations of prostaglandin E2(PGE2) and cytokines(TNF-${\alpha}$, IL-8) were measured by enzyme-linked immunosorbant assay. Results: NK-EtOAc extract($10{\sim}50{\mu}g/ml$) significantly inhibited the productions of $PGE_2$, TNF-${\alpha}$ and IL-8 in PMA/A23187-stimulated HMC-1 cells without cell toxicity($0{\sim}50{\mu}g/ml$). NK-EtOAc extract also inhibited PMA/A23187-induced phosphorylation of ERK1/2 MAPK and the NF-${\kappa}B$ p65 subunit translocation into the nuclear of HMC-1 cells. Conclusions: This study suggests that NK-EtOAc extract may have an anti-inflammatory property through suppressing the production of inflammatory mediators in activated mast cells and its molecular mechanism underlies the blocking of NF-${\kappa}B$ pathway.

• The Korea Journal of Herbology
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• v.23 no.4
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• pp.91-101
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• 2008

Objectives: In this study, we investigated the inhibitory effects of Ampelopsis Radix methanol(AR-M) extract on allergic inflammation in activated human mast cells and its potential therapeutic or toxic effects. Methods: Ampelopsis Radix(AR) was extracted with 80% methanol. HMC-1 cells, a human mast cell line, were treated with different concentrations of AR-M extract, and then stimulated with PMA plus A23187. The cell toxicity of AR-M extract was determined by MTT assay. The concentrations of $PGE_2$ and cytokines were measured by ELISA. The gene expression of COX-2 and its protein levels were determined by RT-PCR and Western blot. The phosphorylation of ERK MAPK and the NF-${\kappa}B$ activation were determined by Western blot. Results: AR-M extract was significantly inhibited the production of PGE2 and inflammatory cytokines(TNF-${\alpha}$, IL-6 and IL-8) in PMA/A23187-stimulated HMC-1 cells. AR-M extract also attenuated the mRNA expression of COX-2 and its protein induction. Furthermore, AR-M extract attenuated PMA/A23187-induced phophorylation of ERK1/2 MAPK and the NF-${\kappa}B$ p65 subunit translocation into nuclear of HMC-1 cells. AR-M extract significantly decreased PMN A23187-induced release of histamine in a dose-dependent manner. Conclusions: These results indicate that Ampelopsis Radix shows the property of anti-allergic inflammation In vitro through suppressing the production of inflammatory mediators released from mast cells, suggesting have a potential for the treatment of allergic diseases.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.3
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• pp.406-416
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• 2011

In this study, we have verified the memory and cognitive enhancing effect of Longanae Arillus, the fruit of Euphoria longana Lamarck, which has been used as a tonic and for the treatment of amnesia, insomnia, and palpitations in oriental medicine. To investigate the effect of Longanae Arillus water extract(LAE) on the memory and cognitive dysfunction, scopolamine (1 mg/kg, i.p.) was injected in C57BL/6 mice and several behavior tests including Y-maze, Morris water-maze, passive avoidance and fear conditioning tests were conducted. Administration of LAE (100 or 200 mg/kg/day, p.o.) effectively improved scopolamine-induced memory impairment and dysfunction. To further determine the possible molecule mechanism of LAE, we have examined the activity and/or mRNA expression of diverse proteins involved in the acetylcholine metabolism. LAE particularly increased the amount of acetylcholine in the cortex which was mediated by suppression of acetylcholine esterase (AchE) activity. In addition, LAE elevated the mRNA expression of muscarinic acetylcholine receptors (mAchRs) without affecting the mRNA levels of choline acetyltransferase (ChAT) and acetylcholine esterase (AchE). In another experiment, LAE effectively inhibited mRNA expression of pro-inflammatory cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-$1{\beta}$ (IL1-${\beta}$), which seemed to be mediated by inhibition of upstream transcription factor NF-${\kappa}B$ and extracellular-regulated kinase 1/2 (ERK1/2). These results demonstrate that Longanae Arillus can increase acetylcholine amount the cortex via regulation of AchE activity as well as mAchRs expression and decrease pro-inflammatory responses via inhibition of NF-${\kappa}B$ signaling pathway, thereby having therapeutic potential to improve memory and cognitive deficit in amnesia.