• Journal of the Korean Chemical Society
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• v.51 no.3
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• pp.251-257
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• 2007

The Tumor necrosis factor-α, (TNF-α), is involved in the pathogenesis of multiple sclerosis and contributes to the degeneration of oligodendrocytes as well as neurons. Nicotine has been found to have immunosuppressive and inflammation-suppressing effects. Astrocytes, the major glial cells in the CNS, are capable of producing TNF-α at both the mRNA and protein levels in response to interleukin-1 (IL-1) or TNF-α. Nicotine has been shown to influence glial cell functions. To order to explore the role of astrocytes in the production of TNF-α, astrocytes were pretreated with nicotine and are stimulated with IL-1β to determine their effects on TNF-α production. The results are as follows. Cytotoxic effects of nicotine on human fetal astrocytes were noted above 10 μg/ml of nicotine. The effect of IL-1β on TNF-α mRNA expression in primary cultured human fetal astrocytes was maximal at 2 h after IL- 1β(100 pg/ml) treatment. Human fetal astrocytes were pretreated with 0.1, 1, and 10 μg/ml of nicotine and then stimulated with IL-1β (100 pg/ml) for 2 h. The inhibitory effect of nicotine on expressions of TNF-α mRNA in human fetal astrocytes with pretreated 0.1 μg/ml of nicotine is first noted at 8 hr, and the inhibitory effect is maximal at 12 h. The inhibitory effect at 1 μg/ml of nicotine is inhibited maximal at 24 h. Nicotine at 0.1, 1 and 10 μg/ml concentrations significantly inhibits IL-1β-induced NF-κB activation. Collectively, this study indicates that nicotine might inhibit the expression of TNF-α in activated human fetal astrocytes.

• Korean Journal of Microbiology
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• v.55 no.3
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• pp.206-212
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• 2019

Propionibacterium acnes (P. acnes) lives in the hair follicles and pores, and it uses cell debris, sebum and metabolic byproducts of surrounding skin tissues as energy and nutrients. Increased production of sebum due to sebaceous hyperplasia or blockage of the follicle can cause growth and proliferation of P. acnes. The rapid growth of P. acnes in follicles produces cell damage, metabolic byproducts and bacterial chips, which can cause inflammation. In this study, we examined the possibility of Senecio iscoensis Hieron. (S. iscoensis) extract to regulate P. acnes-induced inflammatory signaling pathways. We observed that S. iscoensis extract effectively inhibited P. acnes-induced pro-inflammatory cytokine expressions such as IL-$1{\beta}$, TNF-${\alpha}$, and iNOS in mouse macrophage cell line Raw 264.7. The inhibitory effect of S. iscoensis in pro-inflammatory cytokine levels was accompanied by the inhibition of the transcription factors NF-${\kappa}B$ and NF-AT. However, S. iscoensis did not alter the P. acnes-induced MAPK signaling pathways. This study first suggests the potential of using S. iscoensis extract as an alternative agent for the treatment of acne.

• Biomedical Science Letters
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• v.10 no.2
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• pp.65-73
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• 2004

I report that single-stranded antisense as a part of large circular (LC-) genomic DNA of recombinant M13 phage exhibits enhanced stability, sequence specific antisense activity, and no need for target site search. A cDNA fragment (708 bp) of rat TNF-$\alpha$ was inserted into a phagemid vector, and TNF-$\alpha$ antisense molecules (TNF$\alpha$-LCAS) were produced as single-stranded circular DNA. When introduced into a rat monocyte/macrophage cell line, WRT7/P2, TNF$\alpha$-LCAS was able to ablate LPS-induced TNF-$\alpha$ mRNA to completion. The antisense effect of TNF$\alpha$-LCAS was shown to be sequence-specific because expressions of three control genes ($\beta$-actin, GAPDH and IL-1$\beta$) were not significantly altered by the antisense treatment. Further, TNF$\alpha$-LCAS was found to be highly efficacious as only 0.1 $\mu$g (0.24 nM) of TNF$\alpha$-LCAS was sufficient to block TNF-$\alpha$ expression in 1$\times10^5$ WRT7/P2 cells. I have also observed specific antisense activity in reduction of NF-$\kappa$B gene expression. The results suggest that an antisense sequence as a part of single-stranded circular genomic DNA has a specific antisense activity.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10483-10487
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• 2015

Heptaphylline derivatives are carbazoles in Clausena harmandiana, a medicinal plant that is utilized for headache, stomach ache, and other treatments of illness. The present study examined the effects of heptaphylline and 7-methoxyheptaphylline on apoptosis of human colon adenocarcinoma cells (HT-29 cell line). Quantification of cell viability was performed using cell proliferation assay (MTT assay) and of protein expression through immunoblotting. The results showed that only heptaphylline, but not 7-methoxyheptaphylline, significantly significantly activated cleaved of caspase-3 and poly (ADP-ribose) polymerase (PARP-1) which resulted in HT-29 cell death. We found that heptaphylline activated BH3 interacting-domain death agonist (Bid) and Bak, proapoptotic proteins. In contrast, it suppressed X-linked inhibitor-of-apoptosis protein (XIAP), Bcl-xL and survivin, inhibitors of apoptosis. In addition, heptaphylline inhibited activation of NF-${\kappa}B$/p65 (rel), a regulator of apoptotic regulating proteins by suppressing the activation of Akt and $IKK{\alpha}$, upstream regulators of p65. The findings suggested that heptaphylline induces apoptosis in human colon adenocarcinoma cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.3
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• pp.678-683
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• 2008

Aconitum pseudo-laeve var. erectum has traditionally been used for the treatment of water retention in the body. Administration of the aqueous extract of Aconitum pseudo-laeve var. erectum has the efficiency of anti-inflammatory activity and modulates the intestinal immune system. However, the mechanism of anti-inflammatory action of Aconitum pseudo-laeve var. erectum has not been clarified yet. In the present study, the effect of Aconitum pseudo-laeve var. erectum against LPS-stimulated expressions of COX-2 and iNOS in cells of the murine RAW 264.7 macrophages was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, reverse transcription- polymerase chain reaction (RT-PCR), PGE2 immunoassay, and NO detection. The results of the present study indicate that Aconitum pseudo-laeve var. erectum is a potent inhibitor of the LPS-induced NO and $PGE_{2}$ production by blocking iNOS and $NF{\kappa}B$ activation in RAW 264.7 macrophages. These findings suggest that Aconitum pseudo-laeve var. erectum is a potential therapeutic for the treatment of inflammatory syndrome.

• Molecules and Cells
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• v.38 no.10
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• pp.904-910
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• 2015

Negative regulator of reactive oxygen species (NRROS) is known to repress ROS generation in phagocytes. In this study, we examined the roles of NRROS in both osteoclasts and osteoblasts. Our results demonstrate that NRROS negatively regulates the differentiation of osteoclasts, but not osteoblasts. Further, overexpression of NRROS in osteoclast precursor cells attenuates RANKL-induced osteoclast differentiation. Conversely, osteoclast differentiation is enhanced upon siRNA-mediated knock-down of NRROS. Additionally, NRROS attenuates RANKL-induced $NF-{\kappa}B$ activation, as well as degradation of the NOX1 and NOX2 proteins, which are required for ROS generation. Based on our observations, we present NRROS as a novel negative regulator of RANKL-induced osteoclastogenesis.

• Korean Journal of Pharmacognosy
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• v.54 no.1
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• pp.1-8
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• 2023

The skin is an important barrier that protects the body from harmful environments such as UV rays. When the skin is repeatedly stimulated, such as UV rays, ROS and pro-inflammatory cytokines are overproduced. As a result, the proteins and nucleic acids that make up the skin are damaged, and aging occurs. Esculetin is known to have anti-inflammatory, antioxidant and UV-induced MMP-1 inhibitory effects. However, the inhibitory effect of MMP-1 on TNF-α-induced fibroblasts is not known. Therefore, in this study, the MMP-1 inhibitory effect of esculetin was confirmed in TNF-α-induced fibroblasts. As a result of confirming the cytotoxicity of esculetin in Hs68 cells by MTT assay, there was no significant toxicity up to 200 µM. As a result of real-time PCR and ELISA, it was confirmed that esculetin inhibited the expression of MMP-1. Esculetin did not inhibit MAPK (ERK, JNK, p38) phosphorylation, but inhibited phosphorylation of the mTOR-p70S6k signaling pathway. In addition, it was confirmed that the phosphorylation of the transcription factor NF-κB was inhibited. These results suggest that esculetin has potential as an anti-aging material.

• BMB Reports
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• v.45 no.3
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• pp.200-205
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• 2012

Enzymatic oxidation of commercially available pyrogallol was efficiently transformed to an oxidative product, purpurogallin. Purpurogallin plays an important role in inhibiting glutathione S-transferase, xanthine oxidase, catechol O-methyltransferase activities and is effective in the cell protection of several cell types. However, the anti-inflammatory functions of purpurogallin are not well studied. Here, we determined the effects of purpurogallin on lipopolysaccharide (LPS)-mediated proinflammatory responses. The results showed that purpurogallin inhibited LPS-mediated barrier hyper-permeability, monocyte adhesion and migration and such inhibitory effects were significantly correlated with the inhibitory functions of purpurogallin on LPS-mediated cell adhesion molecules (vascular cell adhesion molecules, intracellular cell adhesion molecule, E-selectin). Furthermore, LPS-mediated nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) releases from HUVECs were inhibited by purpurogallin. Given these results, purpurogallin showed its anti-inflammatory activities and could be a candidate as a therapeutic agent for various systemic inflammatory diseases.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.5
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• pp.1297-1302
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• 2007

Uncaria sinensis(OIi.) Havil (USH) is used in traditional Korean medicine to treat inflammation such as amebic dysentery. In this study, we investigated the anti-inflammatory effect of USH. The water extract of USH significantly inhibits lipopolysaccharide (LPS)-induced nitrite oxide (NO), tumor necrosis factor $(TNF)-{\alpha}$, interleukin (IL)-6and IL-12 productions in murine peritoneal macrophages. Furthermore, USH selectively inhibited activation of the extracellular signal-regulated kinase (ERK) but not of p38 MAPK, c-Jun N-terminal kinase (JNK) and nuclear $factor-{\kappa}B$ $(NF-{\kappa}B)$. In murine model, we found that administration of USH reduced serum levels of $TNF-{\alpha}$, IL-6 and IL-12 productions in LPS-treated mice. Our results suggest that USH exerts ant-inflammatory effects in macrophages via inhibition of ERK activation and may be a useful therapeutic approach to inflammatory diseases.

• BMB Reports
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• v.45 no.2
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• pp.108-113
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• 2012

Protopine is an isoquinoline alkaloid contained in plants in northeast Asia. In this study, we investigated whether protopine derived from Hypecoum erectum L could suppress lipopolysaccharide (LPS)-induced inflammatory responses in murine macrophages (Raw 264.7 cells). Protopine was found to reduce nitric oxide (NO), cyclooxygenase-2 (COX-2), and prostaglandin $E_2$ ($PGE_2$) production by LPS-stimulated Raw 264.7 cells, without a cytotoxic effect. Pre-treatment of Raw 264.7 cells with protopine reduced the production of pro-inflammatory cytokines. These inhibitory effects were caused by blocking phosphorylation of mitogen-activated protein kinases (MAP kinases) and also blocking activation of a nuclear factor kappa-light-chain-enhancer of activated B cells (NF-${\kappa}B$).