• BMB Reports
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• 제42권9호
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• pp.574-579
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• 2009

The regulatory effects of honokiol on the cellular responses of macrophages and monocytes were evaluated. Specifically, we investigated the effects of honokiol with respect to lipopolysaccharide (LPS)-induced cytotoxicity, LPS- or phorbol-12-myristate-13-acetate (PMA)-mediated morphological changes, and relevant events (FITC-dextran-induced phagocytic uptake). Honokiol blocked the LPS-induced cytotoxicity of RAW264.7 cells in a dose-dependent manner. In addition, honokiol appeared to block the production of cytotoxic cytokines such as interleukin (IL)-$1{\beta}$ and tumor necrosis factor (TNF)-$\alpha$, nitric oxide (NO), and reactive oxygen species (ROS). Moreover, honokiol strongly prevented the morphological changes in RAW 264.7 and U937 cells that were induced by LPS and PMA. The surface levels of marker proteins, which are up-regulated under the morphological changes of RAW264.7 and U937 cells, were also diminished. The data presented here strongly suggest that the honokiol modulates various cellular responses managed by macrophages and monocytes.

• 생약학회지
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• 제38권2호통권149호
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• pp.152-156
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• 2007

Protein-bound polysaccharide is derived from Acanthopananx senticosus by the cold water extraction. The aim of the study was to evaluate the effects of PS against weight loss and hematological change as a indication of toxicity produced by the treatment of cisplatin. PS protected the weight loss caused by cisplatin (6 mg/kg) and significantly recovered hematological change. Treatment of PS showed the recovery on the weight loss and hematological change as indicators of toxicity of cisplatin treatment. By increasing lymphocyte proliferation and cytokine production, PS may be highly effective in protecting against cisplatin-induced toxicity. The results suggest PS might have a role in reducing toxicity or permitting larger dose of cisplatin to be given.

• BMB Reports
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• 제41권9호
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• pp.657-663
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• 2008

The present study was undertaken to investigate the protective role of taurine (2-aminoethanesulfonic acid) against cadmium (Cd) induced oxidative stress in murine erythrocytes. Cadmium chloride ($CdCl_2$) was chosen as the source of Cd. Experimental animals were treated with either $CdCl_2$ alone or taurine, followed by Cd exposure. Cd intoxication reduced hemoglobin content and the intracellular Ferric Reducing/Antioxidant Power of erythrocytes, along with the activities of antioxidant enzymes, glutathione content, and total thiols. Conversely, intracellular Cd content, lipid peroxidation, protein carbonylation, and glutathione disulphides were significantly enhanced in these cells. Treatment with taurine before Cd intoxication prevented the toxin-induced oxidative impairments in the erythrocytes of the experimental animals. Overall, the results suggest that Cd could cause oxidative damage in murine erythrocytes and that taurine may play a protective role in reducing the toxic effects of this particular metal.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2004년도 Annual Meeting of KSAP : New Drug Development from Natural Products
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• pp.21-35
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• 2004

Heme oxygenase (HO)-l catabolizes heme into three products: carbon monoxide, bilirubin, and free iron. HO-l serves as a protective gene by virtue of the anti-inflammatory, anti-apoptotic and anti-proliferative actions of one or more of these three products. HO-l can be regarded as a potential therapeutic target in a variety of oxidant-mediated and inflammatory diseases. In this respect, it would be valuable to develop potent and selective inducers of HO-1 for therapeutic use. Here, we have shown that 1,2,3,4,6-penta-O-galloyl-beta-D-glucose, catalposide and dehydrocostus lactone are potent inducers of HO-1 and exert cytoprotective and anti-inflammatory activities via HO-1-ependent machanism.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
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• pp.124-124
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• 1998

Portal hypertensive gastropathy (PHG) is part of a complex syndrome which occurs as a complication of chronic liver disease and portal hypertension. The gastric mucosa in these patients shows typical congestion of ‘mosaic-like’ pattern and vulnerable to various noxious agents such as NSAIDs and ethanol. We previously reported that DA-9601, a quality-controlled extract from Artemisia asiatica, exhibits cytoprotection against various gastritis models. In the present study we investigated the effect of DA-9601 on ethanol-induced gastric damage in PHG rats. Experimental PHG was produced by CBD ligation in SD rats. DA-9601 was orally administered at a dose of 30 mg/kg or 100 mg/kg daily for 2 weeks.

• Journal of Ginseng Research
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• 제33권4호
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• pp.305-310
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• 2009

Phenanthrene, one of the polycyclic aromatic hydrocarbons, has been known to be toxic to the environment. In this investigation, the protective effect of red ginseng on phenanthrene-induced oxidative DNA damage was evaluated using Comet assay in A549 cells. Red ginseng's cytoprotective effect on phenanthrene-induced hemolysis was also investigated. This study's findings show that oxidative DNA damage and hemolysis were significantly prevented by red ginseng treatment. Notably, it was found that pulverizing red ginseng into ultra-fine particles even enhanced its protective effects against DNA damage and hemolysis. The results suggest that particle size reduction seems to effectively enhance red ginseng's pharmacological efficacies.

• Biomolecules & Therapeutics
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• 제9권2호
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• pp.69-78
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• 2001

Cyclooxygenase (COX) is an enzyme, which catalyzes the production of prostaglandins from arachi-donic acid and exists in two isoforms (COX-1 and COX-2). COX-1 is involved in the maintenance of physiological functions such as platelet aggregation, cytoprotection in the stomach and maintenance of normal kidney function. COX-2 is induced significantly in vivo under inflammatory conditions. COX-1 and COX-2 serve different physiological and pathological functions. All commercially available nonsteroidal antiinflammatory drugs (NSAIDS) are inhibitors of both COX-1 and COX-2. Therefore, selective inhibitors of COX-2 may be effective antiinflammatory agents without the ulcerogenic effects associated with current NSAms. Since the mid 1990s, a number of reports have been appeared on the preparation and biological activity of selective COX-2 inhibitors. Recently celecoxib, and rofecoxib, the representative COX-2 inhibitors, are introduced in the drug market. In this paper the relationship of structure-activity for selective COX-2 inhibitors is reviewed.

• The Korean Journal of Physiology and Pharmacology
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• 제19권6호
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• pp.507-514
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• 2015

Nitric oxide (NO) is important in the regulation of bone remodeling, whereas high concentration of NO promotes cell death of osteoblast. However, it is not clear yet whether NO-induced autophagy is implicated in cell death or survival of osteoblast. The present study is aimed to examine the role of NO-induced autophagy in the MC3T3-E1 cells and their underlying molecular mechanism. The effect of sodium nitroprusside (SNP), an NO donor, on the cytotoxicity of the MC3T3-E1 cells was determined by MTT assay and expression of apoptosis or autophagy associated molecules was evaluated by western blot analysis. The morphological observation of autophagy and apoptosis by acridine orange stain and TUNEL assay were performed, respectively. Treatment of SNP decreased the cell viability of the MC3T3-E1 cells in dose- and time-dependent manner. SNP increased expression levels of p62, ATG7, Beclin-1 and LC3-II, as typical autophagic markers and augmented acidic autophagolysosomal vacuoles, detected by acridine orange staining. However, pretreatment with 3-methyladenine (3MA), the specific inhibitor for autophagy, decreased cell viability, whereas increased the cleavage of PARP and caspase-3 in the SNP-treated MC3T3-E1 cells. AMP-activated protein kinase (AMPK), a major autophagy regulatory kinase, was activated in SNP-treated MC3T3-E1 cells. In addition, pretreatment with compound C, an inhibitor of AMPK, decreased cell viability, whereas increased the number of apoptotic cells, cleaved PARP and caspase-3 levels compared to those of SNP-treated MC3T3-E1 cells. Taken together, it is speculated that NO-induced autophagy functions as a survival mechanism via AMPK activation against apoptosis in the MC3T3-E1 cells.

• Food Science and Biotechnology
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• 제17권5호
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• pp.1079-1085
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• 2008

The chemopreventive activity of sulforaphane (SFN) occurs through its inhibition of carcinogen-activating enzymes and its induction of detoxification enzymes. However, the exact mechanisms by which SFN exerts its anti-carcinogenic effects are not fully understood. Therefore, the mechanisms underlying the cytoprotective effects of SFN were examined in MCF-7 breast cancer cells. Exposure of cells to SFN (10 ${\mu}M$) induced a transcriptional change in the AKR1C3 gene, which is one of aldo-keto reductases (AKRs) family that is associated with detoxification and antioxidant response. Further analysis revealed that SFN elicited a dose- and time-dependent increase in the expression of both the NRF2 and AKR1C3 proteins. Moreover, this up-regulation of AKR1C3 was inhibited by pretreatment with antioxidant, N-acetyl-L-cysteine (NAC), which suggests that the up-regulation of AKR1C3 expression induced by SFN involves reactive oxygen species (ROS) signaling. Furthermore, pretreatment of cells with LY294002, a pharmacologic inhibitor of phosphatidylinositol 3-kinase (PI3K), suppressed the SFN-augmented Nrf2 activation and AKR1C3 expression; however, inhibition of PKC or MEK1/2 signaling with $G\ddot{o}6976$ or PD98059, respectively, did not alter SFN-induced AKR1C3 expression. Collectively, these data suggest that SFN can modulate the expression of the AKR1C3 in MCF-7 cells by activation of PI3K via the generation of ROS.

• 대한의생명과학회지
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• 제21권2호
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• pp.60-68
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• 2015

NecroX-7 is a novel small compound of the NecroX series based on the indole moiety, which has potent cytoprotective and antioxidant properties. We previously detected potential immune regulatory effects of NecroX-7 in immune related diseases like Graft-versus-Host Disease. However, the function and the underlying mechanisms of immunological effects of NecroX-7 in the immune system have not been well established. In this study, we investigated the immune response characterization of differentially expressed genes of NecroX-7 administration in $CD4^+$ T cells by microarray analysis. $CD4^+$ T cells stimulated with NecroX-7 ($40{\mu}M$) or vehicle for 72 hours resulted in the identification of 337 differentially expressed genes (1.5 fold, P<0.05) by expression profiling analysis. Twenty eight of the explored NecroX-7-regulated genes were related to immune system processes. These genes were validated by quantitative real-time PCR. The most significant genes were glutathione reductase, eukaryotic translation elongation factor 1, lymphotoxin-alpha, heat shock protein 9 and chloride intracellular channel protein 4. These findings demonstrate the strongly immune response of NecroX-7 in $CD4^+$ T cells, suggesting that cytoprotection and immune regulation may underlie the critical aspects of NecroX-7 exposure.