• BMB Reports
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• v.51 no.7
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• pp.362-367
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• 2018

A major feature of type 1 diabetes mellitus (T1DM) is hyperglycemia and dysfunction of pancreatic ${\beta}$-cells. In a previous study, we have shown that Tat-DJ-1 protein inhibits pancreatic RINm5F ${\beta}$-cell death caused by oxidative stress. In this study, we examined effects of Tat-DJ-1 protein on streptozotocin (STZ)-induced diabetic mice. Wild type (WT) Tat-DJ-1 protein transduced into pancreas where it markedly inhibited pancreatic ${\beta}$-cell destruction and regulated levels of serum parameters including insulin, alkaline phosphatase (ALP), and free fatty acid (FFA) secretion. In addition, transduced WT Tat-DJ-1 protein significantly inhibited the activation of $NF-{\kappa}B$ and MAPK (ERK and p38) expression as well as expression of COX-2 and iNOS in STZ exposed pancreas. In contrast, treatment with C106A mutant Tat-DJ-1 protein showed no protective effects. Collectively, our results indicate that WT Tat-DJ-1 protein can significantly ameliorate pancreatic tissues in STZ-induced diabetes in mice.

• Korean Journal of Pharmacognosy
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• v.45 no.1
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• pp.1-10
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• 2014

Ginsenoside Rg3 (G-Rg3) is one of protopanaxadiol ginsenosides characteristic of red ginseng, steamed and dried ginseng (Panax ginseng), which has recently attracted much attention for its antitumor properties in vitro and in vivo animal models. Experimental studies have demonstrated that it could promote cancer cell apoptosis, inhibit cancer cell growth, the apoptosis of cancer cells, adhesion, invasion and metastasis, and also prevent an angiogenetic formation in prostate, breast, ovarian, colorectal, gastric, liver and lung cancer etc. It has shown the antitumor activities by modulation of diverse signaling pathways, including regulation of cell proliferation mediators (CDKs and cyclins), growth factors (vascular endothelial growth factor), tumor suppressors (p53 and p21), cell death mediators (caspases, Bcl-2, Bax), inflammatory response molecules ($NF-{\kappa}B$ and COX-2), protein kinases (JNK, Akt, and AMP-activated protein kinase) and Wnt/${\beta}$-catenin signaling. In addition, the combination of Rg3 and chemotherapeutic agents have synergistically enhanced therapeutic efficacy and reduced antagonistically side effects. Furthermore, it can reverse the multidrug resistance of cancer cells, prolong the survival duration and improve life quality of cancer patients. Taken together, accumulating evidences could provide the potential of G-Rg3 in the treatment of cancers and the feasibility of further randomized placebo controlled clinical trials.

• The Journal of Internal Korean Medicine
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• v.38 no.6
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• pp.1021-1034
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• 2017

Objectives: The aim of this study was to investigate the effects of Gaejigayonggolmoryo-tang (GYT) on ulcerative colitis induced by dextran sodium sulfate (DSS) in mice. Methods: Colitis was induced by free drinking of 5% DSS in six-week-old male ICR mice. The experimental groups were the sample group, the control group, and the normal group. The sample group was treated with GYT for three days after being was given 5% DSS for five days. The control group was given water, instead of GYT, for three days after the five days of 5% DSS. The normal group was untreated (not given 5% DSS), for comparison purposes. Results: Cellular experiments showed that GYT inhibits the expression of the inflammatory enzymes COX-2 and iNOS, and the production of NO. Based on the primary cellular experiments, the effects of GYT on ulcerative colitis induced by DSS of mouse tissues were investigated. GYT reduced tissue damage and apoptosis by inhibiting the expression of the inflammatory enzymes $NF-{\kappa}B$ p65, COX-2, and iNOS. In the cellular experiment, GYT was more effective in inhibiting the expression of COX-2 than in inhibiting the expression of iNOS. GYT was evidently effective in tissues in inhibiting the expression of COX-2. Conclusions: Based on the results here, GYT may have therapeutic effects on ulcerative colitis induced by DSS. GYT is worthy of research and development as a COX-2 inhibitor and a potential drug for inflammatory bowel diseases from natural products. Further investigations for exact mechanisms will be needed.

• Journal of Oriental Neuropsychiatry
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• v.24 no.3
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• pp.309-320
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• 2013

Objectives : There is a possibility LRE as remedy in Alzheimer disease (AD), but it's nerve protection effect and mechanism have to be elucidate. In this research, we applied LRE on $A{\beta}_{25-35}$ pre-treated SH-SY5Y cells, to find out the nerve protection effect and mechanism in AD cell model. Methods : We tried to confirm that effect by experimenting with 20, 50, and $100{\mu}g/ml$ concentration of LRE as a medicine. Next experiment, we assessed damage effect which induced $A{\beta}_{25-35}$, known to cause AD, on SH-SY5Y cell. In addition, cellular viability test is executed under $H_2O_2$ treatment condition in a SH-SY5Y cell. Results : 1. In $A{\beta}_{25-35}$ treated SH-SY5Y cell, LRE exhibited an anti-phosphorylation effect about tau protein, JNK, and IKB. 2. LRE prevent nerve cell apoptosis, which indued $A{\beta}_{25-35}$ and oxidative stress, modify JNK engaged synaptic structure and $NF{\kappa}B$ induced p75-neurotrophin receptor polymorphism. Conclusions : We found that LRE prevented oxidative stress-induced cellular destruction, for example, increased SOD activity of $A{\beta}_{25-35}$ treated SH-SY5Y cell and reduced toxicity of oxygen free radical. Consequently, the ingredients of LRE have a role as a catalyzer for $A{\beta}_{25-35}$ clearance and as scavenger for active oxygen free radical.

• Journal of Microbiology and Biotechnology
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• v.18 no.6
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• pp.1191-1196
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• 2008

Staphylococcus aureus is a common etiologic agent for Gram-positive sepsis, and its lipoteichoic acid (LTA) may be important in causing Gram-positive bacterial septic shock. Here, we demonstrate that highly purified LTA (pLTA) isolated from Lactobacillus plantarum inhibited S. aureus LTA (aLTA)-induced TNF-${\alpha}$ production in THP-1 cells. Whereas pLTA scarcely induced TNF-${\alpha}$ production, aLTA induced excessive TNF-${\alpha}$ production. Interestingly, aLTA-induced TNF-${\alpha}$ production was inhibited by pLTA pretreatment. Compared with pLTA, aLTA induced a strong signal transduction through the MyD88, NF-${\kappa}B$, and MAP kinases. This signaling, however, was reduced by a pLTA pretreatment, and resulted in the inhibition of aLTA-induced TNF-${\alpha}$ production. Whereas dealanylated LTAs, as well as native LTAs, contributed to TNF-${\alpha}$ induction or TNF-${\alpha}$ reduction, deacylated LTAs did not, indicating that the acyl chain of LTA played an important role in the LTA-mediated immune regulation. These results suggest that pLTA may act as an antagonist for aLTA, and that an antagonistic pLTA may be a useful agent for suppressing the septic shock caused by Gram-positive bacteria.

• Applied Biological Chemistry
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• v.48 no.4
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• pp.411-417
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• 2005

Aqueous extracts were prepared from 21 medicinal herbs including Herba Pogostemi (Agastache rugosa) to examine their modulatory effects on NO production in mouse macrophage cell line RAW264.7 cells. While almost all medicinal herb extracts failed to show marked scavenging activities to NO produced by LPS stimulation, only Herba Pogostemi showed a rather strong induction of NO production in RAW264.7 cells without stimulation with LPS. When we treated the cell with $200{\mu}M\;of\;N^G-monomethyl-L-arginine\;(N^GMMA)$, a NOS2 inhibitor, a significant reduction in NO production could be observed. Moreover, a treatment of $100{\mu}M$ pyrrolidine dithiocarbamate (PDTC) led to about a 79% reduction of NO production. These results demonstrated that the aqueous extract of Herba Pogostemi might provide a second signal for the expression of NOS2 in RAW264.7 cells, and suggested that Herba Pogostemi induces NO production through L-argininedependent pathway.

• Journal of Microbiology and Biotechnology
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• v.20 no.1
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• pp.217-223
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• 2010

To evaluate the antiallergic effect of fermented Ixeris sonchifolia (IS, family Compositae), we prepared IS kimchi, isolated lactic acid bacteria (LAB) from it, fermented IS with these LAB, and investigated their antiallergic effects. IS kimchi inhibited the passive cutaneous anaphylaxis (PCA) reaction induced by an IgE-antigen complex as well as the scratching behavior induced by compound 48/80 or histamine more potently than IS. When IS was fermented with LAB isolated from IS kimchi, its antiallergic effects was also increased. Of LAB used for fermentation, Lactobacillus brevis more potently increased the antiallergic effects. Its main constituents, chlorogenic acid and luteolin, potently inhibited the PCA reaction induced by the IgE-antigen complex as well as the pruritis induced by compound 48/80 or histamine. These constituents inhibited the expression of pro inflammatory and allergic cytokines, TNF-$\alpha$. and IL-4, and transcription factor NF-${\kappa}B$ activation induced by the IgE-antigen complex in RBL-2H3 cells, as well as the degranulation of RBL-2H3 cells induced by the IgE-antigen complex. Luteolin more potently inhibited these allergic reactions than chlorogenic acid. These findings suggest that the antiallergic effect of IS can be increased by LAB fermentation, and the fermented IS might improve allergic reactions such as pruritus, anaphylaxis, and inflammation.

• Journal of Microbiology and Biotechnology
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• v.28 no.9
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• pp.1554-1562
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• 2018

The type I interferons (IFNs) play a vital role in activation of innate immunity in response to viral infection. Accordingly, viruses have evolved to employ various survival strategies to evade innate immune responses induced by type I IFNs. For example, hepatitis E virus (HEV) encoded papain-like cysteine protease (PCP) has been shown to inhibit IFN activation signaling by suppressing K63-linked de-ubiquitination of retinoic acid-inducible gene I (RIG-I) and TANK-binding kinase 1 (TBK1), thus effectively inhibiting down-stream activation of IFN signaling. In the present study, we demonstrated that HEV inhibits polyinosinic-polycytidylic acid (poly(I:C))-induced $IFN-{\beta}$ transcriptional induction. Moreover, by using reporter assay with individual HEV-encoded gene, we showed that HEV methyltransferase (MeT), a non-structural protein, significantly decreases RIG-I-induced $IFN-{\beta}$ induction and $NF-{\kappa}B$ signaling activities in a dose-dependent manner. Taken together, we report here that MeT, along with PCP, is responsible for the inhibition of RIG-I-induced activation of type I IFNs, expanding the list of HEV-encoded antagonists of the host innate immunity.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.5
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• pp.427-433
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• 2013

Receptor activator of NF-${\kappa}B$ ligand (RANKL)-induced osteoclastogenesis is accompanied by intracellular $Ca^{2+}$ mobilization in a form of oscillations, which plays essential roles by activating sequentially $Ca^{2+}$/calmodulin-dependent protein kinase, calcineurin and NFATc1, necessary in the osteoclast differentiation. However, it is not known whether $Ca^{2+}$ mobilization which is evoked in RANKL-independent way induces to differentiate into osteoclasts. In present study, we investigated $Ca^{2+}$ mobilization induced by aluminum fluoride ($AlF_4^-$), a G-protein activator, with or without RANKL and the effects of $AlF_4^-$ on the osteoclastogenesis in primary cultured mouse bone marrow-derived macrophages (BMMs). We show here that $AlF_4^-$ induces intracellular $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) oscillations, which is dependent on extracellular $Ca^{2+}$ influx. Notably, co-stimulation of $AlF_4^-$ with RANKL resulted in enhanced NFATc1 expression and formation of tartrate-resistant acid phosphatase (TRAP) positive multinucleated cells. Additionally, we confirmed that mitogen-activated protein kinase (MAPK) is also activated by $AlF_4^-$. Taken together, these results demonstrate that G-protein would be a novel modulator responsible for $[Ca^{2+}]_i$ oscillations and MAPK activation which lead to enhancement of RANKL-mediated osteoclastogenesis.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.6
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• pp.581-593
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• 2016

The advantages of monounsaturated fatty acids (MUFAs) on insulin resistance and type 2 diabetes mellitus (T2DM) have been well established. However, the molecular mechanisms of the anti-diabetic action of MUFAs remain unclear. This study examined the anti-hyperglycemic effect and explored the molecular mechanisms involved in the actions of fish oil- rich in MUFAs that had been acquired from hybrid catfish (Pangasius larnaudii${\times}$Pangasianodon hypophthalmus) among experimental type 2 diabetic rats. Diabetic rats that were fed with fish oil (500 and 1,000 mg/kg BW) for 12 weeks significantly reduced the fasting plasma glucose levels without increasing the plasma insulin levels. The diminishing levels of plasma lipids and the muscle triglyceride accumulation as well as the plasma leptin levels were identified in T2DM rats, which had been administrated with fish oil. Notably, the plasma adiponectin levels increased among these rats. The fish oil supplementation also improved glucose tolerance, insulin sensitivity and pancreatic histological changes. Moreover, the supplementation of fish oil improved insulin signaling ($p-Akt^{Ser473}$ and p-PKC-${\zeta}/{\lambda}^{Thr410/403}$), $p-AMPK^{Thr172}$ and membrane GLUT4 protein expressions, whereas the protein expressions of pro-inflammatory cytokines (TNF-${\alpha}$ and nuclear NF-${\kappa}B$) as well as p-PKC-${\theta}^{Thr538}$ were down regulated in the skeletal muscle. These data indicate that the effects of fish oil-rich in MUFAs in these T2DM rats were partly due to the attenuation of insulin resistance and an improvement in the adipokine imbalance. The mechanisms of the anti-hyperglycemic effect are involved in the improvement of insulin signaling, AMPK activation, GLUT4 translocation and suppression of pro-inflammatory cytokine protein expressions.