• Journal of Acupuncture Research
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• v.33 no.2
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• pp.1-9
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• 2016

Objectives : I investigated whether snake venom can synergistically strengthen the cytotoxic effects of NK-92 cells, and enhance the inhibition of the growth of lung cancer cells including NCI-H358 through the induction of death receptor dependent extrinsic apoptosis. Methods : Snake venom toxin inhibited cell growth of NCI-H358 Cells and exerted non influence on NK-92 cell viability. Moreover, when they were co-cultured with NK cells and concomitantly treated with $4{\mu}g/m{\ell}$ of snake venom toxin, more influence was exerted on the inhibition of growth of NCI-H358 cells than BV or NK cell co-culture alone. Results : The expression of Fas, TNFR2 and DR3 and in NCI-H358 lung cancer cells was significantly increased by co-culture of NK-92 cells and treatment of $4{\mu}g/m{\ell}$ of snake venom toxin, compared to co-culture of NK-92 cells alone. Coincidentally, Bax, caspase-3 and caspase-8 - expressions of pro-apoptotic proteins in the extrinsic apoptosis pathway, demonstrated significant increase. However, in anti-apoptotic NF-${\kappa}B$ activities, activity of the signal molecule was significantly decreased by co-culture of NK-92 cells and treatment of $4{\mu}g/m{\ell}$ of snake venom toxin, compared to co-culture of NK-92 cells or snake venom toxin treated by NCIH358 alone. Meanwhile, in terms of NO generation, there is a significant increase, in co-culture of NK-92 cells with NCI-H358 cells as well as the co-culture of NK-92 cells and concomitant treatment of $4{\mu}g/m{\ell}$ of snake venom toxin. However, no synergistic increase of NO generation was shown in co-culture of NK-92 cells and treatment of $4{\mu}g/m{\ell}$ of snake venom toxin, compared to co-culture of NK-92 cells with NCI-H358 cells. Conclusion : Consequently, this data provides that snake venom toxin could be useful candidate compounds to suppress lung cancer growth along with the cytotoxic effect of NK-92 cells through extrinsic apoptosis.

• Bulletin of the Korean Chemical Society
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• v.32 no.11
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• pp.4049-4054
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• 2011

A new compound, kalopanaxin F (3), and 11 known compounds (1, 2, 4-12), were isolated from the stem bark of Kalopanax pictus. Their structures were elucidated on the basis of chemical and spectroscopic methods. Five of the compounds (2, 3, 5, 6, and 12) significantly inhibited $TNF{\alpha}$-induced NF-${\kappa}B$ transcriptional activity in HepG2 cells in a dose-dependent manner, with $IC_{50}$ values ranging from 6.2 to 9.1 ${\mu}M$. Furthermore, the transcriptional inhibitory function of these compounds was confirmed based on decreases in COX-2 and iNOS gene expression in HepG2 cells. Compounds 3-7, 9, and 12 significantly activated the transcriptional activity of PPARs dose-dependently, with $EC_{50}$ values ranging from 4.1-$12.7{\mu}M$. Compounds 4 and 5 exhibited $PPAR{\alpha}$, $PPAR{\gamma}$, and $PPAR{\beta}({\delta})$ transactivational activities in a dose-dependent manner, with $EC_{50}$ values of 16.0 and 17.0, 8.7 and 16.5, 26.2 and 26.3 ${\mu}M$, respectively.

• Journal of the East Asian Society of Dietary Life
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• v.25 no.5
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• pp.806-812
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• 2015

Prostatic inflammation plays a crucial role on benign prostate hyperplasia (BPH) pathogenesis and progression. In this study, BPH was induced by testosterone propinate in castrated rats for 8 weeks. Hot water extract from Curcuma longa L. (CL) was administered orally for 4 weeks along with positive controls, saw Palmetto and finasteride. CL supplementation induced histological changes, reduced expression of TNF-${\alpha}$, IL-6, IL-$1{\beta}$, COX-2, and phospo-p65 in prostate tissue compared with the BPH group. These findings suggest that suppression of pro-inflammatory cytokines could be attributed, at least partly, to the anti-inflammatory action of C. longa, and this action may be helpful to understand the inhibitory effect of Curcuma longa L. in BPH.

• BMB Reports
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• v.50 no.12
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• pp.634-639
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• 2017

We aimed to assess the anti-inflammatory and antioxidative properties of KHG26792, a novel azetidine derivative, in amyloid ${\beta}$ ($A{\beta}$)-treated primary microglial cells. KHG26792 attenuated the $A{\beta}-induced$ production of inflammatory mediators such as IL-6, $IL-1{\beta}$, $TNF-{\alpha}$, and nitric oxide. The levels of protein oxidation, lipid peroxidation, ROS, and NADHP oxidase enhanced by $A{\beta}$ were also downregulated by KHG26792 treatment. The effects of KHG26792 against the $A{\beta}-induced$ increases in inflammatory cytokine levels and oxidative stress were achieved by increasing the phosphorylation of $Akt/GSK-3{\beta}$ signaling and by decreasing the $A{\beta}-induced$ translocation of $NF-{\kappa}B$. Our results provide novel insights into the use of KHG26792 as a potential agent against $A{\beta}$ toxicity, including its role in the reduction of inflammation and oxidative stress. Nevertheless, further investigations of cellular signaling are required to clarify the in vivo effects of KHG26792 against $A{\beta}-induced$ toxicity.

• The Korea Journal of Herbology
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• v.22 no.2
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• pp.17-24
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• 2007

Objectives : Licorice has been commonly used as a detoxification agent. We previously reported that licorice and its component, liquiritigenin, exhibits cytoprotective activity against Pb-induced toxicity. The present study was conducted to evaluate the effect of liquiritigenin on the lead-induced cytotoxicity in PC-12 cells. Methods : PC-12 cells were pre-treated with liquiritigenin, and further incubated with lead 100 ${\mu}M$ for $12^{\sim}48$ hours. The viability of PC-12 cells was measured by MTT assay, and the levels of proteins were analysed by western blot. Results : Severe cytotoxicity was induced and nitric oxide (NO) production was augmented by the exposure of lead. Liquiritigenin protected cells from lead-induced cytoxicity and reduced NO production in a dose-dependent manner. The inhibition of NO production was due to the suppression of iNOS protein via the inhibition of $NF-{\kappa}B$ nuclear translocation, determined by western blot analysis. Conclusions : These results suggest that liquiritigenin may exert cytoprotective effect against lead toxicity by inhibiting NO production.

• IMMUNE NETWORK
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• v.13 no.4
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• pp.123-132
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• 2013

Obesity is consistently increasing in prevalence and can trigger insulin resistance and type 2 diabetes. Many lines of evidence have shown that macrophages play a major role in inflammation associated with obesity. This study was conducted to determine metformin, a widely prescribed drug for type 2 diabetes, would regulate inflammation through down-regulation of scavenger receptors in macrophages from obesity-induced type 2 diabetes. RAW 264.7 cells and peritoneal macrophages were stimulated with LPS to induce inflammation, and C57BL/6N mice were fed a high-fat diet to generate obesity-induced type 2 diabetes mice. Metformin reduced the production of NO, $PGE_2$ and pro-inflammatory cytokines ($IL-1{\beta}$, IL-6 and $TNF-{\alpha}$) through down-regulation of $NF-{\kappa}B$ translocation in macrophages in a dose-dependent manner. On the other hand, the protein expressions of anti-inflammatory cytokines, IL-4 and IL-10, were enhanced or maintained by metformin. Also, metformin suppressed secretion of $TNF-{\alpha}$ and reduced the protein and mRNA expression of $TNF-{\alpha}$ in obese mice as well as in macrophages. The expression of scavenger receptors, CD36 and SR-A, were attenuated by metformin in macrophages and obese mice. These results suggest that metformin may attenuate inflammatory responses by suppressing the production of $TNF-{\alpha}$ and the expressions of scavenger receptors.

• International Journal of Oral Biology
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• v.31 no.3
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• pp.87-92
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• 2006

Schwann cells play an important role in peripheral nerve regeneration. Upon nerve injury, Schwann cells are activated and produce various proinflammatory mediators including IL-6, LIF and MCP-1, which result in the recruitment of macrophages and phagocytosis of myelin debris. However, it is unclear how the nerve injury induces Schwann cell activation. Recently, it was reported that necrotic cells induce immune cell activation via toll-like receptors (TLRs). This suggests that the TLRs expressed on Schwann cells may recognize nerve damage by binding to the endogenous ligands secreted by the damaged nerve, thereby inducing Schwann cell activation. To explore the possibility, we stimulated iSC, a rat Schwann cell line, with damaged neuronal cell extracts (DNCE). The stimulation of iSC with DNCE induced the expression of various inflammatory mediators including IL-6, LIF, MCP-1 and iNOS. Studies on the signaling pathway indicate that $NF-{\kappa}B$, p38 and JNK activation are required for the DNCE-induced inflammatory gene expression. Furthermore, treatment of either anti-TLR3 neutralizing antibody or ribonuclease inhibited the DNCE-induced proinflammatory gene expression in iSC. In summary, these results suggest that damaged neuronal cells induce inflammatory Schwann cell activation via TLR3, which might be involved in the Wallerian degeneration after a peripheral nerve injury.

• Toxicological Research
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• v.29 no.3
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• pp.195-201
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• 2013

The anti-inflammatory effects of glycosaminoglycan (GAG) derived from Isaria sinclairii (IS) and of IS extracts were investigated in a complete Freund's adjuvant (CFA)-treated chronic arthritis rat model. Groups of rats were treated orally with 30 mg/kg one of the following: [1] saline control, extracts of [2] water-IS, [3] methanol-IS, [4] butanol-IS, [5] ethyl acetate-IS, or [6] Indomethacin(R) as the positive control for a period of two weeks. The anti-paw edema effects of the individual extracts were in the following order: water-IS ex. > methanol ex. > butanol ex. > ethyl acetate ex. The water/methanol extract from I. sinclairii remarkably inhibited UV-mediated upregulation of NF-${\kappa}B$ activity in transfected HaCaT cells. GAG as a water-soluble alcohol precipitated fraction also produced a noticeable anti-edema effect. This GAG also inhibited the pro-inflammatory cytokine levels of prostaglandin $E_2$-stimulated lipopolysaccharide in LAW 264.7 cells, cytokine TNF-${\alpha}$ production in splenocytes, and atherogenesis cytokine levels of vascular endothelial growth factor (VEGF) production in HUVEC cells in a dose-dependent manner. In the histological analysis, the LV dorsal root ganglion, including the articular cartilage, and linked to the paw-treated IS GAG, was repaired against CFA-induced cartilage destruction. Combined treatment with Indomethacin(R) (5 mg/kg) and IS GAG (10 mg/kg) also more effectively inhibited CFA-induced paw edema at 3 hr, 24 hr, and 48 hr to levels comparable to the anti-inflammatory drug, indomethacin. Thus, the IS GAG described here holds great promise as an anti-inflammatory drug in the future.

• Nutrition Research and Practice
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• v.8 no.5
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• pp.487-493
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• 2014

BACKGROUND/OBJECTIVES: D. candidum is a traditional Chinese food or medicine widely used in Asia. There has been little research into the anticancer effects of D. candidum, particularly the effects in colon cancer cells. The aim of this study was to investigate the anticancer effects of D. candidum in vitro and in vivo. MATERIALS/METHODS: The in vitro anti-cancer effects on HCT-116 colon cancer cells and in vivo anti-metastatic effects of DCME (Dendrobium canidum methanolic extract) were examined using the experimental methods of MTT assay, DAPI staining, flow cytometry analysis, RT-PCR, and Western blot analysis. RESULTS: At a concentration of 1.0 mg/mL, DCME inhibited the growth of HCT-116 cells by 84%, which was higher than at concentrations of 0.5 and 0.25 mg/mL. Chromatin condensation and formation of apoptotic bodies were observed in cancer cells cultured with DCME as well. In addition, DCME induced significant apoptosis in cancer cells by upregulation of Bax, caspase 9, and caspase 3, and downregulation of Bcl-2. Expression of genes commonly associated with inflammation, NF-${\kappa}B$, iNOS, and COX-2, was significantly downregulated by DCME. DCME also exerted an anti-metastasis effect on cancer cells as demonstrated by decreased expression of MMP genes and increased expression of TIMPs, which was confirmed by the inhibition of induced tumor metastasis in colon 26-M3.1 cells in BALB/c mice. CONCLUSIONS: Our results demonstrated that D. candidum had a potent in vitro anti-cancer effect, induced apoptosis, exhibited anti-inflammatory activities, and exerted in vivo anti-metastatic effects.

• 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.