• The Korean Journal of Physiology and Pharmacology
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• v.22 no.4
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• pp.369-377
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• 2018

Spinal tuberculosis (ST) is the tuberculosis caused by Mycobacterium tuberculosis (Mtb) infections in spinal curds. Isoliquiritigenin (4,2',4'-trihydroxychalcone, ISL) is an anti-inflammatory flavonoid derived from licorice (Glycyrrhiza uralensis), a Chinese traditional medicine. In this study, we evaluated the potential of ISL in treating ST in New Zealand white rabbit models. In the model, rabbits (n=40) were infected with Mtb strain H37Rv or not in their $6^{th}$ lumbar vertebral bodies. Since the day of infection, rabbits were treated with 20 mg/kg and 100 mg/kg of ISL respectively. After 10 weeks of treatments, the adjacent vertebral bone tissues of rabbits were analyzed through Hematoxylin-Eosin staining. The relative expression of Monocyte chemoattractant protein-1 (MCP-1/CCL2), transcription factor ${\kappa}B$ ($NF-{\kappa}B$) p65 in lymphocytes were verified through reverse transcription quantitative real-time PCR (RT-qPCR), western blotting and enzyme-linked immunosorbent assays (ELISA). The serum level of interleukin (IL)-2, IL-4, IL-10 and interferon ${\gamma}$ ($IFN-{\gamma}$) were evaluated through ELISA. The effects of ISL on the phosphorylation of $I{\kappa}B{\alpha}$, $IKK{\alpha}/{\beta}$ and p65 in $NF-{\kappa}B$ signaling pathways were assessed through western blotting. In the results, ISL has been shown to effectively attenuate the granulation inside adjacent vertebral tissues. The relative level of MCP-1, p65 and IL-4 and IL-10 were retrieved. $NF-{\kappa}B$ signaling was inhibited, in which the phosphorylation of p65, $I{\kappa}B{\alpha}$ and $IKK{\alpha}/{\beta}$ were suppressed whereas the level of $I{\kappa}B{\alpha}$ were elevated. In conclusion, ISL might be an effective drug that inhibited the formation of granulomas through downregulating MCP-1, $NF-{\kappa}B$, IL-4 and IL-10 in treating ST.

• Korean Journal of Pharmacognosy
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• v.43 no.3
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• pp.231-238
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• 2012

Menthae herba (MH) extracts exhibit anti-inflammatory effects. The purpose of this study was to determine whether the anti-inflammatory effects of MH extracts vary according to the cultivation regions. We performed a comparative analysis of MH extracts by evaluating the production of inflammatory mediators in RAW 264.7 murine macrophage cells and HaCaT human keratinocyte cells. MH extracts obtained from different cultivation regions in Korea and China significantly reduced the production of nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$), and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) in RAW 264.7 cells stimulated with lipopolysaccharide (LPS). No differences in these inhibitory activities were observed between MH extracts. In HaCaT cells stimulated with TNF-${\alpha}$ and interferon-${\gamma}$ (IFN-${\gamma}$), MH extracts did not inhibit the production of macrophage-derived chemokine (MDC/CCL22), but most extracts reduced the production of the regulated on activation normal T-cell expression and secreted (RANTES/CCL5). We used clustering tree analysis of the MH extracts according to the chromatographic pattern and anti-inflammatory potency of MH extracts. We observed differences in the chromatographic pattern of MH extracts but no difference in anti-inflammatory potency. Our findings suggest that MH extracts from different regions do not show any differences in their pharmacological potency in that MH extracts are used as therapeutic agents to treat inflammatory disorders.

• Food Science and Biotechnology
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• v.16 no.4
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• pp.594-599
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• 2007

In this study, we evaluated whether the oral administration of chondroitin from the cartilage of Raja kenojei is effective on the progression of rheumatoid arthritis (RA), using collagen-induced arthritic (CIA) mice. Arthritis development was delayed dose-dependently in the chondroitin-treated groups. The pre- and late-treated groups receiving 1,000 mg/kg of chondroitin had clinical scores that were reduced significantly by 56.9 (p<0.05) and 43.3% (p<0.05), respectively, compared to the vehicle-treated groups. Hematoxylin eosin staining and X-ray radiography showed that the chondroitins reduced the infiltration of inflammatory cells and prevented joint destruction of the knee and paw. Reverse transcription-polyerase chain reaction analysis revealed that chondroitin administration inhibited the expressions of tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), $interlukin-1{\beta}$ ($IL-1{\beta}$), and $interferon-{\gamma}$ ($IFN-{\gamma}$) in joints more than the administration of vehicle. Chondroitin treatment also decreased the production of rheumatoid factors (RF), IgG and IgM, in the serum of CIA mice. These results indicate that chrondroitin administration has a protective effect involving the inhibition of pro-inflammatory cytokine production in CIA mice.

• The Korean Journal of Pharmacology
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• v.32 no.2
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• pp.177-188
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• 1996

The effects of cytokines on the growth and differentiation of glial cells in culture were evaluated to confirm that cytokines could modify the number and function of glial cells. Proliferation of glial cells was determined by the $^3H-thymidine$ uptake and the double immunostain with anti-cell specific marker and anti-bromodeoxyuridine(BrdU) antibody. To check the effect on the differentiation of glial cells, the amount of glial fibrillar acidic protein(GFAP) and the activity of glutamine synthetase(GS) were measured in astrocytes. And also the amounts of myelin basic protein(MBP) and the activity of 2',3'-cyclic nucleotide phosphohydrolase(CNPase) were measured in oligodendrocytes. Among the cytokines used, only interleukin-$1{\beta}(IL-1{\beta})$ stimulated the growth of type 1 and type 2 astrocyte as well as 0-2A precursor cell. When the functional changes in these glial cells by cytokines were tested, $IL-1{\beta}$ did not increase GFAP content in type 1 and type 2 astrocyte, but $IL-1{\beta}$ increased GS activity in type 1 astrocyte, and slightly decreased this enzyme activity in type 2 astrocyte. Also interleukin-2(IL-2) and $interferon-{\gamma}$ $(IFN-{\gamma})$ inhibited the activity of GS in type 1 and type 2 astrocyte. On the other hand, all cytokines used did not modify the growth and differentiation in oligodendrocytes. From these results we could suggest that $IL-1{\beta}$ increases the growth of type 1 and type 2 astrocyte and also promotes the development for 0-2A precursor cell to type 2 astrocyte.

• YAKHAK HOEJI
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• v.54 no.3
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• pp.192-199
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• 2010

Colorectal cancer is one of the most common alimentary malignancies. In this study, the antitumor activity of activated human natural killer (NK) cells against human colorectal cancer was evaluated in vivo. Human NK cells are the key contributors of innate immune response and the effective functions of these cells are enhanced by cytokines. Human peripheral blood mononuclear cells (PBMC) were cultured with interleukin-2 (IL-2)-containing medium for 14 days and resulted in enriched NK cell population. The resulting populations of the cells comprised 7% $CD3^+CD4^+$ cells, 25% $CD3^+CD8^+$ cells, 13% $CD3^-CD8^+$ cells, 4% $CD3^+$CD16/$CD56^+$ cells, 39% $CD3^+$CD16/$CD56^-$ cells, and 52% $CD3^-$CD16/$CD56^+$ cells. Tumor necrosis factor alpha (TNF-$\alpha$), interferon gamma (IFN-$\gamma$), IL-2, IL-4, and IL-5 transcripts of the activated NK cells were confirmed by RT-PCR. In addition, activated NK cells at doses of 2.5, 5 and 10 million cells per mouse inhibited 10%, 34% and 47% of SW620-induced tumor growth in nude mouse xenograft assays, respectively. This study suggests that NK cell-based immunotherapy may be used as an adoptive immunotherapy for colorectal cancer patients.

• Korean Journal of Medicinal Crop Science
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• v.18 no.1
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• pp.1-8
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• 2010

Inonotus obliquus is one of the immune-regulatory substances and is recognized to play the role in the metabolic process of inflammation, allergy and immuntiy. The purpose of this study was to evaluate the effects of water extracts of Inonotus obliquus (IOW) on the liver lymphocyte immune function in the Sprague-Dawley male rats treated with carbon tetrachloride ($CCl_4$) to induce liver damage. Rats were fed with each experimental diet and water for 4 weeks. We found that effects of IOW on interferon-gamma (IFN-$\gamma$), signal transducer and activator of transcription 1 (STAT1), phospho-signal transducer and activator of transcription 1 (pSTAT1) and GATA-binding protein 3 (GATA-3) were decrease in vivo. Interleukin-4 (IL-4), STAT6, pSTAT6 and T-box expressed in T-cells (T-bet) decreased significantly lower in $CCl_4$+IOW group than the $CCl_4$ group. Our data indicated that cytokine protein production were increased in $CCl_4$ group and $CCl_4$+IOW group. As a result of this study, we assume that IOW fed could regulate the immuno-modulating functions through regulate the cytokine production capacity activated by liver damage.

• The Journal of Korean Medicine
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• v.19 no.2
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• pp.420-438
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• 1998

Herba Xanthii(HX), Radix Xantluii(RX) and Fructus Xanthii(FX) is one of the oriental medicine that has been used for the treatment of such infectious diseases and tumors. However, the mechanism of the drug is not investigated much. This study was done to know the effects of HX, RX and FX extract on the such innate immunities as phagocytic function and reactive radical formtions from phagocytes and the such acquired immunities as humoral and cell-mediated immunities. The followings are the results obtained from this study: 1. HX2 and FX1 groups increases the in vivo phagocytic activity of mononuclear phagocytes. 2. HXB, RXB, RXC, FXB and FXC groups increase the in vitro phagocytic activities. 3. RXB group stimulated the macrophages to produce nitric oxide in the presence of $interferon-{\gamma}$ $(IFN-{\gamma})$. 4. HX and RX whole groups increased the luminol-amplified reactive oxygen intermediate production in vivo. 5. HX whole and RX1, FX2 groups increased the lucigenin-amplified reactive oxygen intennediate production in vivo. 6. HXC group only increased the luminol-amplified reactive oxygen intermediate production in vitro. 7. HXB, FXB and FXC groups increased the lucigenin-amplified reactive oxygen intermediate production in vitro. 8. HX2, RX1 and FX whole groups increased the hemolysin formations from B cells. 9. HX, RX and FX whole groups significantly increased the rosette forming cells from the spleen. 10. HX, RX and FX whole groups significantly decreased the delayed-type hypersensitivity measured by footpad swelling. The above results demonstrate that HX, RX and FX has enhancing effects on innate immunity selectively and decreasing effects on delayed-type hypersensitivity of cell-mediated immunity according to medicinal part and diluted condition. This immunomodulating effects of HX, RX and FX might be responsible for the treatment of immune-mediated disorders.

• The Journal of Korean Medicine
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• v.29 no.5
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• pp.96-103
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• 2008

Objectives : Tongqiao-tang(TQT) has been commonly used for the treatment of common cold, rhinitis etc. Nowadays, TQT becomes one of the most frequently used medicines for allergic rhinitis, but the mechanism of TQT in vivo isn't investigated yet. This study was performed to investigate the effect of TQT on OVA-induced allergic rhinitis mouse model by calculating serum cytokines and IgE. Methods : 8 weeks aged male BALB/c mice were divided into three groups: the normal group, the control group and the medicated group (the TQT group). Each group was consisted of 15 mice. The TQT group was administered TQT extract orally one time a day (1g/kg) from the $1^{st}$ day of experiment till the $26^{th}$ day. The control group and the normal group were administered normal saline by the same method of the TQT group. To induce the allergic rhinitis in the control group and the TQT group, mice of each group were sensitized intraperitoneally with ovalbumin (OVA) solution at the $1^{st}$, the $7^{th}$ and the $14^{th}$ day. After then, intranasal sensitization was performed by dropping 0.1% OVA solution in nasal cavity at the $22^{th}$, the $24^{th}$ and the $26^{th}$ day. At the $27^{th}$ day, the mice were killed and the changes of interferon-${\gamma}$, interleukin-4, interleukin-5, total IgE and OVA-specific IgE were checked. Results : IFN-${\gamma}$ was increased 36% more in the TQT group than that in the control group. IL-4, IL-5, the total IgE and OVA-specific IgE were decreased in the TQT group as compared with the control group and these results were statistically significant. Conclusions : Considering the above experimental results, this study showed that TQT could reduce the allergic reaction in allergic rhinitis. Advanced studies are required to investigate the further mechanisms of TQT.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.3
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• pp.372-378
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• 2011

We extracted polysaccharide from the sea hare, Aplysia kurodai, purified it partially, and experimented its immune response using the human blood lymphocytes and macrophage cell lines. Aplysia kurodai polysaccharide fraction (APF) improved the growth of the T cell (Jurkat) up to 40% by treatment for 48 hours, and decreased the growth of blood cancer, Jiyoye cell line. The APF on RAW 264.7 cell also increased interleukin-12 up to 47%. In contrast, the secretion of interleukin-2 and interferon-gamma by treatment of only APF or APF and concanavalin A on Jurkat for 24 hours and 48 hours didn't influence significantly. These results suggest that the APF has possible immune regulating ability.

• Journal of Haehwa Medicine
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• v.16 no.2
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• pp.251-265
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• 2007

Yanhyeoljeseuptang(YHJST) is a traditional herbal medicine used for the treatment of dermatitis. The aim of this study was to confirm whether or not YHJST has a preventive effect on development of atopic dermatitis in dinitrochlorobenzene(DNCB)-applied Nc/Nga mouse. This study was undertaken to develop a reliable mouse model demonstrating similar immunologic phenomena as human atopic dermatitis characterized with predominance of type-2 immune response. NC/Nga mouse were sensitized with $200\;{\mu\ell}$ of 1% 2,4-dinitrochlorobenzene(DNCB) (acetone : olive oil = 3 : 1 mixture) and challenged twice or three times with $150\;{\mu\ell}$ of 0.2% DNCB in a week for the following 4 weeks. YHJST was administered orally to Nc/Nga mouse for 8 weeks, which led to the remarkable suppression on the development of dermatitis, as determined by various immune factors related to pathogenesis of atopic dermatitis in splenocytes and DLN cells. In this study, YHJST selectively suppressed T ce11 (CD4+, CD3+/CD69+, CD4+/CD25+) activation, which may be essential for ratio of IL-4 versus INF-$\gamma$ produced in the splenic T cell culture supernatants was approximately 3-fold higher in the mouse treated with DNCB than their control mouse respectively. Immunologic studies showed down-regulated that the capacity of spleen T cells to produce IL-4, but IFN-$\gamma$ was up-regulated by means of oral intake of these YHJST. These results strongly suggest that YHJST is a promising candidate for treatment of human atopic dermatitis.