• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.259.1-259.1
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• 2002

Many polysaccharides isolated from plants are considered to be biological response modifiers and have been shown to enhance various immune responses in vivo and in vitro. Here we demonstrate that a polysaccharide isolated from cell culture of Acanthopanax senticosus (AS) has a unique mode of immunostimulation with regard to its cell-type specificity. AS was found to markedly increase polyclonal IgM antibody production and the proliferation of B cells. and to activate iNOS transcription and NO production in macrophages. (omitted)

• Advances in Traditional Medicine
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• 제8권4호
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• pp.380-385
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• 2008

Ethanolic extracts of T. cordifolia and C. asiatica were evaluated for immunostimulatory effect in mice against sheep RBCs as antigen by three models viz. delayed type hypersensitivity reaction, ercent change in neutrophil count and haemagglutination titre. Immunostimulatory effect in the presence of immunosuppressant agent, cyclophosphamide (100 mg/kg, i.p.) was also investigated. T. cordifolia and C. asiatica significantly (p < 0.001, p < 0.05 respectively) enhanced foot pad thickness when measured after 24 hours of sheep RBC antigen challenge. Both the plant materials increased foot pad thickness even after being subjected to immunosuppressant exposure. T. cordifolia revealed enhanced neutrophil counts, while C. asiatica had no significant effect on neutrophil counts. T. cordifolia exhibited significantly (P < 0.01) elevated neutrophil levels even in the presence of cyclophosphamide administration. Both the plants exhibited humoral antibody response, as haemagglutination titre values were significantly high as compared to control. T. cordifolia and C. asiatica could combat immunosuppressant effect of cyclophosphamide (P < 0.01). This suggests that T. cordifolia and C. asiatica can be regarded as biological response modifiers and can be utilized for the development of immunostimulating agent among plant sources.

• 혜화의학회지
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• 제9권2호
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• pp.315-324
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• 2001

To investigate the capacity of anti-inflammatory cytokines and biological response modifiers (BRMs) to induce IL-$1{\beta}$, IL-6, TNF-${\alpha}$ gene overexpression from mouse macrophages, we isolated the resident peritoneal macrophages from BALB/c mouse (8 week old) and incubated for 6 h with lipopolysaccaride (LPS) and Moschus moschiferus (MOMS) extracts. Analysis of inflammatory cytokines gene expression was carried out by RT-PCR amplification. Amplified PCR products were electrophoresed on 1.2% agarose gel, and the analysis (Ht) was used to 1D-density program. 1. LPS and MOMS extract treatments resulted in a significant decrease in IL-$1{\beta}$, IL-6, TNF-${\alpha}$ mRNA expression level compared with the LPS treatment. 2. Among four sample of MOMS, Inhibitory effects of MOMS-A and MOMS-D for inflammatory cytokines gene expression were to be fine compared with the MOMS-Band MOMS-C. According to the above data, Because the anti- tumoral and anti-inflammatory response activities of macrophage are known to be dependent on the production of inflammatory cytokines (IL-$1{\beta}$, IL-6, TNF-${\alpha}$) by macrophages, we suggest that evaluations of BRM for the reduction of inflammatory cytokines production by macrophages are important for clinical application.

• Preventive Nutrition and Food Science
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• 제11권4호
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• pp.273-277
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• 2006

Recently, Rhei Rhizoma extracts (RRE) have begun to receive more attention as potential biological response modifiers. In the present study, we studied the antiproliferative effect of RRE on tumor cells and the effect of RRE on macrophage function. A variety of tumor cells and macrophages were treated with RRE at various concentrations. The effect of RRE on cell proliferation was measured by MTT assay and the effect of RRE on the production of nitric oxide (NO) was determined in the macrophage-like cell lines Raw264.7, C6 and peritoneal macrophages (pMQ). RRE inhibited the growth of tumor cells (e.g., B16, HOS). However, the effects of RRE on the production of NO varied with macrophage types. RRE had no effect on C6 cell growth and slightly increased the growth of Raw264.7 cells. In addition, treatment of normal pMQ with RRE enhanced NO production in a concentration-dependent manner, whereas RRE suppressed NO production at $50\;{\mu}g/mL$ in both Raw264.7 and C6 cells. However, RRE suppressed NO production in LPS/IFN-$\gamma$-stimulated C6 cells. Overall, these results suggest that RRE elicits an antiproliferative property and differentially modulates NO production in various macrophages, and have a potential for therapeutic application.

• Food Science and Biotechnology
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• 제17권6호
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• pp.1185-1190
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• 2008

When 10 kinds of herbal medicines were fractionated into hexane, MeOH, cold-water, and hot-water extracts, hot-water extracts from Acanthopanax senticosus (AS), Glycyrrhiza uralensis (GU), Cichorium intybus (CI), and Polygonatum odoratum (PO) showed the potent intestinal immune system modulating activity (1.72-, 1.62-, 1.60-, and 1.53-fold of control at $100{\mu}g/mL$, respectively). Especially, hot-water extracts from AS (215% compared with the control) and GU (187%) also had macrophages stimulating activity and mitogenic activity of splenocytes (7.1- and 6.5-fold) at $100{\mu}g/mL$. In addition, the effects of hot-water extracts from herbal medicines on anticancer activities were studied in mice. Hot-water extracts from AS and GU enhanced cytotoxicity of natural killer cell against cancer cell, Yac-1 (37 and 34% cytotoxicity) at E/T ratio 100:1, and colon 26-M3.1 cancer cell lines had significantly inhibited (82.1 and 75.2%) in experimental lung metastasis. These results suggest that hot-water extracts from A. senticosus and G. uralensis can be used as biological response modifiers to stimulate immune system and inhibit tumor.

• Natural Product Sciences
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• 제11권3호
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• pp.183-187
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• 2005

The objective of the present study was to determine the possible immune-enhancing effects of a substance extracted from a submerged culture of Lentinus edodes with rice bran (SLRB). According to the results obtained by measuring the in vitro macrophage activity of the exo-biopolymer from SLRB, it appears to exhibit activity similar to that of LPS, and this activity seems to occur in a dose-dependent manner. According to the results obtained by measuring splenocyte proliferation, the exo-biopolymer appears to induce an increase in proliferation of approximately 1.4-fold compared to the control group. We measured the proliferation of bone marrow cells in order to evaluate gut immunity and, according to our results, proliferation was increased to 109% that of the control group, and was similar to that associated with LPS. In order to characterize the enhancement of immunological activity in vivo, we orally administered the exo-biopolymer (25, 50, 250 mg/kg bw) to C3H/He mice, and then measured the macrophage activity, determining that the activity was higher than that of the controls at concentrations of 50 and 250 mg/kg. Therefore, the exo-biopolymer from SLRB can be considered to be a useful a BRM agent, as it clearly allows some protection against immunological diseases.

• Journal of Microbiology and Biotechnology
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• 제8권6호
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• pp.618-624
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• 1998

The culture conditions for Bacillus sp. DP-152 in the flask were investigated for the production of polysaccharide locculant, DP-152. The optimum pH and temperature for the locculant production were 8.0 and $30^{\circ}C$, respectively. The avorable substrates for flocculant production were soluble tarch and ammonium nitrate. The medium composition was optimized as follows: 30 g soluble starch, 0.75 g $NH_4NO_3,\; 2.0g\; K_2\;HPO_4,\; 0.1\; g KH_2PO_4,\; 0.2g\; MgSO_4.\; 7H_2O,\; and\; 0.2g\; MnSO_4~5H_2O$ in 11 of distilled water. Under this optimized condition, flocculating activity has been improved 4-fold compared with that of the basal medium. In the culture flask, the highest flocculating activity was obtained after 70 h of cultivation and the amount of bioflocculant DP-152 yielded was 12.4 g/$\ell$. The solution of bioflocculant DP-152 showed non-Newtonian characteristics. Bioflocculant DP-152 exhibited apparently higher viscosity at all concentrations compared to that of zooglan (from Zoogloea ramigera), and it was stable over a wide range of temperatures and pHs.

• Journal of Chest Surgery
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• 제26권1호
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• pp.47-53
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• 1993

The high relapse rate after curative surgery of lung cancer suggests that tumor cells are remained at the site of resection and in the distant organs. Postoperative radiochemoimmunotherapy including protein-bound polysaccharide PS-K[Copolang] and/or chemotherapy to improve the prognosis in lung cancer has been adopted. The patients with lung cancer who were treated with a combined modality therapy after surgery were reviewed to determine the effects of adjuvant immunotherapy[PS-K] and the relationship between midterm survival and clinicopathologic variables. During the past 5 years, 95 patients with lung cancer underwent resective operation. Of them, 30 cases were curative surgery, 29 were relative curative surgery, and the remainders were non-curative surgery. Postoperative combination therapies consisted of three types of therapies: postoperative BRM[biological response modifiers] with PS-K [Copolang] 50 mg/kg for 24 weeks[Group 1], chemoimmunotherapy with chemotherapy[a combination of cisplatin, etoposide, vindesine] and PS-K [Group 2], radioimmunotherapy with postoperative prophylactic irradiation to the mediastinum at total dose of 54 Gy-60 Gy and PS-K [Group 3] and surgery without adjuvant therapy[Group 4]. Twenty months survival rates of localized disease [Stages I and II] treated with PS-K, with radioimmunotherapy and no therapy were 73 %, 60 %, and 50 %, respectively [p [0.05]. Three-year survival rates of regionally advanced cases [stage Ilia and IIIb] were 23 % in Group 1.57 % in Group 2.20 % in Group 3, and 0 % in Group 4, respectively.According to above results, we suggest that postoperative combination therapy including PS-K might improve the prognosis of lung cancer. The similar survival pattern of patients with squamous cell carcinoma and adenocarcinoma treated with BRM, chemoimmunotherapy or radioimmunotherapy need to evaluate the role of postoperative immunotherapy[PS-K] in randomized studies.

• 약학회지
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• 제47권3호
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• pp.159-166
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• 2003

In order to study the clinical usefulness of crude polysaccharides fractionated from Eleutherococcus senticosus, EN-3, in eliminating tumors, we have investigated the effect of combination therapy on the murine tumor metastasis and growth models. In experimental metastasis of colon26-M3.1 cells, prophylactic intravenous (i.v.) administration of EN-3 (0.5, 5, and 50 $\mu\textrm{g}$/mouse) inhibited tumor metastasis compared with tumor control group in 33.6, 66.8, and 81.8％ respectively. The administration of EN-3 (50 $\mu\textrm{g}$/mouse) also exhibited a 66.1％ therapeutic effect on lung tumor metastasis. Although EN-3 induced no toxic effect on both tumor cell and normal splenocyte in the concentration below 100 $\mu\textrm{g}$/mι in in vitro, it induced significant proliferating activity on normal splenocyte in the concentration-dependent manner. In an analysis of NK-cell activity, i.v. administration of EN-3 (4∼100 $\mu\textrm{g}$/mouse) significantly augmented NK cytotoxicity to YAC-1 tumor cells. The combination treatments of cisplatin (10 $\mu\textrm{g}$) and EN-3 (5 $\mu\textrm{g}$) induced synergistic effect on the inhibition of tumor metastasis in experimental tumor metastasis model produced by colon26-M3.1 cells. In addition, the combination treatments also exhibited prolongation of lifespan in S∼180 tumor bearing mouse for over the 60 days. Even though cisplatin (2.5 $\mu\textrm{g}$/mι) exhibited cytotoxicity to tumor cells and inhibited tumor growth over 95％ in in vitro, combination treatment with EN-3 (20 $\mu\textrm{g}$/mι) was induced splenocyte proliferation and produced cytokines, such as TNF-$\alpha$, IL-1 and IL-12, from the macrophages. These results suggested that EN-3 stimulate immune system non-specifically and apply to the biological response modifiers (BRM) in chemo-immunotherapy for tumor prevention.

• Molecules and Cells
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• 제26권1호
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• pp.93-99
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• 2008

Transcriptional silencing is regulated by promoter methylation and histone modifications such as methylation and acetylation. We constructed a Schizosaccaromyces pombe reporter strain, KCT120a, to identify modifiers of transcriptional silencing, by inserting the $ura4^+$ gene into a heterochromatic telomere region. Two compounds inhibited the activity of histone deacetylases, induced acetylation of histone H3 and caused apoptotic cell death in HeLa cells. Expression of gelsolin and $p21^{waf1/cip1}$ also increased, as it does in response to HDAC inhibitors such as TSA. Therefore, these compounds appear to be potent inhibitors of HDACs, and hence potential anti-cancer drugs. Our observations suggest that a yeast cell-based assay system for transcriptional silencing may be useful for identifying histone deacetylase inhibitors and other agents affecting chromatin remodeling.