Rhei Rhizoma Extracts Have Antiproliferative Properties and Differential Effects on NO Production in Macrophages

Pyo, Suh-Kneung,Son, Eun-Wha The Korean Society of Food Science and Nutrition 2006 Preventive Nutrition and Food Science Vol.11 No.4

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.

Immunomodulatory Effects of Cimicifugae Rhizoma Extracts in Macrophages

Pyo, Suh-Kneung,Kim, Byung-Oh,Choi, Hye-Sook,Son, Eun-Wha The Korean Society of Food Science and Nutrition 2006 Preventive Nutrition and Food Science Vol.11 No.4

Cimicifugae Rhizoma (CR) belongs to the Ranunculaceae family, which has been traditionally used to treat climacteric complaints, antipyretics and diaphoresis as an alternative medicine for estrogen hormone replacement therapy with estrogens. Recently, it has been reported that different extract fractions of CR have various effects such as anti-allergic, anti-inflammatory and anti-proliferative activities. The current study investigated the immunomodulatory effects of Cimicifugae Rhizoma water extracts (CRE) in the macrophage-like cell line, Raw 264.7. Our results showed that CRE ($1\sim50\;{\mu}g/mL$) stimulated tumoricidal activity and NO production, whereas phagocytic activity was inhibited at the same concentrations. Additionally, iNOS mRNA expression was significantly increased in Raw 264.7 exposed to CRE as demonstrated by RT-PCR. These results indicate that the tumoricidal activity induced by CRE may be mediated by the production of NO and these activities may be useful for the treatment of diseases such as cancer.

Immunomodulation of NK Cell Activity by Red Ginseng Acidic Polysaccharide (RGAP) in Ovariectomized Rats

Kim, Kyung-Suk,Pyo, Suh-Kneung,Sohn, Eun-Hwa The Korean Society of Ginseng 2009 Journal of Ginseng Research Vol.33 No.2

The in-vitro immunomodulatory function of murine natural-killer (NK) cells induced by red-ginseng acidic polysaccharide (RGAP) in ovariectomized (OVX) rats was examined in this study. The IL-2-induced NK cell activity was significantly decreased in the OVX rats compared to the sham groups, but the normally induced NK cell activity was not. RGAP, however, increased the NK cell activity in both groups, and this effect involved iNOS expression. The inhibition of iNOS activity did not increase the NK cell cytotoxicity by RGAP in the OVX rats. The data that were obtained also demonstrated that the expression of iNOS was increased in the spleen of the OVX rats. These results indicate that RGAP increases the tumoricidal activity of the NK cell in the OVX rats, which is a primed or activated state of innate immune cells resulting from the changes in cytokine production induced by estrogen-deficient stress. Therefore, RGAP has a synergistic effect on the NK cell activities, which are regulated by the iNOS signals in OVX rats. This suggests that RGAP is useful for potential therapeutic strategies as a nutrient in regulating the NK cells in OVX rats.

Immunomodulating Activity of DW-116, A New Quinolone Antibiotic

Moon, Eun-Yi,Choi, Chung-Ha,Pyo, Suh-Kneung,Chung, Yong-Ho,Yoon, Sung-June,Lee, Dug-Keun The Pharmaceutical Society of Korea 1998 Archives of Pharmacal Research Vol.21 No.5

DW-116, [1-(5-fluoro-2-pyridyl)-6-fluoro-7-(4-methyl-1-piperazinyl)-1,4-dihydro-4-oxoquino-line-3-carboxylic acid hydrochloride}, is a new quinolone antibiotic with a broad antibacterial spectrum against G(+) and G(-) bacteria. DW-116 was evaluated for the immunomodulating activities, which is one of the efforts to investigate the mechanism of action related to the good in vivo antibacterial efficacy. The results of in vitro studies revealed there was no statistically significant increase in B and T lymphocyte proliferation. But the results of in vivo studies showed that the number of plaque forming cells (PFC), the amount of polyclonal antibodies and delayed-type hypersensitivity (DTH) were significantly increased after the repeat administration with 12 and 60 mg/kg of DW-116. Taken together, these results proposed that immunostimulting effect of DW-116 could be one of the action mechanisms for demonstrating in vivo antibacterial activities under these experimental conditions.

Enhancement of Murine NK cell Activity in vitro by Red Ginseng Acidic Polysaccharide

Choi, Hye-Sook,Sohn, Eun-Wha,Rhee, Dong-Kwon,Pyo, Suh-Kneung The Korean Society of Ginseng 2009 Journal of Ginseng Research Vol.33 No.4

본 논문은 홍삼 산성 다당류 (RGAP)의 생체외 쥣과 NK 세포 활성 향상에 대한 내용으로 주요 내용은 다음과 같다. RGAP는 Yac-1 종양 세포에서 NK 세포 활성을 향상시켰다. 비장 세포에 16시간 동안 RGAP 10 및 $100{\mu}g$/ml을 처리한 결과, NK 활성이 239와 250% 증가 하였다. 인터페론 (IFN)-$\gamma$ 생성은 17-125% 증가하였고, 종양 괴사 인자 (TNF)-${\alpha}$ 생성도 15-100% 증가 하였다. NK 세포의 세포 독성 증가는 NK 세포가 생성하는 이 두 시토카인 증가가 원인이다. 따라서 RGAP는 NK 세포에 미치는 면역증진 효과가 있다는 내용이다. The in-vitro immunomodulatory function of the activity of murine natural-killer (NK) cells induced by redginseng acidic polysaccharide (RGAP) was examined. RGAP induced the significant enhancement of NK cell activity against the Yac-1 tumor cells. The treatment of splenocytes cultured with RGAP for 16 h resulted in a significant increase in NK activity at the E:T ratio of 100:1, and in a 239 and 250% increase at 10 and $100{\mu}g$/ml, respectively. We also demonstrate that RGAP treatment increased the production of interferon (IFN)-$\gamma$ (17-125%) and tumor necrosis factor (TNF)-${\alpha}$ (15-100%), suggesting that the increase in NK cell cytotoxicity could be due to the enhancement of the NK cell production of both cytokines. In addition, RGAP had a stimulating effect on lymphocyte proliferation in the presence of mitogens. Overall, these results suggest that RGAP has an immunopotentiating effect on NK cells, which can support the development of clinical studies on RGAP.

The Comparative Immunomodulatory Effects of β-Glucans from Yeast, Bacteria, and Mushroom on the Function of Macrophages

Jang, Seon-A,Park, Sul-Kyoung,Lim, Jung-Dae,Kang, Se-Chan,Yang, Kwang-Hee,Pyo, Suh-Kneung,Sohn, Eun-Hwa The Korean Society of Food Science and Nutrition 2009 Preventive Nutrition and Food Science Vol.14 No.2

The comparative immunomodulatory effects of ${\beta}$-glucans isolated from mushroom fungi (Coriolus versicol), yeast (Saccharomyces cerevisiae) and bacteria (Agrobacterium) on the major functions of macrophages were evaluated. As parameters of macrophage functions, we examined tumoricidal activity, phagocytosis, nitric oxide (NO) production, and the induction of inducible NO synthetase (iNOS) in RAW264.7 cells, following treatments with ${\beta}$-glucans from the three different sources. The results indicated that all ${\beta}$-glucan treatments significantly induced tumoricidal activity in the RAW264.7 cells, with a remarkable effect shown by the beta-glucan from Agrobacterium at a concentration of $10{\mu}g/mL$. There was also a significant increase in iNOS-NO system activity in macrophages treated with ${\beta}$-glucans extracted from yeast; however, iNOS-NO system activity was not markedly changed by the treatment of ${\beta}$-glucans from C. versicolor mushroom fungi or Agrobacterium. Furthermore, the ${\beta}$-glucans from C. versicolor had a significant phagocytotic effect at concentrations of 1, 10, and $100{\mu}g/mL$. Taken together, the present data suggest that these ${\beta}$-glucans, isolated from three different sources, have different effects on macrophage function, and therefore, may have different clinical uses in different for various types of diseases.

Effects of Non-Saponin Red Ginseng Components (NSRG) on Functions of Macrophages Isolated from Young and Aged Mice

Kim, Kyung-Ho,Jang, Seon-A,Kim, Kyung-Suk,Park, Sul-Kyoung,Park, Hye-Jin,Lee, Soo-Jin,Pyo, Suh-Kneung,Sohn, Eun-Hwa The Korean Society of Ginseng 2009 Journal of Ginseng Research Vol.33 No.3

Macrophages play an important role in the first line of immunologic effects against tumor cells. The effects of nonsaponin red ginseng (NSRG) components on macrophage functions like tumoricidal activity, phagocytic activity, and NO production in young (8-weeks-old) and aged (82-weeks-old) male C57BL/6 mice were assessed in vitro, respectively. The treatment of tumor cells (melanoma B16 cells) with the supernatants of NSRG-treated macrophages resulted in an increase of cytotoxicity at 300 $\mu$g/ml in the aged mice, whereas the supernatants did not have a cytotoxic effect in the young mice. It was observed that the supernatants induced the increase of tumor cell proliferation at 150 $\mu$g/ml in the young mice, suggesting that the supernatants contain growth factors rather than cytotoxic molecules. In addition, NSRG alone had a direct cytotoxic effect on the B16 tumor cells. NSRG had no effect on the NO production by the macrophages in the young mice, while it significantly increased the level of NO release in the aged mice. There was no difference in the phagocytic activities of the macrophages by NSRG in both groups of mice. These results suggest that NSRG has differential effects on the macrophage functions in young and aged mice.

Effects of Supplementation with Higher Levels of Manganese and Magnesium on Immune Function

Son, Eun-Wha,Lee, Sung-Ryul,Choi, Hye-Sook,Koo, Hyun-Jung,Huh, Jung-Eun,Kim, Mi-Hyun,Pyo, Suh-kneung 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.6

The magnesium (Mg) and manganese (Mn) were evaluated for its effectiveness as an immunomodulator in rats. The treatments were as follows: Group 1, AIN-93M diet (0.05% Mg, 0.001% Mn); Group 2, high-dose Mg (0.1% Mg, 0.001% Mn); and Group 3, high dose Mn(0.05% Mg 0.01% Mn) (n-12/group). After 12 weeks of supplementation, rats were sacrificed to assess the effect on a range of innate responses (tumoricidal activity, oxidative burst and nitric oxide) and the mitogen-stimulated lymphoproliferative response. Immune function was significantly affected in both the high dose Mg and the Mn group. Lymphocyte proliferative responses and NK cell activity were measured in pooled spleen from each group. The mitogen response of lymphocytes to LPS in the spleen was significantly reduced in high dose Mg-treated groups, whereas the response to ConA was not affected in both high dose minerals-treated groups. The reactive oxygen species level of macrophages was decreased in both groups. These effects were more pronounced in high dose Mg-treated group. Nitric oxide production was also decreased in high dose minerals-treated group. In addition, tumoricidal activities of splenic NK cell and peritoneal macrophage in mineral exposed rats were significantly increased. Moreover, percent death of macrophage was reduced in two groups receiving high dose mineral supplements. Taken together, the present data suggest that high dose trace minerals exert a differential effect on the function of immune cells.

Immunosuppressive Effect of Prodigiosin on Murine Splenocyte and Macrophages

( Jung Eun Huh ),( Hyun Jung Koo ),( Kyung Ho Kim ),( Joung Han Yim ),( Hong Kum Lee ),( Eun Wha Sohn ),( Suh Kneung Pyo ) 한국응용약물학회 2008 Biomolecules & Therapeutics(구 응용약물학회지) Vol.16 No.4