• 생약학회지
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• 제29권4호
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• pp.312-317
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• 1998

In this study, the effect of 70% ethyl alcohol fraction of Cervus nippon(CN-E) on mouse T-lymphocyte was investigated in vivo. The administration of CN-E(100 mg/kg) enhanced the proliferation of thymocytes, the population of $CD4^+CD8^-$ single-positive cells and the production of $interferon-{\gamma}$ in thymocytes and splenocytes. The administration of CN-E did not induce DNA fragmentation and reduce mitochondrial transmembrane potential in thymocytes. These results indicate that the CN-E contams a stimulative component on the proliferation of thymocytes, the population of $T_H$ cells and the production of $interferon-{\gamma}$ in T-lymphocytes.

• 한방안이비인후피부과학회지
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• 제22권2호
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• pp.39-49
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• 2009

Objective : Phyllostachyos Folium (PF) has been used to treat patients with febrile disease consuming the body fluids marked by fever with restlessness, thirst etc. In the theory of herbology, PF can clear away heat and promote the production of the body fluids, relieve restlessness. Recently PF is known to have anti-bacterial, anti-oxidantic effects. Methods : The present study was carried out to investigate the effects of PF on solid tumor in mice in terms of immune-potentiating and direct cytotoxic action of PF in vitro and vivo study. The present author investigated thymocyte and splenocyte proliferation to confirm immune-potentiating activity of PF and also investigated tumor/body weight ratio and survival rates in tumor bearing mice. Result : In this study, administration of PF decreased tumor/body weight ratio significantly, and prolonged survival duration compared to non-treated control. In addition, treatment with PF suppressed proliferation rate of Sarcoma 180 (S-180) cells significantly, and elevated proliferation rates of thymocytes isolated from normal mice. These results were co-related with in vivo study. Conclusion : In conclusion, these results suggest that PF is useful to treat patient with solid tumor, because PF has direct toxic action for tumor cell and immune -potentiating action for T cells. Further study will need to elucidate exact mechanisms related in anti-cancer action of PF.

• 동의생리병리학회지
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• 제17권3호
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• pp.656-661
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• 2003

The specific immune response of unripened fruits and ripened fruits of Rubus coreanus Miquel was examined in BALB/C mice. The 70% ethyl alcohol extracts (20 or 100 mg/kg) of unripened fruits (RCE-I) and of ripened fruits (RCE-II) were administered p.o. once a day for 7 days. RCE-I and RCE-II decreased the viability of thymocytes, but increased the viability of splenocytes. Also, RCE-I enhanced the population of helper T and cytotoxic T cells in thymocytes and RCE-II enhanced the population of helper T cells. Furthermore, RCE-I and RCE-II decreased the population of B220/sup +/ cells and Thy1/sup +/ cells and helper T cells in splenocytes. In a general way, the immunosuppressive action of RCE-I was more potent than those of RCE-II. These results suggest that RCE-I and RCE-II have a regulative action of immune response via decrease the viability of thymocytes and increase the viability of splenocytes.

• 생약학회지
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• 제31권2호
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• pp.142-148
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• 2000

The purpose of this research was to investigate effects of Samultang water extract (SMT) on cytokine production from immune cells during the late stage of pregnancy in BALB/c mice. SMT(500 mg/kg) was administered p.o. once a day for 7 days, and then thymocytes and peritoneal macrophages were separated. At the late stage of pregnant mice, the proliferation of thymocytes and the production of ${\gamma}-interferon$ in thymocytes were decreased as compared with normal group, but the production of interleukin-2 and interleukin-4 was increased. The production of tumor necrosis $factor-{\alpha}$, nitric oxide and phagocytic activity in peritoneal macrophage was increased as compared with normal group. At the late stage of pregnant mice administered with SMT, the production of interleukin-2 in thymocytes was decreased as compared with a pregnant group, but the proliferation of thymocytes, the production of ${\gamma}-interferon$ and interleukin-4 was increased. The production of tumor necrosis $factor-{\alpha}$ and nitric oxide in peritoneal macrophages were decreased as compared with a pregnant group, but phagocytic activity were increased. These results suggest that SMT has the regulative action on immune function of thymocytes and peritoneal macrophages at the late stage of pregnant mice.

• 대한한방내과학회지
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• 제28권2호
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• pp.377-384
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• 2007

Objective : Immune potentiation including activation of T cells, B cells, macrophages, and dendritic cells is known to play a key role in prevention and treatment of patients with cancer. In this study, we investigated the effects of Acanthopanax sessiliflorus (AR) on the immune system, especially on thymocytes, splenocytes, and macrophages. Methods : We investigated the effects of AR on proliferation of splenocytes in normal mice, and the effects on proliferation of splenocytes and thymocytes in tumor-bearing mice. In addition, the effect of AR on NO production using macrophages was investigated. Results : Treatment with AR accelerated proliferation of splenocytes in vitro. AR also accelerated thymocyte proliferation, but did not affect splenocytes proliferation in normal mice. In contrast, AR accelerated proliferation of splenocytes and thymocytes significantly in tumor bearing mice. In addition, NO production level from macrophages was elevated by treatment with AR. Conclusion : These results demonstrate that AR has anti-cancer activities and related mechanisms are involved in immune potentiation such as acceleration of immune cell proliferation and elevation of NO production level in macrophages. In addition, we also demonstrate the possibilities of AR as complementary and alternative medicine to standard anti-cancer drugs.

• 생약학회지
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• 제29권2호
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• pp.110-119
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• 1998

Sa-Mul-Tang(SMT) consist of Rehmanniae Radix Preparata, Paeoniae Radix Alba, Cnidii Rhizoma and Angelicae Gigantis Radix. In L1210 cells-transplanted BALB/c mice, T-lymphocyte apoptosis, $CD8^+T_C$ cells population in thymocyte and nitric oxide production in macrophage were enhanced, but phagocytic activity was decreased. SMT suppressed T-lymphocyte apoptosis and enhanced CD^4+T_H$ cells population, but did not affect nitric oxide production and phagocytic activity in L1210 cells-transplanted mice. In antitumor drugs-injected mice, T-lymphocyte apoptosis was enhanced, but $CD4^+T_H/CD8^+T_C$, cells population and T-lymphocyte proliferation were decreased. SMT suppressed T-lymphocyte apoptosis, and enhanced $CD8^+T_C$ cells population, T-lymphocyte proliferation and phagocytic activity in vincristine-injected mice. These results suggest that SMT enhances T cell-mediated immunity in L1210 cell-transplanted mice, and enhances T cell-mediated immunity and phagocytic activity in vincristine-injected mice.

• 한방안이비인후피부과학회지
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• 제21권1호
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• pp.26-37
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• 2008

Objective : The present study was carried out to investigate the effects of NaisoOkseol-Tang (NOT) on solid tumor in mice in terms of immune-potentiating and direct cytotoxic action of NOT in vitro and vivo study. Methods: The present author investigated thymocyte proliferation and NO production to confirm immune-potentiating activity of NOT and also investigated body/tumor weight and survival rates in tumor bearing mice. In this study, administration of NOT decreased tumor/weight ratio significantly, and prolonged survival duration compared to non-treated control. Treatment with NOT also elevated proliferation rates of thymocytes isolated from tumor bearing mice. Results: In vitro study, treatment with NOT suppressed proliferation rate of Sarcoma 180 (S-180) cells. Contrary, treatment with NOT elevated proliferation rate of thymocytes. These results were co-related with in vivo study. In addition, NO production from abdominal macrophages isolated from normal mice was not affected by treatment with NOT. Conclusion : NOT is useful to treat patient with solid tumor, because NOT has direct toxic action for tumor cell and immune-potentiating action for T cells.

• 대한수의학회지
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• 제39권6호
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• pp.1112-1118
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• 1999

Galectin-3 plays an important role in cell development, differentiation and cancer metastasis, including cell-cell/extracellular matrix (ECM) interactions and is supposed to have an effect of apoptosis on T-cells in thymic clonal selection. In this study, to know the effect of galectin-3 on thymocyte development, we used recombinant human galectin-3 (rHgal-3) from Escherichia coli, JM105, which was inserted with human gal-3 gene-transformed plasmid vector (prGal-3) to express human galectin-3. Expressed rHgal-3 was confirmed by western blot using the culture supernant of hybridoma (M3/38) producing monoclonal antibody to human galectin-3. Sepharose gel affinity chromatography was used to purify the expressed rHgal-3. Thymocytes and hepatocytes from 6-week-old male BALB/c mice were incubated with rHgal-3 and showed marked increase of apoptotic population on analysis using flow cytometry with 7-AAD in a dosedependent manner. However, rHgal-3 failed to induce apoptosis on hepatocytes. Interestingly, this apoptotic effect was not inhibited by lactose, a specific lectin domain inhibitor. From these results, we concluded that extrinsic -3 induces apoptosis on mouse thymocytes, and galectin-3 may have an apoptotic effect on T-cells in thymic clonal selection.

• Animal cells and systems
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• 제5권4호
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• pp.267-274
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• 2001

Calpains are a family of cysteine proteases existing primarily in two forms designated by the $Ca^{2+}$ concentration needed for activation in vitro, $\mu$-calpain (calpain-I) and m-calpain (calpain-II). The physiologica1 roles of calpains remain unclear. Many groups have proposed a role for calpains In apoptosis, but their patterns of activation are not well characterized. Calpains have been implicated in neutrophil apoptosis, glucocorticoid-induced thymocyte apoptosis, as well as many other apoptotic pathways. Calpain activation in apoptosis is usually linked upstream or downstream to caspase activation, or in a parallel pathway alongside caspase activation. Calpains have been suggested to be involved in DNA fragmentation (via endonuclease activation), but also as effector proteases that cleave cellular proteins involved in DNA repair, membrane associated proteins and other homeostatic regulatory proteins. Recently, our laboratory demonstrated $\mu$-calpain activation in NAD(P)H: quinone oxidoreducatse 1 (NQO1)-expressing cells after exposure to $\beta$-lapachone, a novel quinone and potential chemo- and radio-therapeutic agent. Increased cytosolic $Ca^{2+}$ in NQO1-expressing cells after $\beta$-lapachone exposures were shown to lead to $\mu$-calpain activation. In turn, $\mu$-calpain activation was important for substrate proteolysis and DNA fragmentation associated with apoptosis. Upon activation, $\mu$-calpain translocated to the nucleus where it could proteolytically cleave PARP and p53. We provided evidence that $\beta$-lapachone-induced, $\mu$-calpain stimulated, apoptosis did not involve any of the known caspases; known apoptotic caspases were not activated after $\beta$-lapachone treatment of NQO1-expressing cells, nor did caspase inhibitors have any effect on $\beta$-1apachone-induced cell death. Elucidation of processes by which $\beta$-1apachone-stimulated $\mu$-calpain activation and calpains ability to activate endonucleases and induce apoptosis independent of caspase activity will be needed to further develop/modulate $\beta$-lapachone for treatment of human cancers that over-express NQO1.

• The Korean Journal of Physiology and Pharmacology
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• 제2권2호
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• pp.241-249
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• 1998

Platelet-activating factor(PAF) enhanced interleukin-1(IL-1) activity by the interaction with a specific receptor in rat alveolar macrophages. In this study, we investigated the role of endogenous arachidonate metabolites and intracellular calcium mobilization in the PAF-induced IL-1 activity. Alveolar macrophages were preincubated with 5-lipoxygenase and cyclooxygenase inhibitors 30 min before the addition of PAF and lipopolysaccharide(LPS). After 24h culture, IL-1 activity was measured in the supernate of sample using the thymocyte proliferation assay. Inhibition of 5-lipoxygenase by nordihydroguaiaretic acid and AA-861 completely blocked the PAF-induced enhancement of IL-1 activity with $IC_{50}\;of\;2\;{\mu}M\;and\;5\;{\mu}M$, respectively. In contrast, the inhibition of cyclooxygenase pathway by indomethacin and ibuprofen resulted in the potentiation in PAF-induced IL-1 activity with maximal effect at $1\;{\mu}M\;and\;5\;{\mu}M$, respectively. In addition, leukotriene $B_4$ and prostaglandin $E_2$ production were observed in PAF-stimulated alveolar macrophage culture. As could be expected, 5-lipoxygenase and cyclooxygenase inhibitors abolished PAF- stimulated leukotriene $B_4$ and prostaglandin $E_2$ production, respectively. The effects of PAF on intracellular calcium mobilization in alveolar macrophages were evaluated using the calcium-sensitive dye fura-2 at the single cell level. PAF at any dose between $10^{-16}\;and\;10^{-8}$ M did not increase intracellular calcium. Furthermore, there was no effective change of intracellular calcium level when PAF was added to alveolar macrophages in the presence of LPS or LPS+LTB4, and 4, 24 and 48h after treatment of these stimulants. Together, the results indicate that IL-1 activity induced by PAF is differently regulated through subsequent induction of endogenous 5-lipoxygenase and cyclooxygenase pathways, but not dependent on calcium signalling pathway.