• Biomolecules & Therapeutics
• /
• v.18 no.2
• /
• pp.211-218
• /
• 2010

Acanthopanax koreanum Nakai (Araliaceae) is a medicinal plant indigenous to Korea. The root and stem barks of Acanthopanax species have been used as a tonic and sedative as well as in the treatment of rheumatism and diabetes. In our study, three lignans, eleutheroside E (EE), tortoside A (TA), and syringaresinol (SY), were isolated from the stem and root of A. koreanum in an effort to study the immunomodulating effect. We treated natural killer cells and dendritic cells with lignans (EE, TA, or SY), and analyzed their cytokine (IL-12 and IFN-${\gamma}$) secretion. EE, TA, or SY markedly enhanced IL-12 secretion in mouse lymphoid (DC1) and myeloid type (DC2.4) dendritic cells after 48 hr of treatment. There were no significant differences in the cytokine stimulatory effects between EE, TA, or SY. Moreover, treatment of EE, TA, or SY significantly induced IFN-${\gamma}$ secretion by human NK cells (NK92MI) confirmed by ELISA assay. This study suggests that lignans from A. koreanum modulate cytokines, and that such modulation may provide the mechanism of action for many of their therapeutic effects.

• Clinical and Experimental Reproductive Medicine
• /
• v.38 no.3
• /
• pp.168-173
• /
• 2011

Objective: To examine the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and hyperhomocysteinemia in women with unexplained recurrent miscarriages (RM) and to investigate the association between MTHFR genotype variants and alloimmune activation, proportion of peripheral blood natural killer (pbNK) cells. Methods: A total of 39 patients with a history of two or more unexplained miscarriages were recruited to this study. The controls were women who had a live birth without a history of RM (n=50). The proportion of pbNK cells was measured by flow cytometry. Plasma homocysteine levels and the incidence of the MTHFR variant of the RM and control groups were compared. The proportion of pbNK cells was compared to the MTHFR variants in the RM group. Results: No differences were found between the two groups' mean plasma homocysteine levels ($7.6{\pm}1.5{\mu}mol$/L vs. $7.1{\pm}2.1{\mu}mol$/L) or incidence of the MTHFR genotype variant (CC, 35% vs. 33%; CT, 40% vs. 53%; and TT, 25% vs. 14%). In the RM group, individuals with the TT variant ($7.7{\pm}1.1{\mu}mol$/L) had higher homocysteine levels than those with the CC and CT variants ($7.4{\pm}1.9{\mu}mol$/L and $7.4{\pm}1.2{\mu}mol$/L) and those with the CT variant ($19.2{\pm}8.1%$) had a higher proportion of CD3-/CD56+ pbNK cells than those with the CC and TT variants ($17.7{\pm}6.6%$ and $17.9{\pm}7.0%$), but the results of both comparisons were statistically insignificant. Conclusion: These preliminary results show no difference in plasma homocysteine levels between the RM and control groups or among MTHFR genotype variants in the RM group, which may suggest that the plasma homocysteine level is difficult to use as a predictive marker of RM in the Korean population. A study of a larger number of patients is needed.

• Journal of Ginseng Research
• /
• v.18 no.3
• /
• pp.151-159
• /
• 1994

To evaluate the anticarcinogenic effect and its mechanism of red ginseng, the mice were treated with red ginseng and received subcutaneous Bl6 melanoma cell line injection on the back. Tumor incidence was same (100%) both in water and red ginseng-treated groups, but tumor production was delayed in red ginseng-treated group. Survival time was somewhat longer in red ginseng-treated group. The histopathological findings were similar in both groups, but lymphocytic infiltration around the tumor and melanin production in the tumor cells were prominent in the red ginseng-treated group. Flow cytometric analysis on T lymphocytes and natural killer cells revealed increased $T_H$/$T_S$ ratio and increased NK cells in red ginseng-treated group. These results suggest that the anticarcinogenic effect of red ginseng may be exerted by the increased cell-mediated immunity and natural killer cell activity.

• IMMUNE NETWORK
• /
• v.16 no.2
• /
• pp.140-145
• /
• 2016

Ophiocordyceps sinensis is a natural fungus that has been valued as a health food and used in traditional Chinese medicine for centuries. The fungus is parasitic and colonizes insect larva. Naturally occurring O. sinensis thrives at high altitude in cold and grassy alpine meadows on the Himalayan mountain ranges. Wild Ophiocordyceps is becoming increasingly rare in its natural habitat, and its price limits its use in clinical practice. Therefore, the development of a standardized alternative is a great focus of research to allow the use of Ophiocordyceps as a medicine. To develop an alternative for wild Ophiocordyceps, a refined standardized extract, CBG-CS-2, was produced by artificial fermentation and extraction of the mycelial strain Paecilomyces hepiali CBG-CS-1, which originated from wild O. sinensis. In this study, we analyzed the in vitro immune-modulating effect of CBG-CS-2 on natural killer cells and B and T lymphocytes. CBG-CS-2 stimulated splenocyte proliferation and enhanced Th1-type cytokine expression in the mouse splenocytes. Importantly, in vitro CBG-CS-2 treatment enhanced the killing activity of the NK-92MI natural killer cell line. These results indicate that the mycelial culture extract prepared from Ophiocordyceps exhibits immune-modulating activity, as was observed in vivo and this suggests its possible use in the treatment of diseases caused by abnormal immune function.

• Toxicological Research
• /
• v.14 no.4
• /
• pp.475-481
• /
• 1998

This study was performed to investigate the modifying effect of the general (GPA) and the fermented pilose antler (FPA) on experimental hepatocarcinogenesis and Natural Killer cell activity in rats. Specific pathogen free, 5-week male Sprague-Dawley rats were divided into four groups. To induce hepatocarcinogenesis, diethylnitrosamine (DEN, 200 mg/kg, i.p.) was used as a tumor initiator and was given in a single dose at experimental onset. All rats were given a partial hepatectomy (PH) at 3 weeks after experimental onset. Sodium phenobarbital (PB, 0.05% in diet), GPA (0.075% in diet) and FPA (0. 075% in diet) were given from 2 to 8 weeks. Group I of the initiation control group was only given DEN. As initiation-promotion group, Group II was given DEN and then PB. Group III and IV were given DEN-PB-GPA and DEN-PB-FPA, respectively. In hematological analysis, as compared with Group I. the number of white blood cells were significantly increased in the GPA (p<0.01) and the FPA treated group (p<0.05), respectively. Natural killer (NK) cell activity by flow cytometer (FCM) analysis was higher in group of treated with the GPA (35%) than that of the FPA (27.5%), but not significant. Result of the immunohistochemical staining of the glutathione S-transferase placental form (GST-p) indicated that the number of and area of the pre-neoplastic lesions was not significantly changed in Group III and IV compared Group II, respectively. In conclusion, the GPA and the FPA treatment significantly increased the number od WBC in peripheral blood, but the enhancing NK activity and the modifying effect on the experimental hepatocarcinogenesis were not observed.

• Archives of Pharmacal Research
• /
• v.28 no.11
• /
• pp.1282-1286
• /
• 2005

The in vivo immunomodulatory function of the activity of murine natural killer (NK) cells induced by high mannuronic acid-containing alginate (HMA) was examined. HMA was injected i.p at doses of 25 and 100 mg/kg. The NK activity was 3 times higher with 100 mg/kg HMA than the baseline. In addition, in vitro studies of splenocytes cultured with HMA for 20 h showed a significant increase in NK activity at E:T ratio of 100: 1; a 160$\%$ and 210$\%$ increase at 10 and 100 $\mu$g/mL, respectively. There was a six fold increase in interferon-$\gamma$ production in a postculture of splenocytes with 100 $\mu$g/mL HMA. HMA had no suppressive effects on the lymphocyte function in the presence or absence of mitogens. This suggests that HMA is useful in cancer immunotherapy.

• Journal of Korean Traditional Oncology
• /
• v.15 no.1
• /
• pp.29-36
• /
• 2010

The anti-metastatic activity of water extract of Samguikoeuitang (WSGKE) consisting of Ginseng Radix, Angelicae Radix, Sophora flavescens and Coicis Semenwas examined. Ethanol extract of Samguikoeuitang (ESGKE) showed significant cytotoxicity against colon 26-M3.1 carcinoma cells, while WSGEK did not. However, WSGKE significantly increased the production of IL-6 and IL-12 in thioglycollate-induced macrophages from Balb/c mice, whereas ESGKE did not. WSGKE significantly increased natural killer (NK) cell cytotoxicity against effecter YAC-1 cells in an Effecter cells/Target ratio dependent manner. Also, WSGKE significantly suppressed lung metastasis after i.v. injection of colon26-M3.1 carcinoma cells. Inhibitory effect of WSGKE on lung metastasis totally abolished in NK cells-deficient mice by treatment with anti-asialo GM1 serum. In addition, the combination treatment of cisplatin and WSGKE (100 ${\mu}g$/mouse) prolonged the lifespan of mice inoculated by colon26-M3.1 cell. These findings suggest that WSGKE can inhibit lung metastasis and prolong life span via immunological enhancement as a Biological Response Modifier.

• Clinical and Experimental Reproductive Medicine
• /
• v.35 no.2
• /
• pp.119-129
• /
• 2008

Objective: The purpose of this study was to quantify decidual $CD56^+$ and $CD16^+$ NK cell subtype population and to evaluate the correlation between decidual NK cell expression and peripheral $CD56^+$ NK cell expression in women with a history of recurrent abortion and increased peripheral NK cells. Methods: Twenty-nine women with recurrent abortion and elevated peripheral $CD56^+$ NK cell percentage who had chromosomally normal conceptus were included in this study. Thirty-two women with recurrent abortion who had chromosomally abnormal conceptus were used as controls. Distribution of $CD56^+$ and $CD16^+$ NK cells in decidual tissues including implantation sites was examined by immunohistochemical staining. The degree of immunohistochemical staining was interpreted by score and percentage. Results: There was a significant difference in decidual $CD56^+$ NK cell score ($43.6{\pm}24.5$ vs. $23.9{\pm}16.3$ P =0.001) and $CD56^+$ NK cell percentage ($42.1{\pm}11.7$ vs. $33.9{\pm}15.8$ P =0.027) between increased peripheral NK cell group and control group. However, there was no statistically significant difference in decidual $CD16^+$ NK cell score ($18.7{\pm}9.5$ vs. $13.2{\pm}39.4$ P =0.108) and $CD16^+$ NK cell percentage ($24.7{\pm}5.9$ vs. $23.4{\pm}11.7$ P =0.599). There was no significant correlation between decidual NK cell score and peripheral NK cell percentage in increase peripheral NK cell group (peripheral $CD56^+$ NK cell percentage vs. decidual $CD56^+$ NK cell score, r=-0.016, P =0.932, peripheral $CD16^+$ NK cell percentage vs. decidual $CD16^+$ NK cell score, r=0.008, P =0.968). Conclusion: This study shows that $CD56^+$ decidual NK cells are increased in decidua of women exhibiting a history of recurrent abortion with increased $CD56^+$ peripheral NK cell. There was no significant correlation between decidual and peripheral NK cell increment in increase peripheral NK cell group. This study suggests the possibility that decidual NK cells may play an important role in the immune mechanism of recurrent abortion.

• YAKHAK HOEJI
• /
• v.46 no.1
• /
• pp.52-57
• /
• 2002

Effects of the butanl fraction of Astragali Radix (BFAR) on the cellular and nonspecific immune responses were investigated in ICR mice. Mice were divided into 4 groups and BFAR at doses of 5, 25 and 125 mg/kg u ere administered orally to mice daily for 3 weeks, and the normal animals were given vehicle. The results of this study are summarized as follows; the relative weight of thymus was greatly increased by BFAR treatment, compared with that in mormal mice. However, the body weight gain was not affected. Delayed-type hypersensitivity (DTH) reaction to sheep red blood cells (SRBC) for cellular immunity was significantly enhanced by BFAR treatment, compared with those in normal mice. In these mice, BFAR also dose-dependently increased activities of phagocyte and natural killer (NK) cells as well as the number of leukocyte resulted from nonspecific immunity Thus, these results demonstrate that BFAF treatment results in a significant increase in both cellular and nonspecific immune responses to antigen in concentrations that enhance humoral immune function.

• Parasites, Hosts and Diseases
• /
• v.31 no.3
• /
• pp.239-248
• /
• 1993

The purpose of this observation was to investigate the natural killer cell activities in mice Infected with pathogenic free-living amoeba, Naegleria fowleri and Acanthomoeba culbertsoni according to the infection doses, and infected with non-pathogenic free-living amoeba, Naegleria fowleri. The natural killer cell activity was examined by means of target binding capacity, active NK cell and maximum recycling capacity of the mice after inoculating free-living amoebae with low and high doses. The mice infected with 1 103, 1 105 A. culbertsoni trophozoites showed mortality rates of 6.9% and 65.5%, respectively. The mice infected with 1 104, 1 105 N.fowleri trophozoites showed mortality rates of 5.9% and 72.2%, respectively. The NK cell activities in all experimental groups increased significantly on day 1 after infection as compared with control group, and then remarkably declined thereafter, there was no difference of the cytotoxic activity of the NK cells In mice among inoculation doses of pathogenic free-living amoebae. The target binding capacities of NK cells and percentages of activated NK cells in mice Infected with pathogenic free-living amoebae were slgrlificantly Increased a day after Infection, as compared Uth control group. There was no difference of the maximal recycling capacities of NK cells in all experimental groups as compared Uth control group. There was significant difference in the cytotoxic activity and single cell cytotoxlcity of NK cells between the experimental groups infected with pathogenic free-living amoebae and that infected with non-pathogenic free-living amoebae.