• The Journal of the Korean Society for Microbiology
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• v.21 no.1
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• pp.133-144
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• 1986

This study was undertaken to assess the effect of ginseng administration on T lymphocyte induced local xenogenic graft-versus-host(GVM) reactions which were induced with thymocyte, spleen cell and lymph node cell of ICR mice. Mice received daily 10mg of 70% alcohol ginseng extract oral1y for 100days and control mice remained untreated for the same period of time. The cells from donor mice were injected intradermally into the closely shaven abdominal skin of Sprague-Dawley rats for GVH tests. The thymocyte from control(ginseng-untreated) mice showed a negative local GVH reaction, whereas thymocyte from experimental(ginseng-treated) mice showed a positive reaction with the rate of 17.4%. When spleen cells were injected, the incidence of positive local GVH reaction was 66.7% among ginseng-treated mice, as opposed to incidence of 45.5% of positive local GVH reaction among control mice. The incidence of positive local GVH reaction of the lymph node cells when injected into a recipient was 71.4% among ginseng-treated mice as compared with that of 18.9% among control mice. The relationship between spleen cell inoculum and intensity of the local GVH reaction was assessed in ginseng-untreated mice. The intensity of GVH reaction clearly appears to be dose related. In ginseng-treated mice, a minimum of $1{\times}10^7$ spleen cell was required for production of positive local GVH reaction with almost linear relationship up to an inoculum of $5{\times}10^8$ cells. In control mice, however, a minimum of $1{\times}10^8$ spleen cells was required for positive GVH reaction. These results strongly suggest that the ginseng administration augments significantly the local xenogenic GVH reaction which was used to assess T lymphocyte function and immunocompetence of mice and in addition to this, these results appear to support previous suggestions that the local GVH reaction consitutes a qualitative test of the functional activity of T lymphocytes. These results may be the first to induce local GVH reaction, employing rats as recipient and mice as donor. This study was also desingned to investigate some of the effects of ginseng extract on lymphocyte-macrophage interactions. This was accomplished by in vitro quantification of 1) migratory inhibitory factor(MIF) synthetic capacity of splenic lymphocytes in mice previously primed with ginseng 2) MIF responsiveness of mouse peritoneal macrophages or chicken peripheral leucocytes under the presence of ginseng extract 3) migration ability of chicken peripheral leucocytes by direct stimulation of ginseng extract or ginseng saponin and 4) immunosuppressive effects of immunosuppressants such as cyclophosphamide, cyclosporin A or dexamethasone. Mice divided equally into the ginseng and the saline groups, which received intraperitoneally daily 0.2ml of ginseng absolute alcohol-extract(5mg/ml) and same amount of saline for 15 days, respectively. The cellular immune responsiveness of these mice was assayed 15 days after ginseng pretreatment. Splenic lymphocytes of mice treated with ginseng, when stimulated with sensitized specific-antigen such as sheep red blood cells or toxoplasmin, or with polyclonal activator concanavalin A, produced significantly more MIF than those of control saline group. MIF responsiveness of normal mouse macrophages was significantly augmented when assayed under the presence of ginseng extract (1mg/ml). The migratory ability of normal chicken leucocytes in the absence of MIF was significantly decreased by the stimulation of ginseng extract alone. MIF response was significantly decreased by immunosuppressants and this impaired response was not restored by ginseng pretreatment. This study was additionally performed to evaluate the effect of ginseng on the expulsion of adult Trichinella spiralis in mice. ICR mice were infected experimentally by esophageal incubation of 300 T. spiralis infective muscle larvae prepared by acid-pepsin digestion of infected mice. and received oral administration of 70% alcohol ginseng extract(10mg/mouse/day) for the indicated days plus 4 days before infection. At various times after infection, the number of adult T. spiralis worms in small intestines was determined. Interestingly, ginseng-treatment was accompanied by accelerated expulson of T. spiralis. These results led to the conclusion that Panax ginseng caused some enhancing effect on GVH reaction, macrophage migration inhibition reaction and expulsion of T. spiralis. In addition these results suggested that the mechanisms responsible for this enhancement of ginseng may be chiefly or partially due to nonspecific stimulation of cell-mediated immune response.

• BMB Reports
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• v.51 no.11
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• pp.572-577
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• 2018

Recent studies showed that the PD-1/PD-L1 checkpoint blockade is a dramatic therapy for melanoma by enhancing antitumor immune activity. Currently, major strategies for the PD-1/PD-L1 blockade have mainly focused on the use of antibodies and compounds. Seeking an alternative approach, others employ endogenous proteins as blocking agents. The extracellular domain of PD-1 (ePD1) includes the binding site with PD-L1. Accordingly, we constructed a PD-1-based recombinantly tailored fusion protein (dFv-ePD1) that consists of bivalent variable fragments (dFv) of an MMP-2/9-targeted antibody and ePD1. The melanoma-binding intensity and antitumor activity were also investigated. We found the intense and selective binding capability of the protein dFv-ePD1 to human melanoma specimens was confirmed by a tissue microarray. In addition, dFv-ePD1 significantly suppressed the migration and invasion of mouse melanoma B16-F1 cells, and displayed cytotoxicity to cancer cells in vitro. Notably, dFv-ePD1 significantly inhibited the growth of mouse melanoma B16-F1 tumor cells in mice and in vivo fluorescence imaging showed that dFv-ePD was gradually accumulated into the B16-F1 tumor. Also the B16-F1 tumor fluorescence intensity at the tumor site was stronger than that of dFv. This study indicates that the recombinant protein dFv-ePD1 has an intensive melanoma-binding capability and exerts potent therapeutic efficacy against melanoma. The novel format of the PD-L1-blocked agent may play an active role in antitumor immunotherapy.

• Journal of Life Science
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• v.25 no.9
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• pp.984-992
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• 2015

Sanguinarine is a benzophenanthridine alkaloid originally isolated from the roots of Sanguinaria canadensis. It has multiple biological activities (e.g., antioxidant and antiproliferative) and immune-enhancing potential. In this study, we explored the proapoptotic properties and modes of action of sanguinarine in human hepatocellular carcinoma HepG2 cells. Our results revealed that sanguinarine inhibited HepG2 cell growth and induced apoptosis in a dose-dependent manner. The induction of apoptosis by sanguinarine was associated with the up-regulation of Fas and Bax, the release of cytochrome c from the mitochondria to the cytosol, and the loss of the mitochondrial membrane potential. In addition, sanguinarine activated caspase-9 and -8, initiator caspases of the intrinsic and death extrinsic pathways, respectively, and caspase-3, accompanied by proteolytic degradation of poly (ADP-ribose) polymerase. Sanguinarine also triggered the generation of reactive oxygen species (ROS). The elimination of ROS by N-acetylcysteine reversed sanguinarine-induced apoptosis. Furthermore, sanguinarine induced the dephosphorylation of Akt and the phosphorylation of mitogen-activated protein kinases, including extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38. The growth inhibition was enhanced by the combined treatment of sanguinarine with a phosphatidylinositol 3'-kinase (PI3K) inhibitor and an ERK inhibitor but not JNK and p38 inhibitors. Overall, our data indicate that the proapoptotic effects of sanguinarine in HepG2 cells depend on ROS production and the activation of both intrinsic and extrinsic signaling pathways, which is mediated by blocking PI3K/Akt and activating the ERK pathway. Thus, our data suggest that sanguinarine may be a natural compound with potential for use as an antitumor agent in liver cancer.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.4
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• pp.1021-1027
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• 2004

Panax ginseng has been used as a typical tonic medicine in Asian countries, such as Korea, China, and Japan. It has been reported that ginsenoside Rg1 in Panax ginseng increases the proportion of T helper cells in the whole T cells and promotes IL-2 gene expression in murine splenocytes. These studies imply that ginsenoside Rg1 increases the immune activity of CD4+ T cell, however the exact mechanism of ginsenoside Rg1 on helper T cell remains to be verified. The present study tried to elucidate the direct effect of Rg1 on helper T cell s activities and its Th1/Th2 lineage development. The results demonstrated that ginsenoside Rg1 had not mitogenic effects on the unstimulated CD4+ T cell, but augmented CD4+ T cell proliferation upon activating with anti-CD3/anti-CD28 antibodies in a dose dependent manner. Rg1 also enhanced the expression of cell surface protein CD69 on CD4+ T cell. In Th0 condition, ginsenoside Rg1 increases the expression of IL-2 mRNA, and enhances the expression of IL-4 mRNA on CD4+ T cells, suggesting Rg1 prefer to induce Th2 lineage development. In addition, ginsenoside Rg1 increases IL-4 secreting CD4+ T cell under Th2 skewed condition, while decreases IFN-γ secreting cell in Th1 polarizing condition. Thus, Rg1 enhances Th2 lineage development from naive CD4+ T cell both by increasing Th2 specific cytokine secretion and by repressing Th1 specific cytokine production. Therefore, these results suggest that ginsenoside Rg1 might be desirable agent for enhancing CD4+ T cell's activity, as well as the correction of Th1 dominant pathological disorders.

• The Korean Journal of Food And Nutrition
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• v.25 no.2
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• pp.407-412
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• 2012

Wild grass is edible, and it grows in the mountains or field areas. Wild grass has diverse biological effects, such as antiobesity, anti-cancer, antioxidant activities and immune stimulation. Currently, many studies are aimed at enhancing the efficacy of medicinal foods on biological activity using a bioconversion technology, including the fermentation process. In this study, the quality characteristics and antioxidative activity of the fermented wild grass was investigated. The antioxidant activity of fermented wild grass was assessed by various radical scavenging assays using DPPH(2,2-diphenyl-1-picrylhydrazyl), FRAP(ferric ion reducing antioxidant power), reducing power, and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)). Moisture contents of the fermented wild grass is $49.6{\pm}0.06%$. Contents of crude ash, crude protein, and crude fat were $0.65{\pm}0.01$, $0.65{\pm}0.04$, and $3.3{\pm}0.59%$, respectively. Moreover, fermented wild grass showed that the hunter's color values were 80.36(lightnees), 11.47(redness), and 44.53(yellowness), respectively. Total phenolic contents of the fermented wild grass was $1,185{\pm}159{\mu}g$ GAE(gallic acid equivalent)/g. The antioxidative activities of the fermented wild grass were significantly increased in a dose dependent manner. In addition, fermented wild grass did not show any cytotoxicity up to 500 ${\mu}g/m{\ell}$. However, the anti-adipogenic effect of the fermented wild grass extract was barely detectable. This antioxidant potential is partly due to the phenolic compounds that are present in the fermented wild grass extracts.

• Microbiology and Biotechnology Letters
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• v.38 no.4
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• pp.467-474
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• 2010

Cheonggukjang is one of the traditional fermented soy-based foods in Korean diets. Studies in cell cultures, humans have revealed anti-hypertension, anti-stress, anticancer, antioxidant, immune enhancing effects. Angelica gigas, Rehmanniae radix, and Red ginseng are popular medicinal plants and widely used for oriental medicine. In this study a strategy had been developed to mobilize beneficial phenolics from Angelica gigas, Rehmanniae radix, and Red ginseng combined with fermented soy by Cheonggukjang fermentation for antioxidant and Type II diabetes management. The quality and functional characteristics of Chenggukjang fermented with Angelica gigas, Rehmanniae radix and Red ginseng. Cheonggukjang (CKJ), Angelica gigas Cheonggukjang (CKJ-DD), Rehmanniae radix Cheonggukjang (CKJ-RG), Angelica gigas and Rehmanniae radix Cheonggukjang (CKJ-DD+RG) and Red ginseng Cheonggukjang (CKJ-RED) were evaluated. The mobilized phenolic profile was evaluated for antioxidant activity and the potential to inhibit ${\alpha}$-amylase linked to hyperglycaemia. This research has important implications for the development of functional soy-based-fermented foods enriched with Angelica gigas, Rehmanniae radix and Red ginseng phenolics for oxidative stress - induced diabetic complications. Furthermore, Hunter's color values of 5 types cheonggukjang, lightness (L-values), redness (a-values) and yellowness (b-values) were evaluated. Free amino acid content of CKJ-RED (0.993 mg/gd. w.) showed higher than that of CKJ (0.205 mg/g-d.w.).

• Journal of Nutrition and Health
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• v.47 no.3
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• pp.157-166
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• 2014

Purpose: Rice bran is a byproduct of the hulling of rice and contains a variety of bioactive components. Various studies have reported on the antioxidative, anticancer, immune-enhancing, and hypocholesterolemic effects of rice bran. However, few studies about the physiological activity of stabilized rice bran supplement on dietary intake of sugars is limited. The aim of this study was to investigate the effect of stabilized rice bran supplement on blood glucose in C57BL/6 mice fed a high sucrose diet. Methods: Animals were randomly divided into three groups respectively, and were fed a normal diet (ND group), a high sucrose diet (HSD group) or a high sucrose diet containing 20% stabilized rice bran (HSD-SRB group) for 12 weeks. Results: In the oral glucose tolerance test (OGTT), after seven weeks of feeding on the experimental diets, a significantly lower result was observed for HSD-SRB than for HSD at 30 and 60 minutes after oral administration in glucose solution (2 g/kg body weight). The incremental area under the curve (IAUC) of HSD-SRB was significantly lower than that of HSD. After 12 weeks, fasting blood glucose level of HSD-SRB was significantly lower than that of HSD. No significant difference in the serum insulin level was observed between HSD and HSD-SRB. However, HOMA-IR was significantly decreased in HSD-SRB compared to HSD. In addition, HOMA ${\beta}$-cell was significantly increased in HSD-SRB compared to HSD. Triglyceride in liver of HSD-SRB was significantly lower than that of HSD. Conclusion: Feeding diets containing 20% rice bran improved insulin resistance and insulin secretion by decreasing triglyceride in liver. Thus, rice bran has a positive effect on glycemic control. In addition, the results are expected to be utilized as a basis for human study and development of food products with added rice bran.

• Food Science and Preservation
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• v.30 no.6
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• pp.1082-1094
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• 2023

The purpose of this study was to examine the characteristics of Leuconostoc spp. isolated from radish kimchi and to investigate the potential for the use of functional ingredients by evaluating enzymatic characteristics, safety, and immune-enhancing effects among the isolates, including Lactobacillus rhamnosus ATCC53103 (LGG) as a control strain. All test strains exhibited β-glucosidase enzyme activity that releases β-1,4 sugar chain bonds. In addition, as a result of antibiotic resistance assay among the isolates, MIC values on 8 antibiotics were below compared to the EFSA standard, and hemolytic experiments confirmed that all showed gamma hemolysis without hemolytic ability. As a result of the antibacterial activity experiment, the Leu. mesenteroides K2-4 strain showed a higher activity than LGG against Bacillus cereus and Staphylococcus aureus. Additionally, the activity of the NF-kB/AP-1 transcription factor increased when the isolates were treated in macrophage RAW cells. These results were related to increasing the high mRNA expression levels on TNF-α and IL-6 by Leu. mesenteroides K2-4 strain to be treated at low concentration. Consequently, we suggest that it will be useful as a candidate for functional food ingredients.

• Journal of Microbiology and Biotechnology
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• v.25 no.10
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• pp.1751-1760
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• 2015

Mucin2 (MUC2), an important regulatory factor in the immune system, plays an important role in the host defense system against bacterial translocation. Probiotics known to regulate MUC2 gene expression have been widely studied, but the interactions among probiotic, pathogens, and mucin gene are still not fully understood. The aim of this study was to investigate the role of MUC2 in blocking effects of probiotics on meningitic E. coli-induced pathogenicities. In this study, live combined probiotic tablets containing living Bifidobacterium, Lactobacillus bulgaricus, and Streptococcus thermophilus were used. MUC2 expression was knocked down in Caco-2 cells by RNA interference. 5-Aza-2'-deoxycytidine (5-Aza-CdR), which enhances mucin-promoted probiotic effects through inducing production of Sadenosyl-L-methionine (SAMe), was used to up-regulate MUC2 expression in Caco-2 cells. The adhesion to and invasion of meningitic E. coli were detected by competition assays. Our studies showed that probiotic agents could block E. coli-caused intestinal colonization, bacteremia, and meningitis in a neonatal sepsis and meningitis rat model. MUC2 gene expression in the neonatal rats given probiotic agents was obviously higher than that of the infected and uninfected control groups without probiotic treatment. The prohibitive effects of probiotic agents on MUC2-knockdown Caco-2 cells infected with E44 were significantly reduced compared with nontransfected Caco-2 cells. Moreover, the results also showed that 5-Aza-CdR, a drug enhancing the production of SAMe that is a protective agent of probiotics, was able to significantly suppress adhesion and invasion of E44 to Caco-2 cells by upregulation of MUC2 expression. Taken together, our data suggest that probiotic agents can efficiently block meningitic E. coli-induced pathogenicities in a manner dependent on MUC2.

• Journal of Animal Science and Technology
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• v.50 no.1
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• pp.89-98
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• 2008

This experiment was carried out to investigate the combination feeding of β-glucan and multi-species probiotics on growth performance, various lipid concentrations of serum, antibody production and cecal microbial profiles in broiler chicks. A total of six hundred 1-d-old male broiler chicks were divided into five groups, placed into four pens per group(30 birds per pen) and fed one of five non-medicated experimental diets(T1, 0.15% multi-species probiotics; T2, 0.1% β-glucan+0.15% multi-species probiotics; T3, 0.3% multi-species probiotics; T4, 0.1% β-glucan+0.3% probiotics or devoid them as control) for 5 wk. There was no significant difference in feed intake among the groups. The average weight gains and FCR in groups fed diet containing 0.3% probiotics were significantly improved(p<0.05) than control in finisher period(22-35d). The concentration of serum cholesterol ester in groups fed 0.3% probiotics were significantly lowered(p<0.05) as compared to that of the control. Relative weights of liver, spleen, bursa of Fabricius, breast and leg were not influenced by the dietary treatments. The average ND or IB antibody titers in groups fed diets containing β-glucan and probiotics were tended to be increased, but not significantly. The number of cecal lactic acid bacteria was significantly increased(p<0.05) by the dietary β- glucan and probiotics. These results indicated that dietary β-glucan and probiotics exerted a growth- promoting and immune-enhancing effects on broiler chicks. In addition, yeast derived β-glucan, and multi-species probiotics modulated the profiles of cecal microflora, reflecting potential alternative substances to replace antibiotics for feeding broiler.