• Korean Journal of Medicinal Crop Science
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• v.24 no.5
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• pp.408-419
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• 2016

Background: In recent years, adjuvants have received increasing attention owing to the development of purified subunit and synthetic vaccines which are poor immunogens and require additional adjuvants to evoke an immune response. Therefore, immunologic adjuvants have been developed and tested. Plant polysaccharides have been recognized as effective biological response modifiers with low toxicity. Methods and Results: In this study, the polysaccharide from the aboveground part of Astragalus membranaceus Bunge containing immunomodulating arabino-3,6-galactan was evaluated for its hemolytic activity and adjuvant potential in the specific cellular and humoral immune responses to ovalbumin. The polysaccharide from the aboveground part of Astragalus membranaceus Bunge was co-immunized with the purified Vi capsular polysaccharide of Salmonella typhi vaccine in mice. The polysaccharide from the aboveground part of Astragalus membranaceus Bunge did not induce any hemolytic activity or side effects at doses up to $500{\mu}g/m{\ell}$. The concanavalin A-, lipopolysaccharide-, and ovalbumin-induced splenocyte proliferation and serum ovalbumin-specific IgG, IgG1 and IgG2b antibody titers in immunized mice were significantly enhanced by AMA. Pharmacological data revealed that the polysaccharide from the aboveground part of Astragalus membranaceus Bunge increased antigen-specific antibody levels in immunized mice. The polysaccharide from the aboveground part of Astragalus membranaceus Bunge-adjuvanted purified Vi capsular polysaccharide of Salmonella typhi vaccine improved the proliferation of splenocytes and macrophages as well as stimulated cytokine production. Conclusions: These results suggest that the polysaccharide from the aboveground part of Astragalus membranaceus Bunge-adjuvanted vaccines enhanced humoral and cellular immunity and that the polysaccharide from the aboveground part of Astragalus membranaceus Bunge is a safe and efficacious adjuvant candidate suitable for use in prophylactic and therapeutic vaccines.

• The Korean Journal of Food And Nutrition
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• v.20 no.1
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• pp.74-78
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• 2007

Ixeris sonchifolia Hance(Godulbaegi), Oenanthe javanica(Dolminari), Fagopyrum esculentum Moench(Buckwheat), Hizikia fusiforme(Seaweed Fusiforme) and Zingiber officinale Roscoe(Ginger) have all been used as one of the traditional remedies as well as food source. There are few studies However, on their immunomodulating effects have been reported. We previously reported that ex vivo supplementation of each of the Ish, Oj, Fem, Hf and Zor water extracts enhanced the splenocytes proliferation compared to the control group. In this study, the combined immunomodulative effects of a plant water extract mixture containing these five food sources(Ish+Oj+Fem+Hf+Zor) was compared to the individual effect of each. The production of cytokine(IL-1${\beta}$, IL-6, and TNF-${\alpha}$), secreted by macrophages stimulated with LPS or without, were detected via ELISA assay using a cytokine kit. After 48hrs of incubation with mitogen(ConA or LPS) stimulation, the mouse splenocyte proliferation in the experimental group had significantly increased at two different concentrations compared to the control group. The results of this study may suggest that the supplementing with a plant water extract mixture could regulate immune function by increasing splenocyte proliferation as well as enhance immune function by regulating the cytokine production capacity activated macrophages in mice.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.11
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• pp.1300-1307
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• 2017

Cheonggukjang is well known as a traditional fermented food in Korea and has various biological activity. In this study, immune-enhancing activity of extract of cheonggukjang fermented with Bacillus amyloliquefaciens (SRCM100730) was examined in RAW 264.7 murine macrophages. Treatment with extract augmented production of nitric oxide (NO) and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) from RAW 264.7 macrophages in a dose-dependent manner. Similarly, increased mRNA expression of inducible nitric oxide synthase (iNOS) and $TNF-{\alpha}$ was observed. In addition, the extract synergistically enhanced production of NO and $TNF-{\alpha}$ from lipopolysaccharide (LPS)-stimulated macrophages. Analysis of intracellular pathways revealed that the immune-enhancing activity of cheonggukjang extract was related to activation of mitogen-activated protein kinases (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$). These results suggest that cheonggukjang fermented with B. amyloliquefaciens (SRCM100730) is a beneficial food effective for activation of immune responses.

• Korean Journal of Food Science and Technology
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• v.41 no.4
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• pp.380-385
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• 2009

The purpose of this study was to investigate the immunomodulatory effect of Ulva pertusa kjellman extract after undergoing a low temperature and high-pressure extraction process. First, the extracts obtained under the extraction conditions of 150 MPa and $80^{\circ}C$showed a relatively high antioxidant activity, with 90% super oxide radical activity compared to the extracts from conventional extraction process with water at $100^{\circ}C$. This extract also improved the growth of both human immune B and T cells up to $14.5{\times}10^4$ cells/mL and $14.2{\times}10^4$ cells/mL compared to $9.1{\times}10^4$ cells/mL in adding the extracts from conventional processes. It was found that the extracts obtained at 100 MPa and $60^{\circ}C$ showed better activities in NK cell growth and NO production from macrophage as $11.8{\times}10^2$ cells/mL and 30.0 ${\mu}M$. Overall, the extracts from high pressure and low temperature extraction process had relatively higher immune activation activity, possibly because the low temperature and high pressure extraction process may have higher yields of active compounds and have less damage to useful ingredients from relatively weak marine natural resources, such as Ulva pertusa kjellmann than that from the conventional extraction system.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.2
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• pp.167-175
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• 2005

Houttuynia cordata THNUB (He; Uh-Sung-Cho) is a medicinal plant which has been widely used as a component of blood-building decoctions. This study was performed to investigate the immunomodulative effect of He in mice. In vitro experiment, the mice splenocytes proliferation and three kinds of cytokines (IL-1$\beta$, IL-6, TNF- $\alpha$) production by mice peritoneal macrophages cultured with six (methanol, hexane, chloroform, ethylacetate, butanol and water) fractions of He were used to indicate the immunomodulative effect. Ex vivo experiment, the different concentrations of He water extract was orally administrated every other day for two weeks. The production of cytokines IL-1$\beta$, IL-6, TNF- $\alpha$) secreted by activated macrophages and the mice splenocytes proliferation were used as an index for the immunocompetence. The supplementation of all six fractions of He enhanced the splenocytes proliferation at the level of 6.58$\pm$1.23∼47.82$\pm$5.48 compared to that of control in the range of 1∼50 $\mu\textrm{g}$/mL. IL-1$\beta$ production was significantly increased with the supplementation of chloroform and water extract of He. Higher level of IL-6 production was detected by the supplementation of ethylacetate, butanol and water extract. TNF - $\alpha$ production was enhanced by the supplementation of all six fractions of He. From the ex vivo study, the highest proliferation of splenocytes was seen from the mice orally administrated with the He water extract at the concentration of 500 mg/kg bw In case of cytokines production, IL-1$\beta$, IL-6, and TNF- $\alpha$ release by activated peritoneal macrophages were augmented by the oral administration of He water extract. These results indicated that He may enhance the immune function by regulating the splenocytes proliferation and cytokines production capacity in mice.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.12
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• pp.1835-1842
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• 2014

Various microorganisms are involved in the fermentation of Mageoli, Korean traditional liquor. Among them, the most predominant microorganism is yeast, including Saccharomyces cerevisae. This study investigated the effects of crude polysaccharides separated from Mageoli mash (CP-M) on activation of peritoneal macrophages in cell culture medium. Four types of yeasts, S. cerevisae 89-1-1, 98-2, 268-3, and 113-4, were used. When peritoneal macrophages were treated with $10{\mu}g/mL$ of CP-M fermented with S. cerevisae 113-4, the concentration of nitric oxide (NO) in the medium was highest ($33.3{\mu}M$). The concentrations of IL-6 and -12 were also highest at 116.3 pg/mL and 59.8 pg/mL, respectively. In the case of CP-M cultured at 15, 20, and $30^{\circ}C$ after inoculation with S. cerevisae 113-4 and fermented at different temperatures, production of NO and IL-6 by peritoneal macrophages did not change compared to the control. For CP-M obtained after fermentation at $25^{\circ}C$, however, NO concentration increased 2.7~3.3 fold and IL-6 concentration by 5.7 fold compared to the control. Furthermore, the effect of fermentation period on expression of CP-M functionality was examined. NO production by CP-M of the 5th day mash was highest, increasing 2.2 fold compared to 0-day CP-M. However, there were no significant differences in concentration of IL-6 or -12 according to different fermentation periods, although CP-M showed a large decrease after 10 days. The results show that fermentation conditions with the highest activity were observed in CP-M inoculated with S. cerevisae 113-4 and fermented at $25^{\circ}C$ for 5 days. CP-M consisted of 78.6% neutral sugar, 11.6% acidic polysaccharide, and 9.8% protein. In particular, the sugar composition of neutral sugar consisted of mannose (47.8%), glucose (29.6%), and galactose (12.7%). Based on the results, CP-M is assumed to be an extracellular polysaccharide originating in yeast with high mannose content.

• Food Science and Preservation
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• v.18 no.6
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• pp.938-945
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• 2011

Epimedium koreanum Nakai is a wild herb commonly consumed in South Korea due to its beneficial health effects. In the present study, the antimutagenic and immunoactivities of extracts from E. koreanum Nakai containing different icariin quantities were investigated for food use. In the Ames test, both the water and ethanol extracts were found not to have a mutagenic effect on Salmonella typhimurium TA98 and TA100, respectively. The E. koreanum Nakai extracts showed over 80 and 90% antimutagenic effects on benzo(${\alpha}$)pyrene (B(a)P) in S. typhimurium TA98 and TA100, respectively. Moreover, all the extracts showed over 70% antimutagenicity on S. typhimurium TA98 and TA100 against 4-nitroquinoline-1-oxide (4NQO). The E. koreanum Nakai extract with ethanol showed strong antimutagenic activity, higher than that of the water extract and the sequenced KE9412, KE9408, and KE9405. In the immunomodulating activity test, the effect of E. koreanum Nakai on the B (Rhamos) and T (Jukat) cells were investigated. The immunoactivity results showed that the growth and viability of the B and T cells increased and were activated more in KE9405 (1.8 times), KE9408 (1.6 times), and KE9412 (1.32 times) in the water extracts, and least in KE9412 (1.74 times), KE9408 (1.52 times), and KE9405 (1.4 times) in the ethanol extracts. In the case of both the water and ethanol extracts ($500{\mu}g/mL$) from E. koreanum Nakai, the highest cell number of the human B (Rhamos) and T (Jukat) cells was observed on day 4 in KE9405 and KE9412, and on day 5 in KE9408. Based on the obtained results, the development of E. koreanum Nakai as a food material is recommended.

• The Korean Journal of Mycology
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• v.26 no.2 s.85
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• pp.246-255
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• 1998

Ganoderan (GAN), an immunomodulating ${\beta}-glucan$ of G. lucidum, induces potent antitumor immunity in tumor-bearing mice. This study was set up to elucidate the ability of macrophage activation of GANs. GAN-treated Raw 264.7 macrophages showed enhanced production of nitric oxide (NO). The ability of GANs to produce NO was based on differences in chemical composition of GANs obtained from the mycelium on various carbon sources and mycelial fractionation. The highest NO production was observed in CW-AS-WS polysaccharide which was extracted from the mycelial wall. GAN-treated Raw 264.7 cells gave a 2-to 5-fold (24 hr) formation of NO levels compared with those treated with medium only. Partial removal of the protein in the extracellular GAN by TCA treatment did appreciably reduce its capacity to secrete NO. The mixture effect of GAN and LPS increased the nitric oxide secretion from RAW 264.7. The cell proliferation of GAN-treated Raw 264.7 cell tines inhibited as compared with its control. Of the culture supernatant of macrophage activated by GAN, the percentage of cytotoxicity against mouse leukemia L1210 cells was slightly dependent on the amount of NO in the culture supernatants of the activated-macrophages. These results indicate that the ${\beta}-glucan-related$ polysaccharides of the higher fungus activate macrophage and release nitric oxide. It also suggests that murine macrophages possess certain receptors for ${\beta}-anomeric$ glucans and play a critical role of ${\beta}-glucan-related$ tumor killing mechanism.

• Journal of Nutrition and Health
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• v.41 no.2
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• pp.141-146
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• 2008

Ixeris sonchifolia Hance (Godulbaegi), Oenanthe javanica (Dolminari), Fagopyrum esculentum Moench (Buckwheat>, Hizikia fusiforme (Seaweed Fusiforme) and Zingiber ojficinale Roscoe (Ginger) have been used respectively as one of folk remedies as well as food materials. However, reportedly few studies on their immunomodulating effects have been made, although it has been known from other preceding studies that the ex vivo supplementation of each Ish, OJ, Fem, Hf, Zor water extracts tends to enhance the proliferation of splenocyte in comparison to the control group. This study on the combined immunomodulative effect of water extract mixture of these five food materials (Ish + Oj + Fem +Hf+Zor) lasted covering seven or eight weeks. The old mice (balb/c) was fed ad libitum on chow diet, and the water extract of plant mixture was orally administrated every other day for four weeks at two different concentrations (50 and 500 mg/kg B.W) . After preparing the single cell suspension, the proliferation of splenocyte was determined by MTT (3-[4,5-dimethylthiazol-2-y]-2,5-diphenyl terazolium bromide) assay. The production of cytokine ($IL-{\beta}$, IL-6, and $TNF-{\alpha}$) which was secreted by macrophages stimulated with LPS or not was detected by ELISA assay using the cytokine kit. After the 48 hours of incubation with the mitogen (ConA or LPS) stimulation, the proliferation of the mice splenocyt in the experimental group statisticaly increased at both of two different concentrations in comparison to the control group. The cytokines production was more significantly enhanced at the lower supplementation (50 mg/kg B.W.) group than at the higher concentration (500 mg/kg B.W.). The result of this study may suggest that the supplementation of water extract of plant mixture can regulate and enhance the immune function by increasing the splenocyte proliferation and regulating the cytokine production capacity by the activated macrophages in mice.

• Journal of Ginseng Research
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• v.33 no.4
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• pp.316-323
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• 2009

Ginseng saponins have various pharmacological effects on the immune system. 20(S)-protopanaxadiol (PPD) and 20(S)-protopanaxatriol (PPT) are the species of ginseng saponin metabolites that are formed by human intestinal bacteria and detected in circulation. The effects of PPD and PPT on the inflammatory mediator release from the activated mast cells were tested. Histamine release was evaluated in activated guinea pig lung mast cells, and the secretion of interleukin-4 (IL-4), interleukin-8 (IL-8), and the tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) was assessed in an HMC-1 cell after treating it with ginseng saponin metabolites. The results are as follows. PPT, at its maximum concentration of $100\;{\mu}M$, completely abolished the secretion of IL-4 from the PMA-stimulated HMC-1 cell. It also inhibited IL-8 secretion from the same cells by about 40-50% of the PMA-treated DMSO control. PPD, at its maximum concentration of $100\;{\mu}M$, showed a tendency to induce histamine release from the guinea pig lung mast cells. It inhibited the secretion of IL-4 (by 89% of the PMA-treated DMSO control) in the PMA-stimulated HMC-1 cell, but did have a significant effect on the IL-8 release from the same cell. Both PPD and PPT showed no effects, however, on the release of TNF-${\alpha}$ from the PMA-stimulated HMC-1 cell. These results suggest that PPD and PPT are from the ginseng metabolites that are responsible for the immunomodulating activity of ginseng extracts when they are taken orally.