• Preventive Nutrition and Food Science
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• v.8 no.1
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• pp.96-104
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• 2003

Ginger (Zingiber officinale Roscoe) is traditionally used as appetite enhancer, improver of the digestive system, antithusive, anti-cold, antipyretic, analgesic, and antiinflammation. In vitro evaluation using human lymphocyte cultures showed almost similar indication with those in in vivo mouse study, NK cell lysing activity was improved significantly. Proliferation activity of B and T cells, and CD3$^{＋}$ and CD3$^{＋}$CD4$^{＋}$T cell subset were better observed using oleoresin or gingerol and shogaol fractions. Although there were higher activities in gingerol, the improvement was almost equal to that by oleoresin. Shogaol did not show better improvement except at higher concentration. It could be concluded that treatment with single bioactive compound, such as gingerol, did not show significant effects compared to oleoresin, the crude extract. In human study, involving healthy male adult, the improvement of NK cell lysing activity was again demonstrated and even more apparent. The mechanism involved in the protection seemed to be through the antioxidant activity of gingerol. However, other mechanism underlying the improvement of NK cell lysing activity must be involved since this improvement seemed to be specifically toward NK cell activity. Since NK cells ave specific for the elimination of virus-infected cell and mutated cells, this positive effect on the immune system are very interesting. This work has also scientifically proved that the traditional beliefs that ginger had preventive effects on common cold appeared to be reasonable.

• IMMUNE NETWORK
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• v.9 no.3
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• pp.98-105
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• 2009

Background: It has been recently noticed that type 2 diabetes (T2D), one of the most common metabolic diseases, causes a chronic low-grade inflammation and activation of the innate immune system that are closely involved in the pathogenesis of T2D. Cordyceps militaris, a traditional medicinal mushroom, produces a component compound, cordycepin (3'-deoxyadenosine). Cordycepin has been known to have many pharmacological activities including immunological stimulating, anti-cancer, and anti-infection activities. The molecular mechanisms of cordycepin in T2D are not clear. In the present study, we tested the role of cordycepin on the anti-diabetic effect and anti-inflammatory cascades in LPS-stimulated RAW 264.7 cells. Methods: We confirmed the levels of diabetes regulating genes mRNA and protein of cytokines through RT-PCR and western blot analysis and followed by FACS analysis for the surface molecules. Results: Cordycepin inhibited the production of NO and pro-inflammatory cytokines such as IL-$1{\beta}$, IL-6, and TNF-${\alpha}$ in LPS-activated macrophages via suppressing protein expression of pro-inflammatory mediators. T2D regulating genes such as $11{\beta}$-HSD1 and PPAR${\gamma}$ were decreased as well as expression of co-stimulatory molecules such as ICAM-1 and B7-1/-2 were also decreased with the increment of its concentration. In accordance with suppressed pro-inflammatory cytokine production lead to inhibition of diabetic regulating genes in activated macrophages. Cordycepin suppressed NF-${\kappa}B$ activation in LPS-activated macrophages. Conclusion: Based on these observations, cordycepin suppressed T2D regulating genes through the inactivation of NF-${\kappa}B$ dependent inflammatory responses and suggesting that cordycepin will provide potential use as an immunomodulatory agent for treating immunological diseases.

• Proceedings of the Ginseng society Conference
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• 2002.10a
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• pp.266-276
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• 2002

A red ginseng acidic polysaccharide(RGAP) with immunomodulating antitumor activities was isolated from Korean red ginseng, The molecular weight of RGAP was estimated to be 12-450 kDa by gel filtration chromatography, RGAP was found to increase survival rate and to inhibit of tumor growth significantly in a dose dependent manner in mice transplanted with tumor cells. RGAP significantly promoted nitric oxide(NO) production from peritoneal macrophages bothin vivo and in vitro. Western blot analysis exhibited a newly synthesized inducible nitric oxide synthase(iNOS) protein band in the RGAP treated group. It seems likely that immunomodulating antitumor activities of RGAP are mainly mediated by NO production of macrophage. RGAP was further purified by ultrafiltration and anion exchange chromatography on DEAE-sepharose, followed by gel filtration on Sephacryl S-300 to give an active fraction(GFP) with stronger NO production in murine macrophages. GFP increased survival rate ten times compared to RGAP in male ICR mice transplanted with sarcoma 180 and also showed more potent tumoricidal activities of natural killer cells than RGAP. Sugar $composition(mol\%)$ of GFP was found to be arabinose:rhamnose:xylose:galacturonic acid:mannose:galactose:glucose(10:9:1:25:8:20:27) by GC/MS. The results suggest that clinical trials of RGAP in immunotherapy against cancer are highly feasible.

• Journal of Applied Biological Chemistry
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• v.64 no.3
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• pp.277-284
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• 2021

The emergence and rapid spread of the potentially fatal coronavirus disease 2019, caused due to infection by severe acute respiratory syndrome coronavirus-2, has led to worldwide interest in developing functional bioactive ingredients that act as immunomodulatory agents. In this study, we aimed to characterize Carica papaya extract and explore its potential as an immunomodulator by performing in vitro cell screening. Papaya leaf water extract (PLW) was found to significantly increase the levels of nitric oxide (NO) and prostaglandin E₂ (PGE₂) by upregulating inducible nitric oxide synthase and cyclo-oxygenase-2 activity, respectively. Additionally, PLW increased the production of tumor necrosis factor-α and interleukin 1β in RAW 264.7 cells. Furthermore, PLW activated the expression of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) but not that of p38 mitogen-activated protein kinase. These results indicate that PLW increased the production of NO, PGE₂, and pro-inflammatory cytokines by activating the JNK and ERK pathways in macrophages, thus demonstrating immunomodulatory properties. Finally, high-performance liquid chromatography fingerprint analysis indicated the presence of rutin, narirutin, and ρ-coumaric acid in PLW (6.30, 119.76, and 47.25 ppm, respectively). Treating cells with these compounds at non-toxic concentrations had no effect on NO production. Taken together, these results suggest that PLW may have potential as an immunity-enhancing supplement.

• Parasites, Hosts and Diseases
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• v.60 no.4
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• pp.255-259
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• 2022

Heliminthic paramyosin is a multifunctional protein that not only acts as a structural protein in muscle layers but as an immune-modulatory molecule interacting with the host immune system. Previously, we found that paramyosin from Clonorchis sinensis (CsPmy) is bound to human complement C9 protein (C9). To analyze the C9 binding region on CsPmy, overlapping recombinant fragments of CsPmy were produced and their binding activity to human C9 was investigated. The fragmental expression of CsPmy and C9 binding assays revealed that the C9 binding region was located at the C-terminus of CsPmy. Further analysis of the C-terminus of CsPmy to narrow the C9 binding region on CsPmy indicated that the region flanking ⁷³¹Leu-⁷⁸⁰Leu was a potent C9 binding region. The CsPmy fragments corresponding to the region effectively inhibited human C9 polymerization. These results provide a precise molecular basis for CsPmy as a potent immunomodulator to evade host immune defenses by inhibiting complement attack.

• The Korea Journal of Herbology
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• v.28 no.6
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• pp.15-23
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• 2013

Objectives : To clarify the possible effects of Sinapis Semen and Raphani Semen on the development of pulmonary eosinophilic inflammation in a asthmatic mouse model. Methods : BALBav/c mice were sensitized to OVA followed intratracheally and by aerosol allergene challenges. We investigated the effect of Sinapis Semen and Raphani Semen on airway hyperresponsiveness, eosinophiic infitratio, immune cell phenotype, The2 cytokine product, and OVA-spedific IgE production. Results : Total lung cells, eosinophils, and lung leukocytes, OVA specific IgE levels, and Th 2cytokine levels such as IL-5, IL-13, IL-17, TNF-alpha, and eotaxin in BALF were reduced compared with those of OVA sensitized asthma mice (control). The absolute numbers of $CD3^+$, $CD3^+/CD69^+$, $CD3^-/CCR3^+$, $CD4^+$, $CD8^+$, $Gr-1^+/CD11b^+$, $B220^+/CD22^+$, $B220^+/IgE^+$ cells in lung tissiues significantly reduced compared to those of control. Specially total lung cells in BALF and the absolute number of $CD3^+/CD69^+$ and, $B220^+/IgE^+$ cells in lung tissiue effectively reduced in Sinapis Semen plus Raphani Semen compared to those of Sinapis Semen and Raphani Semen. Conclusions : These results indicate that Sinapis Semen plus Raphani Semen has deep inhibitory effects on airway inflammation and hyperresponsiveness in asmatic mouse model and also has effect of suppression of IL-5, IL-13, IL-17, OVA specific IgE production in BALF. The results verified that Sinapis Semen, Raphani Semen, and Sinapis Semen plus Raphani Semen could act as a immunomodulator which possess anti-inflammatory and anti-asthmatic property by modulating the relationship of Th1/Th2 cytokine imbalance.

• Journal of Ginseng Research
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• v.45 no.6
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• pp.654-664
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• 2021

Background: Ginsenoside Rg3, isolated from Panax ginseng, has anti-inflammatory and anti-tumor activities. It is known to reduce inflammation in acute lung injury in mice, and to reduce the expression of inflammatory cytokines and COX-2 in human asthmatic airway epithelium. In this study, we attempted to determine whether ginsenoside Rg3 inhibits airway inflammation, oxidative stress, and airway hyperresponsiveness (AHR) in the lungs of asthmatic mice. We also investigated its effects on oxidative stress and the inflammatory response in tracheal epithelial cells. Methods: Asthma symptoms were induced in female BALB/c mice sensitized with ovalbumin (OVA). Mice were divided into five groups: normal controls, OVA-induced asthmatic controls, and asthmatic mice treated with ginsenoside Rg3 or prednisolone by intraperitoneal injection. Inflammatory BEAS-2B cells (human tracheal epithelial cells) treated with ginsenoside Rg3 to investigate its effects on inflammatory cytokines and oxidative responses. Results: Ginsenoside Rg3 treatment significantly reduced eosinophil infiltration, oxidative responses, airway inflammation, and AHR in the lungs of asthmatic mice. Ginsenoside Rg3 reduced Th2 cytokine and chemokine levels in bronchoalveolar lavage fluids and lung. Inflammatory BEAS-2B cells treated with ginsenoside Rg3 reduced the eotaxin and pro-inflammatory cytokine expressions, and monocyte adherence to BEAS-2B cells was significantly reduced as a result of decreased ICAM-1 expression. Furthermore, ginsenoside Rg3 reduced the expression of reactive oxygen species in inflammatory BEAS-2B cells. Conclusion: Ginsenoside Rg3 is a potential immunomodulator that can ameliorate pathological features of asthma by decreasing oxidative stress and inflammation

• Journal of Marine Bioscience and Biotechnology
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• v.15 no.2
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• pp.33-40
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• 2023

This study aimed to investigate the immunomodulatory function of Pyropia yezoensis hydrothermal (water) extract (PYWE) in comparison to the group treated only with lipopolysaccharides (LPS) in RAW264.7 cells. LPS is known to be an inflammatory mediator that activates macrophages, leading to the secretion of nitric oxide (NO), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) as defense responses. Through enzyme-linked immunoassay and western blot analyses, it was observed that PYWE increased the expression levels of NO, iNOS, TNF-α, and IL-6 in RAW264.7 cells in a dose-dependent manner, although to a lesser extent compared with the group treated with LPS alone. In addition, the study examined the mitogen-activated protein kinases (MAPKs) pathway, which regulates various cellular activities, including gene expression, mitosis, cell differentiation, transformation, survival, and death. The western blot analysis confirmed that PYWE also regulated the MAPKs pathway. Furthermore, the expression levels of immunomodulatory-related factors increased in the group treated with PYWE compared with the control group. Even though the effects of PYWE were usually less strong than those of LPS, the effects of PYWE increased with increasing doses compared to the control group. This suggests that PYWE could be used to control the immune system.

• Tuberculosis and Respiratory Diseases
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• v.42 no.5
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• pp.669-676
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• 1995

Background: The cell-mediated immunity is needed for eradicating the tubercle bacilli. Prostaglandin(PG), especially PG $E_2$, is involved in cellular immunosuppression. It is known that the PG $E_2$ is suppressed by indomethacin. For using indomethacin as a immunomodulator of intractable pulmonary tuberculosis(Tbc) patients, we measured the tuberculin skin test(TST) and the plasma PG $E_2$ levels. Method: The forty-eight inpatients with sputum positive acid-fast stain bacilli were classified into 6 groups according to antiTbc chemotherapy history(new and intractable cases), plain chest roetgenogram(minimal and far advanced cases), and TST reaction(nagative and positive cases). Except for one group(n=2; new, minimal, and negative cases of TST reaction) of the 6 groups, all subjects(n=46) were measured for the plasma PG $E_2$, levels with radioimmunoassay. Results: 1) There was no significant difference in the plasma PG $E_2$ levels among A group(far advanced and positive TST reaction cases, n=10, $11.22{\pm}2.86\;pg/ml$), B group(minimal and negative TST reaction cases, n=9, $11.35{\pm}2.20$) and C group(far advanced and positive TST reaction cases, n=7, $11.11{\pm}2.30$) in the new cases(p>0.05). 2) There was no significant difference in the plasma PG $E_2$ levels between positive(n=10, $9.25{\pm}2.21$) and negative(n=10, $8.25{\pm}1.13$) groups by TST in the intractable cases(p>0.05). 3) Comparing the plasma PG $E_2$ levels between new(n=26, $11.35{\pm}2.41$) and intractable(n=20, $8.75{\pm}1.78$) groups, the intractable group had significi- andy lower plasma PG $E_2$ levels(p<0.05). 4) There was no significant difference in the plasma PG $E_2$ levels between negative(n=19, $9.88{\pm}2.43$) and positive(n=27, $10.46{\pm}2.56$) groups by TST(p>0.05). 5) There was no significant difference in the plasma PG $E_2$ levels between male(n=32, $10.07{\pm}2.44$) and female(n=14, $10.56{\pm}2.70$)(p>0.05). 6) There was no significant difference in the plasma PG $E_2$ levels among 2nd(n=5, $10.21{\pm}2.86$), 3rd(n=9, $9.97{\pm}2.47$), 4th(n=13, $11.35{\pm}2.33$) and 5th(n=19, $9.57{\pm}2.48$) decades(p>0.05). 7) There was no significant correlation between the induration sizes of the TST and the plasma PG $E_2$ levels(r=0.054, p>0.05). Conclusion: From the above results, the plasma PG $E_2$ levels of intractable group are not higher as the authors had expected. There was no significant difference in the plasma PG $E_2$ levels by the lesion sizes of plain chest roentgenogram and the induration sizes of TST, so more study will be needed to use the indomethacin as a immunomodulator for intractable pulmonary tuberculosis patients.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.1
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• pp.209-213
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• 2007

In the recent, increased concern has been focused on the pharmacology and clinical utility of herbal extracts and derivatives as a drug or adjunct to chemotherapy and immunotherapy. Salicis Radicis Cortex, A decoction has been mainly used for improvement of ozena and a diuretic effect in oriental medicine, but there was no study on the molecular mechanism of Salicis Radicis Cortex as an immunomodulator. Here we investigated the role of the aqueous extract of Salicis Radicis Cortex in the expression of inflammatory mediators, surface molecule, and related receptors in vitro and in vivo. In murine macrophage RAW 264.7 cells and peritoneal macrophages of C57BL/6N mice, water extract of Salicis Radicis Cortex increased the production of secretary TNF-alpha and Nitric oxide, and the expression level of CD14, LPS co-receptor and CD86, co-stimulatory molecule compared to negative natural extract ex vivo. Moreover, i.p. injection of water extract of Salicis Radicis Cortex significantly increased the secretion level of IFN-gamma and TNF-alpha, IL-2, IL-4 and IL-5 in serum of mice in vivo. Taken together, these results suggest that Salicis Radicis Cortex may regulate the immune response by secreting Th1 and Th2 types of cytokines in vivo and the possibility of its as natural immunostimulator.