• Proceedings of the Plant Resources Society of Korea Conference
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• 2022.09a
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• pp.92-92
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• 2022

Under the COVID-19 pandemic, interest in immune enhancement is increasing. Although the immune-enhancing activity of plants of the genus Hibiscus has been reported, there is no study on the immune-enhancing activity of H. syriacus. Thus, in this study, we investigated the immune-enhancing activity of Hibiscus syriacus leaves (HSL) in mouse macrophages, RAW264.7 cells, and immunosuppressed mice. HSL increased the production of immunostimulatory factors such as nitric oxide (NO), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) and activated the phagocytosis in RAW264.7 cells. The HSL-mediated production of immunostimulatory factors was dependent on toll-like receptor 4 (TLR4), p38, and c-Jun N-terminal kinase (JNK) in RAW264.7 cells. In the immunosuppressed mouse model, HSL increased the spleen index, the levels of the cytokines, and the numbers of lymphocytes, neutrophils, and monocytes. Taken together, HSL may be considered to have immune-enhancing activity and be expected to be used as a potential immune-enhancing agent.

• Korean Journal of Plant Resources
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• v.35 no.6
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• pp.697-703
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• 2022

Under the COVID-19 pandemic, interest in immune enhancement is increasing. Although the immune-enhancing activity of plants of the genus Hibiscus has been reported, there is no study on the immune-enhancing activity of H. syriacus. Thus, in this study, we investigated the immune-enhancing activity of Hibiscus syriacus leaves (HSL) in mouse macrophages, RAW264.7 cells, and immunosuppressed mice. HSL increased the production of immunostimulatory factors such as nitric oxide (NO), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) and activated the phagocytosis in RAW264.7 cells. The HSL-mediated production of immunostimulatory factors was dependent on toll-like receptor 4 (TLR4), p38, and c-Jun N-terminal kinase (JNK) in RAW264.7 cells. In the immunosuppressed mouse model, HSL increased the spleen index, the levels of the cytokines, and the numbers of lymphocytes, neutrophils, and monocytes. Taken together, HSL may be considered to have immune-enhancing activity and be expected to be used as a potential immune-enhancing agent.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2020.08a
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• pp.87-87
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• 2020

In this study, we investigated the immune-enhancing activity of water extracts from Hydrangea macrophylla subsp. serrata (WE-HML). WE-HML increased cell viability and production of immunomodulators, which contributed to activating phagocytic activity in RAW264.7 cells. Inhibition of JNK and NF-κB reduced the production of immunomodulators by WE-HML. ROS inhibition suppressed the production of immunomodulators, and the activation of JNK and NF-κB signaling by WE-HML. TLR4 inhibition attenuated the production of immunomodulators, and activation of JNK and NF-κB signaling by WE-HML. In the immunosuppressed mouse model, WE-HML increased the spleen index, the levels of the cytokines, the numbers of white blood cells, lymphocytes, and neutrophils. However, WE-HML inhibited LPS-mediated overproduction of pro-inflammatory mediators in RAW264.7 cells, which indicated that WE-HML may have anti-inflammatory activity under excessive inflammatory conditions. Taken together, WE-HML may be considered to have immune-enhancing activity and expected to be used as a potential immune-enhancing agent.

• Food Science of Animal Resources
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• v.38 no.6
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• pp.1226-1236
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• 2018

Ovotransferrin (OTF) is a well-known protein of the transferrin family with strong iron chelating activity, resulting in its antimicrobial activity. Furthermore, OTF is known to have antioxidant, anticancer, and antihypertensive activities. However, there have been few studies about the immune-enhancing activity of OTF. In current study, we investigated the immune-enhancing activity of OTF using the murine macrophage cells in vitro. The effect of OTF on production of pro-inflammatory mediators and cytokines were determined using Griess assay and quantitative real-time PCR. Using Neutral Red uptake assay, we confirmed the effect of OTF on phagocytic activity of macrophages. Ovotransferrin significantly increased the production of nitric oxide (NO) and secretion of inducible nitric oxide synthase (iNOS) mRNA with no cytotoxic activity. Ovotransferrin (2 mg/mL) stimulated NO production up to $31.9{\pm}3.5{\mu}M$. Ovotransferrin significantly increased the mRNA expression levels of pro-inflammatory cytokines which are tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), Interleukin-$1{\beta}$ (IL-$1{\beta}$), and IL-6: OTF (2 mg/mL) treatment increased the secretion of mRNA for TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 by 22.20-, 37.91-, and 6.17-fold of the negative control, respectively. The phagocytic activity of macrophages was also increased by OTF treatment significantly compared with negative control. Also, OTF treatment increased phosphorylation level of MAPK signaling pathways. These results indicated that OTF has immune-enhancing activity by activating RAW 264.7 macrophages via MAPK pathways.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2020.08a
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• pp.88-88
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• 2020

Ginseng (Panax ginseng Meyer) is a very well-known traditional herbal medicine that has long been used to enhance the body's immunity. Because it is a type of ginseng, it is believed that wild simulated ginseng (WSG) also has immune-enhancing activity. However, study on the immune-enhancing activity of WSG is quite insufficient compared to ginseng. In this study, we evaluated immune-enhancing activity of WSG through macrophage activation to provide a scientific basis for the immune enhancing activity of WSG. WSG increased the production of immunomodulators such as NO, iNOS, COX-2, IL-1β, IL-6 and TNF-α and activated phagocytosis in mouse macrophages RAW264.7 cells. Inhibition of TLR2 and TLR4 reduced the production of immunomodulators induced by WSG. WSG activated MAPK, NF-κB and PI3K/AKT signaling pathways, and inhibition of such signaling activation blocked WSG-mediated production of immunomodulators. In addition, activation of MAPK, NF-κB and PI3K/AKT signaling pathways by WSG was reversed by TLR2 or TLR4 inhibition. Based on the results of this study, WSG is thought to activate macrophages through the production of immunomodulators and phagocytosis activation through TLR2/4-dependent MAPK, NF-κB and PI3K/AKT signaling pathways. Therefore, it is thought that WSG have the potential to be used as an agent for enhancing immunity.

• Korean Journal of Plant Resources
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• v.37 no.1
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• pp.1-10
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• 2024

This studied the immune-enhancing activity properties of water extracts from the leaves, branches, and fruit of 13 species (Rhamnaceae) collected during the bearing season (Berchemia berchemiifolia, B. floribunda, Hovenia dulcis, Paliurus ramosissimus, Rhamnella franguloides, Rhamnus crenata, R. davurica, R. koraiensis, R. parvifolia, R. ussuriensis, R. yoshinoi, Sageretia thea, and Ziziphus jujube). Immune-enhancing activity were studied using the nitric oxide (NO) production in RAW264.7 cells. Extracts of B. berchemiifolia, H. dulcis, R. franguloides, R. crenata, R. davurica, R. ussuriensis and S. thea showed strong immune-enhancing activity through NO production. In addition, the expression of immune enhancement-related cytokine genes (NOS, COX-2, IL-1β, IL-6 and TNF-α) were confirmed through PCR-electrophoresis. The results of this study suggest that Rhamnaceae extracts can be used as natural antioxidants and immune enhancer.

• Journal of Marine Bioscience and Biotechnology
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• v.15 no.1
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• pp.12-23
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• 2023

Sargassum horneri (SH), a brown macroalgae, has medicinal properties. The present study investigated the immune-enhancing effects of SH extract on peritoneal macrophages (PM). The SH significantly increased the production of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and nitric oxide (NO) in PM. It was confirmed that SH significantly increased NO expression through the increase of iNOS protein expression, which is the up-regulation pathway. Additionally, it was determined if SH activates the mitogen-activated protein kinase (MAPK) pathway, an upper regulatory mechanism that influences TNF-α, IL-6, and NO expression. Consequently, SH significantly increased the phosphorylation of p38, extracellular signal-regulated kinases (ERK), and c-Jun N-terminal kinase (JNK), all of which are MAPK pathway proteins. Moreover, the immune-enhancing effects of SH on another macrophage cell line, bone marrow-derived macrophages were investigated. It was observed that SH significantly enhanced TNF-α, IL-6, and NO production. Overall, this study demonstrates the immune-enhancing effects of SH on macrophages via activated MAPK pathway. Therefore, it suggests that SH has the potential to improve immunological activity in various macrophage cell lines and can be useful as an immune-enhancing treatment.

• Journal of Microbiology and Biotechnology
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• v.33 no.3
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• pp.356-362
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• 2023

The 2'-fucosyllactose (2'-FL) is the richest components in a human milk oligosaccharide. Several studies have reported that 2'-FL has beneficial effects in infants. However, there are few studies on its immune-enhancing effects. This research aimed to examine the immune-enhancing effect of 2'-FL on immunosuppression by cyclophosphamide (CCP) in ICR mice. Mice were orally administered distilled water or 0.5 mg/kg B.W. 2'-FL for 14 days. An immunocompromised mouse model was induced using CCP 80 mg/kg B.W. at 12-14 days. Using the CCP had effects on reducing their body weight, organ weight, spleen index, natural killer (NK) cell activity, and cytokines concentration and expression. This study also used concanavalin A-mediated T-cell proliferation to verify the immune-enhancing effects in the sample. Body weight, spleen index, organ weight, and cytokine levels were measured to estimate the immune-enhancing effects. The body weight at 14 days tended to increase, and the spleen weight and index significantly increased in the 2'-FL group compared to the CCP group. The NK cell activity increased in the 2'-FL group compared to the CCP group, but there was no significant difference. The concentration of interleukin (IL)-2 tended to recover in the 2'-FL group compared to the CCP group. The 2'-FL group showed a significant increase of IL-10 and IFN-gamma concentration compared to the CCP group. In addition, there was a trend of increased IL-10 mRNA expression compared to the CCP group. These results revealed that 2'-FL improved CCP-induced immunosuppression, suggesting that 2'-FL may have the potential to enhance the immune system.

• Journal of Animal Science and Technology
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• v.63 no.5
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• pp.1159-1168
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• 2021

Ovotransferrin (OTF), an egg protein known as transferrin family protein, possess strong antimicrobial and antioxidant activity. This is because OTF has two iron binding sites, so it has a strong metal chelating ability. The present study aimed to evaluate the improved immune-enhancing activities of OTF hydrolysates produced using bromelain, pancreatin, and papain. The effects of OTF hydrolysates on the production and secretion of pro-inflammatory mediators in RAW 264.7 macrophages were confirmed. The production of nitric oxide (NO) was evaluated using Griess reagent and the expression of inducible nitric oxide synthase (iNOS) were evaluated using quantitative real-time polymerase chain reaction (PCR). And the production of pro-inflammatory cytokines (tumor necrosis factor [TNF]-α and interleukin [IL]-6) and the phagocytic activity of macrophages were evaluated using an ELISA assay and neutral red uptake assay, respectively. All OTF hydrolysates enhanced NO production by increasing iNOS mRNA expression. Treating RAW 264.7 macrophages with OTF hydrolysates increased the production of pro-inflammatory cytokines and the phagocytic activity. The production of NO and pro-inflammatory cytokines induced by OTF hydrolysates was inhibited by the addition of specific mitogen-activated protein kinase (MAPK) inhibitors. In conclusion, results indicated that all OTF hydrolysates activated RAW 264.7 macrophages by activating MAPK signaling pathway.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2020.08a
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• pp.86-86
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• 2020

The leaves of Staphylea bumalda (S. bumalda) as a deciduous tree distributed in Korea, China and Japan are used to treat respiratory diseases or inflammation. However, there is no scientific research on the immune-enhancing activity of S. bumalda leaves. Thus, in this study, we investigated the effect of water extracts from S. bumalda leaves (SBL) on the macrophage activity using mouse macrophage cells, RAW264.7. SBL increased production of immunomodulators such as NO, iNOS, IL-1β, IL-6, TNF-α and MCP-1 in RAW264.7 cells and activated phagocytic activity of RAW264.7 cells. Inhibition of TLR2 and TLR4 blocked SBL-mediated production of immunomodulators in RAW264.7 cells. In addition, SBL-mediated production of immunomodulators was attenuated by JNK inhibition in RAW264.7 cells. SBL increased JNK phosphorylation, while Inhibition of TLR2 and TLR4 blocked SBL-mediated JNK phosphorylation in RAW264.7 cells. These results are thought to be evidence that SBL activates JNK through stimulation of TLR2 and TLR4 in macrophage to induce the production of immunomodulators. In LPS-stimulated RAW264.7 cells, SBL inhibited over-production of immunomodulators. Summarizing the results, SBL showed immunostimulatory activity under normal conditions and immunosuppressive activity under LPS-induced excessive immune response conditions.