• Proceedings of the Korean Society of Crop Science Conference
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• 2002.05a
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• pp.77-81
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• 2002

The scope of the research is investigation of immune-modulating activities of A. rugosa (Baechohyang) extract was preformed through the screening active constituents using in vitro assays and evaluating anti-inflammatory activity and anti-atherosclerotic activity of the extract and active compound (tilianin) in vivo. In addition, various functional foods using the extract and whole plant was developed. The extract showed strong anti-inflammatory activity in carrageenan-induced acute edema mouse model and anti-atherogenic lesion activity in LDLR (low density lipoprotein receptor) deficient mouse model. These activities were thought to be resulted from modulation activity of several pathways of inflammation process. Among the main constituents of Baechohyang, polyunsaturated fatty acids (PUFA), Phytosterols, oleanolic acid and rosmarinic acid showed anticomplement activity, and PUFA, acacetin and tilianin newly showed potent ICAM-1 expression inhibition activity. The processes of extraction, mixing ratio of additives and storage conditions were established for drinks, granule tea, leaf tea, mixed tea and furigake.

• Mycobiology
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• v.33 no.3
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• pp.158-162
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• 2005

The immunomodulatory effect of aqueous extract of Inonotus obliquus, called as Chaga, was tested on bone marrow cells from chemically immunosuppressed mice. The Chaga water extract was daily administered for 24 days to mice that had been treated with cyclophosphamide (400 mg/kg body weight), immunosuppressive alkylating agent. The number of colony-forming unit (CFU)-granulocytes/macrophages (GM) and erythroid burst-forming unit (BFU-E), increased almost to the levels seen in non-treated control as early as 8 days after treatment. Oral administration of the extract highly increased serum levels of IL-6. Also, the level of $TNF-{\alpha}$ was elevated by the chemical treatment in control mice, whereas was maintained at the background level in the extract-treated mice, indicating that the extract might effectively suppress $TNF-{\alpha}$ related pathologic conditions. These results strongly suggest the great potential of the aqueous extract from Inonotus obliquus as immune enhancer during chemotherapy.

• IMMUNE NETWORK
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• v.22 no.3
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• pp.21.1-21.21
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• 2022

As far the current severe coronavirus disease 2019 (COVID-19), respiratory disease is still the biggest threat to human health. In addition, infectious respiratory diseases are particularly prominent. In addition to killing and clearing the infection pathogen directly, regulating the immune responses against the pathogens is also an important therapeutic modality. Sirtuins belong to NAD+-dependent class III histone deacetylases. Among 7 types of sirtuins, silent information regulator type-1 (SIRT1) played a multitasking role in modulating a wide range of physiological processes, including oxidative stress, inflammation, cell apoptosis, autophagy, antibacterial and antiviral functions. It showed a critical effect in regulating immune responses by deacetylation modification, especially through high-mobility group box 1 (HMGB1), a core molecule regulating the immune system. SIRT1 was associated with many respiratory diseases, including COVID-19 infection, bacterial pneumonia, tuberculosis, and so on. Here, we reviewed the latest research progress regarding the effects of SIRT1 on immune system in respiratory diseases. First, the structure and catalytic characteristics of SIRT1 were introduced. Next, the roles of SIRT1, and the mechanisms underlying the immune regulatory effect through HMGB1, as well as the specific activators/inhibitors of SIRT1, were elaborated. Finally, the multitasking roles of SIRT1 in several respiratory diseases were discussed separately. Taken together, this review implied that SIRT1 could serve as a promising specific therapeutic target for the treatment of respiratory diseases.

• IMMUNE NETWORK
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• v.15 no.2
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• pp.100-109
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• 2015

Controlling balance between T-helper type 1 (Th1) and T-helper type 2 (Th2) plays a pivotal role in maintaining the biological rhythm of Th1/Th2 and circumventing diseases caused by Th1/Th2 imbalance. Interleukin 4 (IL-4) is a Th2-type cytokine and often associated with hypersensitivity-related diseases such as atopic dermatitis and allergies when overexpressed. In this study, we have tried to elucidate the function of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (EC-18) as an essential modulator of Th1/Th2 balance. EC-18 has showed an inhibitory effect on the production of IL-4 in a dose-dependent manner. RT-PCR analysis has proved EC-18 affect the transcription of IL-4. By analyzing the phosphorylation status of Signal transducer and activator of transcription 6 (STAT6), which is a transcriptional activator of IL-4 expression, we discovered that EC-18 induced the decrease of STAT6 activity in several stimulated cell lines, which was also showed in STAT6 reporter analysis. Co-treatment of EC-18 significantly weakened atopy-like phenotypes in mice treated with an allergen. Collectively, our results suggest that EC-18 is a potent Th2 modulating factor by regulating the transcription of IL-4 via STAT6 modulation, and could be developed for immune-modulatory therapeutics.

• Food Science of Animal Resources
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• v.31 no.5
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• pp.701-709
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• 2011

This study was performed to establish an effective extraction method of pig placenta extract that could be used for a putative functional food supplement with immunomodulatory effects. In the present study, we used different temperatures (4, 37, 60, 80, and $100^{\circ}C$) and different solvents (chloroform, NaOH, and phosphate buffered saline [PBS]) to extract the pig placenta. Among the different placenta extracts yielded by the different extraction methods, placenta extract (PE) in PBS at $80^{\circ}C$ for 30 min (referred to as PE-PBS80) showed a significant increase of nitric oxide production of up to 22.97 ${\mu}M/10^5$ cells at a 1 mg/mL dose (p<0.05 ) in J774A.1 cells than other extracts and control tested. Using PE-PBS80, further animal challenges were performed to identify the immune-enhanced effects. As a result, orally administered PE-PBS80 showed a significant increase in blood T and B cell activities and immunoglobulin (IgG and IgM) production. IgG and IgM levels increased to 41.53 mg/mL at a 20 mg dose on day 7 and to 27.38 mg/mL at a 10 mg dose on day 14, respectively (p<0.05). Furthermore, PE-PBS80 was also able to significantly enhance the immune modulator cytokine levels (p<0.05) compared to the control and vehicle treatments. Among the evaluated cytokines, the tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) level increased to 28.89 pg/mL at extract doses of 20 and 50 mg, the interleukin-$1{\beta}$ (IL-$1{\beta}$) level increased to 21.52 pg/mL at extract doses of 10, 20, 50 and 75 mg and the interferon (IFN)-${\gamma}$ level increased to 18.24 pg/mL at extract doses of 10, 20, and 50 mg. Therefore, this study presents an effective method for extracting pig placenta extracts and also demonstrates that pig placenta extracts had significant immunomodulatory effects not only at the cellular level but also in a mouse model, suggesting that this material could be used as an excellent candidate functional food supplement.

• Parasites, Hosts and Diseases
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• v.55 no.6
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• pp.587-599
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• 2017

The immune response against Trichinella spiralis at the intestinal level depends on the $CD4^+$ T cells, which can both suppress or promote the inflammatory response through the synthesis of diverse cytokines. During the intestinal phase, the immune response is mixed (Th1/Th2) with the initial predominance of the Th1 response and the subsequent domination of Th2 response, which favor the development of intestinal pathology. In this context, the glucocorticoids (GC) are the pharmacotherapy for the intestinal inflammatory response in trichinellosis. However, its therapeutic use is limited, since studies have shown that treatment with GC suppresses the host immune system, favoring T. spiralis infection. In the search for novel pharmacological strategies that inhibit the Th1 immune response (proinflammatory) and assist the host against T. spiralis infection, recent studies showed that resiniferatoxin (RTX) had anti-inflammatory activity, which decreased the serum levels of IL-12, $INF-{\gamma}$, $IL-1{\beta}$, $TNF-{\alpha}$, NO, and $PGE_2$, as well the number of eosinophils in the blood, associated with decreased intestinal pathology and muscle parasite burden. These researches demonstrate that RTX is capable to inhibit the production of Th1 cytokines, contributing to the defense against T. spiralis infection, which places it as a new potential drug modulator of the immune response.

• Biomolecules & Therapeutics
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• v.13 no.3
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• pp.174-180
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• 2005

Antigen presenting cells (APCs), dendritic cells (DCs) and macrophages, playa critical role not only in the initiation of immune responses, but also in the induction of immune tolerance. In an effort to regulate immune responses through the modulation of APC function, we searched for and characterized APC function modulators from natural products. Bifidobacterium pseudocatenulatum SPM1204 (SPM1204) isolated from feces of healthy Korean in the age of 20s was used in this experiment. DCs and macrophages were cultured in the presence of supernatants of SPM 1204 and then examined for their activities for the presentation exogenous antigen in association with major histocompatibility complexes (MHC) and macrophage activation. SPM1204 increased class I MHC-restricted presentation of exogenous antigen (cross-presentation) in a DC cell line, DC2.4 cells. The RAW 264.7 cell line was used to test the nonspecific effect of immune reinforcement of SPM1204 as a source of biological regulating modulator for the macrophage activation, include nitric oxide (NO) production and cytokine production. Results showed that the production of NO, tumor necrosis factor (TNF)-$\alpha$, interleukin 1 (IL-1)-$\beta$ and morphological changes in macrophages were largely affected by SPM1204 in a dose-dependent manner. Our results demonstrated that SPM1204 promote cross-presentation of dendritic cells as well as the induction of NO, TNF-$\alpha$ production, and activation of macrophage.

• Journal of Microbiology and Biotechnology
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• v.29 no.5
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• pp.704-712
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• 2019

Although nanometric dead Lactobacillus plantarum has emerged as a potentially important modulator of immune responses, its underlying mechanism of action has not been fully understood. This study aimed to identify the detailed biochemical mechanism of immune modulation by micronized and heat-treated L. plantarum LM1004 (MHT-LM1004, <$1{\mu}m$ in size). MHT-LM1004 was prepared from L. plantarum LM1004 via culture in a specifically designed membrane bioreactor and heat treatment. MHT-LM1004 was shown to effectively induce the secretion of $TNF-{\alpha}$ and IL-6 and the mRNA expression of inducible nitric oxide synthase (iNOS). MHT-LM1004 enhanced the expression of TLR-2, phosphorylation of MAPKs (ERK), and nuclear translocation of $NF-{\kappa}B$ in a dose-dependent manner. Oral administration of MHT-LM1004 ($4{\times}10^9$ or $4{\times}10^{11}cells/kg$ mouse body weight) increased the splenocyte proliferation and serum cytokine levels. These results suggested that MHT-LM1004 effectively enhances early innate immunity by activating macrophages via the TLR-2/MAPK/$NF-{\kappa}B$ signalling pathway and that this pathway is one of the major routes in immune modulation by the Lactobacillus species.

• BMB Reports
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• v.51 no.5
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• pp.219-224
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• 2018

Necroptosis is an emerging form of programmed cell death occurring via active and well-regulated necrosis, distinct from apoptosis morphologically, and biochemically. Necroptosis is mainly unmasked when apoptosis is compromised in response to tumor necrosis factor alpha. Unlike apoptotic cells, which are cleared by macrophages or neighboring cells, necrotic cells release danger signals, triggering inflammation, and exacerbating tissue damage. Evidence increasingly suggests that programmed necrosis is not only associated with pathophysiology of disease, but also induces innate immune response to viral infection. Therefore, necroptotic cell death plays both physiological and pathological roles. Physiologically, necroptosis induce an innate immune response as well as premature assembly of viral particles in cells infected with virus that abrogates host apoptotic machinery. On the other hand, necroptosis per se is detrimental, causing various diseases such as sepsis, neurodegenerative diseases and ischemic reperfusion injury. This review discusses the signaling pathways leading to necroptosis, associated necroptotic proteins with target-specific inhibitors and diseases involved. Several studies currently focus on protective approaches to inhibiting necroptotic cell death. In cancer biology, however, anticancer drug resistance severely hampers the efficacy of chemotherapy based on apoptosis. Pharmacological switch of cell death finds therapeutic application in drug- resistant cancers. Therefore, the possible clinical role of necroptosis in cancer control will be discussed in brief.

• Journal of Pharmacopuncture
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• v.22 no.1
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• pp.7-15
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• 2019

Portulaca oleracea L. (PO) or Purslane is an annual grassy plant that is distributed in many parts of the world, especially the tropical and subtropical areas. PO has some pharmacological properties such as analgesic, antibacterial, skeletal muscle-relaxant, wound-healing, anti- inflammatory and a radical scavenger. This review article is focused on the anti-inflammatory, immuno-modulatory, anti-oxidant and anti-tumor activities of the PO. Anti-inflammatory, immuno-modulatory, anti-oxidant and Anti-tumor effects of PO were searched using various databases until the end of August 2018. The online literature was searched using PubMed, Science Direct, Scopus, Google Scholar and Web of Science. Our review showed that PO exerts its effects through anti-inflammatory properties and balancing the adaptive and innate immune system depending on situations. PO acts as immune-modulator and anti-oxidant agent in both inflammatory states by the dominance of Th2 response such as asthma, cancer and atopic dermatitis and evoked Th1 disorders including hepatitis and multiple sclerosis.