• Animal Bioscience
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• v.34 no.7
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• pp.1169-1180
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• 2021

Objective: This research aimed to study the effects of Artemisia argyi flavonoids (AAF) supplemented in diets on the growth performance and immune function of broiler chickens challenged with lipopolysaccharide (LPS). Methods: A total of one hundred and ninety-two 1-d-old broiler chicks were assigned into 4 treatment groups, which were, respectively, fed a basal diet (control), fed a diet with 750 mg/kg AAF, fed a basal diet, and challenged with LPS, fed a diet with 750 mg/kg AAF, and challenged with LPS. Each treatment had six pens with 8 chicks per pen. On days 14, 16, 18, 20 (stress phase I) and 28, 30, 32, 34 (stress phase II), broilers were injected with LPS (500 ㎍/kg body weight) or an equivalent amount of saline. Results: The results demonstrated that dietary AAF significantly improved the body weight (d 21) and alleviated the decrease of average daily gain in broilers challenged with LPS on d 21 and d 35 (p<0.05). Dietary AAF increased bursa fabricius index, and dramatically attenuated the elevation of spleen index caused by LPS on d 35 (p<0.05). Furthermore, serum interleukin-6 (IL-6) concentration decreased with AAF supplementation on d 21 (p<0.05). Diet treatment and LPS challenge exhibited a significant interaction for the concentration of IL-1β (d 21) and IL-6 (d 35) in serum (p<0.05). Additionally, AAF supplementation mitigated the increase of IL-1β, IL-6 in liver and spleen induced by LPS on d 21 and 35 (p<0.05). This study also showed that AAF supplementation significantly reduced the expression of IL-1β (d 21) and nuclear transcription factor kappa-B p65 (d 21 and 35) in liver (p<0.05), and dietary AAF and LPS treatment exhibited significant interaction for the gene expression of IL-6 (d 21), toll like receptor 4 (d 35) and myeloid differentiation factor 88 (d 35) in spleen (p<0.05). Conclusion: In conclusion, AAF could be used as a potential natural immunomodulator to improve growth performance and alleviate immune stress in broilers challenged with LPS.

• Journal of Life Science
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• v.32 no.7
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• pp.567-577
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• 2022

Recently, the prevalence of ischemic diseases, such as ischemic heart disease, cerebral ischemia, and peripheral arterial disease, has been continuously increasing due to the aging population. The current standardized treatment for ischemic diseases is reperfusion therapy through pharmacotherapy and surgical approaches. Although reperfusion therapy may restore the function of damaged arteries, it is not effective at restoring the function of the surrounding tissues that have been damaged due to ischemia. Therefore, it is necessary to develop a new treatment strategy that can safely and effectively treat ischemic damage and restore the function of surrounding tissues. To overcome these limitations, stem cell-based therapy to regenerate the damaged region has been studied as a promising strategy for ischemic vascular diseases. Mesenchymal stem cells (MSCs) can be isolated from diverse tissues and have been shown to be promising for the treatment of ischemic disease by regenerating damaged tissues through immunomodulation, the promotion of angiogenesis, and the secretion of various relevant factors. Moreover, new approaches to enhancing MSC function, such as cell priming or enhancing transplantation efficiency using a 3D culture method, have been studied to increase stem cell therapeutic efficacy. In this review, we provide various strategies by which MSCs are used to treat ischemic diseases, and we discuss the challenges of MSC transplantation, such as the differentiation, proliferation, and engraftment of MSCs at the ischemic site.

• Journal of the Korean Applied Science and Technology
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• v.38 no.6
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• pp.1543-1552
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• 2021

Atractylodes japonica has been widely used in a traditional Korean herbal medicine exerting various pharmacological activities such as diauretic action, asriction, anti-allergy, neuroprotective activity, anti-cancer, immunomodulation and gastrointestinal protective effect. This study was to investigate the antioxidant, nitric oxide and inflammatory cytokines production of A. japonica extract by water and 70% ethanol. DPPH and ABTS free radical scavenging activity were increased in a dose-dependent manners with both extracts and there was no difference with extract solvents. 70% ethanol extract of A. japonica showed a very strong inhibitory effect on NO production. Both extracts of A. japonica significantly reduce the expression of iNOS and COX-2 proteins involved in NO prodction. A. japonica extract by water and 70% ethanol inhibited LPS-induced proinflammatory cytokines such as IL-6 and IL-1b. In this study, 70% ethanol extract of A. japonica significantly suppresses LPS-induced NO and inflammatory cytokine production. Therefore it can be widely used to treat and improve inflammatory diseases.

• IMMUNE NETWORK
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• v.23 no.6
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• pp.45.1-45.22
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• 2023

Interstitial lung disease (ILD) involves persistent inflammation and fibrosis, leading to respiratory failure and even death. Adult tissue-derived mesenchymal stem cells (MSCs) show potential in ILD therapeutics but obtaining an adequate quantity of cells for drug application is difficult. Daewoong Pharmaceutical's MSCs (DW-MSCs) derived from embryonic stem cells sustain a high proliferative capacity following long-term culture and expansion. The aim of this study was to investigate the therapeutic potential of DW-MSCs in experimental mouse models of ILD. DW-MSCs were expanded up to 12 passages for in vivo application in bleomycin-induced pulmonary fibrosis and collagen-induced connective tissue disease-ILD mouse models. We assessed lung inflammation and fibrosis, lung tissue immune cells, fibrosis-related gene/protein expression, apoptosis and mitochondrial function of alveolar epithelial cells, and mitochondrial transfer ability. Intravenous administration of DWMSCs consistently improved lung fibrosis and reduced inflammatory and fibrotic markers expression in both models across various disease stages. The therapeutic effect of DW-MSCs was comparable to that following daily oral administration of nintedanib or pirfenidone. Mechanistically, DW-MSCs exhibited immunomodulatory effects by reducing the number of B cells during the early phase and increasing the ratio of Tregs to Th17 cells during the late phase of bleomycin-induced pulmonary fibrosis. Furthermore, DW-MSCs exhibited anti-apoptotic effects, increased cell viability, and improved mitochondrial respiration in alveolar epithelial cells by transferring their mitochondria to alveolar epithelial cells. Our findings indicate the strong potential of DW-MSCs in the treatment of ILD owing to their high efficacy and immunomodulatory and anti-apoptotic effects.

• Journal of Pharmacopuncture
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• v.27 no.2
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• pp.59-69
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• 2024

This study investigates the therapeutic potential of Indigo Naturalis (IN) in treating a Inflammatory Bowel Disease (IBD). The objective is to comprehensively examine the effects and pharmacological mechanisms of IN on IBD, assessing its potential as an novel treatment for IBD. Analysis of 11 selected papers is conducted to understand the effects of IN, focusing on compounds like indirubin, isatin, indigo, and tryptanthrin. This study evaluates their impact on Disease Activity Index (DAI) score, colon length, mucosal damage, and macrophage infiltration in Dextran Sulfate Sodium (DSS)-induced colitis mice. Additionally, It investigate into the anti-inflammatory mechanisms, including Aryl hydrocarbon Receptor (AhR) pathway activation, Nuclear Factor kappa B (NF-κB)/nod-like receptor family pyrin domain containing 3 (NLRP3)/Interleukin 1 beta (IL-1β) inhibition, and modulation of Toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MYD88)/NF-κB and Mitogen Activated Protein Kinase (MAPK) pathways. Immunomodulatory effects on T helper 17 (Th17)/regulatory T cell (Treg cell) balance and Glycogen synthase kinase-3 beta (GSK3-β) expression are also explored. Furthermore, the study addresses the role of IN in restoring intestinal microbiota diversity, reducing pathogenic bacteria, and increasing beneficial bacteria. The findings reveal that IN, particularly indirubin and indigo, demonstrates significant improvements in DAI score, colon length, mucosal damage, and macrophage infiltration in DSS-induced colitis mice. The anti-inflammatory effects are attributed to the activation of the AhR pathway, inhibition of inflammatory pathways, and modulation of immune responses. These results exhibit the potential of IN in IBD treatment. Notably, the restoration of intestinal microbiota diversity and balance further supports its efficacy. IN emerges as a promising and effective treatment for IBD, demonstrating anti-inflammatory effects and positive outcomes in preclinical studies. However, potential side effects necessitate further investigation for safe therapeutic development. The study underscores the need for future research to explore a broader range of active ingredients in IN to enhance therapeutic efficacy and safety.

• International Journal of Stem Cells
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• v.16 no.4
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• pp.425-437
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• 2023

Obesity, which continues to increase worldwide, was shown to irreversibly impair the differentiation potential and angiogenic properties of adipose tissue mesenchymal stromal cells (ADSCs). Because these cells are intended for regenerative medicine, especially for the treatment of inflammatory conditions, and the effects of obesity on the immunomodulatory properties of ADSCs are not yet clear, here we investigated how ADSCs isolated from former obese subjects (Ex-Ob) would influence macrophage differentiation and polarization, since these cells are the main instructors of inflammatory responses. Analysis of the subcutaneous adipose tissue (SAT) of overweight (OW) and Ex-Ob subjects showed the maintenance of approximately twice as many macrophages in Ex-Ob SAT, contained within the CD68⁺/FXIII-A^- inflammatory pool. Despite it, in vitro, coculture experiments revealed that Ex-Ob ADSCs instructed monocyte differentiation into a M2-like profile, and under inflammatory conditions induced by LPS treatment, inhibited HLA-DR upregulation by resting M0 macrophages, originated a similar percentage of TNF-α⁺ cells, and inhibited IL-10 secretion, similar to OW-ADSCs and BMSCs, which were used for comparison, as these are the main alternative cell types available for therapeutic purposes. Our results showed that Ex-Ob ADSCs mirrored OW-ADSCs in macrophage education, favoring the M2 immunophenotype and a mixed (M1/M2) secretory response. These results have translational potential, since they provide evidence that ADSCs from both Ex-Ob and OW subjects can be used in regenerative medicine in eligible therapies. Further in vivo studies will be fundamental to validate these observations.

• Korean Journal of Poultry Science
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• v.39 no.1
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• pp.63-70
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• 2012

This study was conducted to determine the possible use of Red Ginseng marc as stress inhibiter in thermal stress (temperature humidity index 86) and lipopolysaccharide (LPS) - exposed laying hens by investigating their effects on laying performance, blood biochemical parameters, immunoglobulin concentration and serum superoxide dismutase (SOD) like ability. A total of forty-five 52-wk-old laying hens (ISA Brown) were divided into 3 treatment groups with 5 replicates of 3 birds in each group. NC (negative control, no immune substances), PC (positive control, ${\beta}$-glucan 25 ppm) and RGM (Red Ginseng Marc 3%) were added in feed with respective substance. Egg production in RGM was significantly increased in comparison with NC groups for 8 weeks (P<0.05). On blood biochemical parameters, effects of ambient temperature is definite by showing significant difference in aspartate aminotransferase and others (P<0.05), but RGM both before and after thermal stimulation have no significant difference in comparison with other groups. And for 3 weeks after thermal stimulation, laying performance was also not significantly different among treatments. Immunoglobulin M content and SOD like activities after challenge with LPS were higher in the RGM and PC than NC (P<0.05). In conclusion, although ineffective as inhibiter in thermal stress, dietary supplementation of Red Ginseng marc improved SOD like activity and immune system by regulating immunoglobulin content in laying hens. These findings have laid the foundation for future studies of immunomodulation in laying hens fed Red Ginseng Marc and of evaluation of heat stress inhibitor.

• The Journal of the Korean Society for Microbiology
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• v.21 no.3
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• pp.311-329
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• 1986

The experimental exposure of animals to sources of ultraviolet radiation (UVR) which emit their energy primarily in the UVB region (280-320nm) is known to result in a number of well-described changes in the recipient's immune competence. Two such changes include a depressed capacity to effectively respond immunologically to transplants of syngeneic UVR tumors and a markedly reduced responsiveness to known inducers of delayedtype (DTH) and contact hypersensitivity (CH) reactions. The results of experiments that were designed to elucidate the mechanisms responsible for UVR-induced immunomodulation have implicated: 1) an altered pattern of lymphocyte recirculation, 2) suppressor T cells(Ts), 3) deviations in systemic antigen presenting cell (APC) potential. 4) changes in the production of interleukin-1-like molecules, and 5) the functional inactivation of epidermal Langerhans cells in this process. The exposure of skin to UVR, therefore, causes a number of both local and systemic alterations to the normal host immune system. In spite of this seeming complexity and diversity of responses, our recent studies have established that each of the UVR-mediated changes is probably of equal importance to creating the UVR-induced immunocompromised state. Normal animals were exposed to low dose UVR radiation on their dorsal surfaces under conditions where a $3.0\;cm^2$ area of skin was physically protected from the light energy. Contact sensitization of these animals with DNFB, to either the irradiated or protected back skin, resulted in markedly reduced CH responses. This was observed in spite of a normal responsiveness following the skin sensitization to ventral surfaces of the UVR-exposed animals. Systemic treatment of the low dose UVR recipients with the drug indomethacin (1-3 micrograms/day) during the UVR exposures resulted in a complete reversal of the depressions observed following DNFB sensitization to "protected" dorsal skin while the altered responsiveness found in the group exposed to the skin reactive chemical through directly UVR-exposed sites was maintained. These studies implicate the importance of EC as effective APC in the skin and also suggest that some of the systemic influences caused by UVR exposure involve the production of prostaglandins. This concept was further supported by finding that indomethacin treatment was also capable of totally reversing the systemic depressions in CH responsiveness caused by high dose UVR exposure (30K joules/$m^2$) of mice. Attempts to analyze the cellular mechanisms responsible established that the spleens of all animals which demonstrated altered CH responses, regardless of whether sensitization was through a normal or an irradiated skin site, contained suppressor cells. Interestingly, we also found normal levels of T effector cells in the peripheral lymph nodes of the UVR-exposed mice that were contact sensitized through normal skin. No effector cells were found when skin sensitization took place through irradiated skin sites. In spite of such an apparent paradox, insight into the probable mechanisms responsible for these observations was provided by establishing that UVR exposure of skin results in a striking and dose-dependent blockade of the efferent lymphatic vessels in all peripheral lymph nodes. Therefore, the afferent phases of immune responses can apparently take place normally in UVR exposed animals when antigen is applied to normal skin. The final effector responses, however, appear to be inhibited in the UVR-exposed animals by an apparent block of effector cell mobility. This contrasts with findings in the normal animals. Following contact sensitization, normal animals were also found to simultaneously contain both antigen specific suppressor T cells and lymph node effector cells. However, these normal animals were fully capable of mobilizing their effector cells into the systemic circulation, thereby allowing a localization of these cells to peripheral sites of antigen challenge. Our results suggest that UVR is probably not a significant inducer of suppressor T-cell activity to topically applied antigens. Rather, UVR exposure appears to modify the normal relationship which exists between effector and regulatory immune responses in vivo. It does so by either causing a direct reduction in the skin's APC function, a situation which results in an absence of effector cell generation to antigens applied to UVR-exposed skin sites, inhibiting the capacity of effector cells to gain access to skin sites of antigen challenge or by sequestering the lymphocytes with effector cell potential into the draining peripheral lymph nodes. Each of these situations result in a similar effect on the UVR-exposed host, that being a reduced capacity to elicit a CH response. We hypothesize that altered DTH responses, altered alloresponses, and altered graft-versus-host responses, all of which have been observed in UVR exposed animals, may result from similar mechanisms.

• Journal of Life Science
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• v.26 no.1
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• pp.50-58
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• 2016

The root bark of Ulmus macrocarpa has been used in traditional medicine for the treatment of various diseases such as edema, infection and inflammation. Nevertheless, the biological activities and underlying mechanisms of the immunomodulatory effects remain unclear. In this study, as part of our ongoing screening program to evaluate the immunomodulatory potential of new compounds from traditional medicinal resources, we investigated the effects of U. macrocarpa water extract (UME) on immune modulation in a murine RAW 264.7 macrophage model. As immune response parameters, the productions of as nitric oxide (NO) and cytokines such tumor necrotic factor (TNF)-α, interleukin (IL)-1β and IL-10 were evaluated. Although the release of IL-1β remained unchanged in UME-treated RAW 264.7 macrophages, the productions of NO, TNF-α and IL-10 were significantly increased, along with the increased expression of inducible NO synthase, TNF-α and IL-10 expression at concentrations with no cytotoxicity. UME treatment also induced the nuclear translocation of nuclear factor κB (NF-κB), and phosphorylation of Akt and mitogen-activated protein kinases (MAPKs) indicating that UME activated macrophages through the activation of NF-κB, phosphoinositide-3-kinase (PI3K)/Akt and MAPKs signaling pathways in RAW 264.7 macrophages. Furthermore, pre-treatment with UME significantly attenuated the production of NO, but not TNF-α, IL-1β and IL-10, in lipopolysaccharide-stimulated RAW 264.7 cells suggesting that UME may be useful in preventing inflammatory diseases mediated by excessive production of NO. These findings suggest that the beneficial therapeutic effects of UME may be attributed partly to its ability to modulate immune functions in macrophages.

• Journal of Life Science
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• v.23 no.1
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• pp.63-68
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• 2013

The effect of black garlic extract on the activation of spleen cells from a C57BL6 mouse was investigated to examine immune activities of of fermented black garlic containing a variety of bioactive substances. xtract obtained from the concentration of commercial Namhae black garlic was used for the analysis of immune activities. Treatment with the extract increased the expression of interleukin-2 (IL-2) cytokine. The simultaneous administration of the extract plus lipopolysaccharide (LPS) increased the expression of IL-2, tumor necrosis factor (TNF)-${\alpha}$, and interferon (IFN)-${\gamma}$ compared with that of a control group. This result suggests that cellular immunity can be induced by macrophages, resulting in the expression of T lymphocytes and T helper type 1 (Th1) cells. In addition, treatment with the extract increased the late response of IL-6 cytokines, and the extract plus LPS augmented the expression of IL-4 and IL-6 compared with that of an LPS-treated group. Meanwhile, the extract plus LPS decreased the late response of IL-10, suggesting that humoral immunity can be activated by stimulating B lymphocytes, suppressing cellular immunity, and effectively modulating the conversion into humoral immune responses. These findings demonstrate that the black garlic extract activates Th1 and Th2 cells by stimulating T lymphocytes in mouse spleen cells and leads to immunomodulation by activating cellular and humoral immune responses of the immune system.