• Journal of Ginseng Research
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• v.43 no.1
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• pp.154-160
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• 2019

Background: Compound K (CK) is an active metabolite of ginseng saponin, ginsenoside Rb1, that has been shown to have ameliorative properties in various diseases. However, its role in inflammation and the underlying mechanisms are poorly understood. In this report, the antiinflammatory role of CK was investigated in macrophage-like cells. Methods: The CK-mediated antiinflammatory mechanism was explored in RAW264.7 and HEK293 cells that were activated by lipopolysaccharide (LPS) or exhibited overexpression of known activation proteins. The mRNA levels of inflammatory genes and the activation levels of target proteins were identified by quantitative and semiquantitative reverse transcription polymerase chain reaction and Western blot analysis. Results: CK significantly inhibited the mRNA expression of inducible nitric oxide synthase and tumor necrosis factor-${\alpha}$ and morphological changes in LPS-activated RAW264.7 cells under noncytotoxic concentrations. CK downregulated the phosphorylation of AKT1, but not AKT2, in LPS-activated RAW264.7 cells. Similarly, CK reduced the AKT1 overexpression-induced expression of aldehyde oxidase 1, interleukin-$1{\beta}$, interferon-${\beta}$, and tumor necrosis factor-${\alpha}$ in a dose-dependent manner. Conclusion: Our results suggest that CK plays an antiinflammatory role during macrophage-mediated inflammatory actions by specifically targeting the AKT1-mediated signaling pathway.

• Asian-Australasian Journal of Animal Sciences
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• v.32 no.9
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• pp.1363-1372
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• 2019

Objective: This study was designed to investigate the effect of diet supplementation with rubber seed oil and flaxseed oil on serum fatty acids profile, oxidation stability of serum and milk, and immune function of dairy cows. Methods: Forty-eight mid-lactation Holstein dairy cows were randomly assigned to one of four treatments for 8 wk, including basal diet (CON) or the basal diet supplemented with 4% rubber seed oil (RO), 4% flaxseed oil (FO) or 2% rubber seed oil plus 2% flaxseed oil (RFO) on a dry matter basis. Results: Compared with CON, all the oil groups increased the levels of trans-11 C18:1 (vaccenic acid), cis-9, trans-11 C18:2 (conjugated linoleic acid, CLA) and C18:3 (${\alpha}$-linolenic acid, ALA) in serum. Both the activity of glutathione peroxidase and catalase in serum and milk in oil groups were decreased, which were negatively correlated with the levels of cis-9, trans-11 CLA and ALA. The concentrations of proinflammatory factors (tumor necrosis factor ${\alpha}$ and interferon ${\gamma}$) in serum of oil groups were lower than that from the CON cows. Conclusion: These results indicate that diet supplementation with RO or FO could alter serum fatty acid profile and enhance the immune function of dairy cows. However, the negative effect on milk oxidation stability should be considered when feeding these n-3 polyunsaturated fatty acid-enriched oils in dairy production.

• Korean Journal of Medicinal Crop Science
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• v.27 no.2
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• pp.143-150
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• 2019

Background: Skin is an organ that protects the human body from various environmental stimuli that can induce immune system activation. Skin aging can be largely divided into two categories: physiological aging, which is caused by the a decreased physiological function of the skin and structural changes with aging, and photoaging, which is caused by the chemical stress induced by external stimuli such as ultraviolet (UV) radiation. Methods and Results: The objective of this study was to investigate the anti-wrinkle and UV protective effect of catechin-rich green tea extract (CGTE) in activated keratinocyte (HaCaT cells) and UV-induced skin damage in hairless mice. The results showed that CGTE inhibits the tumor necrosis factor-alpha interferon-gamma ($TNF-{\alpha}+IFN-{\gamma}$)-induced expression of matrix metalloproteinase (MMP)-1 in HaCaT cells. In addition, the CGTE treatment significantly reduced wrinkle formation, epidermal thickness, collagen deposition, and transepidermal water loss in dorsal skin irradiated with UVB. However, the ${\beta}$-glucosidase activity was significantly increased. The CGTE treatment inhibits mRNA expression and enzyme activity of MMP-2 and MMP-9 in the dorsal skin irradiated with UVB. Conclusions: It is expected that CGTE can be effectively used as a functional food and cosmetic ingredient to improve skin moisture retention and reduce wrinkle formation.

• Journal of Microbiology and Biotechnology
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• v.29 no.7
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• pp.1155-1164
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• 2019

Lichens contain diverse bioactive secondary metabolites with various chemical and biological properties, which have been widely studied. However, details of the inhibitory mechanisms of their secondary metabolites against influenza A virus (IAV) have not been documented. Here, we investigated the antiviral effect of lichen extracts, obtained from South Korea, against IAV in MDCK cells. Of the lichens tested, Nipponoparmelia laevior (LC24) exhibited the most potent inhibitory effect against IAV infection. LC24 extract significantly increased cell viability, and reduced apoptosis in IAV-infected cells. The LC24 extract also markedly reduced (~ 3.2 log-fold) IAV mRNA expression after 48 h of infection. To understand the antiviral mechanism of LC24 against IAV, proteomic (UPLC-$HDMS^E$) analysis was performed to compare proteome modulation in IAV-infected (V) vs. mock (M) and LC24+IAV (LCV) vs. V cells. Based on Ingenuity Pathway Analysis (IPA), LC24 inhibited IAV infection by modulating several antiviral-related genes and proteins (HSPA4, HSPA5, HSPA8, ANXA1, ANXA2, $HIF-1{\alpha}$, AKT1, MX1, HNRNPH1, HNRNPDL, PDIA3, and VCP) via different signaling pathways, including $HIF-1{\alpha}$ signaling, unfolded protein response, and interferon signaling. These molecules were identified as the specific biomarkers for controlling IAV in vitro and further confirmation of their potential against IAV in vivo is required. Our findings provide a platform for further studies on the application of lichen extracts against IAV.

• Journal of Periodontal and Implant Science
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• v.24 no.2
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• pp.321-339
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• 1994

The cytokines released by osteoblasts induce bone resorption via the differentiation of osteoclast precursors. In this process, $interleukin-1{\beta}$($IL-1{\beta}$)-induced bone resorption is mediated by granulocyte macrophage-colony stimulation factor(GM-CSF), interleukin-6 (IL-6), and tumor necrosis factor ${\alpha}$($TNF-{\alpha}$) released from osteoblasts. Since these cytokines (GM-CSF, IL-6, $TNF-{\alpha}$) are produced by not only osteoblasts but also monocytes, and interleukin-10(I1-10) inhibits the secretion of these cytokines from monocytes, it may be speculated that IL 10 could modulate the production of GM-CSF, IL-6, and $TNF-{\alpha}$ by osteoblasts, then control $IL-1{\beta}-induced$ bone resorption. Therefore, the aims of the present study were to examine the effects of IL-10 on bone resorption. The sixten or seventeen-day pregnant ICR mice were injected with $^{45}Ca$ and sacrificed one day after injection. Then fetal mouse calvaria prelabeled with $^{45}Ca$ were dissected out. In order to confirm the degree of bone resorption, mouse calvaria were treated with Lipopolysaccharide(LPS), $TNF-{\alpha}$, $IL-1{\alpha}$, IL-8, $IL-1{\beta}$, and $IL-1{\alpha}$, Then, IL-10 and $interferon-{\gamma}$ ($IFN-{\gamma}$) were added to calvarial medium, in an attempt to evaluate the effect of $IL-1{\beta}-induced$ bone resorption. In addition, osteoclasts formation in bone marrow cell cultures, and the concentration of IL-6, $TNF-{\alpha}$, and GM-CSF produced from mouse calvarial cells were investigated in response to $IL-1{\beta}$ alone and simultaneously adding f $IL-1{\beta}$ and IL-10. The degree of bone resorption was expressed as the ratio of $^{45}Ca$ release(the treated/the control). The osteoclasts in bone marrow cultures were indentified by tartrate resistant acid phosphatase(TRAP) stain and the concentration of the cytokines was quantified using enzyme linked immunosorbent method. As results of these studies, bone resorption was induced by LPS(1 ng/ml ; the ratio of $^{45}Ca$ release, $1.14{\pm}0.07$). Also $IL-1{\beta}$(1 ng/ml), $IL-1{\alpha}$(1 ng/ml), and $TNF-{\alpha}$(1 ng/ml) resulted in bone resorption(the rations of $^{45}Ca$ release, $1.61{\pm}0.26$, $1.77{\pm}0.03$, $1.20{\pm}0.15$ respectively), but IL-8 did not(the ratio of $^{45}Ca$ release, $0.93{\pm}0.21$). The ratios of $^{45}Ca$ release in response to IL-10(400 ng/ml) and $IFN-{\gamma}$(100 ng/ml) were $1.24{\pm}0.12$ and $1.08{\pm}0.04$ respectively, hence these cytokines inhibited $IL-1{\beta}$(1 ng/ml)-induced bone resorption(the ratio of $^{45}Ca$ release $1.65{\pm}0.24$). While $IL-1{\beta}$(1 ng/ml) increased the number of TRAP positive multinulcleated cells in bone marrow cultures($20{\pm}11$), simultaneously adding $IL-1{\beta}$(1 ng/ml) and IL-10(400 ng/ml) decreased the number of these cells($2{\pm}2$). Nevertheless, IL-10(400 ng/ml) did not affect the IL-6, GM-CSF, and $TNF-{\alpha}$ secretion from $IL-1{\beta}$(1 ng/ml)-activated mouse calvarial cells. From the above results, it may be suggested that IL-10 inhibites $IL-1{\beta}-induced$ osteoclast differntiation and bone resorption. However, the inhibitory effect of IL-10 on the osteoclast formation seems to be mediated not by the reduction of IL-6, GM-CSF, and $TNF-{\alpha}$ production, but by other mechanisms.

• YAKHAK HOEJI
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• v.43 no.2
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• pp.198-207
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• 1999

The aim of the present investigation was to examine whether YH439, a hepatoprotective agent, exerts protective effect against hepatotoxicity and reduces the production of cytokines and NO in lipopolysaccharide (LPS)-primed rats with carbon tetrachloride ($CCl_4$). Administration of LPS following a single dose of CCl4 injection resulted in remarkable elevations of the serum $TNF{\alpha},{\;}IL-l{\beta$ and IL-6 level. The serum NO level was moderately elevated and severe liver damage was evidenced by increases in serum alanine aminotransferase (ALT) and sorbitol dehydrogenase (SDH) activities. YH439 decreased the levels of TNF, $IL-l{\beta}$, IL-6, ALT, SDH as well as NO in the serum elevated by CCl4+LPS in a dose-dependent manner. Inducible nitric oxide synthase (iNOS) level was decreased in the liver of rats treated with YH439. The increased iNOS activity induced by LPS and $interferon-{\gamma}$ was significantly decreased in RAW 264.7 cells by YH439 treatment. YH439 increased the GSH level decreased by $CCl_4+LPS$ and suppressed the ratio of GSSG/GSH. The reduction of hepatotoxicity by YH439 may associated with the decrease in the production of cytokines as well as suppression of iNOS protein in conjunction with an increase in the GSH level.

• Food Science and Biotechnology
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• v.17 no.5
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• pp.947-952
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• 2008

The unripe fruit of Momordica charantia (MC) has been shown to possess antidiabetic activity. However, the mechanism of its antidiabetic action has not been fully understood. In this study, the effects of the aqueous ethanolic extract of MC (AEE-MC) were evaluated on the apoptosis in pancreatic $\beta$-cells treated with a combination of the cytokines, interleukin (IL)-$1{\beta}$, tumor necrosis factor (TNF)-$\alpha$, and interferon (IFN)-$\gamma$. In MIN6N8 cells, the inhibitory effect of AEE-MC was significantly observed at 2 to 50 ${\mu}g/mL$: a 26.2 to 55.6% decrease of cytoplasmic DNA fragments quantified by an immunoassay. The molecular mechanisms, by which AEE-MC inhibited $\beta$-cell apoptosis, appeared to involve the inhibition on the expression of p21, Bax, and Bad, the up-regulation of Bcl-2 and Bcl-$X_L$, and the inhibition on the cleavage of caspase-9, -7, and -3 and poly (ADP-ribose) polymerase. This study suggests that MC may inhibit cytokine-induced apoptosis in $\beta$-cells and, thus, may contribute via this action to the antidiabetic influence in diabetes.

• YAKHAK HOEJI
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• v.48 no.4
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• pp.241-246
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• 2004

Mercury is a widespread metal and consequently there are large populations that currently exposed to low levels of mercury. Endotoxin is a component of the gram-negative bacteria and promotes inflammatory responses. The present study was designed to determine the impact of mercury on lymphocytes phenotype populations and endotoxin-induced inflammatory cytokine expressions in immune organ, spleen and thymus. Male BALB/c mice were exposed continuously to 0, 0.3, 1.5, 7.5, or 37.5 ppm of mercuric chloride in drinking water for 14 days and at the end of the treatment period, lipopolysaccharide (LPS, 0.5 mg/kg) was injected intraperitoneally 2 h prior to euthanasia. The dose-range of mercury used did not cause hepatotoxicity. Mercury at 7.5 and 37.5 ppm dose-dependently decreased CD3$^{+}$ T lymphocytes in spleen; both CD4$^{+}$ and CD8$^{+}$ single positive lymphocyte populations were decreased. Exposure to 7.5 and 37.5 ppm of mercury decreased the CD8$^{+}$ T lymphocyte population in the thymus, whereas double positive CD4$^{+}$ / CD8$^{+}$ and CD4$^{+}$ thymocytes were not altered. Mercury altered LPS-induced inflammatory cytokine gene expressions such as, tumor necrosis factor $\alpha$, interferon ${\gamma}$, and interleukin-12 in spleen and thymus. Results indicated that decreases in T lymphocyte populations in immune organs and altered cytokine gene expression may contribute to the immune-modulative effects of inorganic mercury.ganic mercury.

• The Korea Journal of Herbology
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• v.22 no.1
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• pp.81-87
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• 2007

Objectives: Angelicae Dahuricae Radix (Baek-Ji in Korean, BJ) is well known to be used as a medicine for cold, headache, supraorbital pain, nasal congestion, and toothache. Little is understood about the roles of BJ in the cytokine and chemokine secretion by immune cells. This study was designed to find out the effects of BJ on the cytokine and chemokine secretion in human mast cells (HMC). Methods : We treated BJ according to consistency on HMC and measured cytokines and chemokines levels using flow cytometry CBA system. Results: In BJ treated group. the expression of interferon-inducible protein 10 (IP-l0), monocyte chemoattractant protein-1 (MCP-1), chemokine (C-X-C motif) ligand 9 (MIG), and interleukin 10 (IL-l0) levels were decreased significantly and chemokine (C-C motif) ligand 5 (RANTES), IL-8, $interferone-{\gamma}$ ($IFN-{\gamma}$), and tumor necrosis factor alpha (TNF-a) were decreased significantly. Conclusion : The results of this experiment supposed that the treatment of BJ will ameliorate the secreting levels of some chemokines or cytokines such as IP-10, MCP-1, MIG, IL-10, RANTES, IL-8, $IFN-{\gamma}$, and TNF-a.

• Archives of Pharmacal Research
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• v.21 no.2
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• pp.89-105
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• 1998

In the past decade, significant progress has been achieved in the battle against hepatitis B virus. In addition to the immunomodulating agents such as interferon-.alpha., and thymosin, many novel antiviral agents have been discovered, among which nucleoside analogues are the mainstay. New-generation compounds such as 3TC and famciclovir have shown promise in the treatment of patients chronically infected by this virus, and are on the line for approval. However, viral rebound after cessation of therapy still remains a major problem. Additionally, the reports on the drug resistance to these antiviral agents suggest that combination therapy will be the eventual strategy (Bartholomew et al., 1997; Tipples et al., 1996). Therefore, developments of safe and effective antiviral agents which do not cross-resist with currently available antiviral drugs are still much needed.