• Korean Journal of Medicinal Crop Science
• /
• v.28 no.4
• /
• pp.276-286
• /
• 2020

Background: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease associated with multiple metabolic disorders. The medicinal plant Curcuma longa L. is widely distributed in Asia and has been used to treat a spectrum diseases in clinical practice. To date, there are inadequate reports of the effects of C. longa 50% EtOH extract (CE) on NAFLD. Therefore, in this study, we evaluate the CE on an NAFLD animal and elucidate the mechanism of action. Methods and Results: C57BL/6J mice fed a methionine-choline deficient diet (MCD) were treated with CE or milk thistle, and changes in inflammation and stetosis were assessed. Experimental animals were divided into six group (n = 10); Normal, MCD, MCD + CE 50 mg/kg/day (CE 50), MCD + CE 100 mg/kg/day (CE 100), MCD + CE 150 mg/kg/day (CE 150), and the Control, MCD + Milk thistle 150 mg/kg/day (MT 150). Body weight, liver weight, liver function, and histological changes were assessed in experimental animals. Quantitative real-time polymerase chain reaction and western blot analyses were performed on samples collected after 4 weeks of treatment. We observed that CE administration improved MCD-diet-induced lipid accumulation, and triglyceride (TG) and total cholesterol (TC) levels in serum. Treatment with CE also decreased hepatic lipogenesis through modulation of the sterol regulatory element binding protein-1 (SREBP-1), CCAAT-enhancer binding protein α (C/EBPα), fatty acid synthase (FAS), and peroxisome proliferator-activated receptor γ (PPARγ) expresion. In addition, the use of CE increased adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and inhibited the up-regulation of toll-like receptor (TLR)-2 and TLR-4 signaling and the production of inflammatory mediators. Conclusions: In this report, we observed that CE regulated lipid accumulation in an MCD dietinduced NAFLD model by decreasing lipogenesis. These data suggeste that CE could effectively protect mice against MCD-induced NAFLD, by inhibiting the TLR-2 and TLR-4 signaling cascades.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.20 no.1
• /
• pp.37-42
• /
• 2006

Matrix metalloproteinase-9 (MMP-9) is considered to be an important component in the progression of inflammation. Monocytes/macrophages are prominent at inflammation sites, and activation of these cells by stimulants such as lipopolysaccharide (LPS) leads to the production of significant amounts of MMP-9. Here, we show that LPS-induced MMP-9 production and activation was inhibited by the water extract from the fruit of Chaenomeles sinensis (CS), the root of Polygonum cuspidatum (PC), but increased by the extract from Boswellia carterii (BC). To investigate the mechanism by which those extracts inhibits MMP-9 activation, we examined the level of MMP-9 mRNA expression. We observed a significant change in the MMP-9 expression between LPS alone and LPS plus Chaenomeles sinensis and Polygonum cuspidatum extracts-treated cells. In addition, LPS significantly up-regulated MMP-9 promoter activity in Raw 264.7 cells, which was attenuated by the CS and PS extracts. However, water extracts from Boswellia carterii increased MMP-9 expression and MMP-9 promoter activity which were induced by LPS treatment in Raw 264.7 cells. These data suggest that water extracts from Chaenomeles sinensis and Polygonum cuspidatum can modulate anti-inflammatory immune response, which may be in part associated with the regulation of MMP-9 production and/or activation through the regulation of MMP-9 expression in mouse macrophage cells.

• Biomolecules & Therapeutics
• /
• v.11 no.4
• /
• pp.249-256
• /
• 2003

Pyroligneous liquid(PL) is produced by carbonizing Oak in 350-40$0^{\circ}C$. It is traditionally used for treating stress-related disorder, hepatic disease, immune disorder, G-I disorder and inflammatory disease. The aim of this study is to investigate anti-stress effects of PL. The experiments were performed with the use of young(9 weeks of age) male rats of SD strain and the male ICR mice (20-25 g). Animals of the normal group were not exposed to any stress and the control group were exposed to stress. The rats of the Ginseng, diazepam(BZ) and PL supplementary group were orally administered once a day 100 g of Ginseng extract-kg body weight, 5 mg of BZ/kg body weight and 1 ml of PL100 g body weight and then exposed to stress. The mice of the Ginseng, BZ and PL supplementary group were given water containing 100 g of Ginseng extract/100 ml potable water, 5 mg of BZ/kg 100 ml of drinking water and 10 ml of PL/100 ml of drinking water and exposed to stress. Animals were given materials for 7 days after stabilizing them, and then were given supplementary materials for 5 days with stress. They were stressed by immobilization for 30 minutes and then the animals were exposed to electroshocks for 5 minutes. We recorded stress-related behavioral changes of experimental animals by stressing them using the Etho-vision system and measured the levels of corticosterone in blood While stress suppressed locomotor activity of animals, PL-supplementation partially blocked the stress effect of locomotion in rats and mice, and also partially blocked stress-induced behavioral changes such as freezing, burrowing, smelling and rearing activity in rats and freezing, grooming, tailing and rearing in mice. The staying time of stressed rats and mice in open area decreased and in closed area it increased relatively in elevated plus maze test. However, these changes also partially were blocked by PL-supplementation. PL-supplementation decreased levels of blood corticosterone increased by stress in rats. These results suggest that PL protects partially the living organism from stress attack in some cases.

• Biomolecules & Therapeutics
• /
• v.28 no.5
• /
• pp.456-464
• /
• 2020

Mast cells (MCs) are systemically distributed and secrete several allergic mediators such as histamine and leukotrienes to cause type I hypersensitivity. Dasatinib is a type of anti-cancer agent and it has also been reported to inhibit human basophils. However, dasatinib has not been reported for its inhibitory effects on MCs or type I hypersensitivity in mice. In this study, we examined the inhibitory effect of dasatinib on MCs and MC-mediated allergic response in vitro and in vivo. In vitro, dasatinib inhibited the degranulation of MCs by antigen stimulation in a dose-dependent manner (IC₅₀, ~34 nM for RBL-2H3 cells; ~52 nM for BMMCs) without any cytotoxicity. It also suppressed the secretion of inflammatory cytokines IL-4 and TNF-α by antigen stimulation. Furthermore, dasatinib inhibited MC-mediated passive cutaneous anaphylaxis (PCA) in mice (ED₅₀, ~29 mg/kg). Notably, dasatinib significantly suppressed the degranulation of MCs in the ear tissue. As the mechanism of its effect, dasatinib inhibited the activation of Syk and Syk-mediated downstream signaling proteins, LAT, PLCγ1, and three typical MAP kinases (Erk1/2, JNK, and p38), which are essential for the activation of MCs. Interestingly, in vitro tyrosine kinase assay, dasatinib directly inhibited the activities of Lyn and Fyn, the upstream tyrosine kinases of Syk in MCs. Taken together, dasatinib suppresses MCs and PCA in vitro and in vivo through the inhibition of Lyn and Fyn Src-family kinases. Therefore, we suggest the possibility of repositioning the anti-cancer drug dasatinib as a treatment for various MC-mediated type I hypersensitive diseases.

• Journal of Life Science
• /
• v.23 no.11
• /
• pp.1409-1414
• /
• 2013

Lymph node (LN) is the sites where mature lymphocytes become stimulated to respond to invading pathogens in the body. Lymphocytes screen the surfaces of pathogen-carrying antigen-presenting cells for cognate antigens, while moving along stromal structural back bone. Fibroblastic reticular cells (FRC) is stromal cell forming the 3 dimensional structure networks of the T cell rich zones in LN, and provide a guidance path for immigrating T lymphocytes. In these cooperative environments, the cell to cell bidirectional interactions between FRC and T cells in LN are therefore essential to the normal functioning of these tissues. Not only do FRCs physically construct LN architecture but they are essential for regulating T cell biology within these domains. FRC interact closely with T lymphocytes, is providing scaffolds, secreting soluble factors including cytokine in which FRCs influence T cell immune response. More recently, FRC have been found to induce peripheral T cell tolerance and regulate the extent to which newly activated T cells proliferate within LN. Thus, FRC-T cell crosstalk has important consequences for regulating immune cell function within LN. In addition, FRC have profound effects on innate immune response by secreting anti-microbial peptides and complement, etc in the inflammatory milieu. In summary, we propose a model in which FRC engage in a bidirectional touch to increase the T cell biological efficiency between FRC and T cells. This collaborative feedback loop may help to maintain tissue function during inflammation response.

• Korean Journal of Food Science and Technology
• /
• v.48 no.1
• /
• pp.66-71
• /
• 2016

Delphinidin is a blue-red pigment and one of the major anthocyanins in plants. It plays an important role in anti-oxidant, anti-inflammatory, anti-mutagenic and anti-cancer properties. In this study, we investigated the inhibitory effects of delphinidin on vascular endothelial growth factor (VEGF) gene expression, an important factor involved in angiogenesis and tumor progression in human prostate cancer. Delphinidin decreased levels of epidermal growth factor (EGF)-induced VEGF mRNA expression in PC-3M cells. The expression of the EGF-induced hypoxia inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) and signaling transducer and activator of transcription 3 (STAT3) proteins, which are the major transcription factors for VEGF, were inhibited by delphinidin. In addition, delphinidin decreases HRE-promoter reporter gene activity, suggesting that delphinidin can suppress the transcription of HIF-$1{\alpha}$ under EGF induction, leading to a decrease in the expression of VEGF. Delphinidin specifically suppressed the phosphorylation of Akt, p70S6K, and 4EBP1, but not the phosphorylation of EGFR. Therefore, our results suggest that delphinidin may inhibit human prostate cancer progression and angiogenesis by inhibiting HIF-$1{\alpha}$, STAT3 and VEGF gene expression.

• Korean Journal of Food Science and Technology
• /
• v.50 no.1
• /
• pp.105-110
• /
• 2018

Melittin is the main component of apitoxin (bee venom) that has been reported to have anti-inflammatory and anti-cancer effects. Herein, we demonstrated that inhibition of epithelial-mesenchymal transition (EMT) by melittin causes suppression of cancer cell migration and invasion. Melittin significantly suppressed the epidermal growth factor (EGF)-induced cell migration and invasion in lung cancer cells. Moreover, melittin up-regulated the expression of epithelial marker protein, E-cadherin, and down-regulated the expression of EMT related proteins, vimentin and fibronectin. Mechanistic studies revealed that melittin markedly suppressed the expression of EMT mediated transcription factors, ZEB2, Slug, and Snail. The EGF-induced phosphorylation of AKT, mTOR, P70S6K, and 4EBP1 was also inhibited by melittin, but not that of ERK and JNK. Therefore, the inhibitory effect of melittin on migration and invasion of lung cancer cells may be associated with the inhibition of EMT via blocking of the AKT-mTOR-P70S6K-4EBP1 pathway.

• Korean Journal of Food Science and Technology
• /
• v.50 no.3
• /
• pp.349-355
• /
• 2018

Ginsenoside Rg5, one of the protopanaxadiol ginsenosides of wood-cultivated ginseng, has been implicated in various diseases, such as diabetes, cancer, and hypertension; however, its angiogenic activity and molecular mechanisms have not yet been elucidated. Here, we found that wood-cultivated ginseng extract and ginsenoside Rg5 increase in vitro proliferation, migration, and tube-like structure formation, which are typical phenomena associated with angiogenesis, in cultured human umbilical vein endothelial cells (HUVECs). Moreover, Ginsenoside Rg5 stimulated the phosphorylation of Akt, endothelial nitric oxide (NO) synthase (eNOS), and extracellular-regulated kinase (ERK)1/2, which are well-known signal mediators of the angiogenic pathway. Furthermore, Ginsenoside Rg5 did not accelerate the activation of ICAM-1 and VCAM-1 which are inflammatory response mediators. These results suggest that wood-cultivated ginseng extract and ginsenoside Rg5 stimulated in vitro angiogenesis by activating the Akt/eNOS- and ERK1/2-dependent signal pathways without inducing vascular inflammation.

• The Korean Journal of Food And Nutrition
• /
• v.28 no.2
• /
• pp.253-257
• /
• 2015

Acanthopanax senticosus is an herb that has been used as a traditional remedy and medicine source. Its anti-inflammatory and, anti-oxidative effects have been reported in previous studies. This study aimed to investigate the effect of Acanthopanax senticosus water extracts on mouse macrophage cell in vitro. Mouse splenocyte proliferation increased after application of Acanthopanax senticosus water extract supplement of 5, 10, 50, 100, 250, 500, $1,000{\mu}g/mL$ after 48 h pre-treatment with a mitogen (ConA or LPS). The production of cytokines secreted by LPS and non LPS stimulated macrophages was detected by ELISA assay using a cytokine kit. Cytokine production (IL-2, IFN-${\gamma}$, and TNF-${\alpha}$) increased after water extract supplementation. The result of this in vitro study, showed that splenocyte proliferation and cytokine production by activated peritoneal macrophages were increased after Acanthopanax senticosus water extract in the range of $500{\sim}1,000{\mu}L/mL$. Thus, it is suggested that supplementation with Acanthopanax senticosus water extracts may enhance immune function by regulating splenocyte proliferation and enhancing cytokine production by activated macrophage.

• Journal of The Korean Dental Society of Anesthesiology
• /
• v.14 no.2
• /
• pp.101-106
• /
• 2014

Background: Remifentanil, an ultra-short-acting mu-opioid receptor agonist, is unique from other opioids because of its esterase-based metabolism, minimal accumulation, and very rapid onset and offset of clinical action. Remifentanil can prevent the inflammatory response and can suppress inducible nitric oxide synthase expression in a septic mouse model. However, the effects of remifentanil on human keratinocyte and autophagy have yet to be fully elucidated during hypoxia-reoxygenation. Here we investigated whether remifentanil confers protective effect against hypoxia-reoxygenation in human keratinocyte and, if so, whether autophagy mediates this effect. Methods: The human keratinocytes were cultured under 1% oxygen tension. The cells were gassed with 94% $N_2$, and 5% $CO_2$ and incubated for 24 h at $37^{\circ}C$. To determine whether the administration of affects human keratinocytes hypoxia-reoxygenation injury, cells were then exposed to various concentrations of remifentanil (0.01, 0.1, 0.5 and 1 ng/ml) for 2 h. After remifentanil treatment, to simulate reoxygenation and recovery, the cells were reoxygenated for 12 h at $37^{\circ}C$. Control group did not receive remifentanil treatment. Normoxia group did not receive hypoxia and remifentanil treatment for 36 h. 3-MA group was treated 3-methyladenine (3-MA) for 1h before remifentanil treatment. Cell viability was measured using a quantitative colorimetric assay with MTT, showing the mitochondrial activity of living cells. Cells were stained with fluorescence and analyzed with Western blot analysis to find out any relations with activation of autophagy. Results: Prominent accumulation of autophagic specific staining MDC was observed around the nuclei in RPT group HaCaT cells. Similarly, AO staining, red fluorescent spots appeared in RPT group HaCaT cells, while the Normoxia, control and 3-MA groups showed mainly green cytoplasmic fluorescence. We here examined activation of autophagy related protein under H/R-induced cells by Western blotting analysis. Atg5, Beclin-1, LC3-II (microtubule-associated protein 1 light chain 3 form II) and p62 was elevated in RPT group cells. But they were decreased when autophagy was suppressed by 3-MA (Fig. 5). Conclusions: Although the findings of this study are limited to an in vitro interpretation, we suggest that remifentanil may have a beneficial effect in the recovery of wound from hypoxia-reoxygenation injury.