• Korean Journal of Food Science and Technology
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• v.51 no.2
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• pp.152-159
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• 2019

To characterize new physiologically active components in Korean apple vinegar, a crude polysaccharide (KAV-0) was prepared by precipitation with 80% (v/v) ethanol. KAV-0 mainly comprises 38.2% mannose, 19.1% galactose and 14.3% glucose. In an in vitro cytotoxicity analysis, KAV-0 promoted the proliferation of peritoneal macrophages and RAW 264.7 cells in a dose-dependent manner, and showed no cytotoxicity in B16-BL6 melanoma cells. Murine peritoneal macrophages and RAW 264.7 cells stimulated by KAV-0 produced various cytokines such as interleukin (IL)-6, IL-12, and tumor necrosis factor $(TNF)-{\alpha}$, and nitric oxide (NO). Intravenous (i.v.) administration of KAV-0 significantly augmented NK cell cytotoxicity against Yac-1 tumor cells. In experimental lung metastasis caused by B16-BL6 melanomas, prophylactic i.v. administration of KAV-0 at a dosage of $1,000{\mu}g/mouse$ inhibited lung metastasis by 53.0%. These results suggest that the crude polysaccharide (KAV-0) isolated from Korean apple vinegar has a considerably high anti-metastatic activity and immunomodulatory activities beneficial to human health.

• Journal of Ginseng Research
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• v.43 no.4
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• pp.580-588
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• 2019

Background: Ginsenoside Rg1 has been shown to clear senescence-associated beta-galactosidase (SA-${\beta}$-gal) in cultured cells. It remains unknown whether Rg1 can influence SA-${\beta}$-gal in exercising human skeletal muscle. Methods: To examine SA-${\beta}$-gal change, 12 young men (age $21{\pm}0.2years$) were enrolled in a randomized double-blind placebo controlled crossover study, under two occasions: placebo (PLA) and Rg1 (5 mg) supplementations 1 h prior to a high-intensity cycling (70% $VO_{2max}$). Muscle samples were collected by multiple biopsies before and after cycling exercise (0 h and 3 h). To avoid potential effect of muscle biopsy on performance assessment, cycling time to exhaustion test (80% $VO_{2max}$) was conducted on another 12 participants (age $23{\pm}0.5years$) with the same experimental design. Results: No changes of SA-${\beta}$-gal were observed after cycling in the PLA trial. On the contrary, nine of the 12 participants showed complete elimination of SA-${\beta}$-gal in exercised muscle after cycling in the Rg1 trial (p < 0.05). Increases in apoptotic DNA fragmentation (PLA: +87% vs. Rg1: +133%, p < 0.05) and $CD68^+$ (PLA:+78% vs. Rg1:+121%, p = 0.17) occurred immediately after cycling in both trials. During the 3-h recovery, reverses in apoptotic nuclei content (PLA:+5% vs. Rg1 -32%, p < 0.01) and increases in inducible nitrate oxide synthase and interleukin 6 mRNA levels of exercised muscle were observed only in the Rg1 trial (p < 0.01). Conclusion: Rg1 supplementation effectively eliminates senescent cells in exercising human skeletal muscle and improves high-intensity endurance performance.

• Journal of Life Science
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• v.29 no.9
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• pp.977-985
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• 2019

Aster yomena (Kitam.) Honda is an edible vegetable and perennial herb belonging to the Asteraceae family, and has been used for a long time for the prevention and treatment of various diseases. Although leaf extracts of A. yomena are known to have antioxidant and anti-inflammatory effects, accurate efficacy assessments are still inadequate. In this study, we investigated whether the antioxidant efficacy of ethanol extract of A. yomena leaf (EEAY) is correlated with the anti-inflammatory effect in RAW 264.7 macrophages. The results showed that EEAY significantly inhibited the hydrogen peroxide ($H_2O_2$)-induced growth inhibition in RAW 264.7 cells, which was associated with increased expression of nuclear factor erythroid 2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1). EEAY pretreatment also effectively prevented $H_2O_2$-induced reactive oxygen species generation and apoptosis through inhibition of caspase-3 activation and poly (ADP-ribose) polymerase degradation. Additionally, EEAY significantly increased the expression and production of interleukin-10, a representative anti-inflammatory cytokine, which was associated with increased expression of toll-like receptor 4 and myeloid differentiation factor 88 at transcriptional and translational levels. Furthermore, the increased production of nitric oxide (NO) by lipopolysaccharide was markedly abolished under the condition of EEAY pretreatment, and the inhibitory effect of NO production by EEAY was further increased by hemin, an HO-1 inducer. Overall, our results suggest that EEAY is able to activate the Nrf2/HO-1 signaling pathway to protect RAW 264.7 macrophages from oxidative and inflammatory stress.

• The Korea Journal of Herbology
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• v.37 no.3
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• pp.9-19
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• 2022

Objectives : Angelicae Gigantis Radix (AG) is a plant of the Ranunculus family. AG have been reported to have various pharmacological effects on human health which include uterine growth promotion, anti-inflammatory, analgesic, and immune enhancement. However, research on dermatitis disease is insufficient. Therefore, we investigated the effects of AG on tumor necrosis factor-α (TNF-α)/interferon-γ (IFN-γ) stimulated HaCaT cell. Methods : To investigate the effect of AG on HaCaT cell, HaCaT cells were pre-treated with AG for 1 hour and then stimulated with TNF-α/IFN-γ. After 24 hours, media and cells were harvested to analyze the inflammatory mediators. Concentration of human interleukin-1beta (IL-1β), monocyte chemoattractant protein-1 (MCP-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and TNF-α in the media were assessed by ELISA. mRNA expression of human thymus and activation-regulated chemokine (TARC), IL-6, and IL-8 were analyzed by RT-PCR. Additionally, the mechanisms of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway were investigated by Western blot. Results : The treatment of AG inhibited gene expression levels of IL-6, IL-8, and TARC and protein expression levels of IL-1β, MCP-1, and GM-CSF. Also, AG significantly reduced extracellular signal-regulated kinase (ERK) phosphorylation and NF-κB translocation in TNF-α/IFN-γ stimulated HaCaT cell. Conclusions : Taken together, these results demonstrate that AG can alleviate inflammatory diseases such as atopic dermatitis by regulating the expression of inflammatory cytokines. Also, it suggest that AG may a promising candidate drug for the treatment of inflammatory disease such as atopic dermatitis.

• The Korea Journal of Herbology
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• v.28 no.3
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• pp.53-60
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• 2013

Objectives : DojukSan is known to be effective for treating a urinary diseases and stomatitis. However, there has been a lack of studies regarding the effects of Dojuksan on the inflammatory activities and effector inflammatory disease mechanism about macrophage before is not known. To elucidate the molecular mechanisms of Dojuksan water extract (DJS) on pharmacological and biochemical actions in inflammation, we examined the effect of DJS on pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated macrophages. Methods : In the present study, pro-inflammatory cytokine production was determined by performing enzyme-linked immunosorbent assay, reverse transcription polymerase chain reaction, and western blot analysis to measure the activation of MAPKs. Cells were treated with 200 ng/mL of LPS 1 h prior to the addition of DJS. Cell viability was measured by MTS assay. The investigation focused on whether DJS inhibited nitric oxide (NO) and prostaglandin E2 ($PGE_2$) productions, as well as the expressions of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6) and mitogen-activated protein kinases (MAPKs) in LPS-stimulated RAW 264.7 cells. Results : We found that DJS inhibited LPS-induced NO, $PGE_2$ and IL-6 productions as well as the expressions of iNOS and COX-2. Furthermore, DJS suppressed the LPS-induced phosphorylation of p38 MAPK and c-Jun NH2-protein kinase (JNK). Conclusions : These results suggest that DJS has inhibitory effects on LPS-induced $PGE_2$, NO, and IL-6 production, as well as the expressions of iNOS and COX-2 in the murine macrophage. These inhibitory effects occur through blockades on the MAPKs phosphorylation.

• The Korea Journal of Herbology
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• v.28 no.6
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• pp.119-127
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• 2013

Objectives : ${\beta}$-Asarone (BAS) is an active ingredient in Acori Rhizoma. This study investigated anti-neuroinflammatory and memory ameliorating effects of BAS in systemic lipopolysaccharide (LPS)-treated C57BL/6 mice. Methods : BAS was administered orally at doses of 7.5, 15, and 30 mg/kg for 3 days prior to LPS (3 mg/kg, intraperitoneal) injection. Pro-inflammatory cytokine mRNA, including tumor necrosis factor-${\alpha}$ (TNF-ㅍ), interleukin (IL)-$1{\beta}$ and IL-6, was measured in hippocampus tissue using real-time polymerase chain reaction at 4 h after the LPS injection. An ameliorating effect of 30 mg/kg BAS on learning and memory impairment in the LPS-treated mice was verified using the Morris water maze test. Results : BAS significantly attenuated up-regulation of TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 mRNA in hippocampus tissue of the LPS-treated mice. In acquisition training test, BAS improved learning performance of the LPS-treated mice with a significant decrease of escape latency to the platform. In memory retention test, BAS also ameliorated memory impairment of the LPS-treated mice with a significant increase of swimming time in zones neighboring to the platform, number of target heading, and memory score. Conclusion : The results suggest that inhibition of pro-inflammatory cytokines and neuroinflammation in the hippocampus by BAS could be one of the mechanisms for BAS-mediated ameliorating effect on learning and memory impairment in LPS-treated mice.

• The Korea Journal of Herbology
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• v.32 no.5
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• pp.1-6
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• 2017

Objectives : Corni Fructus (CF) is traditional herbal medicine used on polyuria, low back pain, and tinnitus. This study aimed to evaluate inhibits skin wrinkle formation effect of CF. Methods : To evaluate the produce inhibition effect of CF, SD-rats were distributed into four groups; normal rats (Nor), AGEs (advenced glycation end product)-induced rats (Con), AGEs-induced rats treated with 100mg/kg CF (CF). To induce AGEs, streptozotocin (50mg/kg) was administered intraperitoneally and after 3 days oral administrated 100mM methyl glyoxal for 3 weeks. Results : The oral administration of CF suppressed the reactive oxygen specis (ROS) in serum. The AGEs in skin tissues was significantly reduced through treatment of CF. Furthermore, the expressions of AGEs related proteins such as polyclonal anti-$N^e$-(carboxymethyl)lysine (CML), anti-$N^e$-(carboxyethyl)lysine (CEL), AGE receptors (RAGE) were decreased in CF treated group compared with the control group in skin tissues. Inflammation-related proteins such as Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) reduced in CF treatment group than control group. AGE-induced rats exhibited that the significant decreased collagen however, CF treatment (100mg/kg of body weight) up regulated collagen by improved the expression levels of skin fibril-related genes such as Matrix metalloproteinase (MMP-1). Conclusion : Taken together, our study suggests that CF regulates ROS to prevent accumulation of AGEs and inhibits skin wrinkles. Our finding indicate that CF may be an effective agent for inhibits AGEs formation, and improved skin wrinkle.

• Journal of Korean Medicine Rehabilitation
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• v.32 no.3
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• pp.1-11
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• 2022

Objectives This study was designed to evaluate the healing effect of Cordyceps Militaris (CM) on collagen II-induced arthritis rats. Methods Sprague-Dawley rats were randomly divided into 6 groups (normal, control, positive control, CM with low/medium/high dosage each). Type II collagen mixed with complete Freund's adjuvant (with 1:1 v/v) was injected subcutaneously, and the mixture was injected in a same manner one week after the first injection to boost arthritis. Arthritis index, paw thickness and von Frey test were conducted to observe physical changes. hematoxylin and eosin (H&E) staining was performed to observe knee cartilage. The levels of messenger RNA (mRNA) expressions of interleukin (IL)-1𝛽, IL-6, tumor necrosis factor-alpha (TNF-𝛼) in spleen were assessed by real-time polymerase chain reaction. Results Rheumatoid arthritis is an autoimmune disease that occurs on multiple joints and can lead to temporary shape change of bones or organ failure in severe cases. Here, we aimed to determine the effect of CM extract on rheumatoid arthritis by measuring paw thickness, arthritis index, conducting von Frey test and H&E staining, and evaluating the level of IL-1𝛽, IL-6, TNF-𝛼. As a result, paw thickness, arthritis index significantly decreased in low concentration group, hind leg became less sensitive in all expermental groups. Also, histological analysis showed that the damage of knee cartilage was prevented in all experimental groups. The level of mRNA of IL-1𝛽, IL-6, and TNF-𝛼 in spleen was analyzed to decide the effectiveness of CM extract. IL-1𝛽 did not show significant change, but IL-6 and TNF-𝛼 showed significant decrease in at least one of the experimental groups. Conclusions CM showed protective effect on knee tissue destruction and improved the physical conditions of the leg involving arthritis. Also, it showed that CM has anti-inflammatory effect on specific cytokines inducing rheumatoid arthritis. In conclusion, this study demonstrated that the therapeutic potential of CM for the treatment rheumatoid arthritis, and set the foundation for the further studies.

• Animal Bioscience
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• v.35 no.6
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• pp.916-926
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• 2022

Objective: This study was conducted to evaluate the effects of medium chain triglycerides (MCT) with organic acids (OA) on growth performance, fecal score, blood profiles, intestinal morphology, and nutrient digestibility in weaning pigs. Methods: A total of 120 weaning pigs ([Yorkshire×Landrace]×Duroc) with an average body weight (BW) of 8.00±0.87 kg were assigned in five treatments considering sex and initial BW in 3 replications with 8 pigs per pen in a randomized complete block design. The experimental diets included a corn-soybean meal based basal diet with or without 0.1% or 0.2% MCT and 0.1% OA. The pigs were fed the diets for 5 weeks (phase 1, 0 to 2 weeks; phase 2, 3 to 5 weeks). A total of 15 barrows with an average BW of 12.48±0.37 kg were used to evaluate the nutrient digestibility by total collection method. The BW and feed intake were measured at the end of each phase. Blood samples and small intestine samples were collected at the end of each phase, too. Results: Supplementing 0.1% MCT with 0.1% OA showed greater BW for week 5 and average daily gain (ADG) for overall period than control diet. Supplementing 0.1% MCT increased (p<0.05) ADG and improved (p<0.05) gain:feed ratio for phase 1. Dietary MCT and OA did not affect the fecal score and blood concentration of cortisol, immunoglobulin G, tumor necrosis factor-α, interleukin-1β (IL-1β), IL-6, and IL-10 in weaning pigs. Pigs fed the diets with 0.1% MCT had greater (p<0.05) villus height of duodenum and ileum for phase 1. Also, pigs fed the diet with 0.1% OA showed greater (p<0.05) villus height and villus height to crypt depth ratio of duodenum for phase 2. There was no significant difference in nutrient digestibility and nitrogen retention of pigs. Conclusion: Addition of 0.1% MCT with 0.1% OA in weaning pig's diet improved growth performance partly by enhancing intestinal morphology in weaning pigs.

• Journal of Life Science
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• v.33 no.5
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• pp.397-405
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• 2023

Although glutathione (GSH) has been shown to play an important role in the prevention of oxidative damage as an antioxidant, studies on immune regulation by it have not been properly conducted. In this study, we investigated whether luthione^®, a reduced GSH, has an immune enhancing effect in murine macrophage RAW 264.7 cells. The results of flow cytometry and immunofluorescence experiments indicated that luthione increased phagocytic activity, a representative function of macrophages, compared to the control cells. According to the results of the cytokine array, the expression of interleukin (IL)-5, IL-1β, and IL-27 was significantly increased in the luthione-treated cells. Luthione also enhanced the production of tumor necrosis factor-α and IL-1β through increased expression of their proteins, and increased release of the immune mediators such as nitric oxide (NO) and prostaglandin E₂ was associated with increased expression of inducible NO synthase and cyclooxygenase-2. In addition, the expression of cluster of differentiation 86, an M1 macrophage marker, was dramatically enhanced in RAW 264.7 cells treated with luthione. Furthermore, as a result of heat map analysis, we found that cytokine signaling 1/3-mediated signal transducer and activator of transcription/Janus tyrosine kinase signaling pathway was involved in the immunomodulatory effect by luthione. In conclusion, our data suggested that luthione could act as a molecular regulator in M1 macrophage polarization and enhance immune capacity by promoting macrophage phagocytic function.