• The Journal of Internal Korean Medicine
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• v.35 no.1
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• pp.79-91
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• 2014

Objectives : To investigate the anti-cancer effect of Palbohoichoon-tang (PBHCT) extracts. Methods : The cell viability was assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MMT) assay and cell morphological changes were microscopically analyzed after staining with $10{\mu}M$ 2-[4-amidinophenyl]-6-indolecarbamidine dihydrochloride (DAPI) and TUNEL. We also analyzed expression of Bcl2, $Bcl_{xL}$, Bax, procaspase-3, procaspase-9, and procyclic acidic repetitive protein (PARP) by western blot method. Results : Observations showed that PBHCT induced the apoptotic cell death proved by increased sub-G1 phase cell population, apoptotic body formation and chromatin condensation. Western blot analysis of total cell lysates revealed that the PBHCT induced cleavage of caspase-9, caspase-3 and poly (ADP-ribose) polymerase (PARP). In addition, PBHCT dose-dependently increased the activity of caspase-9, caspase-3 and PARP-1. Furthermore, PBHCT reduced anti-apoptotic Bcl2, $Bcl_{xL}$ expression which contributed to the loss of mitochondrial membrane potential and the activations of caspase-9 and caspase-3. Conclusions : These findings suggest that PBHCT exerts anti-cancer effects on human neuroblastoma SH-SY5Y cells by inducing apoptotic death via down-regulation of anti-apoptotic proteins such as Bcl2 and $Bcl_{xL}$, up-regulation of pro-apoptotic proteins such as Bax, and activation of caspase cascades and PARP-1.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.2
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• pp.133-138
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• 2001

In the present study, we investigated the effect of pretreatment of p-chlorophenylalanine (PCPA), inhibitor of serotonin synthesis, on lipopolysaccharide (LPS)-induced anorexia in rats. First of all, effects of PCPA injection on food intake and body weight in rats were investigated. During 4 days of PCPA injection (300 mg/kg BW once a day), food intake was decreased by 33% and daily gain in body weight was inhibited compared with controls. Twenty-four hours after last PCPA injection, food intake and gain in body weight returned toward almost normal. Pair-feeding to PCPA (PCPAP) injection revealed that body weight of rats in PCPA group was not different from rats in PCPAP groups. To quantify the effects of LPS on food intake and body weight, we administered varying doses $(10,\;100,\;500\;{\mu}g/kg\;BW)$ of LPS to rats. LPS induced a reduction of food intake and weight loss in a dose dependent manner compared with controls. To evaluate the effects of PCPA pretreatment on LPS injection, rats were treated with PCPA for 4 days (300 mg/kg BW once a day), which was followed by LPS injection for 2 days $(500\;{\mu}g/kg\;BW\;once\;a\;day)$ (PCPA+LPS group), while rats in LPS group had injections with normal saline instead of PCPA for 4 days, which was followed by LPS administration. Rats in control group received 0.9% NaCl for 6 days. LPS decreased food intake by 80% and inhibited gain in body weight, while PCPA pretreated rats showed normalized food intake and gain in weight during the days of LPS injections compared with controls. In conclusion, pretreatment of PCPA prevented LPS-induced anorexia.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.3
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• pp.249-257
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• 2020

The aim of the present study was to investigate the pathophysiological etiology of osteoarthritis that is mediated by the apoptosis of chondrocytes exposed to 25-hydroxycholesterol (25-HC), an oxysterol synthesized by the expression of cholesterol-25-hydroxylase (CH25H) under inflammatory conditions. Interleukin-1β induced the apoptosis of chondrocytes in a dose- dependent manner. Furthermore, the production of 25-HC increased in the chondrocytes treated with interleukin-1β through the expression of CH25H. 25-HC decreased the viability of chondrocytes. Chondrocytes with condensed nucleus and apoptotic populations increased by 25-HC. Moreover, the activity and expression of caspase-3 were increased by the death ligand-mediated extrinsic and mitochondria-dependent intrinsic apoptotic pathways in the chondrocytes treated with 25-HC. Finally, 25-HC induced not only caspase-dependent apoptosis, but also induced proteoglycan loss in articular cartilage ex vivo cultured rat knee joints. These data indicate that 25-HC may act as a metabolic pathophysiological factor in osteoarthritis that is mediated by progressive chondrocyte death in the articular cartilage with inflammatory condition.

• Journal of Applied Biological Chemistry
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• v.54 no.1
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• pp.51-55
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• 2011

To develop a health-aid preparation of Dioscorea batatas (DB), lactic acid fermentation was attempted using a mixed starter comprising of Lactobacillus acidophilus, Lactobacillus plantarum, Bifidobacterium longum. The anaerobic fermentation of a 10% DB flour suspension gave a uniform suspension of pH 3.65, containing $8{\times}10^6$ CFU/mL lactic acid bacteria. During the administration of the lactic acid fermented DB (FDB) and DB to trinitrobenzene sulfonic acid (TNBS)-induced colitis mouse model, histological lesions, morphological damage, and myeloperoxidase acitivity were significantly reduced at a dosage of 200 and 400 mg/kg/day. Dose-response (200 and 400 mg/kg/day) studies revealed that FDB pre-treatment of mice significantly ameliorated the appearance of diarrhoea and the disruption of colonic architecture. In FDB-pretreated mice, there was a significant reduction in the degree of both neutrophil infiltration (measured as decrease in myeloperoxidase activity) and weight loss rates. Theses findings suggest that FDB exerts beneficial effects in experimental colitis and may be useful in the treatment of inflammatory bowel disease.

• Journal of Microbiology and Biotechnology
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• v.27 no.6
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• pp.1163-1170
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• 2017

Clostridium difficile releases two exotoxins, toxin A and toxin B, which disrupt the epithelial cell barrier in the gut to increase mucosal permeability and trigger inflammation with severe diarrhea. Many studies have suggested that enteric nerves are also directly involved in the progression of this toxin-mediated inflammation and diarrhea. C. difficile toxin A is known to enhance neurotransmitter secretion, increase gut motility, and suppress sympathetic neurotransmission in the guinea pig colitis model. Although previous studies have examined the pathophysiological role of enteric nerves in gut inflammation, the direct effect of toxins on neuronal cells and the molecular mechanisms underlying toxin-induced neuronal stress remained to be unveiled. Here, we examined the toxicity of C. difficile toxin A against neuronal cells (SH-SY5Y). We found that toxin A treatment time- and dose-dependently decreased cell viability and triggered apoptosis accompanied by caspase-3 activation in this cell line. These effects were found to depend on the up-regulation of reactive oxygen species (ROS) and the subsequent activation of p38 MAPK and induction of $p21^{Cip1/Waf1}$. Moreover, the N-acetyl-$\text\tiny L$-cysteine (NAC)-induced down-regulation of ROS could recover the viability loss and apoptosis of toxin A-treated neuronal cells. These results collectively suggest that C. difficile toxin A is toxic for neuronal cells, and that this is associated with rapid ROS generation and subsequent p38 MAPK activation and $p21^{Cip1/Waf1}$ up-regulation. Moreover, our data suggest that NAC could inhibit the toxicity of C. difficile toxin A toward enteric neurons.

• The Journal of Korean Medicine
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• v.37 no.3
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• pp.13-26
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• 2016

Objectives: Inflammatory bowel disease (IBD) is chronic inflammatory disorders of the intestines. Due to limitation of conventional treatment including steroids, herbal medicines have emerged as possible therapeutic options for IBD. The purpose of the current study was to investigate the therapeutic and prophylactic effects and mechanisms of Zostera Marina water extract (ZME) on DSS-induced colitis. Methods: Colitis was induced by DSS in Balb/c mice. In pre-treatment setting, ZME was administered 7 days before DSS treatment and in co-treatment setting, ZME was simultaneously administrated with DSS treatment. In both settings, ZME 100, 300 and 1000 mg/kg were orally administered twice a day, respectively. Mice weight and clinical findings were measured daily. Colon length, macroscopic findings and histological damages of colon mucosa were assessed at the end of experiments. The levels of cytokines including TNF-${\alpha}$, IFN-${\gamma}$, IL-$1{\beta}$, IL-6, IL-10 and IL-17 were measured by Biometric Multiplex Cytokine Profiling method. Results: In a dose dependent manner, ZME significantly inhibited the colon shortening, and improved macroscopic score and histological score. However, there were insignificant changes on inhibition of weight loss and improvement of clinical score. There were no significant differences of effects between co-treatment and pre-treatment settings. ZME 300 and 1000 mg/kg groups significantly inhibited IFN-${\gamma}$. Only ZME 1000 mg/kg group significantly inhibited TNF-${\alpha}$, IL-$1{\beta}$ and IL-6. Conclusions: The current results show the possibility of therapeutic use and its prophylactic application of ZME on inflammatory bowel diseases. Future studies for targeted mechanisms of ZME are needed.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.2
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• pp.169-175
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• 2016

Here, we investigated whether hyperglycemia and/or free fatty acids (palmitate, PAL) affect the expression level of bone morphogenic protein 4 (BMP4), a proatherogenic marker, in endothelial cells and the potential role of BMP4 in diabetic vascular complications. To measure BMP4 expression, human umbilical vein endothelial cells (HUVECs) were exposed to high glucose concentrations and/or PAL for 24 or 72 h, and the effects of these treatments on the expression levels of adhesion molecules and reactive oxygen species (ROS) were examined. BMP4 loss-of-function status was achieved via transfection of a BMP4-specific siRNA. High glucose levels increased BMP4 expression in HUVECs in a dose-dependent manner. PAL potentiated such expression. The levels of adhesion molecules and ROS production increased upon treatment with high glucose and/or PAL, but this eff ect was negated when BMP4 was knocked down via siRNA. Signaling of BMP4, a pro-inflammatory and pro-atherogenic cytokine marker, was increased by hyperglycemia and PAL. BMP4 induced the expression of inflammatory adhesion molecules and ROS production. Our work suggests that BMP4 plays a role in atherogenesis induced by high glucose levels and/or PAL.

• Current Research on Agriculture and Life Sciences
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• v.30 no.1
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• pp.51-59
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• 2012

Fresh oyster mushrooms (Pleurotus ostreatus) were gamma-irradiated at 0, 1, 2, and 3 kGy. The effects on various quality attributes were determined during storage at $5{\pm}1^{\circ}C$. Color changes were more prominent in the cap region than the stem part. At the start of storage increase of Hunter's L-value (lightness) was observed in the caps of 2 and 3 kGy-irradiated samples. The L-value was higher in the all irradiated samples during storage. The trend was different in the case of stem region, where L-value decreased upon irradiation, but remained high throughout storage. The ${\alpha}$-value declined, whereas the b-value increased following irradiation. Irradiation showed a dose-dependent effect on the firmness, which was clearer during storage, but the samples irradiated at 1 kGy maintained an overall better texture than other irradiated samples. The weight loss was also higher in the all irradiated samples during storage. The samples irradiated at 1 kGy showed good physical appearance without any fungal attack at the end of storage; however color change in cap region was quite apparent. The ultra-structural drastic effect of irradiation was understandable using scanning electron microscopy. E-nose analysis demonstrated a clear change in the volatile profiles of all irradiated samples. Although the effect of irradiation on quality characteristics was quite clear but the all irradiated samples were free from fungal attack that was observed in the case of control sample.

• Journal of Microbiology and Biotechnology
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• v.24 no.12
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• pp.1736-1743
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• 2014

In this study, we evaluated the effect of Lactobacillus plantarum HY7714 on skin hydration in human dermal fibroblasts and in hairless mice. In Hs68 cells, L. plantarum HY7714 not only increased the serine palmitoyltransferase (SPT) mRNA level, but also decreased the ceramidase mRNA level. In order to confirm the hydrating effects of L. plantarum HY7714 in vivo, we orally administered vehicle or L. plantarum HY7714 at a dose of $1{\times}10^9CFU/day$ to hairless mice for 8 weeks. In hairless mice, L. plantarum HY7714 decreased UVB-induced epidermal thickness. In addition, we found that L. plantarum HY7714 administration suppressed the increase in transepidermal water loss and decrease in skin hydration, which reflects barrier function fluctuations following UV irradiation. In particular, L. plantarum HY7714 administration increased the ceramide level compared with that in the UVB group. In the experiment on SPT and ceramidase mRNA expressions, L. plantarum HY7714 administration improved the reduction in SPT mRNA levels and suppressed the increase in ceramidase mRNA levels caused by UVB in the hairless mice skins. Collectively, these results suggest that L. plantarum HY7714 can be a potential candidate for preserving skin hydration levels against UV irradiation.

• Journal of Microbiology and Biotechnology
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• v.29 no.11
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• pp.1830-1840
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• 2019

Loliolide is one of the most ubiquitous monoterpenoid compounds found in algae, and its potential therapeutic effect on various dermatological conditions via agent-induced biological functions, including anti-oxidative and anti-apoptotic properties, was demonstrated. Here, we investigated the effects of loliolide on hair growth in dermal papilla (DP) cells, the main components regulating hair growth and loss conditions. For this purpose, we used a three-dimensional (3D) DP spheroid model that mimics the in vivo hair follicle system. Biochemical assays showed that low doses of loliolide increased the viability and size of 3D DP spheroids in a dose-dependent manner. This result correlated with increases in expression levels of hair growth-related autocrine factors including VEGF, IGF-1, and KGF. Immunoblotting and luciferase-reporter assays further revealed that loliolide induced AKT phosphorylation, and this effect led to stabilization of β-catenin, which plays a crucial role in the hair-inductive properties of DP cells. Further experiments showed that loliolide increased the expression levels of the DP signature genes, ALP, BMP2, VCAN, and HEY1. Furthermore, conditioned media from loliolide-treated DP spheroids significantly enhanced proliferation and the expression of hair growth regulatory genes in keratinocytes. These results suggested that loliolide could function in the hair growth inductivity of DP cells via the AKT/β-catenin signaling pathway.