• Maxillofacial Plastic and Reconstructive Surgery
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• v.31 no.4
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• pp.287-293
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• 2009

Long-term treatment with glucocorticoid leads to the development of osteoporosis and osteonecrosis. In contrast to the marked inhibitory effect of pharmacological doses of glucocorticoids on bone formation, the relationship between physiological concentrations of glucocorticoids and osteoprogenitor cell proliferation and phenotypes has not been elucidated yet. In addition, the effects of dexamethasone treatment on the proliferation and osteoblastic differentiation of osteoprogenitor cells are also controversial. The purpose of this study was to examine the effects of dexamethasone on the proliferation and osteoblastic differentiation of periosteal-derived cells. Periosteal-derived cells were obtained from mandibular periosteums and introduced into the cell culture. After passage 3, the cells were further cultured for 21 days in the osteogenic induction medium with different dexamethasone concentrations of 0, 10, and 100 nM. The proliferation and osteoblastic phenotypes of periosteal-derived cells were promoted in dexamethasone-treated cells than in untreated cells. Among the dexamethasone-treated cells, cell proliferation was slightly greater in 10 nM dexamethasone-treated cells than in 100 nM dexamethasone-treated cells. Histochemical staining and the bioactivity of alkaline phosphatase (ALP) were higher in 100 nM dexamethasone-treated cells than in 10 nM dexamethasone-treated cells. Similarly, von Kossa-positive mineralization nodules and calcium content were also more evident in 100 nM dexamethasone-treated cells than in 10 nM dexamethasone-treated cells. These results suggest that dexamethasone enhances the in vitro osteoblastic differentiation of periosteal-derived cells. The present study also demonstrates that higher dexamethasone concentrations reduce the in vitro proliferation of periosteal-derived cells.

• Journal of Ginseng Research
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• v.42 no.1
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• pp.116-121
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• 2018

Background: Black ginseng (BG) has greatly enhanced pharmacological activities relative to white or red ginseng. However, the effect and molecular mechanism of BG on muscle growth has not yet been examined. In this study, we investigated whether BG could regulate myoblast differentiation and myotube hypertrophy. Methods: BG-treated C2C12 myoblasts were differentiated, followed by immunoblotting for myogenic regulators, immunostaining for a muscle marker, myosin heavy chain or immunoprecipitation analysis for myogenic transcription factors. Results: BG treatment of C2C12 cells resulted in the activation of Akt, thereby enhancing hetero-dimerization of MyoD and E proteins, which in turn promoted muscle-specific gene expression and myoblast differentiation. BG-treated myoblasts formed larger multinucleated myotubes with increased diameter and thickness, accompanied by enhanced Akt/mTOR/p70S6K activation. Furthermore, the BG treatment of human rhabdomyosarcoma cells restored myogenic differentiation. Conclusion: BG enhances myoblast differentiation and myotube hypertrophy by activating Akt/mTOR/p70S6k axis. Thus, our study demonstrates that BG has promising potential to treat or prevent muscle loss related to aging or other pathological conditions, such as diabetes.

• Journal of Hospice and Palliative Care
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• v.19 no.3
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• pp.201-210
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• 2016

Delirium is a common symptom in patients with terminal cancer. The prevalence increases in the dying phase. Delirium causes negative effects on quality of life for both patients and their families, and is associated with higher mortality. However, some studies reported that it tends to remain unrecognized in palliative care setting. That may be related with difficulties to distinguish the symptom from others with overlapping characteristics such as depression and dementia, and a lack of knowledge regarding assessment and diagnostic tools. We suggest that accurate recognition with validated tools and early diagnosis of the symptom should be highly prioritized in delirium management in palliative care setting. After diagnosing delirium, it is important to identify and address reversible precipitants such as medication, dehydration, and infection. Non-pharmacological interventions including comfortable environment for the patient and family education are also essential in the management strategy. If such interventions prove ineffective or insufficient to control hyperactive symptoms, pharmacologic interventions with antipsychotics and benzodiazepine can be considered. Until now, low levels of haloperidol remains the standard treatment despite a lack of evidence. Atypical antipsychotics such as olanzapine, quetiapine and risperidone reportedly have similar efficacy with a stronger sedating property and less adverse effect compared to haloperidol. Currently, delirium medications that can be used in palliative care setting require more clinical trials, and thus, clinical guidelines are not sufficiently available. We suggest that it is warranted to develop clinical guidelines based on well-designed clinical studies for palliative care patients.

• Biomolecules & Therapeutics
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• v.7 no.2
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• pp.178-184
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• 1999

Bamboo salt has been used for the purpose of precaution and treatment of certain diseases including cancer. Therefore, present study was carried out to ascertain the effects of bamboo salt upon anti-cancer, anti-hypertensive, and anti-diabetic activities as well. To examine the anti-cancer activity of bamboo salt, ICR mice implanted with 1$\times$l0$^{6}$ cells of sarcoma 180 intraperitoneally had been treated daily with bamboo salt A, crude salt, and reagent-grade NaCl (0.2, 1.0, and 2.0 g/kg, p.o.) for 60 days using adriamycin (2 mg/kg) as a positive control. Neither survival rate nor body weight had been significantly influenced by all the treatments indicating that bamboo salt A did not exert the anti-cancer effect on ICR mice. Anti-hypertensive activity was examined in spontaneously hypertensive rats (SHR) which had been administered with bamboo salt A, crude salt, and reagent-grade NaCl (0.1, 0.5, and 1.0% in drinking water) for 28 days using hydralazin (2 mg/kg) as a positive control. Blood pressure and heart rate were measured at 1, 3, and 4 weeks after the starting date. Significant anti-hypertensive activity was not observed in any treated group compared to the positive control group. In order to determine if bamboo salt had anti-diabetic activity, rats in which diabetes had been induced by streptozotocin (45 mg/kg, i.m.) were treated daily with bamboo salt A, crude salt, and reagent-grade NaCl (0.2, 1.0, and 2.0 g/kg, p.o.) for 28 days using insulin (50 U/kg, s.c..) as a positive control. Blood samples were taken and analyzed at 1,2, and 4 weeks after the starting date. Bamboo salt did not cause any decreasing effect on the blood glucose levels. These results clearly demonstrated that bamboo salt A did not exert anti-cancer, anti-hypertensive, or anti-diabetic activities in the present experimental animals.

• Biomolecules & Therapeutics
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• v.22 no.1
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• pp.17-26
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• 2014

${\alpha}$-Asarone exhibits a number of pharmacological actions including neuroprotective, anti-oxidative, anticonvulsive, and cognitive enhancing action. The present study investigated the effects of ${\alpha}$-asarone on pro-inflammatory cytokines mRNA, microglial activation, and neuronal damage in the hippocampus and on learning and memory deficits in systemic lipopolysaccharide (LPS)-treated C57BL/6 mice. Varying doses of ${\alpha}$-asarone was orally administered (7.5, 15, or 30 mg/kg) once a day for 3 days before the LPS (3 mg/kg) injection. ${\alpha}$-Asarone significantly reduced TNF-${\alpha}$ and IL-$1{\beta}$ mRNA at 4 and 24 hours after the LPS injection at dose of 30 mg/kg. At 24 hours after the LPS injection, the loss of CA1 neurons, the increase of TUNEL-labeled cells, and the up-regulation of BACE1 expression in the hippocampus were attenuated by 30 mg/kg of ${\alpha}$-asarone treatment. ${\alpha}$-Asarone significantly reduced Iba1 protein expression in the hippocampal tissue at a dose of 30 mg/kg. ${\alpha}$-Asarone did not reduce the number of Iba1-expressing microglia on immunohistochemistry but the average cell size and percentage areas of Iba1-expressing microglia in the hippocampus were significantly decreased by 30 mg/kg of ${\alpha}$-asarone treatment. In the Morris water maze test, ${\alpha}$-asarone significantly prolonged the swimming time spent in the target and peri-target zones. ${\alpha}$-Asarone also significantly increased the number of target heading and memory score in the Morris water maze. The results suggest that inhibition of pro-inflammatory cytokines and microglial activation in the hippocampus by ${\alpha}$-asarone may be one of the mechanisms for the ${\alpha}$-asarone-mediated ameliorating effect on memory deficits.

• Journal of Life Science
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• v.18 no.6
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• pp.814-825
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• 2008

Ascochlorin (ASC) is prenyl-phenol compound that was isolated from the fungus Ascochyta viciae. ASC reduces serum cholesterol and triglyceride levels, and suppresses hypertension, tumor development, ameliorates type I and II diabetes. Here, to better understand the mechanisms by which ASC regulates physiological or pathological events and induces responses in the pharmacological treatment of inflammation, we performed differential analysis of the proteome of the mouse macrophage RAW264.7 cells in response to ASC. In this study, we used a proteomic analysis of LPS-induced RAW264.7 cells treated by ASC, to identify proteins potentially involved in inflammatory processes. The RAW264.7 cell proteomes with and without treatment with ASC were compared using two-dimensional electrophoresis (2-D SDS-PAGE), matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF-MS) and bioinformatics. The largest differences in expression were observed for the calreticulin (4-fold decrease), ${\beta}-actin$ (4-fold decrease) and vimentin (1.5-fold decrease). In addition, rabaptin was increased 3-fold in RAW264.7 cells treated with ASC. The expression of some selected proteins was confirmed by RT-PCR analysis.

• Journal of Pharmacopuncture
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• v.20 no.1
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• pp.52-56
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• 2017

Objectives: Neutrophils represent the front line of human defense against infections. Immediately after stimulation, neutrophilic enzymes are activated and produce toxic mediators such as pro-inflammatory cytokines, nitric oxide (NO) and myeloperoxidase (MPO). These mediators can be toxic not only to infectious agents but also to host tissues. Because flavonoids exhibit antioxidant and anti-inflammatory effects, they are subjects of interest for pharmacological modulation of inflammation. In the present study, the effects of rutin on stimulus-induced NO and tumor necrosis factor $(TNF)-{\alpha}$ productions and MPO activity in human neutrophils were investigated. Methods: Human peripheral blood neutrophils were isolated using Ficoll-Hypaque density gradient centrifugation coupled with dextran T500 sedimentation. The cell preparations containing > 98% granulocytes were determined by morphological examination through Giemsa staining. Neutrophils were cultured in complete Roswell Park Memorial Institute (RPMI) medium, pre-incubated with or without rutin ($25{\mu}M$) for 45 minutes, and stimulated with phorbol 12-myristate 13-acetate (PMA). Then, the $TNF-{\alpha}$, NO and MPO productions were analyzed using enzyme-linked immunosorbent assay (ELISA), Griess Reagent, and MPO assay kits, respectively. Also, the viability of human neutrophils was assessed using tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), and neutrophils were treated with various concentrations of rutin ($1-100{\mu}M$), after which MTT was appended and incubated at $37^{\circ}C$ for 4 hour. Results: Rutin at concentrations up to $100{\mu}M$ did not affect neutrophil viability during the 4-hour incubation period. Rutin significantly decreased the NO and $TNF-{\alpha}$ productions in human peripheral blood neutrophils compared to PMA-control cells (P < 0.001). Also, MPO activity was significantly reduced by rutin (P < 0.001). Conclusion: In this in vitro study, rutin had an anti-inflammatory effect due to its inhibiting NO and $TNF-{\alpha}$ productions, as well as MPO activity, in activated human neutrophils. Treatment with rutin may be considered as a therapeutic strategy for neutrophil-mediated inflammatory/autoimmune diseases.

• Korean Journal of Plant Resources
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• v.27 no.4
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• pp.271-278
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• 2014

Rubus coreanus has been used as a traditional medicine in Asia because of its various pharmacological properties. This study examined the effects of protocatechuic acid (PCA), one of phenolic compounds derived from R. coreanus on the lipid metabolism in high cholesterol diet-induced mice. A total of 30 male C57BL/6 mice were divided into 5 groups with 6 mice in each group as follows: (1) Control mice received normal diet (ND). (2) Mice received high-cholesterol diet (HCD) plus water, 10% sucrose solution and treated daily oral phosphate-buffered-saline (PBS) of equal volumes through gavage. (3) Mice received HCD and treated daily with 25 mg/kg b.w./day of PCA (4) with 50 mg/kg b.w./day or (5) with 10 mg/kg b.w./day of simvastatin via oral gavage for 12 weeks. Body weights were measured weekly for a period of experiment. After treatment, liver, thymus, spleen and kidney were harvested and weighed, and the lipid metabolite profiles (total cholesterol, triglyceride (TG), HDL-cholesterol (HDL-c), LDL-cholesterol (LDL-c) and liver-damaging markers (GOT and GPT) in serum were examined. PCA significantly reduced the total cholesterol, TG, LDL-c level and increased the HDL-c level. PCA administration also significantly reduced the levels of GOT and GPT. These results indicate that the PCA could be used as a functional material for lowering lipid and an adjuvant for the treatment of hyperlipemia.

• Journal of Life Science
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• v.25 no.3
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• pp.285-292
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• 2015

Citrus peel (CP) is used as a traditional herb with diverse beneficial pharmacological activities, such as anti-inflammatory, anti-oxidant, and anti-allergic effects. However, the anti-obesity effects of citrus peel are poorly defined. The aim of this study was to evaluate ethanol extracts of citrus peel (EECP) for its adipocyte differentiation and adipogenesis in 3T3-L1 preadipocytes. The aim of this study was to evaluate an EECP for its adipocyte differentiation and adipogenesis in 3T3-L1 preadipocytes. Treatment with EECP significantly suppressed the terminal differentiation of 3T3-L1 preadipocytes in a dose-dependent manner, as confirmed by a decrease in lipid droplet number and lipid content and an accumulation of cellular triglyceride. EECP exhibited potential adipogenesis inhibition and downregulated the expression of pro-adipogenic transcription factors, such as sterol regulatory elementbinding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancerbinding proteins α (C/EBPα) and C/EBPβ, and adipocyte expressed genes, such as adipocyte fatty acid binding protein (aP2) and Leptin. In addition, EECP treatment effectively activated the AMP-activated protein kinase (AMPK) signaling pathway; however, compound C, a specific inhibitor of AMPK, significantly reduced the EECP-induced inhibition of adipogenesis. Taken together, these results indicate EECP showed strong anti-obesity effects through the AMPK signaling pathway, and further studies will be needed to identify the active compounds that confer the anti-obesity activity of EECP.

• International Journal of Oral Biology
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• v.42 no.4
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• pp.183-190
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• 2017

Ficus carica L. (common fig), one of the first plants cultivated by humans, originated in the Mediterranean basin and currently grows worldwide, including southwest Asia and South Korea. It has been used as a traditional medicine for treatment of metabolic, cardiovascular, and respiratory diseases as well as hemorrhoids and skin infections. Its pharmacological properties have recently been studied in detail, but research on the anti-cancer effect of its latex has been only been studied on a limited basis on several cell lines, such prostate cancer, breast cancer, and leukemia. In this study, we investigated the anti-cancer activity of the latex of Ficus carica L.and its underlying mechanism in FaDu human hypopharynx squamous carcinoma cells. (See Ed. note above) We confirmed through SDS-PAGE analysis and gelatinolytic activity analysis that the latex of Ficus carica contains cysteine protease ficin. Our data showed that the latex inhibited cell growth in a dose-dependent manner. In addition, the latex treatment markedly induced apoptosis in FaDu cells as determined by FACS analysis, elevated expression level of cleaved caspase-9, -3 and PARP (poly (ADP-ribose) polymerase), and. increased the expression of Bax (pro-apoptotic factor) while decreasing the expression of Bcl-2 (anti-apoptotic factor). Taken together, these results suggested that latex containing the ficin inhibited cell growth and induced apoptosis by caspase and the Bcl-2 family signaling pathway in FaDu human hypopharynx squamous carcinoma cells. These findings point to the potential of latex of Ficus carica to provide a novel chemotherapeutic drug due to its growth inhibition effects and induction of apoptosis in human oral cancer cells.