• Microbiology and Biotechnology Letters
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• v.40 no.4
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• pp.371-379
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• 2012

This study was designed to explore new nutraceutical and cosmetic resources possessing biological activities from the plant kingdom. To fulfill this purpose, we analyzed the anti-oxidative, anti-melanogenic, and anti-inflammatory activities of Zanthoxylum schinifolium extract (ZSE) and its solvent fractions using in vitro assays and cell culture model systems. Three kinds of ZSE treated with methanol, ethanol, and water exhibited potent anti-oxidative activities through DPPH radical scavenging capacity, and inhibited in vitro DOPA oxidation. Furthermore, Z. schinifolium methanol extract (ZSME) inhibited the ${\alpha}$-melanocyte stimulating hormone, which induces melanin contents in B16F10 cells. Its anti-melanogenic activity originates from the inhibition of tyrosinase enzyme activity and melanogenesis related protein expression. Moreover, lipopolysaccharide induced nitric oxide production in the RAW 264.7 cell line was also ameliorated by ZSME treatment in a dose dependent manner. Among the four solvent fractions of ZSME treated with dichloromethane, ethyl acetate, n-butanol, and water, three fractions, except water, showed significant anti-melanogenic and anti-inflammatory activities. Taken together, these results provide important new insights into Z. schinifolium, indicating that it possesses numerous biological activities such as anti-oxidative, anti-melanogenic, and anti-inflammatory activities. Therefore, it may well serve as a promising material in the field of nutraceuticals and cosmetics.

• Tuberculosis and Respiratory Diseases
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• v.79 no.3
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• pp.143-152
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• 2016

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the accumulation of excessive fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor ${\beta}1$ (TGF-${\beta}1$)-induced epithelial-to-mesenchymal transition (EMT) is thought to be a possible source of fibroblasts/myofibroblasts in IPF lungs. We have previously reported that apolipoprotein A1 (ApoA1) has anti-fibrotic activity in experimental lung fibrosis. In this study, we determine whether ApoA1 modulates TGF-${\beta}1$-induced EMT in experimental lung fibrosis and clarify its mechanism of action. Methods: The A549 alveolar epithelial cell line was treated with TGF-${\beta}1$ with or without ApoA1. Morphological changes and expression of EMT-related markers, including E-cadherin, N-cadherin, and ${\alpha}$-smooth muscle actin were evaluated. Expressions of Smad and non-Smad mediators and TGF-${\beta}1$ receptor type 1 ($T{\beta}RI$) and type 2 ($T{\beta}RII$) were measured. The silica-induced lung fibrosis model was established using ApoA1 overexpressing transgenic mice. Results: TGF-${\beta}1$-treated A549 cells were changed to the mesenchymal morphology with less E-cadherin and more N-cadherin expression. The addition of ApoA1 inhibited the TGF-${\beta}1$-induced change of the EMT phenotype. ApoA1 inhibited the TGF-${\beta}1$-induced increase in the phosphorylation of Smad2 and 3 as well as that of ERK and p38 mitogen-activated protein kinase mediators. In addition, ApoA1 reduced the TGF-${\beta}1$-induced increase in $T{\beta}RI$ and $T{\beta}RII$ expression. In a mouse model of silica-induced lung fibrosis, ApoA1 overexpression reduced the silica-mediated effects, which were increased N-cadherin and decreased E-cadherin expression in the alveolar epithelium. Conclusion: Our data demonstrate that ApoA1 inhibits TGF-${\beta}1$-induced EMT in experimental lung fibrosis.

• Food Science of Animal Resources
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• v.33 no.3
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• pp.411-416
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• 2013

This study aimed to examine the mechanisms underlying the effects of Garcinia cambogia extract on the adipogenic differentiation of 3T3-L1 cells and long-chain saturated fatty acid-induced lipotoxicity of HepG2 cells. 3T3-L1 preadipocytes, mouse embryonic fibroblast-adipose like cell line, were treated with MDI solution (0.5 mM IBMX, 1 ${\mu}M$ dexamethasone, 10 ${\mu}g/mL$ insulin) to generate a cellular model of adipocyte differentiation. Using this cellular model, the anti-obesity effect of Garcinia cambogia extract was evaluated. MDI-induced lipid accumulation and expression of adipogenesis-related genes were detected by Oil red O staining, Nile Red staining, and Western blot analysis. Effects Garcinia cambogia extract on palmitate-induced lipotoxicity was also analyzed by MTT assay, LDH release, and DAPI staining in HepG2 cells. Garcinia cambogia extract significantly suppressed the adipogenic differentiation of preadipocytes and intracellular lipid accumulation in the differentiating adipocytes. Garcinia cambogia extract also markedly inhibited the expression of peroxisome proliferator- activated receptor ${\gamma}2$ ($PPAR{\gamma}2$), CCAT/enhancer-binding protein ${\alpha}$ ($C/EBP{\alpha}$), and adipocyte protein aP2 (aP2). In addition, Garcinia cambogia extract significantly attenuated palmitate-induced lipotoxicity in HepG2 cells. Palmitateinduced cellular damage and reactive aldehydes were also significantly reduced in the presence of Garcinia cambogia extract. These findings suggest that the Garcinia cambogia extract inhibits the adipogenic differentiation of 3T3-L1 preadipocytes, probably by regulating the expression of multiple genes associated with adipogenesis such as $PPAR{\gamma}2$, $C/EBP{\alpha}$, aP2, and thereby modulating fatty acid-induced lipotoxicity to reduce cellular injury in hepatocytes.

• Journal of Korean Medicine Rehabilitation
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• v.19 no.2
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• pp.73-88
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• 2009

Objectives : Neuronal changes that result from treadmill exercise for patients with Parkinson's disease(PD) have not been well documented, although some clinical and laboratory reports suggest that regular exercise may produce a neuroprotective effect and restore dopaminergic and motor functions. However, it is not clear if the improvements are due to neuronal alterations within the affected nigrostriatal region or result from a more general effect of exercise on affect areas and motivation. In this study, we demonstrate that motorized treadmill exercise improves the neuronal outcomes in rodent models of PD. Methods : We used a chronic mouse model of parkinsonism, which was induced by injecting male C57BL/6 mice with 10 doses(Every 12 hour) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (30 mg/kg) and probenecid (20 mg/kg) over 5 days. These mice were able to sustain an exercise training program on a motorized rodent treadmill at a speed of 18 m/min, $0^{\circ}$ of inclination, 40 min/day, 5 days/week for 4 weeks. At the end of exercise training, we extracted the brain and compared their neuronal and neurochemical changes with the control(saline and sedentary) mice groups. Synphilin protein is the substance that manifestly reacts with ${\alpha}$-synuclein. In this study, we used Synphilin as a manifest sign of recovery from neurodegeneration. We analyze the brain stems of the substantia nigra and striatum region using the western blotting technique. Results : There were no expression of synphilin in the saline-induced groups. The addition of MPTP(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) greatly accelerated synphilin expression which meant an aggregation of ${\alpha}$-synuclein. But, the MPTP-induced treadmill exercise group showed significantly lower expression than the MPTP-induced sedentary group. This means treadmill exercise has a definite effect on the decrease of ${\alpha}$-synuclein aggregation. Conclusions : In this study, our results suggest that treadmill exercise promoted the removal of the aggregation of ${\alpha}$-synuclein, resulting in protection against disease development and blocks the apoptotic process in the chronic parkinsonian mice brain with severe neurodegeneration.

• Journal of the Korean Applied Science and Technology
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• v.37 no.3
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• pp.418-428
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• 2020

The aim of this study was to investigate the effect of resistance exercise(RE) on beta-amyloid(Aβ) metabolism, neuronal cell death, and cognitive function in the transgenic mice model of Alzheimer's disease(AD). Fourteen transgenic(tg) mice and fourteen non-transgenic(non-tg) mice were divided into four groups: (1)non-tg-control(NTC, n=7) (2)non-tg-RE(NTRE, n=7) (3)tg-control(TC, n=7), and (4)tg-RE(TRE, n=7). The groups with RE were performed to progressive RE on ladder equipment for 8 weeks. The groups with RE were performed to progressive RE on ladder equipment for 8 weeks. After then, the cognitive function was measured by using the water maze test, and Aβ metabolism-related proteins, neuronal cell death, and SIRT1/PGC-1α pathway were also measured. Here, we found escape latency and time were significantly increased in the TC compared to the NTC group, but it was significantly reduced in the TRE group, indicating RE may ameliorate cognitive dysfunction. Next, we found an increased in Aβ protein of TC compared to NTC, but it was significantly reduced in the TRE group following RE. In neuronal cell death, Bcl-2 was also significantly decreased and Bax was significantly increased in the TC compared to the NTC group, but RE can increase Bcl-2 and reduce Bax, which may elevate the ratio of Bcl-2/Bax. We further found a decrease in the level of ADAM10 and RARβ protein was significantly increased whereas increased in ROCK1 and BACE1 expression level was significantly reduced following RE in the TRE compared to the TC group. In addition, the level of SIRT1/PGC-1α proteins was decreased in the TC group compared to NTC group, but, these markers were significantly increased in the TRE group following RE. Therefore, our finding indicated that RE may ameliorate cognitive deficits by reducing Aβ protein and neuronal cell death via regulating SIRT1/PGC-1α, amyloidogenic pathway, and non-amyloidogenic pathway, which may play a role in an effective strategy for AD.

• Food Science and Preservation
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• v.24 no.8
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• pp.1149-1157
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• 2017

Inflammation is the first response of the immune system to infection or irritation in our body. The use of medicinal plants has been widely applied as an alternative source for drug development. One of marine natural resources, the anti-inflammatory effect of Ishige sinicola ethanol extract (ISEE), was evaluated by using LPS-induced RAW 264.7 cell and mice model. As a result, the production of nitric oxide (NO) and pro-inflammatory cytokines (IL-6, IL-$1{\beta}$, TNF-${\alpha}$) were inhibited with increasing concentration of ISEE without any cytotoxicity. Furthermore, ISEE suppressed the expression of not only inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-kappa B (NF-${\kappa}B$) p65, and mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK) 1/2, p38, and c-Jun N-terminal kinase (JNK) in a dose-dependent manner. In mice ear edema test, the formation of edema was reduced at the highest dosage of ISEE and the reduction of the number of infiltrated mast cells was observed in histological analysis. These results indicate that ISEE has a potent anti-inflammatory activity and can be used as a pharmaceutical material for many kinds of inflammatory disease.

• Tuberculosis and Respiratory Diseases
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• v.65 no.3
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• pp.177-182
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• 2008

Background: Isoniazid (INH, H) is a key drug of the standard first-line regimen for the treatment of tuberculosis (TB), yet some reports have suggested that treatment efficacy was maintained even though INH was omitted from the treatment regimen. Methods: One hundred forty C57BL/6 mice were infected with the H37Rv strain of M. tuberculosis with using a Glas-Col aerosol generation device, and this resulted in depositing about 100 bacilli in the lung. Four weeks after infection, anti-TB treatment was initiated with varying regimens for 4-8 weeks; Group 1: no treatment (control), Group 2 (4HREZ): 4 weeks of INH, rifampicin (R), pyrazinamide (Z) and ethambutol (E), Group 3: 1HREZ/3REZ, Group 4: 4REZ, Group 5: 4HREZ/4HRE, Group 6: 1HREZ/3REZ/4RE, and Group 7: 4REZ/4RE. The lungs and spleens were harvested at several time points until 28 weeks after infection, and the colony-forming unit (CFU) counts were determined. Results: The CFU counts increased steadily after infection in the control group. In the 4-week treatment groups (Group 2-4), even though the culture was negative at treatment completion, the bacilli grew again at the 12-week and 20-week time points after completion of treatment. In the 8-week treatment groups (Groups 5-7), the bacilli did not grow in the lung at 4 weeks after treatment initiation and thereafter. In the spleens of Group 7 in which INH was omitted from the treatment regimen, the culture was negative at 4-weeks after treatment initiation and thereafter. However, in Groups 5 and 6 in which INH was taken continuously or intermittently, the bacilli grew in the spleen at some time points after completion of treatment. Conclusion: TThe exclusion of INH from the standard first-line regimen did not affect the treatment outcome in a murine model of TB in the early stage of disease. Further studies using a murine model of chronic TB are necessary to clarify the role of INH in the standard first-line regimen for treating TB.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.4
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• pp.218-227
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• 2006

Purpose: The HSV1-tk reporter gene system is the most widely used system because of its advantage that direct monitoring is possible without the introduction of a separate reporter gene in case of HSV1-tk suicide gene therapy. In this study, we investigate the usefulness of the reporter probe (substrate), $9-(4-[^{18}F]Fluoro-3-hydroxymethylbutyl)$guanine ($[^{18}F]FHBG$) for non-invasive reporter gene imaging using PET in HSV1-tk expressing hepatoma model. Materials and Methods: Radiolabeled FHBG was prepared in 8 steps from a commercially available triester. The labeling reaction was carried out by NCA nucleophilic substitution with $K[^{18}F]/K2.2.2.$ in acetonitrile using N2-monomethoxytrityl-9-14-(tosyl)-3-monomethoxytritylmethylbutyl]guanine as a precursor, followed by deprotection with 1 N HCl. Preliminary biological properties of the probe were evaluated with MCA cells and MCA-tk cells transduced with HSV1-tk reporter gene. In vitro uptake and release-out studies of $[^{18}F]FHBG$ were performed, and was analyzed correlation between $[^{18}F]FHBG$ uptake ratio according to increasing numeric count of MCA-tk cells and degree of gene expression. MicroPET scan image was obtained with MCA and MCA-tk tumor bearing Balb/c-nude mouse model. Results: $[^{18}F]FHBG$ was purified by reverse phase semi-HPLC system and collected at around 16-18 min. Radiothemical yield was about 20-25%) (corrected for decay), radiochemical purity was >95% and specific activity was around >55.5 $GBq/{\mu}\;mol$. Specific accumulation of $[^{18}F]FHBG$ was observed in HSV1-tk gene transduced MCA-tk cells but not in MCA cells, and consecutive 1 hour release-out results showed more than 86% of uptaked $[^{18}F]FHBG$ was retained inside of cells. The uptake of $[^{18}F]FHBG$ was showed a highly significant linear correlation ($R^2=0.995$) with increasing percentage of MCA-tk numeric cell count. In microPET scan images, remarkable difference of accumulation was observed for the two type of tumors. Conclusion: $[^{18}F]FHBG$ appears to be a useful as non-invasive PET imaging substrate in HSV1-tk expressing hepatoma model.

• Journal of Life Science
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• v.20 no.4
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• pp.607-613
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• 2010

Osteoporosis is a disease involving a decrease in bone mineral density and an increased risk of fractures. The MC3T3-E1 pre-osteoblastic cell line is a well-accepted model of osteogenesis in vitro. Pine needles have long been used as a traditional health-promoting medicinal food in Korea. In this study, MTT assay, the alkaline phosphatase (ALP) activity and collagen synthesis of osteoblast cells were investigated to determine the effects of pine needle extracts on cell proliferation and differentiation. Pine needle extracts were prepared using hexane, ethanol and water. The effects of the pine needle extracts were examined by comparing the results with those of commercial agents, such as proanthocyanidin. The MC3T3-E1 cells exposed to proanthocyanidin showed increased proliferation in a concentration-dependent manner. The cells exposed to the hexane extract showed a similar increase in proliferation to that observed with proanthocyanidin. The hexane extract showed the highest ALP activity. Moreover, a supplement of pine needle extracts induced collagen synthesis in MC3T3-E1 cells. The pine needle extract produced the highest level of collagen synthesis at concentrations of $10{\sim}50\;{\mu}g/ml$. These results indicate that pine needle extracts have an anabolic effect on bone by promoting osteoblastic differentiation, and may be used in the treatment of common metabolic bone diseases.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.8
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• pp.1121-1127
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• 2015

This study investigated the effects of Myagropsis myagroides ethanol extract (MMEE) on 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD)-like skin lesions in BALB/c mice. The effects of MMEE on DNCB-induced BALB/c mice were evaluated by examining skin symptom severity, levels of total immunoglobulin E (IgE), tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), interleukin (IL)-4, and IL-10 in serum, and levels of IL-4, IL-5, IL-13, and $interferon-{\gamma}$ ($IFN-{\gamma}$) in splenocytes. MMEE significantly reduced the total clinical severity score, total IgE levels, as well as $TNF-{\alpha}$ and IL-4 production in an AD mouse model but increased IL-10 production. Production of IL-4, IL-5, and IL-13 in splenocytes was reduced by MMEE, whereas $IFN-{\gamma}$ production increased. These results suggest that MMEE can inhibit the development of AD-like skin lesions in BALB/c mice by modulating the immune response and may be an effective potential therapeutic agent for AD.