• Journal of Life Science
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• v.27 no.1
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• pp.78-88
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• 2017

Angiogenesis, the formation of new blood vessels, plays an important role in tumor growth and metastasis; therefore, it has become an important target in cancer therapy. Novel anticancer pharmaceutical products that have relatively few side effects or are non-cytotoxic must be developed, and such products may be obtained from traditional herbal medicines. Coptis chinensis Franch. is an herb used in traditional medicine for the treatment of inflammatory diseases and diabetes. However, potential antiangiogenic effects of C. chinensis water extract (CCFWE) have not yet been studied. The purpose of this study was to determine the antiangiogenic effect of CCFWE in order to evaluate its potential for an anticancer drug. We found that the treatment with CCFWE inhibited the major steps of the angiogenesis process, such as the endothelial cell proliferation, migration, invasion, and capillary-like tube formation in response to vascular endothelial growth factor (VEGF), and also resulted in the growth inhibition of new blood vessels in an ex vivo rat aortic ring assay. We also observed that CCFWE treatment arrested the cell cycle at the G0/G1 phase, preventing the G0/G1 to S phase cell cycle progression in response to VEGF. In addition, the treatment reduced the VEGF-induced activation of matrix metalloproteinases 2 and 9. Taken together, these findings indicate that CCFWE should be considered a potential anticancer therapy against pathological conditions where angiogenesis is stimulated during tumor development.

• The Korea Journal of Herbology
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• v.34 no.4
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• pp.27-35
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• 2019

Objectives : Osteoarthritis is characterized by degeneration of articular cartilage, which is characterized by chronic pain, stiffness and decrease range of motion. The present study was designed to compare the therapeutic effect of Dioscoreae Rhizoma water extract (DRW) and Dioscoreae Rhizoma 30% ethanol extract (DRE) on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Methods : Osteoarthritis was induced by injection of MIA ($50{\mu}{\ell}$ with $80mg/m{\ell}$) into the knee joint cavity of rats. After adaptation period for seven days, rats were divided by 5 groups (n=10/group): normal group, control group, positive control (indomethacin 5 mg/kg), DRW 200 mg/kg treated group, DRE 200 mg/kg treated group (n=10/group). The hind paw weight distribution was measured with the changes of reactive oxygen species (ROS), peroxynitrite ($ONOO^-$) in articulation tissue. Also, the cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factoralpha ($TNF{\alpha}$), interleukin-6 (IL-6), matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of metalloproteinases-1 (TIMP-1) were investigated by western blot analysis. Results : The administration of DRW and DRE significantly decreased the hind paw weight distribution. The ROS and $ONOO^-$ levels of cartilaginous tissue were significantly decreased in DRW and DRE compared to control group. The results showed that DRE decreased inflammatory cytokines such as iNOS and $TNF{\alpha}$. Also DRE decreased MMP-1 and increased TIMP-1. Conclusions : Based on the above results, Dioscoreae Rhizoma extract seems to have the therapeutic effect on osteoarthritis via suppression of inflammation.

• Restorative Dentistry and Endodontics
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• v.33 no.2
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• pp.148-161
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• 2008

The purpose of this study was to evaluate the effect of chlorhexidine (CHX) on microtensile bond strength (${\mu}TBS$) of dentin bonding systems. Dentin collagenolytic and gelatinolytic activities can be suppressed by protease inhibitors, indicating that MMPs (Matrix metalloproteinases) inhibition could be beneficial in the preservation of hybrid layers. Chlorhexidine (CHX) is known as an inhibitor of MMPs activity in vitro. The experiment was proceeded as follows: At first, flat occlusal surfaces were prepared on mid-coronal dentin of extracted third molars. GI (Glass Ionomer) group was treated with dentin conditioner, and then, applied with 2 % CHX. Both SM (Scotchbond Multipurpose) and SB (Single Bond) group were applied with CHX after acid-etched with 37% phosphoric acid. TS (Clearfil Tri-S) group was applied with CHX, and then, with adhesives. Hybrid composite Z-250 and resin-modified glass ionomer Fuji-II LC was built up on experimental dentin surfaces. Half of them were subjected to 10,000 thermocycle, while the others were tested immediately. With the resulting data, statistically two-way ANOVA was performed to assess the ${\mu}TBS$ before and after thermo cycling and the effect of CHX. All statistical tests were carried out at the 95 % level of confidence. The failure mode of the testing samples was observed under a scanning electron microscopy (SEM). Within limited results, the results of this study were as follows; 1. In all experimental groups applied with 2 % chlorhexidine, the microtensile bond strength increased, and thermo cycling decreased the micro tensile bond strength (P > 0.05). 2. Compared to the thermocycling groups without chlorhexidine, those with both thermocycling and chlorhexidine showed higher microtensile bond strength, and there was significant difference especially in GI and TS groups. 3. SEM analysis of failure mode distribution revealed the adhesive failure at hybrid layer in most of the specimen. and the shift of the failure site from bottom to top of the hybrid layer with chlorhexidine groups. 2 % chlorhexidine application after acid-etching proved to preserve the durability of the hybrid layer and microtensile bond strength of dentin bonding systems.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.5
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• pp.697-704
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• 2013

The inhibitory effect of ethanol extracts from Curdrania tricuspidata leaves (CTL) on osteoarthritis was investigated in primary cultured rat cartilage cells and a monosodium-iodoacetate (MIA)-induced arthritis rat model. To identify the effects of CTL 80% ethanol extracts (CTL80) and CTL 10% ethanol extracts (CTL10) against $H_2O_2$ treatment in vitro, cell survival was measured by the MTT assay. Cell survival after $H_2O_2$ treatment increased with CTL80 and CTL10 close to normal up to $300{\mu}g/mL\;H_2O_2$. The mRNA expression of matrix metalloproteinases (MMPs) was determined MMP-7 and MMP-13 (known catabolic factors), were significantly inhibited by CTL 80 and CTL10; a $200{\mu}g/mL$ dose of CTL80 especially decreased MMP-13 expression. In vivo, osteoarthritis was induced by an intra-articular injection of MIA into the knee joints of rats, then CTL80 and CTL10 orally administered daily for 35 days. After the animals were sacrificed, histological evaluations of their knee joints revealed a reduction in polymorphonuclear cell infiltration and smooth synovial lining in the CTL80-500 group. Micro-CT analysis of hind paws from CTL80-500 and CTL10 showed a protection against osteophyte formation, soft tissue swelling, and bone resorption. In conclusion, CTL ethanol extracts are effective in ameliorating joint destruction and cartilage erosion in MIA-induced rats. CTL decreases and normalizes articular cartilage through preventing extracellular matrix degradation and chondrocyte injury, and could potentially serve as a therapeutic treatment for humans.

• Journal of Life Science
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• v.20 no.4
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• pp.528-534
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• 2010

Garlic (Allium sativum) has been well-known as a folk remedy for a variety of ailments since ancient times, and it is well documented that enhanced garlic consumption leads to a decrease in incidences of cancer. Tight junctions (TJs) are critical structures for the maintenance of cellular polarity, acting as paracellular permeability barriers and playing an essential role in regulating the diffusion of fluid, electrolytes and macromolecules through the paracellular pathway. Matrix metalloproteinases (MMPs) have been implicated as possible mediators of invasiveness and metastasis in some cancers. In this study, we investigated the potential effects of water extract of aged black garlic (ABG) on the correlation between tightening of TJs and anti-invasive activity in human gastric carcinoma AGS cells. The inhibitory effects of ABG on cell motility and invasiveness were found to be associated with increased tightness of TJs, which was demonstrated by an increase in transepithelial electrical resistance. Additionally, the activities of MMP-2 and -9 in AGS cells were inhibited by treatment with ABG, and this was also correlated with a decrease in the expression of their mRNA and proteins. Furthermore, RT-PCR and immunoblotting results indicated that ABG repressed the levels of the claudin proteins, major components of TJs that play a key role in the control and selectivity of paracellular transport. In conclusion, these results suggest that ABG treatment may inhibit tumor metastasis and invasion, and therefore may act as a dietary source to decrease the risk of developing cancer.

• Korean Journal of Food Science and Technology
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• v.41 no.6
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• pp.700-705
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• 2009

Several studies have demonstrated that chlorophyll has many beneficial properties, including anti-inflammatory, anti-tumor, and antioxidant properties. Chlorophyll has been also shown to have an excellent chemopreventive potential against skin tumor. Its preventive mechanism against skin tumor, however, has not been examined in detail. Furthermore, the effects of chlorophyll on UVB-induced cellular responses have not been investigated. Solar UV radiation, in particular its UVB component, is the primary cause of many adverse biological effects, which is responsible for the photoaging and skin cancer. We investigated the preventive effects of chlorophyll a on UVB-mediated responses in human immortalized HaCaT kerationocytes and normal human fibroblast. We found that treatment of chlorophyll a markedly inhibited UVB-induced generation of reactive oxygen species and lipid peroxidation. Chlorophyll a also prevented UVB-induced MMP-1 expression and MMP-2 activation and increased Type I pN collagen synthesis. These results suggest that chlorophyll a is a potent candidate for the prevention and treatment of UVB-induced skin cancer and photoaging.

• Tuberculosis and Respiratory Diseases
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• v.56 no.3
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• pp.289-296
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• 2004

Background : Mucus hypersecretion in the patients with airway diseases represents poor prognosis as well as discomfort. However, there is no known therapy for its effective control. One important component of mucus is mucin, a glycosylated protein, which endows mucus with viscosity. We studied whether a proteinase has a role in mucin secretion and if so, which. Methods : (1) Inhibition of mucin secretion Group-specific proteinase inhibitors were tested to evaluate whether a proteinase belonging to a group of proteinases plays a role in mucin secretion. Phenylmethylsulfonyl fluoride(PMSF, a serine proteinase inhibitor), E-64(a cysteine proteinase inhibitor), Pepstatin(an aspartic proteinase inhibitor) and 1, 10-Phenanthroline(a metalloproteinase inhibitor) were treated into the Calu-3 cell line for 24 hours. The enzyme linked immunoabsorbant assay(ELISA) for MUC5AC was performed to evaluate the amount of mucin secretion and to compare with a control. (2) Stimulation of mucin secretion Matrix metalloproteinase-9(MMP-9), MMP-12 and TACE(TNF-alpha converting enzyme), which are known to be related with airway diseases, were used to be treated into Calu-3 for 24 hours. ELISA for MUC5AC was performed to evaluate the amount of mucin secretion and to compare with the controls. Results : (1) PMSF($10^{-4}M$), E-64($10^{-4}M$), Pepstatin($10^{-6}M$) and 1, 10-Phenanthroline($10^{-4}M$) reduced the MUC5AC secretion by $1{\pm}4.9%$(mean${\pm}$standard deviation; P=1.0 compared with the control), $-6{\pm}3.9%$(P=0.34), $-13{\pm}9.7%$(P=0.34) and $41{\pm}8.2%$(P=0.03), respectively. (2) The amounts of MUC5AC secretion stimulated by MMP-9(250ng/ml), MMP-12(100ng/ml) and TACE(200ng/ml) were $103{\pm}6%$(P=0.39), $102{\pm}8%$(P=1.0) and $107{\pm}13%$(P=0.39), respectively, compared with the controls. Conclusion : Metalloproteinase(s) is (are) suggested to play a role in mucin secretion. It appears that metalloproteinases, other than MMP-9, MMP-12 or TACE, affect the mucin secretion in this in vitro model.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.30 no.4 s.48
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• pp.439-444
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• 2004

UV irradiation produces free radicals and related reactive oxygen species (ROS), and these are injury to all most of organisms of skin cells and extracellular matrix (ECM). In addition, free radicals and ROS stimulate the overexpression of matrix metalloproteinases (MMPs) that can degrade most components of ECM such as collagen. Since collagen constitutes almost of skin connective tissue, their disarrangement causes wrinkle formation and droop of skin. Therefore, scavenging activity on free radicals, ROS and suppression of MMP-1 is expected to prevent skin photoaging. In this study, to investigate the relationship between photoaging and Draconis sanguis, we examined the effects of antioxidant, in vitro MMP inhibition and expression of UVA-induced MMP-1 in human dermal fibroblasts. Draconis sanguis was found to show scavenging activities of radicals and ROS with the $IC_{50}$ values of $183{\;}{\mu}g/mL$ against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and $30{\;}{\mu}g/mL$ against superoxide radicals in the xanthine/xanthine oxidase system, respectively. Draconis sunguis inhibited the activities of MMP-1 in a does-dependent manner and the $IC_{50}$ value calculated from semi-log plots was $200{\;}{\mu}g/mL$. Also, UVA induced MMP expression was reduced $74\%$ by treatment with Draconis sanguis, and MMP-1 mRNA expression was reduced in a dose-dependent manner. Therefore Draconis sanguis was able to significantly inhibit MMP expression in protein and mRNA level. All these results suggested that Draconis sanguis may act as an anti-photoaging agent by antioxidation and reducing UVA-induced MMP-1 production.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.5
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• pp.631-640
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• 2014

The inhibitory effects of Boswellia serrata (BW) extracts on degenerative osteoarthritis were investigated in primary-cultured rat cartilage cells and a monosodium-iodoacetate (MIA)-induced osteoarthritis rat model. To identify the protective effects of BW extract against $H_2O_2$ ($800{\mu}M$, 2 hr) in vitro, cell survival was measured by MTT assay. Cell survival after $H_2O_2$ treatment was elevated by BW extract at a concentration of $20{\mu}g/mL$. In addition, BW extract treatment significantly reduced and normalized the productions of pro-inflammatory factors, nuclear transcription factor ${\kappa}B$, cyclooxygenase-2, tumor necrosis factor-${\alpha}$, and interleukin-6 at a concentration of $20{\mu}g/mL$. Treatment of chondrocytes with BW extract significantly reduced 5-lipoxygenase activity and production of prostaglandin E2, especially at a concentration of $10{\sim}20{\mu}g/mL$. For the in vivo animal study, osteoarthritis was induced by intra-articular injection of MIA into knee joints of rats. Consumption of a diet containing BW extract (100 and 200 mg/kg) for 35 days significantly inhibited the development and severity of osteoarthritis in rats. To determine the genetic expression of arthritic factors in articular cartilage, real-time PCR was applied to measure matrix metalloproteinases (MMP-3, MMP-9, and MMP-13), collagen type I, collagen type II, and aggrecan, and BW extract had protective effects at a concentration of 200 mg/kg. In conclusion, BW extract was able to inhibit articular cartilage degeneration by preventing extracellular matrix degradation and chondrocyte injury. One can consider that BW extract may be a potential therapeutic treatment for degenerative osteoarthritis.

• Journal of Life Science
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• v.33 no.6
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• pp.498-505
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• 2023

Solanum tuberosum Linnaeus cv Hongyoung, which represents red potato, was developed in Korea. Hongyoung is known to have anti-oxidant, anti-inflammatory, anti-viral, and anti-tumor properties, but no research has been conducted on the growth inhibition and apoptosis effects of hongyoung in YD-10B oral cancer cells. In this study, the combined treatment of hongyoung ethanol extract (HEE) and cisplatin were examined to determine its ability to inhibit cancer cell growth, induce apoptosis, and inhibit matrix metalloproteinases (MMP)-2 and MMP-9 cancer metastasis. The cell viability was investigated using a 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H- tetrazolium monosodium salt (MTS) assay, and the ability to induce apoptosis was analyzed using an FACS analyzer. The mRNA expression and protein activity of MMP-2 and MMP-9 were measured via RT-PCR and zymography. The YD-10B oral cancer cells showed an increase in growth inhibition as the concentration of HEE increased. The combination of 200 µM cisplatin and 500 ㎍/ml HEE reduced the growth of the YD-10B oral cancer cells by more than 50% compared to cisplatin alone. When phorbol 12-myristate 13-acetate (PMA)-treated YD-10B oral cancer cells were co-treated with 200 µM cisplatin and 500 ㎍/ml HEE, both the mRNA expression and protein activity of the MMP-2 and MMP-9 decreased. In addition, the percentage of the sub-G1 phase, which indicates apoptosis ability, more than doubled when treated in combination with 200 µM cisplatin and 500 ㎍/ml HEE than when cisplatin alone was used. The results of this study therefore suggest the possibility of using a combination of HEE and cisplatin in the development of effective drugs to treat oral cancer.