• Maxillofacial Plastic and Reconstructive Surgery
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• v.40
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• pp.44.1-44.17
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• 2018

Background: Coffee extract has been investigated by many authors, and many minor components of coffee are known, such as polyphenols, diterpenes (kahweol and cafestol), melanoidins, and trigonelline, to have anti-inflammatory, anti-oxidant, anti-angiogenic, anticancer, chemoprotective, and hepatoprotective effects. Therefore, it is necessary to know its pharmacological effect on hepatocytes which show the most active cellular regeneration in body. Methods: In order to determine whether coffee extract has a beneficial effect on the liver, 20 C57BL/6J mice were intraperitoneally injected once with dialyzed coffee extract (DCE)-2.5 (equivalent to 2.5 cups of coffee a day in man), DCE-5, or DCE-10, or normal saline (control), and then followed by histological observation and IP-HPLC (immunoprecipitation high performance liquid chromatography) over 24 h. Results: Mice treated with DCE-2.5 or DCE-5 showed markedly hypertrophic hepatocytes with eosinophilic cytoplasms, while those treated with DCE-10 showed slightly hypertrophic hepatocytes, which were well aligned in hepatic cords with increased sinusoidal spaces. DCE induced the upregulations of cellular proliferation, growth factor/RAS signaling, cellular protection, p53-mediated apoptosis, angiogenesis, and antioxidant and protection-related proteins, and the downregulations of NFkB signaling proteins, inflammatory proteins, and oncogenic proteins in mouse livers. These protein expression changes induced by DCE were usually limited to the range ± 10%, suggesting murine hepatocytes were safely reactive to DCE within the threshold of physiological homeostasis. DCE-2.5 and DCE-5 induced relatively mild dose-dependent changes in protein expressions for cellular regeneration and de novo angiogenesis as compared with non-treated controls, whereas DCE-10 induced fluctuations in protein expressions. Conclusion: These observations suggested that DCE-2.5 and DCE-5 were safer and more beneficial to murine hepatocytes than DCE-10. It was also found that murine hepatocytes treated with DCE showed mild p53-mediated apoptosis, followed by cellular proliferation and growth devoid of fibrosis signaling (as determined by IP-HPLC), and subsequently progressed to rapid cellular regeneration and wound healing in the absence of any inflammatory reaction based on histologic observations.

• Asian-Australasian Journal of Animal Sciences
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• v.32 no.2
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• pp.217-223
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• 2019

Objective: An experiment was conducted to investigate the effects of feed intake restriction during late pregnancy on the function, anti-oxidation capability and acute phase protein synthesis of ovine liver. Methods: Eighteen time-mated ewes with singleton fetuses were allocated to three groups: restricted group 1 (RG1, 0.18 MJ ME/kg $W^{0.75}$ d, n = 6), restricted group 2 (RG2, 0.33 MJ ME/kg $W^{0.75}$ d), n = 6) and a control group (CG, ad libitum, 0.67 MJ ME/kg $W^{0.75}$ d, n = 6). The feed restriction period was from 90 days to 140 days of pregnancy. Results: The ewe's body weight, liver weights, water, and protein content of liver in the restricted groups were reduced compared with the CG group (p<0.05), but the liver fat contents in the RG1 group were higher than those of the CG group (p<0.05). The increased hepatic collagen fibers and reticular fibers were observed in the restricted groups with the reduction of energy intake. The concentrations of nonesterified free fatty acids in the RG1 and RG2 groups were higher than those of the CG group with the reduction of energy intake (p<0.05), but there were decreased concentrations of lipoprotein lipase and hepatic lipase in both restricted groups compared with the CG group (p<0.05). In addition, the increased concentrations of ${\beta}$-hydroxybutyric acid, triglycerides, malondialdehyde, total antioxidant capacity and activities of superoxide dismutase activity and catalase were found in the RG1 group, and the concentrations of cholinesterase in the RG1 group were reduced compared with the CG group (p<0.05). For the concentrations of acute phase proteins, the C-reactive protein (CRP) in the RG1 group were reduced compared with the CG group, but there were no differences in haptoglobin relative to the controls (p>0.05). Conclusion: The fat accumulation, increased hepatic fibrosis, antioxidant imbalance and modified synthesis of acute phase proteins were induced in ewe's liver by maternal malnutrition during late pregnancy, which were detrimental for liver function to accommodate pregnancy.

• The Korea Journal of Herbology
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• v.38 no.2
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• pp.17-26
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• 2023

Objectives : A persistent inflammatory response can cause diseases such as fibrosis, cancer, and allergies. This study aimed to investigate the anti-inflammatory activity of Curcumae longae Rhizoma and Cinnamomi Ramulus Mixture (CCM) in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Methods : The total polyphenol and flavonoid contents of CCM were confirmed through an in vitro experiment. Also, radical scavenging activities of 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and Hydroxyl were confirmed. Moreover, ferric reducing antioxidant power (FRAP) activity were confirmed. After, CCM (50, 100, and 200 ㎍/mL) were applied to 0.1 ㎍/mL LPS-stimulated RAW264.7 cells. The levels of nitric oxide (NO) and pro-inflammatory cytokines in the supernatant fraction were determined. Also, the expressions of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways were detected using Western blot. Results : As a result of in vitro experiments, there was an excellent antioxidant activity in CCM-treated cells. In addition, in RAW264.7 cells stimulated with LPS, the increased NO level was inhibited in a concentration-dependent manner by the treatment of CCM. In addition, inflammatory cytokines production were significantly inhibited in a concentration-dependent manner in CCM-treated group. CCM treatment significantly decreased the protein expressions of MAPKs. Moreover, the expressions of NF-κBp65 and cyclooxygenase-2 (COX-2) were significantly decreased when 200 mg/kg of CCM was applied, and phospho-inhibitor of nuclear factor kappa B-α (p-IκBα) and inducible nitric oxide synthase (iNOS) were significantly decreased at all concentrations treated with CCM. Conclusion : Our findings show that CCM exhibited excellent antioxidant activity and exhibited superior anti-inflammatory effect through the MAPKs and NF-κB pathways in LPS-stimulated RAW 264.7 macrophages.

• Herbal Formula Science
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• v.22 no.2
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• pp.105-120
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• 2014

Objectives : This study was investigated the improvement effects of Gangjihwan (DF) and combination of Gangjihwan and Gamisochehwan (GSH) on obesity in a high fat diet-fed obese mouse model. Methods : Eight-week-old C57BL/6N mice were divided into four groups: a normal lean group given a standard diet, an obese control group given a high fat diet, and DF and DF+GSH groups given a high fat diet with DF (40 mg/kg), and DF+GSH (80 mg/kg), respectively. After 8 weeks of treatment, body weight gain, feeding efficiency ratio, blood lipid markers, fat weight and histology were examined. Results : 1. Body weight gain and fat mass were significantly decreased in DF and DF+GSH groups compared with control. The extent of decreases was eminent in DF+GSH group. 2. Feeding efficiency ratio and circulating concentration of leptin were decreased in DF and DF+GSH groups compared with control. These decreases were significant in DF+GSH group. 3. Consistent with their effects on body weight gain and fat mass, circulating concentrations of triglyceride, glucose and insulin were decreased in DF and DF+GSH groups compared with control. 4. The size of adipocytes was decreased by DF and DF+GSH compared with control, whereas the adipocyte number per unit area was increased by them, suggesting that DF and DF+GSH decreased the number of large adipocytes. 5. Consistent with their effects on body weight gain, liver fibrosis was also improved in DF and DF+GSH groups compared with control. Conclusions : In conclusion, these results suggest that DF and DF+GSH groups decrease feeding efficiency ratio, plasma leptin concentration, blood anti-obesity biomarkers and fat mass, improves body weight gain contributing to the inhibition of liver fibrosis. In addition, these effects were more effective in DF+GSH combination group than in DF-only group.

• The Journal of Internal Korean Medicine
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• v.29 no.4
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• pp.871-886
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• 2008

Objective : Gypsum fibrosum has been traditionally used in treatment of febrile diseases and recently been shown to have anti-inflammatory effect. Chronic renal failure has a serious clinical symptoms including proteinuria, azotemia, anemia, and hyperlipidemia and has characteristic histopathological changes, glomerular hypertrophy, infiltration of inflammatory cells, and crescentic sclerosis, We investigated the effects of gypsum fibrosum on renal functional and histopathological disorder in chronic renal failure rat model induced 5/6 nephrectomy. Methods : Using Sprague-Dawley rats, CRF was induced by 5/6 nephrectomy. The rats were divided into 3 groups, normal, conrol, and gypsum administered orally with gypsum fibrosum 500mg/kg/day. Body weight, 24 hr proteinuria, hematologic analysis, and histological morphologic changes were followed up after 8 weeks. The glomerular macrophage/monocyte infiltration, $TGF-{\beta}_1$, type IV collagen, and angiotensin II type1 receptor($AT_1$) were evaluated by immunohistochemistry. Resuls : In the CRF control group, functional parameters and histopathologic changes clearly indicated the development of CRF. 24 hr proteinuria significantly increased in the CRF control group over the normal group, and serum creatinine level was lower in the gypsum group than in the control group, LDL-cholesterol was significantly lower in the gypsum group than in the control group. Morphological investigations showed a variety of characteristic features of CRF, glomerular hypertrophy, increasing cellular density of glomerulus, deposition of extra-cellular matrix, fibrotic change, and glomerular sclerosis in the control group, but in the gypsum group, these features diminished significantly. In observation of renal type IV collagen and $AT_1$ expression, positive area significantly increased in the control group over the normal group, and it significantly decreased in the gypsum group compared to the control group. Conclusions : Our findings suggest that gypsum fibrosum inhibits $AT_1$ and type IV collagen expression in renal tissues and attenuates progression of glomerulosclerosis and interstitial fibrosis in chronic renal failure rats, which lead to amelioration of renal function. From these results, we suggest that gypsum fibrosum may have renoprotective effects and could be a useful remedy agent for treating chronic renal failure.

• Preventive Nutrition and Food Science
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• v.21 no.1
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• pp.38-43
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• 2016

Matrix metalloproteinases (MMPs) are crucial extracellular matrices degrading enzymes that take important roles in metastasis of cancer progression as well as other significant conditions such as oxidative stress and hepatic fibrosis. Natural products are on the rise for their potential to provide remarkable health benefits. In this context, halophytes have been of interest in the nutraceutical field with reported instances of isolation of bioactive compounds. In this study, Limonium tetragonum, an edible halophyte, was studied for its ability to inhibit MMP-2 and -9 using HT1080 fibrosarcoma cells. Results showed that L. tetragonum extract was able to inhibit the enzymatic activity and mRNA expression of MMP-2 and -9 according to gelatin zymography and RT-PCR assays, respectively, but it was not able to significantly change the MMP pathway related factors such as tissue inhibitors of metalloproteinases. Also, Mitogen-activated protein kinases pathway-related protein levels and their phosphorylation were assayed. While the phosphorylated p38 levels were decreased, extracellular signal-regulated kinase and c-Jun N-terminal kinase were not affected by L. tetragonum treatment. In conclusion, it was suggested that L. tetragonum contains substances acting as MMP inhibitors on enzymatic activity rather than intracellular pathway intervention, which could be useful for further utilization of L. tetragonum as a source for anti-MMP agents.

• Preventive Nutrition and Food Science
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• v.22 no.3
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• pp.184-190
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• 2017

Matrix metalloproteinases (MMPs) are endopeptidases that take significant roles in extracellular matrix degradation and therefore linked to several complications such as metastasis of cancer progression, oxidative stress, and hepatic fibrosis. Hizikia fusiformis, a brown algae, was reported to possess bioactivities, including but not limited to, antiviral, antimicrobial, and anti-inflammatory partly due to bioactive polysaccharide contents. In this study, the potential of H. fusiformis against cancer cell invasion was evaluated through the MMP inhibitory effect in HT1080 fibrosarcoma cells in vitro. H. fusiformis crude extract was fractionated with organic solvents, $H_2O$, n-BuOH, 85% aqueous MeOH, and n-hexane (n-Hex). The non-toxicity of the fractions was confirmed by MTT assay. All fractions inhibited the enzymatic activities of MMP-2 and MMP-9 according to the gelatin zymography assay. Cell migration was also significantly inhibited by the n-Hex fraction. In addition, both gene and protein expressions of MMP-2 and -9, and tissue inhibitor of MMPs (TIMPs) were evaluated by reverse transcription-polymerase chain reaction and Western blotting, respectively. The fractions suppressed the mRNA and protein levels of MMP-2, MMP-9 while elevating the TIMP-1 and TIMP-2, with the $H_2O$ fraction being the least effective while n-Hex fraction the most. Collectively, the n-Hex fraction from brown algae H. fusiformis could be a potential inhibitor of MMPs, suggesting the presence of various derivatives of polysaccharides in high amounts.

• Journal of Periodontal and Implant Science
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• v.30 no.3
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• pp.553-569
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• 2000

Many natural medicines have been studied for their capacity and effects of antibacterial, anti-inflammatory and regenerative potential in periodontal tissues. Safflower seed has been traditionally used as a drug for treatment of bone fracture in oriental medicine. The purpose of the present study was to compare the effects of safflower seed extract and bone substitute on bone formation and regeneration in artificial defects in mongrel dogs. The bony defects were made with round bur at mandible and tibia. Extracts of safflower seed and bovine bone were placed directly at each defect for experimental group, and the defect of control group was sutured without any other treatment. Experimental animals were sacrificed at 8 weeks. And then histopathologic reading and histomorphometric study was done. There was not significant differences between control and experimental groups in osteoclastic activity and infiltration of inflammatory cells. However, new capillary proliferation, fibrosis and new bone formation were prominent in safflower seed extract group. The mandibular defects of safflower seed extract group were healed with dense connective and bony tissues, and endochondral bone formation was observed in tibial defect of safflower seed extract group only. New bone area of safflower seed extract group was more significantly increased than that of control and that of bone substitute group. These results indicate that direct local application of safflower seed extracts on bony defects seems to reduces the early inflammatory response and to promotes the bone regeneration.

• Tuberculosis and Respiratory Diseases
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• v.38 no.4
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• pp.347-356
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• 1991

Endobronchial tuberculosis is a serious disase because it frequently leaves airway obstruction as the complication, and the treatment of airway obstruction is generally troublesome. In the tumorous type of endobonchial tuberculosis, the bronchial patency is partially or completely compromised with lymph node contents when the necrotic focus of the lymph node ruptures into the bronchial lumen to form a bronchoglandular fistula. To investigate the transition of endobronchial lesion and to evaluate the therapeutic role of bronchoscopic electrocautery in the tumorous type of endobronchial tuberculosis, we performed electrocautery in addition to the combination chemotherapy with steroid and anti-tuberculous drugs in two cases which had airway obstruction proximal to lobar bronchus with the impairment of pulmonary function. We also treated another two cases only with chemotherapy and we have followed up four cases over a 36-month period. In cases that bronchoscopic electrocautery was done, the bronchial patency was completely restored and the impairment of pulmonary function disappeared just after cautery and these effects have remained for 12 months or more. But in cases of medical treatment only, bronchial stenosis was inevitable as the tumorous type of endobronchial tuberculosis changed to the stenotic type with fibrosis. It can be concluded that bronchoscopic electrocautery can nip the occurence of bronchial stenosis in the bud when it is applied in addition to combination chemotherapy with steroid and antituberculous drugs in the tumorous type of endobronchial tuberculosis.

• The Journal of Internal Korean Medicine
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• v.31 no.3
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• pp.415-424
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• 2010

Objectives : This study was performed to investigate the anti-fibrogenic effect of Angelica Gigantis Radix on cultured rat hepatic stellate cells. Materials and Methods : Hepatic stellate cells(HSC-T6) were treated with various concentrations of Angelica Gigantis Radix extract for both 24 and 48 hours. The extraction was done either with distilled water or 80% EtOH. After the treatment, cell viability, cell proliferation, procollagen production and the mRNA expression of the ASMA, TIMP1, TIMP2, procollagen Type 1a2, and Cytokine IL-6 production were measured by using MTT assay, BrdU assay, RT-PCR, procollagen Type I C-peptide EIA and IL-6 ELISA assay. Results : The cell viability treated with water extraction was significantly increased, but there were no significant changes treated with 80% EtOH extraction. The cell proliferation treated with water extraction decreased only in the 24 hours group, while there were significant decreases either in the 24 and 48 hours groups treated with 80% EtOH extraction. The mRNA expressions of the ASMA, TIMP2 and procollagen 1a2 decreased in a concentration-dependent manner in the 48 hours group. Procollagen production decreased in a concentration-dependent manner in both the 24 and 48 hours groups. Cytokine IL-6 production increased in a concentration-dependent manner in both the 24 and 48 hours groups. Conclusion : These results suggest that Angelica Gigantis Radix is beneficial in the treatment of cirrhotic patients as well as for patients with chronic hepatitis.