• Title/Summary/Keyword: anti-fibrosis

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Effects of feed intake restriction during late pregnancy on the function, anti-oxidation capability and acute phase protein synthesis of ovine liver

  • Yang, Huan;Wang, Ying;Ma, Chi;Sun, Chuan;Liu, Yingchun;Wu, Kaifeng;Li, Ming;Borjigin, Gerelt;Gao, Feng
    • 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.

Effects of Curcumae longae Rhizoma and Cinnamomi Ramulus Mixture on Anti-inflammatory Activities in Lipopolysaccharide-stimulated RAW 264.7 Cells (강황(薑黃) 계지(桂枝) 복합물이 RAW 264.7 세포에서 항염증 활성에 미치는 영향)

  • Ji, Choi;Hae-Jin, Park;Il-ha, Jeong;Min Ju, Kim;Mi-Rae, Shin;Seong-Soo, Roh;Soon-Ae, Park;Mi-Lim, Kim
    • 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.

Comparison of Gangjihwan and Combination of Gangjihwan and Gamisochehwan in the Improvement Effects of Weight Loss in a High Fat Diet-Fed Obese Mice (고지방식이 비만마우스 모델에서 파키스탄산 마황으로 조성된 강지환(降脂丸)의 단독 투여와 강지환합가미소체환(降脂丸合加味消滯丸)의 병용 투여의 체중감량 효과 비교)

  • Seok, Hoa Jun;Yoo, Jae Sang;Ku, Ja Ryong;Yoon, Ki Hyeon;Jo, Ju Heum;Jang, Du Hyon;Jung, Yang Sam;Kim, Jong Hoon;Kim, Byeong Chul;Roh, Jong Seong;Lee, Hye Rim;Lee, Hyunghee;Yoon, Michung;Shin, Soon Shik
    • 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 Effects of Gypsum Fibrosum on Renal Functional and Histopathological Disorder in Chronic Renal Failure Rat Model (석고(石膏)가 만성 신부전 Rat의 신기능 보호 및 조직학적 변화에 미치는 영향)

  • Byun, Sang-Hyuk
    • 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.

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Inhibition of MMP-2 and MMP-9 Activities by Limonium tetragonum Extract

  • Bae, Min-Joo;Karadeniz, Fatih;Lee, Seul-Gi;Seo, Youngwan;Kong, Chang-Suk
    • 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.

Inhibitory Effect of Hizikia fusiformis Solvent-Partitioned Fractions on Invasion and MMP Activity of HT1080 Human Fibrosarcoma Cells

  • Lee, Seul-Gi;Karadeniz, Fatih;Oh, Jung Hwan;Yu, Ga Hyun;Kong, Chang-Suk
    • 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.

Effects of Safflower Seed Extracts and Bovine Bone on Regeneration of Bone Defects in Mongrel Dogs (홍화씨 추출물 및 우골유도합성골이 성견골 결손부 재생에 미치는 영향)

  • Seo, Jae-Jin;Kim, Tak;Pi, Sung-Hee;Yun, Gi-Yun;Yu, Hyung-Keun;Shin, Hyung-Shik
    • 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.

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Bronchoscopic Electrocautery for Airway Obstruction in The Tumorous Type of Endobronchial Tuberculosis (종양형 기관지결핵에서 기도협착에 대한 기관지경적 전기소작요법)

  • Chung, Hee-Soon;Hyun, In-Gyu;Han, Sung-Koo
    • 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.

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Inhibitory Effect of Angelica Gigantis Radix on Fibrogenesis in Rat Hepatic Stellate Cells (당귀(當歸)가 간성상세포의 섬유화 기전 억제에 미치는 영향)

  • Son, Hyun-Soo;Kim, Young-Chul
    • 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.

Anti-inflammatory and antioxidant effects of umbelliferone in chronic alcohol-fed rats

  • Sim, Mi-Ok;Lee, Hae-In;Ham, Ju Ri;Seo, Kwon-Il;Kim, Myung-Joo;Lee, Mi-Kyung
    • Nutrition Research and Practice
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    • v.9 no.4
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    • pp.364-369
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    • 2015
  • BACKGROUND/OBJECTIVES: Inflammation is associated with various types of acute and chronic alcohol liver diseases. In this study, we examined whether umbelliferone (7-hydroxycoumarin, UF) ameliorates chronic alcohol-induced liver damage by modulating inflammatory response and the antioxidant system. METHODS: Rats were fed a Liber-Decarli liquid diet containing 5% alcohol with or without UF (0.05 g/L) for 8 weeks, while normal rats received an isocaloric carbohydrate liquid diet. RESULTS: Chronic alcohol intake significantly increased serum tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin 6 levels and decreased interleukin 10 level; however, UF supplementation reversed the cytokines related to liver damage. UF significantly suppressed hepatic lipopolysaccharide binding protein, toll-like receptor 4 (TLR4), nuclear factor kappa B, and TNF-${\alpha}$ gene expression increases in response to chronic alcohol intake. Masson's trichrome staining revealed that UF improved mild hepatic fibrosis caused by alcohol, and UF also significantly increased the mRNA expressions and activities of superoxide dismutase and catalase in liver, and thus, decreased lipid peroxide and mitochondrial hydrogen peroxide levels. CONCLUSIONS: The findings of this study indicate that UF protects against alcohol-induced liver damage by inhibiting the TLR4 signaling pathway and activating the antioxidant system.