• 약학회지
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• 제45권5호
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• pp.513-521
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• 2001

The chronic cholestasis induce to biliary liver fibrosis (cirrhosis) and the increased products of ROS(reactive oxygen species) cause to the liver damage. In this study ; the antioxidant and antifibrotic effect of dried extracts of oriental medicine (DW) was investigated under the liver fibrotic (cirrhotic) condition. The female Sprague-Dawley rats were divided in 5 groups (Normal, Op-2, Op-4, OpDW-2, OpDW-4). Except for normal group, the rats were induced to biliary liver fibrosis (cirrhosis) by the operation of bile duct ligation/scission (BDU/S) and were observed in 2 weeks or 4 weeks. And the prepared DW was treated p.o.2 ml/day/rats in 2 weeks or 4 weeks for OpDW groups. At the time of sacrifice, the liver, kidney, spleen were weighed and the ratio of organ weight/body weight was calculated. The MDA, the hyp and biochemical parameters (GOT GTP, ALP, t-bili) were measured in sera and liver tissue of rats. The biochemical change was observed on liver tissue. In the result, the hepatomegaly and spleenomegaly appeared in all BDL/S operated rats, and significantly lower liver weight was observed in OpDW-4 group compared with in Op-4 group (p<0.05). The level of clinical parameters in sera of all liver fibrosis (cirrhosis) developed rats was higher than in normal group. Especial1y, the value of GOT in OpDW-2 group and ALP in OpDW-4 group showed significantly lower than in Op-2 group and Op-4 group (p<0.01, p<0.005). The content of hyp in all operation groups was significantly higher than in normal group (p<0.05∼<0.005), and showed significantly lower value in the OpDW-4 group than in Op-4 group (p<0.05). The product of lipid peroxidationUDA) increased significantly under the fibrotic(cirrhotic) condition (p<0.05∼ <0.005), and the MDA value in OpDW-4 group decreased significantly in Op-4 group (p<0.005). The histological change (bile duct proliferation, fibrosis, collagen bundle) was similarly observed in Op-2 group and in OpDW-2 group, but the weak fibrosis and bile duct proliferation were observed in OpDW-4 group compared with in Op-4 group. In conclusion, lipid peroxidation and severe liver damage were activated by bile duct obstruction, and the measurement of MDA and hap can be useful monitor for the screening of antioxidant and antifibrotic effect in experimental liver fibrosis (cirrhosis). The 4 weeks treatment with DW extracts suppressed lipid peroxidation and inhibited fibrotic (cirrhotic) process in BDL/S operated rats.

• 대한약학회:학술대회논문집
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• 대한약학회 2000년도 춘계총회 및 학술대회
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• pp.211.1-211.1
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• 2000

• 대한약학회:학술대회논문집
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• 대한약학회 2001년도 Proceedings of International Convention of the Pharmaceutical Society of Korea
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• pp.308.1-308.1
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• 2001

• Asian Pacific Journal of Cancer Prevention
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• 제13권1호
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• pp.289-294
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• 2012

Background: Myofibroblasts play an important role in the development of oral submucous fibrosis (OSF). In the current study, we investigate the effect of curcumin on growth and apoptosis of myofibroblasts derived from human oral mucosa. Methods: Myofibroblasts were generated by incubating fibroblasts, obtained from human oral mucosa, with transforming growth factor-${\beta}1$ (TGF-${\beta}1$). MTT, PI staining, and FACS assays were used to investigate curcumin's effect on proliferation and cell cycle of fibroblasts and myofibroblasts. Annexin V/PI binding and FACS assays were used to examine apoptosis of myofibroblasts, Western blotting to determine the levels of Bcl-2 and Bax, and enzyme-linked immunosorbant assay was employed to examine the levels of collagen type I and III in the supernatants of myofibroblasts. Results: Curcumin inhibits proliferation of fibroblasts and myofibroblasts; it also disturbs the cell cycle, induces apoptosis and decreases the generation of collagen type I and III in myofibroblasts, which are more sensitive to its effects than fibroblasts. Curcumin induces apoptosis in myofibroblasts by down-regulating the Bcl-2/ Bax ratio. Conclusion: Our results demonstrate the antifibrotic effect of curcumin in vitro. It may therefore be a candidate for the treatment of OSF.

• Biomolecules & Therapeutics
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• 제31권5호
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• pp.484-495
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• 2023

Idiopathic pulmonary fibrosis (IPF) can be defined as a progressive chronic pulmonary disease showing scarring in the lung parenchyma, thereby resulting in increase in mortality and decrease in the quality of life. The pathophysiologic mechanism of fibrosis in IPF is still unclear. Repetitive microinjuries to alveolar epithelium with genetical predisposition and an abnormal restorative reaction accompanied by excessive deposition of collagens are involved in the pathogenesis. Although the two FDA-approved drugs, pirfenidone and nintedanib, are under use for retarding the decline in lung function of patients suffered from IPF, they are not able to improve the survival rate or quality of life. Therefore, a novel therapeutic agent acting on the major steps of the pathogenesis of disease and/or, at least, managing the clinical symptoms of IPF should be developed for the effective regulation of this incurable disease. In the present review, we tried to find a potential of managing the clinical symptoms of IPF by natural products derived from medicinal plants used for controlling the pulmonary inflammatory diseases in traditional Asian medicine. A multitude of natural products have been reported to exert an antifibrotic effect in vitro and in vivo through acting on the epithelial-mesenchymal transition pathway, transforming growth factor (TGF)- β-induced intracellular signaling, and the deposition of extracellular matrix. However, clinical antifibrotic efficacy of these natural products on IPF have not been elucidated yet. Thus, those effects should be proven by further examinations including the randomized clinical trials, in order to develop the ideal and optimal candidate for the therapeutics of IPF.

• Natural Product Sciences
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• 제14권2호
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• pp.81-85
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• 2008

Isorhamnetin isolated from Oenanthe javanica significantly inhibited proliferation and collagen production in HSC-T6 cells in concentration- and time-dependent manners. Pretreatment of HSC-T6 cells with isorhamnetin significantly inhibited serum-induced ERK phosphorylation, in a similar manner as PD98059, a known MEK inhibitor. These results suggested that isorhamnetin reduced collagen production in HSC-T6 cells, in part, via inhibition of ERK signaling pathway.

• BMB Reports
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• 제56권4호
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• pp.225-233
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• 2023

Hepatocellular carcinoma (HCC) is a very common form of cancer worldwide and is often fatal. Although the histopathology of HCC is characterized by metabolic pathophysiology, fibrosis, and cirrhosis, the focus of treatment has been on eliminating HCC. Recently, three-dimensional (3D) multicellular hepatic spheroid (MCHS) models have provided a) new therapeutic strategies for progressive fibrotic liver diseases, such as antifibrotic and anti-inflammatory drugs, b) molecular targets, and c) treatments for metabolic dysregulation. MCHS models provide a potent anti-cancer tool because they can mimic a) tumor complexity and heterogeneity, b) the 3D context of tumor cells, and c) the gradients of physiological parameters that are characteristic of tumors in vivo. However, the information provided by an multicelluar tumor spheroid (MCTS) model must always be considered in the context of tumors in vivo. This mini-review summarizes what is known about tumor HCC heterogeneity and complexity and the advances provided by MCHS models for innovations in drug development to combat liver diseases.

• Journal of Applied Biological Chemistry
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• 제66권
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• pp.138-143
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• 2023

Liver fibrosis is caused by metabolic problems such as cholestasis, genetic problems, or viral infections. Inhibiting hepatic stellate cell (HSC) activation or inducing selective apoptosis of activated HSCs is used as a treatment strategy for liver fibrosis. It has been reported that when HSCs are activated, their apoptosis sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is enhanced because the expression of death receptor 5 is elevated. Finding a natural compound that can enhance the apoptotic effect of TRAIL on HSCs is a necessary strategy for liver fibrosis treatment. It was confirmed here that mangosteen-derived gartanin increased the effect of TRAIL-induced apoptosis by increasing the expression of DR5 in a p38-dependent manner in the hepatic stellate cell line LX-2. Combined treatment with gartanin and TRAIL accelerated DNA cleavage through caspase-3 activation and enhanced antifibrotic effects in LX-2 cells.

• Tuberculosis and Respiratory Diseases
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• 제85권2호
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• pp.185-194
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• 2022

Background: The Korea Interstitial Lung Disease Study Group has made a new nationwide idiopathic pulmonary fibrosis (IPF) registry because the routine clinical practice has changed due to new guidelines and newly developed antifibrotic agents in the recent decade. The aim of this study was to describe recent clinical characteristics of Korean IPF patients. Methods: Both newly diagnosed and following IPF patients diagnosed after the previous registry in 2008 were enrolled. Survival analysis was only conducted for patients diagnosed with IPF after 2016 because antifibrotic agents started to be covered by medical insurance of Korea in October 2015. Results: A total of 2,139 patients were analyzed. Their mean age at diagnosis was 67.4±9.3 years. Of these patients, 76.1% were males, 71.0% were ever-smokers, 14.4% were asymptomatic at the time of diagnosis, and 56.9% were at gender-age-physiology stage I. Occupational toxic material exposure was reported in 534 patients. The mean forced vital capacity was 74.6% and the diffusing capacity for carbon monoxide was 63.6%. Treatment with pirfenidone was increased over time: 62.4% of IPF patients were treated with pirfenidone initially. And 79.2% of patients were treated with antifiboritics for more than three months during the course of the disease since 2016. Old age, acute exacerbation, treatment without antifibrotics, and exposure to wood and stone dust were associated with higher mortality. Conclusion: In the recent Korean IPF registry, the percentage of IPF patients treated with antifibrotics was increased compared to that in the previous IPF registry. Old age, acute exacerbation, treatment without antifibrotics, and exposure to wood and stone dust were associated with higher mortality.

• 동의생리병리학회지
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• 제17권1호
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• pp.118-122
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• 2003

Oxidative stress and its consequent lipid peroxidation exert harmful effects, which have been currently involved in the generation of carbon tetrachloride (CCl₄)-induced fibrosis(cirrhosis). In this study, it was investigated whether dried extract of 田螺(Concha Cipangopaludinae; CC) has liver functional improvement, antioxidative and antifibrotic effect in rats those were induced liver fibrosis by CCl₄ administration. The female Sprague-Dawley rats were divided into 3 groups(Normal, AC, AC-CC) and were observed in 6 weeks. Except for normal group, liver fibrosis(cirrhosis) in rats were developed by CCl₄ administration(0.8 ㎖/rat/week). And the rats were treated with prepared CC(p. o. 2 ㎖/day/rat). At the time of sacrifice, the liver, kidney and spleen were weighed and the ratio of organ weight/body weight was calculated. The MDA, hyp and biochemical parameters(AST, ALT, ALP, t-bili) were measured in sera and liver tissue of rats. The strong yellow color of urine was observed in all CCl₄-treated group compared with normal group, but jaundice didn't appear in CCl₄-treated group. The mortality of CCl₄-treated group is very low(<13%) during 6 weeks of observation time. The ratio of liver/body as well as the weight of liver in CCl₄-treated rats significantly increased compared with that in normal group(p<0.001). The level of clinical parameters in sera of all liver fibrosis(cirrhosis) developed rats were significantly higher than that of normal group(p<0.001-0.05). Especially the value of BUN, ALP, t-bilirubin in AC-CC group showed 20.9%, 19.6%, 47.9% lower than that in AC group. The content of hyp in CCl₄-treated rats was significantly higher than normal group(p<0.001～<0.05), and showed 12.2% lower value in the AC-CC group than AC group(p<0.05). The production of lipid peroxidation(MDA) in sera and liver tissue significantly increased under the fibrotic(cirrhotic) condition(p<0.001～<0.05). Especially the MDA value of AC-CC group in sera significantly 46.5% decreased compared with that of AC group(p<0.05), and the MDA value of AC-CC in liver tissue showed 21.4% lower than that of AC group. Concha Cipangopaludinae can be improved hepatic function, and maybe have effect of liver protection, antioxidation and antifibrosis.