• Proceedings of the PSK Conference
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• 2003.10b
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• pp.86.2-87
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• 2003

Introduction: Liver fibrosis is defined unbalance of collagen metabolism, especially a stimulation of collagen synthesis and inhibition of collagen degradation, and antifibrotic effect is delaying or inhibition of new collagen synthesis and deposition in liver tissue. In this study, we investigated the antifibrotic and antioxidative effect of Solanum lycopersicum (SL) in liver fibrosis induced rats. Methods: : Rats were randomly divided in three groups (normal, CCl$_4$ and CCl$_4$-SL group) and were received 0.6 ml mixture of CCl$_4$ and olived oil (1:1 v/v) 3 times/week for 4 weeks except of the normal group. (omitted)

• YAKHAK HOEJI
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• v.41 no.2
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• pp.220-224
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• 1997

This study was carried out to investigate the dose dependent antifibrotic effects of polysaccharide from mycelium of Ganoderma lucidum. The experimental hepatic cirrhosis was induced by bile duct ligation/scission (BDL/S) in rats. BDL/S rats in each group were dosed 0.5 mg, 2.0 mg, 5.0 mg or 10.O mg/rat/day orally for 4 weeks after the operation. Antifibrotic effects were evaluated by serum biochemical values, hydroxyproline contents, and light microscopical histology. The results obtained were as follows: 1) Hydroxyproline contents in liver of 5.0 and 10.0mg polysaccharide-treated BDL/S rats were significantly reduced 2) In serum test, ALT, AST, ALP values in polysaccharide from Ganoderma lucidum-treated group were lower than BDL/S control group 3) The hepatic damage such as hepatocellular necrosis, inflammation, bile duct proliferation and fibrosis was less severe in the livers of 2.0 mg and 5.0 mg polysaccharide-treated rats. These results suggest that polysaccharide from mycelium of Ganoderma lucidum to be a promising agent for the inhibition of hepatic cirrhosis.

• YAKHAK HOEJI
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• v.46 no.2
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• pp.129-136
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• 2002

The pathogenesis of cholestatic liver injury as well as the modulation of hepatic fibrogenesis is causally associated with involvement of reactive oxygen species (ROS) and free radical reactions. In this study, we investigated whether dried extracts of oriental medicine (LH) have antioxidant and antifibrotic effect under the biliary liver fibrosis (cirrhosis) c ondition. The female Sprague-Dawley rats were divided in six groups (Normal, N-LH, op-2, op-4, opLH-2, opLH-4) and were observed in 2 weeks or 4 weeks. For this purpose the rats were operated by bile duct ligation/scission (BDL/S), which induced to liver fibrosis and cirrhosis. After surgery, the prepared LH was administered p.o. 2 mι/day/rat in 2 weeks or 4 weeks for opLH groups. During the observation period, jaundices appeared in eyes, ears and tail of all BDL/S operated rats. And at the time of sacrifice, cholestasis was observed in proximal bile duct, especially the color of bile juice and urine in opLH-4 group showed more clear than op-2, op-4 and opLH-2 group. The value of clinical parameters and product of lipid peroxidation (MDA) in sera and the hydroxyproline (hyp) content in liver tissue were significantly increased in all liver fibrosis (cirrhosis) developed rats (p＜0.001~0.05). Among the clinical parameters of sera, value of BUN, ALP in opLH-4 group showed significantly lower than in op-4 group (p＜0.05, p＜0.001). The content of hyp in opLH-2, opLH-4 group (478.0 $\pm$ 134.3 $\mu\textrm{g}$/g 897.5 $\pm$ 118.2 $\mu\textrm{g}$/g) showed lower than in op-2, op-4 group (528.9 $\pm$ 220.7 $\mu\textrm{g}$/g, 1023.8 $\pm$ 277.1 $\mu\textrm{g}$/g) and then the value of MDA in opLH-4 was also significantly reduced to 59.4% of that in op-4 group (p＜0.001). The histological change (bile duct proliferation, fibrosis, collagen bundle) was similarly observed in op-2 group and in opLH-2 group, but the weak fibrosis and bile duct proliferation were observed in opLH-4 group compared with in op-4 group. Our data indicate that the 4 weeks treatment with LH extract suppressed lipid peroxidation and inhibited fibrotic (cirrhosis) process, and experimental cholestatic liver disease is associated with increased lipid peroxidation in BDL/S operated rats. Hence we concluded that the measurement of MDA and hyp can be useful monitor for the screening of antioxidant and antifibrotic effect in experimental liver fibrosis (cirrhosis), and LH has been shown to have hepatoprotective effect, antifibrotic effect and antioxidant effect.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.110-110
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• 1995

This study was carried out to investigate the dose dependent antifibrotic effects of G009, the water-soluble fraction of polysaccharide extracted from Ganoderma lucidum. The experimental hepatic cirrhosis was induced by bile duct ligation/scission (BDL/S) in rats. BDL/S rats in each group were dosed 0.5, 2, 5 or 10mg/rat/day orally for 4 weeks after the operation. Antifibrotic effects were evaluated by serum biochemical values, hydroxyproline contents, and light microscopical histology.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.286.2-286.2
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• 2002

Oxidative stress and its consequent lipid peroxidation exert harmful effects, which have been currently involved in the generation of carbon tetrachloride(CC14)-induced fibrosis(cirrhosis). In this study, it was investigated whether dried extract of 田螺(Concha Cipangopaludinae: CC) is liver functional improvement, antioxidative and antifibrotic effect under the liver fibrotic(cirrhotic) condition by CC14 administration. The female Sprague-Dawley rats were divided into 3 groups(Normal, AC, AC-CC), and were observed for 3 weeks. (omitted)

• Archives of Pharmacal Research
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• v.23 no.5
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• pp.501-506
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• 2000

We examined the antifibrotic effect of a methanol extract from Stephania tetrandra (ST) on experimental liver fibrosis. liver fibrosis was induced by bile duct ligation and scission (BDL/S) in rats. In BDL/S rats, activity levels of aspartate transaminase (AST), alanine transaminse (ALT), alkaline phosphatase (ALP), concentration of total bilirubin in serum, and hydroxyproline content of the liver were significantly increased. The ST treatment (either 100 ${m}g/kg/day$ or 200 ${m}g/kg/day$, p.o. for 4 weeks) in BDL/S rats reduced the serum AST, ALT and ALP activity levels significantly (p<0.01). Similarly, when compared to the control group, the concentration of hydroxyproline in the livers of the BDL/S rats treated with 100${m}g$ or 200${m}g$ ST treated rats decreased by 40% and 33% respectively, when compared to the BDL/S control group (p<0.01). The morphological characteristics of fibrotic liver that were observed in the BDL/S control group, improved in the ST treated BDL/S group. In the fibrotic liver of BDL/S rats treated with ST, a marked reduction in the numbers of alpha smooth muscle cell actin positive stellate cells was observed. These results indicate that doses of either 100 or 200 ${m}g/kg/day$ of methanol extract from S. tetrandra, had an antifibrotic effect in rats with liver fibrosis induced by bile duct ligation and scission.

• Archives of Pharmacal Research
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• v.24 no.4
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• pp.327-332
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• 2001

The antifibrotic effects of hot water extract (WEC), intracellular biopolymer (IPC) and extracellular biopolymers (EPC) from mycelial liquid culture of Cordyceps militaris on liver fibrosis were studied. Liver fibrosis was induced by a bile duct ligation and scission (BDL/S) operation, duration of 4 weeks in rats. In BDL/S rats, the levels of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin in serum and hydroxyproline content in liver were dramatically increased. The WEC or IPC treatment (30mg/kg/day for 4 weeks, p.o.) in BDL/S rats reduced the serum AST, ALT and ALP levels significantly (p<0.01). The EPC treatment (30 mg/kg /day for 4 weeks, p.o.) reduced the serum ALT, AST and ALP levels significantly (p<0.01). Malondialdehyde contents in liver treated with WEC, IPC or EPC were significantly reduced (p <0.05). But Liver hydroxyproline content was decreased only in EPC treated BDL/S rats to 55% that of BDL/S control rats (p < 0.01). The morphological characteristics and expression of alpha smooth muscle like actin in fibrotic liver, which appeared in BDL/S control group were improved in EPC treated fibrotic liver. These results indicate that IPC (30 mg/kg /day for 4 weeks, p.o.) has an antifibrotic effect on fibrotic rats induced by BDL/S.

• Journal of Society of Preventive Korean Medicine
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• v.5 no.1
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• pp.116-133
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• 2001

Antifibrotic drugs could be delayed or inhibited massive collagen deposition in liver tissue or inhibited collagen synthesis. we investigated antifibrotic effects by several herbs(Schisnadra chinensis, Ganoderma japonicum, Sedum sarmentosum, Alisma canaliculatum, Plantago asiatica) extract with observations of collagen accumulation in liver tissue and collagen synthesis in sera. Rats were used for experimental animal that were devided 3 groups(sham control, BDL/S, BDL/S-ER). Rats were operated for inducing liver fibrosis(cirrhosis) by bile duct obstruction. Several herbs were prepared by water extraction and were applicated p. o. $3ml/day$ during 4 weeks. After observation period, rats were sacrificed and liver tissue and sera were collected. In result, the mortality of rats was 35% in BDL/S group and 20% in BDL/S-ER The color of bile juice in BDL/S-ER was bright yellow and murky yellow in BDL/S group. The significantly lower weight of liver($16.21g{\pm}5.3,\;20.58{\pm}2.4$) and spleen($1.96g{\pm}0.96,\;3.93{\pm}0.21$) were shown in BDL/S-ER than that of BDL/S(p<0.05) group. The value of collagen in liver tissue(25.7%) in BDL/S-ER was observed significantly lower than that of BDL/S group (Tab. 2). AST. ALT, ALP, t-bilirubin, BUN levels were low in BDL/S-ER as compared with those of BDL/S group, but the significance was not proven. The trichrome stained liver tissue in BDL/S-ER group was observed mild bile duct proliferation and fibrosis compared with BDL/S group. In conclusion, natural products inhibited new collagen synthesis and delayed massive collagen deposition in liver tissue, so that they have noticeable antifibrotic effects in experimental liver fibrosis(cirrhosis).

• BMB Reports
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• v.57 no.3
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• pp.143-148
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• 2024

Pulmonary fibrosis is a serious lung disease that occurs predominantly in men. Genistein is an important natural soybean-derived phytoestrogen that affects various biological functions, such as cell migration and fibrosis. However, the antifibrotic effects of genistein on pulmonary fibrosis are largely unknown. The antifibrotic effects of genistein were evaluated using in vitro and in vivo models of lung fibrosis. Proteomic data were analyzed using nano-LC-ESI-MS/MS. Genistein significantly reduced transforming growth factor (TGF)-β1-induced expression of collagen type I and α-smooth muscle actin (SMA) in MRC-5 cells and primary fibroblasts from patients with idiopathic pulmonary fibrosis (IPF). Genistein also reduced TGF-β1-induced expression of p-Smad2/3 and p-p38 MAPK in fibroblast models. Comprehensive protein analysis confirmed that genistein exerted an anti-fibrotic effect by regulating various molecular mechanisms, such as unfolded protein response, epithelial mesenchymal transition (EMT), mammalian target of rapamycin complex 1 (mTORC1) signaling, cell death, and several metabolic pathways. Genistein was also found to decrease hydroxyproline levels in the lungs of BLM-treated mice. Genistein exerted an anti-fibrotic effect by preventing fibroblast activation, suggesting that genistein could be developed as a pharmacological agent for the prevention and treatment of pulmonary fibrosis.

• Natural Product Sciences
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• v.15 no.2
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• pp.101-105
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• 2009

We previously reported that a novel cerebroside, LCC, isolated from the fruits of Lycium chinense (Solanaceae), significantly exerted hepatoprotective activity against both the carbon tetrachloride-induced and galactosamine-induced toxicities in primary cultures of rat hepatocytes. In the present study, we further attempted to determine the effect of LCC on hepatic fibrosis in animal model. Hepatic fibrosis was induced in rats by bile duct ligation/scission (BDL) for a period of 5 weeks. Treatment of BDL rats with LCC significantly reduced collagen deposition and the activities of serum alkaline phosphatase and ${\gamma}$-glutamyl transpeptidase. In addition, the LCC treatment of BDL rats significantly preserved the decreased hepatic glutathione as well as the activities of glutathione reductase and catalase in BDL rats. From the results, it can be speculated that LCC might exert antifibrotic activity in rats with BDL, in part, through the preservation of antioxidant enzymes and hepatic glutathione.