• CELLMED
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• v.3 no.2
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• pp.15.1-15.5
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• 2013

Previous reports showed that Compound Astragalus and Salvia miltiorrhiza extract (CASE), which was mainly composed of astragalosides, astragalus polysaccharide and salvianolic acids, inhibited hepatic fibrosis by mediating transforming growth factor-${\beta}$ (TGF-${\beta}$)/Smad signaling. Our aim was to examine the effects of CASE on D-galactosamine (D-GalN) treated liver injury in mice and carbon tetrachloride ($CCl_4$)-induced liver fibrosis in rats. CASE was administered to mice with D-GalN-induced liver injury and to rats with $CCl_4$-induced liver fibrosis, respectively. Liver injury was routinely evaluated by relative liver weight, serum levels of ALT, AST, hyaluronic acid (HA), hepatic malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, hydroxyproline (HYP) and histopathologic changes. Treatment of mice with CASE (60, 120, and 240 mg/kg, ig) significantly lowered ALT, relative liver weight, and MDA levels when compared with D-GalN treated mice. CASE (120, 240 mg/kg) significantly lowered ALT, AST, HA, HYP, and MDA levels against $CCl_4$ treated rats. Decreased SOD level was reversed with CASE treatment. Upon histopathological examination, CASE treatment had significantly inhibitory effect on the progression of hepatic fibrosis in rats. These results indicate that CASE might be effective in treatment and prevention of acute and chronic hepatic injury due to its antioxidant activity.

• Herbal Formula Science
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• v.25 no.2
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• pp.155-166
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• 2017

Objectives : Polygoni Multiflori Ramulus has been widely used as a traditional medicinal herb for the treatment of insomnia, limb pain and itch. The extract of Polygoni Multiflori Ramulus (PMRE) is known to have a modulatory effect of many inflammatory responses. This study was performed to investigate the hepatoprotective effect of PMRE against arachidonic acid (AA) + iron-induced oxidative stress on HepG2 cell and carbon tetrachloride ($CCl_4$)-induced liver injury on mice. Methods : The effects of PMRE on cell viability was assessed by MTT assay. And flow cytometric analysis was performed to estimate the effects on mitochondrial function. To investigate its underlying mechanism, apoptosis-related proteins were analysed by using immunoblot analysis. In addition, ICR mouse were administrated (po) with the PMRE (30, 100 mg/kg) for 3 days and then, injected (ip) with $CCl_4$ (0.5 ml/kg body weight) to induce acute liver damage. The level of pro-caspase-3 was measured. Results : Treatment of PMRE increased relative cell viability, prevented a cleavage of poly (ADP ribose) polymerase and pro-caspase-3, and also reduced mitochondrial membrane permeability against AA + iron-induced oxidative stress. In addition, PMRE treatment decreased liver injury induced by $CCl_4$, as evidenced by increases in pro-caspase-3 level. Conclusions : These results demonstrate that PMRE has an ability to anti-oxidant and hepatoprotective effect against AA + iron-induced oxidative stress and $CCl_4$-induced liver injury.

• YAKHAK HOEJI
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• v.35 no.5
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• pp.384-388
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• 1991

To explore the effect of monosodium-L-glutamate(MSG) on CCI$_{4}$-damaged liver in Wister male rat, 5% MSG solution as drink water were administered after S.C. injection of 0.1 mg/kg CC1$_{4}$ twice a week for 4 weeks. After last administration of MSG, heptic glutathione(GSH) dependent system was assayed. It showed that MSG increased significanly hepatic glutathione(GSH) and glutathione peroxidase(GSH$_{px}$), but decreased glutathione-S-transferase(GST) acivity in normal rats. MSG increased significantly the GSH$_{px}$ and GST activities in rats with CCI$_{4}$-induced liver damage. These results indicate that decrease of GSH dependent systems in CC1$_{4}$ liver injury might be partially elevated by coadministration of MSG.

• Korean Journal of Veterinary Research
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• v.51 no.4
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• pp.259-265
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• 2011

Several compounds and extracts isolated from a brown alga, Ishige (I.) okamurae, exhibit anti-oxidant and anti-inflammatory effects. The present study investigated whether the ethyl acetate (EtOAc) fraction of I. okamurae (EFIO) could ameliorate carbon tetrachloride ($CCl_{4}$)-induced hepatotoxicity in rats. Sprague-Dawley rats were intraperitoneally (i.p.) administered with EFIO at 10 or 50 mg/kg per day for 2 consecutive days before $CCl_{4}$ injection (3.3 mL/kg, i.p.). Twenty four hours later, the rats were anesthesized with diethyl ether and dissected. Pretreatment with EFIO significantly reduced the increased serum levels of alanine aminotransferase and aspartate aminotransferase in $CCl_{4}$-treated rats. Pretreatment with EFIO also significantly inhibited the reduced activities of superoxide dismutase and catalase in the $CCl_{4}$-injured liver. Histopathological evaluations showed that hemorrhage, hepatocyte necrosis, inflammatory cell infiltration, and fatty degeneration induced by $CCl_{4}$ treatment were ameliorated by the administration of EFIO. Additionally, liver immunohistochemical analyses revealed the marked reduction in ED1-positive monocyte-like macrophages in EFIO-pretreated rats given $CCl_{4}$. These results suggest that EFIO ameliorates $CCl_{4}$-induced liver injury, possibly through the inhibition of oxidative stress.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.1
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• pp.21-28
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• 2019

Swertiamarin (STM) is an iridoid compound that is present in the Gentianaceae swertia genus. Here we investigated antiapoptotic effects of STM on carbon tetrachloride ($CCl_4$)-induced liver injury and its possible mechanisms. Adult male Sprague Dawley rats were randomly divided into a control group, an STM 200 mg/kg group, a $CCl_4$ group, a $CCl_4+STM$ 100 mg/kg group, and a $CCl_4+STM$ 200 mg/kg group. Rats in experimental groups were subcutaneously injected with 40% $CCl_4$ twice weekly for 8 weeks. STM (100 and 200 mg/kg per day) was orally given to experimental rats by gavage for 8 consecutive weeks. Hepatocyte apoptosis was determined by TUNEL assay and the expression levels of Bcl-2, Bax, and cleaved caspase-3 proteins were evaluated by western blot analysis. The expression of $TGF-{\beta}1$, collagen I, collagen III, CTGF and fibronectin mRNA were estimated by qRT-PCR. The results showed that STM significantly reduced the number of TUNEL-positive cells compared with the $CCl_4$ group. The levels of Bax and cleaved caspase-3 proteins, and $TGF-{\beta}1$, collagen I, collagen III, CTGF, and fibronectin mRNA were significantly reduced by STM compared with the $CCl_4$ group. In addition, STM markedly abrogated the repression of Bcl-2 by $CCl_4$. STM also attenuated the activation of the PI3K/Akt pathway in the liver. These results suggested that STM ameliorated $CCl_4$-induced hepatocyte apoptosis in rats.

• The Journal of Internal Korean Medicine
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• v.21 no.1
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• pp.100-107
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• 2000

Objective : To investigate the effects of Artemisiae Capillaris Fructus on liver injury induced $CCl_4$. Method : Carbon tetrachloride-induced hepatic injury in $CCl_4$,-treated rats caused changes in the glutamic oxaloacetic transaminase(GOT), glutamic pyruvic transaminase(GPT) and alkaline phosphatase(ALP) activities in the serum. Result : The Methanol extract of the Artemisiae Capillaris Fructus was found to protect the rats against such changes significantly. Protective activities were shown to be present in ether-soluble and buthanol-soluble fractions prepared from the above methanol extract. Conclusion : we have examined the detoxyfying effect, one of several medicinal effects of Artemisiae Capillaris Fructus. on liver disorder experimentally induced by $CCl_4$. as an animal model of liver disorder.

• Herbal Formula Science
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• v.27 no.3
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• pp.199-211
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• 2019

Objectives : Present study investigated the hepatoprotective effects of various combinations of lemon balm and dandelion (LD) leaf extract on carbon tetrachloride ($CCl_4$)-induced acute liver injury. Methods : Mice were orally treated with 200 mg/kg of LD extracts [1:1, 1:2, 1:4, 1:6, 1:8, 2:1, 4:1, 6:1, or 8:1 (weight : weight)] for 7 days, and then intraperitoneally injected with $CCl_4$ (0.5 mL/kg). Silymarin (100 mg/kg) was used as reference drug. Body weight gain, relative liver weight, serum biochemistry, histopathologic analyses, and hepatic antioxidant system were examined to elucidate the fittest combination ratio of LD extract. Results : All varying combinations of LD extract significantly increased body weight gain and decreased relative liver weight by $CCl_4$. In addition, LD extract reduced serum aspartate aminotransferase and alanine aminotransferase. Histopathological analyses indicated that LD extract significantly decreased histological activity index score, degenerated hepatocytes, and infiltrated inflammatory cells induced by $CCl_4$. Moreover, LD extract reduced lipid peroxidation, and attenuated the reduction of hepatic glutathione, superoxide dismutase, and catalase by $CCl_4$. Although there were no statistical differences in body weight gain between silymarin- and LD extract-treated groups, administration of 1:1, 2:1, and 4:1 combination of LD extract exhibited more favorable hepatoprotective effects than silymarin. Especially, 2:1 combination of LD extract showed the most potent hepatoprotective effects. Conclusion : Of various combinations of LD extract tested, present results suggest that 2:1 combination of LD extract would be a promising herbal formulation to protect liver from oxidative stress.

• Molecular & Cellular Toxicology
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• v.1 no.4
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• pp.275-280
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• 2005

Carbon tetrachloride ($CCl_4$) is well known hepatotoxicant. Its overdose cause severe centrilobular hepatic necrosis in human and experimental animals. We administered $CCl_{4}$ at low (0.2 mL/kg p.o.) and high (2 mL/kg p.o.) doses to mice. Mice were sacrificed at 24 h after administration. We evaluated liver toxicity by serum AST and ALT level and by microscopic observation. Using cDNA chip, we conducted gene expression analysis in liver. Mean serum activities of the hepatocellular leakage enzymes, ALT and AST, were significantly increased compare to control, respectively, in the low and high dose groups. H&E evaluation of stained liver sections revealed $CCl_{4}-related$ histopathological findings in mice. Moderate centrilobular hepatocellular necrosis was present in all $CCl_{4}$ treated mice. We found that gene expression pattern was very similar between low and high dose group. However, some stress related genes were differently expressed. These results could be a molecular signature for the degree of liver injury. Our data suggest that the degree of severity could be figure out by gene expression profiling.

• Biomolecules & Therapeutics
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• v.12 no.3
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• pp.133-137
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• 2004

Present review is built on base of research work on Ganoderma lucidum in our laboratory. A great deal of experimental evidence has suggested that the pharmacological activities of Ganoderma lucidum (Lingzhi) are related to anti-oxidative and free radical scavenging activity. The anti-oxidative and free radical scavenging effects of polysaccharides and triterpenoids isolated from Ganoderma lucidum in different oxidative injury models including tert-butylhydroperoxide (tBOOH)- damaged mice peritoneal macrophages, alloxan-induced diabetes, experimental liver injury models induced by carbon tetrachloride (CCl4), D-galactosamine (DGal) and Bacillus Calmette-Guerin (BCG) plus lipopolysaccharides (LPS) were investigated. It is also demonstrated that Lugu lingzhi, one of Ganoderma product, significantly inhibited LDL oxidation mediated by endothelial cells and decreased monocyte adhesion to endothelial cell (EC) induced by Oxidative low-density lipoprotein (ox-LDL) and advanced glycation endproducts (AGE). Lugulingzhi-treated serum could markedly inhibit the expression of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-l) induced by ox-LDL and AGE.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2004.04a
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• pp.61-77
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• 2004

Present review is built on base of research work on Ganoderma lucidum in our laboratory. A great deal of experimental evidence has suggested that the pharmacological activities of Ganoderma lucidum(Lingzhi) are related to anti-oxidative and free radical scavenging activity. The anti-oxidative and free radical scavenging effects of polysaccharides and triterpenoids isolated from Ganoderma lucidum in different oxidative injury models including tert-butylhydroperoxide (tBOOH)- damaged mice peritoneal macrophages, alloxan-induced diabetes, experimental liver injury models induced by carbon tetrachloride (CC14), D-galactosamine (DGal) and Bacillus Calmette-Guerin(BCG) plus lipopolysaccharides(LPS) were investigated. It is also demonstrated that Lugu lingzhi, one of Ganoderma product, significantly inhibited LDL oxidation mediated by endothelial cells and decreased monocyte adhesion to endothelial cell (EC) induced by Oxidative low-density lipoprotein (ox-LDL) and advanced glycation endproducts(AGE). Lugulingzhi-treated serum could markedly inhibit the expression of intercellular cell adhesion molecule-l (ICAM-1) and vascular cell adhesion molecule-l (VCAM-1) induced by ox-LDL and AGE.