• Biomolecules & Therapeutics
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• v.26 no.2
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• pp.218-223
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• 2018

The liver is an essential organ for the detoxification of exogenous xenobiotics, drugs and toxic substances. The incidence rate of non-alcoholic liver injury increases due to dietary habit change and drug use increase. Our previous study demonstrated that Ecklonia stolonifera (ES) formulation has hepatoprotective effect against alcohol-induced liver injury in rat and tacrine-induced hepatotoxicity in HepG2 cells. This present study was designated to elucidate hepatoprotective effects of ES formulation against carbon tetrachloride ($CCl_4$)-induced liver injury in Sprague Dawley rat. Sixty rats were randomly divided into six groups. The rats were treated orally with ES formulation and silymarin (served as positive control, only 100 mg/kg/day) at a dose of 50, 100, or 200 mg/kg/day for 21 days. Seven days after treatment, liver injury was induced by intraperitoneal injection of $CCl_4$ (1.5 ml/kg, twice a week for 14 days). The administration of $CCl_4$ exhibited significant elevation of hepatic enzymes (like AST and ALT), and decrease of antioxidant related enzymes (superoxide dismutase, glutathione peroxidase and catalase) and glutathione. Then, it leaded to DNA damages (8-oxo-2'-deoxyguanosine) and lipid peroxidation (malondialdehyde). Administration of ES formulation inhibited imbalance of above factors compared to $CCl_4$ induced rat in a dose dependent manner. Real time PCR analysis indicates that CYP2E1 was upregulated in $CCl_4$ induced rat. However, increased gene expression was compromised by ES formulation treatment. These findings suggests that ES formulation could protect hepatotoxicity caused by $CCl_4$ via two pathways: elevation of antioxidant enzymes and normalization of CYP2E1 enzyme.

• Natural Product Sciences
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• v.10 no.4
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• pp.182-189
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• 2004

To find the action mechanism of the MeOH extract (LFS) of Ligularia fischeri var. spiciformis herbs (Compositae) and its active component, 3,4-dicaffeoylquinic acid (DCQA) on antihepatotoxicity, the effect was investigated on hepatic lipid perxodation and drug-metabolizing enzyme activities in acetaminophen-treated rat. Pretreatment with 250 mg/kg LFS (p.o.) and 10 mg/kg DCQA (p.o.) significantly decreased hepatic lipid peroxidation caused by acetaminophen injection. Further, LFS and DCQA inhibited hepatic microsomal enzyme activation such as hepatic P-450 cytochrome $b_5$, aniline hydroxylase and aminopyrine N-demethylase, suggesting that the two substances might effectively prevent the metabolic activation or scavenge electrophilic intermediates capable of causing hepatotoxicity. Both LFS and DCQA increased hepatic glutathione content and glutathione reductase activity, indicating that both resultantly prevented hepatotoxicity via antioxidative mechanism. Therefore, it was found that LFS had antihepatotoxicity based on the antioxidative action of DCQA.

• Environmental Analysis Health and Toxicology
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• v.14 no.3
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• pp.87-93
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• 1999

Antioxidative and scavenging effects were investigated by using two hyaroxycinnamic acids (caffeetannins). such as caffeic acid and chlorogenic acid, on oxidative stress and hepatotoxicity that induced by paraquat. The results are summerized as follows: 1. To assess radical scavenging ability, reduction concentration (IC$\sub$50/) of 1.1 diphenyl-2-dipicrylhydrazine (DPPH) were measured. IC$\sub$50/ values of caffeic acid and chlorogenic acid were 29.7 ${\pm}$0.6 ${\mu}$M and 26.0${\pm}$0.5 ${\mu}$M respectively. Their radical scavenging activities showed concentration-dependent manner. 2. In H$_2$O$_2$-induced hemolysis assay to rat blood, caffeic acid and chlorogenic acid led to different effects, whose hemolysis inhibition ratios at 100 ${\mu}$M were 45.2${\pm}$7.1% and 11.6${\pm}$3.1% respectively 3. In hypoxanthine-xanthine oxidase system producing superoxide anion, caffeic acid and chlorogenic acid showed different inhibitory activities of xanthine oxidase showing 36.8${\pm}$4.3% and 5.4${\pm}$2.3% respectively. 4. To microsomal NADPH dependent cytochrome p-450 reductase in rat liver, paraquat consumed NADPH at a dose-dependent manner from 0 to 1 ${\mu}$M paraquat concentration. Caffeic acid and chlorogenic acid blocked NADPH consumption rates at concentration-dependent manner and inhibition ratios at 100 ${\mu}$M were 67.6% and 59.2% respectively. 5. Administration (30mg/kg, iv) of paraquat to rats caused the marked elevation of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and lipid peroxides (LPO) in the serum and lipid peroxides in the microsome as compared to the control group. Serum GOT, GPT, LDH, ALP and LPO and liver microsomal LPO were reduced significantly by caffeic acid (50mg/kg), chlorogenic acid (25mg/kg) and silymarin (150 mg/kg) as compared to the paraquat group. From these results, caffeic acid and chlorogenic acid exerted their antioxidative agents by removing reactive oxygen substance (ROS) and scavenging effects by inhibiting ROS generating enzyme. As a general, two hydroxyeinnamic acids showed the useful compounds for scavenger and reducer on the paraquat induced hepatotoxicity.

• Toxicological Research
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• v.23 no.4
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• pp.301-309
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• 2007

Paecilomyces tenuipes (PT), one of the Ascomycetes family, has been used for medicinal purposes due to its broad pharmacological activities. The present study was undertaken to investigate the hepatoprotective effects of PT water extracts against $CCl_4$-induced hepatotoxicity in primary cultures of adult rat hepatocytes. When the extract of PT was directly added into the culture medium at 1, 2, and 5 mg/ml, the extracts not only reduce the $CCl_4$-induced elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase, and lipid peroxide, but also protect cultured hepatocytes from $CCl_4$-induced reduction of reduced glutathione, glutathione reductase, glutathione-S-transferase, glutathione peroxidase, catalase and superoxide dismutase. In addition, the effects of PT water extracts on cytochrome P450 enzymes were relatively marginal, indicating that the hepatoprotective effects of PT extract against $CCl_4$-induced toxicity might not be due to the inhibition of $CCl_4$ activation. In conclusion, the PT extracts were effective in protecting against $CCl_4$ induced hepatotoxicity in hepatocyte cultures, at least in part, by scavenging free radicals, and by modulating enzyme systems involved in cellular oxidative stress.

• Korean Journal of Pharmacognosy
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• v.27 no.3
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• pp.159-166
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• 1996

To evaluate hepatoprotective effects of G009, an hepatoprotective agent which was extracted from the mycelia of Ganoderma lucidum IY009, we were, studied using $CCl_4$-and galactosamine-induced hepatotoxicity in rats. The ratio of liver weight to body weight, the value of glutamic oxaloacetic transaminase(GOT) and glutamic pyruvic transaminase (GPT) activities, the change of a lipids in serum, and the inhibitory activity of malondialdehyde (MDA) formation in serum and liver homogenate were determined in rats. G009 was not significantly changed of the ratio of liver weight to body weight and the content of lipids in serum, but reduced the serum GOT and GPT values in $CCl_4$-and galactosamine-induced hepatotoxicity in rat. Especially, protective effect of G009 on rat hepatic injuries induced by galactosamine was significantly appeared. $CCl_4$ increased markedly the formation of lipid peroxides in the liver homogenate, and serum. The increase of lipid peroxides by $CCl_4$-induced hepatotoxicity was markedly reduced by the treatment with G009. These results suggest that the hepatoprotective effects of G009 may be correlated with its anti-lipid peroxidative activity, therefore, it may be potential agent for hepatic disease.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.6
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• pp.469-476
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• 2012

2,3,7,8-Tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) is an environmental toxicant with a polyhalogenated aromatic hydrocarbon structure and is one of the most toxic man-made chemicals. Exposure to 2,3,7,8-TCDD induces reproductive toxicity, immunotoxicity, and hepatotoxicity. In this study, we evaluated how 2,3,7,8-TCDD-induced hepatotoxicity affect the expression of heat shock proteins and antioxidant enzymes using the real-time polymerase chain reaction (PCR) in rat. 2,3,7,8-TCDD increased heat shock protein (Hsp27, ${\alpha}$-B-crystallin, Mortalin, Hsp105, and Hsp90s) and antioxidant enzymes (SOD-3, GST and catalase) expression after a 1 day exposure in livers of rats, whereas heat shock protein (${\alpha}$-B-crystallin, Hsp90, and GRP78) and antioxidant enzymes (SOD-1, SOD-3, catalase, GST, and GPXs) expression decreased on day 2 and then slowly recovered back to control levels on day 8. These results suggest that heat shock proteins and antioxidant enzymes were induced as protective mechanisms against 2,3,7,8-TCDD induced hepatotoxicity, and that prolonged exposure depressed their levels, which recovered to control levels due to reduced 2,3,7,8-TCDD induced hepatotoxicity.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.1
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• pp.87-91
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• 2002

This study was designed to investigate the effects of Hijikia fusiforme (Harvey) Okamura ethanol extract on the ethanol-induced hepatotoxicity of rat administered orally experimental diets for 6 weeks. Sprague-Dawley rats weighing about 100 g were divided into 4 groups; normal group (NOR), ethanol (35% ethanol 10 mL/kg b.w/day) treated group (CON), ethanol and Hijikia fusiforme ethanol extract 200 mg/kg (HE1) and 400 mg/kg (HE2) concomitantly treated group, respectively. Each group was examined for the growth rate, feed efficiency ratio (FER), activities of antioxidative enzymes and contents of TBARS and glutathione. Hijikia fusiforme ethanol extract showed increasing effects of the growth rate by 43%, and FER was gradually increased by Hijikia fusiforme ethanol extract treatment, compard with ethanol treatment. Ethanol elevated the activities of superoxide dismutase, catalase and glutathione peroxidase of rat liver markedly as compared to normal group, but those activities were significantly decreased in Hijikia fusiforme ethanol extract treatment by 56%, 38% and 25%, respectively. Xanthine oxidase activity elevated by ethanol was not affected by Hijikia fusiforme ethanol extract. The content of TBARS increased by ethanol treatment was signigicantly decreased in HE2, and the glutathione content depleted by ethanol treatment was increased by Hijikia fusiforme ethanol extract administration adjacent to normal level. These results suggest that Hijikia fusiforme ethanol extract is believed to be a possible protective effect for the ethanol-induced hepatotoxicity of rat liver.

• Korean Journal of Plant Resources
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• v.28 no.5
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• pp.551-560
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• 2015

Here we report the protective activity of cultured Acer tegmentosum cell extract against liver damage in rat intentionally instigated by D-galactosamine. Local fat degeneration and infiltration of inflammatory cells were significantly decreased in cultured A. tegmentosum cell extract administered rat. In addition, acutely increased AST, ALT, LDH, ALP activities and lipid peroxidation and lipid content by liver damage were recovered in experimental rat administrated with A. tegmentosum extract. These results showed that cultured A. tegmentosum cell extract has a role in blood enzyme activation and lipid content restoration within damaged rat liver tissues. Moreover expression rate of TNF-α which accelerates inflammation and induces tissue damage and necrosis was significantly decreased. Also activities of antioxidant enzymes were more effectively upregulated comparing to those of the control group induced hepatotoxicity. All data that cultured A. tegmentosum cell extract has a preventive role against liver damages such as inflammation, tissue necrosis in rats by improving activities of blood enzymes, antioxidant enzymes and modulating expression of inflammation factor, suggest that cultured Acer tegmentosum cell extract is an effective medicinal resource for restoration of hepatotoxicity.

• Journal of Ginseng Research
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• v.27 no.1
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• pp.11-16
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• 2003

In this study, we investgated the effect of Red Ginseng (KRG) on liver damage induced by carbon tetrachloride (CTC) and galactosamine (GalN) in rats using indicator enzymes such as serum alanine/aspartate aminotransferases, sorbital dehydrogenase, lactate dehydrogenase, and ${\gamma}$-glutamyltransferase. Treatment of KRG restored these enzyme activities to near normal level compared to CTC or GalN treatment alone. Treatment of KRG also enhanced hepatic microsomal enzyme system, malondialdehyde formation, and depletion of reduced glutathione content, which were reduced by CTC or GalN. We also found that the decreased activities of glutathione S-transferase and glutathine reductase but not ${\gamma}$-glutamycysteine synthetase after KRG treatment restored to normal level. These results indicate that KRG has potent therapeutic activity against CTC- and GalN-induced hepatotoxicity in rat.

• Advances in Traditional Medicine
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• v.10 no.1
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• pp.29-36
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• 2010

The present study was aimed to investigate the hepatoprotective and antioxidant activities of ethanol extract from Monochoria vaginalis (250 mg/kg and 500 mg/kg B/W) on acetaminophen (APAP) induced rat hepatic injury. Monochoria vaginalis is a traditional medicinal plant that is commonly used to treat and improve liver conditions in India and other Asian countries. The development of hepatotoxicity induced by APAP is promoted by oxidative stress. APAP treated group significantly (P < 0.01) elevated the serum enzymatic levels like glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, alkaline phosphatase (SALP), total bilirubin and malondialdehyde (MDA), which were restored towards normalization significantly (P < 0.01) thanol extract of yonochoria vagin is (EEMV). In addition, the EEMV significantly (P < 0.01) elevated the decreased level of total protein and antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione-s-transferase and reduced glutathione. Apart from these, histopathological changes also showed the protective nature of the EEMV against APAP induced hepatic damage in liver tissues. The activity of EEMV at 500 mg/kg B/W was comparable to the standard drug silymarin (25 mg/kg B/W). In conclusion, these data suggest that the EEMV possess hepatoprotective and antioxidant effects against APAP-induced hepatotoxicity and oxidative stress in rats.