• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10413-10420
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• 2015

Side effects are an unavoidable consequence of chemotherapy drugs, during which liver injury often takes place. The current study was designed to investigate the protective effect of Astragalus polysaccharides (APS) against the hepatotoxicity induced by frequently-used chemical therapy agents, cyclophosphamide (CTX), docetaxel (DTX) and epirubicin (EPI)) in mice. Mice were divided into five groups, controls, low or high dose groups ($DTX_L$, $CTX_L$, $EPI_L$ or $DTX_H$, $CTX_H$, $EPI_H$), and low or high dose chemotherapeutics+APS groups ($DTX_L$+APS, $CTX_L$+APS, $EPI_L$+APS or $DTX_H$+APS, $CTX_H$+APS, $EPI_H$+APS). Controls were treated with equivalent normal saline for 28 days every other day; low or high dose group were intraperitoneal (i.p) injected with low or high doses of CTX, DTX and EPI for 28 days every other day; low or high dose chemotherapeutics+APS group were separately intraperitoneal (i.p) injected with chemotherapeutics for 28 days every other day and i.p with APS (100 mg/kg) for 7 days continually from the 22th to the 28th days. The body weight, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), histopathological features, and ultrastructure morphological change of liver tissues, protein expression level of caspase-3 were estimated at different time points. With high dose treatment of DTX, CTX and EPI, weight gain was inhibited and serum levels of ALT and AST were significantly increased. Sections of liver tissue showed massive hepatotoxicity in $CTX_H$ group compared to the control group, including hepatic lobule disorder, granular and vacuolar degeneration and necrosis in hepatic cells. These changes were confirmed at ultrastructural level, including obvious pyknosis, heterochromatin aggregation, nuclear membrane resolution, and chondrosome crystal decrease. Western blotting revealed that the protein levels of caspase-3 increased in $CTX_H$ group. The low dose groups exhibited trivial hepatotoxicity. More interestingly, after 100 mg/kg APS, liver injury was redecued not only regarding serum transaminase activities (low or high dose chemotherapeutics+APS group), but also from pathological and ultrastructural changes and the protein levels of caspase-3 ($CTX_H$+APS group). In conclusion, DTX, CTX and EPI induce liver damage in a dose dependent manner, whereas APS exerted protective effects.

• The Korea Journal of Herbology
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• v.33 no.6
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• pp.61-70
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• 2018

Objectives : Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of hepatic triglycerides (TG) that leads to inflammation and fibrosis. Crataegi Fructus ethanol extract (CE) is a korean traditional herb that used for digestive diseases. It has been investigated that CE has the effect that prevent hepatotoxicity caused by CCl4 or GaIN and regulate the inflammatory in several organs. However, a hypolipidemic effect of CF has not been reported. Methods : The purpose of this study is that examine the lipid accumulation inhibitory effect of CE on NAFLD. We checked the body and liver weight change of MCD-diet induced mice with/without administration of CE. The blood lipid levels of C57BL/6J mice were checked by biochemistry. Also we observed the liver histology of MCD-diet induced mice and investigate the molecular mechanisms in MCD-diet-induced NAFLD in C57BL/6J mice. Results : CE improved MCD-diet-induced lipid accumulation and TG and TC levels. Also, CE decreased hepatic lipogenesis such as SREBP-1, $C/EBP{\alpha}$, $PPAR{\gamma}$, ACC and FAS. Besides, we also found out that CE increased AMPK phosphorylation. These results indicated that CE has the same ability to activate AMPK and then reduce SREBP-1, and FAS expression, finally leading to inhibit hepatic lipogenesis and hepatic antioxidative ability. Conclusions : In this report, we found CE exerted a regulatory effect on lipid accumulation by decreasing lipogenesis in MCD-diet induced NAFLD model. Therefore, CE extract may be active in the prevention of fatty liver.

• The Journal of Internal Korean Medicine
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• v.32 no.4
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• pp.550-564
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• 2011

Objectives : Oxidative stress seems to play a major role in mechanisms by which ethanol causes liver injury. Previous studies have shown that treatment with Yinjinchunggan-tang (Yinchenqinggan-tang, YJCGT) has protective effects on alcoholic liver disease. The aim of this study was to investigate the protective effects of YJCGT on alcohol-induced oxidative stress. Materials and Methods : In vitro, we evaluated the inhibitory activities of YJCHT on DPPH(1,1-diphenyl-2-picryl-hydrazyl), xanthine oxidase, trypsin, and hyaluronidase. In a cell culture model, we measured cell viability and proliferation, and the activities of superoxide dismutase (SOD), and catalase (CAT) after YJCGT treatment in C34 and E47 cell lines, and HepG2 cells transfected with/ without cytochrome P450IIE1 (CYP2E1) gene. In vivo, we estimated serum level of hepatic biochemical markers, and alcohol concentration in the blood. Results : YJCGT showed significant free radical scavenging activity against DPPH and xanthine oxidase and decreased hyaluronidase activity effectively in vitro. YJCGT also increased cell viability, and proliferation in C34 and in E47 cell lines, and increased activities of superoxide dismutase, and catalase in C34 and in E47 cell lines. YJCGT reduced serum AST, LDH, and total cholesterol level in some of the results, and reduced blood alcohol concentration in vivo, as well. Conclusions : This study suggests that YJCGT has protective effects on oxidative stress by inhibiting alcohol-induced suppression of antioxidant enzyme activities.

• YAKHAK HOEJI
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• v.43 no.4
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• pp.516-525
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• 1999

Hedera rhombea (HR) has been used for treatments of hemorrage, chronic catarrh, jaundice, lithisis and convulsion. This study was done to isolate active compounds that have protective effect on liver damage. BuOH and EtOAc fractions of HR recovered serum glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT) and ${\gamma}-glutamyltranspeptidase$ (${\gamma}-GTP$) activities in CCl4 treated rats. We isolated 7 phenolic compounds from BuOH and EtOAc fractions, which were identified as 3-caffeoyl quinic acid, 3,4-di-O-caffeoyl quinic acid, 3,5-di-O-caffeoyl quinic acid, 4,5-di-O-caffeoyl quinic acid, caffeic acid, methyl 3,4-di-O-caffeoyl quinic acid and methyl 3,5-di-O-caffeoyl quinic acid by chemical and spectral analysis. These compounds reduced significantly serum GOT and GPT elevated by CCl4 treatment in rats, and 3-caffeoyl quinic acid, 3,5-di-O-caffeoyl quinic acid and caffeic acid also showed mild inhibitory activity against human immunodeficiency virus.

• Biomolecules & Therapeutics
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• v.7 no.1
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• pp.35-43
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• 1999

Hepatoprotective effects of Malloti cortex extract (MCE) from Mallotus japonicus against the carbon tetrachloride (CCl$_{4}$) and galactosamine (GalN) were investigated. Whereas serum aspartate aminotransferase and alanine aminotransferase levels were markedly elevated after CCl$_{4}$ and GalN administration, pretreatment and posttreatment with MCE before and after the injection of CCl$_{4}$ and GalN resulted in decreases in elevated serum aminotransferase activities. Whereas CCl$_{4}$ and GalN treatment caused 3~7 fold increases in sorbitol dehydrogenase and ${\gamma}$-glutamyltransferase activities, pretreatment and posttreatment with MCE resulted in the blocking of CCl$_{4}$ and GalN-induced liver toxicity. The hepatoprotective effect of MCE was in part due to MCE-induced elevation of hepatic glutathione levels. Pretreatment and posttreatment with MCE also reduced increased lipid peroxidation induced by CCl$_{4}$ and GalN. These results suggest that MCE may be useful for the prevention and therapy of hepatotoxic pathogenesis. It is presumed that protective and therapeutic effects of MCE due to be inducible glutathione S-transferase and glutathione reductase activities, involving in glutathione-medicated detoxication and maintainment of glutathione content, respectively.

• Journal of the Korean Society of Food Science and Nutrition
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• v.25 no.5
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• pp.839-845
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• 1996

To investigate effects of Jujube methanol extract on the carbon tetrachloride-induced liver damage in rats, experimental animals were divided into 4 groups; control group(CON), Jujube methanol extracttreated group(JME), $CCl_4$- treated groups(CCl), and Jujube methanol extract and $CCl_4$-treated group (JMC). Each group was sacrificed after 2 or 4week feeding and determined the activities of serum transaminase(GOT, GPT) and hepatic xanthine oxidase, superoxide dismutase(SOD), catalase and glutathione peroxidase(GSH-Px), and hepatic contents of thiobarbituric acid-reactants(TBARS) and glutathione in liver. The activities of sGOT and sGPT, and the hepatic content of TBARS after $CCl_4$-treatment were markedly increased, compared to CON, but those levels were significantly decreased by the pretreatment of Jujube methanol extract, especially in sGOT after 2 and 4 week and TBARS after 4week respectively. Xanthine oxidase activity was increased by $CCl_4$- treatment as compared to CON, but it was also inhibited by the pretreatment of Jujube methanol extract for 2 and 4 week. The activities of SOD, catalase and GSH-Px were elevated by $CCl_4$-treatment, compared to CON, but those elevated activities were showed significant decreasing effect by pretreatment of Jujube methanol extract after 2 and 4week as compared to CON, however, hepatic catalase activity was not affected significantly. These results suggest that Jujube methanol extract is believed to be a possible protective effect for the carbon tetrachloride-induced hepatotoxicity in rats.

• Journal of Food Hygiene and Safety
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• v.33 no.1
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• pp.77-82
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• 2018

This study was carried out to investigate the effect of natural Eriobotrya japonica Lindl. vinegar on the liver protective effect of animals exposed to carbon tetrachloride. Eriobotrya japonica Lindl. vinegar (200 mg/kg) was administered at the same time for 28 days, and hepatotoxicity was induced by intraperitoneal injection of carbon tetrachloride on the $29^{th}$ day. The aspartate aminotransferase and alanine aminotransferase levels were significantly decreased (p < 0.001) and the superoxide dismutase and catalase activities were significantly increased (p < 0.001) in the Eriobotrya japonica Lindl. vinegar group compared to the control group. Histopathological observations showed that the Eriobotrya japonica Lindl. vinegar showed hepatic cell structure similar to normal group, and these results showed that it had an effect of suppressing and protecting the damage of liver cell. Therefore, Eriobotrya japonical Lindl. vinegar is considered to be a healthy functional food of the liver.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.2
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• pp.413-418
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• 2004

Objectives : Cirsii Japonici Herba (CJH) is one of medicinal plants that has been frequently used for styptic purposes in Asian countries. In order to evaluate a hepatoprotective effects of CJH in the liver fibrotic diseases, the present study investigated how CJH improves a hepatic function in the dimethylnitrosamine(DMN) treated rat. Methods : CJH were orally administered to rats that has been treated with DMN. Subsequently, the amount of blood L-asparate aminotransferase (AST), L-alanine aminotransferase (ALT), and hydroxyproline were quantitated. Several histopathological markers for examining the degree of hepatic fibrosis were investigated by H-E and Masson-Trichrome staining. Results: DMN treatment caused a increase of relative liver weight to the body at 14 days after DMN induction, Administration of CJH with 100mg/kg and 1,000mg/kg dose decreased significantly the AST level elevated by DMN injection(p<0.01). But ALT level was not improved. The hydroxyproline level was reduced by a simultaneous treatment of CJH with DMN for 7 days, but not recovered completely to its normal value, CJH administration improved conspicuously the DMN-induced histopathological changes of liver such as granuloma, but cell necrosis and fibrosis were not improved with CJH 1,000mg/kg dose. Conclusion: These results indicate that CJH has protective effect on liver injury and can inhibit liver fibrosis Induced by DMN in rats.

• The Journal of Korean Medicine
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• v.31 no.5
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• pp.90-102
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• 2010

Objectives: This study was investigated the protective effect of Spatholobi Caulis water extract against cadmium (CdCl2, Cd)-induced hepatic toxicity in rats. Methods: To induce acute hepatic toxicity, Cd (4 mg/kg body weight) was dissolved in normal saline and intravenously injected into rats. Then, the rats received either a vehicle or silymarin (100 mg/kg) or Spatholobi Caulis water extract (30, 50 mg/kg/day) for 3 days, and were exposed to a single injection of Cd 24 h after the last Spatholobi Caulis/vehicle treatment. Results: Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were significantly increased by Cd treatment. In contrast, pretreatment with Spatholobi Caulis reduced ALT, AST and LDH. Cd-intoxicated liver damage was significantly inhibited by treatment of Spatholobi Caulis 30 and 50 mg/kg at histopathological observations in the present study. Conclusions: These results can be considered as direct evidence that Spatholobi Caulis has favorable inhibitory effects on the Cd-intoxicated liver damages. The efficacy of Spatholobi Caulis 30 mg/kg shows similar effects to that of silymarin 100 mg/kg, and more favorable hepatoprotective effects were observed in Spatholobi Caulis 50 mg/kg as compared with silymarin 100 mg/kg against Cd-intoxicated hepatopathies in the present study.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.1
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• pp.15-23
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• 2016

Acetaminophen (APAP) overdose is one of the most common causes of acute liver failure. The study aimed to investigate the protective effect of carnosic acid (CA) on APAP-induced acute hepatotoxicity and its underlying mechanism in mice. To induce hepatotoxicity, APAP solution (400 mg/kg) was administered into mice by intraperitoneal injection. Histological analysis revealed that CA treatment significantly ameliorated APAP-induced hepatic necrosis. The levels of both alanine aminotransferase (ALT) and aspartate transaminase (AST) in serum were reduced by CA treatment. Moreover, CA treatment significantly inhibited APAP-induced hepatocytes necrosis and lactate dehydrogenase (LDH) releasing. Western blot analysis showed that CA abrogated APAP-induced cleaved caspase-3, Bax and phosphorylated JNK protein expression. Further results showed that CA treatment markedly inhibited APAP-induced pro-inflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and MCP-1 mRNA expression and the levels of phosphorylated $I{\kappa}B{\alpha}$ and p65 protein in the liver. In addition, CA treatment reduced APAP- induced hepatic malondialdehyde (MDA) contents and reactive oxygen species (ROS) accumulation. Conversely, hepatic glutathione (GSH) level was increased by administration of CA in APAP-treated mice. Mechanistically, CA facilitated Nrf2 translocation into nuclear through blocking the interaction between Nrf2 and Keap1, which, in turn, upregulated anti-oxidant genes mRNA expression. Taken together, our results indicate that CA facilitates Nrf2 nuclear translocation, causing induction of Nrf2-dependent genes, which contributes to protection from acetaminophen hepatotoxicity.