• Advances in Traditional Medicine
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• 제7권3호
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• pp.311-320
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• 2007

The present study was designed to estimate the protective effect of (-) epigallocatechin gallate (EGCG) on ethanol-induced liver injury in rats. Chronic ethanol administration (6 g/kg/day ${\times}$ 60 days) caused liver damage that was manifested by the elevation of markers of liver dysfunction - aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, bilirubin and ${\gamma}$-glutamyl transferase in plasma and reduction in liver glycogen. The activities of alcohol metabolizing enzymes such as alcohol dehydrogenase and aldehyde dehydrogenase were found to be altered in alcohol-treated group. Ethanol administration resulted in the induction of cytochrome p450 and cytochrome-$b_{5}$ activities and reduction of cytochrome-c reductase and glutathione-S-transferase, a phase II drug metabolizing enzyme. Further, ethanol reduced the viability of isolated hepatocytes (ex vivo) as assessed by trypan blue exclusion test and induced hepatocyte apoptosis as assessed by propidium iodide staining. Treatment of alcoholic rats with EGCG restored the levels of markers of liver injury and mitigated the alterations in alcohol metabolizing and drug metabolizing enzymes and cyt-c-reductase. Increased hepatocyte viability and reduced apoptotic nuclei were observed in alcohol + EGCG-treated rats. These findings suggest that EGCG acts as a hepatoprotective agent against alcoholic liver injury.

• Biomolecules & Therapeutics
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• 제26권2호
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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.

• Journal of Ginseng Research
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• 제44권6호
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• pp.815-822
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• 2020

Background: Recently, beneficial roles of ginsenoside F2 (GF2), a minor constituent of Panax ginseng, have been demonstrated in diverse inflammatory diseases. However, its roles in alcoholic liver inflammation and injury have not been clearly understood. Here, we investigated the underlying mechanism by which GF2 ameliorated alcoholic liver injury. Methods: To induce alcoholic liver injury, C57BL/6J wild type (WT) or interleukin (IL)-10 knockout (KO) mice were orally administered with ethanol (3 g/kg) or ethanol-containing GF2 (50 mg/kg) for 2 wk. Liver injury and infiltration of macrophages and neutrophils were evaluated by serum biochemistry and immunohistochemistry, respectively. The changes of hepatic immune cells were assessed by flow cytometry and polymerase chain reaction analysis. In vitro differentiation of naïve T cells was performed. Results: GF2 treatment significantly attenuated alcoholic liver injury, in which infiltrations of inflammatory macrophages and neutrophils were decreased. Moreover, the frequencies of Foxp3⁺ regulatory T cells (Tregs) increased but IL-17-producing T (Th17) cells decreased in GF2-treated mice compared to controls. Furthermore, the mRNA expression of IL-10 and Foxp3 was significantly increased, whereas IL-17 mRNA expression was suppressed in GF2-treated mice. However, these beneficial roles of GF2 were not observed in GF2-treated IL-10 KO mice, suggesting a critical role of IL-10. Similarly, GF2 treatment suppressed differentiation of naïve T cells into Th17 cells by inhibiting RORgt expression and stimulating Foxp3 expression. Conclusion: The present study suggests that GF2 treatment attenuates alcoholic liver injury by increasing IL-10 expression and Tregs and decreasing IL-17 expression and Th17 cells.

• 대한한의학방제학회지
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• 제26권2호
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• pp.113-122
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• 2018

Objectives : Alcoholic fatty liver is an early and reversible consequence of excessive alcohol consumption. The initial hepatocyte cell death stimulates subsequent inflammatory responses, leading to further liver injury and fibrosis. The objective of this study is to investigate the effects of Injinsaryung-san extract on the alcoholic fatty liver by chronic EtOH administration. Method : Male Sprague Dawley rats were used in this study. All animals were randomly divided into Normal group, treated with saline (n=10); EtOH group, treated with ethanol (n=10); EtOH+IS group, treated with ethanol+Injinsaryung-san extract (n=10). For oral administration of ethanol in Control and Sample group, the ethanol was dissolved in distilled water in concentrations of 25%(v/v). Throughout the experiment of 8 week, the rats were allowed free access to water and standard chow. Sample group were administrated by Injinsaryung-san extract daily for 8 weeks. Results : The levels of hepatic marker such as aspartate aminotransferase and alanine aminotransferase were altered. Histopathological changes were reduced and the expression of tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) was markedly attenuated by Injinsaryung-san extract. Conclusion : These data suggest that Injinsaryung-san extract could be effective in protecting the liver from alcoholic fatty liver. The hepatoprotective mechanisms of Injinsaryung-san may be related to attenuation of $TNF-{\alpha}$ protein, as well as to the inhibition of inflammatory response in the liver. Therefore, Injinsaryung-san can be a candidate to protect against alcoholic fatty liver.

• Journal of Applied Biological Chemistry
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• 제66권
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• pp.159-164
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• 2023

Ferroptosis is a type of regulated cell death recently discovered, characterized by the accumulation of iron-dependent lipid peroxides in the cell membrane, and it involves a complex network of signaling pathways, including iron metabolism, lipid peroxidation, and redox regulation. The dysregulation of these pathways can lead to the induction of ferroptosis and the development of liver diseases, such as alcoholic liver disease, non-alcoholic fatty liver disease, viral hepatitis, and liver cancer. Studies have demonstrated that targeting key molecules involved in iron metabolism, lipid peroxidation, and redox regulation can reduce liver injury and improve liver function in different liver diseases by inhibiting ferroptosis. Thus, modulation of ferroptosis presents a promising therapeutic target for treating liver diseases. However, further research is required to gain a more comprehensive understanding of the mechanisms underlying the role of ferroptosis in liver diseases and to develop more effective and targeted treatments.

• 대한본초학회지
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• 제30권1호
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• pp.51-57
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• 2015

Objectives : The effect of pear extract with Daekumeumjagami and vitamin C medication(PDV) on alcohol metabolism and hepatic injury was assessed following hepatic injury induced by alcohol in mice. Methods : The model of alcoholic hepatic injury was established by orally administration with 3 g/kg 25% alcohol in mice. PDV was orally administrated once a day for 5 days. Mice were randomly divided into 5 groups : normal group, control group, and PDV groups (PDV-A, PDV-B and PDV-C). The activities of aspartate amino transferase (AST) and alanine amino transferase (ALT) and alcohol dehydrogenase (ADH) in serum, superoxide dismutase (SOD) and catalase in liver were determined after alcohol exposure. Results : Compared with control group, treatment with PDV-B and PDV-C significantly elevated activities of ADH. Moreover, the index of hepatic injury in serum was significantly decreased by treatment with PDV-B and PDV-C in ALT activity and PDV-C in AST activity. Additionally, enhanced catalase activities in liver was found in PDV-C treated mice after exposure to alcohol. Also, WBC in blood was significantly lower by treatment with PDV-B and PDV-C. Conclusions : This study suggests that PDV treatment could enhance alcohol metabolism, and prevent hepatic injury after alcoholic hepatic injury and that this effect is likely related to its modulation on the alcohol metabolizing and antioxidant enzymes.

• 대한한의학방제학회지
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• 제28권2호
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• pp.179-187
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• 2020

Objectives : This study investigated the hepatoprotective effects effects of Jageum-jung extract on alcohol-induced liver disease mice model. Methods : Alcoholic liver disease was induced by Ethanol in C57/BL6 male mice, which were fed Lieber-DeCarli liquid diet containing ethanol. Jageum-jung (100,200 and 300 mg/kg bw/day) were orally administered daily in the alcoholic fatty liver disease mice for 16 days. Results : The results indicate that Jageum-jung promotes hepatoprotective effects by significantly reducing aspartate transaminase (AST) and alanine transaminase (ALT) levels as indicators of liver damage in the serum. Furthermore, Jageum-jung decreased accumulation of triglyceride and total cholesterol, increased levels of superoxide dismutase (SOD) and glutathione (GSH) in the serum of the alcoholic fatty liver disease mice model. Additionally, it improved the serum alcohol dehydrogenase (ADH) activity. Conclusions : This study confirmed the anti-oxidative and hangover elimination effects of Jageum-jung extract, and suggests the possibility of using Jageum-jung to treat alcholic liver disease.

• 대한한의학회지
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• 제18권1호
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• pp.411-429
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• 1997

Recent survey shows that chronic liver disease such as chronic hepatitis, liver cirrhosis and hepatoma is the third leading causes for death in Korea. In oriental medicine, viral hepatitis is related to Hwangdal(黃疸) and alcoholic liver disease is related to Joosang(酒傷). ARTEMISIAE HERBA and PUERARIAE RADIX have long been used in treating those symptoms. This study was done to evaluate the effect of AR1EMISIAE HERBA and PUERARIAE RADIX on viral and alcoholic hepatitis. ARTEMISIAE HERBA and PUERARIAE RADIX were decocted respectively with water and followed by vaccum evaporation. The solution was diluted to adequate concentration. Sprague-Dawley rats were used in this experiment. Each group was given PUERARIAE RADIX or ARTEMISIAE HERBA solution orally and CCl4, d-galactosamine or alcohol was given orally 30 minutes later. After 24 hours of starvation, blood samples were taken to check serum GOT, GPT, LDH and ALP activities, TC, TG, glucose and BUN levels. These results show that ARTEMISIAE HERBA has better effect on liver injury induced by d-Galactosamine than PUERARIAE RADIX and that both ARTEMISIAE HERBA and PUERARlAE RADIX have good effect on acute alcoholic liver disease while in the liver injury induced by $CCl_{4}$, PUERARIAE RADIX has better inhibitory effect on serum AST, ALT and ALP levels and ARTEMISIAE HERBA has better inhibitory effect on serum total cholesterol and triglyceride. And the result that high concentration group has better effect shows these effects are concentration-dependent. Further study on the mechanism of these herbs is still required.

• 대한한의학방제학회지
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• 제28권2호
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• pp.189-198
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• 2020

Objectives : This study investigated the liver-protective effects of MJY2018, a Herbal formula, against alcoholic fatty liver disease and anti-oxidative effects. Methods : Its effects were investigated in an alcoholic fatty liver disease model in male C57BL/6 mice, which were fed Lieber-DeCarli liquid diet containing ethanol. MJY2018 (100 and 200 mg/kg bw/day) or silymarin (50 mg/kg bw/day) were orally administered daily in the alcoholic fatty liver disease mice for 16 days. Results : The results indicate that MJY2018 promotes hepatoprotection by significantly reducing aspartate transaminase (AST) and alanine transaminase (ALT) levels as indicators of liver damage in the serum. Furthermore, MJY2018 reduced accumulation of triglyceride and total cholesterol, increased levels of superoxide dismutase (SOD) and glutathione (GSH) in the livers of the alcoholic fatty liver disease mice model. Additionally, it improved the serum alcohol dehydrogenase (ADH) activity. Conclusions : These results indicate that MJY2018 were effective in improving and protecting oxidative stress and alcoholic liver disease.

• Journal of Nutrition and Health
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• 제49권6호
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• pp.420-428
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• 2016

본 연구에서는 Sprague-Dawley 종 흰 쥐 수컷을 정상 대조군 (C), 알코올 군 (E), 알코올 + 100 mg/kgBW 곤드레 에탄올 추출물군 (E+LCS), 알코올 + 500 mg/kgBW 곤드레 에탄올 추출물군 (E+HCS)으로 나누어 Lieber-DeCarli control diet 혹은 Lieber-DeCarli ethanol diet를 8주간 공급하였으며, 이때 곤드레 에탄올 추출물은 액상 사료에 직접 섞어 공급하였다. 알코올과 곤드레 에탄올 추출물의 식이 공급 종료 후 간 조직의 지방구 축적 정도를 살펴본 결과, E+LCS군과 E+HSC군은 E군에 비해 지방간 발생이 유의적으로 억제되었으며, 정상 대조군인 C군과 유의적인 차이가 없었다. 이와 비슷하게, 곤드레 에탄올 추출물의 공급은 알코올에 의해 증가된 간 조직과 혈청의 중성지방 농도를 유의적으로 낮추었으며, 혈청 AST와 혈청 ALT 활성도 정상 대조군 수준으로 회복시키는 것으로 나타났다. 한편, 곤드레 에탄올 추출물의 공급은 p-AMPK과 p-ACC 단백질 수준을 농도 의존적으로 증가시켰으며, 두 단백질 모두 E군에 비해 E+HSC군에서 유의적으로 높게 나타났다. 또한 FAS mRNA와 SCD1 mRNA 수준은 E군에 비해 E+HSC군에서 유의적으로 낮게 나타났다. 곤드레 에탄올 추출물은 간 조직에서 알코올 공급에 의해 증가된 $NF{\kappa}B$의 활성을 유의적으로 낮추었으며, $NF{\kappa}B$의 표적 단백질인 $TNF{\alpha}$ 단백질 수준을 농도의존적으로 낮추었다. 본 연구 결과를 통해 곤드레는 알코올에 의한 지방간 발생 및 관련된 간 손상을 유의적으로 억제할 수 있음을 확인하였으며 이 과정에서 AMPK 활성 증가와 $NF{\kappa}B$ 활성 억제가 관여함을 제시하였다.