• Toxicological Research
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• 제30권1호
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• pp.49-54
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• 2014

In this study, we investigated the hepatoprotective effects of aged black garlic (ABG) in rodent models of liver injury. ABG inhibited carbon tetrachloride-induced elevation of aspartate transaminase (AST) and alanine transaminase (ALT), which are markers of hepatocellular damage, in SD rats. D-galactosamine-induced hepatocellular damage was also suppressed by ABG treatment. However, ABG does not affect the elevation of alkaline phosphatase (ALP), a marker of hepatobilliary damage, in rats treated with carbon tetrachloride or D-galactosamine. We also examined the effect of ABG on high-fat diet (HFD)-induced fatty liver and subsequent liver damage. ABG had no significant effect on body weight increase and plasma lipid profile in HFD-fed mice. However, HFD-induced increase in AST and ALT, but not ALP, was significantly suppressed by ABG treatment. These results demonstrate that ABG has hepatoprotective effects and suggest that ABG supplementation might be a good adjuvant therapy for the management of 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.

• 한국자원식물학회지
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• 제19권6호
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• pp.649-654
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• 2006

The objective of present study was to investigate the anti oxidative and hepatoprotective effects of tomato extracts. Total antioxidant capacity and total antioxidant response were 5.5 and $19.8{\mu}g$ Trolox equivalent per mg of tomato extract, respectively. DPPH radical scavenging activity of tomato extracts ($10mg\;ml^{-1}$) was 70% as compared to 100% by pyrogallol solution as a reference. The effect of the tomato extracts on lipid peroxidation was examined using rat liver mitochondria induced by iron/ascorbate. Tomato extracts at the concentration of $0.5mg\;ml^{-1}$ significantly decreased TBARS concentration. Tomato extracts prevented lipid peroxidation in a dose-dependent manner. The effect of the tomato extracts on reactive oxygen species (ROS) generation was examined using cell-free system induced by $H_2O_2/FeSO_4$. Addition of $1mg\;ml^{-1}$ of tomato extracts significantly reduced dichlorofluorescein (DCF) fluorescence. Tomato extracts caused concentration-dependent attenuation of the increase in DCF fluorescence, indicating that tomato extracts significantly prevented ROS generation in vitro. The effect of tomato extracts on cell viability and proliferation was examined using hepatocyte culture. Primary cultures of rat hepatocytes were incubated with 1mM tert-butyl hydroperoxide (t-BHP) for 90 min in the presence or absence of tomato extracts. MTT values by addition of tomato extracts at the concentration of 2, 10, and $20mg\;ml^{-1}$ in the presence of t-BHP were 13, 33 and 48%, respectively, compared to 100% as control. Tomato extracts increased cell viability in a dose-dependent manner. These results demonstrate that tomato extracts suppressed lipid peroxidation and t-BHP-induced hepatotoxicity and scavenged ROS generation. Thus antioxidant and hepatoprotective effects of tomato extracts seem to be due to, at least in part, the prevention from free radicals-induced oxidation, followed by inhibition of lipid peroxidation.

• 약학회지
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• 제42권1호
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• pp.82-88
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• 1998

The effect of hepatoprotective agents and bile acids on tumor necrosis factor-alpha, (TNF-${\alpha}$) production in murine and human macrophage cell line (RAW264.7 and U937) was inve stigated. The hepatoprotective agents including silymarin and its major component, silybin, significantly inhibited TNF-alpha production in a concentration dependent manner ($IC_50$ of silybin=67.7${\mu}g$/ml (140.3${\mu}g$M)). In differentiated U937 cells, especially, silybin showed more effective inbitory activity ($IC_50$=35.1${\mu}g$g/ml (72.7${\mu}g$M)). These results suggest that silymarin and silybin may inhibit TNF-alpha production in the process of hepatic diseases in human. However, biphenyldimethyl dicarboxylate (DDB) was not effective. In the case of bile acids, chenodeoxycholic acid (CDCA) showed a concentration dependent inhibitory effect on TNF-alpha production ($IC_50$ of CDCA= 71.5${\mu}g$g/ml (182.1${\mu}g$M)). In contrast, glycine or taurine conjugated form (G-CDCA or T-CDCA) restored to the control level or significantly increased TNF-${\alpha}$ production. And also ursodeoxycholic acid (UDCA) and its conjugated forms (G-UDCA and T-UDCA) showed a variety of patterns on TNF-${\alpha}$ production by changes of functional groups and concentration. These results also indicate that bile acids may regulate TNF-${\alpha}$ production in normal hepatic function or disease conditions.

• Advances in Traditional Medicine
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• 제6권1호
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• pp.45-52
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• 2006

The methanol extracts of the roots, root bark and stem of Berberis tinctoria, were investigated for their hepatoprotective activity against carbon tetrachloride $(CCl_4)$ induced toxicity in freshly isolated rat hepatocytes, HEp-G2 cells and animal models. The methanol extracts were able to significantly normalise the levels of aspartate amino transferase, alanine aminotransferase, alkaline phosphatase, triglycerides, total proteins, albumin, total bilirubin and direct bilirubin, which were altered due to $CCl_4$ intoxication in freshly isolated rat hepatocytes and also in animal models. The anti-hepatotoxic effect of the methanol extracts in vitro were observed at $600\;-\;1,000\;{\mu}g/ml$ concentrations. A dose dependent increase in the percentage viability was observed when $CCl_4$ exposed HEp-G2 cells were treated with different concentrations of the methanol extracts. The highest percentage viability of HEp-G2 was observed at a concentration of $1,000\;{\mu}g/ml$. The results from the present investigations also indicate good correlation between the in vivo and in vitro studies.

• Biomolecules & Therapeutics
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• 제7권1호
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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.

• 한국식품영양과학회지
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• 제41권1호
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• pp.7-13
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• 2012

본 연구에서는 산화적 스트레스에 의한 간 손상 개선 소재 개발을 위하여 꾸지뽕나무 각 부위별(잎, 줄기, 열매), 용매별(80% 에탄올, 10% 에탄올, 물) 추출물의 항산화 활성 및 간세포 보호효과를 측정하였다. 총 폴리페놀 함량과 플라보노이드 함량은 꾸지뽕 잎 80% 에탄올 추출물에서 가장 높게 나타났으며, 부위별로는 잎>줄기>열매 순이었고, 추출용매별로는 80% 에탄올>10% 에탄올>물 추출물 순으로 나타났다. DPPH 라디칼 소거능과 ABTS 라디칼 소거능 또한 잎80% 에탄올 추출물이 가장 높았으며, HepG2 세포에서 $H_2O_2$로 유도된 산화적 손상에 대해서는 꾸지뽕 잎 80% 에탄올 추출물만 유의적으로 높은 세포보호활성을 나타내었으며, HepG2/2E1 세포에서 알코올로 유도된 산화적 손상에 대한 각 부위별, 용매별 추출물의 간세포보호효과 또한 꾸지뽕잎 80% 에탄올 추출물이 가장 높게 나타났다. 부위별로는 잎>줄기>열매 순이었고, 추출 용매별로는 꾸지뽕 잎의 경우 80% 에탄올>10% 에탄올>물 순이었으며, 줄기와 열매의 경우는 용매별로 유의적인 차이가 나타나지 않았다. 이상의 결과로부터 꾸지뽕나무 잎 추출물은 우수한 항산화활성을 가질 뿐만 아니라 $H_2O_2$와 알코올로 유도된 간 손상으로부터 간세포 보호활성을 보임을 확인하였다. 이에 꾸지뽕나무 잎 추출물은 산화적 스트레스에 의한 간 손상으로부터 간세포 보호효과를 갖는 기능성 소재로 활용될 수 있을 것으로 사료된다.

• 한국식품과학회지
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• 제38권1호
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• pp.99-103
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• 2006

국내에서 선별 육종된 불로 구기자의 처리방법에 따른 간기능 보호효과를 측정하기 위하여 사염화탄소$(CCl_4)$ 투여로 급성 간독성을 유발시킨 흰쥐를 대상으로 연구하였다. 건조구기자 추출물(DFE), 볶은 구기자 추출물 (RFE), 그리고 생과즙(FFE)을 경구 투여한 결과 군간의 체중증가량은 차이를 나타내지 않았다. 한편, 체중 100 g 당 간 무게는 처리조건에 관계없이 구기자 추출물 및 생과즙 투여군이 유의적으로 낮은 간 무게를 나타내었다(p<0.01). 이것은 구기자 추출물과 생과즙 섭취가 $CCl_4$ 투여에 의한 지방간 형성 또는 간 독성에 의한 간 무게증가를 다소 완화하여준 효과를 나타내는 것으로 판단된다. 사염화탄소$(CCl_4)$ 투여에 의하여 흰쥐의 혈청 GPT 및 GOT 활성과 LDH 활성은 유의적으로 증가하였으나 볶은 구기자 추출물 투여군(RFEC)과 생과즙 투여군(FFJC) 모두 GPT, GOT 활성이 유의적으로 감소되었다. 혈중 총 콜레스테롤 함량은 구기자 추출물과 생과즙 투여군 모두 대조군(CON)과 비교하여 유의적인 증가를 나타내지 않았고 중성 지방함량은 대조군에 비해 유의적인 증가를 나타내었다(p<0.05). 간 조직의 MDA 함량과 GST, cytochrome P-450 활성 결과로 보아 구기자 추출물과 생과즙을 섭취 시 사염화탄소에 의한 독성을 완화시키는 것으로 나타났다. 따라서 이러한 모든 결과를 종합해 볼 때, 구기자 추출물과 생과즙은 $CCl_4$ 투여로 인한 지질 과산화, 지방변성, 간 세포 괴사 등을 억제 시키는 간 독성 보호 효과가 있는 것으로 생각된다.

• 생약학회지
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• 제33권4호통권131호
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• pp.324-331
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• 2002

This study was performed to investigate the protective effect of Houttuynia cordata Thunb on hepatotoxicity in carbon tetrachloride$(CCI_4)$ intoxicated rats. The examined effects hexane, chloroform, butanol and water fractions prepared from the Houttuynia cordata Thunb methanol exlract and rats were administrated with those orally once a day for successive 6 days, fellowed by treaoent with $CCl_4$ on the sixth day. After 6 days, the activities of aminotransferase, alkalinephosphatase, ${\gamma}-glutamyl$ transpeptidase, lactate dehydrogenase and contents of triglyceride, hepatic lipid peroxide in butanol fraction pretreated rats were significantly decreased compared to the only $CCl_4$ treated rats, also depletion glutathione content induced by treatment with $CCl_4$ was prevented by butanol fraction pretreated rats. In addition, activities of hepatic superoxide dismutase, catalase, glutathione peroxidase in butanol fiaction pretreated rats were significantly decreased compared to the only $CCl_4$ treated rats, but the activity of hepatic glutathione-S-transferase was not significantly effect. These results suggest that butanol fiuction of Houttuynia cordata Thunb methanol extract have potent hepatoprotective effect against carbon tetrachloride intoxicated rats.

• 한국식생활문화학회지
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• 제30권1호
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• pp.97-104
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• 2015

Antioxidant activity of dropwort fermented extract (DFE) was measured according to fermentation period, and liver protective effects were examined using Sprague-Dawley rats. Total polyphenol and flavonoid contents as well as DPPH and ABTS radical scavenging activities increased up to 60~80 days and then decreased slightly. Proper fermentation time for DFE was more than 60 days and less than 80 days. Administration of alcohol to rats for 10 days at 10 mL/kg/day raised serum AST, ALT, total cholesterol, and triglyceride (TG) levels, which were then lowered by DFE and sugar liquid with the same soluble solids. While sugar liquid increased the blood lipid profile, especially TG levels, DFE had no effect due to its antioxidant activity. When TBARS content of the DFE group in liver tissue significantly decreased in a concentration-dependent manner compared to that of the ALH group (p<0.05). Liver damage was recovered by DFE treatment and was confirmed by hamatoxylin-eosin staining. These results suggest that DFE has a protective effect against alcohol-induced hepatotoxicity in SD rats.