• Archives of Pharmacal Research
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• 제28권3호
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• pp.330-334
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• 2005

The effect of a new hepatoprotective agent, YH-439, on the hepatobiliary transport of a model organic cation (OC), TBuMA (tributylmethylammonium), was investigated. The area under the plasma concentration-time curve (AUC) from time zero to 4 h following iv administration of TBuMA (6.6 $\mu$mol/kg) was increased significantly when YH-439 in corn oil (300 mg/kg) was orally administered to rats 24 h prior to the experiment. Nevertheless, the cumulative biliary excretion of TBuMA remained unchanged. As a consequence, the apparent biliary clearance ($CL_b$) of TBuMA was decreased significantly as a result of YH-439 pretreatment, consistent with the fact that the in vivo excretion clearance of TBuMA across the canalicular membrane ($CL_{exc}$) was not changed by the pretreatment. The in vitro uptake of TBuMA into isolated hepatocytes was decreased by one half by the pretreatment, owing to a decrease in the apparent V$_{max}$ and $CL_{linear}$, but the $K_m$ for the process remained constant. Most interestingly, however, the sinusoidal uptake of glucose, a nutrient, into hepatocytes was not influenced by the pretreatment, suggesting the YH-439 pretreatment specifically impaired the sinusoidal uptake of OCs. Thus, the OC-specific inhibition of hepatic uptake, without influencing the uptake of glucose, a nutrient, appeared to be associated with the hepatoprotective activity of YH-439.

• Archives of Pharmacal Research
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• 제27권9호
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• pp.947-953
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• 2004

The antioxidative and hepatoprotective potentials of two anthraquinones, alaternin (2-hydroxy-emodin) and emodin, to scavenge and/or inhibit hydroxyl radicals generated by the Fenton reaction and to protect tacrine-induced cytotoxicity in human liver derived HepG2 cells were evaluated, respectively. The inhibitory activity on hydroxyl radical generated in a cell-free chemical system (FeSO$_4$/$H_2O$$_2$) was investigated by a fluorescence spectrophotometer using a highly fluorescent probe, 2$^1$,7$^1$-dichlorofluorescein. The hydroxyl radical scavenging activity was determined by electron spin resonance spectroscopy using 5,5-dimethy-1-pyrroline-N-oxide as hydroxyl radicals trapping agents. Tacrine-induced HepG2 cell toxicity was determined by a 3-［4,5-dimethylthiazole-2yl］-2,5-diphenyltertrazolium bromide assay. Although the scavenging activity of alaternin on hydroxyl radical was similar to that of emodin in dose-dependent pat-terns, the inhibitory activity exhibited by the former on hydroxyl radical generation was stron-ger than that of the latter, with $IC_{50}$/ values of 3.05$\pm$0.26 $\mu$M and 13.29$\pm$3.20 $\mu$M, respectively. In addition, the two anthraquinones, alaternin and emodin showed their hepatoprotective activ-ities on tacrine-induced cytotoxicity, and the EC$_{50}$ values were 4.02 11M and 2.37 $\mu$M, respec-tively. Silymarin, an antihepatotoxic agent used as a positive control exhibited the EC$_{50}$ value of 2.00 $\mu$M. These results demonstrated that both alaternin and emodin had the simultaneous antioxidant and hepatoprotective activities.ies.

• 동의생리병리학회지
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• 제22권1호
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• pp.155-161
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• 2008

Carbon tetrachloride $(CCl_4)-induced$ liver injury depends on a toxic agent that has to be metabolized by the liver NAPDH-cytochrome P450 enzyme system to a highly reactive intermediate. Although several isoforms of cytochrome P450 may metabolize $CC1_4$, attention has been focused largely on the cytochrome P450 2E1 (CYP2E1), which is ethanol-inducible. Alternations in the activity of CYP2E1 affect the susceptibility to hepatic injury from $CC1_4$. In this study, the liver protective effect of the hot water extracts of Scutellaria radix (SR) was investigated. The SR exhibited a hepatoprotective activity against $CCl_4-induced$ liver damage in Chang liver cells. The expression of CYP2E1, measured by RT-PCR and Western blot analysis, was significantly decreased by SR treatment in Chang cells. Based on these findings, it is suggested that hepatoprotective effect of SR possibly related to downregulation of CYP2E1 expression.

• 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.

• 사상체질의학회지
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• 제15권1호
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• pp.90-108
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• 2003

Osuyubujaijung-tang(OBT) and Sipyimiguanjung-tang(SGT) has been developed as prescriptions for the Soyeumin constitution. The hepatoprotective effect of the water extract of Osuyubujaijung-tang(OBT) and Sipyimiguanjung-tang(SGT) was investigated against carbon tetrachloride (CCl4)-induced hepatic damage. A single intra-peritoneal injection of CCl4 produced liver damage in rats as manifested by the significant rise of aspartate aminotransferase(AST), alanine aminotransferase(ALT), and alkaline phosphatase(ALP) in serum as compared to those of untreated normal group. Pretreatments of rats with Osuyubujaijung-tang(OBT) and Sipyimiguanjung-tang(SGT) 500 mg/kg for 7 days) were significantly reduced AST, ALT, and ALP levels compared with CCl4-treated control group. Treatment of rats with CCl4 led to significantly increase in lipid peroxidation and significantly decrease in cytochrome P450 and P450 reductase. The oral administration of Osuyubujaijung-tang(OBT) and Sipyimiguanjung-tang(SGT) water extract significantly inhibited the accumulation of microsomal thiobarbituric acid reactive substance (TBARS) and increased the cytochrome P450 and P450 reductase activity. All these biochemical alterations resulting from CCl4 administration were inhibited by the pretreatment with Osuyubujaijung-tang(OBT) and Sipyimiguanjung-tang(SG1) extract. These results suggest that Osuyubujaijung-tang(OBT) and Sipyimiguanjung-tang(SGT) water extract can be useful as a hepatoprotective agent. And the effect of NO modulation by NO synthesis or precursors, and Osuyubujaijung-tang(OBT) and Sipyimiguanjung-tang (SGT) water extract was researched on chronic liver damage induced by CCl4 administration. It was observed that endogenous NO protected the liver from lipid peroxidation, fibrosis, and damage. Osuyubujaijung-tang(OBT) and Sipyimiguanjung-tang(SGT) water extract showed the hepatoprotective effect on the chronic liver cirrhosis model and relationship with NO modulation.

• 대한본초학회지
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• 제28권4호
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• pp.25-32
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• 2013

Objectives : The purpose of this study was to evaluate the hepatoprotective effect of Hovenia dulcis extract on acute and chronic liver injuries induced by alcohol and $CCl_4$ in mice and rats. Methods : In acute alcohol-induced liver injury, mice were administered Hovenia dulcis extracts (60 and 200 mg/kg) orally before and after alcohol administration. In chronic alcohol-induced liver injury, mice were administered alcohol containing liquid diet for 4 weeks. The mice were administered H. dulcis extracts (60 and 200 mg/kg) mixed with the liquid diet. In acute $CCl_4$-induced liver injury, rats received a single dose of $CCl_4$ (2 mL/kg in olive oil, intraperitoneally). Rats were administered H. dulcis extracts (30, 100 and 300 mg/kg) before and after $CCl_4$ administrations. After the ends of the administrations, the serum levels of AST and ALT were measured using chemical analyzer, and ${\gamma}$-GTP levels were measured using spectrophotometer. Results : In acute alcohol-induced liver injury, H. dulcis extracts treated group showed significant reduction in ALT levels compared to those of control group. In chronic alcohol-induced liver injury, it inhibited weight-loss compared to normal group and showed significant reduction in AST, ALT and ${\gamma}$-GTP levels compared to control group. In acute $CCl_4$-induced liver injury, it also showed significant reduction in AST, ALT levels compared to control group. Conclusions : The results show that H. dulcis extract has hepatoprotective effect in acute and chronic alcohol-induced liver injury and acute $CCl_4$-induced liver injury. These findings suggest that H. dulcis could be a potent hepatoprotective agent.

• 대한한방내과학회지
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• 제31권1호
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• pp.11-24
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• 2010

Objectives : This study was carried out to investigate the hepatoprotective effects of mixture with Hovenia dulcis Thunb (HDT) and Acer tegmentosum Maxim(ATM) on D-galactosamine-induced liver failure in rats. Methods : The animals were divided into 4 groups: control, with liver failure and no treatment; H1A1, with liver failure and oral treatment with HDT 1 and ATM 1; H1A2, with liver failure and oral treatment with HDT 1 and ATM 2; H1A4, with liver failure and oral treatment with HDT 1 and ATM 4. The animals were treated for 3 weeks and then examinations of change of body weight, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase ($\gamma$-GTP), total cholesterol, triglyceride, total bilirubin, superoxide dismutase (SOD), catalase, histopathologic change, and complete blood count (CBC) were performed. Results : All experimental groups had significantly decreased AST in serum and markedly increased activity of SOD as compared with the control group. H1A1, and H1A4 significantly decreased ALT in serum and H1A4 at 2 weeks was significantly higher on the change of body weight as compared with the control group. In histopathologic change of liver tissue by light microscopy, all experimental groups showed recovery effects of liver cells which were damaged by D-galactosamine. Conclusions : Based upon these results, it could be assumed that a mixture of HDT and ATM has hepatoprotective and antioxidative effects on D-galactosamine-induced liver failure. Therefore, a mixture of HDT and ATM might be utilized as a protective agent in therapy for liver diseases.

• Toxicological Research
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• 제12권2호
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• pp.251-258
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• 1996

Panax ginseng has been used for various diseases including hepatic disorders. The aim of the present study was to investigate the hepatoprotective effects of ethanol extract and saponin of Panax ginseng in thioacetamide-intoxicated rats and to compare with silymarin, a known hepatoprotective agent. Male Sprague-Dawley rats were given single intragastric administration of thioacetamide. Aqueous solutions of ethanol extract and saponin of Panax ginseng with or without silymarin were administered intragastrically daily for six days from four days before until one day after thioacetamide administration. At the end of the treatment, the rats were fasted overnight and sacrificed. As a result, thioacetamide caused significant increase in serum levels of AST, ALT, 5'-nucleotidase and bilirubin. Thioacetamide increased $Ca^++$ content but decreased protein content in liver tissue. These thioacetamide-induced biochemical changes were prevented both by ethanol extract of ginseng and silymarin, but not by ginseng saponin. Silymarin did not potentlate the effect of either ethanol extract or saponin of ginseng on these parameters. Thioacetamide-induced confluent necrosis was not protected by the test drugs. In conclusion, ethanol extract of ginseng protects the liver possibly by stabilizing the cell membrane and by inhibiting thioacetamide-induced $Ca^++$ increase in the hepatocytes, which was comparable to that of silymarin.

• 한국식품과학회지
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• 제53권3호
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• pp.260-266
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• 2021

본 연구에서는 발효한 감국 발효 열수 추출물의 luteolin 및 luteolin-7-glucoside 함량, 항산화 활성 및 간세포 보호효과를 비교 분석함으로써 발효에 의한 활성차이를 분석하였다. 감국 내 luteolin 및 luteolin-7-glucoside 함량은 발효 전과 비교하여 유의하게 증가하였고 총 폴리페놀 함량 역시 발효 전보다 증가하는 것으로 나타났다. 유산균 발효에 의해 ABTS radical 소거능은 추출물의 농도가 50, 100, 200 및 400 ㎍/mL의 범위에서 7.30, 15.55, 28.30, 44.48%로 감국 열수 추출물과 비교하여 증가하는 것으로 나타났다. DPPH radical 소거능 역시 ABTS radical 소거능을 비교한 결과와 유사하게 같은 농도의 범위에서 감국 발효 열수 추출물의 경우 각각 6.03, 12.25, 26.18, 41.05%로 감국 열수 추출물과 비교하여 증가하는 것으로 나타났다. HepG2 세포에 감국 열수 추출물과 감국 발효 열수 추출물을 처리한 후 48시간 배양한 결과 모든 처리구에서 세포독성이 없는 것으로 나타났다. HepG2 세포에 에탄올을 처리하여 간독성을 유발한 결과 에탄올 처리한 모든 처리구에서 GGT, AST, ALT 및 LDH 활성이 증가하였고, 감국 발효 열수 추출물을 100 ㎍/mL을 처리하였을 때 대조구과 비교하여 GGT, AST 및 ALT 활성이 유의적으로 감소하는 것으로 나타났으며, LDH 활성은 감국 발효 열수 추출물을 200 ㎍/mL을 처리하였을 때 대조구과 비교하여 감소하는 것으로 나타났다. 이상의 결과로 볼 때 감국 발효 열수 추출물은 luteolin 및 luteolin-7-glucoside 함량 증가, 항산화 활성 증가 및 GGT, AST, ALT, LDH의 활성을 감소시킴으로써 에탄올에 의한 간 손상을 예방하는 것으로 사료되며, 동물실험을 통한 추가적인 간 기능개선 검증이 필요하다고 판단된다.

• Environmental Analysis Health and Toxicology
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• 제16권3호
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• pp.127-131
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• 2001

The antihepatic and hypolipidemic activities and total lipid levels of water extract of Plantaginis Herba, used for respiratory and renal disorder in folk medicine, were evaluated in streptozotocin-induced diabetic rats. Diabetes was induced by a single injection of streptozotocin (50 mg/kg, i.ｐ.). Water extract of Plantaginis Herba recovered enzyme activities such as GOT, GPT, ALP and LDH increased by streptozotocin (STZ) treatment. This crude drug also suppressed the enhanced production of lipid in hyperglycemia. These results strongly suggest that Plantaginis Herba be a promising liver-protective and hypolipidemic agent.