Dawley 계 숫컷 흰쥐(200∼210g)를 정상군, CCl4-대조군, CCl4-실험군으로 나누어 실험군은 애엽 에탄올 추출물을 1,000mg/kg,b.w의 용량으로 1일1회7일간 경구 투여 후 사염화탄소를 0.6mg/kg,b.w의 용량으로 복강내 주사 후 다음날 개복하여 혈청내의 Alanine aminotransferase(ALT), Aspartate aminotransferase(AST),Alkaline phosphatase(ALP), Glutamyltranspeptidase(γ-GT), Lactate dehydrogenase(LDH)의 활성도와 중성지방, 콜레스테롤 함량을 측정한 결과 애엽 추출물 투여군에서 CCl4-대조군과 비교하여 유의적인 감소를 나타내었으며, HDL-콜레스테롤은 유의적인 증가를 나타내었다. 간조직중의 지질과산화 함량은 감소를 glutathione함량은 유의적인 증가를 나타내었다 이 실험 결과 애엽 에탄올 추출물은 사염화탄소 투여에 의한 간 손상을 억제하는 보호물질을 함유하고 있음을 알 수 있었다.

본 연구는 5주령(180~200 g)의 SD계 흰쥐에 사염화탄소로 간 손상을 유발시킨 후 혼합 시료추출물(MSE)을 투여한 다음 혈액학적 및 생화학적인 parameter의 변동과 더불어 간 조직의 면역화학적 변화를 관찰하여 다음과 같은 결과를 얻었다. 실험동물의 식이량을 측정한 결과, 실험대조군(EC)군이 실험군(E1, E2)과 정상대조군(NC)과 양성대조군(PC)에 비해 통계적으로 유의하게 감소하는 경향을 나타내었고, 체중과 식이 섭취율은 실험대조군(EC)에 비해 실험군(E1, E2)과 정상대조군(NC)과 양성대조군(PC)은 통계적으로 유의하게 증가하는 간, 비장 및 흉선의 무게를 측정한 결과, 간의 무게는 실험 대조군(EC)이 정상대조군(NC)과 양성대조군(PC)에 비하여 약간 증가하였으나, 통계적으로 유의한 차이는 없었으며, 혼합 시료추출물(MSE)을 투여한 실험군(E1, E2)은 NC군 및 PC군과 유의한 차이가 없었다. 비장 및 흉선의 절대무게와 상대무게에 있어서도 모든 군에서 유의한 차이가 없었다. 실험대조군(EC)이 정상대조군(NC)에 비하여 혈청 ALT, AST, ALP와 LDH의 활성과 triglyceride(TG)의 함량이 모두 유의하게 증가하였고, 혈청 cholesterol(CHOL)의 함량은 모든 군에서 유의한 변동을 관찰할 수 없었다. 실리마린을 투여한 양성 대조군(PC)은 실험 대조군(EC)에 비하여 혈청 ALT, AST, ALP 와 LDH의 활성 및 TG의 함량 모두 유의하게 감소하였다. 그리고 혼합 시료추출물(MSE)을 투여한 실험군(E1, E2)은 실험 대조군(EC)에 비하여 혈청 ALT, AST, ALP와 LDH의 활성과 TG의 함량 모두 유의하게 감소하였다. 백혈구, 호중구, 림프구, 혈소판 수치와 혈색소의 함량 모두 실험대조군(EC)이 정상대조군(NC)에 비해 유의하게 높았고, 실험대조군(EC)에 비해 양성대조군(PC)인 실리마린 투여군이 유의하게 낮았다. 혼합 시료추출물(MSE)을 투여한 실험군 E1, E2군에서는 실험대조군(EC)에 비해 백혈구와 림프구가 유의하게 낮았고, 각 실험군(E1, E2) 간에는 약간의 차이는 있었으나, 유의성은 나타나지 않았다. 간조직의 면역조직화학적 발현 결과는 정상군대조군(NC) 및 양성대조군(PC)의 간 조직에서 SMA(smooth muscle actin) 항체에 대한 교원섬유 발현 부분이 미세한 양성으로 관찰되었다. 실험대조군(EC)에서는 간 섬유조직 발현 부분에서 얇은 띠를 형성한 강 양성의 갈색으로 관찰되어 통계적으로 유의성 있게 나타났으며, 혼합 시료추출물(MSE) 투여군인 E1과 E2군에서는 간 섬유조직 발현 부분에서 미세하게 갈색으로 염색되어 실험대조군(EC)에 비해 유의하게 낮게 나타났으며, 정상대조군(NC)과 양성대조군(PC)의 발현정도와 큰 차이가 없었다. 이상의 실험결과를 종합해 볼 때, 본 실험의 결과는 간 손상 예방과 치료, 더 나아가 건강기능성 식품 소재로서 혼합 시료추출물의 활용 가능성에 대한 기초자료로 이용할 수 있을 것으로 생각되며, 이와 관련된 추가적인 연구를 계획하고 있다.

비파 식초가 사염화탄소에 의한 간독성에 대한 보호효과를 흰 쥐를 이용하여 확인하고자 연구하였다. 4주간 SD rat 암컷을 정상군, 음성대조군, 양성대조군, 비파 식초군 으로 나누어 샘플을 처리하였고, 29일째 되는 날 사염화 탄소를 처리하였다. 혈청 AST 및 ALT 효소 활성 수치 변화에서 비파 식초가 사염화탄소를 단독으로 투여한 군보 다 유의한 수치로 각각 49.77%, 75.88%로 감소하였다(p < 0.001). 간 조직에서는 CAT 및 SOD 효소 활성은 비파 식초군이 사염화탄소를 단독으로 투여한 음성대조군보다 유의한 차이로 높은 활성 수치를 보였다. 조직학적 관찰에 서는 비파식초군이 사염화탄소를 단독으로 투여한 음성대 조군에 비해 지방변성이 적게 분포하고, 조직의 섬유화가 진행되지 않았으며, 정상군과 비슷한 간세포의 구조가 관찰 되었다. 이와 같은 결과를 보아 비파 식초는 항산화 효소의 증가로 활성산소를 제거하여 간 손상을 억제할 뿐 아니라 혈청의 AST 및 ALT 효소 활성을 감소시켜 간 보호 효과가 있는 것으로 건강기능식품으로써 긍정적인 가능성이 있다고 사료된다.

Dawley 계 숫컷 흰쥐(200∼210g)를 정상군, CCl4-대조군, CCl4-실험군으로 나누어 실험군은 갈근 에탄올 추출물을 1,000mg/kg,b.w의 용량으로 1일1회7일간 경구 투여 후 사염화탄소를 0.6mg/kg,b.w의 용량으로 복강내 주사 후 다음날 개복하여 혈청내의 Alanine aminotransferase(ALT), Aspartate aminotransferase(AST), Alkaline phosphatase(ALP), Glutamyltranspeptidase(γ-GT), Lactate dehydro-genase(LDH)의 활성도와 중성지방, 콜레스테롤 함량을 측정한 결과 갈근 추출물 투여 군에서 CCl4-대조군과 비교하여 유의적인 감소(p<0.05)를 나타내었으며, HDL-콜레스테롤은 유의적인 증가(P0.05)를 나타내었다. 간조직중의 지질과산화 함량과 Catalase(CAT),Glutathione peroxiddase (GSH-Px)의 항산화 효소 활성은 유의적인 감소를 나타내었다. 반면에 간 조직중의 glutathione 함량은 유의적인 증가를 나타내었다. 이 실험 결과 갈근 에탄올 추출물은 사염화탄소 투여에 의한 간 손상을 억제하는 보호물질과 항산화 물질을 함유하고 있음을 알 수 있었다.

We previously prepared a standardized and purified extract of Salvia miltiorrhiza, PF2401-SF, and showed that it protected against hepatic injury more effectively than ethanol based extraction. In this study, we determined the hepatoprotective mechanisms of PF2401-SF in vivo. Hepatic injury was induced in mice by using carbon tetrachloride (CCl4). Treatment with PF2401-SF (1 or 10 mg/kg, p.o.) significantly reduced the levels of alanine transaminase (ALT) and aspartate transaminase (AST) in the plasma. PF2401-SF treatment resulted in further elevation of the CCl4-induced heme oxygenase-1 (HO-1) expression, which contributed to the PF2401-SF-mediated liver protection. Additionally, PF2401-SF treatment significantly reduced the c-Jun NH2-terminal kinase (JNK) phosphorylation induced by CCl4. Taken together, these results suggest that the protective effect of PF2401-SF, a standardized fraction of S. miltiorrhiza, against CCl4-induced hepatic injury in mice arises from its induction effect on HO-1 and inhibitory effect on JNK phosphorylation.

Extraction of Sedum sarmentosum Bunge by super critical carbon dioxide was operated under 40-50℃and 200-250 atm, thus, yield of extraction was very low as 4 wt%. Rats were administrated with the extract orally once a day for succesive 6 days, followed by treatment with carbon tetrachloride (CCl4) on the sixth day. The activities of aminotransferase, alkaline phosphatase, γ-glutamyl transpeptidase, lactate dehydrogenase and contents of triglyceride, total cholesterol in the extract-pretreated rats were decreased compared to the CCl4controled rats, whereas content of HDL-cholesterol was increased. Especially content of hepatic malondialdehyde (MDA) and atherogenic index (AI) were decreased and HTR was increased in the extract-pretreated rats, and reduced peroxidative liver damage in the CCl4-induced hepatotoxicity rats. In addition, activities of hepatic superoxide dismutase, catalase, glutathione peroxidase in the extract-pretreated rats were significantly decreased compared to the CCl4 controled rats, but the content of glutathione was significantly increased. These results suggest that extract of Sedum sarmentosum Bunge has hepatoprotective effect in the CCl4-intoxicated rats.

The purpose of this study was to investigate the effects of dietary purple sweet potato(Ipomoea batatas) powder on serum lipid levels and antioxidative enzymes in normal and pretective effect on hepatotoxicity rats induced by carbon tetrachlolide. Four groups of rats (3-week-old inbred Sprague-Dawley male rats) were normal rats fed control diet(C), induced hepatotoxicity rats fed control diet(EC), normal rats fed purple sweet potato diet(P), and induced hepatotoxicity rats fed purple potato sweet diet(EP). Rats were induced by single injection of 50% carbon tetrachlolide(0.1 mL/100 g B.W., i.p.). The rats were fed ad libitum each of the experimental diet for 5 weeks. After 5 weeks the rats were sacrificed and activities of antioxidant enzymes and lipid peroxidation products were determined in their liver homogenates. But serum concentrations of lipid was not significant in all groups. Serum alanine aminotransferase(ALT/GPT) and aspartate aminotransferase(AST/GOT) of the EC and EP groups were heigher than the C and P groups. The hepatic glucose 6-phosphatase(G6Pase) activity of the group fed purple potato diet(P) was lower than the other groups(p<0.05). However, The glutathione peroxidase(GPx) activities was not statistically different between the groups. Renal glutathione S-transferase(GST) activity of the EC and EP groups were lower than the C and P groups(p<0.05). In conclusion, these results suggest that purple sweet potato is believed to be possible protective effect on hepatotoxicity rats induced by carbon tetrachlolide.

Protective effect of Corydalis ternata against the carbon tetrachloride-induced toxicity was investigated. Carbon tetrachloride(CCl₄) induces hepatotoxicity due to the reactive free radical(CCl₃*) generated by cytochrome P-450 enzyme. We examined effects of hexane, chloroform, butanol and water fractions prepared from the Corydalas ternata methanol extract. Rats were treated with those for 3 days, and liver microsomes and cytosols were prepared at 24 hour after last treatment. Hepatoprotective activity. of the water fraction was higher than that of other fractions. To examine mechanism of the hepatoprotective effect of Corydalis ternata, we measured contents of malondialdehyde(MDA), cytochrome P450(CYP), glutathione, calcium as well as the activities of NADPH-CYP reductase, glutathione S-transferase(GST), superoxide dismutase(SOD), glutathione peroxidase(GPX) and catalase. The fraction inhibited production of MDA, content of CYP and calcium in liver of water fractions - treated rats as compared with those of CCl₄ treated rats. The GST activity was increased. We speculate that the O₂ radical scavenging activities of the water fraction might play a key role in the mechanism opposing the progression of CCl₄ induced hepatotoxicity, but the activities of SOD, GPX, CAT were decreased. These results suggest that the mechanism might be mainly due to the decrease of CYP contents, act as calcium channel Mocker and increase of GST activity rather than O₂ radical scavenging activities.

산초종피 메탄을 추출물과 hyperoside의 사전투여가 사염화탄소에 의해 예상되는 혈청지질성분의 농도변화에 미치는 효과를 밝히기 위해 TCR계 mouse를 대상으로 실험한 결과는 다음과 같다. 사염화탄소로 혈청 총콜레스테를 농도가 유의적으로 증가되었으나, 산초 메탄올 추출물과 hyperoside의 사전투여는 사염화탄소에 의한 이의 증가를 유의적으로 억제시켰으며, 20㎎/㎏ hyperoside 투여군에서 그 효과가 가장 높았다. 사염화탄소로 혈청 HDL-cholesterol 농도가 유의적으로 감소되었으나, 산초 메탄올 추출물과 hyperoside의 사전투여는 사염화탄소에 의한 이의 감소를 유의적으로 억제시켰으며, 20㎎/㎏ hyperoside 투여군에서 그 효과가 가장 높았다. 사염화탄소로 혈청 LDL-cholesterol 농도가 유의적으로 증가되었으나 산초 메탄올 추출물과 hyperoside의 사전투여는 사염화탄소에 의한 이의 증가를 유의적으로 억제시켰으며, 20㎎/㎏ hyperoside 투여군에서 그 효과가 가장 높았다. 사염화탄소로 혈청 triglyceride 농도가 유의적으로 증가되었으나, 산초 메탄올 추출물과 hyperoside의 사전투여는 사염화탄소에 의한 의의 증가를 유의적으로 억제시켰다.

Previous studies have shown that methanol extract and its butanol fraction of Carthamus tinctorius L. Semen have the hepatoprotective effect on the CCl₄ induced hepatotoxicity. The hepatoprotective effect of the subfractions of butanol fraction has been evaluated by analyzing oxygen free radical scavenging enzyme activities and histopathological examinations. In BS-5 subfraction treated group, the activity of superoxide dismutase has been significantly increased as compared with that of CCl₄ treated rats. Antioxidant activity has been evaluated by the examination of the scavenging activity against 1,1-diphenyl-2-picrylhydrazyl radical. BS-5 subfraction has shown strong antioxidant activities. The histopathological examination showed that the treatment of BS-5 subfraction has relieved the ballooning degeneration of hepatocytes which had been generated by CCl₄. It appears that the protective effect of BS-5 subfraction would be mediated of the attenuation of lipid peroxidation by acting as a free radical scavenger, which were based on the increase of superoxide dismutase activity.

Previous studies have shown that methanol extract and its butanol fraction of Carthamus tinctorius L. Semen have the hepatoprotective effect on the CCl₄-induced hepatotoxicity. The hepatoprotective effect of subfractions has been evaluated by analyzing blood and hepatocyte biochemical analyses and biotransformation enzyme analyses. Treatment of BS-5 subfraction has significantly decreased the activities of alanine aminotransferase and aspartate aminotransferase. In addition, the levels of cholesterol and triglyceride in liver have been decreased as compared with that of CCl₄ treated rats. The hepatoprotective effect of BS-5 subfraction on the CCl₄-induced hepatotocicity would be mediated of the attenuation of the level of cytochrome P450 and the enhancement of the activity of glutathion S-transferase.

Inonotus obliquus is one of the immune-regulatory substances and is recognized to play the role in the metabolic process of inflammation, allergy and immuntiy. The purpose of this study was to evaluate the effects of water extracts of Inonotus obliquus (IOW) on the liver lymphocyte immune function in the Sprague-Dawley male rats treated with carbon tetrachloride (CCl4) to induce liver damage. Rats were fed with each experimental diet and water for 4 weeks. We found that effects of IOW on interferon-gamma (IFN-γ), signal transducer and activator of transcription 1 (STAT1), phospho-signal transducer and activator of transcription 1 (pSTAT1) and GATA-binding protein 3 (GATA-3) were decrease in vivo. Interleukin-4 (IL-4), STAT6, pSTAT6 and T-box expressed in T-cells (T-bet) decreased significantly lower in CCl4+IOW group than the CCl4 group. Our data indicated that cytokine protein production were increased in CCl4 group and CCl4+IOW group. As a result of this study, we assume that IOW fed could regulate the immuno-modulating functions through regulate the cytokine production capacity activated by liver damage.

GATA-binding protein-3 (GATA-3) and T-box expressed in T-cells (T-bet) are now considered as master transcription factors involving Th cell differentiation, but the roles of these factors are still uncertain in vivo. This study was conducted to investigate the expression of these transcription factors in the liver damage induced by carbon tetrachloride (CCl4) in rats. In this study, liver damage were induced with Scutellaria baicalensis Georgi water extracts (SBW) and followed for 4 weeks. The expression of GATA-3 and T-bet protein in liver damage induced by CCl4 and the serum levels of immunoglobulin A (IgA), IgE were studied after 4 weeks of treatment. We found that effect of SBW on IFN-γ, STAT1, pSTAT1 and T-bet was decreased in vivo. Several genes were demonstrated to be IL-4 inducible prior to the discovery of STAT6. CCl4+SBW group was significantly lower than CCl4 group in IL-4, STAT6, pSTAT6 and GATA-3. Our data indicate that cytokine protein production were increased in CCl4 group and CCl4+SBW group. From these results, water extracts obtained from Scutellaria baicalensis Georgi may have an immunoregulatory effect in the liver induced by CCl4 of rats.

Fifty percent ethanol extract of Lythrum salicaria Linne root (LSR) was tested in vitro on antioxidant activity, and furthermore was investigated on antioxidative and fibrosis protecting activities in CCL4-induced liver fibrosis rat model. Ratio of hepatic GSH/GSSG (reduced glutathione/oxidized glutathione) as bio-parameter of antioxidant level in CCL4 plus LSR-treated rats for 6 weeks significantly increased from 2.8- to 5.7-fold than that of CCL4-treated rats at p 〈 0.05. Thiobarbituric acid reactive substances (TBARS) contents in CCL4 plus LSR-treated rats ranged from 1.57- to 2.19-fold of normal rats and were lower than those in CCL4 plus silymarin-treated rats (1.78~2.46-fold of normal rats) (p 〈 0.05). Amounts of hydroxyproline of liver tissue showing the content of total collagen, a parameter of fibrosis, in CCL4 plus LSR-administrated rat livers were 4.9~8.8μg/mg (-47~-71%, compared with that in CCL4-treated rat livers (16.6μg/mg tissue), which were significantly lower than those in CCL4 plus silymarin-administrated rats being 8.4~11.7μg/mg (-30~-50%). This collagen reducing effect of liver tissue in CCL4 plus LSR-treated rats was supported by histological observation using microscopy assay. From the results, we conclude that the root of L. salicaria have efficient antioxidant potential and effective antifibrotic activities.

The purpose of this study evaluated the immunoregulatory effect of phellinus linteus ethanol (PLE) extracts on liver damage on carbon tetrachloride (CCl4) induced in rats. Four-week old Male Sprague-Dawley rats were divided into the three experimental groups randomly; Control group, CCl4 group, CCl4 + PLE group. We found that effect of PLE on IFN-γ, STAT1 and pSTAT1 was decrease in vivo. Several genes were demonstrated to be IL-4 inducible prior to the discovery of STAT6. IL-4, STAT6 and pSTAT6 decreased significantly lower in CCl4 + PLE than the CCl4 group. Our data indicated that cytokine protein production were increased in CCl4 group with CCl4 + PLE group. In our data indicate that IgA levels in MLN lymphocytes were low, while IgE was high in CCl4 + PLE group compared with CCl4 group. Therefore, the results of this study show that PLE can be proposed to protect the liver against CCl4-induced immunoregulatory activity in rats.

본 실험은 간장기능보호를 위한 식품소재를 검토하기 위하여 수행되었다. 인진쑥, 콩나물, 솔잎추출물은 in vitro 간장 fatty acid synthase 활성을 억제하였다. 한편, 솔잎, 콩나물추출물은 사염화탄소를 처리한 횐쥐의 혈청 GPT및 GOT효소활성의 상승을 억제하였다. 인진쑥, 콩나물추출물은 사염화탄소처리에 의한 흰쥐의 간장 microsome의 과산화지질함량의 상승을 억제하였다. 나아가 콩나물추출물은 사염화탄소에 의해 증가한 흰쥐의 간장콜레스테롤 및 중성지질함량을 현저하게 감소시켰다. 이러한 결과는 인진쑥, 솔잎, 콩나물추출물의 사염화탄소에 의한 간장손상의 보호기능을 보여 준다.

The pure compound chloromethanes; methyl chloride, methylene chloride, chloroform and carbon tetrachloride were used as a model of chlorocarbon system with Cl/H ratio to investigate thermal stability and hydrodechlorination process of carbon tetrachloride under excess hydrogen atmosphere. The parent thermal stability on basis of temperature required for 99% destruction at 1 second reaction time was evaluated as 875℃ for CH3Cl, 780℃ for CH2Cl2, 675℃ for CHCl3, and 635℃ for CCl4. Chloroform was thermally less stable than CCl4, at fairly low temperatures (<570℃). The decomposition of CCl4, became more sensitive to increasing temperature, and CCl4 was degraded easier than CHCl3 at above 570℃. The number and quantity of chlorinated products decreases with increasing temperature for the product distribution of CCl4 decomposition reaction system. Formation of non-chlorinated hydrocarbons such as CH4, C2H4 and C2H6 increased as the temperature rise and particularly small amount of methyl chloride was observed above 850℃ in CCl4/H2 reaction system. The less chlorinated products are more stable, with methyl chloride the most stable chlorocarbon in this reaction system.