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.

Hepatocellular carcinoma (HCC) is a representative inflammation-associated cancer and known to be the most frequent tumor. However, the preventive agents for hepatocarcinogenesis are unsatisfactorily identified. We investigated the protective effect of steamed and freeze-dried mature silkworm larval powder (SMSP) on diethylnitrosamine (DEN)-induced hepatotoxicity in mice and compared the effect of three silkworm varieties: white-jade, golden-silk, and light-green strains. The mice were fed with diet containing 0.1, 1, and 10 g/kg of three types of SMSP for two weeks while DEN (100 mg/kg, i.p.) was injected 18 h before the end of this experiment. Liver toxicity was determined as serum indicator, histopathological examination, and expression of inflammatory enzyme. Pretreatment with SMSP reduced necrotic and histopathological changes induced by DEN in the liver. The measurement of serum biochemical indicators showed that pretreatment with SMSP also decreased DEN-induced hepatotoxicity, the levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). In addition, SMSP inhibited the expressions of inflammatory enzymes, cyclooxygenase-2 and inducible nitric oxide synthase. White-jade SMSP showed the most effective hepatoprotective results against hepatotoxicity among the three silkworm strains used in this study. SMSP may have a protective effect against acute liver injury by inhibiting necrosis and inflammatory response in DEN-treated mice.

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.

Although the vegetable Angelica keiskei (AK) has widely been utilized for the purpose of general health improvement among Korean population, its functionalities are not very well defined. In this study, we examined the effects of methanol extract of AK in rats on the biochemical changes induced by two hepatotoxins, D-galactosamine (GalN) and carbon tetrachloride ( CCl₄). AK was orally administered once daily for 7 days to male rats at 200and 500 mg/kg, before hepatotoxins. Effects of AK were assessed 24 hr later. AK pretreatments at 200 and 500 mg/kg significantly blunted GalN-induced elevation in liver lipid peroxidation, plasma aspartate-transaminase (AST) and alanine-transaminase (ALT) activities. AK also prevented, after 500 mg/kg but not after 200 mg/kg, the GalN-induced elevation in triglyceride, total cholesterol and LDL-cholesterol levels. Differently from against GalN-induced toxicity,AK did further elevate the CCl₄-induced rise in AST, ALT and lipid peroxidation. These results suggest that AK, when pre-administered prior to GalN, exerted protective effects against GalN-induced hepatotoxicity, in contrast however,AK exacerbated that induced by CCl₄. To explore possible mechanism for the toxicity-potentiating effects of AK on CCl₄, the activity of hepatic drug metabolism after AK treatment was assessed. It was observed that AK increased the activity of aniline hydroxaylase, a cytochrome P450 isoenzyme responsible for metabolic activation of CCl₄. This finding suggests that hepatoprotective effects of AK are not equally expected depending on hepatotoxins employed.

This study aimed to investigate the protective effect of Solanum nigum Linne total extract (SNT), Solanum nigum Linne leaf extract (SNL), Solanum nigum Linne root extract (SNR) on liver injury induced by Lipopolysaccharide(LPS) in Sprague-Dawley rats. SNT, SNL, SNR of 100 mg/kg concentration was intraperitoneally administered into rats at dose of 1.5 ml/kg for 20 days. on the day 1.5 ml/kg of LPS was injected. Four hours later, they were anesthetization with ether and dissected. Glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) were measured in serum and superoxide dismutase (SOD), catalase and glutathione peroxidase (GPX) were measured in liver homogenate. SNT, SNL, SNR extract inhibited GOT and GPT activities in LPSinduced rats, whereas increased SOD, Catalase and GPX activity in liver tissue of LPS-induced rats. These suggested that SNT, SNL, SNR could be used for functional beverage.

An extract of Allomyrina dichotoma larva (ADL), one of the insects used most frequently in traditional Chinese medicine for the treatment of liver diseases such as hepatocirrhosis and hepatofibrosis, was assessed for antioxidant bioactivity in this study.

The purpose of this study was to investigate the preventive effects of Paeoniae Radix Extract (PRE) against the acute hepatotoxicity-inducing lipopolysaccharide (LPS) in the liver. PRE of 100 mg/kg concentration was intraperitoneally administered into rats at dose of 1.5 ml/kg for 20 days. On day 21, 5 mg/kg of LPS dissolved in saline was injected 4 hours before anesthetization. We examined the levels of glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), lactate dehydrogenase (LDH) in serum of rats, superoxide dismutase (SOD) in mitochondrial fractions, and malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GPx) in liver homogenates. LPS-treatment markedly increased the levels of GOT, GPT, LDH and MDA, and significantly decreased those of SOD, CAT and GPx. But PRE-pretreatment decreased the levels of GOT, GPT, LDH and MDA, by 59.7%, 43.6%, 59.6% and 63.5%, respectively and increased those of SOD, CAT and GPx, by 85.5%, 57.8% and 62.9%, respectively. These results showed that the PRE had the preventive effects against the acute hepatotoxicityinducing LPS in the liver .

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.

녹차카테킨은 다양한 생리활성을 지닌 것으로 알려지고 있다. 본 실험에서는 사염화탄소와 갈락토사민으로 유발된 간독성에 대한 녹차카테킨의 간기능보호효과가 연구되었다. 녹차카테킨(50 mg/kg와 100 mg/kg)은 사염화탄소(0.5 ml/kg)와 갈락토사민(400 mg/kg)이 투여되기 전 그리고 투여 후 3일동안 흰쥐에 경구투여되었고, 간기능지표로 AST와 ALT를 측정하였다. 녹차카테킨(50 mg/kg)은 사염화탄소 처리된 랫드에서 상승된 혈중 AST와 ALT활성을 전투여군(262±11, 80±19 에서 153±33, 55±25로)과 후투여군(156±40, 105±3에서 106±22, 55±9로)모두 감소시켰다. 또한 갈락토사민으로 유도한 경우에도 AST와 ALT 수치는 전투석군(576±24, 276±68에서 236±13. 115±13로) 후 투여군(233±54, 137±11에서 119±23, 44±17로)에서 모두 유의성있게 감소된 결과를 나타내었다 또한 간 조직학적 검사에서도 사염화탄소와 갈락토사민으로 유도된 간경변을 유의성있게 억제하였다. 이상의 결과로 볼 때 녹차카테킨은 간독성에 의한 병변을 예방 및 치료할 수 있는 신약후보물질로서의 가능성을 시사한다.

삼백초가 TCDD 투여로 유발된 rat의 지질대사에 미치는 효과를 알아보기 위해 NTT, TTA, STT군으로 각각 10마리씩 나누어 TCDD를 투여하고 4주 동안 물질을 투여하였다. 4주 후 희생시켜서 생체 내 간 조직 활성 효과 및 항산화 효과를 관찰한 결과는 다음과 같다. 1. Total Cholesterol에서 삼백초를 투여한 STT군은 NTT군 비교해서 14.46% 증가하였으며, 혈청중의 HDL-Cholesterol은 SST군이 TTA군과 비교해서 21.29% 증가하였고 94.98%로 억제되었다. LDL-Cholesterol에서는 STT군이 TTA군 보다 12.86% 감소하였으며, 48.34% 로 억제되었다. 2. 혈청중의 TG의 함량은 TTA군이 NTT군에 비해 34.84% 증가하였다. TTA군에 비해 STT군은 7.06% 감소하였으며, 18.9% 억제시킨다. 3. 간조직중의 MDA량은 STT군이 TTA군에 비해 17.14% 감소하였고, 32.72%의 억제율을 보였다.

삼백초가 TCDD 투여로 유발된 rat의 간손상에 미치는 효과를 알아보기 위해 NTT, TTA, STT군의 3군으로 각각 10마리씩 나누어 TCDD를 투여하고 4주 동안 물질을 투여하였다. 4주 후 희생시켜서 생체 내 간 조직 활성 효과 및 항산화 효과를 관찰한 결과 1. AST 활성도는 STT군이 TTA군과 비교해서 70.05%의 억제 효과를 보였다. 반면에, ALT활성도는 STT군이 TTA군에 비해 24.00% 감소하였으며, 64.80%의 억제 효과를 보였다. 2. SOD는 TTA군이 NTT군보다 137.78% 감소하였으며, STT군은 TTA군에 비해 81.94%로 상승되었다. Catalase는 TTA군은 NTT군 보다 199.13% 감소하였으며, STT군의 catalase 활성도는 TTA 군과 비교하여 52.48% 증가하였고 55.45%의 회복율을 보였다. 3. TTA군의 GSH함량은 NTT군 보다 291.29% 감소하고 STT군은 TTA군과 비교하여 74.20% 증가하였으며, 98.72%로 회복되었다. TTA군의 GSSG함량은 NTT꾼 보다 46.80% 증가하였고 STT군의 간 조직중의 GSSG 함량은 TTA군과 비교하여 61.08% 감소하였으며, 81.01%로 억제되었다.

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.

The acetaminophen (APAP), an antipyretic and analgesic agent, induces the hepatotoxicity by increasing influx of calcium and destabilizing the cellular membrane which can be caused by N-acetyl p-benzoquinoneimine generated by cytochrome P-450 (CYP-450) when it is overdosed. Diltiazem (DIL), a calcium channel blocking agent, has been known to suppress the CYP-450 activities. To study the effect of DIL in APAP treated rats, the serum biotransformational enzyme analyses and the liver histopathologic examination were conducted on the rats which had been administered DIL at 3, 6, 9 and 12 hours after the 3,000 mg/kg of APAP administration. Following a single dose of DIL administered 12 hours after APAP administration, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, malondialdehyde and calcium contents of liver and microsome were significantly reduced. Glutathione S-transferase (GST) activity was significantly increased. Histopathologic studies showed that DIL had prevented the development of centrilobular necrosis induced by APAP in liver tissue. Our results suggested that diltiazem could inhibit the formation of free radical and the influx of calcium and could increase GST activity. Therefore, diltiazem can be administered at the time of 12 hours after overdosed APAP to diminish the liver damage.

The purpose of current study is to investigate the beneficial effect of enzyme (Alcalase) hydrolysates of silk protein in rat. Alcalase-treated silk protein hydrolysate (ATSH) itself did not show any cytotoxicity on the hepatic tissues and blood biochemistry, similar to the normal condition. ATSH played a protective role in tert-butyl hydroperoxide (t-BHP)-induced hepatotoxicity and liver damage. The values of AST (aspartate aminotransferase) and ALT (alanine aminotransferase), which are the indicators of the liver function, were effectively alleviated with the ATSH treatment in a dose dependent manner. The level of Lactate dehydrogenase (LDH) and Malondialdehyde (MDA), which were increased with t-BHP treatment, were significantly reduced by ATSH. High dose of ATSH (2 g/kg) reduced the t-BHP-induced LDH release by 48%. Antioxidant and antioxidant enzymes in liver cells were significantly increased by ATSH treatment in their level and activities. ATSH (2 g/kg) increased glutathione (GSH), an intracelluar antioxidant, by 2.5-fold compared with the t-BHP treated group. The activities of glutathione-s-transferase (GST), superoxide dismutase (SOD), and catalase were also elevated by 38%, 60%, and 45%, respectively, with ATSH (2 g/kg) treatment. The antioxidative effect of ATSH was recapitulated to the protection from t-BHP induced liver damages in hematoxylin and eosin (H&E) staining. Thus, ATSH might be used as a hepatoprotective agent.

본 연구는 4종의 별의별간(SS) 음료의 간보호 소재로서 의 이용 가능성을 조사하고자 항산화능 평가, t-BHP 와 CCl4로 산화적 손상 및 급성 간독성 유도한in vitro, in vivo 모델을 활용하여 간보호능을 평가하였다. 실험결과, 별의별간 01~04는 50 μM vitamin C 와 유사한 항산화 효과를 나타내었다. HepG2 세포에 t-BHP로 산화 스트레스를 유도한 뒤 나타나는 세포독성에 대해 별의별간 01 및 04에서 농도 의존적인 세포 보호효과를 보였으며, ROS 생성 억제에서 별의별간 01, 03, 04에서 농도의존적인 억제를 나타내었다. 미나리가 혼합된 별의별간 04에 대한 급성 간손상in vivo 모델을 활용하여 간보호능 검증 결과, 별의별간 04는 CCl4로 증가된 혈중 ALT, AST의 유의적 감소, 간 조직중 증가된 MDA 함량 감소 및 감소된 GSH의 유의적 증가를 나타내었다. 또한, 혈청 및 간 조직에서 증가 된 중성지방과 콜레스테롤을 유의적으로 감소시켰다. 이러 한 결과를 종합하며, 별의별간 04는in vitro 및in vivo 모델 에서 산화적 손상에 대해 간보호 효과를 나타내었다