• Herbal Formula Science
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• v.25 no.4
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• pp.509-526
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• 2017

Background and objectives : Soeumin Bojungykgi-tang (seBYTE) has been used to supplement qi in Korean medicine. It has been demonstrated to possess various biological functions such as anti-cancer, anti-aging and anti-inflammatory effects. The present study evaluated the protective roles of seBYTE in hepatotoxic in vitro and in vivo model. Methods : To investigate cytoprotective effect of seBYTE, HepG2 cells were pretreated with seBYTE and then subsequently exposed to $10{\mu}m$ AA for 12 h, followed by $5{\mu}m$ iron. Cell viability was examined by MTT assay, and expression of apoptosis-related proteins was evaluated by immunoblot analysis. For responsible molecular mechanisms, ROS production, GSH contents, and mitochondrial membrane potential were measured. In addition, hepatoprotective effect of seBYTE in vivo was assessed in $CCl_4$-induced animal model. Results : seBYTE prevented AA + iron-induced cytotoxicity in concentration dependent manner. In addition, ROS production, GSH depletion, and mitochondrial dysfunction induced by AA + iron were significantly reduced by seBYTE pretreatment. Furthermore, seBYTE recovered expression of the pro-apoptotic proteins such as PARP and pro-caspase-3. In animal experiment, plasma ALT and AST levels were significantly elevated in $CCl_4$ treatment, but seBYTE significantly decreased the ALT and AST levels. Moreover, seBYTE alleviated the numbers of histological activity index, percentages of degenerative regions, degenerated hepatocytes, infiltrated inflammatory cells, nitrotyrosine- and 4-hydroxynonenal-positive cells in liver. Conclusions : These results showed that hepatoprotective effect of seBYTE against on $CCl_4$-induced hepatic damages is partly due to antioxidative and anti-apoptotic process.

• Journal of fish pathology
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• v.33 no.1
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• pp.83-89
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• 2020

In the study, we investigated the effect of Taurine-F^TM, which is a commercially available fishery nutritional supplements complex, on anti-hepatotoxicity stressed with thioacetamide (TAA) and innate immune responses in olive flounder. To investigate the change in liver toxicity, firstly, TAA (30 ppm/100 g of fish) was intraperitoneally (i.p.) administered 12 hr after the intramuscular (i.m.) injection of Taurine-F^TM (0.02 ml/100 g of fish)(Taurine/TAA). Secondly, Taurine-F^TM was i.m. injected 24 hr after the administration of TAA (TAA/Taurine). Finally, TAA was administered simultaneously with Taurine-F^TM (TAA+Taurine). All blood samples were collected 24 hr after injection. GOT level in group Taurine/TAA appeared similar to the control, whereas group TAA/Taurine and TAA+Taurine showed significantly increased (p<0.05) levels compared to the control. In GPT level, group Taurine/TAA and TAA/Taurine showed elevated levels compared to the control, whereas no significant difference was observed between group TAA+Taurine and the control. Serum ACH₅₀ activity was significantly (p<0.05) augmented 24 hr after Taurine-F^TM injection compared to the control group, whereas no significant increase was observed 48 hr after Taurine-F^TM injection. On the other hand, serum lysozyme activity elevated in an acute stressed condition appeared significantly down-regulated 24 and 48 hr after Taurine-F^TM injection compared to the control. In conclusion, i.m. injected Taurine-F^TM augmented flounder serum complement activity and decreased a possible handling stress resulting in reducing a serum lysozyme activity and recovering hepatotoxicity. Thus, it is assumed that i.m. injection of Taurine-F^TM mixed with antibiotics or available vaccines could be utilized as an anti-hepatotoxic recipe in fish culture industry.

• Journal of Korean Traditional Oncology
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• v.16 no.2
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• pp.19-23
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• 2011

Objectives : The aim of this study was to evaluate safety of Rhus Verniciflua STOKES as a combination therapy of Oriental and conventional cancer treatment. So, We investigated liver function test(especially total bilirubin, AST, ALT, and ALP) levels in outpatients at an oriental medical clinic, to know whether Rhus Verniciflua STOKES decotion (Chijongtang) was hepatotoxic. The outpatients were treated with Rhus Verniciflua STOKES decotion(Chijongtang) during intravenous or oral chemotherapy. Methods : We surveyed whether Chijongtang caused liver injury in patients, who visited and took Chijongtang at Hana oriental medical clinic, from March, 2008 to November 2011. We looked over all the liver function tests of those patients, done during medication. Patients who had no records of liver function tests or with basal liver disease were excluded. And patients were classified into normal and abnormal liver function groups. Results and Conclusions : 48 patients were enrolled, and their mean dosage was 300ml/day, and the mean medication period was 9.3 (2-42) months. During and after medication, there were no abnormal liver function test results at all, in the normal liver function group. and 10 out of 11 patients in the abnormal liver function group showed normal liver function test levels. Roughly speaking, according to the above results, it seems that taking Chijongtang did not cause hepatotoxicity. And it seems Chijongtang has hepatoprotective effect. But we still need more laboratory and clinical research to reach a more definitive conclusion.

• Biomolecules & Therapeutics
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• v.26 no.6
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• pp.599-607
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• 2018

Fasiglifam (TAK-875) a G-protein coupled receptor 40 (GPR40) agonist, significantly improves hyperglycemia without hypoglycemia and weight gain, the major side effects of conventional anti-diabetics. Unfortunately, during multi-center Phase 3 clinical trials, unexpected liver toxicity resulted in premature termination of its development. Here, we investigated whether TAK-875 directly inflicts toxicity on hepatocytes and explored its underlying mechanism of toxicity. TAK-875 decreased viability of 2D and 3D cultures of HepG2, a human hepatocarcinoma cell line, in concentration-(>$50{\mu}M$) and time-dependent manners, both of which corresponded with ROS generation. An antioxidant, N-acetylcysteine, attenuated TAK-875-mediated hepatotoxicity, which confirmed the role of ROS generation. Of note, knockdown of GPR40 using siRNA abolished the hepatotoxicity of TAK-875 and attenuated ROS generation. In contrast, TAK-875 induced no cytotoxicity in fibroblasts up to $500{\mu}M$. Supporting the hepatotoxic potential of TAK-875, exposure to TAK-875 resulted in increased mortality of zebrafish larvae at$25{\mu}M$. Histopathological examination of zebrafish exposed to TAK-875 revealed severe hepatotoxicity as manifested by degenerated hypertrophic hepatocytes with cytoplasmic vacuolation and acentric nuclei, confirming that TAK-875 may induce direct hepatotoxicity and that ROS generation may be involved in a GPR40-dependent manner.

• Toxicological Research
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• v.22 no.2
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• pp.87-93
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• 2006

The KFDA (Korea Food & Drug Administration) has performed a collaborative toxico-genomics project since 2003. Its aim is to construct a toxicologenomic database of 12 hepatotoxic compounds from mice livers. Phenylbutazone which is non-steroidal anti-inflammatory drug was assigned. It was administered at low (0.0238 mg/kg) and at high (0.238 mg/kg) dose (5 mice per group) orally to the postnatal 6 weeks ICR mice, then the serum and liver were collected at the indicated time (6, 24 and 72 h) after administration. Serum biochemical markers for liver toxicity were measured and histopathologic studies also were carried out. The gene expression profiling was carried out by using Applied Biosystems 1700 Full Genome Expression Mouse. The 2-way ANOVA was used to find genes that reflected phenylbutazone-induced acute toxicity or dose-dependant changes. By self-organization maps (SOM), we identified groups with unique gene expression patterns, some of them are supposed to be related to phenylbutazone induced toxicity, including lipid metabolism abnormality, oxidative stress, cell death and cytoskeleton destruction.

• YAKHAK HOEJI
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• v.34 no.5
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• pp.341-347
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• 1990

The anti-hepatotoxic activity of Panax ginseng was studied using galactosamine (GalN)-induced cytotoxicity in primary cultured rat hepatocytes. Panax ginseng was fractionated into dammarane glycosides and protein fractions. The dammarane glycosides was further fractionated into panaxadiol and panaxatriol glycosides fractions. The protein fraction was further fractionated into four groups according to the molecular weight; larger than 10,000 dalton, between 5,000 and 10,000 dalton, between 1,000 and 5,000 dalton and between 500 and 1,000 dalton. A significant lowering action on the elevated glutamicpyruvic transaminase (GPT) activity in the culture medium of hepatocytes treated with 1.5 mM GalN was noticed with all four protein fractions studied at the concentration of both $50\;{\mu}g/ml$ and $100\;{\mu}g/ml$. However, the effect of dammarane glycosides fractions was not significant. It was noted that the addition of $100\;{\mu}g/ml$ of protein fractions smaller than 5,000 dalton significantly enhanced the syntheses of protein and RNA in the damaged hepatocytes induced by the treatment of 1.5 mM GalN. Dammarane glycosides fractions significantly enhanced protein synthesis at the concentration of $100\;{\mu}g/ml$ in the damaged hepatocytes by treatment of 1.5 mM GalN.

• CELLMED
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• v.2 no.4
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• pp.34.1-34.5
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• 2012

The present study aimed to determine the hepatoprotective activity of the chloroform extract of D. linearis leaves (CEDL) using the paracetamol (PCM)- and carbon tetrachloride ($CCl_4$)-induced liver injury models in rats. The rats received $dH_2O$ (negative control), 200 mg/kg of silymarin (positive control) or CEDL (50, 250 and 500 mg/kg) orally once daily for 7 days and then were subjected to the hepatotoxic induction on the $7^{th}$ day. The samples (i.e. blood and liver) were collected and underwent biochemical and microscopical analysis, respectively. From the data obtained, both inducers caused significant (p < 0.05) increase in the levels of AST and ALT when compared to the control group, which were significantly (p < 0.05) reduced by CEDL in a generally dose-dependent manner. These biochemical findings were supported by the histopathological analysis and histological scoring. In conclusion, CEDL possesses potential hepatoprotective activity, which could be associated with its flavonoid and tannin contents with the mechanisms of hepatoprotection linked to either its antioxidant or anti-inflammtory/immunomodulating activities. Further in-depth studies are required to identify the responsible bioactive compound.

• The Korea Journal of Herbology
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• v.26 no.3
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• pp.65-73
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• 2011

Objectives : The present study was evaluated the protective roles of Spatholobi Caulis in hepatotoxic rats due to APAP overdose. Methods : In experiments, rats were orally administrated with the aqueous extract of Spatholobi Caulis (SCE; 50, 100 mg/kg) for 4 days and then, orally gavage with APAP (1.2 g/kg) to induce acute liver damage. Results : Oral injection of APAP caused severe hepatic injury. Plasma ALT, AST and LDH levels were significantly elevated, but SCE significantly decreased ALT, AST and LDH to the normal level. In histopathological analysis, peripheral hemorrhage around portal triads and central necrosis around central veins were founded after APAP treatment. However, these histopathological changes were recovered by SCE pretreatment. SCE also decreased the percentage of generative hepatic regions (%/$mm^2$ hepatic parenchyma), the numbers of inflammatory cells (cells/$mm^2$ hepatic parenchyma) and the number of degenerative hepatic cells (N/100 hepatic cellls) which were significantly elevated after APAP injection. Furthermore, SCE down-regulated the contents of hepatic MDA and up-regulated hepatic GSH. SCE also inhibited the decrease in the expression of pro-caspase-3 by APAP treatment. Conclusions : Collectively, these data indicate that SCE protected APAP-induced hapatic damages through antioxidative and anti-apoptotic process. These findings the significant therapeutic potential of SCE during APAP-induced liver injury.

• Food Industry And Nutrition
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• v.10 no.3
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• pp.37-42
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• 2005

홍경천의 간보호 효과를 알아보고자 사염화탄소를 투여하여 간손상을 유발시킨 흰쥐에 홍경천 물추출물을 투여한 후 간독성 보호효과를 알아본 결과, 혈청중 ALT, AST, LDH, ALP 활성도는 사염화탄소 투여에 의해 증가하였으나, 사염화탄소 투여 후 홍경천 물추출물의 투여로 유의적인 감소를 나타내었다. Total cholesterol, total lipid, triglyceride는 사염화탄소 투여에 의해 증가하였으나, 사염화탄소 투여 후 홍경천 물추출물의 투여로 유의적인 감소를 나타내었다. 한편 phospholipid는 사염화탄소만 투여한 CCL군과 사염화탄소 투여 후 홍경천 물추출물을 투여 한 군 모두 유의성 차이는 없었으나 홍경천 물추출물을 투여함으로 증가함을 알 수 있었다. HDL-cholesterol의 함량은 사염화탄소만 투여한 CCL군에 비해 사염화탄소 투여 후 홍경천 물추출물을 투여 한 RSLIII군에서 유의적으로 높은 수치를 보였다. LDL-cholesterol은 사염화탄소만 투여 한 군과 사염화탄소를 투여후 홍경천 물추출물을 투여한 군간 유의적 차이를 확인할 수 없었다 이상의 결과에서 사염화탄소 투여로 각종 효소 활성도 및 지질의 함량이 증가되었는데 이는 사염화탄소 투여로 간세포에 손상이 유발되었음을 알 수 있었고, 사염화탄소 투여 후 홍경천 물추출물을 투여한 군에서 사염화탄소 투여로 증가된 각종 효소 활성도 및 각종 지질의 함량을 저하시키므로서 홍경천 물추출물이 손상된 간기능을 회복시킬 수 있을 것으로 사료된다.

• Journal of Life Science
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• v.25 no.3
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• pp.307-316
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• 2015

Beetle larvae have been used as a traditional medicine to treat various human liver diseases. To prove the liver protective function of Allomyrina dichotoma larvae (ADL), we induced liver damage by the intraperitoneal injection of a hepatotoxic reagent, diethylnitrosamine (DEN), to C3H/HeN male mice and orally administered freeze-dried ADL powder. ADL powder lessened DEN-induced hepatotoxicity considering the reduced signs of acute and chronic hepatotoxicities, such as the ALP level in the blood serum, TUNEL-positive hepatocytes, ductural reactions, steatotic hepatocytes, and collagen deposition of the Masson’s trichrome staining. In addition to hepatoprotection, the anti-cancer activity of ADL has been examined. The ADL powder was extracted with ethanol and then fractionated with hexane, ethyl acetate, and water by a solvent partition technique. The ethyl acetate fraction showed cytotoxicity to various cancer cells through induction of apoptosis and necrosis, as well as the perturbed metabolism of the cancer cell to trigger autophagy. Collectively, ADL contains bioactive substances that can protect hepatocytes from toxic chemicals and trigger cell death in cancer cells. Thus, further purification and analyses of ADL fractions could lead to the identification of novel bioactive compounds.