• Journal of Microbiology
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• v.37 no.2
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• pp.90-96
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• 1999

The core protein of the hepatitis C virus (HCV) is a multifunctional protein. The HCV core protein was reported to regulate cellular gene expression and transform primary rat embryo fibroblast cells. However, the role of the core protein in the pathogenesis of HCV-associated liver diseases is not well understood. To investigate the functional role of the core protein in cytophathogenicity, we have constructed stable expression systems of full length or truncated HCV core protein lacking the C-terminal hyderophobic domains and established HepG2 cell clones constitutively expressing the core protein. The full length core protein was localized in the cytoplasm and the C-terminal truncated core protein was localized in the nucleus. HepG2 cells expressing nuclear, truncated core protein showed elevated cell death during cultivation compared to untransfected cells and full length core-expressing cells. In the treatment with bleomycin, both cell clones expressing full length or truncated core protein appeared to be more sensitive to blemoycin than the parental HepG2 cells. These results suggest that the core protein may play a role in HCV pathogenesis promoting apoptotic cell death of infected cells.

• Korean Journal of Pharmacognosy
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• v.21 no.3
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• pp.223-234
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• 1990

Hepatoprotective activities of 26 traditional Korean herbal prescriptions described in Donghibogam were evaluated in vivo and in vitro screening system. Twenty one prescriptions appeared to be active. Six prescriptions among them showed highly significant hepatoprotective activities; Shihogyegy-Tang(柴胡桂枝湯), Soshiho-Tang(小柴胡湯), Shiho plus Younggolmoryo-Tang(柴胡加龍骨牡蠣湯), Yinjinho-Tang(茵蔯蒿湯), Yinsam-Tang(人蔘湯) and Shashim-Tang(瀉心湯). Shihogyegy-Tang was most active. They reduced the release of transaminases from dissociated hepatocytes by thioacetamide, and serum transaminases and alkaline phosphatase activities of rat with carbontetrachloride-induced hepatitis. They inhibited significantly lipid peroxidation and cellular fatty change of liver by carbontetrachloride.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.5
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• pp.375-383
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• 2013

Hepatocellular carcinoma (HCC) related to hepatitis B virus (HBV) and hepatitis C virus (HCV) infections is thought to account for more than 80% of primary liver cancers. Both HBV and HCV can establish chronic liver inflammatory infections, altering hepatocyte and liver physiology with potential liver disease progression and HCC development. Cyclophilin A (CypA) has been identified as an essential host factor for the HCV replication by physically interacting with the HCV non structural protein NS5A that in turn interacts with RNA-dependent RNA polymerase NS5B. CypA, a cytosolic binding protein of the immunosuppressive drug cyclosporine A, is overexpressed in many cancer types and often associated with malignant transformation. Therefore, CypA can be a good target for molecular cancer therapy. Because of antiviral activity, the CypA inhibitors have been tested for the treatment of chronic hepatitis C. Nonimmunosuppressive Cyp inhibitors such as NIM811, SCY-635, and Alisporivir have attracted more interests for appropriating CypA for antiviral chemotherapeutic target on HCV infection. This review describes CypA inhibitors as a potential HCC treatment tool that is contrived by their obstructing chronic HCV infection and summarizes roles of CypA in cancer development.

• Molecules and Cells
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• v.44 no.9
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• pp.688-695
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• 2021

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has become a global health concern. Various SARS-CoV-2 vaccines have been developed and are being used for vaccination worldwide. However, no therapeutic agents against coronavirus disease 2019 (COVID-19) have been developed so far; therefore, new therapeutic agents are urgently needed. In the present study, we evaluated several hepatitis C virus direct-acting antivirals as potential candidates for drug repurposing against COVID-19. Theses include asunaprevir (a protease inhibitor), daclatasvir (an NS5A inhibitor), and sofosbuvir (an RNA polymerase inhibitor). We found that asunaprevir, but not sofosbuvir and daclatasvir, markedly inhibited SARS-CoV-2-induced cytopathic effects in Vero E6 cells. Both RNA and protein levels of SARS-CoV-2 were significantly decreased by treatment with asunaprevir. Moreover, asunaprevir profoundly decreased virion release from SARS-CoV-2-infected cells. A pseudoparticle entry assay revealed that asunaprevir blocked SARS-CoV-2 infection at the binding step of the viral life cycle. Furthermore, asunaprevir inhibited SARS-CoV-2 propagation in human lung Calu-3 cells. Collectively, we found that asunaprevir displays broad-spectrum antiviral activity and therefore might be worth developing as a new drug repurposing candidate for COVID-19.

• Toxicological Research
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• v.34 no.1
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• pp.23-29
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• 2018

Ethanol-induced fat accumulation, the earliest and most common response of the liver to ethanol exposure, may be involved in the pathogenesis of liver diseases. Isoliquiritigenin (ISL), an important constituent of Glycyrrhizae Radix, is a chalcone derivative that exhibits antioxidant, anti-inflammatory, and phytoestrogenic activities. However, the effect of ISL treatment on lipid accumulation in hepatocytes and alcoholic hepatitis remains unclear. Therefore, we evaluated the effect and underlying mechanism of ISL on ethanol-induced hepatic steatosis by treating AML-12 cells with 200 mM ethanol and/or ISL ($0{\sim}50{\mu}M$) for 72 hr. Lipid accumulation was assayed by oil red O staining, and the expression of sirtuin1 (SIRT1), sterol regulatory element-binding protein-1c (SREBP-1c), AMP-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor alpha ($PPAR{\alpha}$) was studied by western blotting. Our results indicated that ISL treatment upregulated SIRT1 expression and downregulated SREBP-1c expression in ethanol-treated cells. Similarly, oil red O staining revealed a decrease in ethanol-induced fat accumulation upon co-treatment of ethanol-treated cells with 10, 20, and $50{\mu}M$ of ISL. These findings suggest that ISL can reduce ethanol induced-hepatic lipogenesis by activating the SIRT1-AMPK pathway and thus improve lipid metabolism in alcoholic fatty livers.

• The Journal of Internal Korean Medicine
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• v.33 no.4
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• pp.609-614
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• 2012

Drug-induced liver injury (DILI) is a common cause of acute hepatitis. Regarding the risk of DILI from herbal preparations, there are controversial issues such as exaggerated reports straying far from the truth and lack of discrimination between herbal drugs and folk remedies or food supplements. This study reported one case of a patient with DILI caused by Smilacis Chinae Radix and cured in an Oriental hospital. Smilacis Chinae Radix has been used as an anti-inflammatory, anti-microbial, detoxification and anticancer compound, as a folk remedy. This report would provide helpful information for management of DILI by folk remedies or herbal drugs.

• YAKHAK HOEJI
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• v.48 no.6
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• pp.379-383
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• 2004

Biphenyl dimethyl dicarboxylate (DDB) has been used for the treatment of chronic viral hepatitis B and drug-induced hepatitis through the inhibition of lipid peroxidation and c ovalent binding of drug metabolites to lipids of microsomes. The bioequivalence of two DDB products was evaluated according to the guidelines of KFDA. The test product was Hepaphil soft capsule(R) made by KMS Pharm. Co. Containing 3 mg DDB and the reference product was Nissel tablet(R) made by Taerim Pharm. Co. Containing 25 mg DDB. Twenty healthy male subjects, 25.4(22~30) years old and 66.7(54~77)kg, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After two tablets or two capsules were orally administered, blood was taken at predetermined time intervals and the concentration of DDB in plasma was determined using a validated HPLC method with UV detector. Two pharmacokinetic parameters, $AUC_t$ and $C_{max}$, were calculated and analyzed statistically for the evaluation of bioequivalence of the two products. Analysis of variance was carried out using logarithmically transformed parameter values. The 90% confidence intervals of $AUC_t$ and $C_{max}$ were log 0.91~log1.00 and log 1.05~log 1.15, respectively. These values were within the acceptable bioequivalence intervals of log 0.8 to log 1.25. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating that Hepaphil soft capsule is bioequivalent to Nissel tablet.

• Clinical and Experimental Pediatrics
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• v.51 no.11
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• pp.1228-1231
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• 2008

Drug hypersensitivity syndrome (DHS) has rarely been reported in association with vancomycin treatment. Here, we describe an 11-year-old girl who developed fever and a maculopapular rash on day 18 of intravenous vancomycin for treatment of infective endocarditis. The patient presented with fever, a maculopapular skin rash, hepatitis, and acute renal failure caused by vancomycin-induced DHS. The symptoms resolved in less than 24 h after withdrawal of vancomycin and treatment with corticosteroids. We present this case of DHS associated with vancomycin.

• The Journal of Internal Korean Medicine
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• v.37 no.2
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• pp.374-380
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• 2016

Objective: Although the incidence of chronic hepatitis B has decreased around the world due to widespread national preventative control measures, mortality from the same condition can increase if the condition leads to liver cancer or liver cirrhosis. In most cases, herbal medicine does not show any statistically significant effects related to liver damage, but preconceptions do exist that herbal medicine can be toxic and cause such liver damage. To investigate this situation, this study therefore investigated a patient with hepatitis B who had combined traditional Korean medicine therapy and the use of analgesic drugs during a hospitalization period.Method: A patient with hepatitis B was given combined traditional Korean medicine therapy and the use of analgesic drugs during a hospitalization period.Results: Within 26 days, the patient was free from liver damage during the hospitalization period. She was followed up with a liver function test and was discharged after her condition improved; she also reported decreased back pain.

• The Journal of Internal Korean Medicine
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• v.30 no.1
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• pp.249-255
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• 2009

Currently, drug-induced liver injury (DILl) has been reported to be common cause of acute hepatitis, and oriental medicine and folk remedies are no exception. However, because many studies about DILl have been reported by western medical society. they has taken the initiative of DILl not only for western drugs but also herbs. So, academia of oriental medicine should make an effort to progress herb-related DILl studies. We describe a patient of acute liver injury which had been caused by comfrey, albizzia julibrissin, ulmus davidiana var. japonica, red ginseng. We hope that this report helps for studying the diagnosis and management of herb-derived DILl. and for establishing a standard of oriental therapy to DILL.