Nuclear factor erythroid 2-related factor 2 활성화를 통한 해간전(解肝煎)의 간세포 보호 효능 및 분자기전을 활용한 해간전(解肝煎) 구성 약물의 최적화 연구

김재광,정지윤,박상미,박정아,구세광,변성희,조일제,김상찬,Kim, Jae Kwang,Jung, Ji Yun,Park, Sang Mi,Park, Chung A,Ku, Sae Kwang,Byun, Sung Hui,Cho, Il Je,Kim, Sang Chan 대한한의학방제학회 2018 大韓韓醫學方劑學會誌 Vol.26 No.3

Objectives : Present study investigated hepatoprotective effect of Haegan-jeon extract (HE) and tried to elucidate molecular mechanism involved. According to molecular mechanism, present study optimized herbal composition of HE (op-HE) and compared in vitro and in vivo hepatoprotective effects of op-HE to HE. Methods : For in vitro experiments, HepG2 cells were exposed to arachidonic acid (AA, $10{\mu}M$) and iron ($5{\mu}M$) for inducing oxidative stress. Cell viability, GSH contents, $H_2O_2$ production, mitochondrial membrane potential, immunoblot and reporter gene assay were performed to investigate cytoprotective effects and responsible molecular mechanisms. For in vivo experiments, hepatoprotective effect of HE and op-HE were assessed on $CCl_4-induced$ liver injury mice model. Results : HE pretreatment prevented AA+iron-mediated hepatocytes apoptosis. In addition, AA+iron-induced mitochondrial dysfunction, $H_2O_2$ production, glutathione depletion were reduced by HE pretreatment. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation, antioxidant response element (ARE)-driven reporter gene activity, and antioxidant genes expression were increased by HE. Based on reporter gene and MTT assays, we found that op-HE consisting three medicinal herbs also significantly increased transactivation of Nrf2 and reduced the AA+iron-mediated cytotoxicity. Moreover, in $CCl_4-induced$ liver injury mice model, HE-op had an ability to ameliorate $CCl_4-mediated$ increases in serum alanine transferase and aspartate aminotransferase activity, hepatic degeneration, inflammatory cell infiltration, and collagen deposition. Hepatoprotective effects of op-HE were comparable to those of HE. Conclusions : Present study suggests that op-HE as well as HE exhibit hepatoprotective effect against oxidative stress-mediated liver injury via Nrf2 activation.

Hepatoprotective Effects of Potato Peptide against D-Galactosamineinduced Liver Injury in Rats

Kiyoshi Ohba,Kyu-Ho Han,Ruvini Liyanage,Megumi Nirei,Naoto Hashimoto,Ken-ichiro Shimada,Mitsuo Sekikawa,Keiko Sasaki,Chi-Ho Lee,Michihiro Fukushima 한국식품과학회 2008 Food Science and Biotechnology Vol.17 No.6

The effect of some peptides on hepatoprotection and cecal fermentation against D-galactosamine (GalN)-treated rats was studied. In acute hepatic injury tests, serum alanine aminotransferase (ALT), aspartate aminotranferase (AST), and lactic dehydrogenase (LDH) activities were remarkably increased after injection of GalN. However, potato and soybean peptides significantly decreased GalN-induced alterations of serum ALT and AST activities. Hepatic thiobarbituric acidreactive substance (TBARS) concentration in GalN-treated groups fed potato and soybean peptides was significantly lower than that in GalN-treated control group. Hepatic glutathione level in the GalN-treated group fed potato peptide was significantly higher than that in GalN-treated control group. Furthermore, cecal Lactobacillus level in GalN-treated groups fed potato and soybean peptides was significantly higher than that in GalN-treated control group, and cecal short-chain fatty acid concentrations in GalN-treated group fed potato peptide were significantly higher than in GalN-treated control group. These results indicate that potato peptide may improve the cecal fermentation and prevent the GalN-induced liver damage in rats.

결명자의 타크린으로 유발한 간 세포독성 보호 성분

변에리사,정길생,안인파,리빈,이동성,고은경,윤권하,김윤철 한국생약학회 2007 생약학회지 Vol.38 No.4

is an acetylcholinesterase inhibitor that is approved for the treatment of Alzheimer’s disease. However,tacrine treatment for Alzheimer’s disease results in reversible hepatotoxicity in 30-50% of patients, which seriously limits itsclinical use. Accordingly, the identification of constituents in natural products that have protective efects on tacrine-inducedhepatotoxicity would be valuable. In the present study, an immortalized human hepatoma cell line, HepG2 was employed toscreen for agents that protect against tacrine-induced hepatotoxicity. The bioassay-guided fractionation of water extract of Cas-siae Semen furnished two anthraquinones, aurantio-obtusin (1) and obtusifolin (2). Compounds 1 and 2 showed hepato-protective effects with the protection ratio values of 55.3 +/ 0.5% and 41.2 +/ 0.8% at 160M, respectively.Key words Cassia obtusifolia L, aurantio-obtusin, obtusifolin, tacrine, hepatoprotection, HepG2

Hepatoprotective Effect of Chitosan Oligosaccharides on CCl4-induced Liver Injury in Rats

강기영,김정우,강기영 한국키틴키토산학회 2010 한국키틴키토산학회지 Vol.15 No.2

Various toxic materials cause hepatocellular injury and finally hepatic fibrosis or cirrhosis. It is well known that development of hepatic fibrosis is mediated by hepatic stellate cells (HSCs) and transforming growth factor-betas (TGF-ßs) signalling mechanism. The aim of this study is to demonstrate hepatoprotective effect of chitosan oligosaccharides (COS) using carbon tetrachloride (CCl4) intoxicated rat model. For this study, three groups of animals were prepared. Group A was given corn oil only, but group B and C were given CCl4 once a week for 4 weeks. And group C was additively given COS daily for 4 weeks. After then, serological, histological, and western blot analyses were performed. COS treatment prevented increment of liver weight and elevation of serum ALT level. It also reduced hepatocellular damages and prevented development of hepatic fibrosis and collagen deposit. The immunohistochemistry and western blot analysis showed that COS treatment decreased activation of HSCs and expression of type I TGF-ß receptor. These results suggest that COS effectively protects liver from CCl4-induced hepatocellular injuries and hepatic fibrosis.

Nrf2활성화를 통한 삼출건비탕(蔘朮健脾湯)의 간세포보호효과

김예림,진효정,박상미,변성희,송창현,김상찬,Ye Lim Kim,Hyo Jeong Jin,Sang Mi Park,Sung Hui Byun,Chang Hyun Song,Sang Chan Kim 대한한의학방제학회 2023 大韓韓醫學方劑學會誌 Vol.31 No.2

Objectives : Oxidative stress is an important cause of many diseases including liver injury. Therefore, adequate regulation of oxidative stress plays a pivotal role in maintaining liver function. Until recently, there has been no studies on the hepatoprotective effect of Samchulgeonbi-tang (SCGBT). Therefore, the hepatoprotective effect of SCGBT was investigated in HepG2 cells. In this study, oxidative stress was induced by arachidonic acid (AA) and iron. Methods : To analyze the hepatoprotective effects of SCGBT against oxidative stress induced by AA + iron, the cell viability, apoptosis-related proteins and intracellular ROS, glutathione (GSH), and mitochondrial membrane permeability (MMP) were measured. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) transcription activation and expressions of Nrf2 target gene were analyzed through immunoblot analysis. Results : SCGBT increased the cell viability from AA + iron - induced cell death and inhibited apoptosis by regulating apoptosis related proteins. SCGBT protected cells by inhibiting ROS production, GSH depletion, and MMP degradation against AA + iron induced oxidative stress. Furthermore, Nrf2 activation was increased by SCGBT, and the Nrf2 target genes were also activated by SCGBT. Conclusions : These results suggest that the SCGBT has a hepatocyte protection effect and antioxidant effect from AA + iron induced oxidative stress.

Hepatoprotective Effect of Chitosan Oligosaccharides on CCl4-induced Liver Injury in Rats

( Rack Jong Song ),( Jung Woo Kim ),( Ki Young Kang ) 한국키틴키토산학회 2010 한국키틴키토산학회지 Vol.15 No.2

Various toxic materials cause hepatocellular injury and finally hepatic fibrosis or cirrhosis. It is well known that development of hepatic fibrosis is mediated by hepatic stellate cells (HSCs) and transforming growth factor-betas (TGF-ßs) signalling mechanism. The aim of this study is to demonstrate hepatoprotective effect of chitosan oligosaccharides (COS) using carbon tetrachloride (CCl4) intoxicated rat model. For this study, three groups of animals were prepared. Group A was given corn oil only, but group B and C were given CCl4 once a week for 4 weeks. And group C was additively given COS daily for 4 weeks. After then, serological, histological, and western blot analyses were performed. COS treatment prevented increment of liver weight and elevation of serum ALT level. It also reduced hepatocellular damages and prevented development of hepatic fibrosis and collagen deposit. The immunohistochemistry and western blot analysis showed that COS treatment decreased activation of HSCs and expression of type I TGF-ß receptor. These results suggest that COS effectively protects liver from CCl4-induced hepatocellular injuries and hepatic fibrosis.

Antioxidant Properties of Taraxacum officinale Leaf Extract Are Involved in the Protective Effect Against Hepatoxicity Induced by Acetaminophen in Mice

Dirleise Colle,Leticia Priscilla Arantes,Priscila Gubert,Soˆnia Cristina Almeida da Luz,Margareth Linde Athayde,Joa˜o Batista Teixeira ocha,Fe´lix Alexandre Antunes Soares 한국식품영양과학회 2012 Journal of medicinal food Vol.15 No.6

Acetaminophen (APAP) hepatotoxicity has been related to several cases of hepatitis, cirrhosis, and hepatic transplant. As APAP hepatotoxicity is related to reactive oxygen species (ROS) formation and excessive oxidative stress,natural antioxidant compounds have been tested as an alternative therapy to diminish the hepatic dysfunction induced by APAP. Taraxacum officinale Weber (Family Asteraceae), commonly known as dandelion, is used for medicinal purposes because of its choleretic, diuretic, antioxidant, anti-inflammatory, and hepatoprotective properties. This study evaluated the hepatoprotective activity of T. officinale leaf extract against APAP-induced hepatotoxicity. T. officinale was able to decrease thiobarbituric acid–reactive substance levels induced by 200 mg/kg APAP (p.o.), as well as prevent the decrease in sulfhydryl levels caused by APAP treatment. Furthermore, histopathological alterations, as well as the increased levels of serum aspartate and alanine aminotransferases caused by APAP, were prevented by T. officinale (0.1 and 0.5 mg/mL). In addition, T. officinale extract also demonstrated antioxidant activity in vitro, as well as scavenger activity against 2,2-diphenyl-1-picrylhydrazyl and nitric oxide radicals. Our results clearly demonstrate the hepatoprotective effect of T. officinale against the toxicity induced by APAP. The possible mechanisms involved include its scavenger activities against ROS and reactive nitrogen species, which are attributed to the content of phenolic compounds in the extract.

다래나무의 tert-butyl Hydroperoxide로 유도된 산화적 스트레스에 대한 간 보호 효과

조은혜,강경수,이희주,김철영,신일식,노주원 대한암예방학회 2011 Journal of cancer prevention Vol.16 No.1

The fruits and leaves of Actinidia arguta are a well-known Korean folk medicine for treatment of jaundice, fever, acute hepatitis and bleeding by an external wound. The purpose of this study was to investigate the hepatoprotective effect of A. arguta on tert-butyl hydroperoxide (t-BHP) induced oxidative stress in HepG2 human liver cancer cells. Cell viability, generation of reactive oxygen species, quantification of total glutathione, total polyphenolic compounds were evaluated in this study. Pretreatment of the extract from A. arguta extract, butanol and ethyl acetate fractions strongly prevented cytotoxicity induced by t-BHP. Reactive oxygen species generation induced by t-BHP was significantly decreased when the cells were pretreated for 24 h with either 10∼40μg/ml extract or hexane, ethyl acetate, butanol fractions. In addition, lower levels of total glutathione (GSH) caused by t-BHP in HepG2 cells were recovered by a pre-treatment with extract and 3 fractions. The contents of total polyphenolic compounds were also determined using a modified Folin-Ciocalteu colorimetric method. The ethyl acetate and butanol fractions had high phenolic compounds, and they showed 136.61μg/100 g and 211.64μg/100 g, respectively, suggesting that these antioxidants content was correlated with their hepatoprotective activity. Therefore, these result suggest that the A. arguta could be a potential candidate of hepatoprotective agents against oxidative stress. (Cancer Prev Res 16, 74-79, 2011)

Hepatoprotective effects of Gamisoyo-san against acetaminophen-induced liver injuries

Seong Eun Jin,Hyeun Kyoo Shin,하혜경 한국한의학연구원 2021 Integrative Medicine Research Vol.10 No.1

Background: Acetaminophen (N-acetyl-p-aminophenol, APAP) is a safe and effective analgesic at therapeutic dosage. However, APAP overdose is a major cause of acute liver injury. Gamisoyo-san (GMSYS; Jiaweixiaoyao-san in Chinese, Kamishoyo-san in Japanese), a traditional herbal formula, is used to treat phlegm and cough in Korea. The purpose of this study was to investigate the hepatoprotective effect of GMSYS against APAP-induced liver injury in vitro and in vivo. Methods: We evaluated the effect of GMSYS on APAP-induced hepatotoxicity by measuring cell viability in murine BNL CL.2 liver cells. Additionally, BALB/c mice were orally administered with GMSYS once daily for 7 days. Eighteen hours after the last administration, mice were intraperitoneally injected with 200 mg/kg APAP. Plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, hepatic antioxidants, and histological changes were examined. Results: Pretreatment with GMSYS attenuated the decrease in cell viability induced by APAP in BNL CL.2 cells. In mice, pre-administration with GMSYS alleviated APAP-induced hepatotoxicity by decreasing plasma ALT and AST activities and hepatic malondialdehyde, and by increasing the total glutathione (GSH)/reduced GSH ratio and the activities of several antioxidants such as superoxide dismutase, catalase, GSH peroxidase, GSH reductase, GSH-S-transferase, and heme oxygenase-1. Conclusion: GMSYS has a protective effect against APAP-induced acute liver injury by decreasing plasma transaminases and increasing antioxidants. GMSYS may be an effective candidate for the prevention of acute liver injury.

Hepatoprotective and antineoplastic properties of Protaetia brevitarsis larvae

이지은,조다은,이안중,박혜경,윤금주,윤은영,황재삼,전미라,강병헌 한국곤충학회 2014 Entomological Research Vol.44 No.6

Protaetia brevitarsis larvae have been used as a traditional medicine to treat various liver diseases. Freeze‐dried powder and solvent partitioned fractions of Protaetia brevitarsis larvae, in this study, were examined for hepatoprotective and antitumor activities in vivo and in vitro. Oral administration of the powder reduced signs of acute and chronic liver injuries in diethylnitrosamine‐induced hepatotoxic mouse model. Various cancer cell types, but not normal primary hepatocytes, were killed by the hexane, ethyl acetate and butanol fractions, which were partitioned from larval extracts. Apoptosis and autophagy were primarily induced in cancer cells by hexane and ethyl acetate fractions, respectively, and can be the cytotoxic mechanisms of the fractions. Further analyses of the insect fractions could lead to identification of novel bioactive substances that can be exploited as therapeutics for various human liver diseases.