• Journal of Microbiology and Biotechnology
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• 제33권4호
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• pp.463-470
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• 2023

This study confirmed the change in functional composition and alcohol-induced acute liver injury in Aloe arborescens after fermentation. An acute liver injury was induced by administration of ethanol (3 g/kg/day) to C57BL/6J mice for 5 days. A fermented A. arborescens Miller leaf (FAAL) extract was orally administered 30 minutes before ethanol treatment. After fermentation, the emodin content was approximately 13 times higher than that of the raw material. FAAL extract significantly attenuated ethanol-induced aspartate aminotransferase, alanine aminotransferase, and triglyceride increases in serum and liver tissue. Histological analysis revealed that FAAL extract inhibits inflammatory cell infiltration and fat accumulation in liver tissues. The cytochrome P450 2E1, superoxide dismutase, and glutathione (GSH), which involved in alcohol-induced oxidative stress, were effectively regulated by FAAL extract in serum and liver tissues, except for GSH. FAAL also maintained the antioxidant defense system by upregulating heme oxygenase 1 and nuclear factor erythroid 2-related factor 2 protein expression. In addition, FAAL extract inhibited the decrease in alcohol dehydrogenase and aldehyde dehydrogenase activity, which promoted alcohol metabolism and prevented the activation of inflammatory response. Our results suggest that FAAL could be used as a potential therapeutic agent for ethanol-induced acute liver injury.

• Archives of Pharmacal Research
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• 제28권4호
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• pp.438-442
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• 2005

A series of 3-[1-(4-(2-methylpropyl) phenyl) ethyl]-1,2,4-triazole-5-thione (I) and its bicyclic condensed derivatives 6-benzylidenethiazolo[3,2-b]-1, 2,4-triazole-5(6H)-ones (IIa-IIf) were investigated for the prevention of ethanol-induced oxidative stress in liver and brain of mice. Administration of ethanol (0.1 mL/mice, p.o.) resulted in a drop of total thiol groups (T-SH) and non-protein thiol groups (NP-SH), and an increase in thiobarbituric acid reactive substances (TBARS) in both liver and brain tissue of mice (p<0.001). Among the compounds investigated (at a dose of 200 mg/kg, p.o.), I and IId ameliorated the peroxidative injury in these tissues effectively. Compounds IIa, IIc and IIe improved the peroxidative tissue injury only in brain. These findings suggest that certain condensed thiazolo-triazole compounds may contribute to the control of ethanol-induced oxidative stress in an organ selective manner.

• 대한한의학방제학회지
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• 제24권3호
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• pp.163-174
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• 2016

Objectives : Rheum undulatum Linne and Glycyrriza uralensis Fischer are widely used herbal medicine. In this study, anti-oxidant and liver protective effects of R. undunlatum extract (RUE) and G. uralensis extract (GUE) were investigated in HepG2 cells, respectively. Oxidative stress and liver fibrosis were induced by arachidonic acid (AA) and iron, and CCl₄.Methods : MTT assay was assessed for cell viability, and immunoblotting analysis was performed to detect expression of apoptosis related proteins. In addition, reactive oxygen species (ROS) and mitochondrial dysfunction were measured. In vivo, BALB/c mouse were orally administrated with the aqueous extract of 10 mg/kg RUE and 100 mg/kg GUE for 3 days and then, injected with CCl₄ 0.5 ml/kg body weight to induce acute liver damage. Serum ALT level was measured, and histological change was observed in Harris's hematoxylin and eosin stainResults : RUE and GUE pre-treatment increased relative cell viability in concentration dependent manner and altered the expression levels of apoptosis-related proteins such as procaspase 3, PARP and Bcl-xL. RUE and GUE also inhibited the mitochondrial dysfunction and excessive reactive oxygen species (ROS) production induced by AA and iron. In addition, RUE and GUE activated liver kinase B1 (LKB1), by increasing phosphorylation. Moreover, RUE and GUE treatment decreased liver injuries induced by CCl₄, as evidenced by decreases in histological liver damage as well as serum alanine amino transferase (ALT) level.Conclusions : These data suggest that RUE and GUE has anti-oxidant and liver protective effects against AA and iron-induced oxidative stress and CCl₄-induced liver injury.

• Journal of Acupuncture Research
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• 제32권1호
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• pp.13-22
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• 2015

Objectives : Alcohol-related liver disease is a major cause of morbidity and mortality worldwide. The present study was undertaken to determine whether Ganoderma lucidum pharmacopuncture(GLP) could protect against chronic liver injury induced by ethanol intoxication in rats. Methods : Sprague-Dawley rats were divided into 4 groups: normal, control, normal saline pharmacopuncture(NP), and GLP, with 8 animals in each. Each group, except normal, received ethanol orally. The NP and GLP groups were treated daily with NP and GLP respectively. The control group was not treated. All rats except the normal group were intoxicated for 4 weeks by oral administration of EtOH(6 g/kg BW). Two acupuncture points were used: Qimen($LR_{14}$) and Taechung($LR_3$). Body weight, histopathological analysis, liver function, activities of antioxidant enzymes, and immunohistochemistry were assessed. Results : GLP reduced the histological changes due to chronic liver injury induced by EtOH and significantly reduced the increase in the alanine aminotransferase(ALT) and aspartate aminotransferase(AST) enzymes. It significantly reversed the superoxide dismutase(SOD) and the catalase activities(CAT). It also significantly decreased BAX and increased Bcl-2 immunoreactivity expression. Conclusions : This study showed the protective efficacy of GLP against EtOH-induced chronic liver injury in SD rats by modulating ethanol metabolizing enzymes activity, attenuating oxidative stress, and inhibiting mitochondrial damage-mediated apoptosis.

• 대한본초학회지
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• 제36권2호
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• pp.31-42
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• 2021

Objectives : This study was undertaken to investigate the hepatoprotective effect of Spatholobi Caulis water extract (SC) to thioacetamide (TAA)-induced acute liver injury (ALI) in rats. Methods : The rats were injected intraperitoneally with TAA (200 mg/kg body weight) and orally administered SC (100 or 200 mg/kg b.w.) daily for 3 days. Liver biomarkers were assessed by serum glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and ammonia levels. Malondialdehyde (MDA) was measured both serum and liver tissue. In addition, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, anti-oxidant, and inflammation-related proteins were investigated by western blot analysis. Histological examination further confirmed though hematoxylin and eosin stain. Results : The SC treatment reduced liver function markers like GOT and GPT and also remarkably decreased ammonia level. Moreover, the elevated MDA level in TAA-induced group was significantly reduced by SC treatment. NADPH oxidase expression associated with oxidative stress including NOX2, NOX4, and p47phox markedly inhibited by SC administration. SC treatment exerted anti-oxidant effect through the increase of anti-oxidant enzyme including superoxide dismutase (SOD), Catalase, and heme oxygenase-1 (HO-1). The protein expressions of inflammatory cytokines such as tumor necrosis factor-�� (TNF-��), IL-6, and IL-1�� induced by nuclear factor-kappa B (NF-��B) activation were modulated through blocking the phosphorylation of inhibitor of nuclear factor ��B�� (I��B)��. SC treatment also improved histological alterations. Conclusion : These findings suggested that SC administration may be a potential candidate for the prevention or treatment of ALI.

• Biomolecules & Therapeutics
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• 제8권2호
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• pp.119-124
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• 2000

We hypothesized that the extent of hypoxic injury would be involved in reduction of oxygen delivery to the tissue. Livers isolated from 18 hr-fasted rats were subjected to $N_2$-induced hypoxia or low flow hypoxia. Livers were perfused with nitrogen/carbon dioxide gas for 45min or perfused with normoxic Krebs-Henseleit bicarbonate buffer (KHBB) at low flow rates around 1 ml/g liver/min far 45min, which caused cells to become hypoxic because of insufficient delivery of oxygen. When normal flow rates(4 ml/g liver/min) of KHBB (pH 7.4, 37$^{\circ}C$, oxygen/carbon dioxide gas) were restored for 30min reoxygenation injury occurred. Lactate dehydrogenase release gradually increased in $N_2$-induced hypoxia, whereas it rapidly increased in low flow hypoxia. Total glutathione in liver tissue was not changed but oxidized glutathione markedly increased after hypoxia and reoxygenation, expecially in $N_2$-induced hypoxia. Similarly, lipid peroxidation in liver tissue significantly increased after hypoxia and reoxygenation in low flow hypoxia. Hepatic drug metabolizing functions (phase I, II) were suppressed during hypoxia, especially in $N_2$-induced hypoxia but improved by reoxygenation in both models. Our findings suggest that hypoxia results in abnormalities in drug metabolizing function caused by oxidative stress and that this injury is dependent on hypoxic conditions.

• The Korean Journal of Physiology and Pharmacology
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• 제21권3호
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• pp.317-325
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• 2017

Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease in parallel with worldwide epidemic of obesity. Reactive oxygen species (ROS) contributes to the development and progression of NAFLD. Peroxisomes play an important role in fatty acid oxidation and ROS homeostasis, and catalase is an antioxidant exclusively expressed in peroxisome. The present study examined the role of endogenous catalase in early stage of NAFLD. 8-week-old male catalase knock-out (CKO) and age-matched C57BL/6J wild type (WT) mice were fed either a normal diet (ND: 18% of total calories from fat) or a high fat diet (HFD: 60% of total calories from fat) for 2 weeks. CKO mice gained body weight faster than WT mice at early period of HFD feeding. Plasma triglyceride and ALT, fasting plasma insulin, as well as liver lipid accumulation, inflammation (F4/80 staining), and oxidative stress (8-oxo-dG staining and nitrotyrosine level) were significantly increased in CKO but not in WT mice at 2 weeks of HFD feeding. While phosphorylation of Akt (Ser473) and $PGC1{\alpha}$ mRNA expression were decreased in both CKO and WT mice at HFD feeding, $GSK3{\beta}$ phosphorylation and Cox4-il mRNA expression in the liver were decreased only in CKO-HF mice. Taken together, the present data demonstrated that endogenous catalase exerted beneficial effects in protecting liver injury including lipid accumulation and inflammation through maintaining liver redox balance from the early stage of HFD-induced metabolic stress.

• Nutrition Research and Practice
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• 제14권4호
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• pp.334-351
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• 2020

BACKGROUND/OBJECTIVES: This study was designed to investigate the improvement effect of white ginseng extract (GS-KG9) on D-galactosamine (Ga1N)-induced oxidative stress and liver injury. SUBJECTS/METHODS: Sixty Sprague-Dawley rats were divided into 6 groups. Rats were orally administrated with GS-KG9 (300, 500, or 700 mg/kg) or silymarin (25 mg/kg) for 2 weeks. The rats of the GS-KG9- and silymarin-treated groups and a control group were then intraperitoneally injected Ga1N at a concentration of 650 mg/kg for 4 days. To investigate the protective effect of GS-KG9 against GalN-induced liver injury, blood liver function indicators, anti-oxidative stress indicators, and histopathological features were analyzed. RESULTS: Serum biochemical analysis indicated that GS-KG9 ameliorated the elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in GalN-treated rats. The hepatoprotective effects of GS-KG9 involved enhancing components of the hepatic antioxidant defense system, including glutathione, glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT). In addition, GS-KG9 treatment inhibited reactive oxygen species (ROS) production induced by GalN treatment in hepatocytes and significantly increased the expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins, which are antioxidant proteins. In particular, by histological analyses bases on hematoxylin and eosin, Masson's trichrome, α-smooth muscle actin, and transforming growth factor-β1 staining, we determined that the administration of 500 mg/kg GS-KG9 inhibited hepatic inflammation and fibrosis due to the excessive accumulation of collagen. CONCLUSIONS: These findings demonstrate that GS-KG9 improves GalN-induced liver inflammation, necrosis, and fibrosis by attenuating oxidative stress. Therefore, GS-KG9 may be considered a useful candidate in the development of a natural preventive agent against liver injury.

• Journal of Nutrition and Health
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• 제54권2호
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• pp.224-237
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• 2021

본 연구는 백작약 열수 추출물의 in vitro 항산화능을 평가하였으며, TAA를 유발한 급성 간손상 동물 모델을 이용하여 항산화 활성으로 인한 산화적 스트레스 억제 효과와 간 기능 보호효과 여부를 검증하였다. 총 폴리페놀, 총 플라보노이드 함량, DPPH 및 ABTS 자유 라디칼 소거능 측정 결과 높은 항산화능을 나타냈으며, 체중, 간무게 및 간중량 비율 (%)이 대조군에 비해 S100군과 PR100군보다 PR200군에서 더욱 감소하였다. 약물투여군의 혈중 암모니아, GOT 및 GPT 수준의 유의적인 감소를 확인하였으며, western blot 실시 후 대부분의 인자에서 유의적인 차이를 확인하였다. 이 결과를 토대로 백작약 열수 추출물이 Nrf2-Keap1경로의 활성화를 통해 항산화 효소를 증가시켰으며, 항산화능을 통한 산화적 스트레스 개선에 긍정적인 효과가 있음을 확인할 수 있었다. 따라서 백작약 열수 추출물은 급성 간손상시 간보호 효과를 위한 후보 소재로서 가능성이 있다고 판단된다.

• Korean Journal of Acupuncture
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• 제20권4호
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• pp.41-52
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• 2003

Objectives : Circii Herba has been used as a natural drug for the treatment of stress digestive system disease. The aim of this study is to investigate the role of Circii Herba aqua-acupuncture solution (CHAS) in experimental oxidative liver injury. Methods : In order to investigate the effects of CHAS on acute liver injury, male ICR mice were pretreated with CHAS(0.2 ml/mouse/day) at the loci of BL18 and CV12 for 6days, starved for 24hrs, and administerated acetaminophen(500 mg/kg, i.p.). After acetaminophen administeration, mice were sacrificed, and the liver was removed, rinsed with ice-cold $1.15{\%}$ KCI buffer, and homogenized at $4^{\circ}C$. Fractions(fraction Ⅰ, Ⅱ, Ⅲ) were isolated by differential centrifugation. Lipidperoxide, total SH, and glutathione(GSH) levels were measured in the Fraction Ⅰ. In addition, activities of hepatic enzyme, such as catalase, glutathione peroxidase(GSH-Px) were measured in the Fraction Ⅱ, and glutathione S-transferase(GST) was measured in the Fraction Ⅲ. Results : In vivo treatment of CHAS(BL18 and CV12) showed effective inhibition of acetaminophen induced lipid peroxidation, and showed elevations of total SH, GSH level, catalase, GSH-Px, GST activities. Conclusions : These results suggested that CHAS might suppress the formation of oxidative metabolites, and prevent acetaminophen induced hepatotoxicity.