• Nutrition Research and Practice
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• v.13 no.6
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• pp.473-479
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• 2019

BACKGROUND/OBJECTIVES: Anti-inflammatory and antioxidative activities of luteolin and luteolin-7-O-glucoside were compared in galactosamine (GalN)/lipopolysaccharide (LPS)-induced hepatitic ICR mice. MATERIALS/METHODS: Male ICR mice (6 weeks old) were divided into 4 groups: normal control, GalN/LPS, luteolin, and luteolin-7-O-glucoside groups. The latter two groups were administered luteolin or luteolin-7-O-glucoside (50 mg/kg BW) daily by gavage for 3 weeks after which hepatitis was induced by intraperitoneal injection of GalN and LPS (1 g/kg BW and $10{\mu}g/kg\;BW$, respectively). RESULTS: GalN/LPS produced acute hepatic injury by a sharp increase in serum AST, ALT, and $TNF-{\alpha}$ levels, increases that were ameliorated in the experimental groups. In addition, markedly increased expressions of cyclooxygenase (COX)-2 and its transcription factors, nuclear factor $(NF)-{\kappa}B$ and activator protein (AP)-1, were also significantly attenuated in the experimental groups. Compared to luteolin-7-O-glucoside, luteolin more potently ameliorated the levels of inflammatory mediators. Phase II enzymes levels and NF-E2 p45-related factor (Nrf)-2 activation that were decreased by GalN/LPS were increased by luteolin and luteolin-7-O-glucoside administration. In addition, compared to luteolin, luteolin-7-O-glucoside acted as a more potent inducer of changes in phase II enzymes. Liver histopathology results were consistent with the mediator and enzyme results. CONCLUSION: Luteolin and luteolin-7-O-glucoside protect against GalN/LPS-induced hepatotoxicity through the regulation of inflammatory mediators and phase II enzymes.

• Nutrition Research and Practice
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• v.13 no.5
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• pp.367-376
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• 2019

BACKGROUND/OBJECTIVE: The blue honeysuckle berry (Lonicera caerulea var. edulis L.) is a small deciduous shrub belonging to the Caprifoliaceae family that is native to Russia, China, Japan, and Korea. The berry of this shrub is edible, sweet and juicy and is commonly known as the blue honeyberry (BHB). This study examined the anti-diabetic potential of BHB on high-fat-diet-induced mild diabetic mice. The hypoglycemic, and nephroprotective effects of the 12-week oral administration of blue honeyberry extract were analyzed. MATERIALS/METHODS: The hypoglycemic effects were based on the observed changes in insulin, blood glucose, and glycated hemoglobin (HbA1c). Furthermore, the changes in the weight of the pancreas, including its histopathology and immunohistochemical investigation were also performed. Moreover, the nephroprotective effects were analyzed by observing the changes in kidney weight, its histopathology, blood urea nitrogen (BUN), and serum creatinine levels. RESULTS: The results showed that the high-fat diet (HFD)-induced control mice showed a noticeable increase in blood glucose, insulin, HbA1c, BUN, and creatinine levels. Furthermore, growth was observed in lipid droplet deposition related to the degenerative lesions in the vacuolated renal tubules with the evident enlargement and hyperplasia of the pancreatic islets. In addition, in the endocrine pancreas, there was an increase in the insulin-and glucagon-producing cells, as well as in the insulin/glucagon cell ratios. On the other hand, compared to the HFD-treated mice group, all these diabetic and related complications were ameliorated significantly in a dose-dependent manner after 84 days of the continuous oral administration of BHBe at 400, 200 and 100 mg/kg, and a dramatic resettlement in the hepatic glucose-regulating enzyme activities was observed. CONCLUSIONS: By assessing the key parameters for T2DM, the present study showed that the BHBe could act as a potential herbal agent to cure diabetes (type II) and associated ailments in HFD-induced mice.

• Natural Product Sciences
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• v.26 no.4
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• pp.326-333
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• 2020

The aerial parts of Eclipta prostrata is used as a traditional medicine and vegetable. In traditional folk medicine, it is used for treatment of hemorrhages, hepatic, disease, renal injuries, hair loss, tooth mobility, and viper bites. In this study, ten compounds (1 - 10) were isolated from the aerial parts of E. prostrata. A reliable high performance liquid chromatography equipped with photometric diode array detector (HPLC-PDA) method was developed to simultaneously quantitate 10 marker compounds [chlorogenic acid (1), paratensein 7-O-��-ᴅ-glucoside (2), quercetin 7-O-��-ᴅ-glucoside (3), luteolin 7-O-��-ᴅ-glucoside (4), apigenin 7-O-��-ᴅ-glucoside (5), apigenin 4'-O-��-ᴅ-glucoside (6), apigenin (7), luteolin (8), wedelolactone (9), and paratensein (10)]. In addition, compounds 5 and 6 showed considerable inhibitory effects against protein-tyrosine phosphatase 1B (PTP1B) enzyme. Moreover, compounds 6 - 8, and 10 exhibited potent α-glucosidase inhibitory effects with IC50 values of 24.5 ± 1.9, 33.0 ± 0.5, 45.5 ± 0.1, and 23.8 ± 1.0 µM, respectively. All compounds (1 - 10) showed considerable acetylcholinesterase (AChE) inhibitory effects with IC50 ranging from 30.1 to 75.2 µM.

• Journal of the Korean Society of Food Science and Nutrition
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• v.23 no.4
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• pp.574-580
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• 1994

The effect of dietary zinc(Zn) levels on cadmium (Cd)-induced hepatotoxicity was studied in serum and liver of rats. Adult male Spraque-Dawley rats were fed on diets containing one of three levels of zinc carbonate(0, 56, $560\mu\textrm{g}/kg$ diet) and Cd-treated groups were administrated oral intubation with cadmium chloride 95.0 mg/kg of body weight) at the sametime once a week. Net weight gain (NWG), feed intake (FI) and feed effciiency ratio (FER) in Zn deficiency groups significantly decreased as compared to that of control and excessive groups. Cd oral intubation caused a decrease in NWG and FI but an increase in Zn deficiency group in FER. GSH-Px, GST and catalase activity showed significant decrease in Zn deficiency and Zn excessive group. LPO content in liver significantly increased in Zn deficiency group. Cd oral intubation increased the content of LPO in Zn deficiency group as compared to control. GSH content and GST activity of hepatic tissue significantly decreased in Zn deficiency and excessive group. The activity of AST and ALT in serum were markedly increased in Zn deficiency, Zn excessive and Cd-treated groups. LDH and ALP activities significantly increased in Cd-treated group while ALP activity decreased by Zn deficiency. It was observed that the livers of rats exposed to Cd and Zn excessive group showed a marked increase of hepatic enzyme as compare to only Cd-treated in rats.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.5
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• pp.840-846
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• 2002

Male Sprague-Bawler rats were blocked into four groups which were normal rats fed control diet (NC) diabetic rats fed control diet (DC), normal rats fed Hamcho powder diet (NH), and diabetic rats fed Hamcho powder diet (DH). Diabetes was induced by single injection of streptozotocin (60 mg/kg B.W. i.p.). The animals were fed ad libitum for 5 weeks. Malondialdehyde (MDA), glucose 6-phosphtase (Gspase), glutathione S-transferase (GST) glutathione Peroxidase (GPx), and glutathione reductase (GR) activities were measured in the homogenates of liver and kidney, and total lipid, total cholesterol, triglyceride, and HDL-cholesterol concentrations in the blood serum. Food and water intakes were markedly higher in diabetic groups than those of normal groups and were not significantly decreased by Hamcho powder supplementation, But, FER (Feed efficiency ratio) of DH Brood was higher than that of U group. Total cholesterol level of DH group was decreased in the second and third week, and the weekly change of blood sugar was also decreased in the 5th week. Dietary Hamcho intake showed 41.2% of hypoglycemic effect in diabetics rats. Levels of total lipid and triglycerides of DH group were lower than those of DC group. Hepatic GR activity of DH group was higher than those of other groups. However, renal GR activity was lower than those of other groups. Hepatic G6Pase activity was significantly high in DH group and reduced by Hamcho powder supplementation. GST was reduced by Hancho diet in diabetic rats. In conclusion Hamcho supplementation decreased serum lipid and glucose concentration in STZ-induced diabetic rats and this effects of Hamcho might exert antidiabetic effect of Hamcho powder diet.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.5
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• pp.1081-1086
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• 2007

This study was performed to investigate the medicinal effects of the herbal combination extracts-2 (HCE-2), consisting of Artemisia capillaris Thunb., Lonicera japonica Thunb., Prunella vulgaris var. lilacina, and Hovenia dulcis Thunb. on the alcohol-induced liver injury in rats. The rats were randomly divided into four groups: normal group (n =6), non-treated control group (n =6), saline-treated group (n =6) and the herbal combination extract (HCE-2)-treated group (n =6). The rats in the alcohol-loaded groups were orally administered with ethanol at a daily dose of 4 g/kg-body weight for 5 weeks. Thirty minutes before the ethanol injection, saline or herbal combination extracts was administered by using a gastrogavage. Blood and liver tissue samples were taken out from the hearts and livers of the rats, respectively, on 15th and 38th days. The activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured using an enzyme-linked immunosorbent assay (ELISA). We also investigated the protective effect of the herbal combination extracts by Hematoxylin-Eosin staining on histological sections of rat liver. In this study, the oral administration of the herbal combination extracts significantly reduced the serum levels of AST and ALT, which had been raised by alcohol-induced liver injury. Histological analysis and apparent observation of liver also showed the preventive effect of the herbal combination extracts in a chronic alcohol-induced rat model. Theses results revealed that the herbal combination extracts effectively prevented hepatic damage consequent to the chronic exposure to repetitive administration of ethanol and could be used as a primary resource of a health beverage or herbal medicine, alleviating the alcohol-induced hepatic injury and hangover symptoms.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.5
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• pp.611-616
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• 2013

Alcoholic liver disease (ALD) is a major cause of morbidity and mortality around the world. Although much progress has been made in understanding the pathogenesis of ALD, there remains no effective therapy for it. Accumulated evidence indicates that oxidative stress is the main pathological factors in the development of ALD. Ethanol administration causes accumulation of reactive oxygen species (ROS), including superoxide, hydroxyl radical, and hydrogen peroxide. ROS, in turn, cause lipid peroxidation of cellular membranes, and protein and DNA oxidation, which results in hepatocyte injury. In addition to pro-oxidants formation, antioxidants depletion caused by ethanol administration also results in oxidative stress. The objective of this study is to investigate the effects of Shiryung-tang extract on the chronic alcoholic liver injury induced by EtOH. Male Sprague Dawley rats were used in this study. All rats were maintained under standard laboratory conditions ($23{\pm}1^{\circ}C$, 12h light/12h dark cycles). All animals (n=30) were randomly divided into following groups: (1) Normal group, treated with distilled water (n=10); (2) Control group, treated with ethanol (n=10); (3) Sample group, treated with ethanol + pharmacopuncture (n=10). For oral administration of ethanol in Control and Sample group, the ethanol was dissolved in distilled water in concentrations of 25%(v/v). Throughout the experiment of 8 week, the rats were allowed free access to water and standard chow. Sample group were administrated by Shiryung-tang extract daily for 8 weeks. Control group were given normal saline for same weeks. As a results, the oral administration of ethanol for 8 weeks leads to hepatotoxicity. The levels of hepatic marker such as HDL-cholesterol, triglyceride, aspartate aminotransferase and alanine aminotransferase were altered. The ethanol also increased lipid peroxidation and depletion of antioxidant enzyme activities as well as hepatic tissue injury. However, the treatment of Shiryung-tang extract prevented all the alterations induced by ethanol and returned their levels to near normal. These data suggest that Shiryung-tang extract could have a beneficial effect in inhibiting the oxidative damage induced by chronic ethanol administration. Therefore, Shiryung-tang extract can be a candidate to protect against EtOH-induced liver injury.

• Korean Journal of Veterinary Service
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• v.40 no.2
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• pp.107-117
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• 2017

This study was conducted to investigate of hepatoprotective effect of dandelion water extract (DWE) according to repeated administration of thioacetamide (TAA) induced hepatotoxicity in Spraque-Dawley rats. Thirty rats were randomly assigned to 5 groups; normal control, DWE-control, TAA-control (TAA injection during the feeding of normal diet), TAA&DWE600 (TAA repeated injection during the feeding of DWE 600 mg/kg BW), TAA&DWE1200 (TAA repeated injection during the feeding of DWE 1,200 mg/kg BW). Rats in DWE-control and TAA&DWE groups were treated with DWE (600 or 1,200 mg/kg BW daily) by gavage for 20 days (twice a day). All the rats in the TAA-control and TAA&DWE groups were repeated injection of TAA (100 mg/kg BW) into the abdominal cavity 3 days interval and 12 hrs later, all rats were sacrificed. At the same time, normal control and DWE-control groups were injected normal saline. In TAA&DWE groups, serum alanine and aspartate aminotransferase (ALT, AST) were significantly decreased and triglyceride (TG) synthesis was significantly increased compared to TAA group. As well as total billilubin and GGT were slightly decreased by the treatment of DWE. Lipid peroxidation (MDA) concentration was significantly decreased and hepatic GSH content was slightly or significantly increased in the TAA&DWE groups compared to TAA group. Hepatic anti-oxidative enzyme activities, such as GSH, GST, SOD and catalase were slightly or significantly elevated by the treatment of DWE. According to these results, When dandelion extract was long term supplied, it could be used as a potential protective material for a longer time liver damage by repeated adminstration of the TAA.

• The Korean Journal of Pharmacology
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• v.11 no.1 s.17
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• pp.47-53
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• 1975

The metabolism of many drugs and also of steroid hormones is mediated by enzymes located in the microsomal fraction in smooth surfaced endoplasmic reticulum of mammalian liver. The duration and intensity of action of many drugs are largely determined by the speed at which they are metabolized in the body. Repeated administration of phenobarbital results in the induction of enzymes that metabolize a number of drugs. Lee et al. reported that daily administration of phenobarbital in rats significantly increased the activities of amylase in the pancreatobiliary juice, but the concentration of cholate in the bile was significantly lower in the treated group than that in the control group. After animals were treated with $CCl_4$, histological changes were shown in the endoplasmic reticulum, decreased microsomal enzyme activity and decreased hepatic protein synthesis were apparent. The purpose of the present report was to study the interaction between a 'microsomal-stimulating' agent such as phenobarbital and a 'microsomal- depressing' agent such as $CCl_4$ on hepatic and pancreatic functions in rats. The results obtained are summarized as follows: 1. The mortality rate of $CCl_4$ treated group was 34% and was decreased this figure to 15% with phenobarbital pretreatment. 2. In animals treated with phenobarbital the volume of biliary-pancreatic secretion was markedly elevated but the volume was decreased significantly in animals treated with $CCl_4$. 3. Total bilirubin output was elevated markedly in the $CCl_4$ treated group of rats pretreated with phenobarbital. The bilirubin concentration was increased in $CCl_4$ treated group and decreased in the group treated phenobarbital alone. 4. The concentration and total output of cholate in the bile were significantly lower in the all experimental group than control group. 5. In the animals treated with phenobarbital alone and phenobarbital plus $CCl_4$, the activity of lipase in pancreatobiliary juice was elevated, while in the animals treated with $CCl_4$ alone no change was observed. 6. The activity of amylase in the pancreatobiliary juice was decreased in the $CCl_4$ treated group, but elevated markedly in phenobarbital group and also elevated in phenobarbital-$CCl_4$ group. By the above results, it is concluded, when the liver was damaged by $CCl_4$, the exocrine function of pancreas and liver was decreased simultaneously. However, in the animals pretreated with phenobarbital, the toxicity of $CCl_4$ on the liver and pancreas was reduced.

• Journal of Food Hygiene and Safety
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• v.29 no.2
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• pp.85-91
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• 2014

Deoxynivalenol (DON) and related trichothecene mycotoxins are extensively distributed in the cereal-based food and feed stuffs worldwide. Recent climate changes and global grain trade increased chance of exposure to more DON and related toxic metabolites in poorly managed production systems. Monitoring the biological and environmental exposures to the toxins are crucial in protecting human and animals from toxicities of the hazardous contaminants in food or feeds. Exposure biomarkers including urine DON itself are prone to shift to less harmful metabolites by intestinal microbiota and liver metabolic enzymes. De-epoxyfication of DON by gut microbes such as Eubacterium strain BBSH 797 and Eubacterium sp. DSM 11798 leads to more fecal secretion of DOM-1. By contrast, most of plant-derived DON-glucoside is also easily catabolized to free DON by gut microbes, which produces more burden to body. Phase 2 hepatic metabolism also contributes to the glucuronidation of DON, which can be useful urine biomarkers. However, chemical modification could be very typical depending on the anthropologic or genetic background, luminal bacteria, and hepatic metabolic enzyme susceptibility to the toxins in the diet. After toxin exposure, effect biomarkers are also important in estimating the linkage and mechanisms of foodborne diseases in human and animal population. Most prominent adverse effects are demonstrated in the DON-induced immunological and behavioral disorders. For instance, acutely elevated interleukin-8 from insulted gut exposed to dietaty DON is a dominant clinical biomarker in human and animals. Moreover, subchronic exposure to the toxins is associated with high levels of serum IgA, a biological mediator of IgA nephritis. In particular, anorexia monitoring using mouse models are recently developed to monitor the biological activities of DON-induced feed refusal. It is also mechanistically linked to alteration of serotoin and peptide YY, which are promising biomarkers of neurological disorders by the toxins. As animal-alternative biomonitoring, huamn enterocyte-based assay has been developed and more realistic gut mimetic models would be useful in monitoring the effect biomarkers in resposne to toxic contaminants in the future investigations.