• Journal of Life Science
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• v.34 no.4
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• pp.227-235
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• 2024

Hepatocyte damage caused by medications or herbal products is one of the important problem when these compounds are chronically administrated. Thus, improving hepatocyte survival during treatment offers a wide range of opportunities. Valproic acid (VPA), a branched short-chain fatty acid derived from naturally occurring valeric acid, is commonly used to treat epilepsy and seizures. Although VPA exerts numerous effects in cancer, HIV therapy, and neurodegenerative disease, its effects on the liver and its mechanism of action have not been fully elucidated. Here, we demonstrated that VPA caused moderate liver cell toxicity and apoptosis. Interestingly, VPA treatment increased transcription levels of PPAR alpha (PPAR-α) and fibroblast growth factor 21 (FGF21) in murine (Hepa1c1c7) hepatoma cells in a time and concentration dependent manner. VPA-induced FGF21 expression was significantly weaker under PPAR-α silencing condition than in cells transfected with non-targeting control siRNA. Subsequent experiments showed that cell viability was significantly lowered when the FGF21 signaling pathway was blocked by FGF receptor antagonist. Finally, we further determined that AMPK phosphorylation was not responsible for VPA-induced FGF21 expression and PPAR-a increments. These results indicate that increases of FGF21 expression alleviate VPA-induced hepatic toxicity, thereby making FGF21 a potential biomarker for predicting liver damage during VPA treatments.

• Herbal Formula Science
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• v.32 no.1
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• pp.63-82
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• 2024

Objective : Saengkankunbi-tang (SKT) is used as a traditional Korean herbal formula for treatment of liver diseases. We investigated the hepatoprotective effects of SKT plus Epimedium koreanum Nakai (EKE) against arachidonic acid (AA) + iron-mediated cytotoxicity in HepG2 cells and carbon tetrachloride (CCl₄)-mediated acute liver damage in mice. Methods : The cyto-protective effects of SKT + EKE were determined by MTT assay, western blot and fluorescence activated cell sorting analysis. In mice, blood biochemistry and western blot were assessed in CCl₄-induced acute hepatic damage. The animal groups included vehicle-treated control, CCl₄, SKT (200 mg/kg/day), EKE (100 mg/kg/day), SKT (200 mg/kg/day) + EKE (100 mg/kg/day) and silymarin (200 mg/kg/day). Results : In HepG2 cells, pretreatment with SKT + EKE significantly suppressed cytotoxicity induced by AA + iron and reduced the expression of proteins related to apoptosis. In addition, pretreatment with SKT + EKE significantly prevented the increase in H₂O₂ production, GSH depletion, and lower mitochondrial membrane potential induced by AA + iron. In CCl₄-induced liver damage mice, the administration of SKT + EKE prevented the liver damage by inhibition of hepatocyte damage and expression of apoptosis proteins in liver. More importantly, in vitro and in vivo assay, SKT + EKE showed significant effect compare with SKT alone or EKE alone in all parameters. Conclusions : These results indicated that SKT + EKE could protect against oxidative stress-induced liver damage, and SKT + EKE is more effective than SKT alone or EKE alone.

• The Korean Journal of Zoology
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• v.16 no.2
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• pp.79-96
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• 1973

In order to elucidate the effects of copper on Corassius carassius, the following were studied: 1) lactate dehydrogenase isozyme patterns by cellulose acetate electrophoresis, 2) LDH activity and copper effect on LDH enzyme system y spectrophotometry, 3) esterase isozyme patterns by agar thin layer electrophoresis, 4) hemoglobin patterns by starch gel electrophoresis, and 5) histological study. 1. There were two bands of LDH isozymes (LDH-3 and LDH-5) in the gill, three bands (LDH-2, LDH-4, and LDH-5) in the liver, and two bands (LDH-3 and LDH-4) in the muscle of the normal fish. The LDH-1 bond was not found in the above three tissues. When the fish were exposed to copper, LDH-3 appeared in the liver, LDH-5 in the muscle, but no new LDH band appeared in the gill. 2. The sepcific activities of the LDH were lowest in the gill and highest in the muscle of the normal fish, and they were gradually decreassed in the gill and highest in the muscle of the normal fish, and they were gradually decreased in the liver and mucle except in the gill from 1-day to 10-day exposure to copper. It indicates that LDH activities in the liver and muscle of the fish were inhibited by copper. 3. Through in vitro experiment, it is clear that the decrease of the LDH activities of the liver and muscle of the fish exposed to copper is mainly caused by the inhibition on the M-LDH in the fish. 4. The numbers of the esterase isozyme bands of the gill, liver, muscle, blood, brain, and kidney of the normal fish were 3, 6, 2, 2, 2, and 2 respectively, and these numbers were the same as those exposed to copper. The relative mobilities of the esterase bands in the gill, liver, blood, and kidney of the exposed group were different from those of the control. 5. There was one hemoglobin band on the anode in the normal fish. It seems that the nobility of hemoglobin band of the fish exposed to copper was slightly faster than that of the normal fish. 6. The normal gill lamellae of the fish consisted of centrally located pillar cells and a number of mucus cells. When the fish were exposed to copper, the epithelial layer was divorced first, disintegrated, and then destroyed completely. 7. The liver of the normal fish had prominent central veins, cords of hepatic cells, and sinusoids. When the fish were exposed to copper, numerous droplets of fat appeared in the cells around the central vein of the liver. It is assumed that the fatty droplets were accumulated by the lesion due to fatty metamorphosis of the liver caused by copper. 8. There was no histological difference between the muscle of the normal fish and that of the fish exposed to copper. 9. In the normal fish, the tubules of the kidney were surrounded by hemopoetic tissues. However, the kidney tissue of the fish exposed to copper received some damage on the proximal tubules. Since the tubule cells were reduced in height, the lumens of the tubules were enlarged. Consequently many proximal tubules exhibited some pink-stained granular casts and various stages of degeneration.

• Korean Journal of Environmental Biology
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• v.38 no.2
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• pp.271-277
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• 2020

Toxicities to many organs caused by humidifier disinfectants have been reported. Recently, humidifier disinfectants have been reported to cause cardiovascular, embryonic, and hepatic toxicities. This study was designed to investigate the toxic mechanism of humidifier disinfectants and compare toxicity in a cellular model and a zebrafish animal model. Because brain toxicity and skin toxicity have been less studied than other organs, we evaluated toxicity in a human dermal cell line and zebrafish under various concentrations of humidifier disinfectants that included polyhexamethyleneguanidine phosphate (PHMG), oligo-[2-(2-ethoxy)-ethoxyethyl-guanidinium-chloride] (PGH) and methylchloroisothiazolinone/methylisothiazolinone (CMIT/MIT). A human dermal fibroblast cell line was treated with disinfectants (0, 2, 4, 6, 8, and 16 mg L^-1) to compare their cytotoxicity. The fewest PHMG-treated cells survived (up to 33%), while 49% and 40% of the PGH- and CMIT/MIT-treated cells, respectively, survived. The quantification of oxidized species in the media revealed that the PHMG-treated cells had the highest MDA content of around 28 nM, while the PGH- and CMIT/MIT-treated cells had 13 and 21 nM MDA, respectively. As for brain toxicity, treatment of the zebrafish tank water with CMIT/MIT (final 40 mg L^-1) for 30 min resulted in a 17-fold higher production of reactive oxygen species (ROS) than in the control. Treatment with PGH or PHMG (final 40 mg L^-1) resulted in 15- and 11-fold higher production, respectively. The humidifier disinfectants (PHMG, PGH, and CMIT/MIT) showed severe dermal cell toxicity and brain toxicity. These toxicities may be relevant factors in understanding why some children have language disorders, motor delays, and developmental delays from exposure to humidifier disinfectants.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.7
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• pp.953-958
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• 2005

This study was conducted to investigate the effect of beverage (beverage HC and beverage PG) using herbs on antimicrobial activity, proliferation of hepatic cancer cell (Hep3B) lines and sarcoma 180 (S-180) and antiallergy, respectively. Beverage PG showed higher antimicrobial activity than beverage HC against Staphylococcus aureus and Pseudomonas aeruginosa. Beverage HC and PG showed the tumor suppressive effect in mice injected with S-180 cells. The growth-inhibitoy ratio against tumor cells were $66\%\;for\;10\%$ beverage HC, $61\%\;for\;10\%$ beverage PG. In an anti-cancer test using Hep3B cells, beverage PG showed higher anti-proliferating effect than beverage HC. Beverage PG showed growth-inhibitory effect of $69.2\%\;at\;100\%$ beverage PG. Beverage PG inhibited histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80. In conclusion, these results suggest that beverage using herbs have an antimicrobial activity, anti-proliferating effect against Hep3B cell and S-180 tumor and will be beneficial in treatment of allergic reaction.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.17 no.10
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• pp.432-438
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• 2016

This study was conducted to investigate the effects of Lespedeza caneata extract on the livers of alcohol-administered mice. The study subjects were divided into a control (Con), alcohol administration (AL), alcohol and Lespedeza Caneata extract 200 mg/kg administration (AL-LC 200), and alcohol and Lespedeza caneata extract400 mg/kg administration (AL-LC 400) group. Distilled water was administrated orally to control and alcohol groups for ten days, while Lespedeza caneata extract was administered orally to alcohol and Lespedeza caneata extract groups for ten days. All experimental groups were fasted for twelve hours seven days after the oral administration, after which distilled water was administered orally to Con five times at twelve-hour intervals. At the same time, 50% ethanol (MERCK, USA) at 10 g/kg concentration was administered orally to AL and AL-LC groups five times at 12-hour intervals. The AST, ALT enzyme activation in blood and histology of the liver were then evaluated. AST and ALT in AL-LC groups were lower than in the AL group. Particularly, the AL-LC 200 and AL-LC 400 groups had significantly lower AST activation than the AL group. Histological results showed that most of the subjects in the AL group had necrosis and deformation in their livers, while fat droplets were accumulated in hepatic cells around the central vein. AL-LC 200 group revealed that a portion of the central vein was swollen, liver cells were expanded, and small fat droplets were accumulated. In the AL-CL 400 group, the central vein was normal and small fat droplets were accumulated in some liver cells. However, most of the liver cells appeared normal in the AL-CL 400 group. These results suggest that the extracts of Lespedeza caneata prevented alcohol induced liver damage in mice and have great potential for use as natural health products.

• Journal of Nutrition and Health
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• v.55 no.4
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• pp.462-475
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• 2022

Purpose: Allomyrina dichotoma larvae are one of the approved edible insects with nutritional value and various functional and medicinal properties. Previously we have demonstrated that the Allomyrina dichotoma larval extract (ADLE) ameliorates hepatic insulin resistance in high-fat diet (HFD)-induced diabetic mice through the activation of adenosine monophosphate-activated protein kinase (AMPK). This study investigated the effects of ADLE on insulin resistance in the skeletal muscle and explored mechanisms for enhancing the glucose uptake in palmitate (PAL)-treated C2C12 myotubes. Methods: To induce insulin resistance, the differentiated C2C12 myotubes were treated with PAL (0.5 mM) for 24 hours, and then treated with a 0.5 mg/ml concentration of ADLE, and the resultant effects were measured. The expression levels of glucose transporter-4 (GLUT4), AMPK, and the mitochondrial metabolism-related proteins were analyzed by western blotting. The mRNA expression levels of lipogenesis- related genes were determined by quantitative reverse-transcriptase PCR. Results: The exposure of C2C12 myotubes to 0.5 mg/ml of ADLE increased cell viability significantly compared to PAL-treated cells. ADLE upregulated the protein expression of GLUT4 and enhanced glucose uptake in the PAL-treated cells. ADLE increased the phosphorylated AMPK in both the PAL-treated C2C12 myotubes and HFD-treated skeletal muscle. The reduced expression levels of peroxisome-proliferator-activated receptor gamma co-activator-1 alpha (PGC1α) and uncoupling protein 3 (UCP3) due to the PAL and HFD treatment were reversed by the ADLE treatment. The citrate synthase activity was also significantly increased with the PAL and ADLE co-treatment. Moreover, the mRNA and protein expressions of fatty acid synthesis-related factors were reduced in the PAL and HFD-treated muscle cells, and this effect was significantly attenuated by the ADLE treatment. Conclusion: ADLE activates AMPK, which in turn induces mitochondrial metabolism and reduces fatty acid synthesis in C2C12 myotubes. Therefore, ADLE could be useful for preventing or treating insulin resistance of skeletal muscles in diabetes.

• Asian-Australasian Journal of Animal Sciences
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• v.9 no.1
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• pp.1-25
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• 1996

The pathogenesis of atherosclerosis can not be summarized as a single process. Lipid infiltration hypothesis and endothelial injury hypothesis have been proposed and investigated. Recent developments show that there are many points of potential interactions between them and that they can actually be regarded as two phases of a single, unifying hypothesis. Among the many risk factors of atherosclerosis, plasma homocysteine and lipoprotein(a) draw a considerable interest because they are independent indicators of atherogenicity. Triglyceride (TG)-rich lipoproteins (chylomicron and VLDL) are not considered to be atherogenic but they are related to the metabolism of HDL cholesterol and indirectly related to coronary heart disease (CHD). LDL can of itself be atherogenic but the oxidative products of this lipoprotein are more detrimental. HDL cholesterol has been considered to be a favorable cholesterol. The so-called 'causalist view' claims that HDL traps excess cholesterol from cellular membranes and transfers it to TG-rich lipoproteins that are subsequently removed by hepatic receptors. In the so-called 'noncausalist view', HDL does not interfere directly with cholesterol deposition in the arterial wall but instead reflects he metabolism of TG-rich lipoproteins and their conversion to atherogenic remnants. Approximately 70-80% of the human population shows an effective feedback control mechanism in cholesterol homeostasis. Type of dietary fat has a significant effect on the lipoprotein cholesterol metabolism and atherosclerosis. Generally, saturated fatty acids elevate and PUFA lower serum cholesterol, whereas MUFA have no specific effect. EPA and DHA inhibit the synthesis of TG, VLDL and LDL, and may have favourable effects on some of the risk factors. Phospholipids, particularly lecithin, have an antiatherosclerotic effect. Essential phospholipids (EPL) may enhance the formation of polyunsaturated cholesteryl ester (CE) which is less sclerotic and more easily dispersed via enhanced hydrolysis of CE in the arterial wall. Also, neutral fecal steroid elimination may be enhanced and cholesterol absorption reduced following EPL treatment. Antioxidants protect lipoproteins from oxidation, and cells from the injury of toxic, oxidized LDL. The rationale for lowering of serum cholesterol is the strong association between elevation of plasma or serum cholesterol and CHD. Cholesterol-lowing, especially LDL cholesterol, to the target level could be achieved using diet and combination of drug therapy. Information on the link between cholesterol and CHD has decreased egg consumption by 16-25%. Some clinical studies have indicated that dietary cholesterol and egg have a significant hypercholesterolemic effect, while others have indicated no effect. These studies differed in the use of purified cholesterol or cholesterol in eggs, in the range of baseline and challenge cholesterol levels, in the quality and quantity of concomitant dietary fat, in the study population demographics and initial serum cholesterol levels, and clinical settings. Cholesterol content of eggs varies to a certain extent depending on the age, breed and diet of hens. However, egg yolk cholesterol level is very resistant to change because of the particular mechanism involved in yolk formation. Egg yolk contains a factor of factors responsible for accelerated cholesterol metabolism and excretion compared with crystalline cholesterol. One of these factors could be egg lecithin. Egg lecithin may not be as effective as soybean lecithin in lowering serum cholesterol level due probably to the differences of fatty acid composition. However, egg lecithin may have positive effects in hypercholesterolemia by increasing serum HDL level and excretion of fecal cholesterol. The association of serum cholesterol with egg consumption has been widely studied. When the basal or control diet contained little or no cholesterol, consumption of 1 or 2 eggs daily increased the concentration of plasma cholesterol, whereas that of the normolipemic persons on a normal diet was not significantly influenced by consuming 2 to 3 eggs daily. At higher levels of egg consumption, the concentration of HDL tends to increase as well as LDL. There exist hyper-and hypo-responders to dietary (egg) cholesterol. Identifying individuals in both categories would be useful from the point of view of nutrition guidelines. Dietary modification of fatty acid composition has been pursued as a viable method of modifying fat composition of eggs and adding value to eggs. In many cases beneficial effects of PUFA enriched eggs have been demonstrated. Generally, consumption of n-3 fatty acids enriched eggs lowered the concentration of plasma TG and total cholesterol compared to the consumption of regular eggs. Due to the highly oxidative nature of PUFA, stability of this fat is essential. The implication of hepatic lipid accumulation which was observed in hens fed on fish oils should be explored. Nutritional manipulations, such as supplementation with iodine, inhibitors of cholesterol biosynthesis, garlic products, amino acids and high fibre ingredients, have met a limited success in lowering egg cholesterol.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.9
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• pp.1126-1135
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• 2008

This study was carried out to investigate the anti-oxidative and anti-inflammatory actions of genistein in BALB/c mice injected with lopopolysaccharide (LPS), called endotoxin. Mice (10 weeks of age) weighing approximately 20 g were divided into 4 groups. Endotoxin shock was induced by intraperitoneal injection of LPS (100 mg/kg BW). LPS and genistein+LPS groups were injected with LPS 30 min after phosphate buffered saline (PBS) solution and genistein (200 mg/kg BW) injections, respectively. Genistein group was injected with genistein, followed by PBS, while PBS group received two injections of PBS. Superoxide anion generation of peritoneal macrophage cells was significantly (p<0.05) lower in the genistein+LPS group than in the LPS injection group at 8 h after intraperitoneal injection, while SOD activity was significantly higher in genistien+LPS group than LPS group. Tumor necrosis factor-$\alpha$ levels of plasma were significant lower (p<0.05) in the genistein+LPS injection group than LPS group at 8 h after intraperitoneal injection. Plasma TBARS was lower in genistein+LPS group than LPS group, while hepatic TBARS were not different among groups. Hepatic glutathione concentrations and antioxidant enzyme activities were ignificantly higher in the genistein+LPS group than in the LPS group at 1 h and 8 h after intraperitoneal injection. Nuclear factor-kappa B (NF-${\kappa}B$) transactivation was significantly (p<0.05) inhibited in LPS group. These results demonstrate genistein may ameliorate inflammatory diseases through inhibition of NF-${\kappa}B$ transactivation and oxidative stress, which may be mediated partially by anti-oxidative effect of genistein.

• Journal of Nutrition and Health
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• v.43 no.4
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• pp.333-341
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• 2010

The aim of this study was to investigate the hypolgycemic activity of water extract of fermented yacon (Smallanthus sonchifolius) leaves tea (Yacon LWE) in high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mice. Male ICR mice were fed with a HFD (37% calories from fat) for 4 weeks prior to intraperitoneal injection with STZ (100 mg/kg body weight). Diabetic mice were supplemented with two doses of Yacon LWE (0.16% and 0.8%, wt/wt) for 6 weeks. The supplementation of high-dose Yacon LWE significantly lowered blood glucose levels and plasma ALT and AST activities compared with the control group. High-dose Yacon LWE also improved the insulin tolerance without any changes in plasma and pancreatic insulin concentrations in HFD/STZ-induced diabetic mice. Yacon LWE supplementation increased the insulin staining of pancreatic $\beta$-cells in a dose-dependent manner. Both 0.16% and 0.8% of Yacon LWE significantly elevated plasma leptin concentration, hepatic glucokinase activity and glucokinase/glucose-6-phosphatase ratio compared with the control group. However, glycosylated hemoglobin concentration was not different among the groups. These results suggest that high-dose Yacon LWE lowers the blood glucose level partly by enhancing insulin sensitivity and hepatic glucose metabolism in type 2 diabetic mice.