• Journal of Ginseng Research
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• v.42 no.4
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• pp.540-548
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• 2018

Background: Acute hepatic failure is a life-threatening critical condition associated with rapid deterioration of liver function and liver transplantation. Several studies have shown that Panax ginseng Mayer has antidiabetic and hepatoprotective effects. However, the hepatoprotective effect of ginseng berry is still unveiled. In this study, we evaluated the hepatoprotective effects of ultrasonication-processed ginseng berry extract (UGBE) on acute hepatic failure model in rats. Methods: Ginseng berry extract (GBE) was ultrasonically processed. The GBE, silymarin, and UGBE were orally administered to male Sprague-Dawley rats for 4 wk. Twenty-four h after the last administration, rats were challenged with D-galactosamine (D-GalN)/lipopolysaccharide (LPS). Results: After ultrasonication, the component ratio of ginsenosides Rg2, Rg3, Rh1, Rh4, Rk1, Rk3, and F4 in GBE had been elevated. Administration of UGBE significantly increased the survival rate of D-GalN/LPS-challenged rats. Pretreatment with UGBE significantly decreased serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels in D-GalN/LPS-challenged rats in a dose-dependent manner. The levels of enzymatic markers for oxidative stress (superoxide dismutase, glutathione peroxidase, catalase, and glutathione) were increased by UGBE treatment in a dose-dependent manner. Tumor necrosis factor alphalevel, inducible nitric oxide synthase activities, and nitric oxide productions were reduced by UGBE treatment. In addition, hemeoxygenase-1 levels in liver were also significantly increased in the UGBE-treated group. The protein expression of toll-like receptor 4 was decreased by UGBE administration. Hematoxylin and eosin staining results also supported the results of this study showing normal appearance of liver histopathology in the UGBE-treated group. Conclusion: UGBE showed a great hepatoprotective effect on D-GalN/LPS-challenged rats via the toll-like receptor 4 signaling pathway.

• Journal of Ginseng Research
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• v.39 no.4
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• pp.376-383
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• 2015

Background: Panax ginseng has a wide range of biological activities including anti-inflammatory, antioxidant, and immunomodulatory functions. Wild ginseng cambial meristematic cells (CMCs) were obtained from P. ginseng cambium. This study examined the protective mechanism of wild ginseng CMCs against $\small{D}$-galactosamine (GalN)-induced liver injury. GalN, a well-known hepatotoxicant, causes severe hepatocellular inflammatory damage and clinical features similar to those of human viral hepatitis in experimental animals. Methods: Hepatotoxicity was induced in rats using GalN (700 mg/kg, i.p.). Wild ginseng CMCs was administered orally once a day for 2 wks, and then 2 h prior to and 6 h after GalN injection. Results: Wild ginseng CMCs attenuated the increase in serum aminotransferase activity that occurs 24 h after GalN injection. Wild ginseng CMCs also attenuated the GalN-induced increase in serum tumor necrosis factor-${\alpha}$, interleukin-6 level, and hepatic cyclooxygenase-2 protein and mRNA expression. Wild ginseng CMCs augmented the increase in serum interleukin -10 and hepatic heme oxygenase-1 protein and mRNA expression that was induced by GalN, inhibited the increase in the nuclear level of nuclear factor-kappa B, and enhanced the increase in NF-E2-related factor 2. Conclusion: Our findings suggest that wild ginseng CMCs protects liver against GalN-induced inflammation by suppressing proinflammatory mediators and enhancing production of anti-inflammatory mediators.

• YAKHAK HOEJI
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• v.54 no.1
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• pp.55-61
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• 2010

Gardenia jasminoides is one of the most widely used herbal preparations for the treatment of liver disorders. This study evaluated the potential beneficial effect of G. jasminoides in a mouse model of carbon tetrachloride ($CCl_4$)-induced liver injury. The mice were treated intraperitoneally with $CCl_4$ (10 ${\mu}l$/kg). They received G. jasminoides (30, 100, 300 mg/kg) 48 h, 24 h and 2 h before and 6 h after administering $CCl_4$. The serum activities of aminotransferase and the hepatic level of malondialdehyde were significantly higher 24 h after the $CCl_4$ treatment, while the concentration of reduced glutathione was lower. These changes were attenuated by G. jasminoides. $CCl_4$ increased the level of circulating tumor necrosis factor-$\alpha$ (TNF-$\alpha$) markedly, which was reduced by G. jasminoides. The levels of hepatic inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression were markedly higher after the $CCl_4$ treatment. G. jasminoides diminished these alterations. $CCl_4$ increased the level of TNF-$\alpha$, iNOS and COX-2 mRNA expressions, and these increases were attenuated by G. jasminoides. These results suggest that G. jasminoides alleviates $CCl_4$-induced liver injury, and this protection is likely due to the reduced oxidative stress and the downregulation of proinflammatory mediators.

• Toxicological Research
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• v.25 no.1
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• pp.29-33
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• 2009

Phellinus gilvus (PG) is a widely used mushroom for health promotion. We studied the hepatoprotective effect of the polysaccharide aqueous extract of PG (PGP) against carbon tetrachloride ($CCl_4$)-induced liver injury in rats. Sprague Dawley rats were divided into 5 groups: Normal control, $CCl_4$ control, PGP 50, 100, and 200 mg/kg + $CCl_4$. The levels of serum biochemical parameters, liver lipid peroxide and antioxidant enzymes, and histological appearances were evaluated. The $CCl_4$-induced increments of alanine aminotransferase, asparate aminotransferase, and alkaline phosphatase levels in serum were significantly decreased by PGP-pretreatments. The PGP dose-dependently decreased hepatic malondialdehyde formations in $CCl_4$-treatment groups. Hepatic antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) were elevated by PGP in $CCl_4$-treatment groups. Histopathological evaluation of liver showed that the loss of hepatocytes, fatty changes, swelling and extensive necrosis of hepatocytes in centrilobular regions of the $CCl_4$-treated rats were ameliorated by PGP pretreatment. The PGP has hepatoprotective and antioxidative effects in $CCl_4$-induced liver injury of rat.

• YAKHAK HOEJI
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• v.42 no.1
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• pp.82-88
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• 1998

The effect of hepatoprotective agents and bile acids on tumor necrosis factor-alpha, (TNF-${\alpha}$) production in murine and human macrophage cell line (RAW264.7 and U937) was inve stigated. The hepatoprotective agents including silymarin and its major component, silybin, significantly inhibited TNF-alpha production in a concentration dependent manner ($IC_50$ of silybin=67.7${\mu}g$/ml (140.3${\mu}g$M)). In differentiated U937 cells, especially, silybin showed more effective inbitory activity ($IC_50$=35.1${\mu}g$g/ml (72.7${\mu}g$M)). These results suggest that silymarin and silybin may inhibit TNF-alpha production in the process of hepatic diseases in human. However, biphenyldimethyl dicarboxylate (DDB) was not effective. In the case of bile acids, chenodeoxycholic acid (CDCA) showed a concentration dependent inhibitory effect on TNF-alpha production ($IC_50$ of CDCA= 71.5${\mu}g$g/ml (182.1${\mu}g$M)). In contrast, glycine or taurine conjugated form (G-CDCA or T-CDCA) restored to the control level or significantly increased TNF-${\alpha}$ production. And also ursodeoxycholic acid (UDCA) and its conjugated forms (G-UDCA and T-UDCA) showed a variety of patterns on TNF-${\alpha}$ production by changes of functional groups and concentration. These results also indicate that bile acids may regulate TNF-${\alpha}$ production in normal hepatic function or disease conditions.

• Toxicological Research
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• v.35 no.1
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• pp.13-24
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• 2019

Numerous ethnomedicinal uses have been attributed to different parts of Annona senegalensis (ASE), including its uses as food and food additives. The present study investigated toxicological and antioxidant effects of 28 days administration of ethanol extracts of ASE stem bark to Wistar strain albino rats. Acute toxicity test was done to determine lethal dose in Wistar rats while sub-acute toxicity test was conducted on rats divided into four groups (A - control, B - 50 mg/kg, C - 100 mg/kg, D - 150 mg/kg, respectively and treated for 28 days. Oxidative stress markers in liver and kidney as well as hepatic succinate dehydrogenase activity in the mitochondrial and post mitochondrial fractions (PMF) were evaluated. The $LD_{50}$ value of ASE was > 2,000 mg/kg. White blood cell counts gradually increased, but red blood cell counts and haematocrits level decreased significantly (p < 0.05) by about 50%. Liver enzymes in the serum and mitochondrial succinate dehydrogenase activity increased significantly (p < 0.05). Superoxide dismutase and catalase activities also increased in liver mitochondria and PMF while malondialdehyde (MDA) and reduced glutathione levels increased only in the PMF. Furthermore, only MDA levels increased significantly in the kidney after 28 days extract administration. Histopathological examination showed hepatic necrosis and no obvious signs of nephrotoxicity. Anona senegalensis is relatively safe, but prolonged ingestion could induce oxidative stress and impair ATP synthesis through the modulation of the activity of mitochondrial succinate dehydrogenase.

• Nutrition Research and Practice
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• v.13 no.1
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• pp.3-10
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• 2019

BACKGROUND/OBJECTIVES: The $NAD^+$ precursor nicotinamide riboside (NR) is a type of vitamin $B_3$ found in cow's milk and yeast-containing food products such as beer. Recent studies suggested that NR prevents hearing loss, high-fat diet-induced obesity, Alzheimer's disease, and mitochondrial myopathy. The objective of this study was to investigate the effects of NR on inflammation and mitochondrial biogenesis in AML12 mouse hepatocytes. MATERIALS/METHODS: A subset of hepatocytes was treated with palmitic acid (PA; $250{\mu}M$) for 48 h to induce hepatocyte steatosis. The hepatocytes were treated with NR ($10{\mu}M$ and 10 mM) for 24 h with and without PA. The cell viability and the levels of sirtuins, inflammatory markers, and mitochondrial markers were analyzed. RESULTS: Cytotoxicity of NR was examined by PrestoBlue assay. Exposure to NR had no effect on cell viability or morphology. Gene expression of sirtuin 1 (Sirt1) and Sirt3 was significantly upregulated by NR in PA-treated hepatocytes. However, Sirt1 activities were increased in hepatocytes treated with low-dose NR. Hepatic pro-inflammatory markers including tumor necrosis factor-alpha and interleukin-6 were decreased in NR-treated cells. NR upregulated anti-inflammatory molecule adiponectin, and, tended to down-regulate hepatokine fetuin-A in PA-treated hepatocytes, suggesting its inverse regulation on these cytokines. NR increased levels of mitochondrial markers including peroxisome proliferator-activated receptor ${\gamma}$ coactivator-$1{\alpha}$, carnitine palmitoyltransferase 1, uncoupling protein 2, transcription factor A, mitochondrial and mitochondrial DNA in PA-treated hepatocytes. CONCLUSIONS: These data demonstrated that NR attenuated hepatic inflammation and increased levels of mitochondrial markers in hepatocytes.

• The Korea Journal of Herbology
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• v.36 no.1
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• pp.1-8
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• 2021

Objective : Citri Unshius Pericarpium (Citrus unshiu peel) has been used in Korean medicine to treat indigestion, vomiting, coughing and phlegm. This study investigated the hepatoprotective effect of ethanol extract of Citrus unshiu peel (CEE) in cadmium (CdCl2)-treated mouse model. Methods : CEE was dissolved in water and administered orally to mice once a day for 7 consecutive days. The mice were then exposed to a single intraperitoneal (i.p.) injection of cadmium (4 mg/kg body weight) to induce acute hepatotoxicity. At the end of the experiment, blood and liver tissue samples were collected, analyzed for alanine aminotransferase (ALT), aspartate aminotransferase (AST), and histopathological evaluation. Liver damage was assessed as the percentage of degenerative areas of the hepatic parenchyma, the number of degenerative hepatocytes, and the number of infiltrated inflammatory cells. Results : In cadmium-treated rats, pretreatment with CEE significantly reduced the serum ALT and AST levels associated with liver damage. Histopathologically, CEE prevented degenerative changes on the hepatic tissues including confluent necrosis, congestions and infiltration of inflammatory cells. CEE also reduced the elevation of oxidative stress markers (nitrotyrosine and 4-hydroxynonenal) and apoptosis markers (cleaved caspase-3 and cleaved PARP) positive cells. PARP protein expression in liver tissue was also restored by CEE. Conclusion : This study showed that CEE exerted antioxidant and anti-apoptotic effects against cadmium-induced liver injury. Thus, it can be concluded that CEE can be used to prevent liver damage caused by cadmium.

• Microbiology and Biotechnology Letters
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• v.27 no.1
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• pp.28-34
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• 1999

Ganoderan (GAN), an immunomodulating ${\beta}$-glucan from mushroom Ganoderma lucidum, was evaluated for its ability to induce formation of nitric oxide (NO), tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) and transforming growth factor (TGF-${\beta}$) from rat Kupffer cell in vitro. Hepatic macrophages activated by GAN significantly elevated concentration of NO and TNF-${\alpha}$ in cultured medium, but not significantly elevated that of TGF-${\beta}$. GAN-activated Kupffer cells secrete 14.9${\mu}$M (p<0.01) of NO and 2619.5${\rho}$g/ml (p<0.01) of TNF-${\alpha}$after 36hr of incubation at 37$^{\circ}C$. The results revealed that GAN enhanced 4-fold production of NO and 19 fold formation of TNF-${\alpha}$ compared to the control. The proliferation of GAN-activated Kupffer cells was inhibited as compared with its negative control. Comparing the activity among glucans derived from microorganisms, highly branched zymosan, glucomannan from Saccharomyces cerevisiae, significantly increased TNF-${\alpha}$ and NO production. These results indicate that the ${\beta}$-glucan from G. lucidum activates rat Kupffer cell and secretes NO and TNF-${\alpha}$. It also suggest that rat Kupffer cell posses certain receptor for ${\beta}$-anomeric glucan.

• Korean Journal of Poultry Science
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• v.44 no.4
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• pp.283-290
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• 2017

Totally, one hundred and sixty 1-day-old Ross 308 broiler chicks were fed with a diet containing 0, 0.5, 1.0, and 2.0 mg of aflatoxin $B_1(AFB_1)/kg$ of feed for 21 days. Body weight was lower for the $AFB_1$-treated broilers than for the control group. At 14 and 21 DPF, the broilers fed with 2.0 mg of $AFB_1/kg$ of feed weighed significantly lower than those of the other groups (p<0.05). Relative liver weights increased significantly in a dose-dependent manner, and relative spleen weights were significantly high in the chicks fed with 2.0 mg of $AFB_1/kg$ of feed at 21 DPF (p<0.001). Biochemical analyses showed that total protein and albumin levels decreased significantly at 7 and 14 DPF for the chicks of the group fed with 2.0 of mg $AFB_1/kg$ of feed, compared with those fed with 0.5 and 1.0 mg of $AFB_1/kg$ of feed (p<0.05). AST and ALT levels increased significantly at 14 and 21 DPF (p<0.05), and the AST levels, particularly, increased dose-dependently (p<0.05). Histopathological analyses showed that the liver tissues of the $AFB_1$-treated chicks showed significant lesions, including hemorrhage, hepatocyte necrosis, inflammatory cell infiltration, and fatty degeneration. The severity of both hepatocyte necrosis and inflammatory cell infiltration appeared to increase dose- and time-dependently. Similarly, hepatic fibrosis increased dose-dependently (p<0.05). The results of this study could improve our understanding of parameters used for evaluating aflatoxicosis in poultry.