• Bulletin of the Korean Chemical Society
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• v.33 no.7
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• pp.2365-2368
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• 2012

The $11{\beta}$-hydroxysteroid dehydrogenase type 1 ($11{\beta}$-HSD1) enzyme is involved in modulation of glucocorticoid activity within target tissues. This enzyme may contribute to obesity and/or metabolic disease through its action in adipose or liver tissue. Inhibition of $11{\beta}$-HSD1 has major therapeutic potential for glucocorticoid-associated diseases, including obesity, diabetes (wound healing), and muscle atrophy. To develop such therapeutics, we performed a pharmacophore-based virtual screening (VS) for identification of novel $11{\beta}$-HSD1 inhibitors and found that the VS hit compounds show potent inhibition of $11{\beta}$-HSD1 enzyme activity. Further, we present a binding model for active compounds. The proposed pharmacophore may serve as a useful guideline for future design of new chemical entities as $11{\beta}$-HSD1-targeted antidiabetic agents.

• Journal of Veterinary Clinics
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• v.15 no.1
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• pp.79-82
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• 1998

This study was performed to determine the changes of serum enzyme activities in rats with hepatic injury induced by the administration of AAPH. Minor behavioral change, brittleness of skin hair and decreased water and fled intake were observed in rats administered intraperitoneally with AAPH. Serum AST and ALT activities pre-treatment were $65{\pm} 13.8 and 32{\pm}$ 12.6 IU/L, respectively and increased sharply from 2 hours of administration and reached $1248{\pm} 77.6 and 946{\pm}$ 45.6 IU/L, respectively at 48 hours of administration. Serum ALP and $\gamma -GTP activities pretreatment were 221 {\pm} 75.6 and 2.2{\pm}$ 0.35 IU/L respectively and increased sharply from 8 hours of administration and reached $767{\pm} 44.9 IU/L and 8.0{\pm} 1.23 IU/L,$ respectively at 48 hours of administration.

• Journal of Life Science
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• v.12 no.3
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• pp.281-287
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• 2002

Quinone reductase was purified to homogeneity from bovine liver and the purified enzyme catalyzed the reduction of phenanthrenequinone as well as benzo- and naphthoquinones. The enzyme catalyzed the biotransformation of arylnitroso nitroso compound and the reaction product was identified by TLC, GC, CC-MS and NMR. The reaction was almost entirely inhibitable by Cibacron blue 3GA or dicumarol, potent inhibitors of mammalian quinone reductase.

• Korean Journal of Veterinary Service
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• v.29 no.3
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• pp.347-364
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• 2006

This study is concerned with assessment of diethylnitrosamine (DEN 0.01 %) induced liver cell carcinogenesis by measurement of changes preceding the development of neoplasms. Therefore, it was undertaken to investigate changes of liver-specific enzyme activities in Sprague-Dawley (SD) rats by ad libitum feeding of DEN. And also. the changes of hepatic morphology in SD rats were detected by haematoxylineosin stain and immunohistochemistry (PCNA). 5- Fluorouracil (5- FU) is one of the most widely used anticancer agents for digestive cancers including hepatocellular carcinoma, and is known to affect the cell cycle and induce apoptosis of cancer cells. In the present study, SD rats were given drinking water containing 0.01% diethylnitrosamine (DEN) for 8 weeks. Minor behavioral change, brittleness of hair and decreased amount of water and diet intake were observed in rats 4 weeks after DEN administration. The body and liver weights were significantly (p < 0.05) decreased in rats 11 weeks after DEN administration. The liver weight ratio to body weight was rather stable and not significantly decreased in the all treatment groups. The liver specific enzyme activities (AST, ALT, ${\gamma}$-GTP) were significantly increased in all treatment groups compared to control group (p < 0.05). Variable size of liver tumor and hepatomegaly were observed in rats treated with DEN after 10 weeks. Numerous vacuoles were seen on the midzonal and or peripheral areas of hepatic lobules. The large and polymorphological hepatocytes with eosinophilic cytoplasm or densely basophilic mitotic nucleoli were seen. Several proliferative small round cells were seen on vacuolated and necrotic areas in peripheral hepatic lobules or portal areas. PCNA-positive cells were seen on the vacuolated portal areas and peripheral areas of hepatic lobules in the areas of small round cells. We examined functional and morphological changes of livers by 5 - FU treatments on DEN -treated rat. The DEN -treated rats compared to 5 - FU -treated rats after DEN treatment for 8 weeks. The serum total protein and triglyceride were significantly (p < 0.05) decreased, and the liver enzyme activities of AST and ALT were significantly(p < 0.05) increased. After 8 weeks, in the non-5-FU -treated group, the size of liver tumor were varied and hepatomegaly were observed, hepatocellular vacuolization, necrosis and steatosis were observed on the midzonal and peripheral areas of hepatic lobules. The large and polymorphological hepatocytes were seen, the interlobular connective tissues were proliferated. PCNA positive cells were seen in the portal areas and peripheral areas of hepatic lobules in the non-5-FU-treated group. In hepatocytes, condensation of nuclear chromatin and vacuolization were observed, shape of the nuclei were irregular, the degraded nuclei and organelles were observed. The livers of rats in the 5 - FU treatment group were seen grossly brilliant, red-brown color, and the vacuolated and degenerated regions, hyperplastic nodules were not nearly observed. In the electron microscope, the cytoplasm of the hepatocytes contained a large number of mitochondria, rough endoplasmic reticulum, developed organelles surrounding nuclei. The above findings suggest that 5 - FU will be effective as anti -liver tumor drug.

• Journal of Ginseng Research
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• v.45 no.2
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• pp.316-324
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• 2021

Background: Korea Red Ginseng (KRG) has been used as remedies with hepato-protective effects in liver-related condition. Microbiota related gut-liver axis plays key roles in the pathogenesis of chronic liver disease. We evaluated the effect of KRG on gut-liver axis in patients with nonalcoholic statohepatitis by the modulation of gut-microbiota. Methods: A total of 94 patients (KRG: 45 and placebo: 49) were prospectively randomized to receive KRG (2,000 mg/day, ginsenoside Rg1+Rb1+Rg3 4.5mg/g) or placebo during 30 days. Liver function test, cytokeraton 18, and fatigue score were measured. Gut microbiota was analyzed by MiSeq systems based on 16S rRNA genes. Results: In KRG group, the mean levels (before vs. after) of aspartate aminotransferase (53 ± 19 vs. 45 ± 23 IU/L), alanine aminotransferase (75 ± 40 vs. 64 ± 39 IU/L) and fatigue score (33 ± 13 vs. 26 ± 13) were improved (p < 0.05). In placebo group, only fatigue score (34 ± 13 vs. 31 ± 15) was ameliorated (p < 0.05). The changes of phyla were not statistically significant on both groups. In KRG group, increased abundance of Lactobacillus was related with improved alanine aminotransferase level and increased abundance of Clostridium and Intestinibacter was associated with no improvement after KRG supplementation. In placebo group, increased abundance of Lachnospiraceae could be related with aggravation of liver enzyme (p < 0.05). Conclusion: KRG effectively improved liver enzymes and fatigue score by modulating gut-microbiota in patients with fatty liver disease. Further studies are needed to understand the mechanism of improvement of nonalcoholic steatohepatitis. ClnicalTrials.gov: NCT03945123 (www.ClinicalTrials.gov).

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.5
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• pp.911-913
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• 2002

Rubi Fructus (fruit of Rubus coreanus Miq.), oriental medicine, has been used for remedy of the liver diseases and for tonic. In order to investigate the oxygen free radical, a harmful factor of aging, in liver of rats fed diets supplemented with the Rubi Fructus water extract(RX), Sprague-Dawley male rats have been fed a diet supplemented with 3% or 5% RX for a month. In rats fed 3% RX supplemented diet, hepatic cytochrome P-450 contents appeared to be increased, and catalase and superoxide dismutase activities were significantly increased compared with the control. There was no difference in glutathione peroxide and glutathione-S-transferase activities between the rats fed RX supplemented diets and the control diet. In conclusion, it is likely that rats fed a diet supplemented with RX may have the oxygen free radicals detoxication potential.

• Journal of Korean Academy of Nursing
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• v.19 no.3
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• pp.299-306
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• 1989

In order to evaluate the effect of fish oil on lipid drogenase(G6PDH), malic enzyme(ME), glucose-6-phosphatase(G6Pase) activities were measured in liver and adipose tissue of rats fed 13 days supplemented fish oil at the level of 10% (W/W). Two other groups of rats were fed 10% soybean oil or lard to compare with the effect of fish oil. In all groups, activities of hepatic G6PDH and ME were depressed from the beginning of feeding. This effect was greatest (50%) in fish oil group. Hepatic G6Pase was highest in rats fed lard. When the level of fish oil was reduced to half, as total fat content was maintained at the level of 10% by complementary lard, lipogenic enzyme depressing effect of fish oil was as significant as shown in 10% fish oil diet. Hepatic G6PDH was depressed significantly(14%) in rats fed fish oil as low as 2％. On the other hand, changes in adipose tissue G6PDH and ME activities were small. Adipose tissue G6Page activity increased slightly in rats fed with increasing fish oil(above 0.5%). It is suggested that fish oil alter, more markedly than either soybean oil or lard, cellular lipid metabolism by reducing activities of hepatic lipogenic enzymes.

• Korean Journal of Pharmacognosy
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• v.10 no.1
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• pp.17-22
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• 1979

The investigation is involved with the effect of Capsicum component on the drug metabolism. To investigate the effects of Capsicum component on, in vivo, drug metabolism in rat, Capsicum acetone extract was given intraperitoneally to mice or rats. The duration of loss of righting reflex was determined as hexobarbital sleeping time in mice. Plasma hexobarbital concentration was also measured by Brodie's method. The rats were pretreated with Capsicum extract acutely or chronically. As the results, hexobarbital sleeping time and plasma hexobarbital concentration were increased by 31.2% and 12.3% in acute study, whereas were decreased by 27.5% and 23.0% in chronic study. An attempt was made to determine if there were any influences on enzyme activities in rats pretreated with Capsicum extract chronically. Microsomal fraction was isolated from rat liver and quantity of cytochrome $P_{450}$ and $b_5$ in the microsomal fraction were determined by Omura's method. It was found that the quantity of cytochome $P_{450}$ was increased by 22.4%. The results suggest that microsomal drug metabolizing enzyme may be induced by chronic administration of Capsicum component, whereas it may be inhibited by acute administration of Capsicum component.

• Natural Product Sciences
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• v.20 no.1
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• pp.65-70
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• 2014

This study was carried out to investigate the potential effects of Gardenia jasminoides (GJ) extracts, on hepatic steatosis and lipid metabolism in mice fed with high-fat diet (HFD). GJ extracts (100 mg/kg, ${\times}10$ weeks) fed mice showed reduced body weight, adipose tissue weight, reduced aminotransferase level in plasma and hepatic lipid (triglyceride, total cholesterol) content. These effects were accompanied by decreased expression of lipogenic genes, sterol regulatory element binding protein-1c (SREBP-1c), liver X receptor (LXR), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), cluster of differentiation 36 (CD36), lipoprotein lipase (LPL) and decreased lipogenic enzyme FAS and HMG-CoAR enzyme activities while elevating carnitine palmitoyltrasferase-1 (CPT) activity. Based on these results, we speculated that the inhibitory effect on hepatic steatosis of GJ extract containing geniposide is the result of suppression of lipid synthesis in mice fed with HFD, suggesting that GJ extract may be beneficial in preventing hepatic steatosis.

• Korean Journal of Pharmacognosy
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• v.34 no.4 s.135
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• pp.297-302
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• 2003

Cnidii Rhizoma water extract (CRW) was tested for liver cancer chemopreventive potential by measuring the inhibition of phase I enzyme and benzo[a]pyrene-DNA adduct formation and induction of phase II detoxification enzymes. There was 17.0% inhibition in the activity of cytochrome P450 1A1 enzyme with the treatment of 150 mg/ml CRW. At concentration of 30 mg/ml CRW, the binding of $[^3H]B[a]P$ metablites to DNA of NCTC-clone 1469 cell was inhibited by 33.3%. CRW was potent inducer of quinone reductase (QR) and glutathione S-transferase (GST) activities in cultured murine hepatoma Hepalc1c7 cells. However, hepatic glutathione (GSH) level was not influenced by CRW. These findings suggest that CRW has chemopreventive potential of liver cancer by inhibiting cytochrome P450 1A1 activity and benzo[a]pyrene-DNA adduct formation and inducing QR and GST activities.