• Archives of Pharmacal Research
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• v.29 no.4
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• pp.333-338
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• 2006

The aim of this study was to investigate the effect of morin on the bioavailability of nimodipine after administering nimodipine (15 mg/kg) orally to rabbits either co-administered or pretreated with morin (2, 10 and 20 mg/kg). The plasma concentrations of nimodipine in the rabbits pretreated with morin were increased significantly (p<0.05 at 10 mg/kg, p<0.01 at 20 mg/kg) compared with the control, but the plasma concentrations of nimodipine co-administered with morin were not significant. The areas under the plasma concentration-time curve (AUC) and the peak concentrations $(C_{max})$ of the nimodipine in the rabbits pretreated with morin were significantly higher (p<0.05 at 10 mg/kg, p<0.01 at 20 mg/kg), but only the $C_{max}$ of nimodipine coadministered with morin 10 mg/kg was increased significantly (p<0.05). The absolute bioavailability $(A.B\%)$ of nimodipine in the rabbits pretreated with morin was significantly (p<0.05 at 10 mg/kg, p<0.01 at 20 mg/kg) higher $(54.1-65.0\%)$ than the control $(36.7\%)$. The increased bioavailability of nimodipine in the rabbits pretreated with morin might have been resulted from the morin, which inhibits the efflux pump P-glycoprotein and the first-pass metabolizing enzyme by cytochrome P-450 3A4 (CYP 3A4).

• BMB Reports
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• v.55 no.12
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• pp.621-626
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• 2022

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by the degeneration of motor neurons in the spinal cord. Main symptoms are manifested as weakness, muscle loss, and muscle atrophy. Some studies have reported that alterations in sphingolipid metabolism may be intimately related to neurodegenerative diseases, including ALS. Acid sphingomyelinase (ASM), a sphingolipid-metabolizing enzyme, is considered an important mediator of neurodegenerative diseases. Herein, we show that ASM activity increases in samples from patients with ALS and in a mouse model. Moreover, genetic inhibition of ASM improves motor function impairment and spinal neuronal loss in an ALS mouse model. Therefore, these results suggest the role of ASM as a potentially effective target and ASM inhibition may be a possible therapeutic approach for ALS.

• Journal of Life Science
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• v.19 no.9
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• pp.1321-1327
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• 2009

The present study examined the comparative effects of various amino acids on the alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) activities of yeast Saccharomyces cereviciae and rat liver homogenate in vitro. Methionine showed the highest activity in yeast ADH among the amino acids used in this study, but this was not higher than that of the hangover product, Condition-Power (CP) used as positive control. Methionine was also found to be the best amino acid in terms of the ALDH activity in rat liver homogenate among the treatment amino acids, which was comparatively higher than that of positive control CP. It was chosen for further experiments and yeast ADH activity increased in parallel with increased methionine concentration, but not rat liver ALDH activity, and it was comparatively higher than those of the positive control. Arginine showed the highest values in yeast ALDH and rat liver ADH activities among amino acids, and it was chosen for further experiments. Yeast ALDH activity increased in parallel with increased arginine concentration, which was higher than that of positive control CP, and rat liver ADH activity was also comparatively higher in all treatment concentrations of arginine than that of positive control CP. The native electrophoresis of ADH and ALDH from cell-free extracts of yeast Saccharomyces cerevisiae cultured in the growth medium containing various arginine concentrations by $0{\sim}0.1%$ showed two active bands upon zymogram staining analysis, and the straining intensity of ADH and ALDH active bands in arginine treatment yeast was stronger than that of non-yeast or low treatment yeast. These results indicate that alcohol metabolizing enzyme activities can be enhanced by arginine and methionine, suggesting that arginine and methionine have potent ethanol-metabolizing activities.

• Journal of the Korean Society of Food Science and Nutrition
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• v.30 no.4
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• pp.668-672
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• 2001

To investigate the oxygen free radical and alcohol metabolizing system in liver of rats fed diets with 30% ethanol extract of Lycium chinense (LCEE), Sprague-Dawley male rats weighing 225~235g have been fed a diet supplemented with 2% or 4% LCEE for a month. The rats fed LCEE supplemented diets gained less body weight compared with the control, and had no remarkable changes of liver function. In rats fed 2% LCEE supplemented diet, hepatic cytochrome P450 contents appeared to be increased, but catalase (204.88$\pm$20.06 $H_2O$$_2$nmoles/mg protein/min), and superoxide dismutase (13.18$\pm$0.74 Unit/mg protein) activities were significantly increased compared with control 120.28$\pm$26.99 $H_2O$$_2$nmoles/mg protein/min and 10.49$\pm$0.80 Units/mg protein). There was no difference in hepatic glutathione content, glutathione peroxidase, and glutathione-S-transferase ctivities between the rats fed LCEE suplemented diets and the control diet. On the other hand, hepatic alcohol dehydrogenase activity were not changed by LCEE feeding, but hepatic aldehyde dehydrogenase activities were significantly increased in rats fed both 2 and 4% LCEE diets(5.01$\pm$0.21 and 4.47$\pm$0.06 $\mu$moles NADPH/mg protein/min) compared with control (3.28$\pm$0.21 $\mu$moles NADPH/mg protein/min) and its Vmax value was 1.9 fold increased in rats fed 2% LCEE and 1.5 fold in those fed 4% LCEE compared with control. In conclusion, it is likely that rats receiving a diet supplemented with LCEE may have the oxygen free radicals and alcohol detoxication potential.

• Biomolecules & Therapeutics
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• v.23 no.5
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• pp.486-492
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• 2015

Drug metabolism mostly occurs in the liver. Cytochrome P450 (CYP) is a drug-metabolizing enzyme that is responsible for many important drug metabolism reactions. Recently, the US FDA and EU EMA have suggested that CYP enzyme induction can be measured by both enzymatic activity and mRNA expression. However, these experiments are time-consuming and their interassay variability can lead to misinterpretations of the results. To resolve these problems and establish a more powerful method to measure CYP induction, we determined CYP induction by using luminescent assay. Luminescent CYP assays link CYP enzyme activity to firefly luciferase luminescence technology. In this study, we measured the induction of CYP isozymes (1A2, 2B6, 2C9, and 3A4) in cryopreserved human hepatocytes (HMC424, 478, and 493) using a luminometer. We then examined the potential induction abilities (unknown so far) of mesalazine, a drug for colitis, and mosapride citrate, which is used as an antispasmodic drug. The results showed that mesalazine promotes CYP2B6 and 3A4 activities, while mosapride citrate promotes CYP1A2, 2B6, and 3A4 activities. Luminescent CYP assays offer rapid and safe advantages over LC-MS/MS and qRT-PCR methods. Furthermore, luminescent CYP assays decrease the interference between the optical properties of the test compound and the CYP substrates. Therefore, luminescent CYP assays are less labor intensive, rapid, and can be used as robust tools for high-throughput CYP screening during early drug discovery.

• Journal of the Korean Society of Food Science and Nutrition
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• v.20 no.6
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• pp.527-537
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• 1991

To evaluate an effect of liver xanthine oxidase on the induction of liver damage, carbon tetrachloride (CCl4) was intraperitoneally injected twice at 0.1ml/100g body weight to the rate fed a low (LP)or high protein diet(HP) while the control group fed LP or HP received only olive oil. The changing rate of liver xanthine oxidas activity was compared with that of a free radical generating enzyme, liver aniline hydroxylase and a scavenging enzyme, glutathions S-transferase activity between the rate fed a LP and those fed HP, and the two groups treated with CCl4. Concomitantly, the degree of liver damage which could be considered as the paramete for CCl4 metabolism in case of CCl4-intoxicated animal was observed in the present experimental conditions and the effect of allopurinol, xanthine oxidase inhibitor, on the CCl4-toxicity of rate liver was alos demostrated. On the other hand, the comparative effect of actinomycin D on the liver and serum xanthine oxidase of CCl4-treated rats fed HP with that of those fed LP and the kinetics of purifed liver enzyme from the liver of CCl4-treated rats fed HP was also compared with that of those fed LP to clarify the differences of xanthine oxidase activity between two groups. The increasing rate of liver weigth/body wt, serum levels of ALT and the decreasing rate of hepatic ALT activity and protein contents to each control group were higher in CCl4-treated rats fed HP than those fed LP. Under the animal models as indentified by the present data herein, the liver xanthine oxidase activity was higher in CCl4-treated rats fed HP than those fed LP, and the control group fed HP also showed the much higher activity xanthine oxidase than that fed LP, whereas there were no differences in the activity of hepatic aniline hydroxylase and glutathions S-transferase between the two group treated with CCl4. Although the hepatic aniline hydroxylase activity was somewhat higher in the rats fed HP than those fed LP, the increasing rate of liver xanthine oxidase to the rats fed LP was higher in those fed HP than that of liver aniline hydroxylase. The degree of liver damage identified such as liver weight and serum ALT activity was less in the CCl4-treated rats pretreated with allopurinol. These results suggest that even a system at which xanthine oxidase acts as well as the drug metabolizing enzyme may influence the acelatin of CCl4 metabolism. In addition, the purified liver xanthine oxidase from CCl4-treated rats fed HP showed decreased Km value when compared to its control group. The Km value of liver xanthine oxidase of CCl4-treated rats fed LP showed a similar Km value with its control group. Furthermore, the decreasing rate of liver and serum xanthine oxidase acitivity in CCl4-treated rats pretreated with actinomycin D to the CCl4-treated rats was higher in rats fed HP than in those fed LP. These results suggest that the inductino of xanthine oxidase in CCl4-treated rats fed HP may be greater than in those fed LP.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.3
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• pp.393-400
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• 2011

This study investigates the effects of a hangover beverage (MIX) that contains minerals (highly-salty mineral water, HSMW) and several medicinal plant extracts, on antioxidant and alcohol-metabolizing enzymes in alcohol administered Sprague-Dawley rats. HSMW is pumped from below the sedimentary rock layer of Dadaepo, Busan, South Korea, which is 1,050 m below the land surface; it tastes salty, like sea water. In terms of medicinal plant extracts, the total phenolic and flavonoid contents of Rubus coreanus and Cornus officinalis were measured as being significantly higher than those in Curcuma longa. The results suggest that treatment with MIX significantly increases superoxide dismutase (SOD) activity and DPPH radical scavenging activity. In the 10% HSMW-, for MIX- and company product (CP)-treated groups, the concentration of blood alcohol was significantly reduced 1~5 hr after alcohol loading, compared to that in the control group. In hepatic alcohol-metabolizing enzyme activities, alcohol dehydrogenase (ADH) activity was found to be higher in the MIX- and CP-treated groups than in controls, whereas acetaldehyde dehydrogenase (ALDH) activity was significantly higher in the CP-treated groups than other groups. This study concludes, therefore, that MIX (HSMW) minerals, like as Zn, Ca, Mg, Mn, and others stimulate alcohol-metabolizing enzymes, while the antioxidants of plant extracts prevent the damage otherwise incurred by alcohol toxicity. These results suggest that the hangover beverage (MIX) alleviates alcohol hangover symptoms by stimulating activities related to hepatic alcohol-metabolizing enzymes and antioxidant effects.

• Journal of Life Science
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• v.27 no.11
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• pp.1262-1268
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• 2017

Lemon myrtle (Backhousia citriodora), a plant in the Myrtaceae family, is native to the semitropical rain-forests of Queensland and is presumably the most commercialized native spice. In Australian thousands of lemon-myrtle trees are under tillage. This study was carried out to investigate the alcohol metabolism, hepatoprotective effects and antidiabetic, tyrosinase inhibitory activity of hot-water (LMW) and 80% ethanol (LME) extracts from lemon-myrtle leaves. The alpha-glucosidase (${\alpha}$-glucosidase) inhibitory activities of the LMW and LME extracts were 7.66% and 40.29% at 1 mg/ml (p<0.05), respectively. The tyrosinase inhibitory activity of the LME extract was about 38.26 % at 1 mg/ml. The effects the LMW and LME extracts had on alcohol-metabolizing activities were determined by measuring the generation of reduced nicotinamide-adenine dinucleotide (NADH) by acetaldehyde dehydrogenase (ALDH) and alcohol dehydrogenase (ADH). The ADH activities of the LMW and LME extracts significantly increased in a dose-dependent manner and were about 154.40% and 192.03% at 1 mg/ml, respectively (p<0.05). The ALDH activities of the LMW and LME extracts also significantly increased in a dose-dependent manner and were about 151.14% and 192.34% at 1 mg/ml, respectively (p<0.05). At $100{\mu}g/ml$, the LMW and LME extracts showed significant protective effects against tacrine-induced cytotoxicity in Hep G2 cells. The results suggested that Backhousia citriodora leaf extracts have the potential to be significant sources for natural health products.

• Biomedical Science Letters
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• v.1 no.1
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• pp.37-43
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• 1995

To evaluate an effect of xanthine oxidase(XO) reaction system on the carbon tetrachloride($CCl_4$) metabolism, $CCl_4$ was given twice at 0.1ml/100g body wt. at intervals of 18 hour to the rats and those pretreated with allopurinol (50mg/kg. body wt.). The influence of XO on the metabolism of $CCl_4$ was focused on the degree of liver damage and the activities of a $CCl_4$ metabolizing marker enzyme, glucose-6-phosphatase. The increasing rate of liver weight per body weight and the levels of serum alanine aminotransferase to the control group were more decreased in allopurinol-pretreated rats than in those treated with $CCl_4$ alone. The liver XO activities were more increased in $CCl_4$-treated rats than the control group and the $CCl_4$-treated rats pretreated with allopurinol showed a decreased activities of XO compared to the $CCl_4$-treated rats. The type conversion (type D --> type O) rate was more decreased tendency in allopurinol pretreated rats than those treated $CCl_4$ alone. In dialyzed liver enzyme preparations, all of the xanthine oxidase activities: $CCl_4$-treated, allopurinol and $CCl_4$-treated rats pretreated with allopurinol showed the more increased Vmax value than the control group, but similar Km value. Moreover, $CCl_4$-treated rats pretreated with allopurinol showed the more increased Vmax value than the group treated with $CCl_4$ alone. In conclusion, it can not be negate the possibility of metabolism of $CCl_4$ by the xanthine oxidase enzyme system.

• Korean journal of food and cookery science
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• v.30 no.5
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• pp.613-619
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• 2014

For the development of a hangover soup containing blue mussel, 11 kinds of hot water extracts were prepared - A (mistletoe); B (shepherd's purse); C (arrowroot); D (bean sprout); E (oriental raisin); F (blue mussel); G (blue mussel and mistletoe); H (blue mussel and shepherd's purse); I (blue mussel and arrowroot); J (blue mussel and bean sprout); and K (blue mussel and oriental raisin). Extract C showed the highest effect for increasing the activities of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH); however, the addition of blue mussel did not provide a synergy effect on extract C. Other than the arrowroot-containing extracts (C and I), extract H showed relatively higher ADH ($237.4{\pm}1.7%$) and ALDH ($136.5{\pm}2.1%$) activities. Moreover, extract H showed the highest DPPH radical scavenging activity ($93.9{\pm}0.1%$) and angiotensin I converting enzyme (ACE) inhibitory activity ($42.7{\pm}1.6%$). The combination of blue mussel with shepherd's purse had a synergic effect on its ADH and ACE inhibitory activities.