• The Journal of Internal Korean Medicine
• /
• v.24 no.2
• /
• pp.374-379
• /
• 2003

Herbal remedies are enjoying a growing popularity in the world. But, we still pay few attention to the potential hepatotoxicity of herbal remedies, and there are only a few reports about that. We recently experienced a case of drug induced hepatitis caused by ingestion of Dyctamnus dasycarpus, one of herbs used for dermatologic disorders. The patient, a 38 year old woman, was admitted due to jaundice after ingestion of some herbal mixture containing Dyctamnus dasycarpus to treat her atopic dermatitis for 4 months. Other possible causes of liver injury were excluded by laboratory test and imaging studies, and we could find a report on similar cases caused by ingestion of Dyctamnus dasycarpus. During conservative treatment, elevated liver enzyme and total bilirubin level slowly returned to normal value. This case stresses the need to warn the potential hepatotoxicity of Dyctamnus dasycarpus, especially for a long time ingestion. So we suggest the necessity of toxicology screen at regular intervals during long time ingestion of herbal medicine, and further evaluation of the safety and toxicity of Dyctamnus dasycarpus.

• Toxicological Research
• /
• v.12 no.2
• /
• pp.155-161
• /
• 1996

The enzymatic properties for NADPH-P450 reductase domain of a fusion protein between human cytochrome P450 1A1 and rat NADPH-P450 reductase expressed in Escherichia coli were investigated. The fusion plasmid pCW/1A1OR-expressed E. coli membrane showed high NADPH-cytochrome c reductase activity ($830.1\pm 85.8 nmol\cdot min^{-1}\cdot mg protein^{-1}$), while pCW control vector and P 450 1A1 expression vector pCW/1A1 showed relatively quite low activity ($4.35\pm 0.49, 3.27\pm 0.50 nmol\cdot min^{-1}\cdot mg protein^{-1}$, respectively). The kinetic curves for NADPH-cytochrome c reductase followed typical Michaelis-Menten kinetics. The $K_{max}$ and $V_{max}$ for NADPH-dependent reductase activity were $8.24\pm 2.61\mu $and $817.9\pm 60.8 nmol\cdot min^{-1}\cdot mg protein^{-1}$, respectively, whereas those for cytochrome c-dependent reductase activity were $19.97\pm 2.86\mu M$ and $1303.5\pm 67.1 nmol\cdot min^{-1}\cdot mg protein^{-1}$. The reductase activities were also compared with those of rat, porcine and human liver microsomes. The activity of pCW/ 1A1OR-expressed E. coli membrane was 15.2-fold higher than that of rat liver microsome. Treatment with benzo(a)pyrene, 7-ethoxyresorufin and $\alpha$-naphthofiavone which are known as specific substrates or inhibitor for human P450 1A1 increased NADPH-cytochrome c reductase activity of fusion protein in E. coli membrane dose-dependently. These results demonstrate that the membrane topology of fused enzyme may be important for activity of its NADPH-P450 reductase domain.

• Journal of Nutrition and Health
• /
• v.24 no.5
• /
• pp.420-430
• /
• 1991

To compare the hypolipidemic effects of n6 linoleic acid. n3 $\alpha$-linolenic acid and n3 eicosapentaenoic acid in rats fed high carbohydrate(70% Cal) diet. male Sprague Dawley rats were fed different experimental diets for 6 weeks. which were different only in fatty acid composition. The dietary fats were beer tallow(BT) as a source of saturated fatty acid (SFA), corn oil(CO) for n6 linoleic acid(LA), perilla oil(PO) for n3 $\alpha$-linolenic acid(LL) and fish oil(FO) for n3 eicosapentaenoic acid(EPA) and docosahexaenoic acid (DHA) Plasma total cholesterol(Chol) level was increased by n6 LA but decreased by n3 LL and n3 EPA and most effectively reduced by n3 EPA. HDL-Chol level was raised by n6 LA, but there was no significant change in HDL-Chol levels by n3 LL and was lowered by n3 EPA. Plasma TG level was reduced by n6 LA, but lipogenesis in liver was not affected by n6 LA. However, plasma TG level was lowered by n3 LL and EPA. Both lipogenic enzyme activity and liver TC level were also decreased by n3 PUFA. The relative proportions of TG in VLDL was significantly lowered by n3 EPA. but the proportions of Apo B in VLDL was not changed by n3 EPA. Overall. the hypolipidemic effect was in the order of EPA+ DHA(n3) >LL(n3) >LA(n6) and fish oil and perilla oil rich in n3 PUFA may have important nutritional applications in the prevention and treatment of hypertriglyceridemia.

• Nutrition Research and Practice
• /
• v.10 no.1
• /
• pp.26-32
• /
• 2016

BACKGROUND/OBJECTIVES: It has been shown that vitamin A supplementation has different effects on skeletal health and the antioxidant system. Deficiency or excess of this vitamin can lead to health problems. Vitamin A can work as either an antioxidant or prooxidant depending on its concentration. The present study was conducted to investigate the effects of different doses of vitamin A supplementation on the antioxidant system in rats. MATERIALS/METHODS: Forty Spargue-Dawley male rats were divided into four groups according to the dose of vitamin A received: 0 (A0), 4,000 (A1), 8,000 (A2), and 20,000 (A3) IU retinyl palmitate/kg diet. After a feeding period of 4 wks, lipid peroxide levels, glutathione concentration, antioxidant enzyme activities, and vitamins A and E concentrations were measured. Histopathological changes were observed in rat liver tissue using an optical microscope and transmission electron microscope. RESULTS: Lipid peroxide levels in plasma were significantly decreased in the A1 and A2 groups compared to the A0 rats. Erythrocyte catalase and hepatic superoxide dismutase activities of the A2 group were significantly higher than those of the A0 group. Hepatic glutathione peroxidase activity was significantly lower in the A3 group compared to the other groups. Total glutathione concentrations were significantly higher in the A1 and A2 groups than in the A0 group. Histological examination of liver tissue showed that excessive supplementation of vitamin A might lead to lipid droplet accumulation and nuclear membrane deformation. CONCLUSIONS: These results indicate that appropriate supplementation of vitamin A might have a beneficial effect on the antioxidant system in rats.

• Nutrition Research and Practice
• /
• v.7 no.4
• /
• pp.273-280
• /
• 2013

Bamboo salt, a Korean folk medicine, is prepared with solar salt (sea salt) and baked several times at high temperatures in a bamboo case. In this study, we compared the preventive effects of bamboo salt and purified and solar salts on hepatic damage induced by carbon tetrachloride in Sprague-Dawley rats. Compared with purified and solar salts, bamboo salts prevented hepatic damage in rats, as evidenced by significantly reduced serum levels of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase (P < 0.05). Bamboo salt (baked $9{\times}$) triggered the greatest reduction in these enzyme levels. In addition, it also reduced the levels of the proinflammatory cytokines interleukin (IL)-6, interferon (IFN)-${\gamma}$, and tumor necrosis factor (TNF)-${\alpha}$. Histopathological sections of liver tissue demonstrated the protective effect of bamboo salt, whereas sections from animals treated with the other salt groups showed a greater degree of necrosis. We also performed reverse transcription-polymerase chain reaction and western blot analyses of the inflammation-related genes iNOS, COX-2, TNF-${\alpha}$, and IL-$1{\beta}$ in rat liver tissues. Bamboo salt induced a significant decrease (~80%) in mRNA and protein expression levels of COX-2, iNOS, TNF-${\alpha}$, and IL-$1{\beta}$, compared with the other salts. Thus, we found that baked bamboo salt preparations could prevent $CCl_4$-induced hepatic damage in vivo.

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

• The Journal of Traditional Korean Medicine
• /
• v.15 no.1
• /
• pp.97-105
• /
• 2006

To study on antioxidant effects in the liver of 40-week-old mouse, the sample were orally pretreated 5mg/kg/day for 5 days with red ginseng saponin components(total saponin, protopanaxadiol saponin, protopanaxatriol saponin, ginsenoside-Rd, ginsenoside-Re, compound-K) for 5 days. The ability of saponin to protect the mouse liver from oxidative damage was examined by determining the activity of superoxide dismutase(SOD), glutathione peroxidase(GPx) and the contents of glutathione, the level of malondialdehyde, The only protopanaxadiol among the ginseng saponin fractions was significantly increased the hepatic SOD activity(p<0.01). The red ginseng saponin induced a slight increase of GPx activity, especially ginsenoside Rd, compound K and protopanaxatriol treatments significantly increased its activity. The content of glutathione was significantly increased by total saponin, protopanaxadiol and ginsenoside Rd(p<0.01), but the oxidized glutathione level was lowered in all the red ginseng saponin. Finally, the level of malondialdehyde was significantly decreased by ginsenoside Rd and protopanaxadiol. In conclusion, protopanaxadiol and ginsenoside Rd among the saponin fraction were especially increased in the activity of hepatic antioxidative enzyme and decreased the lipid peroxidation that was expressed in term of MDA formation. This comprehensive antioxidant effects of red ginseng saponin seems to be by a certain action of saponin other than a direct antioxidant action.

• Herbal Formula Science
• /
• v.26 no.4
• /
• pp.307-318
• /
• 2018

Objectives : Endoplasmic reticulum (ER) stress designates cellular responses to the accumulation of misfolded and unfolded proteins in ER, which is related to a variety of liver diseases. Present study investigated the inhibitory effects of Litsea japonica flesh water extract (LJE) aganist ER stress. Methods : After HepG2 cells were pretreated with LJE and subsequently exposed to tunicamycin (Tm) or thapsigargin (Tg), expression of C/EBP homologous protein (CHOP), glucose regulated protein 78 kDa (GRP78), asparagine synthetase (ASNS), and endoplasmic reticulum DnaJ homologue 4 (ERDJ4) were determined by immunoblot and real-time PCR analysis. Three canonical signaling pathways in response to ER stress were examined to explore molecular mechanisms involved. Results : Pretreatment of 1 mg/mL LJE inhibited Tm- or Tg-induced CHOP expression, while L. japonica fruit water extract did not. In addition, LJE decreased the levels of GRP78, ASNS, and ERDJ4 mRNA by Tm. Moreover, phosphorylations of eukaryotic translation initiation factor $2{\alpha}$ and inositol-requiring enzyme 1, expression of nuclear form of activating transcription factor $6{\alpha}$, and transactivation of ER stress response element- and unfolded protein response element-harboring luciferase activities were inhibited by LJE pretreatment. Conclusions : Present results suggest that LJE would be a candidate to prevent or treat ER stress-mediated liver injuries.

• Nutrition Research and Practice
• /
• v.13 no.4
• /
• pp.286-294
• /
• 2019

BACKGROUND/OBJECTIVES: Docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid (LCPUFA), is acquired by dietary intake or the in vivo conversion of ${\alpha}$-linolenic acid. Many enzymes participating in LCPUFA synthesis are regulated by peroxisome proliferator-activated receptor alpha ($PPAR{\alpha}$). Therefore, it was hypothesized that the tissue accretion of endogenously synthesized DHA could be modified by $PPAR{\alpha}$. MATERIALS/METHODS: The tissue DHA concentrations and mRNA levels of genes participating in DHA biosynthesis were compared among $PPAR{\alpha}$ homozygous (KO), heterozygous (HZ), and wild type (WT) mice (Exp I), and between WT mice treated with clofibrate ($PPAR{\alpha}$ agonist) or those not treated (Exp II). In ExpII, the expression levels of the proteins associated with DHA function in the brain cortex and retina were also measured. An n3-PUFA depleted/replenished regimen was applied to mitigate the confounding effects of maternal DHA. RESULTS: $PPAR{\alpha}$ ablation reduced the hepatic Acox, Fads1, and Fads2 mRNA levels, as well as the DHA concentration in the liver, but not in the brain cortex. In contrast, $PPAR{\alpha}$ activation increased hepatic Acox, Fads1, Fads2, and Elovl5 mRNA levels, but reduced the DHA concentrations in the liver, retina, and phospholipid of brain cortex, and decreased mRNA and protein levels of the brain-derived neurotrophic factor in brain cortex. CONCLUSIONS: LCPUFA enzyme expression was altered by $PPAR{\alpha}$. Either $PPAR{\alpha}$ deficiency or activation-decreased tissue DHA concentration is a stimulus for further studies to determine the functional significance.

• Korean Journal of Clinical Pharmacy
• /
• v.28 no.4
• /
• pp.342-346
• /
• 2018

Background: Green tea extracts are approved as nonprescription drug and available as health functional foods, health foods, and beverages. Clinical information on the products is lacking. Methods: Information about the products on green tea nonprescription drugs was obtained from the website of the Korea Pharmaceutical Information Center. The Naver, i.e., a top ranking online search portal, was used for compiling the list of the health functional food products using key words of 'green tea catechin' on August 23, 2018. The recommended daily dosages of catechins were calculated as 30% of the total dried mass of green tea and about 50% of the catechins were considered as epigallocatechin gallate (EGCG). Results: A total of two types of nonprescription drugs containing green tea powder or extracts, nine health functional food products, and three types of health foods were found. The regulatory requirements of the EGCG exceeding 800 mg were reported to be associated with adverse effects of elevated liver enzyme. If consumers take several green tea products concurrently, such as nonprescription drugs with health functional foods or health foods, it could exceed the recommended amount of EGCG. Conclusion: The concurrent use of green tea products as nonprescription drugs, health functional foods, and healthy foods may lead to an increased exposure to EGCG. Pharmacists should be aware the availability of various types of green tea products and the potential risk of liver toxicity due to excessive consumption of EGCG.