• 대한한의학방제학회지
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• 제17권2호
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• pp.123-132
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• 2009

Acetaminophen (AP) is widely used as an over-the-counter analgesic and antipyretic drug. AP-induced hepatotoxicity is a common consequence of AP overdose and may lead to acute liver failure. In this study, we investigated the liver damage in mice using single dose (300 mg/kg) of AP and the possible protective effects of administration (50-200 mg/kg body weight) of Joo-Juk on acetaminophen-induced liver damage in mice. The alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities were determined in the plasma of mice. The effect of Joo-Juk on lipid peroxidation product thiobarbituric reacting substances (TBARS) and some antioxidant enzymes superoxide dismutase (SOD), catalase, d-aminolevulinate dehydratase ($\sigma$-ALA-D) activities, and gluthathione peroxidase (GPx), were also evaluated in the mouse liver homogenate. AP caused liver damage as evident by statistically significant increased in plasma activities of AST and ALT. There were statistically significant losses in the activities of SOD, catalase, $\sigma$-ALA-D, and GPx and an increase in TBARS in the liver of AP-treated group compared with the control group. However, Joo-Juk was able to counteract these effects. These results suggest that Joo-juk can act as hepato-protectant against AP toxicity and is a good candidate for further evaluation as an effective chemotherapeutic agent.

• 대한한의학방제학회지
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• 제16권2호
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• pp.183-191
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• 2008

Acetaminophen (N-acety1-p-aminophenol, paracetamol) is widely used as an over-the-counter analgesic and antipyretic drug. Intake of a over dose of acetaminophen may result in severe hepatic necrosis. In this study, we investigated the liver damage in mice using single dose (300 mg/kg) of acetaminophen and the possible protective effects of administration (50-200 mg/kg body weight) of SB-Ex on acetaminophen-induced liver damage in mice. The alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities were determined in the plasma of mice. The effect of SB-Ex on lipid peroxidation product thiobarbituric reacting substances (TBARS) and some antioxidant enzymes superoxide dismutase (SOD), catalase, d-aminolevulinate dehydratase (${\sigma}$-ALA-D) activities, and gluthathione peroxidase (GPx), were also evaluated in the mouse liver homogenate. Acetaminophen caused liver damage as evident by statistically significant increased in plasma activities of AST and ALT. There were general statistically significant losses in the activities of SOD, catalase, ${\sigma}$-ALA-D, and GPx and an increase in TBARS in the liver of acetaminophen-treated group compared with the control group. However, SB-Ex was able to counteract these effects. These results suggest that SB-Ex can act as hepatoprotectives against acetaminophen toxicity and is a good candidate for further evaluation as an effective chemotherapeutic agent.

• 대한한의학회지
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• 제32권4호
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• pp.1-24
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• 2011

Backgrounds: Danggui, one of the major herbs in Korean traditional medicine consists of three species: Angelica gigas of Korea, Angelica sinensis of China, and Angelica acutiloba of Japan. Despite its importance in Korean traditional medicine, recognition of the clinical differences between its three species is insufficient. Objectives: The purpose of the present review is to suggest evidence in using Angelica gigas, Angelica sinensis, and Angelica acutiloba distinctively in clinic, by comparing their pharmacological effects and bioactive compounds. Methods: We searched articles published from 2000 to 2009 in Pubmed, EMbase, and RISS. The search keywords were "Angelica gigas", "Angelica sinensis", "Angelica acutiloba", "dongquei", "toki", "Angelicae Radix", "Archangelica officinalis Hoffm.", "Garden Angelica", "Chinese angelica root", "tangkuei", and "danggui". 861 articles were searched. Among them, we selected 143 articles which met our inclusion criteria. Results: This review summarizes active constituents, experimental studies, clinical studies, pharmacokinetics, side effects and toxicity, drug interaction, and industrial use of Angelica gigas, Angelica sinensis, and Angelica acutiloba. Conclusions: While Angelica sinensis and Angelica acutiloba are relatively similar, Angelica gigas is quite different from the others in main active constituents and genetic form. The main experimental studies of Danggui are cardiovascular studies, central nervous system studies and anti-cancer activity. Even though there were cases in which the three species show similar pharmacological effects, the mechanism was not always shared. Therefore, distinguished use of Angelica gigas, Angelica sinensis and Angelica acutiloba is needed.

• 대한한방내과학회지
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• 제29권1호
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• pp.177-188
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• 2008

Objectives : This study was performed to investigate the anti-fibrogenic effect of Artemisiae Capillaris Herba on cultured rat hepatic stellate cells. Materials and Methods : Hepatic stellate cells(HSC-T6) were treated with various concentrations of Artemisiae Capillaris Herba extract for 24 hours. The extraction was done either with distilled water or 50% EtOH. After the treatment, cell viability, proliferation, procollagen levels and the mRNA of the collagen type 1a2 and ASMA were measured by using MTT assay, BrdU assay, RT-PCR, and Procollagen Type I C-peptide EIA Kit. Results : The viability and proliferation of the hepatic stellate cells were decreased as the concentration increased. The mRNA expression decreased consistently with the volume of the secreted procollagen with the extraction made with distilled water, which indicates the herb has inhibitory effect on fibrogenesis of the liver by regulating one of the fibrosis associated genes in transcription. However, it increased in 50% EtOH extraction, which shows that a more stable reaction is expected of the extraction made with distilled water than the extraction made with 50% EtOH. The production of procollagen was decreased by a low-concentration treatment with Artemisiae Capillaris Herba, but increased by a high concentration. It seemed that the cells were responding to Artemisiae Capillaris Herba in low- concentrations, thus producing small amounts of collagen. When the drug was administered at high enough concentration to give direct toxicity to cells, the ability of cells to produce collagen was activated, and the overproduction of collagen was observed as an undesirable results. Conclusion : These results suggest that Artemisiae Capillaris Herba is beneficial in the treatment of cirrhotic patients as well as for the patients with chronic hepatitis when extracted with water in the proper concentrations.

• Toxicological Research
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• 제28권3호
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• pp.165-172
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• 2012

Raphanus sativus (Cruciferaceae), commonly known as radish is widely available throughout the world. From antiquity it has been used in folk medicine as a natural drug against many toxicants. The present study was designed to evaluate the hepatoprotective activity of radish (Raphanus sativus) enzyme extract (REE) in vitro and in vivo test. The $IC_{50}$ values of REE in human liver derived HepG2 cells was over 5,000 ${\mu}g/ml$ in tested maximum concentration. The effect of REE to protect tacrine-induced cytotoxicity in HepG2 cells was evaluated by MTT assay. REE showed their hepatoprotective activities on tacrine-induced cytotoxicity and the $EC_{50}$ value was 1,250 ${\mu}g/ml$. Silymarin, an antihepatotoxic agent used as a positive control exhibited 59.7% hepatoprotective activity at 100 ${\mu}g/ml$. Moreover, we tested the effect of REE on carbon tetrachloride ($CCl_4$)-induced liver toxicity in rats. REE at dose of 50 and 100 mg/kg and silymarin at dose of 50 mg/kg were orally administered to $CCl_4$-treated rats. The results showed that REE and silymarin significantly reduced the elevated levels of serum enzyme markers induced by $CCl_4$. The biochemical data were supported by evaluation with liver histopathology. These findings suggest that REE, can significantly diminish hepatic damage by toxic agent such as tacrine or $CCl_4$.

• Biomolecules & Therapeutics
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• 제28권4호
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• pp.370-379
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• 2020

Econazole, a potent broad-spectrum antifungal agent and a Ca²⁺ channel antagonist, induces cytotoxicity in leukemia cells and is used for the treatment of skin infections. However, little is known about its cytotoxic effects on solid tumor cells. Here, we investigated the molecular mechanism underlying econazole-induced toxicity in vitro and evaluated its regulatory effect on the metastasis of gastric cancer cells. Using the gastric cancer cell lines AGS and SNU1 expressing wild-type p53 we demonstrated that econazole could significantly reduce cell viability and colony-forming (tumorigenesis) ability. Econazole induced G0/G1 phase arrest, promoted apoptosis, and effectively blocked proliferation- and survival-related signal transduction pathways in gastric cancer cells. In addition, econazole inhibited the secretion of matrix metalloproteinase- 2 (MMP-2) and MMP-9, which degrade the extracellular matrix and basement membrane. Econazole also effectively inhibited the metastasis of gastric cancer cells, as confirmed from cell invasion and wound healing assays. The protein level of p53 was significantly elevated after econazole treatment of AGS and SNU1 cells. However, apoptosis was blocked in econazole-treated cells exposed to a p53-specific small-interfering RNA to eliminate p53 expression. These results provide evidence that econazole could be repurposed to induce gastric cancer cell death and inhibit cancer invasion.

• Natural Product Sciences
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• 제12권4호
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• pp.247-253
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• 2006

The antitumor activity of crude saponin mixture obtained from Luffa tuberosa (Roxb.) (Fam; Cucurbitaceae) hairy roots (CSLT) in mice transplanted with Ehrlich ascites carcinoma (EAC) was investigated. The EAC-bearing mice receiving 150 and $300{\mu}g/kg$ body weight, (i.p) of CSLT have shown a dose dependent elevation in tumor-tree survival and a highest number of survivors were observed after administration of CSLT $(300{\mu}g/kg)$, which was considered as an optimum dose for its antineoplastic action. The mean survival time (MST) for this dose was approximately $47.1{\pm}0.74d$, when compared with $19.0{\pm}0.36d$ of untreated control. Administration of $300{\mu}g/kg$ CSLT resulted in 130% long-term increased survival time. The measurement of body weight, tumor volume, packed cell volume, viable and non-viable count indicated the efficacy of CSLT in tumor-bearing mice, there was a significant recovery in hematological profiles, and there was depletion in lipid peroxidation levels, and the antioxidant enzyme activities such as GSH, SOD and CAT were restored to near the normal levels. The CSLT was found to be devoid of conspicuous short-term toxicity in the mice when animals were intraperitoneally injected with 250, 500, 750 and $1000{\mu}g/kg$ bodyweight. The treated mice showed conspicuous toxic symptoms only at a dose of $1500{\mu}g/kg$. Mortality of the animals was monitored up to 14 d post drug treatment, $1/7^{th}$ of the $LD_{50}$ dose has been considered for the optimal antineoplastic activity.

• Molecular & Cellular Toxicology
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• 제1권4호
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• pp.268-274
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• 2005

Bromobenzene (BB) is well known hepatotoxicant. Also, BB is an industrial solvent that arouses toxicity predominantly in the liver where it causes centrilobular necrosis. BB is subjected to Cytochrome P450 mediated epoxidation followed by either conjugation with glutathione, enzymatic hydrolysis or further oxidation. In this study, we focused on BB-induced gene expression at non-hepatotoxic dose. Mice were exposed to two levels of BB, sampled at 24 h, and hepatic gene expression levels were determined to evaluate dose dependent changes. When examining the toxic dose of BB treated group in other previous studies, genes related to heat shock protein, oxidative stress, and drug metabolism are expressed. Compared to these results, our study, in which non-toxic dose of BB was administrated, showed similar patterns as the toxic conditions above. The purpose of the study was to select genes that showed changes in relation to the differing dose through confirmation of the difference within transcriptomic boundaries, but those that are not detected by the existing classic toxicology tools in non-hepatotoxic dose.

• 한국식품위생안전성학회지
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• 제27권1호
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• pp.1-17
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• 2012

T-2 toxin and HT-2 toxin, belong to type A trichothecences, are the most toxic mycotoxins among the trichothecene family. These mycotoxins are commonly found in cereals such as maize, wheat, barley, oats and rice, and their occurrence in food can be of concern. This review investigated the current trends of patents and researches on T-2 toxin and HT-2 toxin pertaining to natural occurrence, toxicity, metabolism, risk assessment, analytical and screening methods, and reduction/detoxification techniques. As compared with other $Fusarium$ mycotoxins, there are limited data for natural occurrence and risk assessment, and regulatory limit and official analytical methods on T-2 toxin and HT-2 toxin in domestic and foreign countries. In particular, selective deacetylation at the C3 and/or C4 positions of T-2 toxin by carboxyesterase present in foods was reported to cause the disappearance of T-2 and the extremely high HT-2 recoveries. Currently, regulatory limits for T-2 and HT-2 are under discussion in EU. For enforcement purposes it is essential to have available precise and reliable analytical methods applicable at the regulatory levels for the T-2 toxin and HT-2 toxin and relevant commodities. In addition, a further study on natural occurrence, risk assessment and reduction/detoxification techniques will be recommended.

• 한국식품위생안전성학회지
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• 제8권4호
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• pp.215-223
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• 1993

클로람페니콜은 광벙위 항생물질로서 수의축산분야에서 널리 사용되어 왔으나 이 제제의 잠재적인 독성과 축산식풍 중 잔류성 때문에 세계 각국에서는 식용동물에서의 사용을 금지하고 있다. 따라서 이 시험에서는 미생물학척 방법에 의한 우유 및 식육 중 미량의 잔류클로람페니콜을 측정할 수 있는 방법을 확립하고자 M. luteus ATCC 9341을 시험용 균주로 설정하여 다음과 같은 결과를 얻었다. 1. 검출감도를 향상시키고자 시험명판용 Mueller-Hinton 배지의 배지량을 최소화하고 ethylacetate로 추출 농축하여 ml당 0.15/lg의 옥시테트라사이클린을 첨가한 회석용 인산염 완충액 (pH 6.0) 으로 잔류물을 용해하여 사용하였을 때 가기장 좋은 검출강도를 나타내였다. 2. 시료별 최저검출농도는 원유가 0.025 ppm이었으며, 식육은 0.05 ppm까지 검출할 수 있었다. 3. 시료별 평균 회수율은 원유가 68.5%이었으며, 쇠고기, 돼지고기 및 닭고기는 각각 65.1%. 63.8% 및 59.4%이었다. 이들 시료의 회수율에 대한 변이계수 (CV)는 1.8~15.1%이었다.