• Title/Summary/Keyword: antitumor antibiotic

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Review of Pharmacological Effects of Scutellaria Baicalensis and Its Bioactive Compounds (황금(黃芩)과 구성 화합물의 약리작용에 대한 고찰)

  • Lee, Keon-Suk;Park, Min-Hee;Cheon, Mog-Eun;Hong, Jin-Woo;Cho, Su-In
    • Journal of Society of Preventive Korean Medicine
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    • v.15 no.2
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    • pp.69-99
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    • 2011
  • Objective : Scutellaria baicalensis is one of the most popular and multi-purpose herb in traditional medicine. It is also useful for its practicability to cultivate in Korea. The purpose of this study is to contribute to researches and applications of scutellaria baicalensis by analyzing and reviewing international researches on the compositions and the effects of scutellaria baicalensis. Methods : This study analyzed 146 articles from PubMed by searching with the keyword "Scutellaria baicalensis", "Huang quin", "Baical Skullcap", "Huang qin", "baical skullcap root", "ogon", "Hwanggeum" and "Hwangkeum", published within the last 10 years(from 2000 to 2009). We reviewed the 146 articles on Scutellaria baicalensis and its active constituents in terms of 'Active constituents', 'Experimental studies', 'Clinical studies', 'Drug interaction', 'Side Effects/Toxicity' and 'Pharmacokinetics'. Results : The active constituents of Scutellaria baicalensis are flavonoids such as baicalein, baicalin, wogonin and oroxylin-A. It is reported that scutellaria baicalensis and its active compounds have antiinflammatory activity, antitumor activity, antioxidant activity, antiviral and antibiotic activity, neuroprotective effects, hepatoprotective effects and cardiovascular effect. Conclusions : This study is aimed to summarize the results obtained within the last 10 years and to contribute to following researches and applications of Scutellaria baicalensis.

Single Dose Intravenous Toxicity Study of A New Anthracycline Anticancer Agent (DA-125) in Rats and Mice (새로운 안트라사이클린계 항암제 DA-125의 랫드 및 마우스에서의 정맥투여 급성 독성시험)

  • 신천철;송시환;서정은;강부현;김원배;한상섭
    • Biomolecules & Therapeutics
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    • v.8 no.1
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    • pp.84-92
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    • 2000
  • This Study was conducted to assess the single dose toxicity of DA-125, a new anthracycline anti-cancer agent, in rats and mice. The Drug was administered once intravenously to both sexes of rats and mice. Then followed a 14-day period of observation. The $LD_{50}$ Values (95% confidence limit) were estimated to be 60.9 mg/kg (57.5~64.3 mg/kg) for male rats and 60.2 mg/kg (56.2~64.5 mg/kg) for female rats, and 85.8 mg/kg (81.0~90.9 mg/kg) for male mice and 84.5 mg/kg (78.2~91.9 mg/kg) for female mice. Both sexes of rats and mice given the drug revealed the clinical sign of decreased locomotor activity, emaciation, hair loss, red-dish brown urine, salivation, and watery diarrhea. In addition, body weight from the next day to the 7th day tended to be decreased slightly in rats and mice treated with DA-125. Death occurred from the next day after administration to the 12th day. Macroscopically, congestion of gastrointestinal organ, lung, and adrenal glands were found in both sexes on the dead rats and mice. Histopathological examination of dead rats manifested atrophy of spleen, hypoplasia of bone marrow, hypcplasia and necrosis of lymphocyte in thymus, atrophy of villi in small intestine (duodenum, jejunum, and ileum), hyperplasia of granular epithelium in small intestine, degeneration of germinal epithelium in testis, defer oration of tubular epithelium in kidney, and vacuolation and myolysis of myocardium in heart. Histopathological examination of dead mice revealed hypoplasia of spleen and mesenteric lymph node, local necrosis of liver, atrophy of villi in small intestine, hyperplasia of glandular epithelium in small and large intestine, degeneration of tubular in kidney, degeneration of germinal cells in testis, and slight vacuolar degeneration of myocardium in heart.

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Toxicogenomics Study on TK6 Human Lymphoblast Cells Treated with Mitomycin C

  • Kim, Joo-Hwan;Koo, Ye-Mo;Lee, Woo-Sun;Suh, Soo-Kyung;Kang, Jin-Seok;Han, Eui-Sik;Kim, Seung-Hee;Park, Sue-N.
    • Molecular & Cellular Toxicology
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    • v.3 no.3
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    • pp.165-171
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    • 2007
  • Mitomycin C (MMC), an antitumor antibiotic isolated from Streptomyces caespitosus, is used in chemotherapy of gastric, bladder and colorectal cancer. MMC is activated in vivo to alkylate and crosslink DNA, via G-G interstrand bonds, thereby inhibiting DNA synthesis and transcription. This study investigates gene expression changes in response to MMC treatment in order to elucidate the mechanisms of MMC-induced toxicity. MMC was admistered with single dose (0.32 and 1.6 ${\mu}M$) to TK6 cells. Applied Biosystem's DNA chips were used for identifying the gene expression profile by MMC-induced toxicity. We identified up- or down-regulated 90 genes including cyclin M2, cyclin-dependent kinase inhibitor 1A (p21, cip1), programmed cell death 1, tumor necrosis factor (ligand) superfamily, member 9, et al. The regulated genes by MMC associated with the biological pathways apoptosis signaling pathway. Further characterization of these candidate markers related to the toxicity will be useful to understand the detailed mechanism of action of MMC.

Pretreatment Hepatoprotective Effect of Regular Aerobic Training Against Hepatic Toxicity Induced by Doxorubicin In Rats

  • Zolfagharzadeh, Fatemeh;Roshan, Valiollah Dabidi
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.2931-2936
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    • 2013
  • Background: Doxorubicin is an anthracycline antibiotic commonly used to treat a variety of cancers as a most effective antitumor. However, its clinical use is associated with the toxic effects in numerous healthy tissues. Here we investigated the pretreatment effect of regular aerobic exercise on oxidative stress in rats acutely exposed to DOX-induced hepatotoxicity. Materials and Methods: Forty-eight Wistar male rats were randomly divided into 2 groups: control and training. The training protocol included treadmill running between 25 to 54 min/day and 15 to 20m/min, 5 days/week for 6 weeks. At the end of the exercise training protocol, rats from the control and trained groups were again randomly separated into 3 subgroups: DOX10mg/kg, DOX20mg/kg and saline. All treatments were carried 24 h after the last exercise bout and animals were sacrificed 24 h after DOX and saline injections. Results: Administration of DOX (10 and 20 $mg.kg^{-1}$) resulted in imbalance in biomarkers related to oxidants and antioxidants in liver tissue, as compared to control groups. Six weeks of pretreatment training led to a significant increase in nitric oxide (NO), superoxide dismutase (SOD) and glutathione peroxidase (GPX) as compared to the control+DOX 10 mg/kg group. Training before DOX 20 mg/kg administration also led to a significant increase in NO and SOD, and a significant decrease in malondialdehyde (MDA). In addition, there was a significant difference between DOX 10 mg/kg and DOX 20 mg/kg treatments in MDA levels, only. Conclusions: The results of the present study indicate that pretreatment with aerobic exercise induces positive adaptations and has a potential protective effect against doxorubicin (DOX)-induced hepatotoxicity with doses of 10 and 20 mg.kg.

Evidence for a Common Molecular Basis for Sequence Recognition of N3-Guanine and N3-Adenine DNA Adducts Involving the Covalent Bonding Reaction of (+)-CC-1065

  • Park, Hyun-Ju
    • Archives of Pharmacal Research
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    • v.25 no.1
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    • pp.11-24
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    • 2002
  • The antitumor antibiotic (+)-CC-1065 can alkylate N3 of guanine in certain sequences. A previous high-field $^1H$ NMR study on the$(+)-CC-1065d[GCGCAATTG*CGC]_2$ adduct ($^*$ indicates the drug alkylation site) showed that drag modification on N3 of guanine results in protonation of the cross-strand cytosine [Park, H-J.; Hurley, L. H. J. Am. Chem. Soc.1997, 119,629]. In this contribution we describe a further analysis of the NMR data sets together with restrained molecular dynamics. This study provides not only a solution structure of the (+)-CC-1065(N3- guanine) DNA duplex adduct but also new insight into the molecular basis for the sequence- specific interaction between (+)-CC-1065 and N3-guanine in the DNA duplex. On the basis of NOESY data, we propose that the narrow minor groove at the 7T8T step and conformational kinks at the junctions of 16C17A and 18A19T are both related to DNA bending in the drugDNA adduct. Analysis of the one-dimensional $^1H$ NMR (in $H_2O$) data and rMD trajectories strongly suggests that hydrogen bonding linkages between the 8-OH group of the (+)-CC-1065 A-sub-unit and the 9G10C phosphate via a water molecule are present. All the phenomena observed here in the (+)-CC-1065(N3-guanine) adduct at 5'$-AATTG^*$are reminiscent of those obtained from the studies on the (+)-CC-1065(N3-adenine) adduct at $5'-AGTTA^*$, suggesting that (+)-CC-1065 takes advantage of the conformational flexibility of the 5'-TPu step to entrap the bent structure required for the covalent bonding reaction. This study reveals a common molecular basis for (+)-CC-1065 alkylation at both $5'-TTG^*$ and $5'-TTA^*$, which involves a trapping out of sequence-dependent DNA conformational flexibility as well as sequence-dependent general acid and general base catalysis by duplex DNA.

Residual Nitrite Content and Storage Properties of Pork Patties Added with Gardenia Fructus Extract (치자 추출물이 돈육 패티의 아질산염 잔류량과 저장성에 미치는 영향)

  • Jeon, Mi-Ran;Choi, Seong-Hee
    • Food Science of Animal Resources
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    • v.31 no.5
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    • pp.741-747
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    • 2011
  • Gardenia fructus has been reported to have bioactivities of lowering blood glucose, antitumor, antithrombosis, repression of neogenesis of blood vessels, antioxidant and antibiosis. However, the nitrite scavenging activity and utilization in meat products have not been studied. The substitution effect for nitrite and antibiosis of Gardenia fructus extract (GFE) were investigated by measuring the residual nitrite contents and storage properties of pork patties prepared with nitrite (50, 100, and 150 ppm) and GFE (0, 0.25, 0.5%). The CIE $L^*$ and CIE $a^*$ of pork patties decreased, while CIE $b^*$ increased as the addition of GFE increased. Patties with more GFE added tended to be lower in pH when stored at $4^{\circ}C$ for 6 wk, but TBARS and VBN were not affected by the addition of GFE. Residual nitrite in patties was lowered as the storage period was lengthened and as the GFE addition was increased. During the storage at $4^{\circ}C$, Escherichia coli was not detected, and the total aerobic bacterial count was decreased as more GFE was added, showing the substitution effect of GFE for nitrite in antimicrobial activity. In conclusion, the results show that GFE has nitrite scavenging and antibiotic activities in meat products, suggesting its potential use in healthy and sustainable foods with diverse biofunctionalities.