• Title/Summary/Keyword: Synergistic inhibition

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Antifungal Activity of Salvia miltiorrhiza Against Candida albicans Is Associated with the Alteration of Membrane Permeability and (1,3)-β-D-Glucan Synthase Activity

  • Lee, Heung-Shick;Kim, Younhee
    • Journal of Microbiology and Biotechnology
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    • v.26 no.3
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    • pp.610-617
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    • 2016
  • Candidiasis has posed a serious health risk to immunocompromised patients owing to the increase in resistant yeasts, and Candida albicans is the prominent pathogen of fungal infections. Therefore, there is a critical need for the discovery and characterization of novel antifungals to treat infections caused by C. albicans. In the present study, we report on the antifungal activity of the ethanol extract from Salvia miltiorrhiza against C. albicans and the possible mode of action against C. albicans. The increase in the membrane permeability was evidenced by changes in diphenylhexatriene binding and release of both 260-nm-absorbing intracellular materials and protein. In addition, inhibition of cell wall synthesis was demonstrated by the enhanced minimal inhibitory concentration in the presence of sorbitol and reduced (1,3)-β-D-glucan synthase activity. The above evidence supports the notion that S. miltiorrhiza has antifungal activity against C. albicans by the synergistic activity of targeting the cell membrane and cell wall. These findings indicate that S. miltiorrhiza displays effective activity against C. albicans in vitro and merits further investigation to treat C. albicans-associated infections.

Metformin Synergistically Potentiates the Antitumor Effects of Imatinib in Colorectal Cancer Cells

  • Lee, Jaeryun;Park, Deokbae;Lee, Youngki
    • Development and Reproduction
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    • v.21 no.2
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    • pp.139-150
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    • 2017
  • Metformin is the most commonly prescribed anti-diabetic drug with relatively minor side effect. Substantial evidence has suggested that metformin is associated with decreased cancer risk and anticancer activity against diverse cancer cells. The tyrosine kinase inhibitor imatinib has shown powerful activity for treatment of chronic myeloid leukemia and also induces growth arrest and apoptosis in colorectal cancer cells. In this study, we tested the combination of imatinib and metformin against HCT15 colorectal cancer cells for effects on cell viability, cell cycle and autophagy. Our data show that metformin synergistically enhances the imatinib cytotoxicity in HCT15 cells as indicated by combination and drug reduction indices. We also demonstrate that the combination causes synergistic down-regulation of pERK, cell cycle arrest in S and $G_2/M$ phases via reduction of cyclin B1 level. Moreover, the combination resulted in autophagy induction as revealed by increased acidic vesicular organelles and cleaved form of LC3-II. Inhibition of autophagic process by chloroquine led to decreased cell viability, suggesting that induction of autophagy seems to play a cell protective role that may act against anticancer effects. In conclusion, our present data suggest that metformin in combination with imatinib might be a promising therapeutic option in colorectal cancer.

Hepatoprotective Activity of Chungpesagan-tang is Related to the Inhibition of ${\beta}-Glucuronidase$

  • Kim, Jae-Kwan;Bae, Hyung-Sup;Kim, Young-Suk;Cho, Ki-Ho;Lee, Kyung-Sup;Lee, Hae-Ung;Kim, Dong-Hyun
    • Natural Product Sciences
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    • v.7 no.3
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    • pp.63-67
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    • 2001
  • ${\beta}-Glucuronidase-inhibitory$ and hepatoprotective effects of Chungpesagan-tang, which has been used for liver diseases and stroke, on $CCl_4-induced$ hepatotoxicity of rats was investigated. Chungpesagan-tang potently inhibited ${\beta}-glucuronidases$. Serum AST, ALT and LDH levels of the $CCl_4$ group orally treated with Chungpesagan-tang (100 mg/kg) were lowered to 47, 28 and 58% of the $CCl_4-treated$ group, respectively. Among the ingredients of Chungpesagan-tang, Puerariae Radix, Scutellariae Radix and Rhei Rhizoma potently inhibited the ${\beta}-glucuronidase$ and protected $CCl_4-induced$ liver injury. The hepatoprotective activity of Puerariae Radix was affected by ingredients of Chungpesagan-tang: Scutellariae Radix had the synergistic activity, but Angelicae Tenussimae Radix exhibited the antagonistic activity. These results suggest that the ${\beta}-glucuronidase$ inhibitor of herbal medicines may protect $CCl_4-induced$ liver injury and puerarin should be a natural prodrug for the hepatoprotective effect.

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Toxicity on Laboratory Grown Plankton by the Oils Released from the Hebei Spirit Spill with Emphasis on a Dispersant Used in the Aftermath

  • Choi, Keun-Hyung;Lim, Sang-Min;Lee, Sung-Mi;Park, Gyung-Soo
    • Journal of Environmental Science International
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    • v.19 no.4
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    • pp.389-397
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    • 2010
  • The in vitro toxicities of three crude oils of the Hebei Spirit were examined on laboratory grown plankton, with a focus on the effects of a dispersant. The specific growth rate of phytoplankton and the mortalities of two zooplankton were measured in response to exposure to various concentrations of water accommodated oil, dispersant or both. The effects of the oils varied among the plankton, but were generally low within the range of the oil concentrations used, with little difference in toxicity among the three oils. Such low toxicity appeared to be associated with weathering of the crude oils. Exposure to the dispersant, however, dramatically increased the mortality of zooplankton, with complete inhibition of phytoplankton growth. No synergistic toxic effect was observed with the crude oil and dispersant combination. A better decision making process could be crafted for future application of dispersant in the event of an oil spill in Korean waters to better protect the marine plankton community from the excessive use of dispersant.

Antimicrobial Effect of Pulsatilla Koreana Extracts on Food-Borne Pathogens (백두옹 추출물의 식중독성 미생물에 대한 항균효과)

  • 배지현
    • Journal of Nutrition and Health
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    • v.37 no.8
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    • pp.655-661
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    • 2004
  • This study was performed to investigate the antimicrobial effect of the Pulsatilla koreana extracts against food-borne pathogens. First, the Pulsatilla koreana was extracted with methanol at room temperatures, and fractionation of the methanol extracts from Pulsatilla koreana was carried out by using petroleum ether, chloroform, and ethyl acetate, and methanol respectively. The antimicrobial activity of the Pulsatilla koreana extracts was determined using a paper disc method against food-borne pathogens and food spoilage bacteria. The ethyl acetate extracts of Pulsatilla koreana showed the highest antimicrobial activity against Staphylococcus aureus, Salmonella enteritidis and Shigella dysenteriae. The Staphylococcus aureus and Shigella dysenteriae were inhibited by petroleum ether and chloroform extracts of Pulsatilla koreana as well as ethyl acetate extracts of Pulsatilla koreana. The synergistic effect has been found in combined extracts of Pulsatilla koreana and Portulaca oleracea as compared to each extracts alone. Finally, the growth inhibition curve was determined using ethyl acetate extracts of Pulsatilla koreana against Staphylococcus aureus and Shigella dysenteriae. The ethyl acetate extract of Pulsatilla koreana showed strong antimicrobial activity against Staphylococcus aureus at the concentration of 2,000 ppm. The 2,000 ppm of ethyl acetate extract from Pulsatilla koreana retarded the growth of S. aureus more than 12 hours and Shigella dysenteriae up to 9 hours.

Hepatoprotective and free radical scavenging activities of Lagerstroemia speciosa Linn. leaf extract

  • Thambi, Priya;Sabu, Mandumpal Chacko;Chungath, Jolly
    • Advances in Traditional Medicine
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    • v.9 no.3
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    • pp.225-231
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    • 2009
  • The present study deals with the amelioration by Lagerstroemia speciosa Linn. leaf extract against hepatotoxicity induced by carbon tetrachloride ($CCl_4$), which was evaluated in terms of serum marker enzymes like serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, alkaline phosphatase, serum total bilirubin, total protein levels along with concomitant hepatic and antioxidants like superoxide dismutase, catalase, glutathione, glutathione peroxidase and lipid peroxidation enzymes were monitored. These biochemical parameters altered by the single dose level of $CCl_4$ (0.75 ml/kg body weight, i.p). Pre treatment with L. speciosa prior to the administration of $CCl_4$, at the doses of 50 and 250 mg/kg. body weight/day, p.o. for 7 days, significantly restored all the serum and liver tissue parameters near to the normal levels, respectively. Silymarin was used as a reference standard, prior to the administration of $CCl_4$ to rats. These findings indicate the protective potential of L. speciosa against hepato toxicity which possibly involve mechanism related to its ability of selective inhibitors of (reactive oxygen species like antioxidants brought about significant inhibition of TBARS suggesting possible involvement of $O_2{\cdot}-$, $HO_2{\cdot}$, and ${\cdot}OH$. In conclusion, the amelioration may be attributed to the synergistic effects of its constituents rather than to any single factor as the leaves are rich in tannins, sterols, flavonoids, saponins etc.

Metabolism of Glycyrrhizin in Polyprescriptions Containing Glycyrrhizae Radix by Human Intestinal Bacteria and Their Inhibitory Effects on Some Enzymes (감초 함유 처방의 글리치리진 대사와 몇가지 효소저해효과)

  • Kim, Nam-Jae;Bae, Eun-Ah;Han, Myung-Joo;Kim, Dong-Hyun
    • Korean Journal of Pharmacognosy
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    • v.30 no.3
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    • pp.269-274
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    • 1999
  • To analyze scientifically the prescription principle of polyprescriptions (Gamchotang, Daewhanggamchotang, Jakyakgamchotang, Gamchogungangtang and Gilkyungtang) containing Glycyrrhizae Radix, the transforming rate of glycyrrhizin in these polyprescriptions to 18 ${\beta}-glycyrrhetinic$ acid and their inhibitory effect on ${\beta}-glucuronidase$, hyaluronidase, phosphodiesterase and trypsin were investigated. When Glycyrrhizae Radix containing polyprescriptions were extracted with water, the contents of glycyrrhizin in water extract of Glycyrrhizae Radix with Rhei Rhizoma or with Zingiberis Rhizoma were higher than that of Glycyrrhizae Radix only, but that in water extract of Glycyrrhizae Radix with Platicodi Radix was lower than that of Glycyrrhizae Radix only. By human intestinal bacteria, glycyrrhizin was metabolized to 18 ${\beta}-glycyrrhetinic$ acid. These metabolism of glycyrrhizin in polyprescriptions containing Glycyrrhizae Radix was inhibited by Rhei Rhizoma, Paeoniae Radix and Platicodi Radix, but was not affected by Zingiberis Rhizoma. The inhibitory activity of Glycyrrhizae Radix on hyaluronidase and ${\beta}-glucuronidase$, was synergistic with Rhei Rhizoma or Zingiberis Rhizoma, but was antagonistic by Platicodi Radix.

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Development of novel method for evaluation of antitumor effect of anticancer drugs on hepatocellular carcinoma induced using 3'-methyl-4-diethylaminoazobenzene in Sprague-Dawley rat (3'-methyl-4-diethylaminoazobenzene으로 유발된 랫트 hepatocellula carcinoma 모델에서 항암제의 항암효과에 대한 평가기법 개발)

  • Kim, Gon-sup;Kim, Jong-shu
    • Korean Journal of Veterinary Research
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    • v.37 no.3
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    • pp.509-523
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    • 1997
  • This study was carried out for investigating antitumor effects of 5-fluorouracil(5-FU), methotrexate(MTX) and retinoic acid(RA) on hepatocellular carcinoma induced in Sprague-Dawley rat. Antitumor effects were examined a flow cytometric DNA distributions by flow cytometry and stuied ATP/Pi using nuclear magnetic resorance, and the enzymatic activity of thymidylate synthetase and dihydrofolate reductase as well as contents of total collagen and sialic acid were measured with spectrophotometer. In this study, S phase fraction, contents of sialic acid and total collagen were decreased in the induced hepatocellular carcinoma treated with 5-FU and MTX, and synergistic effects of anticancer drugs were exhibited in the hepatocellular carcinoma treated with 5-FU and MTX simultaneously, and the inhibition of thymidylate synthetic and dihydrofolate reductase activity were shown in the hepatocellular carcinoma treated with 5-FU, MTX, and 5-FU and MTX simultaneously. On the other hand, the ratio of ATP/Pi were increased in all groups except group treated with RA. The experimental results suggest that above method may be valuable for evaluating antitumor effect of anticancer drugs.

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Effects of the Saponin of Polygalae Radix on the Renal Function and CNS-Depression (원지(遠志) Saponin의 이뇨효과(利尿效果) 및 중추억제작용(中樞抑制作用)에 관한 연구(硏究))

  • Park, Dai-Kyu;Lee, Wan-Ha
    • Korean Journal of Pharmacognosy
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    • v.14 no.4
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    • pp.178-192
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    • 1983
  • Polygalae Radix was used as diuretics, analgesics and expertorants in oriental medicine. The root of Polygala tenuifolia Willd. (Polygalaceae) is comprised saponin (Onjisaponin A,B,C,D,E,F and G) polygalitol, onsitin and sugars. The pharmacological action of crude Polygala-saponin (PS) obtained from the roots are studied. The following results were obtained; 1) The median lethal dose $(LD_{50})$ of PS in mice is presented 71.1mg/kg s.c. and 694. 5mg/kg p.o.. 2) PS demonstrated diuretic action of relatively long acting duration in mice. 3) The diuretic mechanism of PS was found due to inhibitory effect of renal tubular reabsorption of electrolytes and glomerular vascular dilatation. 4) The group, administered simultaneously PS and cefadroxil monobydrate was significantly increased with PS alone group on diuretic action. Synergistic effect cefadroxil monohydrate on the diuretic action of PS seems due to competitive inhibition of plasma protein binding with PS. 5) PS demonstrated analgesic action by the acetic acid stimulating method and Randall-Selitto test in mice. 6) PS presented antipyretic action against febrile treated with the typhoid vaccine. 7) PS was significantly prolonged against the hypnotic duration of pentobarbital in mice. 8) Onset time convulsion and death induced by picrotoxin and strychnine in mice were not delayed. According to the above results, the PS was identified as a pharmacological active component obtained from roots of Polygala tenuifolia Willd.

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Pharmacological Test for a Combined Products Containing Sucralfate as a Suspended Antiulcer drug.

  • Kang, Seog-Youn;Kim, Seung-Hee;Jung, Sook-Young;Lee, Song-Deuk
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1995.04a
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    • pp.93-93
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    • 1995
  • The three combined products were prepared as suspended solutions composed of various ratio of Sucralfate, Hydrotalcite and Neusilin, into which 30% ethanol extracts of Machili cortex, and of Atractylodis rhizoma were added. The efficacy for these products was examined in vivo using a pyrous ligation method in rats. The influence of these products on the intestinal motility was also examined in mice. In all experimental setting, the antisecretory effect of the combined treatment was more pronounced than that of each drug alone. The combined treatment consisted of Sucralfate, Hydrotalcite, Neusilin ratios of 2:2:1 produced the highest inhibitory effect for the gastric secretion. The intestinal motility was not influenced significantly by the treatment of all experimental setting. The above results revealed that the therapeutic dose of Sucralfate, Hydrotalcite, Neusilin given in combination showed a synergistic effect for the inhibition of gastric secretion and little side effect on the intestinal motility. Therefore, the combined product with Sucralfate, Hydrotalcite, Neusilin ratio of 2:2:1 is recommended for the useful drug to heal the gastrointestinal diseases with no side effect on the intestinal motility.

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