• Journal of Microbiology and Biotechnology
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• v.19 no.12
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• pp.1582-1589
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• 2009

Bacterial UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) catalyzes the transfer of enolpyruvate from phosphoenolpyruvate (PEP) to uridine diphospho-N-acetylglucosamine (UNAG), which is the first step of bacterial cell wall synthesis. We identified thimerosal, thiram, and ebselen as effective inhibitors of Haemophilus influenzae MurA by screening a chemical library that consisted of a wide range of bioactive compounds. When MurA was preincubated with these inhibitors, their 50% inhibitory concentrations ($IC_{50}s$) were found to range from 0.1 to $0.7\;{\mu}M$. In particular, thimerosal suppressed the growth of several different Gram-negative bacteria such as Escherichia coli, Pseudomonas aeruginosa, and Salmonella typhimurium at a concentration range of $1-2\;{\mu}g/ml$. These inhibitors covalently modified the cysteine residue near the active site of MurA. This modification changed the open conformation of MurA to a more closed configuration, which may have prevented the necessary conformational change from occurring during the enzyme reaction.

• Journal of Microbiology and Biotechnology
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• v.27 no.5
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• pp.878-895
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• 2017

Phosphorylation, a critical mechanism in biological systems, is estimated to be indispensable for about 30% of key biological activities, such as cell cycle progression, migration, and division. It is synergistically balanced by kinases and phosphatases, and any deviation from this balance leads to disease conditions. Pathway or biological activity-based abnormalities in phosphorylation and the type of involved phosphatase influence the outcome, and cause diverse diseases ranging from diabetes, rheumatoid arthritis, and numerous cancers. Protein tyrosine phosphatases (PTPs) are of prime importance in the process of dephosphorylation and catalyze several biological functions. Abnormal PTP activities are reported to result in several human diseases. Consequently, there is an increased demand for potential PTP inhibitory small molecules. Several strategies in structure-based drug designing techniques for potential inhibitory small molecules of PTPs have been explored along with traditional drug designing methods in order to overcome the hurdles in PTP inhibitor discovery. In this review, we discuss druggable PTPs and structure-based virtual screening efforts for successful PTP inhibitor design.

• YAKHAK HOEJI
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• v.53 no.1
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• pp.1-5
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• 2009

This study was performed to investigate the effects of acteoside and isoacteoside isolated from Clerodendron trichotomum Thunberg on melanin production in B16 melanoma cells. In DPPH radical scavenging activity, acteoside and isoacteoside had a potent anti-oxidant activity in a dose-dependent manner. Both acteoside and isoacteoside dose-dependently inhibited silica-induced ROS (reactive oxygen species) generation in B16 melanoma cells. They significantly inhibited tyrosinase activity and melanin production in MSH-stimulated B16 melanoma cells. The inhibitory effect of acteoside was more potent than that of isoacteosidee. In Western blot of tyrosinase, acteoside inhibited MSH-induced tyrosinase expression in B16 melanoma cells, which is related to the inhibitory action of acteoside on tyrosinase activity and melanin production. These results show that acteoside and isoacteoside from Clerodendron trichotomum Thunberg has a potent antioxidant activity and whitening activity. The underlying mechanism of acteoside on whitening activity may be due to the inhibition of tyrosinase activity and tyrosinase expression.

• Environmental Mutagens and Carcinogens
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• v.19 no.2
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• pp.112-115
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• 1999

The action mechanism of the inhibitory effect of some natural products on the DNA strand break and DNA damage was investigated in vitro and in vivo. In the E. coli chromosomal DNA strand break experiment in vitro, three mushroom water extracts were effective on the DNA strand breaking by daunorubicin. Phellinus linteus water extract inactivated daunorubicin, a DNA strand breaking agent, but did not protect DNA from daunorubicin-induced DNA strand breaking. Agaricus blazei water extract inhibited DNA strand breaking action of daunorubicin not only by daunorubicin inactivation, but also by DNA protection from daunorubicin. An inhibitory effect of Ganoderma lucidum water extract on the DNA strand break was based on the DNA protection rather than daunorubicin inactivation. In vivo mutagen assay system (SOS-chromotest), among three mushroom water extracts Phellinus linteus water extract was the most effective one on the inhibition of DNA damage by 4-NQO. The results suggest that all three mushroom water extracts inhibit daunorubicin-induced DNA damage and in vivo DNA damaging action of 4-NQO by the reaction of mutagen inactivation or DNA protection from the mutagen.

• Journal of the Korean Society of Food Science and Nutrition
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• v.27 no.3
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• pp.367-375
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• 1998

The physicochemical properties of the $\alpha$-amylase inhibitors from black bean and naked barley is Korea were investigated. Preincubation time for maximum inhibition was 30min and no activity change was seen after that time. Optimum pH of the $\alpha$-amylase inhibitors from the black bean and naked barley was pH 7.0 and the inhibitory activities were stable in the range of pH 6.0~8.0 in both phosphate and Tris-HCI buffer solutions. Both inhibitors maintained more than 50% of activity after incubation for 17 min at 7$0^{\circ}C$. The inhibitors from the black bean and naked barley maintained more than 50% of activities after treatment for 40 min and 30 min with pepsin, and 30 min and 50 min with trypsin, respectively. Both inhibitors functioned via a noncompetitive mechanism and were active against porcine pancreatic and human salivary $\alpha$-amylases. The activities of both inhibitors were linear for the ionic stength ranging from 0 to 0.9. The addition of 70 mM maltose to the reaction mixture caused a maximum increase in the relative activities of both inhibitors, but it did not affect the dissociation of the EI complex. The activities of both inhibitors were significantly enhanced by adding 1mM of K+ or Mg2+.

• International Journal of Oral Biology
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• v.39 no.1
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• pp.35-40
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• 2014

Halitosis is caused by consumption of certain foods or drinks and production of volatile sulfur compounds (VSCs) by periodontopathogens. VSCs-related halitosis is not easily removed using mechanical or chemical therapies such as dental floss, plaque control and mouth rinse. Lactobacillus are known to be probiotics and stimulate immune systems of human. Furthermore, L. casei ATCC 334 and L. rhamnosus GG have an effect on protection of dental caries in vitro studies. The aim of this study was to investigate effect of Lactobacillus on halitosis by Fusobacterium nucleatum- and Porphyromonas gingivalis-producing VSCs and to analyze inhibitory mechanism. The periodontopathogens were cultivated in the presence or the absence Lactobacillus, and the level of VSCs was measured by gas chromatograph. For analysis of inhibitory mechanisms, the susceptibility assay of the spent culture medium of Lactobacillus against F. nucleatum and P. gingivalis was investigated. Also, the spent culture medium of Lactobacillus and periodontopathogens were mixed, and the emission of VSCs from the spent culture medium was measured by gas chromatograph. L. casei and L. rhamnosus significantly reduced production of VSCs. L. casei and L. rhamnosus exhibited strong antibacterial activity against F. nucleatum and P. gingivalis. The spent culture medium of L. casei inhibited to emit gaseous hydrogen sulfide, methyl mercaptan and dimethyl sulfide from the spent culture medium of periodontopathogens. However, the spent medium of L. rhamnosus repressed only dimethyl sulfide. L. casei ATCC 334 may improve halitosis by growth inhibition of periodontopathogens and reduction of VSCs emission.

• Toxicological Research
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• v.11 no.2
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• pp.267-271
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• 1995

A single large dose of ethanol as well as chronic ethanol consumption produces alcoholic fatty liver in human and experimental animals. We examined the effects of YH439, a potential hepatoprotective agent, on alcoholic fatty liver generation in adult female rats. In rats treated with YH439 (250 mg/kg, po) 4 hr prior to a single dose of ethanol (6 g/kg, po), a significant decrease in hepatic triglyceride accumulation was observed. YH439 also has an inhibitory effect on hepatic triglyceride and cholesterol accumulation induced by repeated ethanol treatments for one week. Because it has been known that induction of alcoholic fatty liver is associated with lipid peroxidation and/or hepatic glutathione depression, the effect of YH439 on these parameters was determined in the livers of rats treated with ethanol. Coadministration with YH439 inhibited MDA formation and gIutathione depression induced by acute or repeated ethanol administration. In order to determine the effect of YH439 on ethanol metabolism in vivo, disappearance of ethanol from blood was measured. In rats treated with a single dose of ethanol (6 g/kg, po), the ethanol concentration in blood reached a peak approximately 120 min following the treatment which declined linearly for 18 hrs. YH439 had no effect on the decline of blood ethanol concentration regardless of the dose of ethanol given to rats. These results in this study suggest that YH439 has an inhibitory effect on fatty liver generation induced by acute or repeated ethanol consumption through a mechanism not directly related to the rate of ethanol metabolism in vivo.

• Archives of Pharmacal Research
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• v.24 no.5
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• pp.441-445
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• 2001

Resveratrol, a trihydroxystilbene found in grapes and several plants, has been shown to be active in inhibiting multistage carcinogenic process. Using resveratrol as the prototype, we synthesized several analogs and evaluated their growth inhibitory effect using cultured human cancer cells. In the present report we show that one of the resveratrol analogs, 3, 5,2',4'-tetramethoxy-trans-stilbene, potentiated the inhibition of cancer cell growth. Prompted by the strong growth Inhibitory activity of the compound ($IC_{50}$; $0.8{\mu}$ g/ml) compared to resveratrol ($IC_{50}$; $18{\mu}$ug/ml) in cultured human colon cancer cells (Col2), we performed an action mechanism study using the compound. The compound induced the accumulation of cellular DNA contents in the sub-CO phase DNA contents of the cell cycle by in a time-dependent manner. The morphological changes were also consistent with an apoptotic process. This result indicated that the compound induced apoptosis of cancer cells, and may be a candidate for use in the development of potential cancer chemotherapeutic or cancer chemopreventive agents.

• Natural Product Sciences
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• v.15 no.2
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• pp.83-89
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• 2009

Polygoni multiflori Ramulus (PM), the stem of Polygonum multiflorum Thunb. has been widely used as a traditional medicine for the treatment of lots of diseases. In macrophages, nitric oxide is released as an inflammatory mediator and has been proposed to be an important modulator of many pathophysiological conditions in inflammation. In the present study, it was investigated that the inhibitory effects on NO and proinflammatory cytokines such as tumor necrosis factor alpha (TNF-${\alpha}$), interleukin-6 (IL-6) and the mechanism of down-regulation of immune response by 85% methanol extracts of PM in mouse (C57BL/6) peritoneal macrophages. Extracts of PM (0.1, 1 mg/ml) suppressed NO production and showed inhibition of proinflammatory cytokines like TNF-${\alpha}$, IL-6 and it attenuated iNOS and COX-2 expression via down-regulation of NF-${\kappa}$B activation. The present results indicate that the 85% methanol extracts of PM has an inhibitory effect on the production of NO through down-regulation of iNOS expression in LPS stimulated mouse peritoneal macrophages and therefore may be beneficial in diseases which related to macrophage-mediated inflammatory disorders.

• Biomolecules & Therapeutics
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• v.14 no.3
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• pp.125-131
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• 2006

The inhibitory effects of (-)-epigallocatechin gallate (EGCG), a major compound of green tea, on the development of locomotor sensitization, conditioned place preference (CPP) and dopamine receptor supersensitivity induced by the repeated administration of morphine were investigated in mice. A single administration of morphine produces hyperlocomotion. The repeated administration of morphine develops sensitization, a progressive enhancement of locomotion, which is used as a model for studying the craving and drug-seeking behaviors characterizing addiction, and CPP, which is used as a model for studying drug reinforcement, respectively. EGCG inhibited morphine-induced hyperlocomotion, sensitization and CPP. In addition, EGCG inhibited the development of postsynaptic dopamine receptors supersensitivity, which may be an underlying common mechanism that mediates the morphine-induced dopaminergic behaviors such as sensitization and CPP. Apomorphine (a dopamine agonist)-induced climbing behaviors also were inhibited by a single direct administration of EGCG These results provide evidence that EGCG has anti-dopaminergic activity, as inhibiting the development of dopamine receptor supersensitivity and apomorphine-induced climbing behaviors. Therefore, it is suggested that green tea may be useful for the prevention and therapy of these adverse actions of morphine.