Red wines and flavonoids diminish Staphylococcus aureus virulence with anti-biofilm and anti-hemolytic activities.

Cho, Hyun Seob,Lee, Jin-Hyung,Cho, Moo Hwan,Lee, Jintae Harwood Academic Publishers 2015 Biofouling Vol.31 No.1

<P>The emergence of antibiotic resistant Staphylococcus aureus presents a worldwide problem that requires non-antibiotic strategies. This study investigated the anti-biofilm and anti-hemolytic activities of four red wines and two white wines against three S. aureus strains. All red wines at 0.5-2% significantly inhibited S. aureus biofilm formation and hemolysis by S. aureus, whereas the two white wines had no effect. Furthermore, at these concentrations, red wines did not affect bacterial growth. Analyses of hemolysis and active component identification in red wines revealed that the anti-biofilm compounds and anti-hemolytic compounds largely responsible were tannic acid, trans-resveratrol, and several flavonoids. In addition, red wines attenuated S. aureus virulence in vivo in the nematode Caenorhabditis elegans, which is killed by S. aureus. These findings show that red wines and their compounds warrant further attention in antivirulence strategies against persistent S. aureus infection.</P>

Preventive effect of 20(S)-ginsenoside Rg3 against lipopolysaccharide-induced hepatic and renal injury in rats

Kang, Ki Sung,Kim, Hyun Young,Yamabe, Noriko,Park, Jeong Hill,Yokozawa, Takako Harwood Academic 2007 Free radical research Vol.41 No.10

<P> The preventive effect of 20(S)-ginsenoside Rg3 (20(S)-Rg3) on lipopolysaccharide (LPS)-induced oxidative tissue injury in rats was investigated in this study. The elevated serum nitrite/nitrate, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and creatinine levels in LPS-treated control rats were significantly decreased following 15 consecutive days of 20(S)-Rg3 administration. In addition, thiobarbituric acid-reactive substance levels in the serum, liver and kidney were dose-dependently lower in 20(S)-Rg3-treated groups than in the LPS-treated control group. The nuclear factor-&kgr;B (NF-&kgr;B), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1) protein expressions in the liver and kidney were significantly increased by LPS treatment. However, the 20(S)-Rg3 administrations significantly decreased these protein expressions except for HO-1 in the liver. On the other hand, in the kidney, oral administration of 20(S)-Rg3 showed a tendency to reduce NF-&kgr;B and iNOS protein expressions and also significantly reduced the elevated COX-2 and HO-1 protein expressions at a dose of 10 mg/kg body weight/day. All these results suggest the preventive effect of 20(S)-Rg3 against LPS-induced acute oxidative damage in the liver and kidney and the preventive effect of 20(S)-Rg3 administration against LPS toxicity was thought to be more predominant in the liver than kidney.</P>

8-Oxo-7,8-dihydroguanosine triphosphate(8-oxoGTP) down-regulates respiratory burst of neutrophils by antagonizing GTP toward Rac, a small GTP binding protein

Kim, Hee Joon,Yoon, Sun-Hee,Ryu, Hyun-Ok,Yoon, Byung-Hak,Choi, Seongwon,Ye, Sang-Kyu,Chung, Myung-Hee Harwood Academic 2007 Free radical research Vol.41 No.6

<P> 8-Oxo-7,8-dihydroguanosine triphosphate (8-oxoGTP) has been regarded simply as a oxidative mutagenic byproduct. The results obtained in this study imply that it may act as a down-regulator of respiratory burst of neutrophils. Human neutrophils treated with PMA produced superoxides and at the same time, the cytosol of these cells was intensely immunostained by 8-oxo-7,8-dihydroguanosine(8-oxoG) antibody, indicating that 8-oxoG-containing chemical species including 8-oxoGTP are produced. Human neutrophil lysates treated with PMA also produced superoxides, which was stimulated by GTP&ggr;S but inhibited by 8-oxoGTP&ggr;S. Moreover, 8-oxoGTP&ggr;S suppressed the stimulatory action of GTP&ggr;S. Likewise, GTP&ggr;S stimulated Rac activity in neutrophil lysates but 8-oxoGTP&ggr;S and GDP inhibited it. The inhibitory effect of GDP was one tenth that of 8-oxoGTP&ggr;S. Here again, 8-oxoGTP&ggr;S also suppressed the stimulatory action of GTP&ggr;S on Rac activity. These results imply the possibility that 8-oxoGTP is formed during respiratory burst of neutrophils and limits neutrophil production of superoxides by antagonizing GTP toward Rac.</P>

Hydrogen peroxide induces the death of astrocytes through the down-regulation of the constitutive nuclear factor-kappaB activity

Choi, Jung-Jin,Choi, JiWoong,Kang, Chi-Dug,Chen, Xia,Wu, Chun-Fu,Ko, Kwang Ho,Kim, Won-Ki Harwood Academic 2007 Free radical research Vol.41 No.5

<P> Nuclear factor-kappaB (NF-&kgr;B) has a dual role in the promotion or attenuation of cell death. Here, we demonstrated the role of NF-&kgr;B in the H2O2-induced death of astrocytes. H2O2 evoked the release of lactate dehydrogenase (LDH), a marker of cell death, and concomitantly decreased the DNA binding and transcriptional activity of NF-&kgr;B in cultured astrocytes. H2O2-induced astrocyte death was markedly increased by the co-treatment with pyrrolidinedithiocarbamate, an NF-&kgr;B inhibitor. Moreover, the elevation of constitutive NF-&kgr;B activity by overexpressing p65 NF-&kgr;B subunit attenuated H2O2 toxicity, whereas NF-&kgr;B inhibition by overexpressing I&kgr;B potentiated the toxicity. NF-&kgr;B activity and H2O2 cytotoxicity was further found to be dependent on cell density. Compared with astrocytes in low cell density, those in high cell density exhibited a higher constitutive NF-&kgr;B activity and a stronger resistance to H2O2 cytotoxicity. These results indicate that the constitutive activity of NF-&kgr;B in astrocytes is required for their survival under oxidative stress such as H2O2.</P>

[6]-Gingerol prevents UVB-induced ROS production and COX-2 expression in vitro and in vivo

Kim, Jin-Kyoung,Kim, Younghwa,Na, Kwang-Min,Surh, Young-Joon,Kim, Tae-Yoon Harwood Academic 2007 Free radical research Vol.41 No.5

<P> [6]-Gingerol, a naturally occurring plant phenol, is one of the major components of fresh ginger (Zingiber officinale Roscoe, Zingiberaceae) and has diverse pharmacologic effects. Here, we describe its novel anti-oxidant, anti-apoptotic, and anti-inflammatory activities in vitro and in vivo. In vitro, pre-treatment with [6]-gingerol reduced UVB-induced intracellular reactive oxygen species levels, activation of caspase-3, -8, -9, and Fas expression. It also reduced UVB-induced expression and transactivation of COX-2. Translocation of NF-&kgr;B from cytosol to nucleus in HaCaT cells was inhibited by [6]-gingerol via suppression of I&kgr;Bα phosphorylation (ser-32). Examination by EMSAs and immunohistochemistry showed that topical application of [6]-gingerol (30 μM) prior to UVB irradiation (5 kJ/m2) of hairless mice, also inhibited the induction of COX-2 mRNA and protein, as well as NF-&kgr;B translocation. These results suggest that [6]-gingerol could be an effective therapeutic agent providing protection against UVB-induced skin disorders.</P>

Prevention of Pseudomonas aeruginosa adhesion by electric currents.

Shim, Soojin,Hong, Seok Hoon,Tak, Yongsug,Yoon, Jeyong Harwood Academic Publishers 2011 Biofouling Vol.27 No.2

<P>The process of controlling bacterial adhesion using an electric current deserves attention because of its ease of automation and environmentally friendly nature. This study investigated the role of electric currents (negative, positive, alternating) for preventing adhesion of Pseudomonas aeruginosa and achieving bacterial inactivation. Indium tin oxide (ITO) film was used as a working electrode to observe adhesion and inactivation under electric polarization. Electric current types were classified into negative, positive, and alternating current. The working electrode acted as a cathode or anode by applying a negative or positive current, and an alternating current indicates that the negative current was combined sequentially with the positive current. The numbers of adhered cells were compared under a flow condition, and the in situ behavior of the bacterial cells and the extent of their inactivation were also investigated using time-lapse recording and live/dead staining, respectively. The application of a negative current prevented bacterial adhesion significantly (??1% at 15.0 관A cm(-2)). The positive current did not significantly inhibit adhesion (<20% at 15.0 관A cm(-2)), compared to the nonpolarized case. The alternating current had a similar effect as the negative current on preventing bacterial adhesion, but it also exhibited bactericidal effects, making it the most suitable method for bacterial adhesion control.</P>

Enhancement of fluoride activity against Streptococcus mutans biofilms by a substance separated from Polygonum cuspidatum.

Pandit, Santosh,Kim, Hye-Jin,Park, Sung-Hee,Jeon, Jae-Gyu Harwood Academic Publishers 2012 BIOFOULING -CHUR- Vol.28 No.3

<P>Polygonum cuspidatum is a plant with spreading rhizomes and numerous reddish-brown stems that has been used in Korean folk medicine to improve oral hygiene. Nevertheless, there are no reports related to its possible effect on the virulence of dental biofilms. In this study, the ability of a fraction (F1) separated from P. cuspidatum, alone or in combination with fluoride, to disrupt virulence factors and the composition of Streptococcus mutans biofilms was examined. F1 was mainly composed of resveratrol, emodin and physcion (approximately 16.2%, 18.9% and 2.07% of the weight of F1, respectively). F1 showed inhibitory effects on acid production and F-ATPase activity of S. mutans in biofilms, and could enhance fluoride activity against acid production and acid tolerance of S. mutans in biofilms. When S. mutans biofilms were briefly treated with F1 (10 min, a total of five times), the biomass accumulation, water-insoluble polysaccharides and intracellular iodophilic polysaccharides were reduced. Furthermore, the fluoride activity against biomass accumulation was enhanced by F1. These results suggest that F1 may be useful in the control of dental biofilms and in improving the cariostatic properties of fluoride without increasing its exposure.</P>

Apurinic/apyrimidinic endonuclease 1 on aging-associated deteriorations in rat kidneys

Chang, In Youb,Lee, Jung-Hee,Kim, Jin Nam,Lee, Kun Ho,Park, Kyung Soo,Yoon, Sang Pil Harwood Academic 2015 Free radical research Vol.49 No.1

<P>We have reported a possible involvement of apurinic/apyrimidinic endonuclease 1 (APE1), one of the DNA repair pathways, in various nephropathy models and found that there is a close connection between APE1 and p53-dependent apoptosis. Therefore, we investigated the changes of APE in aging rat kidney since aging is the consequence of increased susceptibility to apoptosis and impaired repair. Characteristics of chronological aging were compared among 6-, 24- and 28-month-old male Sprague-Dawley rats. Serum blood urea nitrogen and creatinine were measured for renal function. Western blot assay was compared for p53, bax, cleaved caspase 3, rH2AX, and APE1. Immunohistochemical staining of 8-hydroxy-2’-deoxyguanosine (8-OHdG) and APE1 was performed. Cellular senescence was checked by beta-galactosidase staining. Compared with young rats, aged rats showed significant increase in creatinine level with cellular senescence in the proximal convoluted tubules confirmed by beta-galactosidase staining. All the checked variables were significantly increased with aging: 1) increased p53, bax, and caspase 3 may activate the apoptotic pathway, 2) increased rH2AX and 8-OHdG immunolocalization in the proximal convoluted tubules might mean augmented DNA damage, and 3) increased APE1 might be caused by the immunoreactivity in the distal convoluted tubules while decreased in the proximal convoluted tubules. These results suggested that APE1 might have little protective effects on p53-dependent apoptosis irrespective of DNA repair activities in aged renal proximal tubules. Therefore, researchers should use older animals than 24-month-old rats in future studies for investigating the relationship between the apoptosis and DNA repair in the aging kidneys.</P>

Antioxidative effects of ethyl 2-(3-(benzo[d]thiazol-2-yl)ureido)acetate against amyloid β-induced oxidative cell death via NF-κB, GSK-3β and β-catenin signaling pathways in cultured cortical neurons

Kim, E.-A.,Cho, C. H.,Kim, D. W.,Choi, S. Y.,Huh, J.-W.,Cho, S.-W. Harwood Academic 2015 Free radical research Vol.49 No.4

<P>We have previously shown that 2-(3-(benzo[d]thiazol-2-yl)ureido)acetate (KHG21834) attenuates amyloid beta(Aβ)<SUB>25-35</SUB>-induced apoptotic death and shows anti-inflammatory activity against Aβ<SUB>25-35</SUB>-induced microglial activation. However, antioxidative effects of KHG21834 against Aβ-induced oxidative stress have not yet been reported. In the present study, we investigated the antioxidative function of KHG21834 in primary cultured cortical neurons, to expand the potential therapeutic efficacy of KHG21834. Pretreatment with KHG21834 protected against Aβ-induced neuronal cell death and mitochondrial damage, and significantly restored GSH levels and the activities of catalase, superoxide dismutase, and glutathione peroxidase, and also suppressed the production of reactive oxygen species and protein oxidation. These results imply that KHG21834 may play a role in cellular defense mechanisms against Aβ-induced oxidative stress in cultured cortical neurons. Furthermore, KHG21834 significantly attenuated the effects of Aβ treatment on levels of NF-κB, β-catenin, and GSK-3β proteins in cortical neurons. Taken together, our results suggest that the antioxidant effects of KHG21834 may result at least in part from its ability to regulate the NF-κB, β-catenin, and GSK-3β signaling pathways. To our knowledge, this is the first report showing that KHG21834 significantly attenuates Aβ<SUB>25-35</SUB>-induced oxidative stress in primary cortical neurons, and provides novel insights into KHG21834 as a possible therapeutic agent for the treatment of Aβ-mediated neurotoxicity involving oxidative stress.</P>

The Rho-kinase (ROCK) inhibitor Y-27632 protects against excitotoxicity-induced neuronal death in vivo and in vitro.

Jeon, Byeong Tak,Jeong, Eun Ae,Park, Sun-Young,Son, Hyeonwi,Shin, Hyun Joo,Lee, Dong Hoon,Kim, Hyun Joon,Kang, Sang Soo,Cho, Gyeong Jae,Choi, Wan Sung,Roh, Gu Seob Harwood Academic Publishers 2013 Neurotoxicity research Vol.23 No.3

<P>Rho-associated coil kinase (ROCK) inhibitors reportedly prevent neurodegeneration, and abnormal ROCK activation in the central nervous system induces neurite collapse and retraction. However, it is unclear whether the ROCK inhibitor Y-27632 directly protects hippocampal neurons from excitotoxicity. Here, we determined the effects of Y-27632 on neuroprotection following kainic acid (KA)-induced seizures in mice and during glutamate-induced excitotoxicity in HT22 cells. One day after Y-27632 injection, mice were treated with KA and killed 1-2 days later. Fluoro-Jade B and rapid Golgi staining showed that Y-27632 protected against KA-induced neurodegeneration and neurite dystrophy. Y-27632 inhibited increases in hippocampal RhoA and ROCK2 in KA-treated mice as determined by western blot analysis. Immunohistochemical analysis revealed ROCK2-positive neurons and astrocytes in the KA-treated hippocampus. In HT22 cells, Y-27632 also protected neurons and neurite formation during glutamate-induced excitotoxicity in vitro. These results indicate that ROCK inhibition modulates neurite growth and protects neurons from excitotoxicity-induced cell death.</P>