The mechanism of antibacterial activity of tetrandrine against Staphylococcus aureus.

Tetrandrine (TET) is a bis-benzylisoquinoline alkaloid derived from the radix of Stephania tetrandra S. Moore. TET performs a wide spectrum of biological activities. The radix of S. tetrandrae has been used traditionally in Asia, including Korea, to treat congestive circulatory disorders and inflammatory diseases. The aim of this study was to examine the mechanism of antibacterial activity of tetrandrine against Staphylococcus aureus. The mechanism was investigated by studying the effects of TET in combination with detergent or membrane potential un-couplers. In addition, the direct involvement of peptidoglycan (PGN) was assessed in titration assays. TET activity against S. aureus was 125-250 µg/mL, and the minimum inhibitory concentration (MIC) of the two reference strains was 250 µg/mL. The OD(600) of each suspension treated with a combination of ethylenediaminetetraacetic acid (EDTA), tris(hydroxymethyl) aminomethane (TRIS), and Triton X-100 (TX) with TET (0.25×MIC) had been reduced from 43% to 96%. Additional structure-function studies on the antibacterial activity of TET in combination with other agents may lead to the discovery of more effective antibacterial agents.

Anti-allergic effects of sinomenine by inhibition of prostaglandin D2 and leukotriene C4 in mouse bone marrow-derived mast cells.

Sinomenine is an alkaloid compound and a prominent anti-allergic agent found in the root of the climbing plant Sinomenium acutum. However, its effects on the bone marrow-derived mast cell (BMMC) mediated allergy and inflammation mechanism remain unknown. In this study, the biological effects of sinomenine were evaluated while focusing on its effects on the allergic mediator in PMA plus A23187-stimulated BMMCs. An investigation was also conducted to determine its effects on the production of several allergic mediators including interleukin-6 (IL-6), prostaglandin D(2) (PGD(2)), leukotriene C(4) (LTC(4)), ß-Hexosaminidase (ß-Hex), and cyclooxygenase-2 (COX-2) protein. The results revealed that sinomenine inhibited the PMA plus A23187-induced production of IL-6, PGD(2), LTC(4), ß-Hex, and COX-2 protein. Taken together, these findings indicate that sinomenine has the potential for use in the treatment of allergy.

Gomisin N has anti-allergic effect and inhibits inflammatory cytokine expression in mouse bone marrow-derived mast cells.

Gomisin N is a bioactive compound and a prominent anti-allergic agent found in the fruits of tree Schizandra chinensis. However, its effects on the bone marrow-derived mast cell (BMMC)-mediated allergy and inflammation mechanism remain unknown. In this study, the biological effects of gomisin were evaluated while focusing on its effects on the allergic mediator in PMA + A23187-stimulated BMMCs. The anti-allergic effect of gomisin has shown that inhibited PMA + A23187-induced interleukin-6 (IL-6) production. An investigation was also conducted to determine its effects on the production of several allergic mediators including prostaglandin D(2) (PGD(2)), leukotriene C(4) (LTC(4)), ß-hexosaminidase (ß-Hex), and cyclooxygenase-2 (COX-2) protein. The results revealed that gomisin inhibited the PMA + A23187-induced production of IL-6, PGD(2), LTC(4), ß-Hex, and COX-2 protein. Taken together, these findings indicate that gomisin N has the potential for use in the treatment of allergy.

In vitro potentiation of ampicillin, oxacillin, norfloxacin, ciprofloxacin, and vancomycin by sanguinarine against methicillin-resistant Staphylococcus aureus.

Few new drugs are available against methicillin-resistant Staphylococcus aureus (MRSA), because MRSA has the ability to acquire resistance to most antibiotics, which consequently increases the cost of medication. The objective of this study is to evaluate the potentiation of sanguinarine (SN) with selected antibiotics (ampicillin [AC], oxacillin [OX], norfloxacin [NR], ciprofloxacin [CP], and vancomycin [VC]) against MRSA. Minimum inhibitory concentration was determined by using the broth microdilution method and the synergistic effect of AC, OX, NR, CP, and VC in combination with SN was examined by the checkerboard dilution test. The results of the checkerboard test suggested that all combinations exhibited some synergy, partial synergy, or additivity. None of the combinations showed an antagonism effect. The combination of SN plus CP exhibited maximum synergistic effect in 11/13 strains, followed by SN plus NR in 9/13 strains, and AC and OX in 7/13 strains each. The combination of SN with VC, however, mostly showed partial synergy in 11/13 strains. The time-kill assay showed that SN in combination with other antibiotics reduced the bacterial count by 10(2)-10(3) colony forming units after 4 h and to less than the lowest detectable limit after 24 h. Although in vivo synergy and clinical efficacy of SN cannot be predicted, it can be concluded that SN has the potential to restore the effectiveness of the selected antibiotics, and it can be considered in an alternative MRSA treatment.

Methane Gas Cofiring Effects on Combustion and NO x Emission in 550 MW Tangentially Fired Pulverized-Coal Boiler.

A shift from coal to liquefied natural gas for electricity generation can mitigate CO2 emissions and respond to the intermittent and variable characteristics of renewable energy. With this objective, numerical simulation was performed in this study to determine the optimal position of the methane injector and evaluate the achievable reduction in NO x emissions before applying methane cofiring to an existing 550 MW tangentially fired pulverized-coal boiler (Boryeong Unit 3). The combustion and NO x reduction in the furnace were intensively analyzed based on the methane cofiring rate (up to 40%). The optimal position of the methane injector was found to be inside the oil port based on the spatial distribution of NO x and the stoichiometric ratio along the furnace height. The NO x reduction rate was logarithmically proportional to the methane cofiring rate, and compared to the base case, a 69.8% reduction was achieved at the 40% cofiring rate. In addition, the fraction of unburned char at the boiler outlet was equivalent to that of the existing boiler as the increase in the flow rates of the close-coupled and separated overfire air improved fuel and air mixing. Simultaneously, methane cofiring led to a reduction in the total fuel loss and CO emissions. Finally, this study showed that the recommended optimum cofiring rate was 20% based on the furnace exit gas temperature. Under the 20% methane cofiring condition, the boiler achieved a 57.3% reduction in NO x emissions and a 7.4% improvement in fuel loss.

Synergistic effect of emodin in combination with ampicillin or oxacillin against methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is a substantial contributor to morbidity and mortality. In search of a natural products capable of inhibiting this multidrug resistant bacteria, we have investigated the antimicrobial activity of emodin (EM) isolated from Rheum palmatum L. (Polygonaceae) against 17 different strains of the bacterium. New antimicrobial activity was found using the paper disc diffusion method, agar dilution as well as checkerboard method. Against the 17 strains, the disc diffusion test was in the range of 18-30 mm, and the minimum inhibitory concentrations (MICs) of EM were in the range of 1.5-25 µg/mL. From those results we performed the checkerboard test to determine the synergism of EM in combination with ampicillin (AM) or oxacillin (OX) against all strains. The combined activity of EM and two antimicrobial agents (AM, OX) against all strains resulted in a fractional inhibitory concentrations index (FICI) ranging from 0.37-0.5 and from 0.37-0.75, respectively. The effect of EM with AM and OX was found to be synergistic or partially synergistic. We found that EM reduced the MICs of AM and OX. EM and in combination with AM or OX could lead to the development of new combination antibiotics against MRSA infection.

The anti-inflammatory effect of Cheongseoikki-tang ethanol extract on allergic reactions mediated by bone marrow-derived mast cells.

OBJECTIVE: Cheongseoikki-tang (CIT, Korean), also called Qingshu Yiqi decoction () and Seisho-ekki-to (Japanese), is well known as an effective traditional combination of herbs for treating cardiovascular diseases. This study was to research its effects on bone marrow-derived mast cell (BMMC)-mediated allergy and inflammation mechanisms. METHODS: In this study, the biological effect of Cheongseoikki-tang ethanol extract (CITE) was evaluated, focusing on its effects on the production of allergic mediators by phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187 (A23187)-stimulated BMMCs. These allergic mediators included interleukin-6 (IL-6), prostaglandin D2 (PGD2), leukotriene C4 (LTC4), and ß-hexosaminidase (ß-hex). RESULTS: Our data revealed that CITE inhibited the production of IL-6, PGD2, LTC4, and ß-hex induced by PMA plus A23187 (P<0.05). CONCLUSION: These findings indicate that CITE has the potential for use in the treatment of allergy.

Anti-inflammatory effects of Danggui Liuhuang Decoction () in RAW 264.7 cells.

OBJECTIVE: To elucidate the molecular mechanisms underlying the anti-inflammatory effects of Danggui Liuhuang Decoction () or Dangkwiyughwang-tang (DGLHT) water extract. METHODS: Effect of DGLHT on the lipopolysaccharide (LPS)-induced production of several pro-inflammatory mediators, including nitric oxide (NO), prostaglandin E(2) (PGE(2)), and interleukin-6 (IL-6) were examined by using enzymelinked immunosorbent assay. To determine the underlying mechanism of the inhibitory effects of DGLHT, the expression levels of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) protein, as well as iNOS, COX-2, and IL-6 mRNA levels were examined by Western blot and reverse transcription polymerase chain reaction (RT-PCR). Mitogen-activated protein kinases (MAPKs) in LPS-stimulated RAW 264.7 cells were also examined by Western blot. RESULTS: DGLHT inhibited LPS-induced production of NO, PGE(2), and IL-6 productions and the expressions of iNOS and COX-2. Furthermore, DGLHT suppressed LPS-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). CONCLUSIONS: DGLHT has inhibitory effects on the LPSinduced production of PGE(2), NO, and IL-6 and on the expressions of iNOS and COX-2 in murine macrophages. These anti-inflammatory effects occur through inhibition of MAPK phosphorylation.

The mechanism of action of sanguinarine against methicillin-resistant Staphylococcus aureus.

Sanguinarine is a benzophenanthridine alkaloid derived from the root of Sanguinaria canadensis. It is known to perform a wide spectrum of biological activities. The aim of this study is to examine the antimicrobial actions of sanguinarine against methicillin-resistant Staphylococcus aureus (MRSA). Sanguinarine antimicrobial activity was assessed by broth dilution method; its mechanism of action was investigated by bacteriolysis, detergent or ATPase inhibitors and transmission electron microscopy were used to monitor the survival characteristics and the changes in bacteria morphology. The activity of sanguinarine against MRSA strains ranged from 3.12 to 6.25 µg/ml, while the minimum inhibitory concentrations of the two reference strains are 3.12 µg/ml and 1.56 µg/ml. The treatment of the cells with sanguinarine induced the release of membrane-bound cell wall autolytic enzymes, which eventually resulted in lysis of the cell. The OD(600s) of the suspensions treated with the combination of Tris-(hydroxymethyl) aminomethane and Triton X-100 with sanguinarine were reduced to 40% and 8%, respectively. Transmission electron microsco-py of MRSA treated with sanguinarine showed alterations in septa formation. The predisposition of lysis and the altered morphology seen by transmission electron microscopy suggest that sanguinarine compromises the cytoplasmic membrane.

Synergistic effect of tetrandrine and ethidium bromide against methicillin-resistant Staphylococcus aureus (MRSA).

Methicillin-resistant Staphylococcus aureus (MRSA) along with other resistant bacteria have become a significant social and clinical problem. Therefore, there is an urgent need to develop bioactive compounds from natural products as alternatives to the very few antibiotics that remain effective. Recently, the efflux mechanism has been identified as the main contributor to antibiotic resistance in bacteria. This study therefore aimed to evaluate tetrandrine (TET), an efflux pump inhibitor (EPI), as a potential antibiotic against MRSA. We investigated the antimicrobial activity of TET against 17 MRSA strains, of which 3 selected strains were studied in further detail using a time-kill assay. When these bacterial strains (1 × 10(6) colony-forming units (cfu)/ml) were incubated with TET in a time-kill assay, log-scale bactericidal activity was observed, which lasted for 24 hr. In addition, TET exhibits a synergistic effect when combined with the multi-drug resistance (MDR)-efflux pump substrate ethidium bromide (EtBr). Structure-function studies of the antibiotic activity of TET in combination with EtBr may lead to the discovery of more effective efflux pump inhibitors.