Sung-Hwan Eom

Antimicrobial effect of phlorotannins from marine brown algae

Marine organisms exhibit a rich chemical content that possess unique structural features as compared to terrestrial metabolites. Among marine resources, marine algae are a rich source of chemically diverse compounds with the possibility of their potential use as a novel class of artificial food ingredients and antimicrobial agents. The objective of this brief review is to identify new candidate drugs for antimicrobial activity against food-borne pathogenic bacteria. Bioactive compounds derived from brown algae are discussed, namely phlorotannins, that have anti-microbial effects and therefore may be useful to explore as potential antimicrobial agents for the food and pharmaceutical industries.

Pancreatic lipase inhibitory activity of phlorotannins isolated from Eisenia bicyclis.

Pancreatic lipase is a potential therapeutic target for the treatment of diet‐induced obesity in humans. In an ongoing search for new pancreatic lipase inhibitors from natural sources, a methanolic extract of marine brown algae, Eisenia bicyclis, showed a significant inhibitory effect against pancreatic lipase. Bioassay‐guided isolation of this methanolic extract using a pancreatic lipase inhibitory assay led to the isolation and identification of six known phlorotannins: eckol (1), fucofuroeckol A (2), 7‐phloroeckol (3), dioxindehydroeckol (4), phlorofucofuroeckol A (5), and dieckol (6). The structures were established on the basis of nuclear magnetic resonance and mass spectrometry spectroscopic data interpretation. Among the isolated phloroglucinol polymers, compounds 2 and 3 showed potent inhibitory effects on pancreatic lipase with IC50 values ranging from 37.2 ± 2.3 to 12.7 ± 1.0 μM, respectively. Copyright

In Vitro Antibacterial Activity and Synergistic Antibiotic Effects of Phlorotannins Isolated from Eisenia bicyclis Against Methicillin-Resistant Staphylococcus aureus

Six phlorotannins, isolated from Eisenia bicyclis, were evaluated for antibacterial activity against methicillin‐resistant Staphylococcus aureus (MRSA). The minimum inhibitory concentrations (MIC) of the compounds were in the range 32 to 64 µg/mL. Phlorofucofuroeckol‐A (PFF) exhibited the highest anti‐MRSA activity, with an MIC of 32 µg/mL. An investigation of the interaction between these compounds and the β‐lactam antibiotics ampicillin, penicillin, and oxacillin revealed synergistic action against MRSA in combination with compound PFF. To our knowledge, this is the first report on the anti‐MRSA activity of phlorotannins from E. bicyclis. The results obtained in this study suggest that the compounds derived from E. bicyclis can be a good source of natural antibacterial agents against MRSA. Copyright

Antibacterial and synergic effects of gallic acid-grafted-chitosan with β-lactams against methicillin-resistant Staphylococcus aureus (MRSA)

Methicillin-resistant Staphylococcus aureus (MRSA) is spreading worldwide, emphasizing the need to search for new antibiotics. The anti-MRSA activities of gallic acid-grafted-chitosans (GA-g-chitosans) were investigated against 2 MRSA standards and 10 MRSA clinical isolates by determining the minimum inhibitory concentrations (MICs). GA-g-chitosan (I), which has the highest gallic acid content, exhibited the strongest anti-MRSA activities, with MICs of 32-64 μg/mL. A time-kill investigation revealed that GA-g-chitosan (I) exhibited a bactericidal effect at twice the MIC, also demonstrating good thermal and pH stability. Investigation of cell envelope integrity showed the release of intracellular components with an increasing absorbance value at 260 nm, indicating cell envelope damage caused by the GA-g-chitosan (I), which was further confirmed by transmission electron microscopy. When GA-g-chitosans were combined with β-lactams, including ampicillin and penicillin, synergistic effects were observed on the 2 standard MRSA strains and on the 10 clinical isolates, with fractional inhibitory indices ranging from 0.125 to 0.625. In the time-kill dynamic confirmation test, synergistic bactericidal effects were observed for the combinations of GA-g-chitosans with β-lactams, and over 4.0 log CFU/mL reductions were observed after 24 h when combination treatment was used. These results may prove GA-g-chitosans to be a potent agent when combined with ampicillin and penicillin for the elimination of MRSA.

Protective effect of phlorotannins from Eisenia bicyclis against lipopolysaccharide-stimulated inflammation in HepG2 cells

In this study, four bioactive phloroglucinol derivates including phloroglucinol (1), eckol (2), dioxinodehydroeckol (3), and dieckol (4) were isolated from Eisenia bicyclis and characterized by nuclear magnetic resonance (NMR) spectroscopic methods. Moreover, the anti-inflammatory activity of these compounds was investigated on human hepatoma cell line HepG2 cells stimulated by lipopolysaccharide (LPS). It was demonstrated that LPS can induce the production of pro-inflammatory cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) as well as the expression of inflammatory mediators as cyclooxygenase-2 (COX-2), and inducible nitric oxide synthases (iNOS) from HepG2 cells. Among isolated compounds, compound (1) exhibited significant inhibition on LPS-stimulated inflammatory responses in HepG2 cells without any cytotoxicity. Herein, compound (1) suppresses the production of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α and the expression of COX-2 and iNOS. Thus, these results indicated that phlorotannins isolated from E. bicyclis, especially compound (1), can be used as a beneficial source for preventing and treating inflammation response.

Enhancement of the Antioxidant and Anti-inflammatory Activity of Hizikia fusiforme Water Extract by Lactic Acid Bacteria Fermentation

We previously reported that fermentation by Lactobacillus brevis LB-20 isolated from Kimchi resulted in improvement of the sensory quality of Hizikia fusiforme water extract. This study was conducted to evaluate the possible application of lactic acid bacteria fermentation to improve the functional qualities of H. fusiforme extract. L. brevis LB-20 was inoculated and cultivated in H. fusiforme extract. The antioxidant and anti-inflammatory activities of extract were then assayed both before and following fermentation for two days. Antioxidant activity was determined by assaying levels of radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl, superoxide, and alkyl radical. Lactic acid bacterial fermentation of H. fusiforme extract resulted in enhancement of antioxidant activity. The greatest enhancement of antioxidant activity was seen in the hydroxyl radical scavenging assay that incorporated 0.5 mg/mL of raw and fermented H. fusiforme extract. Fermented extract exhibited greater (21.95%) inhibition of nitric oxide synthesis than did raw extract (14.66%) at a concentration of 1 mg/mL. The fermented extract exerted its potent anti-inflammatory activity via attenuation of expression of inflammation-related cytokine proteins (TNF-α and iNOS).

The mechanism of antibacterial activity of phlorofucofuroeckol-A against methicillin-resistant Staphylococcus aureus.

To find more effective ways of overcoming methicillin-resistant Staphylococcus aureus (MRSA), there has been considerable interest in the use of marine-derived constituents as alternatives to control pathogenic microorganisms. In this study, we investigated whether phlorofucofuroeckol-A (PFF) isolated from the edible brown alga Eisenia bicyclis suppressed production or function of penicillin-binding protein 2a (PBP2a). The antimicrobial mode of action of PFF in MRSA was identified by measuring cell membrane integrity and using the time-kill curve method. We attempted to determine the antimicrobial effects of PFF on the expression level of the resistance determinants mecA and its regulatory genes mecI and mecR1 in MRSA by reverse transcriptase polymerase chain reaction. PFF suppressed mecI, mecR1, and mecA gene expression in a dose-dependent manner. In addition, we revealed PFF mediates the suppressive effect of PBP2a expression in MRSA by Western blot analysis. PFF suppressed production of the PBP2a protein, suggesting that PFF probably acts by controlling the methicillin resistance-associated genes involved in the cell wall and production of PBP2a. These results demonstrate that PFF isolated from E. bicyclis significantly suppressed the expression of the methicillin resistance-associated genes and production of PBP2a, which is considered the primary cause of methicillin resistance.

Antimicrobial Activity of Brown Alga Eisenia bicyclis against Methicillin-resistant Staphylococcus aureus

Abstract We screened for antibacterial substances against methicillin-resistant Staphylococcus aureus (MRSA). Methanolic extract of Eise-nia bicyclis exhibited anti-MRSA activity according to a disk diffusion assay. To identify the active compound(s), the methanolic extract was further fractionated using hexane, dichloromethane, ethyl acetate, and n -butanol. The ethyl acetate-soluble fraction showed both the greatest anti-MRSA activity and the highest polyphenol content. The minimum inhibitory concentrations of the ethyl acetate fraction ranged from 32 to 64 μg per mL against methicillin-susceptible S. aureus and MRSA strains. High-perfor-mance liquid chromatography analysis revealed that both the methanolic extract and the ethyl acetate soluble fraction contained sizeable quantities of dieckol, which is a known anti-MRSA compound. Thus, these data strongly suggest that the anti-MRSA activity of E. bicyclis may be mediated by phlorotannins such as dieckol. Key words: Anti-MRSA activity,

Marine bacteria: potential sources for compounds to overcome antibiotic resistance

Methicillin-resistant Staphylococcus aureus (MRSA) is the most problematic Gram-positive bacterium in the context of public health due to its resistance against almost all available antibiotics except vancomycin and teicoplanin. Moreover, glycopeptide-resistant S. aureus have been emerging with the increasing use of glycopeptides. Recently, resistant strains against linezolid and daptomycin, which are alternative drugs to treat MRSA infection, have also been reported. Thus, the development of new drugs or alternative therapies is clearly a matter of urgency. In response to the antibiotic resistance, many researchers have studied for alternative antibiotics and therapies. In this review, anti-MRSA substances isolated from marine bacteria, with their potential antibacterial effect against MRSA as potential anti-MRSA agents, are discussed and several strategies for overcoming the antibiotic resistance are also introduced. Our objective was to highlight marine bacteria that have potential to lead in developing novel antibiotics or clinically useful alternative therapeutic treatments.

Synergistic Antibacterial Effect and Antibacterial Action Mode of Chitosan-Ferulic Acid Conjugate against Methicillin-Resistant Staphylococcus aureus.

We evaluated the synergistic antibacterial effect in combination with the chitosan-ferulic acid conjugate (CFA) and β-lactam antibiotics, such as ampicillin, penicillin, and oxacillin, against methicillin-resistant Staphylococcus aureus (MRSA) using fractional inhibitory concentration (FIC) indices. CFA clearly reversed the antibacterial activity of ampicillin, penicillin, and oxacillin against MRSA in the combination mode. Among these antibiotics, the combination of oxacillin-CFA resulted in a ∑FICmin range of 0.250 and ∑FICmax of 0.563, suggesting that the oxacillin-CFA combination resulted in an antibacterial synergy effect against MRSA. In addition, we determined that CFA inhibited the mRNA expression of gene mecA and the production of PBP2a, which is a key determinant for β-lactam antibiotic resistance, in a dosedependent manner. Thus, the results obtained in this study supported the idea on the antibacterial action mechanism that oxacillin will restore the antibacterial activity against MRSA through the suppression of PBP2a production by CFA.