Fucoxanthin is converted to fucoxanthinol and amarouciaxanthin A in mice. It was previously reported that fucoxanthinol attenuated the adipogenesis of 3T3-L1 cells. However, the effects of amarouciaxanthin A on adipocyte differentiation have not been clarified. This study examined the effects of amarouciaxanthin A on 3T3-L1 adipogenesis by comparing the effects of fucoxanthinol, isofucoxanthinol, and amarouciaxanthin B. Amarouciaxanthin A significantly decreased glycerol-3-phosphate dehydrogenase (GPDH) activity, which was measured as an indicator of adipocyte differentiation. The suppressive effect of amarouciaxanthin A was stronger than that of fucoxanthinol, amarouciaxanthin B, and isofucoxanthinol. The mRNA expressions of adipocyte fatty acid-binding protein (aP2), lipoprotein lipase (LPL), and glucose-transporter 4 (Glut4) in 3T3-L1 cells were markedly down-regulated by amarouciaxanthin A compared to fucoxanthinol. Furthermore, the expression levels of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT-enhancer-binding protein α (C/EBPα),, which are the key adipogenic transcriptional factors, were also decreased by amarouciaxanthin A during adipocyte differentiation. These results show that amarouciaxanthin A, which is a dominant metabolite of fucoxanthin in white adipose tissue, suppressed 3T3-L1 adipocyte differentiation.

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Osteoarthritis (OA) is a degenerative joint disease that is characterized by irreversible articular cartilage destruction by inflammatory reaction. Among inflammatory stimuli, interleukin-1β (IL-1β) is known to play a crucial role in OA pathogenesis by stimulating several mediators that contribute to cartilage degradation. Recently, the marine brown alga Sargassum serratifolium has been reported to exhibit antioxidant and anti-inflammatory effects in microglial and human umbilical vein endothelial cell models using lipopolysaccharide and tumor necrosis factor-α, but its beneficial effects on OA have not been investigated. This study aimed to evaluate the anti-osteoarthritic effects of ethanol extract of S. serratifolium (EESS) in SW1353 human chondrocytes and, in parallel, primary rat articular chondrocytes. Our results showed that EESS effectively blocked the generation of reactive oxygen species in IL-1β-treated SW1353 and rat primary chondrocytes, indicating that EESS has a potent antioxidant activity. EESS also attenuated IL-1β-induced production of nitric oxide (NO) and prostaglandin E2, major inflammatory mediators in these cells, which was associated with the inhibition of inducible NO synthase and cyclooxygenase-2 expression. Moreover, EESS downregulated the level of gene expression of matrix metalloproteinase (MMP)-1, -3 and -13 in SW1353 chondrocytes treated with IL-1β, resulting in their extracellular secretion reduction. In addition, the IL-1β-induced activation of nuclear factor-kappa B (NF-κB) was restored by EESS. Furthermore, EESS reduced the activation of p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathways upon IL-1β stimulation. These results indicate that EESS has the potential to exhibit antioxidant and anti-inflammatory effects through inactivation of the NF-κB, p38 MAPK, and PI3K/Akt signaling pathways. Collectively, these findings demonstrate that EESS may have the potential for chondroprotection, and extracts of S. serratifolium could potentially be used in the prevention and treatment of OA.

Abstract:It is well known that fucoidan, a natural sulfated polysaccharide present in various brown algae, mediates anticancer effects through the induction of cell cycle arrest and apoptosis. Nevertheless, the role of tumor suppressor p53 in the mechanism action of fucoidan remains unclear. Here, we investigated the anticancer effect of fucoidan on two p53 isogenic HCT116 (p53+/+ and p53−/−) cell lines. Our results showed that inhibition of cell viability, induction of apoptosis and DNA damage by treatment with fucoidan were similar in two cell lines. Flow cytometric analysis revealed that fucoidan resulted in G1 arrest in the cell cycle progression, which correlated with the inhibition of phosphorylation of retinoblastoma protein (pRB) and concomitant association of pRB with the transcription factor E2Fs. Furthermore, treatment with fucoidan obviously upregulated the expression of cyclin-dependent kinase (CDK) inhibitors, such as p21WAF1/CIP1 and p27KIP1, which was paralleled by an enhanced binding with CDK2 and CDK4. These events also commonly occurred in both cell lines, suggesting that fucoidan triggered G1 arrest and apoptosis in HCT116 cells by a p53-independent mechanism. Thus, given that most tumors exhibit functional p53 inactivation, fucoidan could be a possible therapeutic option for cancer treatment regardless of the p53 status.

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.

Stearoyl-coenzyme A desaturase-1 (SCD1) is a rate-limiting enzyme that catalyzes the biosynthesis of monounsaturated fatty acids from saturated fatty acids. Recently, SCD1 down-regulation has been implicated in the prevention of obesity, and the improvement of insulin and leptin sensitivity. In this study, we examined the effect of fucoxanthin, a marine carotenoid, on hepatic SCD1 in obese mouse models of hyperleptinemia KK-A(y) and leptin-deficiency ob/ob. In KK-A(y) mice, providing a diet containing 0.2 % fucoxanthin for 2 weeks markedly suppressed SCD1 mRNA and protein expressions in the liver. The fatty acid composition of liver lipids was also affected by an observed decrease in the ratio of oleic acid to stearic acid. Furthermore, serum leptin levels were significantly decreased in hyperleptinemia KK-A(y) mice after 2 weeks of fucoxanthin feeding. However, the suppressive effects of fucoxanthin on hepatic SCD1 and body weight gain were not observed in ob/ob mice. These results show that fucoxanthin down-regulates SCD1 expression and alters fatty acid composition of the liver via regulation of leptin signaling in hyperleptinemia KK-A(y) mice but not in leptin-deficient ob/ob mice.

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.

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