Taek-Jeong Nam

Anti-inflammatory effects of fucoidan through inhibition of NF-κB, MAPK and Akt activation in lipopolysaccharide-induced BV2 microglia cells.

Fucoidan, a sulfated polysaccharide extracted from brown seaweed, displays a wide variety of internal biological activities; however, the cellular and molecular mechanisms underlying fucoidans anti-inflammatory activity remain poorly understood. In this study, we investigated the inhibitory effects of fucoidan on production of lipopolysaccharide (LPS)-induced pro-inflammatory mediators in BV2 microglia. Our data indicated that fucoidan treatment significantly inhibited excessive production of nitric oxide (NO) and prostaglandin E₂ (PGE₂) in LPS-stimulated BV2 microglia. It also attenuated expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, monocyte chemoattractant protein-1 (MCP-1), and pro-inflammatory cytokines, including interleukin-1β (IL-1β) and tumor necrosis factor (TNF)-α. Moreover, fucoidan exhibited anti-inflammatory properties by suppression of nuclear factor-kappa B (NF-κB) activation and down-regulation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and AKT pathways. These finding suggest that fucoidan may offer substantial therapeutic potential for treatment of neurodegenerative diseases that are accompanied by microglial activation.

Protective effects of a polysaccharide from Hizikia fusiformis against ethanol toxicity in rats.

Hizikia fusiformis is an edible brown alga that is widely consumed in Korea, Japan, and China and possesses a number of potentially beneficial compounds, including antioxidants and anticoagulants. No reports have investigated potential H. fusiformis protectants against ethanol-induced peptic injury. We extracted a polysaccharide from H. fusiformis (Hf-PS-1) that exhibited protective effects against ethanol-induced peptic injury and related mechanisms in rats. Experimental animals were divided into three groups: control, ethanol-only, and ethanol+Hf-PS-1. The ethanol-only group exhibited decreased levels of total glutathione (GSH) and increased levels of jun N-terminal kinase (JNK) phosphorylation relative to the control group, whereas levels were significantly increased and decreased, respectively, in the ethanol+Hf-PS-1 group. The ethanol-only group also exhibited increased levels of extracellular signal-regulated kinase 1/2 (ERK 1/2) phosphorylation relative to the control group; these levels were not significantly different in the ethanol+Hf-PS-1 group. Hf-PS-1 appeared to reduce ethanol-induced gastric injury. Therefore, we suggest that Hf-PS-1 could protect against ethanol-induced peptic ulcers primarily through a mechanism associated with the inhibition of JNK activation.

A polysaccharide of the marine alga Capsosiphon fulvescens induces apoptosis in AGS gastric cancer cells via an IGF-IR-mediated PI3K/Akt pathway

Because seaweed extracts have recently been found to have antioxidant and anti‐tumor activities, we analyzed a hot‐water‐soluble polysaccharide (PS) of the marine alga Capsosiphon fulvescens for its potential as a functional foodstuff by determining its effects on cell growth and DNA synthesis. MTS assays showed that the C. fulvescens PS (Cf‐PS) significantly inhibited the proliferation of cultured human cancer cells in a dose‐dependent manner. Cf‐PS‐treated AGS cells exhibited a marked increase in caspase‐3 activation and a decrease in Bcl‐2 expression. In addition, phosphorylation of insulin‐like growth factor‐I receptor (IGF‐IR) was decreased in Cf‐PS‐treated AGS cells as compared to non‐treated control cells, which is consistent with PI3‐kinase (PI3K)/Akt activation. Cf‐PS also decreased IGF‐I‐stimulated recruitment of p85 to IGF‐IR and IRS‐1. These results indicate that Cf‐PS inhibits cell proliferation and induces apoptosis by inhibiting IGF‐IR signaling and the PI3K/Akt pathway.

A glycoprotein from Laminaria japonica induces apoptosis in HT-29 colon cancer cells.

We isolated a novel glycoprotein from the brown alga Laminaria japonica that has antiproliferative effects on HT-29 colon cancer cells. We also identified the mechanism by which this glycoprotein, named LJGP, induces apoptosis. MTS assays showed that LJGP inhibited the proliferation of several cancer cell lines (AGS, HepG2, HT-29) in a dose-dependent manner. Especially in HT-29 cells, proliferation was significantly decreased. LJGP treatment on HT-29 displayed several apoptotic features, such as DNA fragmentation, sub-G1 arrest, caspase-3 activation, and PARP degradation. Consistent with sub-G1 arrest, LJGP decreased the expression of Cdk2, cyclin E, cyclin D1, PCNA, E2F-1, and phosphorylated pRb. Furthermore, the increase of p27 expression was observed. We also determined that LJGP-induced apoptosis leads to the formation of a death-induced signaling complex of Fas, FADD, and procaspase-8. LJGP induced the reduction of mitochondrial membrane potential with activation of the Bcl-2 family of proteins and caspase-9. These findings suggest that LJGP inhibits HT-29 cell proliferation by inducing apoptosis, which may be mediated via multiple pathways, including the Fas signaling pathway, the mitochondrial pathway, and cell cycle arrest. Therefore, LJGP can be a useful treatment option for colon cancer in humans.

Antiproliferative activity of fucoidan was associated with the induction of apoptosis and autophagy in AGS human gastric cancer cells.

Fucoidan, a sulfated polysaccharide purified from brown algae, possesses a variety of pharmacologic effects, including antiinflammatory, antioxidant, and anticancer properties; however, the underlying action mechanisms are not completely understood. This study investigated the possible mechanisms through which fucoidan exerts its antiproliferative action in cultured AGS human gastric adenocarcinoma cells. We found that fucoidan effectively inhibits the growth of AGS cells by inducing autophagy, as well as apoptosis. Apoptosis by fucoidan treatment was associated with the downregulation of antiapoptotic Bcl-2 and Bcl-xL expression, loss of mitochondrial membrane potential, activation of caspases, and concomitant degradation of poly-(ADP-ribose) polymerase protein. In addition, the morphological study indicated a characteristic finding of autophagy, such as the formation of autophagosomes in fucoidan-treated AGS cells. Furthermore, markers of autophagy, namely, the conversion of microtubule-associated protein light chain 3 (LC3)-I to LC3-II and increased beclin-1 accumulation, were observed. Overall, the present data suggest that fucoidan induces apoptotic and autophagic cell death, and both apoptotic and autophagic mechanisms contribute to the fucoidan-induced AGS cell death.

Protective effect of porphyra-334 on UVA-induced photoaging in human skin fibroblasts

The significant increase in life expectancy is closely related to the growing interest in the impact of aging on the function and appearance of the skin. Skin aging is influenced by several factors, and solar ultraviolet (UV) irradiation is considered one of the most important causes of skin photoaging. The aim of this study was to examine the anti-photoaging role of porphyra-334 from Porphyra (P.) yezoensis, a mycosporine-like amino acid (MAA), using high-performance liquid chromatography (HPLC), and electrospray ionization-mass spectrometry (ESI-MS). In the present study, extracted UV-absorbing compounds from P. yezoensis included palythine, asterina-330 and porphyra-334. Porphyra-334 was the most abundant MAA in P. yezoensis, and it was therefore used for conducting antiphotoaging experiments. The effect of porphyra-334 on the prevention of photoaging was investigated by measuring reactive oxygen species (ROS) production and matrix metalloproteinase (MMP) levels, as well as extracellular matrix (ECM) components and protein expression in UVA-irradiated human skin fibroblasts. Porphyra-334 suppressed ROS production and the expression of MMPs following UVA irradiation, while increasing levels of ECM components, such as procollagen, type I collagen, elastin. These results suggest that porphyra-334 has various applications in cosmetics and toiletries because of its anti-photoaging activities and may serve as a novel anti-aging agent.

Effect of a glycoprotein from Hizikia fusiformis on acetaminophen-induced liver injury

In this study, we isolated a glycoprotein from the brown alga Hizikia fusiformis (HFGP) and examined whether it could protect against Acetaminophen (AAP)-induced liver injury in vivo and in vitro. AAP, one of the most commonly abused drugs, may cause fatal liver injury. An analysis of the effects of HFGP on AAP toxicity in rats revealed that the serum glutamic pyruvic transaminase level was restored to the control level and glutathione level was also increased by co-treatment with HFGP and AAP. Furthermore, HFGP co-treatment decreased caspase-3/-9 activity. These results indicate that HFGP may inhibit AAP-induced liver injury in Sprague-Dawley rats. Several lines of evidence indicate that oxidative stress plays an important role in AAP-induced liver injury and mitogen-activated protein kinase (MAPK) signaling is involved in the regulation of oxidative stress. Therefore, Western blotting was used to determine which MAPK signaling pathway is involved in the protective effect of HFGP against AAP toxicity in HepG2 cells. We found that ERK activation was involved in the protective effect of HFGP against AAP-induced cell death. Therefore, we propose that MAPK signaling is involved in the protective effect of HFGP against AAP-induced liver injury.

The effect of polysaccharide extracted from the marine alga Capsosiphon fulvescens on ethanol administration

Seaweed extracts have recently been found to have antioxidant and antitumor activities. Capsosiphon fulvescens (Cf) is a green alga and nutrient-dense food source. In a previous study, we extracted polysaccharide from Cf (Cf-PS) and demonstrated its antitumor effect in gastric cancer cells. In this report, we describe the protective effect of Cf-PS against alcohol-induced gastric injury in rats and adenocarcinoma (AGS) cells. In vivo assay revealed stomach damage in rats treated with alcohol alone; however, the stomach condition of rats co-treated with Cf-PS and alcohol matched that of the control group. Cf-PS also inhibited alcohol-induced cell death in AGS cells. Compared with alcohol treatment alone, Cf-PS and alcohol co-treatment increased phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt but inhibited poly-ADP-ribose polymerase (PARP) cleavage. Thus, ERK1/2 and Akt activation are instrumental in the protective effect of Cf-PS against alcohol-induced cell death in AGS cells. Moreover, Cf-PS treatment reduced the expressions of cyclooxygenase-2 (COX-2) and the inducible form of nitric oxide (iNOS), proteins related to ulcers. These results suggest that Cf-PS could help protect against alcohol-induced peptic ulcers.

Chemoprotective effects of a protein from the red algae Porphyra yezoensis on acetaminophen-induced liver injury in rats.

Seaweeds contribute to the maintenance of health through their nutritional and medicinal properties. The effects of PYP, a 14 kDa protein isolated from a hot‐water extract of the marine alga Porphyra yezoensis, on AAP‐induced liver injury in rats was evaluated. AAP induced acute liver injury and AAP‐induced hepatotoxicity is the leading cause of liver failure. In this study, male Sprague–Dawley rats were assigned to one of three treatment groups: control, AAP, or AAP + PYP. Compared with the control group, liver tissue from the AAP group showed increased levels of caspase‐3 activity and DNA fragmentation, decreased levels of GSH and increased serum GOT/GPT levels. In contrast, treatment with AAP + PYP produced levels of caspase‐3 activity, DNA fragmentation, GSH and GOT/GPT that matched the values seen in the control group. It is concluded that PYP may prevent AAP‐induced liver injury. Copyright

A glycoprotein from Porphyra yezoensis produces anti-inflammatory effects in liposaccharide-stimulated macrophages via the TLR4 signaling pathway

The purpose of this study was to investigate the antioxidant and anti-inflammatory effects of a glycoprotein isolated from the alga Porphyra yezoensis in LPS-stimulated RAW 264.7 mouse macrophages. First, we extracted a novel material with antioxidant activity from P. yezoensis, confirmed by SDS-PAGE to be a glycoprotein, which we named P. yezoensis glycoprotein (PGP). PGP inhibited the production of NO and ROS and expression of iNOS, COX-2, TNF-α and IL-1β, which are involved in the pathogenesis of many inflammation-associated human diseases, including septic shock, hemorrhagic shock and rheumatoid arthritis. Next, we determined the mechanisms behind the antioxidant and anti-inflammatory activities of PGP. We focused on the Toll-like receptor 4 (TLR4) signaling pathway because it is well-known to induce the pro-inflammatory proteins that trigger MAPK and NF-κB activation in lipopolysaccharide (LPS)-induced oxidative events. PGP treatment reduced the formation of the TLR4-IRAK4 and TLR4-TRIF binding complexes in response to LPS. Moreover, it inhibited LPS-induced activation and nuclear translocation of NF-κB by abrogating IκB phosphorylation. PGP also suppressed the phosphorylation of ERK1/2 and JNK in a dose-dependent manner. These results suggest that PGP exerts its anti-inflammatory effects by modulating TLR4 signaling and thus inhibiting the activation of NF-κB and MAP kinases.