Seon-Heui Cha

Effect of phlorotannins isolated from Ecklonia cava on melanogenesis and their protective effect against photo-oxidative stress induced by UV-B radiation.

In the present study, three kinds of phlorotannins, marine algal polyphenol, were isolated from a brown alga Ecklonia cava, and their inhibitory effect on melanogenesis as well as the protective effect against photo-oxidative stress induced by UV-B radiation was investigated. The effect on melanogenesis was evaluated via the inhibitory effects of tyrosinase and melanin synthesis. Among the phlorotannins, dieckol showed higher effect than that of the other phlorotannins in the both assays; especially the value of dieckol in the tyrosinase inhibition assay was relatively higher than that of a commercial tyrosinase inhibitor (kojic acid). The UV-B protection effect was evaluated via DCFH-DA, MTT, comet assays, and morphological changes in fibroblast. Intracellular ROS induced by UV-B radiation was reduced by the addition of phlorotannins and cell viability was dose-dependently increased. Moreover, dieckol demonstrated strong protective properties against UV-B radiation-induced DNA damage via damaged tail intensity and morphological changes in fibroblast. Hence, these results indicated that dieckol isolated from E. cava has potential whitening effects and prominent protective effects on UV-B radiation-induced cell damages, which might be used in pharmaceutical and cosmeceutical industries.

Inhibitory effect of diphlorethohydroxycarmalol on melanogenesis and its protective effect against UV-B radiation-induced cell damage

In this study, potential inhibitory effect of 21 species of marine algae on melanogenesis was assessed via tyrosinase inhibitory effect. The Ishige okamurae extract tested herein evidenced profound tyrosinase inhibitory effect, compared to that exhibited by other marine algae extracts. Thus, I. okamurae was selected for use in further experiments, and was partitioned with different organic solvents. Profound tyrosinase inhibitory effect was detected in the ethyl acetate fraction, and the active compound was identified as the carmalol derivative, diphlorethohydroxycarmalol (DPHC), which evidenced higher levels of activity than that of commercial whitening agent. Intracellular reactive oxygen species (ROS) induced by ultraviolet (UV)-B radiation was reduced by the addition of DPHC and cell viability was dose-dependently increased. Moreover, DPHC demonstrated strong protective properties against UV-B radiation via damaged DNA tail length and morphological changes in fibroblast. Hence, these results indicate that DPHC isolated from I. okamurae has potential whitening effects and prominent protective effects on UV-B radiation-induced cell damages which might be used in pharmaceutical and cosmeceutical industries.

Protective effect of marine algae phlorotannins against AAPH-induced oxidative stress in zebrafish embryo

In this study the protective effect of phlorotannins, including phloroglucinol, eckol, dieckol, eckstolonol and triphloroethol A, isolated from brown algae Ecklonia cava was investigated against AAPH-induced oxidative stress toxicity in zebrafish embryos. Zebrafish embryos were exposed to AAPH and compared with other groups that were co-exposed with phlorotannins until 2-days post-fertilisation. All phlorotannins scavenged intracellular ROS and prevented lipid peroxidation and reduced AAPH-induced cell death in zebrafish embryos. Negative changes in morphological phenomena, such as pericardial oedema, yolk sac oedema, and growth retardation in zebrafish embryos exposed to AAPH were not observed in groups exposed to phlorotannins. These results clearly indicate that phlorotannins possess prominent antioxidant activity against AAPH-mediated toxicity and might be potential therapeutic agents for treating or preventing several diseases implicated with oxidative stress. This study provides a useful tool for examining the protective effect of antioxidants against AAPH-induced oxidative stress in an alternative in vivo model.

Screening of marine algae for potential tyrosinase inhibitor: those inhibitors reduced tyrosinase activity and melanin synthesis in zebrafish

In order to find new anti‐browning and whitening agents in this study, we investigated 43 indigenous marine algae for tyrosinase inhibitory activity. The extracts from Endarachne binghamiae, Schizymenia dubyi, Ecklonia cava (EC) and Sargassum silquastrum (SS) evidenced potent tyrosinase inhibitory activity similar to that of positive control, kojic acid. Among those marine algae, EC and SS are distributed abundantly on Jeju Island. Therefore, we selected those two species for further studies. Our results evidenced that both species reduced cellular melanin synthesis and tyrosinase activity. On the other hand, we utilized zebrafish as an alternative in vivo model. All the tested samples evidenced excellent inhibitory effects on the pigmentation of zebrafish, most likely due to their potential tyrosinase inhibitory activity. In simultaneous in vivo toxicity tests, no toxicity was observed in either algal species, on the other hand, toxicity was observed in positive controls. These results provided that EC and SS extract could be used as an ingredient for whiting cosmetics and that zebrafish is an alternative in vivo model.

Antioxidant Activities of Red Algae from Jeju Island

The aim of the present study was to evaluate the antioxidant activity of red algae in Jeju Island. The algal extracts were obtained with MeOH and fresh water at 20 and 70°C, and screened for antioxidant activities using hydroxyl radical (HO·), superoxide anion (O2–), hydrogen peroxide (H2O2) and DPPH free radical scavenging assays. Among them, Gracilaria verrucosa methanolic extract at 20°C (20ME, 96.85%), G. textorii aqueous extract at 20°C (20AE, 88.01%), Grateloupia filicina 20AE (85.35%), and Polysiphonia japonica 20ME (94.92%) exhibited the highest scavenging activities against HO·, O2–, H2O2, and DPPH free radicals, respectively. Moreover, P. japonica (20ME and 70ME) is correlated between DPPH free radical scavenging activity and polyphenolic contents. These results indicate that some red algae in Jeju Island could be potential candidates for development of antioxidants.

Neuroprotective effects of phlorotannins isolated from a brown alga, Ecklonia cava, against H2O2-induced oxidative stress in murine hippocampal HT22 cells.

Exposure of neurons to hydrogen peroxide (H(2)O(2)) results in oxidative stress and the activation of a cascade of intracellular toxic events resulting in oxidation, lipid peroxidation, and Ca(2+) elevation, ultimately resulting in cell death. In this study, we attempted to characterize the neuroprotective effects of phlorotannins isolated from Ecklonia cava, including phloroglucinol, eckol, triphloroethol A, eckstolonol, and dieckol, against H(2)O(2)-induced cell damage in murine hippocampus neuronal (HT22) cells. We measured the reactive oxygen species (ROS) and lipid peroxidation levels and evaluated the resultant cell death and alterations in Ca(2+)-concentrations. All phlorotannins were to scavenge intracellular ROS and repress ROS accumulation, thus preventing lipid peroxidation. Consquently, all phlorotannins reduced H(2)O(2)-induced cell death in HT22 cells. Moreover, phlorotannins inhibited H(2)O(2)-induced Ca(2+) release. This study provides a new useful strategy for preventing neuronal H(2)O(2)-induced oxidative stress.

Protective effect of Ecklonia cava on UVB-induced oxidative stress: in vitro and in vivo zebrafish model

Chronic exposure of the skin to ultraviolet B (UVB) radiation induces oxidative stress, which plays a crucial role in the induction of skin aging. In this study, potential protective effect of extracts of six species of brown seaweeds on UVB radiation-induced cell damage was assessed via cell viability in HaCaT cells. The Ecklonia cava extract showed a profound protective effect against UVB radiation-induced cell damage, compared to that exhibited by other brown seaweed extracts. Thus, E. cava was selected for use in further experiments and was extracted with different solvents. The protection effect was evaluated via DCFH-DA, MTT, and morphological changes in HaCaT cells. Profound protective effect against UVB radiation-induced cell damage was detected in the 100% methanol extract. Partitioning of the 100% methanol extract with different organic solvents revealed a pronounced protective effect in the ethyl acetate fraction. The isolated active compounds were phlorotannins, especially dieckol, as identified using ultra-performance liquid chromatography-tandem mass spectrometry. Among the phlorotannins, dieckol showed a higher protective effect on UVB-induced cell damage in HaCaT cells than the other phlorotannins. Therefore, UVB protection of dieckol was evaluated via DCFH-DA, DAF-FM DA, acridine orange, and morphological changes in zebrafish model. Reactive oxygen species, nitric oxide, and cell death in live zebrafish induced by UVB radiation were reduced by the addition of dieckol. These results indicated that dieckol has potential protective effects on UVB-induced skin damage, which might be useful in pharmaceutical and cosmetic formulations.

Screening of Extracts from Red Algae in Jeju for Potentials MarineAngiotensin - I Converting Enzyme (ACE) Inhibitory Activity

Hypertension is a worldwide problem of epidemic proportions, affecting 15-20% of adults. It is the most common serious chronic health problem because it carries a high risk factor for arteriosclerosis, stroke, myocardial infarction and end-stage renal disease. Angiotensin I Converting Enzyme (ACE) belongs to the class of zinc metal proteases and is located in the vascular endothelial lining of the lungs (Miyoshi et al. 1991). This enzyme plays a key role in the control of blood pressure, by virtue of the rennin-angiotensin system (Ondetti et al . 1982; Rencland and Lithell 1994; Fujita and Yokoyama 2000). ACE acts as an exo-peptidase that cleaves a dipeptide of C-terminus of angiotensin I peptide to produce the potent vasoconstrictor angiotensin II (Curtiss et al. 1978; Maruyama et al. 1989; Dzau 2001) and inactivates bradykinin (Ukeda et al. 1991). A number of ACE inhibitors have been extensively used in the treat of essential hypertension and heart failure in human; these include alacepril, benazepril, captopril, cilazapril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, tandolapril, and zofenopril (Kato and Suzuki 1971; Ondetti 1977; Sawayama et al. 1990). However, these commercial drugs are believed to cause certain side effects, such as cough, taste disturbances and skin rashes (Atkinson and Robertson 1979). Therefore, searching ACE inhibitors from natural resources have become more important. Recently, many researchers have studied inhibitory activities on anti-ACE and antihypertensive effects after oral or intravenous administration in animal experiments and in clinical trials (Shin et al. 2001; Sato et al. 2002; Seppo et al. 2003). Also, much attention for the natural products and functional natural biomaterials has been paid to marine algae. In fact, for several centuries mankind has been exploiting the properties of certain foods to mitigate or prevent diseases. A number of investigators have studied the various bioactivities of algae and have found that seaweeds have not only nutritional effects but also beneficial properties to cure various diseases and keep good health (Joshipura et al. 2001). Marine algae have been consumed in Asian countries since ancient times, while in Western countries they have been utilized as sources of phycocolloids, Algae Volume 21(3): 343-348, 2006

Neuroprotective Effect of Phlorotannin Isolated from Ishige okamurae Against H2O2-Induced Oxidative Stress in Murine Hippocampal Neuronal Cells, HT22

The present study is designed to investigate the neuroprotective effect of a kind of phlorotannins, diphlorethohydroxycarmalol (DPHC) isolated from Ishige okamurae against hydrogen peroxide (H2O2)-induced oxidative stress in murine hippocampal neuronal cells, HT22. H2O2 treatment induced neurotoxicity, whereas DPHC prevented cells from H2O2-induced damage then restoring cell viability was significantly increased. DPHC slightly reduced the expression of Bax induced by H2O2 but recovered the expression of Bcl-xL as well as caspase-9 and -3 mediated PARP cleavage by H2O2. Intracellular reactive oxygen species (ROS) and lipid peroxidation was overproduced as the result of the addition of H2O2; however, these ROS generations and lipid peroxidation were effectively inhibited by addition of DPHC in a dose-dependent manner. Moreover, DPHC suppressed the elevation of H2O2-induced Ca2+ release. These findings indicate that DPHC has neuroprotective effects against H2O2-induced damage in neuronal cells, and that an inhibitory effect on ROS production may contribute to the underlying mechanisms.

Loss of parkin promotes lipid rafts-dependent endocytosis through accumulating caveolin-1: implications for Parkinson’s disease

BackgroundParkinson’s disease (PD) is characterized by progressive loss of midbrain dopaminergic neurons, resulting in motor dysfunctions. While most PD is sporadic in nature, a significant subset can be linked to either autosomal dominant or recessive mutations. PARK2, encoding the E3 ubiquitin ligase, parkin, is the most frequently mutated gene in autosomal recessive early onset PD. It has recently been reported that PD-associated gene products such as PINK1, α-synuclein, LRRK2, and DJ-1, as well as parkin associate with lipid rafts, suggesting that the dysfunction of these proteins in lipid rafts may be a causal factor of PD. Therefore here, we examined the relationship between lipid rafts-related proteins and parkin.ResultsWe identified caveolin-1 (cav-1), which is one of the major constituents of lipid rafts at the plasma membrane, as a substrate of parkin. Loss of parkin function was found to disrupt the ubiquitination and degradation of cav-1, resulting in elevated cav-1 protein level in cells. Moreover, the total cholesterol level and membrane fluidity was altered by parkin deficiency, causing dysregulation of lipid rafts-dependent endocytosis. Further, cell-to-cell transmission of α-synuclein was facilitated by parkin deficiency.ConclusionsOur results demonstrate that alterations in lipid rafts by the loss of parkin via cav-1 may be a causal factor of PD, and cav-1 may be a novel therapeutic target for PD.