Marine Drugs

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Open AccessArticle

Secondary Metabolites from Penicillium pinophilum SD-272, a Marine Sediment-Derived Fungus

by Ming-Hui Wang, Xiao-Ming Li, Chun-Shun Li, Nai-Yun Ji and Bin-Gui Wang

Mar. Drugs 2013, 11(6), 2230-2238; https://doi.org/10.3390/md11062230 - 21 Jun 2013

Cited by 47 | Viewed by 8133

Two new secondary metabolites, namely, pinodiketopiperazine A (1) and 6,7-dihydroxy-3-methoxy-3-methylphthalide (2), along with alternariol 2,4-dimethyl ether (3) and l-5-oxoproline methyl ester (4), which were isolated from a natural source for the first time but have [...] Read more.

Two new secondary metabolites, namely, pinodiketopiperazine A (1) and 6,7-dihydroxy-3-methoxy-3-methylphthalide (2), along with alternariol 2,4-dimethyl ether (3) and l-5-oxoproline methyl ester (4), which were isolated from a natural source for the first time but have been previously synthesized, were characterized from the marine sediment-derived fungus Penicillium pinophilum SD-272. In addition, six known metabolites (5–10) were also identified. Their structures were elucidated by analysis of the NMR and mass spectroscopic data. The absolute configuration of compound 1 was determined by experimental and calculated ECD spectra. Compound 2 displayed potent brine shrimp (Artemia salina) lethality with LD₅₀ 11.2 μM. Full article

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426 KiB

Open AccessReview

Marine Compounds with Therapeutic Potential in Gram-Negative Sepsis

by Tamara Solov'eva, Viktoria Davydova, Inna Krasikova and Irina Yermak

Mar. Drugs 2013, 11(6), 2216-2229; https://doi.org/10.3390/md11062216 - 19 Jun 2013

Cited by 45 | Viewed by 9718

Abstract

This paper concerns the potential use of compounds, including lipid A, chitosan, and carrageenan, from marine sources as agents for treating endotoxemic complications from Gram-negative infections, such as sepsis and endotoxic shock. Lipid A, which can be isolated from various species of marine [...] Read more.

This paper concerns the potential use of compounds, including lipid A, chitosan, and carrageenan, from marine sources as agents for treating endotoxemic complications from Gram-negative infections, such as sepsis and endotoxic shock. Lipid A, which can be isolated from various species of marine bacteria, is a potential antagonist of bacterial endotoxins (lipopolysaccharide (LPSs)). Chitosan is a widespread marine polysaccharide that is derived from chitin, the major component of crustacean shells. The potential of chitosan as an LPS-binding and endotoxin-neutralizing agent is also examined in this paper, including a discussion on the generation of hydrophobic chitosan derivatives to increase the binding affinity of chitosan to LPS. In addition, the ability of carrageenan, which is the polysaccharide of red alga, to decrease the toxicity of LPS is discussed. We also review data obtained using animal models that demonstrate the potency of carrageenan and chitosan as antiendotoxin agents. Full article

(This article belongs to the Special Issue Selected Papers from the 1st Symposium on Marine Enzymes and Polysaccharides)

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705 KiB

Open AccessArticle

Conopeptides from Cape Verde Conus crotchii

by Jorge Neves, Alexandre Campos, Hugo Osório, Agostinho Antunes and Vitor Vasconcelos

Mar. Drugs 2013, 11(6), 2203-2215; https://doi.org/10.3390/md11062203 - 19 Jun 2013

Cited by 12 | Viewed by 8529

Abstract

Marine Cone snails of the genus Conus contain complex peptide toxins in their venom. Living in tropical habitats, they usually use the powerful venom for self-defense and prey capture. Here, we study Conus crotchii venom duct using a peptide mass-matching approach. The C. [...] Read more.

Marine Cone snails of the genus Conus contain complex peptide toxins in their venom. Living in tropical habitats, they usually use the powerful venom for self-defense and prey capture. Here, we study Conus crotchii venom duct using a peptide mass-matching approach. The C. crotchii was collected on the Cape Verde archipelago in the Boa Vista Island. The venom was analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). About 488 molecular masses between 700 Da and 3000 Da were searched bymatching with known peptide sequences from UniProtKB protein sequence database. Through this method we were able to identify 12 conopeptides. For validation we considered the error between the experimental molecular mass (monoisotopic) and the calculated mass of less than 0.5 Da. All conopeptides detected belong to the A-, O1-, O2-, O3-, T- and D-superfamilies, which can block Ca²⁺ channels, inhibit K⁺channels and act on nicotinic acetylcholine receptors (nAChRs). Only a few of the detected peptides have a 100% UniProtKB database similarity, suggesting that several of them could be newly discovered marine drugs. Full article

(This article belongs to the Special Issue Marine Peptides and Their Mimetics)

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1372 KiB

Open AccessArticle

Deep Sea Water Modulates Blood Pressure and Exhibits Hypolipidemic Effects via the AMPK-ACC Pathway: An in Vivo Study

by Ming-Jyh Sheu, Pei-Yu Chou, Wen-Hsin Lin, Chun-Hsu Pan, Yi-Chung Chien, Yun-Lung Chung, Fon-Chang Liu and Chieh-Hsi Wu

Mar. Drugs 2013, 11(6), 2183-2202; https://doi.org/10.3390/md11062183 - 17 Jun 2013

Cited by 45 | Viewed by 13488

Abstract

Deep sea water (DSW), originally pumped from the Pacific Rim off the coast of Hualien County (Taiwan), and its mineral constituents, were concentrated by a low-temperature vacuum evaporation system to produce a hardness of approximately 400,000 mg/L of seawater mineral concentrate. The primary [...] Read more.

Deep sea water (DSW), originally pumped from the Pacific Rim off the coast of Hualien County (Taiwan), and its mineral constituents, were concentrated by a low-temperature vacuum evaporation system to produce a hardness of approximately 400,000 mg/L of seawater mineral concentrate. The primary composition of this seawater mineral concentrate was ionic magnesium (Mg²⁺), which was approximately 96,000 mg/L. Referring to the human recommended daily allowance (RDA) of magnesium, we diluted the mineral concentrate to three different dosages: 0.1 × DSW (equivalent to 3.75 mg Mg²⁺/kg DSW); 1 × DSW (equivalent to 37.5 mg Mg²⁺/kg DSW); and 2 × DSW (equivalent to 75 mg Mg²⁺/kg DSW). Additionally, a magnesium chloride treatment was conducted for comparison with the DSW supplement. The study indicated that 0.1 × DSW, 1 × DSW and 2 × DSW decreased the systolic and diastolic pressures in spontaneous hypertensive rats in an eight-week experiment. DSW has been shown to reduce serum lipids and prevent atherogenesis in a hypercholesterolemic rabbit model. Our results demonstrated that 1 × DSW and 2 × DSW significantly suppressed the serum cholesterol levels, reduced the lipid accumulation in liver tissues, and limited aortic fatty streaks. These findings indicated that the antiatherogenic effects of DSW are associated with 5′-adenosine monophosphate-activated protein kinase (AMPK) stimulation and the consequent inhibition of phosphorylation of acetyl-CoA carboxylase (ACC) in atherosclerotic rabbits. We hypothesize that DSW could potentially be used as drinking water because it modulates blood pressure, reduces lipids, and prevents atherogenesis. Full article

(This article belongs to the Special Issue Deep-Sea Natural Products)

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Open AccessArticle

Synchronized Regulation of Different Zwitterionic Metabolites in the Osmoadaption of Phytoplankton

by Björn Gebser and Georg Pohnert

Mar. Drugs 2013, 11(6), 2168-2182; https://doi.org/10.3390/md11062168 - 17 Jun 2013

Cited by 61 | Viewed by 8553

Abstract

The ability to adapt to different seawater salinities is essential for cosmopolitan marine phytoplankton living in very diverse habitats. In this study, we examined the role of small zwitterionic metabolites in the osmoadaption of two common microalgae species Emiliania huxleyi and Prorocentrum minimum [...] Read more.

The ability to adapt to different seawater salinities is essential for cosmopolitan marine phytoplankton living in very diverse habitats. In this study, we examined the role of small zwitterionic metabolites in the osmoadaption of two common microalgae species Emiliania huxleyi and Prorocentrum minimum. By cultivation of the algae under salinities between 16‰ and 38‰ and subsequent analysis of dimethylsulfoniopropionate (DMSP), glycine betaine (GBT), gonyol, homarine, trigonelline, dimethylsulfonioacetate, trimethylammonium propionate, and trimethylammonium butyrate using HPLC-MS, we could reveal two fundamentally different osmoadaption mechanisms. While E. huxleyi responded with cell size reduction and a nearly constant ratio between the major metabolites DMSP, GBT and homarine to increasing salinity, osmolyte composition of P. minimum changed dramatically. In this alga DMSP concentration remained nearly constant at 18.6 mM between 20‰ and 32‰ but the amount of GBT and dimethylsulfonioacetate increased from 4% to 30% of total investigated osmolytes. Direct quantification of zwitterionic metabolites via LC-MS is a powerful tool to unravel the complex osmoadaption and regulation mechanisms of marine phytoplankton. Full article

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Open AccessArticle

Cembrane Derivatives from the Soft Corals, Sinularia gaweli and Sinularia flexibilis

by Li-Chung Hu, Wei-Hsuan Yen, Jui-Hsin Su, Michael Yen-Nan Chiang, Zhi-Hong Wen, Wu-Fu Chen, Ting-Jang Lu, Yu-Wei Chang, Yung-Husan Chen, Wei-Hsien Wang, Yang-Chang Wu and Ping-Jyun Sung

Mar. Drugs 2013, 11(6), 2154-2167; https://doi.org/10.3390/md11062154 - 17 Jun 2013

Cited by 27 | Viewed by 7308

Abstract

A new norcembranoidal diterpene, 1-epi-sinulanorcembranolide A (1), and a new cembranoidal diterpene, flexibilin D (2), were isolated from the soft corals, Sinularia gaweli and Sinularia flexibilis, respectively. The structures of new metabolites 1 and 2 were [...] Read more.

A new norcembranoidal diterpene, 1-epi-sinulanorcembranolide A (1), and a new cembranoidal diterpene, flexibilin D (2), were isolated from the soft corals, Sinularia gaweli and Sinularia flexibilis, respectively. The structures of new metabolites 1 and 2 were elucidated by spectroscopic methods, and compound 2 was found to significantly inhibit the accumulation of the pro-inflammatory iNOS and COX-2 proteins of the lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. In addition, S. flexibilis yielded a known cembrane, 5-dehydrosinulariolide (3); the structure, including its absolute stereochemistry, was further confirmed by single-crystal X-ray diffraction analysis. Full article

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Open AccessArticle

Tetrodotoxin Blockade on Canine Cardiac L-Type Ca²⁺ Channels Depends on pH and Redox Potential

by Bence Hegyi, István Komáromi, Kornél Kistamás, Ferenc Ruzsnavszky, Krisztina Váczi, Balázs Horváth, János Magyar, Tamás Bányász, Péter P. Nánási and Norbert Szentandrássy

Mar. Drugs 2013, 11(6), 2140-2153; https://doi.org/10.3390/md11062140 - 14 Jun 2013

Cited by 10 | Viewed by 7858

Abstract

Tetrodotoxin (TTX) is believed to be one of the most selective inhibitors of voltage-gated fast Na⁺ channels in excitable tissues. Recently, however, TTX has been shown to block L-type Ca²⁺ current (I_Ca) in canine cardiac cells. In the present [...] Read more.

Tetrodotoxin (TTX) is believed to be one of the most selective inhibitors of voltage-gated fast Na⁺ channels in excitable tissues. Recently, however, TTX has been shown to block L-type Ca²⁺ current (I_Ca) in canine cardiac cells. In the present study, the TTX-sensitivity of I_Ca was studied in isolated canine ventricular myocytes as a function of (1) channel phosphorylation, (2) extracellular pH and (3) the redox potential of the bathing medium using the whole cell voltage clamp technique. Fifty-five micromoles of TTX (IC₅₀ value obtained under physiological conditions) caused 60% ± 2% inhibition of I_Ca in acidic (pH = 6.4), while only a 26% ± 2% block in alkaline (pH = 8.4) milieu. Similarly, the same concentration of TTX induced 62% ± 6% suppression of I_Ca in a reductant milieu (containing glutathione + ascorbic acid + dithiothreitol, 1 mM each), in contrast to the 31% ± 3% blockade obtained in the presence of a strong oxidant (100 μM H₂O₂). Phosphorylation of the channel protein (induced by 3 μM forskolin) failed to modify the inhibiting potency of TTX; an IC₅₀ value of 50 ± 4 μM was found in forskolin. The results are in a good accordance with the predictions of our model, indicating that TTX binds, in fact, to the selectivity filter of cardiac L-type Ca channels. Full article

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Open AccessArticle

Site-Specific Variability in the Chemical Diversity of the Antarctic Red Alga Plocamium cartilagineum

by Ryan M. Young, Jacqueline L. Von Salm, Margaret O. Amsler, Juan Lopez-Bautista, Charles D. Amsler, James B. McClintock and Bill J. Baker

Mar. Drugs 2013, 11(6), 2126-2139; https://doi.org/10.3390/md11062126 - 14 Jun 2013

Cited by 26 | Viewed by 7984

Abstract

Plocamium cartilagineum is a common red alga on the benthos of Antarctica and can be a dominant understory species along the western Antarctic Peninsula. Algae from this region have been studied chemically, and like “P. cartilagineum” from other worldwide locations where [...] Read more.

Plocamium cartilagineum is a common red alga on the benthos of Antarctica and can be a dominant understory species along the western Antarctic Peninsula. Algae from this region have been studied chemically, and like “P. cartilagineum” from other worldwide locations where it is common, it is rich in halogenated monoterpenes, some of which have been implicated as feeding deterrents toward sympatric algal predators. Secondary metabolites are highly variable in this alga, both qualitatively and quantitatively, leading us to probe individual plants to track the possible link of variability to genetic or other factors. Using cox1 and rbcL gene sequencing, we find that the Antarctic alga divides into two closely related phylogroups, but not species, each of which is further divided into one of five chemogroups. The chemogroups themselves, defined on the basis of Bray-Curtis similarity profiling of GC/QqQ chromatographic analyses, are largely site specific within a 10 km² area. Thus, on the limited geographical range of this analysis, P. cartilagineum displays only modest genetic radiation, but its secondary metabolome was found to have experienced more extensive radiation. Such metabogenomic divergence demonstrated on the larger geographical scale of the Antarctic Peninsula, or perhaps even continent-wide, may contribute to the discovery of cryptic speciation. Full article

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Open AccessArticle

Antibacterial and Cytotoxic New Napyradiomycins from the Marine-Derived Streptomyces sp. SCSIO 10428

by Zhengchao Wu, Sumei Li, Jie Li, Yuchan Chen, Kumar Saurav, Qingbo Zhang, Haibo Zhang, Wenjun Zhang, Weimin Zhang, Si Zhang and Changsheng Zhang

Mar. Drugs 2013, 11(6), 2113-2125; https://doi.org/10.3390/md11062113 - 14 Jun 2013

Cited by 54 | Viewed by 9736

Abstract

Three new napyradiomycins (1–3) were isolated from the culture broth of a marine-derived actinomycete strain SCSIO 10428, together with six known related analogues napyradiomycin A1 (4), 18-oxonapyradiomycin A1 (5), napyradiomycin B1 (6), napyradiomycin [...] Read more.

Three new napyradiomycins (1–3) were isolated from the culture broth of a marine-derived actinomycete strain SCSIO 10428, together with six known related analogues napyradiomycin A1 (4), 18-oxonapyradiomycin A1 (5), napyradiomycin B1 (6), napyradiomycin B3 (7), naphthomevalin (8), and napyradiomycin SR (9). The strain SCSIO 10428 was identified as a Streptomyces species by the sequence analysis of its 16S rRNA gene. The structures of new compounds 1–3, designated 4-dehydro-4a-dechlorona pyradiomycin A1 (1), 3-dechloro-3-bromonapyradiomycin A1 (2), and 3-chloro-6, 8-dihydroxy-8-α-lapachone (3), respectively, were elucidated by comparing their 1D and 2D NMR spectroscopic data with known congeners. None of the napyradiomycins 1–9 showed antioxidative activities. Napyradiomycins 1–8 displayed antibacterial activities against three Gram-positive bacteria Staphylococcus and Bacillus strains with MIC values ranging from 0.25 to 32 μg mL⁻¹, with the exception that compound 3 had a MIC value of above 128 μg mL⁻¹ against Staphylococcus aureus ATCC 29213. Napyradiomycins 2, 4, 6, and 7 exhibited moderate cytotoxicities against four human cancer cell lines SF-268, MCF-7, NCI-H460, and HepG-2 with IC₅₀ values below 20 μM, while the IC₅₀ values for other five napyradiomycins 1, 3, 5, 8 and 9 were above 20 μM. Full article

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Open AccessReview

Protease Inhibitors from Marine Venomous Animals and Their Counterparts in Terrestrial Venomous Animals

by Caroline B. F. Mourão and Elisabeth F. Schwartz

Mar. Drugs 2013, 11(6), 2069-2112; https://doi.org/10.3390/md11062069 - 14 Jun 2013

Cited by 80 | Viewed by 10654

Abstract

The Kunitz-type protease inhibitors are the best-characterized family of serine protease inhibitors, probably due to their abundance in several organisms. These inhibitors consist of a chain of ~60 amino acid residues stabilized by three disulfide bridges, and was first observed in the bovine [...] Read more.

The Kunitz-type protease inhibitors are the best-characterized family of serine protease inhibitors, probably due to their abundance in several organisms. These inhibitors consist of a chain of ~60 amino acid residues stabilized by three disulfide bridges, and was first observed in the bovine pancreatic trypsin inhibitor (BPTI)-like protease inhibitors, which strongly inhibit trypsin and chymotrypsin. In this review we present the protease inhibitors (PIs) described to date from marine venomous animals, such as from sea anemone extracts and Conus venom, as well as their counterparts in terrestrial venomous animals, such as snakes, scorpions, spiders, Anurans, and Hymenopterans. More emphasis was given to the Kunitz-type inhibitors, once they are found in all these organisms. Their biological sources, specificity against different proteases, and other molecular blanks (being also K⁺ channel blockers) are presented, followed by their molecular diversity. Whereas sea anemone, snakes and other venomous animals present mainly Kunitz-type inhibitors, PIs from Anurans present the major variety in structure length and number of Cys residues, with at least six distinguishable classes. A representative alignment of PIs from these venomous animals shows that, despite eventual differences in Cys assignment, the key-residues for the protease inhibitory activity in all of them occupy similar positions in primary sequence. The key-residues for the K⁺ channel blocking activity was also compared. Full article

(This article belongs to the Special Issue Marine Peptides and Their Mimetics)

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Open AccessArticle

Bioactive Phenylalanine Derivatives and Cytochalasins from the Soft Coral-Derived Fungus, Aspergillus elegans

by Cai-Juan Zheng, Chang-Lun Shao, Lu-Yong Wu, Min Chen, Kai-Ling Wang, Dong-Lin Zhao, Xue-Ping Sun, Guang-Ying Chen and Chang-Yun Wang

Mar. Drugs 2013, 11(6), 2054-2068; https://doi.org/10.3390/md11062054 - 10 Jun 2013

Cited by 79 | Viewed by 9668

Abstract

One new phenylalanine derivative 4′-OMe-asperphenamate (1), along with one known phenylalanine derivative (2) and two new cytochalasins, aspochalasin A1 (3) and cytochalasin Z24 (4), as well as eight known cytochalasin analogues (5–12 [...] Read more.

One new phenylalanine derivative 4′-OMe-asperphenamate (1), along with one known phenylalanine derivative (2) and two new cytochalasins, aspochalasin A1 (3) and cytochalasin Z24 (4), as well as eight known cytochalasin analogues (5–12) were isolated from the fermentation broth of Aspergillus elegans ZJ-2008010, a fungus obtained from a soft coral Sarcophyton sp. collected from the South China Sea. Their structures and the relative configurations were elucidated using comprehensive spectroscopic methods. The absolute configuration of 1 was determined by chemical synthesis and Marfey’s method. All isolated metabolites (1–12) were evaluated for their antifouling and antibacterial activities. Cytochalasins 5, 6, 8 and 9 showed strong antifouling activity against the larval settlement of the barnacle Balanus amphitrite, with the EC₅₀ values ranging from 6.2 to 37 μM. This is the first report of antifouling activity for this class of metabolites. Additionally, 8 exhibited a broad spectrum of antibacterial activity, especially against four pathogenic bacteria Staphylococcus albus, S. aureus, Escherichia coli and Bacillus cereus. Full article

(This article belongs to the Special Issue Bioactive Compounds from Marine Fungi)

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Open AccessArticle

Four New Briarane Diterpenoids from Taiwanese Gorgonian Junceella fragilis

by Chia-Ching Liaw, Yu-Chi Lin, Yun-Sheng Lin, Chung-Hsiung Chen, Tsong-Long Hwang and Ya-Ching Shen

Mar. Drugs 2013, 11(6), 2042-2053; https://doi.org/10.3390/md11062042 - 10 Jun 2013

Cited by 20 | Viewed by 6095

Abstract

Four new 8-hydroxybriarane diterpenoids, frajunolides P–S (1–4), together with umbraculolide A, juncenolide C, junceellonoid A and juncin R, were isolated from the acetone extract of the gorgonian Junceella fragilis, collected from the southeast coast of Taiwan. Compound 1 [...] Read more.

Four new 8-hydroxybriarane diterpenoids, frajunolides P–S (1–4), together with umbraculolide A, juncenolide C, junceellonoid A and juncin R, were isolated from the acetone extract of the gorgonian Junceella fragilis, collected from the southeast coast of Taiwan. Compound 1 contains an unusual pivaloyloxy group at C-2, while 3 is a rare compound having a chlorine atom on the olefinic carbon (C-6). The structures of the isolated compounds were established by extensive spectroscopic analysis, including 1D- and 2D-NMR, as well as HRMS data. Compound 1 was further confirmed by X-ray crystallographic analysis. In the anti-inflammatory test, compounds 1 and 2 exhibited moderate inhibition on superoxide anion generation and elastase release by human neutrophils in response to formylmethionylleucyl-phenylalanine/dihydrocytochalasin B (fMLP/CB). Full article

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Open AccessReview

Antifreeze Peptides and Glycopeptides, and Their Derivatives: Potential Uses in Biotechnology

by Jeong Kyu Bang, Jun Hyuck Lee, Ravichandran N. Murugan, Sung Gu Lee, Hackwon Do, Hye Yeon Koh, Hye-Eun Shim, Hyun-Cheol Kim and Hak Jun Kim

Mar. Drugs 2013, 11(6), 2013-2041; https://doi.org/10.3390/md11062013 - 10 Jun 2013

Cited by 40 | Viewed by 12885

Abstract

Antifreeze proteins (AFPs) and glycoproteins (AFGPs), collectively called AF(G)Ps, constitute a diverse class of proteins found in various Arctic and Antarctic fish, as well as in amphibians, plants, and insects. These compounds possess the ability to inhibit the formation of ice and are [...] Read more.

Antifreeze proteins (AFPs) and glycoproteins (AFGPs), collectively called AF(G)Ps, constitute a diverse class of proteins found in various Arctic and Antarctic fish, as well as in amphibians, plants, and insects. These compounds possess the ability to inhibit the formation of ice and are therefore essential to the survival of many marine teleost fishes that routinely encounter sub-zero temperatures. Owing to this property, AF(G)Ps have potential applications in many areas such as storage of cells or tissues at low temperature, ice slurries for refrigeration systems, and food storage. In contrast to AFGPs, which are composed of repeated tripeptide units (Ala-Ala-Thr)_n with minor sequence variations, AFPs possess very different primary, secondary, and tertiary structures. The isolation and purification of AFGPs is laborious, costly, and often results in mixtures, making characterization difficult. Recent structural investigations into the mechanism by which linear and cyclic AFGPs inhibit ice crystallization have led to significant progress toward the synthesis and assessment of several synthetic mimics of AFGPs. This review article will summarize synthetic AFGP mimics as well as current challenges in designing compounds capable of mimicking AFGPs. It will also cover our recent efforts in exploring whether peptoid mimics can serve as structural and functional mimics of native AFGPs. Full article

(This article belongs to the Special Issue Marine Peptides and Their Mimetics)

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Open AccessArticle

Flexibilins A–C, New Cembrane-Type Diterpenoids from the Formosan Soft Coral, Sinularia flexibilis

by Li-Chung Hu, Jui-Hsin Su, Michael Yen-Nan Chiang, Mei-Chin Lu, Tsong-Long Hwang, Yung-Husan Chen, Wan-Ping Hu, Nai-Cheng Lin, Wei-Hsien Wang, Lee-Shing Fang, Yueh-Hsiung Kuo and Ping-Jyun Sung

Mar. Drugs 2013, 11(6), 1999-2012; https://doi.org/10.3390/md11061999 - 10 Jun 2013

Cited by 20 | Viewed by 6759

Abstract

Three new cembrane-type diterpenoids, flexibilins A–C (1–3), along with a known cembrane, (−)-sandensolide (4), were isolated from the soft coral, Sinularia flexibilis. The structures of cembranes 1–4 were elucidated by spectroscopic methods. The structure of 4, including its absolute stereochemistry, was further [...] Read more.

Three new cembrane-type diterpenoids, flexibilins A–C (1–3), along with a known cembrane, (−)-sandensolide (4), were isolated from the soft coral, Sinularia flexibilis. The structures of cembranes 1–4 were elucidated by spectroscopic methods. The structure of 4, including its absolute stereochemistry, was further confirmed by single-crystal X-ray diffraction analysis. Cembrane 2 displayed a moderate inhibitory effect on the release of elastase by human neutrophils. Full article

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Open AccessArticle

Comparative Analysis of Glycoside Hydrolases Activities from Phylogenetically Diverse Marine Bacteria of the Genus Arenibacter

by Irina Bakunina, Olga Nedashkovskaya, Larissa Balabanova, Tatyana Zvyagintseva, Valery Rasskasov and Valery Mikhailov

Mar. Drugs 2013, 11(6), 1977-1998; https://doi.org/10.3390/md11061977 - 10 Jun 2013

Cited by 21 | Viewed by 7979

Abstract

A total of 16 marine strains belonging to the genus Arenibacter, recovered from diverse microbial communities associated with various marine habitats and collected from different locations, were evaluated in degradation of natural polysaccharides and chromogenic glycosides. Most strains were affiliated with five [...] Read more.

A total of 16 marine strains belonging to the genus Arenibacter, recovered from diverse microbial communities associated with various marine habitats and collected from different locations, were evaluated in degradation of natural polysaccharides and chromogenic glycosides. Most strains were affiliated with five recognized species, and some presented three new species within the genus Arenibacter. No strains contained enzymes depolymerizing polysaccharides, but synthesized a wide spectrum of glycosidases. Highly active β-N-acetylglucosaminidases and α-N-acetylgalactosaminidases were the main glycosidases for all Arenibacter. The genes, encoding two new members of glycoside hydrolyses (GH) families, 20 and 109, were isolated and characterized from the genomes of Arenibacter latericius. Molecular genetic analysis using glycosidase-specific primers shows the absence of GH27 and GH36 genes. A sequence comparison with functionally-characterized GH20 and GH109 enzymes shows that both sequences are closest to the enzymes of chitinolytic bacteria Vibrio furnissii and Cellulomonas fimi of marine and terrestrial origin, as well as human pathogen Elisabethkingia meningoseptica and simbionts Akkermansia muciniphila, gut and non-gut Bacteroides, respectively. These results revealed that the genus Arenibacter is a highly taxonomic diverse group of microorganisms, which can participate in degradation of natural polymers in marine environments depending on their niche and habitat adaptations. They are new prospective candidates for biotechnological applications due to their production of unique glycosidases. Full article

(This article belongs to the Special Issue Selected Papers from the 1st Symposium on Marine Enzymes and Polysaccharides)

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Open AccessArticle

Fucoidan Derived from Undaria pinnatifida Induces Apoptosis in Human Hepatocellular Carcinoma SMMC-7721 Cells via the ROS-Mediated Mitochondrial Pathway

by Lili Yang, Peisheng Wang, Huaxin Wang, Qiaomei Li, Hongming Teng, Zhichao Liu, Wenbo Yang, Lin Hou and Xiangyang Zou

Mar. Drugs 2013, 11(6), 1961-1976; https://doi.org/10.3390/md11061961 - 10 Jun 2013

Cited by 140 | Viewed by 12323

Abstract

Fucoidans, fucose-enriched sulfated polysaccharides isolated from brown algae and marine invertebrates, have been shown to exert anticancer activity in several types of human cancer, including leukemia and breast cancer and in lung adenocarcinoma cells. In the present study, the anticancer activity of the [...] Read more.

Fucoidans, fucose-enriched sulfated polysaccharides isolated from brown algae and marine invertebrates, have been shown to exert anticancer activity in several types of human cancer, including leukemia and breast cancer and in lung adenocarcinoma cells. In the present study, the anticancer activity of the fucoidan extracted from the brown seaweed Undaria pinnatifida was investigated in human hepatocellular carcinoma SMMC-7721 cells, and the underlying mechanisms of action were investigated. SMMC-7721 cells exposed to fucoidan displayed growth inhibition and several typical features of apoptotic cells, such as chromatin condensation and marginalization, a decrease in the number of mitochondria, and in mitochondrial swelling and vacuolation. Fucoidan-induced cell death was associated with depletion of reduced glutathione (GSH), accumulation of high intracellular levels of reactive oxygen species (ROS), and accompanied by damage to the mitochondrial ultrastructure, depolarization of the mitochondrial membrane potential (MMP, Δψm) and caspase activation. Moreover, fucoidan led to altered expression of factors related to apoptosis, including downregulating Livin and XIAP mRNA, which are members of the inhibitor of apoptotic protein (IAP) family, and increased the Bax-to-Bcl-2 ratio. These findings suggest that fucoidan isolated from U. pinnatifida induced apoptosis in SMMC-7721 cells via the ROS-mediated mitochondrial pathway. Full article

(This article belongs to the Collection Marine Compounds and Cancer)

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Open AccessArticle

New Invertebrate Vectors for PST, Spirolides and Okadaic Acid in the North Atlantic

by Marisa Silva, Aldo Barreiro, Paula Rodriguez, Paz Otero, Joana Azevedo, Amparo Alfonso, Luis M. Botana and Vitor Vasconcelos

Mar. Drugs 2013, 11(6), 1936-1960; https://doi.org/10.3390/md11061936 - 5 Jun 2013

Cited by 32 | Viewed by 7916

Abstract

The prevalence of poisoning events due to harmful algal blooms (HABs) has declined during the last two decades through monitoring programs and legislation, implemented mainly for bivalves. However, new toxin vectors and emergent toxins pose a challenge to public health. Several locations on [...] Read more.

The prevalence of poisoning events due to harmful algal blooms (HABs) has declined during the last two decades through monitoring programs and legislation, implemented mainly for bivalves. However, new toxin vectors and emergent toxins pose a challenge to public health. Several locations on the Portuguese coast were surveyed between 2009 and 2010 for three distinct biotoxin groups [saxitoxin (PST), spirolide (SPX) and okadaic acid (OA)], in 14 benthic species of mollusks and echinoderms. Our main goals were to detect new vectors and unravel the seasonal and geographical patterns of these toxins. PSTs were analyzed by the Lawrence method, SPXs by LC-MS/MS, and OA by LC-MS/MS and UPLC-MS/MS. We report 16 new vectors for these toxins in the North Atlantic. There were differences in toxin contents among species, but no significant geographical or seasonal patterns were found. Our results suggest that legislation should be adjusted to extend the monitoring of marine toxins to a wider range of species besides edible bivalves. Full article

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Perna canaliculus Lipid Complex PCSO-524™ Demonstrated Pain Relief for Osteoarthritis Patients Benchmarked against Fish Oil, a Randomized Trial, without Placebo Control

by Marek Zawadzki, Claudia Janosch and Jacek Szechinski

Mar. Drugs 2013, 11(6), 1920-1935; https://doi.org/10.3390/md11061920 - 5 Jun 2013

Cited by 29 | Viewed by 12771

Abstract

Osteoarthritis (OA) typically generates pain, reduced mobility and reduced quality of life. Most conventional treatments for osteoarthritis, such as non-steroidal anti-inflammatory drugs (NSAIDs) and simple analgesics, have side effects. PCSO-524™, a non polar lipid extract from the New Zealand Green Lipped Mussel, is [...] Read more.

Osteoarthritis (OA) typically generates pain, reduced mobility and reduced quality of life. Most conventional treatments for osteoarthritis, such as non-steroidal anti-inflammatory drugs (NSAIDs) and simple analgesics, have side effects. PCSO-524™, a non polar lipid extract from the New Zealand Green Lipped Mussel, is rich in omega-3 fatty acids and has been shown to reduce inflammation in both animal studies and patient trials. This OA trial examined pain relief changes in relation to quality of life and safety of use for OA patients who took PCSO-524™ compared with patients who took fish oil (containing an industry standard EPA-18% and DHA-12% blend). PCSO-524™ patients showed a statistically significant improvement compared with patients who took fish oil. There was an 89% decrease in their pain symptoms and 91% reported an improved quality of life. Patients treated with fish oil showed significantly less improvement and a greater level of physical discomfort during the study. These results suggest that PCSO-524™ might offer a potential alternative complementary therapy with no side effects for OA patients. Full article

(This article belongs to the Special Issue Marine Compounds and Inflammation)

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Effect of Astaxanthin on Human Sperm Capacitation

by Gabriella Donà, Ivana Kožuh, Anna Maria Brunati, Alessandra Andrisani, Guido Ambrosini, Guglielmo Bonanni, Eugenio Ragazzi, Decio Armanini, Giulio Clari and Luciana Bordin

Mar. Drugs 2013, 11(6), 1909-1919; https://doi.org/10.3390/md11061909 - 3 Jun 2013

Cited by 43 | Viewed by 9242

Abstract

In order to be able to fertilize oocytes, human sperm must undergo a series of morphological and structural alterations, known as capacitation. It has been shown that the production of endogenous sperm reactive oxygen species (ROS) plays a key role in causing cells [...] Read more.

In order to be able to fertilize oocytes, human sperm must undergo a series of morphological and structural alterations, known as capacitation. It has been shown that the production of endogenous sperm reactive oxygen species (ROS) plays a key role in causing cells to undergo a massive acrosome reaction (AR). Astaxanthin (Asta), a photo-protective red pigment belonging to the carotenoid family, is recognized as having anti-oxidant, anti-cancer, anti-diabetic and anti-inflammatory properties and is present in many dietary supplements. This study evaluates the effect of Asta in a capacitating buffer which induces low ROS production and low percentages of acrosome-reacted cells (ARC). Sperm cells were incubated in the presence or absence of increasing concentrations of Asta or diamide (Diam) and analyzed for their ROS production, Tyr-phosphorylation (Tyr-P) pattern and percentages of ARC and non-viable cells (NVC). Results show that Asta ameliorated both sperm head Tyr-P and ARC values without affecting the ROS generation curve, whereas Diam succeeded in enhancing the Tyr-P level but only of the flagellum without increasing ARC values. It is suggested that Asta can be inserted in the membrane and therefore create capacitation-like membrane alteration which allow Tyr-P of the head. Once this has occurred, AR can take place and involves a higher numbers of cells. Full article

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The Extract of Rhodobacter sphaeroides Inhibits Melanogenesis through the MEK/ERK Signaling Pathway

by Wen-Sheng Liu, Yu-Diao Kuan, Kuo-Hsun Chiu, Wei-Kuang Wang, Fu-Hsin Chang, Chen-Hsun Liu and Che-Hsin Lee

Mar. Drugs 2013, 11(6), 1899-1908; https://doi.org/10.3390/md11061899 - 3 Jun 2013

Cited by 40 | Viewed by 8342

Abstract

Reducing hyperpigmentation has been a big issue for years. Even though pigmentation is a normal mechanism protecting skin from UV-causing DNA damage and oxidative stress, it is still an aesthetic problem for many people. Bacteria can produce some compounds in response to their [...] Read more.

Reducing hyperpigmentation has been a big issue for years. Even though pigmentation is a normal mechanism protecting skin from UV-causing DNA damage and oxidative stress, it is still an aesthetic problem for many people. Bacteria can produce some compounds in response to their environment. These compounds are widely used in cosmetic and pharmaceutical applications. Some probiotics have immunomodulatory activities and modulate the symptoms of several diseases. Previously, we found that the extracts of Rhodobacter sphaeroides (Lycogen™) inhibited nitric oxide production and inducible nitric-oxide synthase expression in activated macrophages. In this study, we sought to investigate an anti-melanogenic signaling pathway in α-melanocyte stimulating hormone (α-MSH)-treated B16F10 melanoma cells and zebrafish. Treatment with Lycogen™ inhibited the cellular melanin contents and expression of melanogenesis-related protein, including microphthalmia-associated transcription factor (MITF) and tyrosinase in B16F10 cells. Moreover, Lycogen™ reduced phosphorylation of MEK/ERK without affecting phosphorylation of p38. Meanwhile, Lycogen™ decreased zebrafish melanin expression in a dose-dependent manner. These findings establish Lycogen™ as a new target in melanogenesis and suggest a mechanism of action through the ERK signaling pathway. Our results suggested that Lycogen™ may have potential cosmetic usage in the future. Full article

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Subtilomycin: A New Lantibiotic from Bacillus subtilis Strain MMA7 Isolated from the Marine Sponge Haliclona simulans

by Robert W. Phelan, Matthieu Barret, Paul D. Cotter, Paula M. O'Connor, Rui Chen, John P. Morrissey, Alan D. W. Dobson, Fergal O'Gara and Teresa M. Barbosa

Mar. Drugs 2013, 11(6), 1878-1898; https://doi.org/10.3390/md11061878 - 3 Jun 2013

Cited by 83 | Viewed by 12015

Abstract

Bacteriocins are attracting increased attention as an alternative to classic antibiotics in the fight against infectious disease and multidrug resistant pathogens. Bacillus subtilis strain MMA7 isolated from the marine sponge Haliclona simulans displays a broad spectrum antimicrobial activity, which includes Gram-positive and Gram-negative [...] Read more.

Bacteriocins are attracting increased attention as an alternative to classic antibiotics in the fight against infectious disease and multidrug resistant pathogens. Bacillus subtilis strain MMA7 isolated from the marine sponge Haliclona simulans displays a broad spectrum antimicrobial activity, which includes Gram-positive and Gram-negative pathogens, as well as several pathogenic Candida species. This activity is in part associated with a newly identified lantibiotic, herein named as subtilomycin. The proposed biosynthetic cluster is composed of six genes, including protein-coding genes for LanB-like dehydratase and LanC-like cyclase modification enzymes, characteristic of the class I lantibiotics. The subtilomycin biosynthetic cluster in B. subtilis strain MMA7 is found in place of the sporulation killing factor (skf) operon, reported in many B. subtilis isolates and involved in a bacterial cannibalistic behaviour intended to delay sporulation. The presence of the subtilomycin biosynthetic cluster appears to be widespread amongst B. subtilis strains isolated from different shallow and deep water marine sponges. Subtilomycin possesses several desirable industrial and pharmaceutical physicochemical properties, including activity over a wide pH range, thermal resistance and water solubility. Additionally, the production of the lantibiotic subtilomycin could be a desirable property should B. subtilis strain MMA7 be employed as a probiotic in aquaculture applications. Full article

(This article belongs to the Special Issue Marine Peptides and Their Mimetics)

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Self-Association of Okadaic Acid: Structural and Pharmacological Significance

by Patricia G. Cruz, Manuel Norte, Alberto Hernández Creus, José J. Fernández and Antonio Hernández Daranas

Mar. Drugs 2013, 11(6), 1866-1877; https://doi.org/10.3390/md11061866 - 29 May 2013

Cited by 14 | Viewed by 6897

Abstract

Okadaic acid (OA) has been an invaluable pharmacological tool in the study of cellular signaling. The great affinity of this polyether for its targets together with its high specificity to inhibit certain protein phosphatases enables the differential study of these proteins. Crystallographic structures [...] Read more.

Okadaic acid (OA) has been an invaluable pharmacological tool in the study of cellular signaling. The great affinity of this polyether for its targets together with its high specificity to inhibit certain protein phosphatases enables the differential study of these proteins. Crystallographic structures of protein phosphatases in complex with OA show a 1:1 protein to toxin ratio. Nevertheless, it has been found that OA is able to self-associate under certain conditions although very little is known about the importance of this phenomenon. Here we review the available knowledge on the latter topic and we report on the existence of an unusual self-associated tetrameric form. The structure of these oligomers is proposed based on spectroscopic data and molecular modeling calculations. Full article

(This article belongs to the Special Issue Okadaic Acid and Dinophysis Toxins)

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Cytotoxic and Anti-Inflammatory Metabolites from the Soft Coral Scleronephthya gracillimum

by Hui-Yu Fang, Chi-Hsin Hsu, Chih-Hua Chao, Zhi-Hong Wen, Yang-Chang Wu, Chang-Feng Dai and Jyh-Horng Sheu

Mar. Drugs 2013, 11(6), 1853-1865; https://doi.org/10.3390/md11061853 - 29 May 2013

Cited by 23 | Viewed by 6745

Abstract

Five new pregnane-type steroids, sclerosteroids J–N (1–5), and a diterpenoid with a new chemotype 3-methyl-5-(10′-acetoxy-2′,6′,10′-trimethylundecyl)-2-penten-5-olide (6), have been isolated from a soft coral Scleronephthya gracillimum. The structures of the metabolites were determined by extensive spectroscopic analysis. [...] Read more.

Five new pregnane-type steroids, sclerosteroids J–N (1–5), and a diterpenoid with a new chemotype 3-methyl-5-(10′-acetoxy-2′,6′,10′-trimethylundecyl)-2-penten-5-olide (6), have been isolated from a soft coral Scleronephthya gracillimum. The structures of the metabolites were determined by extensive spectroscopic analysis. Compound 4 exhibited cytotoxicity against HepG2, A549, and MDA-MB-231 cancer cell lines. Furthermore, steroids 2 and 4 were found to significantly inhibit the accumulation of the pro-inflammatory iNOS protein, and 1, 2, 4 and 5 could effectively reduce the accumulation of COX-2 protein in LPS-stimulated RAW264.7 macrophage cells. Full article

(This article belongs to the Special Issue Marine Compounds and Inflammation)

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Anti-Microbial, Anti-Biofilm Activities and Cell Selectivity of the NRC-16 Peptide Derived from Witch Flounder, Glyptocephalus cynoglossus

by Ramamourthy Gopal, Jun Ho Lee, Young Gwon Kim, Myeong-Sun Kim, Chang Ho Seo and Yoonkyung Park

Mar. Drugs 2013, 11(6), 1836-1852; https://doi.org/10.3390/md11061836 - 28 May 2013

Cited by 44 | Viewed by 9097

Abstract

Previous studies had identified novel antimicrobial peptides derived from witch flounder. In this work, we extended the search for the activity of peptide that showed antibacterial activity on clinically isolated bacterial cells and bacterial biofilm. Pseudomonas aeruginosa was obtained from otitis media and [...] Read more.

Previous studies had identified novel antimicrobial peptides derived from witch flounder. In this work, we extended the search for the activity of peptide that showed antibacterial activity on clinically isolated bacterial cells and bacterial biofilm. Pseudomonas aeruginosa was obtained from otitis media and cholelithiasis patients, while Staphylococcus aureus was isolated from otitis media patients. We found that synthetic peptide NRC-16 displays antimicrobial activity and is not sensitive to salt during its bactericidal activity. Interestingly, this peptide also led to significant inhibition of biofilm formation at a concentration of 4–16 μM. NRC-16 peptide is able to block biofilm formation at concentrations just above its minimum inhibitory concentration while conventional antibiotics did not inhibit the biofilm formation except ciprofloxacin and piperacillin. It did not cause significant lysis of human RBC, and is not cytotoxic to HaCaT cells and RAW264.7 cells, thereby indicating its selective antimicrobial activity. In addition, the peptide’s binding and permeation activities were assessed by tryptophan fluorescence, calcein leakage and circular dichroism using model mammalian membranes composed of phosphatidylcholine (PC), PC/cholesterol (CH) and PC/sphingomyelin (SM). These experiments confirmed that NRC-16 does not interact with any of the liposomes but the control peptide melittin did. Taken together, we found that NRC-16 has potent antimicrobial and antibiofilm activities with less cytotoxicity, and thus can be considered for treatment of microbial infection in the future. Full article

(This article belongs to the Special Issue Marine Peptides and Their Mimetics)

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Diarrhetic Shellfish Toxins and Other Lipophilic Toxins of Human Health Concern in Washington State

by Vera L. Trainer, Leslie Moore, Brian D. Bill, Nicolaus G. Adams, Neil Harrington, Jerry Borchert, Denis A. M. Da Silva and Bich-Thuy L. Eberhart

Mar. Drugs 2013, 11(6), 1815-1835; https://doi.org/10.3390/md11061815 - 28 May 2013

Cited by 129 | Viewed by 12082

Abstract

The illness of three people in 2011 after their ingestion of mussels collected from Sequim Bay State Park, Washington State, USA, demonstrated the need to monitor diarrhetic shellfish toxins (DSTs) in Washington State for the protection of human health. Following these cases of [...] Read more.

The illness of three people in 2011 after their ingestion of mussels collected from Sequim Bay State Park, Washington State, USA, demonstrated the need to monitor diarrhetic shellfish toxins (DSTs) in Washington State for the protection of human health. Following these cases of diarrhetic shellfish poisoning, monitoring for DSTs in Washington State became formalized in 2012, guided by routine monitoring of Dinophysis species by the SoundToxins program in Puget Sound and the Olympic Region Harmful Algal Bloom (ORHAB) partnership on the outer Washington State coast. Here we show that the DSTs at concentrations above the guidance level of 16 μg okadaic acid (OA) + dinophysistoxins (DTXs)/100 g shellfish tissue were widespread in sentinel mussels throughout Puget Sound in summer 2012 and included harvest closures of California mussel, varnish clam, manila clam and Pacific oyster. Concentrations of toxins in Pacific oyster and manila clam were often at least half those measured in blue mussels at the same site. The primary toxin isomer in shellfish and plankton samples was dinophysistoxin-1 (DTX-1) with D. acuminata as the primary Dinophysis species. Other lipophilic toxins in shellfish were pectenotoxin-2 (PTX-2) and yessotoxin (YTX) with azaspiracid-2 (AZA-2) also measured in phytoplankton samples. Okadaic acid, azaspiracid-1 (AZA-1) and azaspiracid-3 (AZA-3) were all below the levels of detection by liquid chromatography tandem mass spectrometry (LC-MS/MS). A shellfish closure at Ruby Beach, Washington, was the first ever noted on the Washington State Pacific coast due to DSTs. The greater than average Fraser River flow during the summers of 2011 and 2012 may have provided an environment conducive to dinoflagellates and played a role in the prevalence of toxigenic Dinophysis in Puget Sound. Full article

(This article belongs to the Special Issue Okadaic Acid and Dinophysis Toxins)

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A New Antiproliferative and Antioxidant Peptide Isolated from Arca subcrenata

by Lili Chen, Liyan Song, Tingfei Li, Jianhua Zhu, Jian Xu, Qin Zheng and Rongmin Yu

Mar. Drugs 2013, 11(6), 1800-1814; https://doi.org/10.3390/md11061800 - 24 May 2013

Cited by 29 | Viewed by 7606

Abstract

A new antitumor and antioxidant peptide (H3) was isolated from Arca subcrenata Lischke using ion exchange and hydrophobic column chromatography. The purity of H3 was over 99.3% in reversed phase-high performance liquid chromatography (RP-HPLC) and the molecular weight was determined to be 20,491.0 [...] Read more.

A new antitumor and antioxidant peptide (H3) was isolated from Arca subcrenata Lischke using ion exchange and hydrophobic column chromatography. The purity of H3 was over 99.3% in reversed phase-high performance liquid chromatography (RP-HPLC) and the molecular weight was determined to be 20,491.0 Da by electrospray-ionization mass spectrometry (ESI-MS/MS). The isoelectric point of H3 was measured to be 6.65 by isoelectric focusing-polyacrylamide gel electrophoresis. Partial amino acid sequence of this peptide was determined as ISMEDVEESRKNGMHSIDVNH DGKHRAYWADNTYLM-KCMDLPYDVLDTGGKDRSSDKNTDLVDLFELDMVPDRK NNECMNMIMDVIDTN-TAARPYYCSLDVNHDGAGLSMEDVEEDK via MALDI-TOF/ TOF-MS and de novo sequencing. The in vitro antitumor activity of H3 was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The result indicated that H3 exhibited significant antiproliferative activity against HeLa, HepG2 and HT-29 cell lines with IC₅₀ values of 10.8, 10.1 and 10.5 μg/mL. The scavenging percentage of H3 at 8 mg/mL to 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radicals were 56.8% and 47.5%, respectively. Full article

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The Promoting Effect of Ishige sinicola on Hair Growth

by Jung-Il Kang, Eun-JI Kim, Min-Kyoung Kim, You-Jin Jeon, Sung-Myung Kang, Young-Sang Koh, Eun-Sook Yoo and Hee-Kyoung Kang

Mar. Drugs 2013, 11(6), 1783-1799; https://doi.org/10.3390/md11061783 - 24 May 2013

Cited by 31 | Viewed by 9927

Abstract

This study was conducted to evaluate the promoting effect of Ishige sinicola, an alga native to Jeju Island, Korea, on hair growth. When vibrissa follicles were cultured in the presence of I. sinicola extract for 21 days, I. sinicola extract increased hair-fiber [...] Read more.

This study was conducted to evaluate the promoting effect of Ishige sinicola, an alga native to Jeju Island, Korea, on hair growth. When vibrissa follicles were cultured in the presence of I. sinicola extract for 21 days, I. sinicola extract increased hair-fiber length. After topical application of I. sinicola extract onto the back of C57BL/6 mice, anagen progression of the hair shaft was induced. The I. sinicola extract significantly inhibited the activity of 5α-reductase. Treatment of immortalized vibrissa dermal papilla cells (DPCs) with I. sinicola extract resulted in increase of cell proliferation, which was accompanied by the increase of phospho-GSK3β level, β-catenin, Cyclin E and CDK2, whereas p27^kip1 was down-regulated. In particular, octaphlorethol A, an isolated component from the I. sinicola extract, inhibited the activity of 5α-reductase and increased the proliferation of DPCs. These results suggest that I. sinicola extract and octaphlorethol A, a principal of I. sinicola, have the potential to treat alopecia via the proliferation of DPCs followed by the activation of β-catenin pathway, and the 5α-reductase inhibition. Full article

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Identification of Dynamic Changes in Proteins Associated with the Cellular Cytoskeleton after Exposure to Okadaic Acid

by Jill A. Opsahl, Sonja Ljostveit, Therese Solstad, Kristin Risa, Peter Roepstorff and Kari E. Fladmark

Mar. Drugs 2013, 11(6), 1763-1782; https://doi.org/10.3390/md11061763 - 24 May 2013

Cited by 31 | Viewed by 8250

Abstract

Exposure of cells to the diarrhetic shellfish poison, okadaic acid, leads to a dramatic reorganization of cytoskeletal architecture and loss of cell-cell contact. When cells are exposed to high concentrations of okadaic acid (100–500 nM), the morphological rearrangement is followed by apoptotic cell [...] Read more.

Exposure of cells to the diarrhetic shellfish poison, okadaic acid, leads to a dramatic reorganization of cytoskeletal architecture and loss of cell-cell contact. When cells are exposed to high concentrations of okadaic acid (100–500 nM), the morphological rearrangement is followed by apoptotic cell death. Okadaic acid inhibits the broad acting Ser/Thr protein phosphatases 1 and 2A, which results in hyperphosphorylation of a large number of proteins. Some of these hyperphosphorylated proteins are most likely key players in the reorganization of the cell morphology induced by okadaic acid. We wanted to identify these phosphoproteins and searched for them in the cellular lipid rafts, which have been found to contain proteins that regulate cytoskeletal dynamics and cell adhesion. By using stable isotope labeling by amino acids in cell culture cells treated with okadaic acid (400 nM) could be combined with control cells before the isolation of lipid rafts. Protein phosphorylation events and translocations induced by okadaic acid were identified by mass spectrometry. Okadaic acid was shown to regulate the phosphorylation status and location of proteins associated with the actin cytoskeleton, microtubules and cell adhesion structures. A large number of these okadaic acid-regulated proteins have previously also been shown to be similarly regulated prior to cell proliferation and migration. Our results suggest that okadaic acid activates general cell signaling pathways that induce breakdown of the cortical actin cytoskeleton and cell detachment. Full article

(This article belongs to the Special Issue Okadaic Acid and Dinophysis Toxins)

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Mar. Drugs, Volume 11, Issue 6 (June 2013) – 28 articles , Pages 1763-2238

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