Table of Contents

Abstract: Red seaweeds synthesize a great variety of sulfated galactans. Sulfated polysaccharides (PLSs) from seaweed are comprised of substances with pharmaceutical and biomedical potential. The aim of the present study was to evaluate the protective effect of the PLS fraction extracted from the seaweed Gracilaria birdiae in rats with naproxen-induced gastrointestinal damage. Male Wistar rats were pretreated with 0.5% carboxymethylcellulose (control group—vehicle) or PLS (10, 30, and 90 mg/kg, p.o.) twice daily (at 09:00 and 21:00) for 2 days. After 1 h, naproxen (80 mg/kg, p.o.) was administered. The rats were killed on day two, 4 h after naproxen treatment. The stomachs were promptly excised, opened along the greater curvature, and measured using digital calipers. Furthermore, the guts of the animals were removed, and a 5-cm portion of the small intestine (jejunum and ileum) was used for the evaluation of macroscopic scores. Samples of the stomach and the small intestine were used for histological evaluation, morphometric analysis and in assays for glutathione (GSH) levels, malonyldialdehyde (MDA) concentration, and myeloperoxidase (MPO) activity. PLS treatment reduced the macroscopic and microscopic naproxen-induced gastrointestinal damage in a dose-dependent manner. Our results suggest that the PLS fraction has a protective effect against gastrointestinal damage through mechanisms that involve the inhibition of inflammatory cell infiltration and lipid peroxidation.

Abstract: Gloiopeltis tenax (G. tenax) is widely distributed along the Chinese coastal areas and is commonly used in the treatment of diarrhea and colitis. This study aimed at investigating the bioactivities of the volatile constituents in G. tenax. We extracted the essential constituents of G. tenax by supercritical carbon dioxide extraction (CO₂-SFE), then identified and analyzed the constituents by gas chromatography-mass spectrometry (GC-MS). In total, 30 components were identified in the G. tenax extract. The components showed remarkable antioxidant activity (radical scavenging activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH)), lipid peroxidation inhibition capacity (in a β-carotene/linoleic acid-coupled oxidation reaction), and hydroxyl radical-scavenging activity (by deoxyribose degradation by iron-dependent hydroxyl radical), compared to butylated hydroxytoluene. In microdilution assays, G. tenax extracts showed a moderate inhibitory effects on Staphyloccocus aureus (minimum inhibitory concentration (MIC) = 3.9 mg/mL), Enterococcus faecalis (7.8 mg/mL), Pseudomonas aeruginosa (15.6 mg/mL), and Escherichia coli (3.9 mg/mL). Antioxidant and antimicrobial activities of G. tenax were related to the active chemical composition. These results suggest that the CO₂-SFE extract from G. tenax has potential to be used as a natural antioxidant and antimicrobial agent in food processing.

Abstract: This study evaluates the effects of Sargassum pallidum polysaccharides (SPP) on the immune responses in a chicken model. The adjuvanticity of Sargassum pallidum polysaccharides in Newcastle disease (ND), infectious bronchitis (IB) and avian influenza (AI) was investigated by examining the antibody titers and lymphocyte proliferation following immunization in chickens. The chickens were administrated combined ND, IB and AI inactivated vaccines containing SPP at 10, 30 and 50 mg/mL, using an oil adjuvant vaccine as a control. The ND, IB and AI antibody titers and the lymphocyte proliferation were enhanced at 30 mg/mL SPP. In conclusion, an appropriate dose of SPP may be a safe and efficacious immune stimulator candidate that is suitable for vaccines to produce early and persistent prophylaxis.

Abstract: Urinary bladder cancer is one of the most common cancers worldwide, with the highest incidence in industrialized countries. Patients with cancer commonly use unconventional and complementary therapy including nutraceuticals. In this study we evaluated the efficacy of chitooligosaccharides (in orange juice) in rat bladder cancer chemoprevention and as therapeutic agent, on a rat model of urinary bladder carcinogenesis induced with N-butyl-N-(4-hydroxybutyl) nitrosamine. Results indicate that chitooligosaccharides may have a preventive effect on bladder cancer development and a curative effect upon established bladder tumors, dependent on the concentration ingested 500 mg/kg b.w., every three days, showed capacity to inhibit and prevent the proliferation of bladder cancer; however, this was associated with secondary effects such as hypercholesterolemia and hypertriglyceridemia. The use of lower doses (50 and 250 mg/kg b.w.) showed only therapeutic effects. It is further suggested that this antitumor effect might be due to its expected anti-inflammatory action, as well as by mechanisms not directly dependent of COX-2 inhibition, such as cellular proliferation control and improvement in antioxidant profile.

Abstract: The marine opisthobranch Scaphander lignarius has been analyzed in the systematic search for novel bioactive compounds in Arctic marine organisms using bioassay guided fractionation. A number of highly cytotoxic fractions were shown to contain mainly polyunsaturated fatty acids (PUFAs). Selected PUFAs were isolated and identified using both liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR). It was shown that the opisthobranch contained unusual PUFAs such as several ω3 fatty acids and the ω7 heneicosa-5,8,11,14-tetraenoic acid (21:4 n-7) not isolated before. The organism was shown to be a very rich source of PUFAs and the activity of the isolated compounds against a range of human cancer cell lines (melanoma, colon carcinoma and breast carcinoma) is further reported. The ω7 PUFA was significantly more cytotoxic in comparison with reference ω6 arachidonic and ω3 eicosapentaenoic acid. A noteworthy non-selective cytotoxicity against normal lung fibroblasts was also established. The paper contains isolation protocols in addition to cytotoxicity data of the isolated compounds. The potential of marine mollusks as a source for rare PUFAs is also discussed.

Abstract: 1-Hydroxy-10-methoxy-dibenz[b,e]oxepin-6,11-dione (1) was obtained from the culture broth of a marine-derived fungus, Beauveria bassiana TPU942, isolated from a marine sponge collected at Iriomote Island in Okinawa, together with two known compounds, chrysazin (2) and globosuxanthone A (3). The structure of 1 was elucidated on the basis of its spectroscopic data (HREIMS, 1D and 2D NMR experiments including ¹H–¹H COSY, HMQC and HMBC spectra). Dibenz[b,e]oxepines are rare in nature, and only six natural products have been reported. Therefore, compound 1 is the seventh natural product in this class. Compounds 2 and 3 showed an antifungal activity against Candida albicans, and 3 inhibited the cell growth against two human cancer cell lines, HCT-15 (colon) and Jurkat (T-cell lymphoma). Compound 1 did not show an apparent activity in the same bioassays.

Abstract: In particular niches of the marine environment, such as abyssal trenches, icy waters and hot vents, the base of the food web is composed of bacteria and archaea that have developed strategies to survive and thrive under the most extreme conditions. Some of these organisms are considered “extremophiles” and modulate the fatty acid composition of their phospholipids to maintain the adequate fluidity of the cellular membrane under cold/hot temperatures, elevated pressure, high/low salinity and pH. Bacterial cells are even able to produce polyunsaturated fatty acids, contrarily to what was considered until the 1990s, helping the regulation of the membrane fluidity triggered by temperature and pressure and providing protection from oxidative stress. In marine ecosystems, bacteria may either act as a sink of carbon, contribute to nutrient recycling to photo-autotrophs or bacterial organic matter may be transferred to other trophic links in aquatic food webs. The present work aims to provide a comprehensive review on lipid production in bacteria and archaea and to discuss how their lipids, of both heterotrophic and chemoautotrophic origin, contribute to marine food webs.

Abstract: Deoxybostrycin (1) is an anthraquinone compound derived from the marine mangrove fungus Nigrospora sp. No. 1403 and has potential to be a lead for new drugs because of its various biological properties. A series of new derivatives (2–22) of deoxybostrycin were synthesized. The in vitro cytotoxicity of all the new compounds was tested against MDA-MB-435, HepG2 and HCT-116 cancer cell lines. Most of the compounds exhibit strong cytotoxicity with IC₅₀ values ranging from 0.62 to 10 μM. Compounds 19, 21 display comparable cytotoxicity against MDA-MB-435 to epirubicin, the positive control. The primary screening results indicate that the deoxybostrycin derivatives might be a valuable source of new potent anticancer drug candidates.

Abstract: Pine wilt disease (PWD), a destructive disease for pine trees, is caused by the pine wood nematode (PWN), Bursaphelenchus xylophilus and additional bacteria. In this study, extracts of Zostera marina showed a high nematicidal activity against PWN and some of the bacteria that it carries. Light yellow crystals were obtained from extracts of Z. marina through solvent extraction, followed by chromatography on AB-8 resin and crystallization. The NMR and HPLC analysis showed that the isolated compound was rosmarinic acid (RosA). RosA showed effective nematicidal activity, of which the LC₅₀ (50% lethal concentration) to PWN at 24 h, 48 h and 72 h was 1.18 mg/g, 1.05 mg/g and 0.95 mg/g, respectively. To get a high yield rate of RosA from Z. marina, single factor experiments and an L₉ (3⁴) orthogonal experiment were performed. This extraction process involved 70% ethanol for 3 h at 40 °C. The extraction dosage was 1:50 (w/v). The highest yield of RosA from Zostera was 3.13 mg/g DW (dried weight). The crude extracts of Zostera marina (10 mg/mL) and RosA (1 mg/mL) also showed inhibitory effects to some bacterial strains carried by PWN: Klebsiella sp., Stenotrophomonas maltophilia, Streptomyces sp. and Pantoea agglomerans. The results of these studies provide clues for preparing pesticide to control PWD from Z. marina.

Abstract: Five new diterpenoids 1–5 were isolated from an Okinawan soft coral, Cespitularia sp., together with the known diterpenoid, alcyonolide (6). New diterpenoid structures were elucidated by spectroscopic methods and by comparison of their NMR data with those of related compounds. Alcyonolide (6) was cytotoxic against HCT 116 cells (IC₅₀ 5.85 μM), while these new diterpenoids 1–5 were much less active (IC₅₀ 28.2–91.4 μM).

Abstract: The lack of highly active endogenous promoters to drive the expression of transgenes is one of the main drawbacks to achieving efficient transformation of many microalgal species. Using the model chlorophyte Chlamydomonas reinhardtii and the paromomycin resistance APHVIII gene from Streptomyces rimosus as a marker, we have demonstrated that random insertion of the promoterless marker gene and subsequent isolation of the most robust transformants allows for the identification of novel strong promoter sequences in microalgae. Digestion of the genomic DNA with an enzyme that has a unique restriction site inside the marker gene and a high number of target sites in the genome of the microalga, followed by inverse PCR, allows for easy determination of the genomic region, which precedes the APHVIII marker gene. In most of the transformants analyzed, the marker gene is inserted in intragenic regions and its expression relies on its adequate insertion in frame with native genes. As an example, one of the new promoters identified was used to direct the expression of the APHVIII marker gene in C. reinhardtii, showing high transformation efficiencies.

Abstract: Purified phlorotannin extracts from four brown seaweeds (Cystoseira nodicaulis (Withering) M. Roberts, Cystoseira tamariscifolia (Hudson) Papenfuss, Cystoseira usneoides (Linnaeus) M. Roberts and Fucus spiralis Linnaeus), were characterized by HPLC-DAD-ESI-MSⁿ. Fucophloroethol, fucodiphloroethol, fucotriphloroethol, 7-phloroeckol, phlorofucofuroeckol and bieckol/dieckol were identified. The antioxidant activity and the hyaluronidase (HAase) inhibitory capacity exhibited by the extracts were also assessed. A correlation between the extracts activity and their chemical composition was established. F. spiralis, the species presenting higher molecular weight phlorotannins, generally displayed the strongest lipid peroxidation inhibitory activity (IC₅₀ = 2.32 mg/mL dry weight) and the strongest HAase inhibitory capacity (IC₅₀ = 0.73 mg/mL dry weight). As for superoxide radical scavenging, C. nodicaulis was the most efficient species (IC₅₀ = 0.93 mg/mL dry weight), followed by F. spiralis (IC₅₀ = 1.30 mg/mL dry weight). These results show that purified phlorotannin extracts have potent capabilities for preventing and slowing down the skin aging process, which is mainly associated with free radical damage and with the reduction of hyaluronic acid concentration, characteristic of the process.

Abstract: Arca subcrenata Lischke is a marine traditional Chinese medicine. The study investigated the antitumor effects of P2, a polypeptide fraction from A. subcrenata, and its toxicity in vitro and in vivo. The results showed that P2 could inhibit the proliferation of seven tumor cell lines, especially in HeLa and HT-29 cell lines. The IC₅₀ values were 11.43 μg/mL for HeLa and 13.00 μg/mL for HT-29 treated by P2 for 48 h. P2 had little cytotoxicity on normal liver cells (L-02). The maximum tolerated dose (MTD) of P2 on KM mice was 1000 mg/kg by i.p. or i.v. The tumor growth inhibitory ratios of P2 were 26.4%, 41.4% and 46.4% for H-22, and 34.0%, 45.8% and 60.1% for S-180 tumor-bearing mice. The results demonstrated that P2 might be a potential antitumor agent with high efficiency in dose-dependent and time-dependent manners and low toxicity.

Abstract: Recently, the studies on the antiviral activities of marine natural products, especially marine polysaccharides, are attracting more and more attention all over the world. Marine-derived polysaccharides and their lower molecular weight oligosaccharide derivatives have been shown to possess a variety of antiviral activities. This paper will review the recent progress in research on the antiviral activities and the mechanisms of these polysaccharides obtained from marine organisms. In particular, it will provide an update on the antiviral actions of the sulfated polysaccharides derived from marine algae including carrageenans, alginates, and fucans, relating to their structure features and the structure–activity relationships. In addition, the recent findings on the different mechanisms of antiviral actions of marine polysaccharides and their potential for therapeutic application will also be summarized in detail.

Abstract: In addition to 13 known compounds, four new bisabolane sesquiterpenes, okamurenes A–D (1–4), a new chamigrane derivative, okamurene E (5), and a new C₁₂-acetogenin, okamuragenin (6), were isolated from the marine red alga Laurencia okamurai. The structures of these compounds were determined through detailed spectroscopic analyses. Of these, okamurenes A and B (1 and 2) are the first examples of bromobisabolane sesquiterpenes possessing a phenyl moiety among Laurencia-derived sesquiterpenes, while okamuragenin (6) was the first acetogenin aldehyde possessing a C₁₂-carbon skeleton. Each of the isolated compounds was evaluated for the brine shrimp (Artemia salina) lethal assay and 7-hydroxylaurene displayed potent lethality with LD₅₀ 1.8 μM.

Abstract: The present study investigated the photoprotective properties of an ethanol extract derived from the red alga Bonnemaisonia hamifera against ultraviolet B (UVB)-induced cell damage in human HaCaT keratinocytes. The Bonnemaisonia hamifera ethanol extract (BHE) scavenged the superoxide anion generated by the xanthine/xanthine oxidase system and the hydroxyl radical generated by the Fenton reaction (FeSO₄ + H₂O₂), both of which were detected by using electron spin resonance spectrometry. In addition, BHE exhibited scavenging activity against the 1,1-diphenyl-2-picrylhydrazyl radical and intracellular reactive oxygen species (ROS) that were induced by either hydrogen peroxide or UVB radiation. BHE reduced UVB-induced apoptosis, as shown by decreased apoptotic body formation and DNA fragmentation. BHE also attenuated DNA damage and the elevated levels of 8-isoprostane and protein carbonyls resulting from UVB-mediated oxidative stress. Furthermore, BHE absorbed electromagnetic radiation in the UVB range (280–320 nm). These results suggest that BHE protects human HaCaT keratinocytes against UVB-induced oxidative damage by scavenging ROS and absorbing UVB photons, thereby reducing injury to cellular components.

Abstract: The zoanthids Palythoa caribaeorum and Protopalythoa variabilis are among the most abundant marine species along the Brazilian coast. We now report the isolation and structure elucidation of two unprecedented sulfonylated ceramides, palyosulfonoceramide A (1) and palyosulfonoceramide B (2) from specimens collected off Brazil’s northeastern coast. The structures of 1 and 2 were established using a combination of NMR analyses, including: evaluation of ¹H, ¹³C, ¹H–¹H COSY, ¹H–¹³C HSQC, ¹H–¹³C HMBC, and ¹H–¹⁵N HMBC NMR spectra, high-resolution mass spectrometry and chemical degradation. In addition, we also isolated the corresponding known ceramides, N-((2S,3R,4E,8E)-1, 3-dihydroxyoctadeca-4,8-dien-2-yl)-hexadecanamide (3) and N-((2S,3R,4E)-1,3-dihydroxy octadeca-4-en-2-yl)-hexadecanamide (4), which provided further support for the assignments of 1 and 2.

Abstract: Glycobiology is the study of complex carbohydrates in biological systems and represents a developing field of science that has made huge advances in the last half century. In fact, it combines all branches of biomedical research, revealing the vast and diverse forms of carbohydrate structures that exist in nature. Advances in structure determination have enabled scientists to study the function of complex carbohydrates in more depth and to determine the role that they play in a wide range of biological processes. Glycobiology research in marine systems has primarily focused on reproduction, in particular for what concern the chemical communication between the gametes. The current status of marine glycobiology is primarily descriptive, devoted to characterizing marine glycoconjugates with potential biomedical and biotechnological applications. In this review, we describe the current status of the glycobiology in the reproductive processes from gametogenesis to fertilization and embryo development of marine animals.

Abstract: Sinulariolide, an isolated compound from the soft coral Sinularia flexibilis, possesses the anti-proliferative, anti-migratory and apoptosis-inducing activities against the TSGH bladder carcinoma cell. The anti-tumor effects of sinulariolide were determined by 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, cell migration assay and flow cytometry, respectively. Sinulariolide inhibited the growth and migration of bladder carcinoma cells in a dose-dependent manner, as well as induced both early and late apoptosis as determined by the flow cytometer. Also, the sinulariolide-induced apoptosis is related to the mitochondrial-mediated apoptosis via caspase-dependent pathways, elucidated by the loss of mitochondrial membrane potential, release of cytochrome C, activation of caspase-3/-9, Bax and Bad, as well as suppression of Bcl-2/Bcl-xL/Mcl-1. Detection of the PARP-1 cleaved product suggested the partial involvement of caspase-independent pathways. Moreover, inhibition of p38MAPK activity leads to the rescue of the cell cytotoxicity of sinulariolide-treated TSGH cells, indicating that the p38MAPK pathway is also involved in the sinulariolide-induced cell apoptosis. Altogether, these results suggest that sinulariolide induces apoptosis against bladder cancer cells through mitochondrial-related and p38MAPK pathways.

Abstract: The marine-derived filamentous fungus Asteromyces cruciatus 763, obtained off the coast of La Jolla, San Diego, USA, yielded the new pentapeptide lajollamide A (1), along with the known compounds regiolone (2), hyalodendrin (3), gliovictin (4), ¹N-norgliovicitin (5), and bis-N-norgliovictin (6). The planar structure of lajollamide A (1) was determined by Nuclear Magnetic Resonance (NMR) spectroscopy in combination with mass spectrometry. The absolute configuration of lajollamide A (1) was unambiguously solved by total synthesis which provided three additional diastereomers of 1 and also revealed that an unexpected acid-mediated partial racemization (2:1) of the l-leucine and l-N-Me-leucine residues occurred during the chemical degradation process. The biological activities of the isolated metabolites, in particular their antimicrobial properties, were investigated in a series of assay systems.