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Mar. Drugs, Volume 20, Issue 4 (April 2022) – 54 articles

Cover Story (view full-size image): Cryptosporidium sp. are apicomplexan parasites that cause diarrheal disease in humans and livestock worldwide. A Cryptosporidium growth inhibition assay was used to screen the HBOI fraction library. Bioassay-guided fractionation of active fractions from a deep-sea sponge, Leiodermatium sp., resulted in the purification of leiodolide A as the major active compound in the organism. Leiodolide A displayed specific anti-Cryptosporidium activity at an EC50 of 103.5 nM with good selectivity over host cells and other mammalian cell lines. Leiodolide A provides a valuable drug scaffold on which to develop new anti-Cryptosporidium compounds and encourages screening natural products for new chemical scaffolds. View this paper
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15 pages, 3520 KiB  
Article
Sinuhirtone A, An Uncommon 17,19-Dinorxeniaphyllanoid, and Nine Related New Terpenoids from the Hainan Soft Coral Sinularia hirta
by Zi-Hui Chen, Si-Qi Lu, Guan-Ying Han, Xu-Wen Li and Yue-Wei Guo
Mar. Drugs 2022, 20(4), 272; https://doi.org/10.3390/md20040272 - 18 Apr 2022
Cited by 8 | Viewed by 2624
Abstract
Chemical investigation of the Hainan soft coral Sinularia hirta resulted in the isolation and identification of a library of sixteen structurally diverse terpenoids, including a dinorditerpenoid with an uncommon 17,19-dinorxeniaphyllane skeleton, namely sinuhirtone A (7), six new xeniaphyllane-type diterpenoids (1 [...] Read more.
Chemical investigation of the Hainan soft coral Sinularia hirta resulted in the isolation and identification of a library of sixteen structurally diverse terpenoids, including a dinorditerpenoid with an uncommon 17,19-dinorxeniaphyllane skeleton, namely sinuhirtone A (7), six new xeniaphyllane-type diterpenoids (16), one new norxeniaphyllanoid (8), two new norcaryophyllene-type sesquiterpenoids (9 and 10), together with six known related compounds (1116). Compounds 13 are three new furanone-containing xeniaphyllane-type diterpenoids. The structures of the new compounds, including their absolute configurations, were determined by extensive spectroscopic analysis and a series of quantum chemical calculations, including quantum mechanical-nuclear magnetic resonance (QM–NMR), time-dependent density functional theory–electronic circular dichroism (TDDFT–ECD), and optical rotatory dispersion (ORD) methods. A plausible biosynthetic connection between new compounds 19 was also proposed. New compounds 24, 7, and 8 were evaluated for in vitro cytotoxicity against four cancer cell lines. Full article
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24 pages, 2171 KiB  
Review
Phytoplankton Toxins and Their Potential Therapeutic Applications: A Journey toward the Quest for Potent Pharmaceuticals
by Biswajita Pradhan and Jang-Seu Ki
Mar. Drugs 2022, 20(4), 271; https://doi.org/10.3390/md20040271 - 18 Apr 2022
Cited by 20 | Viewed by 5367
Abstract
Phytoplankton are prominent organisms that contain numerous bioactive substances and secondary metabolites, including toxins, which can be valuable to pharmaceutical, nutraceutical, and biotechnological industries. Studies on toxins produced by phytoplankton such as cyanobacteria, diatoms, and dinoflagellates have become more prevalent in recent years [...] Read more.
Phytoplankton are prominent organisms that contain numerous bioactive substances and secondary metabolites, including toxins, which can be valuable to pharmaceutical, nutraceutical, and biotechnological industries. Studies on toxins produced by phytoplankton such as cyanobacteria, diatoms, and dinoflagellates have become more prevalent in recent years and have sparked much interest in this field of research. Because of their richness and complexity, they have great potential as medicinal remedies and biological exploratory probes. Unfortunately, such toxins are still at the preclinical and clinical stages of development. Phytoplankton toxins are harmful to other organisms and are hazardous to animals and human health. However, they may be effective as therapeutic pharmacological agents for numerous disorders, including dyslipidemia, obesity, cancer, diabetes, and hypertension. In this review, we have focused on the properties of different toxins produced by phytoplankton, as well as their beneficial effects and potential biomedical applications. The anticancer properties exhibited by phytoplankton toxins are mainly attributed to their apoptotic effects. As a result, phytoplankton toxins are a promising strategy for avoiding postponement or cancer treatment. Moreover, they also displayed promising applications in other ailments and diseases such as Alzheimer’s disease, diabetes, AIDS, fungal, bacterial, schizophrenia, inflammation, allergy, osteoporosis, asthma, and pain. Preclinical and clinical applications of phytoplankton toxins, as well as future directions of their enhanced nano-formulations for improved clinical efficacy, have also been reviewed. Full article
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14 pages, 1648 KiB  
Article
Development of a High-Performance Thin-Layer Chromatography Method for the Quantification of Alkyl Glycerolipids and Alkenyl Glycerolipids from Shark and Chimera Oils and Tissues
by Marion Papin, Cyrille Guimaraes, Benoit Pierre-Aue, Delphine Fontaine, Jeoffrey Pardessus, Hélène Couthon, Gaëlle Fromont, Karine Mahéo, Aurélie Chantôme, Christophe Vandier and Michelle Pinault
Mar. Drugs 2022, 20(4), 270; https://doi.org/10.3390/md20040270 - 18 Apr 2022
Cited by 3 | Viewed by 2694
Abstract
Ether lipids are composed of alkyl lipids with an ether bond at the sn-1 position of a glycerol backbone and alkenyl lipids, which possess a vinyl ether bond at the sn-1 position of the glycerol. These ether glycerolipids are present either as polar [...] Read more.
Ether lipids are composed of alkyl lipids with an ether bond at the sn-1 position of a glycerol backbone and alkenyl lipids, which possess a vinyl ether bond at the sn-1 position of the glycerol. These ether glycerolipids are present either as polar glycerophospholipids or neutral glycerolipids. Before studying the biological role of molecular species of ether glycerolipids, there is a need to separate and quantify total alkyl and alkenyl glycerolipids from biological samples in order to determine any variation depending on tissue or physiopathological conditions. Here, we detail the development of the first high-performance thin-layer chromatography method for the quantification of total alkyl and alkenyl glycerolipids thanks to the separation of their corresponding alkyl and alkenyl glycerols. This method starts with a reduction of all lipids after extraction, resulting in the reduction of neutral and polar ether glycerolipids into alkyl and alkenyl glycerols, followed by an appropriate purification and, finally, the linearly ascending development of alkyl and alkenyl glycerols on high-performance thin-layer chromatography plates, staining, carbonization and densitometric analysis. Calibration curves were obtained with commercial alkyl and alkenyl glycerol standards, enabling the quantification of alkyl and alkenyl glycerols in samples and thus directly obtaining the quantity of alkyl and alkenyl lipids present in the samples. Interestingly, we found a differential quantity of these lipids in shark liver oil compared to chimera. We quantified alkyl and alkenyl glycerolipids in periprostatic adipose tissues from human prostate cancer and showed the feasibility of this method in other biological matrices (muscle, tumor). Full article
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15 pages, 7594 KiB  
Article
Discovery of New Secondary Metabolites from Marine Bacteria Hahella Based on an Omics Strategy
by Shufen He, Peishan Li, Jingxuan Wang, Yanzhu Zhang, Hongmei Lu, Liufei Shi, Tao Huang, Weiyan Zhang, Lijian Ding, Shan He and Liwei Liu
Mar. Drugs 2022, 20(4), 269; https://doi.org/10.3390/md20040269 - 18 Apr 2022
Cited by 5 | Viewed by 4044
Abstract
Hahella is one characteristic genus under the Hahellaceae family and shows a good potential for synthesizing new natural products. In this study, we examined the distribution of the secondary metabolite biosynthetic gene cluster (SMBGC) under Hahella with anti-SMASH. The results derived from five [...] Read more.
Hahella is one characteristic genus under the Hahellaceae family and shows a good potential for synthesizing new natural products. In this study, we examined the distribution of the secondary metabolite biosynthetic gene cluster (SMBGC) under Hahella with anti-SMASH. The results derived from five genomes released 70 SMBGCs. On average, each strain contains 12 gene clusters, and the most abundant ones (45.7%) are from the family of non-ribosomal peptide synthetase (NRPS) and non-ribosomal peptide synthetase hybrid with polyketide synthase (NRPS/PKS), indicating a great potential to find bioactive compounds. The comparison of SMBGC between H. chejuensis and other species showed that H. chejuensis contained two times more gene clusters than H. ganghwensis. One strain, designed as NBU794, was isolated from the mangrove soil of Dongzhai Port in Haikou (China) by iChip. The 16S rRNA gene of NBU794 exhibited 99% identity to H. chejuensis KCTC 2396 and clustered with the H. chejuensis clade on the phylogenetic trees. Genome mining on strain NBU794 released 17 SMBGCs and two groups of bioactive compounds, which are chejuenolide A-C and nine prodiginines derivatives. The prodiginines derivatives include the well-known lead compound prodigiosin and two new compounds, 2-methyl-3-pentyl-4-O-methyl-prodiginine and 2-methyl-3-octyl-prodiginine, which were identified through fragmentation analysis based on LC-MS/MS. The anti-microbial activity assay showed prodigiosin and 2-methyl-3-heptyl-prodiginine exhibited the best performance in inhibiting Escherichia coli, Salmonella paratyphi B, MASA Staphylococcus aureus, Bacillus subtilis, and Candida albicans. Moreover, the yield of prodigiosin in H. chejuensis NBU794 was also evaluated, which could reach 1.40 g/L under the non-optimized condition and increase to 5.83 g/L in the modified ISP4 medium with macroporous adsorption beads added, indicating that NBU794 is a promising source of prodigiosin. Full article
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11 pages, 835 KiB  
Article
A Survey on the Distribution of Ovothiol and ovoA Gene Expression in Different Tissues and Cells: A Comparative Analysis in Sea Urchins and Mussels
by Carola Murano, Annalisa Zuccarotto, Serena Leone, Marco Sollitto, Marco Gerdol, Immacolata Castellano and Anna Palumbo
Mar. Drugs 2022, 20(4), 268; https://doi.org/10.3390/md20040268 - 15 Apr 2022
Cited by 6 | Viewed by 2692
Abstract
Ovothiols are histidine-derived thiols produced by a variety of marine invertebrates, protists and bacteria. These compounds, which are among the strongest natural antioxidants, are involved in controlling the cellular redox balance due to their redox exchange with glutathione. Although ovothiols were initially reported [...] Read more.
Ovothiols are histidine-derived thiols produced by a variety of marine invertebrates, protists and bacteria. These compounds, which are among the strongest natural antioxidants, are involved in controlling the cellular redox balance due to their redox exchange with glutathione. Although ovothiols were initially reported as protective agents against environmental stressors, new evidence suggests that they can also act as pheromones and participate in fundamental biological processes such as embryogenesis. To get further insight into the biological roles of ovothiols, we compared ovothiol biosynthesis in the sea urchin Paracentrotus lividus and in the mussel Mytilus galloprovincialis, the two species that represent the richest sources of these compounds among marine invertebrates. Ovothiol content was measured in different tissues and in the immune cells from both species and the expression levels of ovoA, the gene responsible for ovothiol biosynthesis, was inferred from publicly available transcriptomes. A comparative analysis of ovothiol biosynthesis in the two species allowed the identification of the tissues and cells synthesizing the metabolite and highlighted analogies and differences between sea urchins and mussels. By improving our knowledge on the biological roles of ovothiols and pointing out the existence of sustainable natural sources for their isolation, this study provides the basis for future biotechnological investigations on these valuable compounds. Full article
(This article belongs to the Special Issue Sulfur-Containing Marine Bioactives 2.0)
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16 pages, 4904 KiB  
Article
Astaxanthin Confers a Significant Attenuation of Hippocampal Neuronal Loss Induced by Severe Ischemia-Reperfusion Injury in Gerbils by Reducing Oxidative Stress
by Joon Ha Park, Tae-Kyeong Lee, Dae Won Kim, Ji Hyeon Ahn, Choong-Hyun Lee, Jong-Dai Kim, Myoung Cheol Shin, Jun Hwi Cho, Jae-Chul Lee, Moo-Ho Won and Soo Young Choi
Mar. Drugs 2022, 20(4), 267; https://doi.org/10.3390/md20040267 - 14 Apr 2022
Cited by 10 | Viewed by 2631
Abstract
Astaxanthin is a powerful biological antioxidant and is naturally generated in a great variety of living organisms. Some studies have demonstrated the neuroprotective effects of ATX against ischemic brain injury in experimental animals. However, it is still unknown whether astaxanthin displays neuroprotective effects [...] Read more.
Astaxanthin is a powerful biological antioxidant and is naturally generated in a great variety of living organisms. Some studies have demonstrated the neuroprotective effects of ATX against ischemic brain injury in experimental animals. However, it is still unknown whether astaxanthin displays neuroprotective effects against severe ischemic brain injury induced by longer (severe) transient ischemia in the forebrain. The purpose of this study was to evaluate the neuroprotective effects of astaxanthin and its antioxidant activity in the hippocampus of gerbils subjected to 15-min transient forebrain ischemia, which led to the massive loss (death) of pyramidal cells located in hippocampal cornu Ammonis 1-3 (CA1-3) subfields. Astaxanthin (100 mg/kg) was administered once daily for three days before the induction of transient ischemia. Treatment with astaxanthin significantly attenuated the ischemia-induced loss of pyramidal cells in CA1-3. In addition, treatment with astaxanthin significantly reduced ischemia-induced oxidative DNA damage and lipid peroxidation in CA1-3 pyramidal cells. Moreover, the expression of the antioxidant enzymes superoxide dismutase (SOD1 and SOD2) in CA1-3 pyramidal cells were gradually and significantly reduced after ischemia. However, in astaxanthin-treated gerbils, the expression of SOD1 and SOD2 was significantly high compared to in-vehicle-treated gerbils before and after ischemia induction. Collectively, these findings indicate that pretreatment with astaxanthin could attenuate severe ischemic brain injury induced by 15-min transient forebrain ischemia, which may be closely associated with the decrease in oxidative stress due to astaxanthin pretreatment. Full article
(This article belongs to the Special Issue Marine Anti-inflammatory and Antioxidant Agents 2.0)
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14 pages, 340 KiB  
Review
Jellyfish from Fisheries By-Catches as a Sustainable Source of High-Value Compounds with Biotechnological Applications
by Isabella D’Ambra and Louise Merquiol
Mar. Drugs 2022, 20(4), 266; https://doi.org/10.3390/md20040266 - 14 Apr 2022
Cited by 14 | Viewed by 5604
Abstract
The world’s population growth and consequent increased demand for food, energy and materials together with the decrease of some natural resources have highlighted the compelling need to use sustainably existing resources and find alternative sources to satisfy the needs of growing and longer-aging [...] Read more.
The world’s population growth and consequent increased demand for food, energy and materials together with the decrease of some natural resources have highlighted the compelling need to use sustainably existing resources and find alternative sources to satisfy the needs of growing and longer-aging populations. In this review, we explore the potential use of a specific fisheries by-catch, jellyfish, as a sustainable source of high-value compounds. Jellyfish are often caught up with fish into fishing gear and nets, then sorted and discarded. Conversely, we suggest that this by-catch may be used to obtain food, nutraceutical products, collagen, toxins and fluorescent compounds to be used for biomedical applications and mucus for biomaterials. These applications are based on studies which indicate the feasibility of using jellyfish for biotechnology. Because jellyfish exhibit seasonal fluctuations in abundance, jellyfish by-catches likely follow the same pattern. Therefore, this resource may not be constantly available throughout the year, so the exploitation of the variable abundances needs to be optimized. Despite the lack of data about jellyfish by-catches, the high value of their compounds and their wide range of applications suggest that jellyfish by-catches are a resource which is discarded at present, but needs to be re-evaluated for exploitation within the context of a circular economy in the era of zero waste. Full article
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30 pages, 10822 KiB  
Article
Cytotoxic Alkylynols of the Sponge Cribrochalina vasculum: Structure, Synthetic Analogs and SAR Studies
by Dimitry Kovalerchik, Ana Zovko, Petra Hååg, Adam Sierakowiak, Kristina Viktorsson, Rolf Lewensohn, Micha Ilan and Shmuel Carmeli
Mar. Drugs 2022, 20(4), 265; https://doi.org/10.3390/md20040265 - 13 Apr 2022
Cited by 2 | Viewed by 2612
Abstract
A series of twenty-three linear and branched chain mono acetylene lipids were isolated from the Caribbean Sea sponge Cribrochalina vasculum. Seventeen of the compounds, 1–17, are new, while six, 18–23, were previously characterized from the same sponge. Some of the [...] Read more.
A series of twenty-three linear and branched chain mono acetylene lipids were isolated from the Caribbean Sea sponge Cribrochalina vasculum. Seventeen of the compounds, 1–17, are new, while six, 18–23, were previously characterized from the same sponge. Some of the new acetylene-3-hydroxy alkanes 1, 6, 7, 8, 10 were tested for selective cytotoxicity in non-small cell lung carcinoma (NSCLC) cells over WI-38 normal diploid lung fibroblasts. Compound 7, presented clear tumor selective activity while, 1 and 8, showed selectivity at lower doses and 6 and 10, were not active towards NSCLC cells at all. The earlier reported selective cytotoxicity of some acetylene-3-hydroxy alkanes (scal-18 and 23), in NSCLC cells and/or other tumor cell types were also confirmed for 19, 20 and 22. To further study the structure activity relationships (SAR) of this group of compounds, we synthesized several derivatives of acetylene-3-hydroxy alkanes, rac-18, scal-S-18, R-18, rac-27, rac-32, R-32, S-32, rac-33, rac-41, rac-42, rac-43, rac-45, rac-48 and rac-49, along with other 3-substituted derivatives, rac-35, rac-36, rac-37, rac-38, rac-39 and rac-40, and assessed their cytotoxic activity against NSCLC cells and diploid fibroblasts. SAR studies revealed that the alcohol moiety at position 3 and its absolute R configuration both were essential for the tumor cell line selective activity while for its cytotoxic magnitude the alkyl chain length and branching were of less significance. Full article
(This article belongs to the Special Issue Marine Sponge Biotechnology)
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15 pages, 2287 KiB  
Article
Evaluation of the Potential of Lipid-Extracted Chlorella vulgaris Residue for Yarrowia lipolytica Growth at Different pH Levels
by Guillaume Delfau-Bonnet, Nabila Imatoukene, Tiphaine Clément, Michel Lopez, Florent Allais and Anne-Lise Hantson
Mar. Drugs 2022, 20(4), 264; https://doi.org/10.3390/md20040264 - 13 Apr 2022
Viewed by 2955
Abstract
Projections show that the cultivation of microalgae will extend to the production of bio-based compounds, such as biofuels, cosmetics, and medicines. This will generate co-products or residues that will need to be valorized to reduce the environmental impact and the cost of the [...] Read more.
Projections show that the cultivation of microalgae will extend to the production of bio-based compounds, such as biofuels, cosmetics, and medicines. This will generate co-products or residues that will need to be valorized to reduce the environmental impact and the cost of the process. This study explored the ability of lipid-extracted Chlorella vulgaris residue as a sole carbon and nitrogen source for growing oleaginous yeasts without any pretreatment. Both wild-type Yarrowia lipolytica W29 and mutant JMY3501 (which was designed to accumulate more lipids without their remobilization or degradation) showed a similar growth rate of 0.28 h−1 at different pH levels (3.5, 5.5, and 7.5). However, the W29 cell growth had the best cell number on microalgal residue at a pH of 7.5, while three times fewer cells were produced at all pH levels when JMY3501 was grown on microalgal residue. The JMY3501 growth curves were similar at pH 3.5, 5.5, and 7.5, while the fatty-acid composition differed significantly, with an accumulation of α-linolenic acid on microalgal residue at a pH of 7.5. Our results demonstrate the potential valorization of Chlorella vulgaris residue for Yarrowia lipolytica growth and the positive effect of a pH of 7.5 on the fatty acid profile. Full article
(This article belongs to the Special Issue Biotechnology Applications of Microalgae)
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16 pages, 2260 KiB  
Article
Effect of Extraction Temperature on Pressurized Liquid Extraction of Bioactive Compounds from Fucus vesiculosus
by Adane Tilahun Getachew, Susan Løvstad Holdt, Anne Strunge Meyer and Charlotte Jacobsen
Mar. Drugs 2022, 20(4), 263; https://doi.org/10.3390/md20040263 - 12 Apr 2022
Cited by 22 | Viewed by 3486
Abstract
This study was aimed at investigating the effect of low polarity water (LPW) on the extraction of bioactive compounds from Fucus vesiculosus and to examine the influence of temperature on the extraction yield, total phenolic content, crude alginate, fucoidan content, and antioxidant activity. [...] Read more.
This study was aimed at investigating the effect of low polarity water (LPW) on the extraction of bioactive compounds from Fucus vesiculosus and to examine the influence of temperature on the extraction yield, total phenolic content, crude alginate, fucoidan content, and antioxidant activity. The extractions were performed at the temperature range of 120–200 °C with 10 °C increments, and the extraction yield increased linearly with the increasing extraction temperature, with the highest yields at 170–200 °C and with the maximum extraction yield (25.99 ± 2.22%) at 190 °C. The total phenolic content also increased with increasing temperature. The extracts showed a high antioxidant activity, measured with DPPH (2,2-Diphenyl-1-picrylhydrazyl) radicals scavenging and metal-chelating activities of 0.14 mg/mL and 1.39 mg/mL, respectively. The highest yield of alginate and crude fucoidan were found at 140 °C and 160 °C, respectively. The alginate and crude fucoidan contents of the extract were 2.13% and 22.3%, respectively. This study showed that the extraction of bioactive compounds from seaweed could be selectively maximized by controlling the polarity of an environmentally friendly solvent. Full article
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10 pages, 1947 KiB  
Article
Protective Effects of Marine Alkaloid Neolamellarin A Derivatives against Glutamate Induced PC12 Cell Apoptosis
by Kai Zhang, Xian Guan, Xiao Zhang, Lu Liu, Ruijuan Yin and Tao Jiang
Mar. Drugs 2022, 20(4), 262; https://doi.org/10.3390/md20040262 - 12 Apr 2022
Cited by 1 | Viewed by 2171
Abstract
Marine alkaloids obtained from sponges possess a variety of biological activities and potential medicinal value. The pyrrole-derived lamellarin-like alkaloids, especially their permethyl derivatives, show low cytotoxicity and potent MDR reversing activity. Neolamellarin A is a novel lamellarin-like alkaloid which was extracted from marine [...] Read more.
Marine alkaloids obtained from sponges possess a variety of biological activities and potential medicinal value. The pyrrole-derived lamellarin-like alkaloids, especially their permethyl derivatives, show low cytotoxicity and potent MDR reversing activity. Neolamellarin A is a novel lamellarin-like alkaloid which was extracted from marine animal sponges. We reported the synthetic method of permethylated Neolamellarin A and its derivatives by a convergent strategy in 2015. In 2018, we reported the synthesis and the neuroprotective activity in PC12 cells of 3,4-bisaryl-N-alkylated permethylated Neolamellarin A derivatives. In this report, another series of 15 different 3,4-bisaryl-N-acylated permethylated Neolamellarin A derivatives were synthesized, and the outstanding protective effects of these compounds against glutamate induced PC12 cell apoptosis were presented and discussed. These Neolamellarin A derivatives which possessed low cytotoxicity and superior neuroprotective activity may have the potential to be developed into antagonists against glutamate induced nerve cell apoptosis. Full article
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14 pages, 1488 KiB  
Article
The Effects of Freshwater Clam (Corbicula fluminea) Extract on Serum Tumor Necrosis Factor-Alpha (TNF-α) in Prediabetic Patients in Taiwan
by Tse-Hung Huang, Chiao-Hsu Ke, Chin-Chang Chen, Cheng-Hsun Chuang, Kuang-Wen Liao, Yi-Hsien Shiao and Chen-Si Lin
Mar. Drugs 2022, 20(4), 261; https://doi.org/10.3390/md20040261 - 10 Apr 2022
Cited by 4 | Viewed by 3382
Abstract
Freshwater clam extract (FCE) is a functional food that regulates the immune system and has been demonstrated in numerous studies to display desirable anti–tumor necrosis factor-alpha (TNF-α) responses. In addition, excess TNF-α production is positively associated with type 2 diabetes. However, few longitudinal [...] Read more.
Freshwater clam extract (FCE) is a functional food that regulates the immune system and has been demonstrated in numerous studies to display desirable anti–tumor necrosis factor-alpha (TNF-α) responses. In addition, excess TNF-α production is positively associated with type 2 diabetes. However, few longitudinal clinical studies evaluating the efficiency and toxicity of FCE are available. This article reports that patients with prediabetes who received FCE had a desirable outcome of a reduction in serum TNF-α for a long period. This was a double-blind, randomized, parallel clinical trial conducted using FCE intervention and placebo groups, and 36 patients with prediabetes were enrolled. Two grams of FCE or placebo was consumed daily for 180 consecutive days. The serum of the participants was collected at four time points (0M: before the intervention; 3M: after 3 months of intervention; 6M: after 6 months of intervention; 12M: 6 months after cessation of intervention at 6M). A serum TNF-α concentration higher than 4.05 pg/mL was defined as a cut-off value. FCE reduced serum TNF-α in all participants at 6M and 12M. Moreover, FCE significantly suppressed serum TNF-α concentrations at 6M and 12M and inhibited TNF-α release with time series in subjects with elevated TNF-α values. FCE intervention effectively reduced serum TNF-α and persistently sustained the effects for half a year in patients with prediabetes. Gas chromatography–mass spectrometry (GS-MS) analysis revealed that the major components of FCE were phytosterols and fatty acids, which exerted anti-inflammatory and anti-TNF-α abilities. Hence, FCE has the potential to be developed as a natural treatment for prediabetic patients in Taiwan. Full article
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13 pages, 2828 KiB  
Article
Phycocyanin Ameliorates Colitis-Associated Colorectal Cancer by Regulating the Gut Microbiota and the IL-17 Signaling Pathway
by Dongjin Pan, Bingyao Huang, Yuman Gan, Chenghai Gao, Yonghong Liu and Zhenzhou Tang
Mar. Drugs 2022, 20(4), 260; https://doi.org/10.3390/md20040260 - 9 Apr 2022
Cited by 21 | Viewed by 4271
Abstract
Phycocyanin (PC) is a pigment-protein complex. It has been reported that PC exerts anti-colorectal cancer activities, although the underlying mechanism has not been fully elucidated. In the present study, azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced mice were orally administrated with PC, followed by microbiota [...] Read more.
Phycocyanin (PC) is a pigment-protein complex. It has been reported that PC exerts anti-colorectal cancer activities, although the underlying mechanism has not been fully elucidated. In the present study, azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced mice were orally administrated with PC, followed by microbiota and transcriptomic analyses to investigate the effects of PC on colitis-associated cancer (CAC). Our results indicated that PC ameliorated AOM/DSS induced inflammation. PC treatment significantly reduced the number of colorectal tumors and inhibited proliferation of epithelial cell in CAC mice. Moreover, PC reduced the relative abundance of Firmicutes, Deferribacteres, Proteobacteria and Epsilonbacteraeota at phylum level. Transcriptomic analysis showed that the expression of genes involved in the intestinal barrier were altered upon PC administration, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed the IL-17 signaling pathway was affected by PC treatment. The study demonstrated the protective therapeutic action of PC on CAC. Full article
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11 pages, 1601 KiB  
Article
Aromatic Acids and Leucine Derivatives Produced from the Deep-Sea Actinomycetes Streptomyces chumphonensis SCSIO15079 with Antihyperlipidemic Activities
by Ziqi Su, Kunlong Li, Xiaowei Luo, Yongyan Zhu, Shao-Yu Mai, Quanhong Zhu, Bin Yang, Xuefeng Zhou and Huaming Tao
Mar. Drugs 2022, 20(4), 259; https://doi.org/10.3390/md20040259 - 7 Apr 2022
Cited by 5 | Viewed by 2706
Abstract
Six new aromatic acids (16) and three new leucine derivatives containing an unusual oxime moiety (79) were isolated and identified from the deep-sea-derived actinomycetes strain Streptomyces chumphonensis SCSIO15079, together with two known compounds (10 [...] Read more.
Six new aromatic acids (16) and three new leucine derivatives containing an unusual oxime moiety (79) were isolated and identified from the deep-sea-derived actinomycetes strain Streptomyces chumphonensis SCSIO15079, together with two known compounds (1011). The structures of 19 including absolute configurations were determined by detailed NMR, MS, and experimental and calculated electronic circular dichroism spectroscopic analyses. Compounds 19 were evaluated for their antimicrobial and cytotoxicity activities, as well as their effects on intracellular lipid accumulation in HepG2 cells. Compounds 3 and 4, with the most potent inhibitory activity on intracellular lipid accumulation at 10 μM, were revealed with potential antihyperlipidemic effects, although the mechanism needs to be further studied. Full article
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17 pages, 5450 KiB  
Article
The Emerging Evidence for a Protective Role of Fucoidan from Laminaria japonica in Chronic Kidney Disease-Triggered Cognitive Dysfunction
by Zhihui Ma, Zhiyou Yang, Xinyue Feng, Jiahang Deng, Chuantong He, Rui Li, Yuntao Zhao, Yuewei Ge, Yongping Zhang, Cai Song and Saiyi Zhong
Mar. Drugs 2022, 20(4), 258; https://doi.org/10.3390/md20040258 - 7 Apr 2022
Cited by 12 | Viewed by 3773
Abstract
This study aimed to explore the mechanism of fucoidan in chronic kidney disease (CKD)-triggered cognitive dysfunction. The adenine-induced ICR strain CKD mice model was applied, and RNA-Seq was performed for differential gene analysis between aged-CKD and normal mice. As a result, fucoidan (100 [...] Read more.
This study aimed to explore the mechanism of fucoidan in chronic kidney disease (CKD)-triggered cognitive dysfunction. The adenine-induced ICR strain CKD mice model was applied, and RNA-Seq was performed for differential gene analysis between aged-CKD and normal mice. As a result, fucoidan (100 and 200 mg kg−1) significantly reversed adenine-induced high expression of urea, uric acid in urine, and creatinine in serum, as well as the novel object recognition memory and spatial memory deficits. RNA sequencing analysis indicated that oxidative and inflammatory signaling were involved in adenine-induced kidney injury and cognitive dysfunction; furthermore, fucoidan inhibited oxidative stress via GSK3β-Nrf2-HO-1 signaling and ameliorated inflammatory response through regulation of microglia/macrophage polarization in the kidney and hippocampus of CKD mice. Additionally, we clarified six hallmarks in the hippocampus and four in the kidney, which were correlated with CKD-triggered cognitive dysfunction. This study provides a theoretical basis for the application of fucoidan in the treatment of CKD-triggered memory deficits. Full article
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12 pages, 2239 KiB  
Article
One-Step Preparative Separation of Fucoxanthin from Three Edible Brown Algae by Elution-Extrusion Countercurrent Chromatography
by Danting Chen, Yating Jin, Di Hu, Jing Ye, Yanbin Lu and Zhiyuan Dai
Mar. Drugs 2022, 20(4), 257; https://doi.org/10.3390/md20040257 - 7 Apr 2022
Cited by 5 | Viewed by 4025
Abstract
A method for batch preparation of fucoxanthin from brown algae was established, which possessed the advantages of high yield and high purity. The ultrasonic-assisted extraction method was used to obtain a crude extract from Sargassum fusiforme as the separation sample. Then the crude [...] Read more.
A method for batch preparation of fucoxanthin from brown algae was established, which possessed the advantages of high yield and high purity. The ultrasonic-assisted extraction method was used to obtain a crude extract from Sargassum fusiforme as the separation sample. Then the crude extract was separated by elution-extrusion countercurrent chromatography. The optimum preparation conditions of fucoxanthin were determined as follows: n-hexane-ethanol-water (20:9:11, v:v:v) as a two-phase solvent system, the mobile phase flow rate was 5 mL min−1, the revolution speed was 800 r min−1, the loading capacity was 60 mg 10 mL−1 and the temperature was 25 °C. By this method, 12.8 mg fucoxanthin with a purity of 94.72% was obtained from the crude extract of Sargassum fusiforme. In addition, when the loading capacity was 50 mg 10 mL−1, the purity of fucoxanthin reached 96.01%. Two types of by-products, chlorophyll and pheophytin, could also be obtained during the process of separation. This optimal method was further applied to separate fucoxanthin from Laminaria japonica and Undaria pinnatifida, and 6.0 mg and 9.7 mg fucoxanthin with a purity of 96.24% and 92.62% were acquired, respectively. Therefore, it was demonstrated that the preparation method of fucoxanthin established in this study had an applicability to brown algae, which improved the utilization value of raw materials. Full article
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9 pages, 8826 KiB  
Article
A Glimpse at Siderophores Production by Anabaena flos-aquae UTEX 1444
by Roberta Teta, Germana Esposito, Karishma Kundu, Mariano Stornaiuolo, Silvia Scarpato, Antonino Pollio and Valeria Costantino
Mar. Drugs 2022, 20(4), 256; https://doi.org/10.3390/md20040256 - 6 Apr 2022
Cited by 6 | Viewed by 2989
Abstract
In this study, a strain of Anabaena flos-aquae UTEX 1444 was cultivated in six different concentrations of iron (III). Cultures were extracted with organic solvents and analyzed using our dereplication strategy, based on the combined use of high-resolution tandem mass spectrometry and molecular [...] Read more.
In this study, a strain of Anabaena flos-aquae UTEX 1444 was cultivated in six different concentrations of iron (III). Cultures were extracted with organic solvents and analyzed using our dereplication strategy, based on the combined use of high-resolution tandem mass spectrometry and molecular networking. The analysis showed the presence of the siderophores’ family, named synechobactins, only in the zero iron (III) treatment culture. Seven unknown synechobactin variants were present in the extract, and their structures have been determined by a careful HRMS/MS analysis. This study unveils the capability of Anabaena flos-aquae UTEX 1444 to produce a large array of siderophores and may be a suitable model organism for a sustainable scale-up exploitation of such bioactive molecules, for the bioremediation of contaminated ecosystems, as well as in drug discovery. Full article
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11 pages, 2055 KiB  
Article
New 3-Acyl Tetramic Acid Derivatives from the Deep-Sea-Derived Fungus Lecanicillium fusisporum
by Xinya Xu, Yanhui Tan, Chenghai Gao, Kai Liu, Zhenzhou Tang, Chunju Lu, Haiyan Li, Xiaoyong Zhang and Yonghong Liu
Mar. Drugs 2022, 20(4), 255; https://doi.org/10.3390/md20040255 - 6 Apr 2022
Cited by 5 | Viewed by 2478
Abstract
Seven rare C3-C6 reduced 3-acyl tetramic acid derivatives, lecanicilliumins A–G (17), along with the known analogue cladosporiumin D (8), were obtained from the extract of the deep-sea-derived fungus Lecanicillium fusisporum GXIMD00542 within the family Clavipitacae. Their structures [...] Read more.
Seven rare C3-C6 reduced 3-acyl tetramic acid derivatives, lecanicilliumins A–G (17), along with the known analogue cladosporiumin D (8), were obtained from the extract of the deep-sea-derived fungus Lecanicillium fusisporum GXIMD00542 within the family Clavipitacae. Their structures were elucidated by extensive spectroscopic data analysis, quantum chemistry calculations and chemical reaction. Compounds 1, 2, 57 exhibited moderate anti-inflammatory activity against NF-κB production using lipopolysaccharide (LPS) induced RAW264.7 cells with EC50 values range of 18.49–30.19 μM. Full article
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19 pages, 4488 KiB  
Article
Degradation of Alginate by a Newly Isolated Marine Bacterium Agarivorans sp. B2Z047
by Xun-Ke Sun, Ya Gong, Dan-Dan Shang, Bang-Tao Liu, Zong-Jun Du and Guan-Jun Chen
Mar. Drugs 2022, 20(4), 254; https://doi.org/10.3390/md20040254 - 4 Apr 2022
Cited by 10 | Viewed by 3366
Abstract
Alginate is the main component of brown algae, which is an important primary production in marine ecosystems and represents a huge marine biomass. The efficient utilization of alginate depends on alginate lyases to catalyze the degradation, and remains to be further explored. In [...] Read more.
Alginate is the main component of brown algae, which is an important primary production in marine ecosystems and represents a huge marine biomass. The efficient utilization of alginate depends on alginate lyases to catalyze the degradation, and remains to be further explored. In this study, 354 strains were isolated from the gut of adult abalones, which mainly feed on brown algae. Among them, 100 alginate-degrading strains were gained and the majority belonged to the Gammaproteobacteria, followed by the Bacteroidetes and Alphaproteobacteria. A marine bacterium, Agarivorans sp. B2Z047, had the strongest degradation ability of alginate with the largest degradation circle and the highest enzyme activity. The optimal alginate lyase production medium of strain B2Z047 was determined as 1.1% sodium alginate, 0.3% yeast extract, 1% NaCl, and 0.1% MgSO4 in artificial seawater (pH 7.0). Cells of strain B2Z047 were Gram-stain-negative, aerobic, motile by flagella, short rod-shaped, and approximately 0.7–0.9 µm width and 1.2–1.9 µm length. The optimal growth conditions were determined to be at 30 °C, pH 7.0–8.0, and in 3% (w/v) NaCl. A total of 12 potential alginate lyase genes were identified through whole genome sequencing and prediction, which belonged to polysaccharide lyase family 6, 7, 17, and 38 (PL6, PL7, PL17, and PL38, respectively). Furthermore, the degradation products of nine alginate lyases were detected, among which Aly38A was the first alginate lyase belonging to the PL38 family that has been found to degrade alginate. The combination of alginate lyases functioning in the alginate-degrading process was further demonstrated by the growth curve and alginate lyase production of strain B2Z047 cultivated with or without sodium alginate, as well as the content changes of total sugar and reducing sugar and the transcript levels of alginate lyase genes. A simplified model was proposed to explain the alginate utilization process of Agarivorans sp. B2Z047. Full article
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17 pages, 2454 KiB  
Review
Alzheimer’s Disease and Toxins Produced by Marine Dinoflagellates: An Issue to Explore
by Maria João Botelho, Jelena Milinovic, Narcisa M. Bandarra and Carlos Vale
Mar. Drugs 2022, 20(4), 253; https://doi.org/10.3390/md20040253 - 2 Apr 2022
Cited by 6 | Viewed by 3884
Abstract
This paper examined the toxins naturally produced by marine dinoflagellates and their effects on increases in β-amyloid plaques along with tau protein hyperphosphorylation, both major drivers of Alzheimer’s disease (AD). This approach is in line with the demand for certain natural compounds, namely [...] Read more.
This paper examined the toxins naturally produced by marine dinoflagellates and their effects on increases in β-amyloid plaques along with tau protein hyperphosphorylation, both major drivers of Alzheimer’s disease (AD). This approach is in line with the demand for certain natural compounds, namely those produced by marine invertebrates that have the potential to be used in the treatment of AD. Current advances in AD treatment are discussed as well as the main factors that potentially affect the puzzling global AD pattern. This study focused on yessotoxins (YTXs), gymnodimine (GYM), spirolides (SPXs), and gambierol, all toxins that have been shown to reduce β-amyloid plaques and tau hyperphosphorylation, thus preventing the neuronal or synaptic dysfunction that ultimately causes the cell death associated with AD (or other neurodegenerative diseases). Another group of toxins described, okadaic acid (OA) and its derivatives, inhibit protein phosphatase activity, which facilitates the presence of phosphorylated tau proteins. A few studies have used OA to trigger AD in zebrafish, providing an opportunity to test in vivo the effectiveness of new drugs in treating or attenuating AD. Constraints on the production of marine toxins for use in these tests have been considered. Different lines of research are anticipated regarding the action of the two groups of toxins. Full article
(This article belongs to the Special Issue Anti-Alzheimer Agents from Marine Sources)
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14 pages, 65725 KiB  
Article
Theragra chalcogramma Hydrolysate, Rich in Gly-Leu-Pro-Ser-Tyr-Thr, Alleviates Photoaging via Modulating Deposition of Collagen Fibers and Restoration of Extracellular Components Matrix in SD Rats
by Defeng Xu, Caihong Li and Mouming Zhao
Mar. Drugs 2022, 20(4), 252; https://doi.org/10.3390/md20040252 - 1 Apr 2022
Cited by 6 | Viewed by 2752
Abstract
Excessive exposure of the skin to ultraviolet irradiation induces skin photoaging, which seriously deteriorates the barrier functions of skin tissue, and even causes skin damages and diseases. Recently, dietary supplements from marine sources have been found to be useful in modulating skin functions [...] Read more.
Excessive exposure of the skin to ultraviolet irradiation induces skin photoaging, which seriously deteriorates the barrier functions of skin tissue, and even causes skin damages and diseases. Recently, dietary supplements from marine sources have been found to be useful in modulating skin functions and can be used to alleviate photoaging. Herein, the low-molecular-weight hydrolysates with a photoaging-protection effect were prepared by enzymatic hydrolysis from Theragra chalcogramma (TCH), and the potential mechanism were subsequently explored. The results revealed that TCH desirably improved the barrier functions of photoaged skin and stimulated the deposition of ECM components Col I, Hyp, and HA in the dermal layer. Histologically, TCH reduced the epidermal hyperplasia and restored the impaired architectures in a dose-dependent manner. Meanwhile, the activity of matrix metalloproteinase-1 (MMP-1) in photoaging skin was inhibited, and the expression levels of elastin and fibrillin-1 were elevated accordingly after TCH administration, and the significant improvements were observed at high-dose level (p < 0.05). Taken together, the efficacy of TCH against skin photoaging is highly associated with the regulation on ECM metabolism and the repairing of damaged mechanical structure. Full article
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21 pages, 2009 KiB  
Article
Evaluating Age and Growth Relationship to Ciguatoxicity in Five Coral Reef Fish Species from French Polynesia
by Hélène Taiana Darius, Christelle Paillon, Gérard Mou-Tham, André Ung, Philippe Cruchet, Taina Revel, Jérôme Viallon, Laurent Vigliola, Dominique Ponton and Mireille Chinain
Mar. Drugs 2022, 20(4), 251; https://doi.org/10.3390/md20040251 - 1 Apr 2022
Cited by 4 | Viewed by 3212
Abstract
Ciguatera poisoning (CP) results from the consumption of coral reef fish or marine invertebrates contaminated with potent marine polyether compounds, namely ciguatoxins. In French Polynesia, 220 fish specimens belonging to parrotfish (Chlorurus microrhinos, Scarus forsteni, and Scarus ghobban), surgeonfish [...] Read more.
Ciguatera poisoning (CP) results from the consumption of coral reef fish or marine invertebrates contaminated with potent marine polyether compounds, namely ciguatoxins. In French Polynesia, 220 fish specimens belonging to parrotfish (Chlorurus microrhinos, Scarus forsteni, and Scarus ghobban), surgeonfish (Naso lituratus), and groupers (Epinephelus polyphekadion) were collected from two sites with contrasted risk of CP, i.e., Kaukura Atoll versus Mangareva Island. Fish age and growth were assessed from otoliths’ yearly increments and their ciguatoxic status (negative, suspect, or positive) was evaluated by neuroblastoma cell-based assay. Using permutational multivariate analyses of variance, no significant differences in size and weight were found between negative and suspect specimens while positive specimens showed significantly greater size and weight particularly for E. polyphekadion and S. ghobban. However, eating small or low-weight specimens remains risky due to the high variability in size and weight of positive fish. Overall, no relationship could be evidenced between fish ciguatoxicity and age and growth characteristics. In conclusion, size, weight, age, and growth are not reliable determinants of fish ciguatoxicity which appears to be rather species and/or site-specific, although larger fish pose an increased risk of poisoning. Such findings have important implications in current CP risk management programs. Full article
(This article belongs to the Special Issue Marine Biotoxins 2.0)
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14 pages, 1843 KiB  
Article
Characterization of an Unknown Region Linked to the Glycoside Hydrolase Family 17 β-1,3-Glucanase of Vibrio vulnificus Reveals a Novel Glucan-Binding Domain
by Yuya Kumagai, Hideki Kishimura, Weeranuch Lang, Takayoshi Tagami, Masayuki Okuyama and Atsuo Kimura
Mar. Drugs 2022, 20(4), 250; https://doi.org/10.3390/md20040250 - 31 Mar 2022
Cited by 4 | Viewed by 3093
Abstract
The glycoside hydrolase family 17 β-1,3-glucanase of Vibrio vulnificus (VvGH17) has two unknown regions in the N- and C-termini. Here, we characterized these domains by preparing mutant enzymes. VvGH17 demonstrated hydrolytic activity of β-(1→3)-glucan, mainly producing laminaribiose, but not of β-(1→3)/β-(1→4)-glucan. The C-terminal-truncated [...] Read more.
The glycoside hydrolase family 17 β-1,3-glucanase of Vibrio vulnificus (VvGH17) has two unknown regions in the N- and C-termini. Here, we characterized these domains by preparing mutant enzymes. VvGH17 demonstrated hydrolytic activity of β-(1→3)-glucan, mainly producing laminaribiose, but not of β-(1→3)/β-(1→4)-glucan. The C-terminal-truncated mutants (ΔC466 and ΔC441) showed decreased activity, approximately one-third of that of the WT, and ΔC415 lost almost all activity. An analysis using affinity gel containing laminarin or barley β-glucan revealed a shift in the mobility of the ΔC466, ΔC441, and ΔC415 mutants compared to the WT. Tryptophan residues showed a strong affinity for carbohydrates. Three of four point-mutations of the tryptophan in the C-terminus (W472A, W499A, and W542A) showed a reduction in binding ability to laminarin and barley β-glucan. The C-terminus was predicted to have a β-sandwich structure, and three tryptophan residues (Trp472, Trp499, and Trp542) constituted a putative substrate-binding cave. Linker and substrate-binding functions were assigned to the C-terminus. The N-terminal-truncated mutants also showed decreased activity. The WT formed a trimer, while the N-terminal truncations formed monomers, indicating that the N-terminus contributed to the multimeric form of VvGH17. The results of this study are useful for understanding the structure and the function of GH17 β-1,3-glucanases. Full article
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18 pages, 1436 KiB  
Article
Encapsulation of Salmon Peptides in Marine Liposomes: Physico-Chemical Properties, Antiradical Activities and Biocompatibility Assays
by Amine Hanachi, Arnaud Bianchi, Cyril J. F. Kahn, Emilie Velot, Elmira Arab-Tehrany, Céline Cakir-Kiefer and Michel Linder
Mar. Drugs 2022, 20(4), 249; https://doi.org/10.3390/md20040249 - 31 Mar 2022
Cited by 16 | Viewed by 3106
Abstract
Salmon byproducts (Salmo salar) generated by the food chain represent a source of long-chain polyunsaturated fatty acids (eicosapentaenoic acid (EPA): 20:5n-3; docosahexaenoic acid (DHA): 22:6n-3) and peptides that can be used as supplements in food for nutraceutical [...] Read more.
Salmon byproducts (Salmo salar) generated by the food chain represent a source of long-chain polyunsaturated fatty acids (eicosapentaenoic acid (EPA): 20:5n-3; docosahexaenoic acid (DHA): 22:6n-3) and peptides that can be used as supplements in food for nutraceutical or health applications, such as in the prevention of certain pathologies (e.g., Alzheimer’s and cardiovascular diseases). The extraction of polar lipids naturally rich in PUFAs by enzymatic processes without organic solvent (controlled by pH-Stat method), coupled with the production of 1 kDa salmon peptides by membrane filtration, allowed the formulation of nanocarriers. The physicochemical properties of the nanoliposomes (size ranging from 120 to 140 nm, PDI of 0.27, zeta potential between −32 and −46 mV and encapsulation efficiency) were measured, and the bioactivity of salmon hydrolysate peptides was assessed (antioxidant and antiradical activity: ABTS, ORAC, DPPH; iron metal chelation). Salmon peptides exhibited good angiotensin-conversion-enzyme (ACE) inhibition activity, with an IC50 value of 413.43 ± 13.12 µg/mL. Cytotoxicity, metabolic activity and proliferation experiments demonstrated the harmlessness of the nanostructures in these experimental conditions. Full article
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15 pages, 25564 KiB  
Article
Pan-Genomic and Transcriptomic Analyses of Marine Pseudoalteromonas agarivorans Hao 2018 Revealed Its Genomic and Metabolic Features
by Yuhao Jv, Chenxiang Xi, Yanqiu Zhao, Wei Wang, Yiling Zhang, Kai Liu, Wenlin Liu, Kai Shan, Chunlei Wang, Ruiwen Cao, Cunxi Dai, Yiting Jv, Wenxing Zhu, Haiyong Wang, Qiuxia He and Lujiang Hao
Mar. Drugs 2022, 20(4), 248; https://doi.org/10.3390/md20040248 - 31 Mar 2022
Cited by 1 | Viewed by 2453
Abstract
The genomic and carbohydrate metabolic features of Pseudoalteromonas agarivorans Hao 2018 (P. agarivorans Hao 2018) were investigated through pan-genomic and transcriptomic analyses, and key enzyme genes that may encode the process involved in its extracellular polysaccharide synthesis were screened. The pan-genome of [...] Read more.
The genomic and carbohydrate metabolic features of Pseudoalteromonas agarivorans Hao 2018 (P. agarivorans Hao 2018) were investigated through pan-genomic and transcriptomic analyses, and key enzyme genes that may encode the process involved in its extracellular polysaccharide synthesis were screened. The pan-genome of the P. agarivorans strains consists of a core-genome containing 2331 genes, an accessory-genome containing 956 genes, and a unique-genome containing 1519 genes. Clusters of Orthologous Groups analyses showed that P. agarivorans harbors strain-specifically diverse metabolisms, probably representing high evolutionary genome changes. The Kyoto Encyclopedia of Genes and Genomes and reconstructed carbohydrate metabolic pathways displayed that P. agarivorans strains can utilize a variety of carbohydrates, such as d-glucose, d-fructose, and d-lactose. Analyses of differentially expressed genes showed that compared with the stationary phase (24 h), strain P. agarivorans Hao 2018 had upregulated expression of genes related to the synthesis of extracellular polysaccharides in the logarithmic growth phase (2 h), and that the expression of these genes affected extracellular polysaccharide transport, nucleotide sugar synthesis, and glycosyltransferase synthesis. This is the first investigation of the genomic and metabolic features of P. agarivorans through pan-genomic and transcriptomic analyses, and these intriguing discoveries provide the possibility to produce novel marine drug lead compounds with high biological activity. Full article
(This article belongs to the Special Issue Bioinformatics of Marine Natural Products 2.0)
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14 pages, 4230 KiB  
Article
Simultaneous Inhibitory Effects of All-Trans Astaxanthin on Acetylcholinesterase and Oxidative Stress
by Xin Wang, Tao Zhang, Xiaochen Chen, Yating Xu, Zhipeng Li, Yuanfan Yang, Xiping Du, Zedong Jiang and Hui Ni
Mar. Drugs 2022, 20(4), 247; https://doi.org/10.3390/md20040247 - 31 Mar 2022
Cited by 8 | Viewed by 2459
Abstract
Alzheimer´s disease is a global neurodegenerative health concern. To prevent the disease, the simultaneous inhibition of acetylcholinesterase and oxidative stress is an efficient approach. In this study, the inhibition effect of all-trans astaxanthin mainly from marine organisms on acetylcholinesterase and oxidative stress was [...] Read more.
Alzheimer´s disease is a global neurodegenerative health concern. To prevent the disease, the simultaneous inhibition of acetylcholinesterase and oxidative stress is an efficient approach. In this study, the inhibition effect of all-trans astaxanthin mainly from marine organisms on acetylcholinesterase and oxidative stress was evaluated by a chemical-based method in vitro and cell assay model. The results show that all-trans astaxanthin was a reversible competitive inhibitor and exhibited a strong inhibition effect with half inhibitory concentration (IC50 value) of 8.64 μmol/L. Furthermore, all-trans astaxanthin inhibited oxidative stress through reducing malondialdehyde content and increasing the activity of superoxide dismutase as well as catalase. All-trans astaxanthin could induce the changes of the secondary structure to reduce acetylcholinesterase activity. Molecular-docking analysis reveals that all-trans astaxanthin prevented substrate from binding to acetylcholinesterase by occupying the space of the active pocket to cause the inhibition. Our finding suggests that all-trans astaxanthin might be a nutraceutical supplement for Alzheimer´s disease prevention. Full article
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24 pages, 15648 KiB  
Article
Exploring the Diversity of Red Microalgae for Exopolysaccharide Production
by Aldo Borjas Esqueda, Christine Gardarin and Céline Laroche
Mar. Drugs 2022, 20(4), 246; https://doi.org/10.3390/md20040246 - 31 Mar 2022
Cited by 18 | Viewed by 3908
Abstract
Microalgae constitute a remarkable biological diversity but a limited number of them have been the object of study for their ability to produce exoplysaccharides (EPS). Among them, the red marine microalgae Porphyridium or Rhodella produce sulphated EPS, exhibiting some biological activities with potential [...] Read more.
Microalgae constitute a remarkable biological diversity but a limited number of them have been the object of study for their ability to produce exoplysaccharides (EPS). Among them, the red marine microalgae Porphyridium or Rhodella produce sulphated EPS, exhibiting some biological activities with potential interest in the pharmaceutical and cosmetic industries. EPS from Porphyridium and Rhodella being relatively similar in their composition, it has long been considered that all the red microalgae produced similar EPS and no attention was paid to other red microalgae. The objective of our work was then to explore the diversity of red microalgae for the production of EPS, focusing in this first step on the screening of the strains for their ability to produce EPS and preliminary structural characterization. The study was conducted with 11 microalgae strains belonging to the proteorhodophytina subphylum. All microalgae were able to produce EPS, released in the culture medium (strains belonging to Porphyridiophyceae and Rhodellophyceae classes) or remaining bound to the cells (strains from Stylonematophyceae class). The analysis of monosaccharides composition was found significantly different, with for instance high levels of glucuronic acids in the EPS from C. japonica and N. cyanea, but also strong differences in the sulphation degrees of polymers (between 1.2 and 28.7% eq. SO4). Full article
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17 pages, 3077 KiB  
Article
Fucoxanthin Prevents Long-Term Administration l-DOPA-Induced Neurotoxicity through the ERK/JNK-c-Jun System in 6-OHDA-Lesioned Mice and PC12 Cells
by Jingwangwei Liu, Yujia Lu, Min Tang, Fanghao Shao, Dongzi Yang, Shuchang Chen, Ziyi Xu, Leilei Zhai, Juanjuan Chen, Qian Li, Wei Wu and Haimin Chen
Mar. Drugs 2022, 20(4), 245; https://doi.org/10.3390/md20040245 - 31 Mar 2022
Cited by 13 | Viewed by 2832
Abstract
As the most abundant marine carotenoid extracted from seaweeds, fucoxanthin is considered to have neuroprotective activity via its excellent antioxidant properties. Oxidative stress is regarded as an important starting factor for neuronal cell loss and necrosis, is one of the causes of Parkinson’s [...] Read more.
As the most abundant marine carotenoid extracted from seaweeds, fucoxanthin is considered to have neuroprotective activity via its excellent antioxidant properties. Oxidative stress is regarded as an important starting factor for neuronal cell loss and necrosis, is one of the causes of Parkinson’s disease (PD), and is considered to be the cause of adverse reactions caused by the current PD commonly used treatment drug levodopa (l-DA). Supplementation with antioxidants early in PD can effectively prevent neurodegeneration and inhibit apoptosis in dopaminergic neurons. At present, the effect of fucoxanthin in improving the adverse effects triggered by long-term l-DA administration in PD patients is unclear. In the present study, we found that fucoxanthin can reduce cytotoxicity and suppress the high concentration of l-DA (200 μM)-mediated cell apoptosis in the 6-OHDA-induced PC12 cells through improving the reduction in mitochondrial membrane potential, suppressing ROS over-expression, and inhibiting active of ERK/JNK-c-Jun system and expression of caspase-3 protein. These results were demonstrated by PD mice with long-term administration of l-DA showing enhanced motor ability after intervention with fucoxanthin. Our data indicate that fucoxanthin may prove useful in the treatment of PD patients with long-term l-DA administration. Full article
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22 pages, 969 KiB  
Review
Marine Demospongiae: A Challenging Treasure of Bioactive Compounds
by Roberta Esposito, Serena Federico, Marco Bertolino, Valerio Zupo and Maria Costantini
Mar. Drugs 2022, 20(4), 244; https://doi.org/10.3390/md20040244 - 31 Mar 2022
Cited by 12 | Viewed by 4232
Abstract
In the last decades, it has been demonstrated that marine organisms are a substantial source of bioactive compounds with possible biotechnological applications. Marine sponges, in particular those belonging to the class of Demospongiae, have been considered among the most interesting invertebrates for their [...] Read more.
In the last decades, it has been demonstrated that marine organisms are a substantial source of bioactive compounds with possible biotechnological applications. Marine sponges, in particular those belonging to the class of Demospongiae, have been considered among the most interesting invertebrates for their biotechnological potential. In this review, particular attention is devoted to natural compounds/extracts isolated from Demospongiae and their associated microorganisms with important biological activities for pharmacological applications such as antiviral, anticancer, antifouling, antimicrobial, antiplasmodial, antifungal and antioxidant. The data here presented show that this class of sponges is an exciting source of compounds, which are worth developing into new drugs, such as avarol, a hydroquinone isolated from the marine sponge Disidea avara, which is used as an antitumor, antimicrobial and antiviral drug. Full article
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27 pages, 2768 KiB  
Review
Molecular Targets of Brown Algae Phlorotannins for the Therapy of Inflammatory Processes of Various Origins
by Natalya N. Besednova, Boris G. Andryukov, Tatyana S. Zaporozhets, Tatyana A. Kuznetsova, Sergey P. Kryzhanovsky, Svetlana P. Ermakova, Irina V. Galkina and Mikhail Yu. Shchelkanov
Mar. Drugs 2022, 20(4), 243; https://doi.org/10.3390/md20040243 - 30 Mar 2022
Cited by 23 | Viewed by 3750
Abstract
Inflammatory reactions are part of a complex biological response that plays a vital role in the appearance of various stimuli resulting from tissue and cell damage, the invasion of pathogenic bacteria, and the formation of the subsequent adaptive immune response. The production of [...] Read more.
Inflammatory reactions are part of a complex biological response that plays a vital role in the appearance of various stimuli resulting from tissue and cell damage, the invasion of pathogenic bacteria, and the formation of the subsequent adaptive immune response. The production of many triggers and mediators of inflammation, which are inducers of pro-inflammatory factors, is controlled by numerous differentiation programs, through which inflammation is resolved and tissue homeostasis is restored. However, prolonged inflammatory responses or dysregulation of pro-inflammatory mechanisms can lead to chronic inflammation. Modern advances in biotechnology have made it possible to characterize the anti-inflammatory activity of phlorotannins, polyphenolic compounds from brown seaweed, and the mechanisms by which they modulate the inflammatory response. The purpose of this review is to analyze and summarize the results of numerous experimental in vitro and in vivo studies, illustrating the regulatory mechanisms of these compounds, which have a wide range of biological effects on the body. The results of these studies and the need for further research are discussed. Full article
(This article belongs to the Special Issue Advances in Medicinal Research of Phlorotannins)
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