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Mar. Drugs, Volume 20, Issue 11 (November 2022) – 73 articles

Cover Story (view full-size image): Whenever a new natural product is isolated, it must be structurally unequivocally identified. However, the intrinsic complexity of some molecular architectures makes this task problematic. NMR spectroscopy is the most widely used technique in structure elucidation, but more recently computational methods have been frequently used to support data analysis. The impact of force field selection in DP4 and J-DP4 computational approaches was assessed, along with geometry and energy cutoffs. A new approach named mix-J-DP4, which provides a remarkable increase in the confidence level of complex stereochemical assignments with a very modest increment in computational cost, is proposed. View this paper
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22 pages, 6555 KiB  
Article
Anti-Biofilm Activity of a Hyaluronan-like Exopolysaccharide from the Marine Vibrio MO245 against Pathogenic Bacteria
by Marie Champion, Emilie Portier, Karine Vallée-Réhel, Isabelle Linossier, Eric Balnois, Guillaume Vignaud, Xavier Moppert, Claire Hellio and Fabienne Faÿ
Mar. Drugs 2022, 20(11), 728; https://doi.org/10.3390/md20110728 - 21 Nov 2022
Cited by 5 | Viewed by 2110
Abstract
Biofilms, responsible for many serious drawbacks in the medical and marine environment, can grow on abiotic and biotic surfaces. Commercial anti-biofilm solutions, based on the use of biocides, are available but their use increases the risk of antibiotic resistance and environmental pollution in [...] Read more.
Biofilms, responsible for many serious drawbacks in the medical and marine environment, can grow on abiotic and biotic surfaces. Commercial anti-biofilm solutions, based on the use of biocides, are available but their use increases the risk of antibiotic resistance and environmental pollution in marine industries. There is an urgent need to work on the development of ecofriendly solutions, formulated without biocidal agents, that rely on the anti-adhesive physico-chemical properties of their materials. In this context, exopolysaccharides (EPSs) are natural biopolymers with complex properties than may be used as anti-adhesive agents. This study is focused on the effect of the EPS MO245, a hyaluronic acid-like polysaccharide, on the growth, adhesion, biofilm maturation, and dispersion of two pathogenic model strains, Pseudomonas aeruginosa sp. PaO1 and Vibrio harveyi DSM19623. Our results demonstrated that MO245 may limit biofilm formation, with a biofilm inhibition between 20 and 50%, without any biocidal activity. Since EPSs have no significant impact on the bacterial motility and quorum sensing factors, our results indicate that physico-chemical interactions between the bacteria and the surfaces are modified due to the presence of an adsorbed EPS layer acting as a non-adsorbing layer. Full article
(This article belongs to the Collection Marine Polysaccharides)
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15 pages, 2053 KiB  
Article
Orchestrated Response of Intracellular Zwitterionic Metabolites in Stress Adaptation of the Halophilic Heterotrophic Bacterium Pelagibaca bermudensis
by Muhaiminatul Azizah and Georg Pohnert
Mar. Drugs 2022, 20(11), 727; https://doi.org/10.3390/md20110727 - 19 Nov 2022
Cited by 4 | Viewed by 1854
Abstract
Osmolytes are naturally occurring organic compounds that protect cells against various forms of stress. Highly polar, zwitterionic osmolytes are often used by marine algae and bacteria to counteract salinity or temperature stress. We investigated the effect of several stress conditions including different salinities, [...] Read more.
Osmolytes are naturally occurring organic compounds that protect cells against various forms of stress. Highly polar, zwitterionic osmolytes are often used by marine algae and bacteria to counteract salinity or temperature stress. We investigated the effect of several stress conditions including different salinities, temperatures, and exposure to organic metabolites released by the alga Tetraselmis striata on the halophilic heterotrophic bacterium Pelagibaca bermudensis. Using ultra-high-performance liquid chromatography (UHPLC) on a ZIC-HILIC column and high-resolution electrospray ionization mass spectrometry, we simultaneously detected and quantified the eleven highly polar compounds dimethylsulfoxonium propionate (DMSOP), dimethylsulfoniopropionate (DMSP), gonyol, cysteinolic acid, ectoine, glycine betaine (GBT), carnitine, sarcosine, choline, proline, and 4-hydroxyproline. All compounds are newly described in P. bermudensis and potentially involved in physiological functions essential for bacterial survival under variable environmental conditions. We report that adaptation to various forms of stress is accomplished by adjusting the pattern and amount of the zwitterionic metabolites. Full article
(This article belongs to the Collection Bioactive Compounds from Marine Plankton)
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13 pages, 2530 KiB  
Article
Isolation of Scalimides A–L: β-Alanine-Bearing Scalarane Analogs from the Marine Sponge Spongia sp.
by A-Young Shin, Hyi-Seung Lee and Jihoon Lee
Mar. Drugs 2022, 20(11), 726; https://doi.org/10.3390/md20110726 - 18 Nov 2022
Cited by 4 | Viewed by 1496
Abstract
A chemical investigation of a methanol extract of Spongia sp., a marine sponge collected from the Philippines, identified 12 unreported scalarane-type alkaloids—scalimides A–L (112)—together with two previously described scalarin derivatives. The elucidation of the structure of the scalaranes based [...] Read more.
A chemical investigation of a methanol extract of Spongia sp., a marine sponge collected from the Philippines, identified 12 unreported scalarane-type alkaloids—scalimides A–L (112)—together with two previously described scalarin derivatives. The elucidation of the structure of the scalaranes based on the interpretation of their NMR and HRMS data revealed that 112 featured a β-alanine-substituted E-ring but differed from each other through variations in their oxidation states and substitutions occurring at C16, C24, and C25. Evaluation of the antimicrobial activity of 112 against several Gram-positive and Gram-negative bacteria showed that 10 and 11 were active against Micrococcus luteus and Bacillus subtilis, respectively, with MIC values ranging from 4 to 16 μg/mL. Full article
(This article belongs to the Section Structural Studies on Marine Natural Products)
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18 pages, 2621 KiB  
Article
Neoagaro-Oligosaccharides Ameliorate Chronic Restraint Stress-Induced Depression by Increasing 5-HT and BDNF in the Brain and Remodeling the Gut Microbiota of Mice
by Yan Zhuang, Runying Zeng, Xiao Liu, Longhe Yang and Zhuhua Chan
Mar. Drugs 2022, 20(11), 725; https://doi.org/10.3390/md20110725 - 18 Nov 2022
Cited by 6 | Viewed by 2772
Abstract
Neoagaro-oligosaccharides (NAOs) belong to the algae oligosaccharides. NAOs have been found to have diverse biological activities. However, the effects of NAOs on depression and their underlying mechanism have not been thoroughly studied. A chronic restraint stress (CRS)-induced C57BL/6J mouse model was used to [...] Read more.
Neoagaro-oligosaccharides (NAOs) belong to the algae oligosaccharides. NAOs have been found to have diverse biological activities. However, the effects of NAOs on depression and their underlying mechanism have not been thoroughly studied. A chronic restraint stress (CRS)-induced C57BL/6J mouse model was used to assess the antidepressant effects of NAOs. Anxiety and depression behaviors were assessed by open field tests (OFT) and forced swimming tests (FST), while interleukin 18 (IL-18), 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) were the molecular biomarkers of depression. Fecal microbiota transplantation (FMT) was performed. The results showed that NAO treatment significantly improved the body weight of depressed mice and reduced the central area time in the OFT and immobility time in the FST. NAO treatment decreased the levels of IL-18 in the serum and increased the levels of 5-HT in the serum and whole brain and of BDNF in the whole brain. NAO treatment mitigated the gut microbiota dysbiosis in the depressed mice and reversed the decreased levels of short-chain fatty acids (SCFAs) in the cecum of the depressed mice. FMT indicated that the gut microbiota is, indeed, linked to depression, which was reflected in the changes in weight gain and behaviors. In a word, NAOs effectively reversed the CRS-induced mice model of depression, which depended on the changes in the gut microbiota and SCFAs, as well as its modulation of 5-HT and BDNF. Full article
(This article belongs to the Collection Marine Polysaccharides)
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14 pages, 2668 KiB  
Article
Continuous Production of Biogenic Magnetite Nanoparticles by the Marine Bacterium Magnetovibrio blakemorei Strain MV-1T with a Nitrous Oxide Injection Strategy
by Tarcisio Correa, Mateus G. Godoy, Dennis A. Bazylinski and Fernanda Abreu
Mar. Drugs 2022, 20(11), 724; https://doi.org/10.3390/md20110724 - 18 Nov 2022
Cited by 2 | Viewed by 1542
Abstract
Magnetotactic bacteria (MTB) produce magnetosomes, which are membrane-embedded magnetic nanoparticles. Despite their technological applicability, the production of magnetite magnetosomes depends on the cultivation of MTB, which results in low yields. Thus, strategies for the large-scale cultivation of MTB need to be improved. Here, [...] Read more.
Magnetotactic bacteria (MTB) produce magnetosomes, which are membrane-embedded magnetic nanoparticles. Despite their technological applicability, the production of magnetite magnetosomes depends on the cultivation of MTB, which results in low yields. Thus, strategies for the large-scale cultivation of MTB need to be improved. Here, we describe a new approach for bioreactor cultivation of Magnetovibrio blakemorei strain MV-1T. Firstly, a fed-batch with a supplementation of iron source and N2O injection in 24-h pulses was established. After 120 h of cultivation, the production of magnetite reached 24.5 mg∙L−1. The maximum productivity (16.8 mg∙L−1∙day−1) was reached between 48 and 72 h. However, the productivity and mean number of magnetosomes per cell decreased after 72 h. Therefore, continuous culture in the chemostat was established. In the continuous process, magnetite production and productivity were 27.1 mg∙L−1 and 22.7 mg∙L−1∙day−1, respectively, at 120 h. This new approach prevented a decrease in magnetite production in comparison to the fed-batch strategy. Full article
(This article belongs to the Special Issue Marine Drugs Research in Brazil)
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15 pages, 3411 KiB  
Article
In Silico Analysis of Tetrodotoxin Binding in Voltage-Gated Sodium Ion Channels from Toxin-Resistant Animal Lineages
by Shana L. Geffeney, Jennie Ann Cordingley, Kenyon Mitchell and Charles T. Hanifin
Mar. Drugs 2022, 20(11), 723; https://doi.org/10.3390/md20110723 - 18 Nov 2022
Cited by 1 | Viewed by 1924
Abstract
Multiple animal species have evolved resistance to the neurotoxin tetrodotoxin (TTX) through changes in voltage-gated sodium ion channels (VGSCs). Amino acid substitutions in TTX-resistant lineages appear to be positionally convergent with changes in homologous residues associated with reductions in TTX block. We used [...] Read more.
Multiple animal species have evolved resistance to the neurotoxin tetrodotoxin (TTX) through changes in voltage-gated sodium ion channels (VGSCs). Amino acid substitutions in TTX-resistant lineages appear to be positionally convergent with changes in homologous residues associated with reductions in TTX block. We used homology modeling coupled with docking simulations to test whether positionally convergent substitutions generate functional convergence at the level of TTX–channel interactions. We found little evidence that amino acids at convergent positions generated similar patterns among TTX-resistant animal lineages across several metrics, including number of polar contacts, polar contact position, and estimates of binding energy. Though binding energy values calculated for TTX docking were reduced for some TTX-resistant channels, not all TTX-resistant channels and not all of our analyses returned reduced binding energy values for TTX-resistant channels. Our results do not support a simple model of toxin resistance where a reduced number of bonds between TTX and the channel protein prevents blocking. Rather models that incorporate flexibility and movement of the protein overall may better describe how homologous substitutions in the channel cause changes in TTX block. Full article
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13 pages, 4008 KiB  
Article
Echinochrome A Reverses Kidney Abnormality and Reduces Blood Pressure in a Rat Model of Preeclampsia
by Huixing Cui, Junxian Liu, Elena A. Vasileva, Natalia P. Mishchenko, Sergey A. Fedoreyev, Valentin A. Stonik and Yinhua Zhang
Mar. Drugs 2022, 20(11), 722; https://doi.org/10.3390/md20110722 - 17 Nov 2022
Cited by 3 | Viewed by 1585
Abstract
We aimed to observe the effects of Echinochrome A (Ech A) on systemic changes using a rat model of preeclampsia. The results showed that an infusion of angiotensin II (Ang II) through an osmotic pump (1 μg/kg/min) on GD 8 increased systolic and [...] Read more.
We aimed to observe the effects of Echinochrome A (Ech A) on systemic changes using a rat model of preeclampsia. The results showed that an infusion of angiotensin II (Ang II) through an osmotic pump (1 μg/kg/min) on GD 8 increased systolic and diastolic blood pressures and reduced fetal weight and placental weight. The diameters of the glomeruli were expended and glomeruli capillaries were diminished. No change was observed in the heart and liver in the Ang II group, but epithelial structures were disrupted in the uterus. Ech A treatment on GD 14 (100 μg/μL) through the jugular vein reduced systolic and diastolic blood pressures and reversed glomerulus alterations, but the fetal or placental parameters were unaffected. Ech A only partly reversed the effect on the uterus. The mRNA expression of TNF–α was increased and IL–10 and VEGF were reduced in the uterus of the Ang II group, while Ech A restored these changes. A similar trend was observed in the kidney, liver, and heart of this group. Furthermore, Bcl–2 was reduced and Bcl–2/Bax ratios were significantly reduced in the kidney and heart of the Ang II group, while Ech A reversed these changes. We suggest that Ech A modulates inflammation and apoptosis in key systemic organs in Ang II-induced rat preeclampsia and preserves kidney and uterus structures and reduces blood pressure. Full article
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13 pages, 3854 KiB  
Review
Carbonic Anhydrase Inhibitors from Marine Natural Products
by Claudiu T. Supuran
Mar. Drugs 2022, 20(11), 721; https://doi.org/10.3390/md20110721 - 17 Nov 2022
Cited by 11 | Viewed by 1947
Abstract
Carbonic anhydrases (CAs, EC 4.2.1.1) are widespread metalloenzymes in organisms in all life kingdoms, being involved in pH regulation, metabolic processes and many other physiological and pathological conditions. CA inhibitors and activators thus possess applications as pharmacological agents in the management of a [...] Read more.
Carbonic anhydrases (CAs, EC 4.2.1.1) are widespread metalloenzymes in organisms in all life kingdoms, being involved in pH regulation, metabolic processes and many other physiological and pathological conditions. CA inhibitors and activators thus possess applications as pharmacological agents in the management of a range of diseases. Marine natural products have allowed the identification of some highly interesting CA inhibitors, among which are sulfonamides, phenols, polyamines, coumarins and several other miscellaneous inhibitors, which are reviewed here. Psammaplin C and some bromophenols were the most investigated classes of such marine-based inhibitors and have been used as lead molecules for developing interesting types of potent and, in some cases, isoform-selective inhibitors, with applications as antitumor agents by inhibiting human CA XII and P-glycoprotein activities. Some phenols have shown interesting bacterial and fungal β-CA inhibitory effects. Marine natural products thus constitute a gold mine for identifying novel CA inhibitors, some of which may lead to the development of novel types of pharmacological agents. Full article
(This article belongs to the Special Issue The Mechanisms of Action of Bioactive Marine Natural Products)
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12 pages, 2179 KiB  
Article
New Polyketides from a Hydrothermal Vent Sediment Fungus Trichoderma sp. JWM29-10-1 and Their Antimicrobial Effects
by Changrong Lai, Jiayi Chen, Jing Liu, Danmei Tian, Donghe Lan, Tongzheng Liu, Bin Wu, Hongkai Bi and Jinshan Tang
Mar. Drugs 2022, 20(11), 720; https://doi.org/10.3390/md20110720 - 16 Nov 2022
Cited by 11 | Viewed by 2010
Abstract
Marine fungi-derived secondary metabolites are still an important source for the discovery of potential antimicrobial agents. Here, five new polyketides (1, 2, and 68) and seven known compounds (35 and 912) [...] Read more.
Marine fungi-derived secondary metabolites are still an important source for the discovery of potential antimicrobial agents. Here, five new polyketides (1, 2, and 68) and seven known compounds (35 and 912) were obtained from the culture of the marine-derived fungus Trichoderma sp. JWM29-10-1. Their structures were identified by extensive spectrographic data analyses, including 1D and 2D NMR, UV, IR, and HR-ESI-MS. Further, the absolute configurations of new compounds were determined by circular dichroism (CD) spectrum and alkali-hydrolysis in combination with the in situ dimolybdenum CD method. Subsequently, the antimicrobial effects of these isolated compounds were assessed by examining the minimal inhibition concentration (MIC) with the broth microdilution assay. Compounds 1 and 2 exhibited potent antimicrobial activity against Helicobacter pylori, including multidrug-resistant strains, with MIC range values of 2–8 µg/mL. Moreover, compound 1 showed significant inhibitory effects on the growth of Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecalis, and vancomycin-resistant Enterococcus faecium, which greatly threaten human health. This study demonstrates that chromone derivatives 12, especially for 1, could be potential lead compounds for the development of new antimicrobial agents and provides insight for future medicinal chemistry research. Full article
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19 pages, 3956 KiB  
Article
Preparation and Hepatoprotective Activities of Peptides Derived from Mussels (Mytilus edulis) and Clams (Ruditapes philippinarum)
by Qian Wang, Fu-Jun Liu, Xin-Miao Wang, Guan-Hua Zhao, Dong Cai, Jing-Han Yu, Fa-Wen Yin and Da-Yong Zhou
Mar. Drugs 2022, 20(11), 719; https://doi.org/10.3390/md20110719 - 16 Nov 2022
Cited by 6 | Viewed by 1599
Abstract
Low molecular weight (<5 kDa) peptides from mussels (Mytilus edulis) (MPs) and the peptides from clams (Ruditapes philippinarum) (CPs) were prepared through enzymatic hydrolysis by proteases (dispase, pepsin, trypsin, alcalase and papain). Both the MPs and the CPs showed [...] Read more.
Low molecular weight (<5 kDa) peptides from mussels (Mytilus edulis) (MPs) and the peptides from clams (Ruditapes philippinarum) (CPs) were prepared through enzymatic hydrolysis by proteases (dispase, pepsin, trypsin, alcalase and papain). Both the MPs and the CPs showed excellent in vitro scavenging ability of free radicals including OH, DPPH and ABTS in the concentration range of 0.625–10.000 mg/mL. By contrast, the MPs hydrolyzed by alcalase (MPs-A) and the CPs hydrolyzed by dispase (CPs-D) had the highest antioxidant activities. Furthermore, MPs-A and CPs-D exhibited protective capabilities against oxidative damage induced by H2O2 in HepG2 cells in the concentration range of 25–800 μg/mL. Meanwhile, compared with the corresponding indicators of the negative control (alcohol-fed) mice, lower contents of hepatic MDA and serums ALT and AST, as well as higher activities of hepatic SOD and GSH-PX were observed in experiment mice treated with MPs-A and CPs-D. The present results clearly indicated that Mytilus edulis and Ruditapes philippinarum are good sources of hepatoprotective peptides. Full article
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24 pages, 6045 KiB  
Article
3D Biocomposites Comprising Marine Collagen and Silica-Based Materials Inspired on the Composition of Marine Sponge Skeletons Envisaging Bone Tissue Regeneration
by Eva Martins, Gabriela S. Diogo, Ricardo Pires, Rui L. Reis and Tiago H. Silva
Mar. Drugs 2022, 20(11), 718; https://doi.org/10.3390/md20110718 - 16 Nov 2022
Cited by 10 | Viewed by 2423
Abstract
Ocean resources are a priceless repository of unique species and bioactive compounds with denouement properties that can be used in the fabrication of advanced biomaterials as new templates for supporting the cell culture envisaging tissue engineering approaches. The collagen of marine origin can [...] Read more.
Ocean resources are a priceless repository of unique species and bioactive compounds with denouement properties that can be used in the fabrication of advanced biomaterials as new templates for supporting the cell culture envisaging tissue engineering approaches. The collagen of marine origin can be sustainably isolated from the underrated fish processing industry by-products, while silica and related materials can be found in the spicules of marine sponges and diatoms frustules. Aiming to address the potential of biomaterials composed from marine collagen and silica-based materials in the context of bone regeneration, four different 3D porous structure formulations (COL, COL:BG, COL:D.E, and COL:BS) were fabricated by freeze-drying. The skins of Atlantic cod (Gadus morhua) were used as raw materials for the collagen (COL) isolation, which was successfully characterized by SDS-PAGE, FTIR, CD, and amino acid analyses, and identified as a type I collagen, produced with a 1.5% yield and a preserved characteristic triple helix conformation. Bioactive glass 45S5 bioglass® (BG), diatomaceous earth (D.E.) powder, and biosilica (BS) isolated from the Axinella infundibuliformis sponge were chosen as silica-based materials, which were obtained as microparticles and characterized by distinct morphological features. The biomaterials revealed microporous structures, showing a porosity higher than 85%, a mean pore size range of 138–315 μm depending on their composition, with 70% interconnectivity which can be favorable for cell migration and ensure the needed nutrient supply. In vitro, biological assays were conducted by culturing L929 fibroblast-like cells, which confirmed not only the non-toxic nature of the developed biomaterials but also their capability to support cell adhesion and proliferation, particularly the COL:BS biomaterials, as observed by calcein-AM staining upon seven days of culture. Moreover, phalloidin and DAPI staining revealed well-spread cells, populating the entire construct. This study established marine collagen/silica biocomposites as potential scaffolds for tissue engineering, setting the basis for future studies, particularly envisaging the regeneration of non-load-bearing bone tissues. Full article
(This article belongs to the Special Issue Biomedical and Pharmacological Applications of Marine Collagen)
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17 pages, 3507 KiB  
Article
Double Valorization for a Discard—α-Chitin and Calcium Lactate Production from the Crab Polybius henslowii Using a Deep Eutectic Solvent Approach
by Colin McReynolds, Amandine Adrien, Arnaud Petitpas, Laurent Rubatat and Susana C. M. Fernandes
Mar. Drugs 2022, 20(11), 717; https://doi.org/10.3390/md20110717 - 16 Nov 2022
Cited by 1 | Viewed by 1937
Abstract
Polybius henslowii, an abundant yet unexploited species of swimming crab, was investigated as a potential source of α-chitin and calcium lactate using deep eutectic solvents (DES) as extracting solvents. Choline chloride–malonic acid (CCMA) and choline chloride–lactic acid (CCLA) were used to obtain [...] Read more.
Polybius henslowii, an abundant yet unexploited species of swimming crab, was investigated as a potential source of α-chitin and calcium lactate using deep eutectic solvents (DES) as extracting solvents. Choline chloride–malonic acid (CCMA) and choline chloride–lactic acid (CCLA) were used to obtain high purity α-chitin from ball-milled P. henslowii exoskeleton in 2 h at 120 °C, with yields of 12.05 ± 2.54% and 12.8 ± 1.54%, respectively. The physical and chemical characteristics of the obtained chitins were assessed using CHN elemental analysis, attenuated total reflectance–Fourier transform infrared spectroscopy, thermogravimetric analysis, and scanning electron microscopy. Furthermore, the CCLA solvent was reusable three times with little effect on the extract purity, and calcium lactate was produced at the end of the recycling cycles. The ensuing calcium lactate was also characterized in terms of chemical and physical properties. The obtained chitin is a promising raw material for downstream processing and the double valorization pathway with the obtention of calcium salts may increase the viability of a DES-based approach for the processing of mineralized substrates. Full article
(This article belongs to the Section Biomaterials of Marine Origin)
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24 pages, 1347 KiB  
Article
Potentially Beneficial Effects on Healthy Aging by Supplementation of the EPA-Rich Microalgae Phaeodactylum tricornutum or Its Supernatant—A Randomized Controlled Pilot Trial in Elderly Individuals
by Lena Stiefvatter, Konstantin Frick, Katja Lehnert, Walter Vetter, Alexander Montoya-Arroyo, Jan Frank, Ulrike Schmid-Staiger and Stephan C. Bischoff
Mar. Drugs 2022, 20(11), 716; https://doi.org/10.3390/md20110716 - 15 Nov 2022
Cited by 10 | Viewed by 2330
Abstract
Dietary supplements that promote healthy aging are mostly warranted in an aging society. Because of age-related risks, anti-inflammatory and anti-oxidative agents such as microalgae are potential candidates for intervention. In a randomized controlled trial, we tested Phaeodactylum tricornutum (PT), a microalgae rich in [...] Read more.
Dietary supplements that promote healthy aging are mostly warranted in an aging society. Because of age-related risks, anti-inflammatory and anti-oxidative agents such as microalgae are potential candidates for intervention. In a randomized controlled trial, we tested Phaeodactylum tricornutum (PT), a microalgae rich in eicosapentaenoic acid (EPA), carotenoids, vitamins, and β-glucans, cultured in bioreactors. In this pilot trial, 19 healthy elderly received supplements for two weeks based on either the whole PT (A), the β-1,3-glucan-rich PT supernatant (SupB), the combination thereof (A+SupB), or a Comparator product (Comp). The primary outcome variable plasma interleukin-6 was reduced after treatment with A+SupB compared to the Comp group (p = 0.04). The mobility parameters 5 s sit-to-stand test (p = 0.04 in the A group) and by trend gait speed (p = 0.08 in the A+SupB diet) were improved compared to Comp. No treatment effects were observed for fatty acids, compared to Comp but omega-6 to -3 fatty acid ratio (p = 0.006) and arachidonic acid/EPA ratio (p = 0.006) were reduced within group A+SupB. Further, the SupB study product reduced faecal zonulin (p = 0.03) compared to the Comp. The data revealed an anti-inflammatory and potentially anti-oxidative effect of particular PT preparations, suggesting that they might be suitable for effects in healthy elderly. Full article
(This article belongs to the Special Issue Fatty Acids from Marine Organisms)
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20 pages, 3644 KiB  
Article
Structural Characterization and In Vivo Anti-Inflammatory Activity of Fucoidan from Cystoseira crinita (Desf.) Borry
by Elisaveta Apostolova, Paolina Lukova, Alexandra Baldzhieva, Cédric Delattre, Roland Molinié, Emmanuel Petit, Redouan Elboutachfaiti, Mariana Nikolova, Ilia Iliev, Marianna Murdjeva and Vesela Kokova
Mar. Drugs 2022, 20(11), 714; https://doi.org/10.3390/md20110714 - 15 Nov 2022
Cited by 20 | Viewed by 2371
Abstract
The aim of this study was to evaluate the effects of fucoidan isolated from C. crinita on histamine-induced paw inflammation in rats, and on the serum levels of TNF-α, IL-1β, IL-6, and IL-10 in rats during systemic inflammation response. The levels of TNF-α [...] Read more.
The aim of this study was to evaluate the effects of fucoidan isolated from C. crinita on histamine-induced paw inflammation in rats, and on the serum levels of TNF-α, IL-1β, IL-6, and IL-10 in rats during systemic inflammation response. The levels of TNF-α in a model of acute peritonitis in rats were also investigated. The isolated crude fucoidan was identified as a sulfated xylogalactofucan with high, medium, and low molecular weight fractions and a content of fucose of 39.74%, xylose of 20.75%, and galactose of 15.51%. Fucoidan from C. crinita showed better anti-inflammatory effects in the rat paw edema model, and this effect was present during all stages of the experiment. When compared to controls, a commercial fucoidan from F. vesiculosus, the results also displayed anti-inflammatory activity on the 60th, 90th, and 120th minute of the experiment. A significant decrease in serum levels of IL-1β in rats treated with both doses of C. crinita fucoidan was observed in comparison to controls, whereas TNF-α concentrations were reduced only in the group treated with fucoidan from C. crinita at the dose of 25 mg/kg bw. In the model of carrageenan-induced peritonitis, we observed a tendency of decrease in the levels of the pro-inflammatory cytokine TNF-α in peritoneal fluid after a single dose of C. crinita fucoidan, but this did not reach the statistical significance margin. Single doses of C. crinita fucoidan did not alter serum levels of the anti-inflammatory cytokine IL-10 in animals with lipopolysaccharide-induced systemic inflammation. Full article
(This article belongs to the Special Issue Fucoidans: Structures-Based Bioactivities)
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14 pages, 1617 KiB  
Article
Implication of Echinochrome A in the Plasticity and Damage of Intestinal Epithelium
by Ji-Su Ahn, Ye Young Shin, Su-Jeong Oh, Min-Hye Song, Min-Jung Kang, So Yeong Park, Phuong Thao Nguyen, Dang Khoa Nguyen, Hyoung Kyu Kim, Jin Han, Elena A. Vasileva, Natalia P. Mishchenko, Sergey A. Fedoreyev, Valentin A. Stonik, Yoojin Seo, Byung-Chul Lee and Hyung-Sik Kim
Mar. Drugs 2022, 20(11), 715; https://doi.org/10.3390/md20110715 - 14 Nov 2022
Cited by 1 | Viewed by 1650
Abstract
The diverse therapeutic feasibility of the sea urchin-derived naphthoquinone pigment, Echinochrome A (Ech A), has been studied. Simple and noninvasive administration routes should be explored, to obtain the feasibility. Although the therapeutic potential has been proven through several preclinical studies, the biosafety of [...] Read more.
The diverse therapeutic feasibility of the sea urchin-derived naphthoquinone pigment, Echinochrome A (Ech A), has been studied. Simple and noninvasive administration routes should be explored, to obtain the feasibility. Although the therapeutic potential has been proven through several preclinical studies, the biosafety of orally administered Ech A and its direct influence on intestinal cells have not been evaluated. To estimate the bioavailability of Ech A as an oral administration drug, small intestinal and colonic epithelial organoids were developed from mice and humans. The morphology and cellular composition of intestinal organoids were evaluated after Ech A treatment. Ech A treatment significantly increased the expression of LGR5 (~2.38-fold change, p = 0.009) and MUC2 (~1.85-fold change, p = 0.08). Notably, in the presence of oxidative stress, Ech A attenuated oxidative stress up to 1.8-fold (p = 0.04), with a restored gene expression of LGR5 (~4.11-fold change, p = 0.0004), as well as an increased expression of Ly6a (~3.51-fold change, p = 0.005) and CLU (~2.5-fold change, p = 0.01), markers of revival stem cells. In conclusion, Ech A is harmless to intestinal tissues; rather, it promotes the maintenance and regeneration of the intestinal epithelium, suggesting possible beneficial effects on the intestine when used as an oral medication. Full article
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22 pages, 2920 KiB  
Article
A Metabolomics-Based Toolbox to Assess and Compare the Metabolic Potential of Unexplored, Difficult-to-Grow Bacteria
by Federica Fiorini, Felizitas Bajerski, Olga Jeske, Cendrella Lepleux, Jörg Overmann and Mark Brönstrup
Mar. Drugs 2022, 20(11), 713; https://doi.org/10.3390/md20110713 - 14 Nov 2022
Cited by 1 | Viewed by 2277
Abstract
Novel high-throughput cultivation techniques create a demand to pre-select strains for in-depth follow-up studies. We report a workflow to identify promising producers of novel natural products by systematically characterizing their metabolomes. For this purpose, 60 strains from four phyla (Proteobacteria, Bacteroidetes, Actinobacteria and [...] Read more.
Novel high-throughput cultivation techniques create a demand to pre-select strains for in-depth follow-up studies. We report a workflow to identify promising producers of novel natural products by systematically characterizing their metabolomes. For this purpose, 60 strains from four phyla (Proteobacteria, Bacteroidetes, Actinobacteria and Firmicutes) comprising 16 novel species and six novel genera were cultivated from marine and terrestrial sources. Their cellular metabolomes were recorded by LC-MS/MS; data analysis comprised databases MS/MS matching, in silico compound assignment, and GNPS-based molecular networking. Overall, 1052 different molecules were identified from 6418 features, among them were unusual metabolites such as 4-methoxychalcone. Only a minor portion of the 755 features were found in all phyla, while the majority occurred in a single phylogroup or even in a single strain. Metabolomic methods enabled the recognition of highly talented strains such as AEG42_45, which had 107 unique features, among which a family of 28 potentially novel and related compounds according to MS/MS similarities. In summary, we propose that high-throughput cultivation and isolation of bacteria in combination with the presented systematic and unbiased metabolome analysis workflow is a promising approach to capture and assess the enormous metabolic potential of previously uncultured bacteria. Full article
(This article belongs to the Special Issue Marine Metabolomics 2023)
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17 pages, 3156 KiB  
Article
Eremophilane-Type Sesquiterpenes from a Marine-Derived Fungus Penicillium Copticola with Antitumor and Neuroprotective Activities
by Jianping Zhang, Dong Liu, Aili Fan, Jian Huang and Wenhan Lin
Mar. Drugs 2022, 20(11), 712; https://doi.org/10.3390/md20110712 - 13 Nov 2022
Cited by 5 | Viewed by 2003
Abstract
Chemical examination of a marine sponge-associated Penicillium copticola fungus resulted in the isolation of ten undescribed eremophilanes, namely copteremophilanes A–J (110), along with two new glycosides, 5-glycopenostatin F (11) and 5-glucopenostatin I (12). Their structures [...] Read more.
Chemical examination of a marine sponge-associated Penicillium copticola fungus resulted in the isolation of ten undescribed eremophilanes, namely copteremophilanes A–J (110), along with two new glycosides, 5-glycopenostatin F (11) and 5-glucopenostatin I (12). Their structures were determined by extensive spectroscopic data, in association with ECD data and chemical conversions for configurational assignments. Analogs 1, 2, and 10 represent a group of uncommon skeletons of eremophilanes with an aromatic ring and a methyl migration from C-5 to C-9, and analogs 11 and 12 are characteristic of a PKS scaffold bearing a glucose unit. The incorporation of a chlorinated phenylacetic unit in 39 is rarely found in nature. Analog 7 showed neuroprotective effect, whereas 8 exhibited selective inhibition against human non-small cell lung cancer cells (A549). This study enriched the chemical diversity of eremophilanes and extended their bioactivities to neuroprotection. Full article
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11 pages, 2747 KiB  
Article
Anti-Inflammatory Polyketide Derivatives from the Sponge-Derived Fungus Pestalotiopsis sp. SWMU-WZ04-2
by Peng Jiang, Jinfeng Luo, Yao Jiang, Liping Zhang, Liyuan Jiang, Baorui Teng, Hong Niu, Dan Zhang and Hui Lei
Mar. Drugs 2022, 20(11), 711; https://doi.org/10.3390/md20110711 - 13 Nov 2022
Cited by 2 | Viewed by 1613
Abstract
Five undescribed polyketide derivatives, pestaloketides A–E (15), along with eleven known analogues (616), were isolated from the sponge-derived fungus Pestalotiopsis sp. Their structures, including absolute configurations, were elucidated by analyses of NMR spectroscopic HRESIMS data [...] Read more.
Five undescribed polyketide derivatives, pestaloketides A–E (15), along with eleven known analogues (616), were isolated from the sponge-derived fungus Pestalotiopsis sp. Their structures, including absolute configurations, were elucidated by analyses of NMR spectroscopic HRESIMS data and electronic circular dichroism (ECD) calculations. Compounds 5, 6, 9, and 14 exhibited weak cytotoxicities against four human cancer cell lines, with IC50 values ranging from 22.1 to 100 μM. Pestaloketide A (1) is an unusual polyketide, featuring a rare 5/10/5-fused ring system. Pestaloketides A (1) and B (2) exhibited moderately inhibited LPS-induced NO production activity, with IC50 values of 23.6 and 14.5 μM, respectively, without cytotoxicity observed. Preliminary bioactivity evaluations and molecular docking analysis indicated that pestaloketides A (1) and B (2) had the potential to be developed into anti-inflammatory activity drug leads. Full article
(This article belongs to the Special Issue Bioactive Compounds from the Deep-Sea-Derived Microorganisms)
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14 pages, 3235 KiB  
Article
Sargachromenol Isolated from Sargassum horneri Attenuates Glutamate-Induced Neuronal Cell Death and Oxidative Stress through Inhibition of MAPK/NF-κB and Activation of Nrf2/HO-1 Signaling Pathway
by Eui-Jeong Han, Chunying Zhang, Hyun-Soo Kim, Ji-Yul Kim, Sang-Muyn Park, Won-Kyo Jung, Ginnae Ahn and Seon-Heui Cha
Mar. Drugs 2022, 20(11), 710; https://doi.org/10.3390/md20110710 - 12 Nov 2022
Cited by 3 | Viewed by 1759
Abstract
Oxidative stress-induced neuronal cell loss is considered to be the major mechanism underlying the pathogenesis of neurodegenerative diseases, which could be induced by a high concentration of glutamate. In this study, sargachromenol (SC) was isolated from a marine brown seaweed Sargassum horneri ( [...] Read more.
Oxidative stress-induced neuronal cell loss is considered to be the major mechanism underlying the pathogenesis of neurodegenerative diseases, which could be induced by a high concentration of glutamate. In this study, sargachromenol (SC) was isolated from a marine brown seaweed Sargassum horneri (S. horneri) and its neuroprotective effects against glutamate-induced oxidative stress in HT22 cells were investigated. An MTT assay was applied to assess the cytotoxicity of the SC, and the efficacies of SC were determined by flow cytometry, an analysis of ROS production, quantitative Real-Time PCR, and the Western blot assay. Our results showed that the pretreatment of SC reduced glutamate-induced apoptosis in HT22 cells via inhibiting the sub-G1 population, DNA fragmentation, and nuclear condensation, as well as up-regulating anti-apoptotic protein (Bcl-2) and down-regulating apoptotic proteins (Bax, p53, cleaved-PARP, caspase-3, caspase-9, and cytochrome c). Additionally, SC attenuated glutamate-induced oxidative stress by suppressing mitogen-activated protein kinases (MAPKs;ERK, JNK, and p38) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling (IκBα and NF-κB p65), while activating nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) signaling (Nrf2; HO-1, and NQO-1). Our results suggest that SC could be used as a pharmacological candidate for the prevention and treatment of neurodegenerative diseases. Full article
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14 pages, 1991 KiB  
Article
Efficient Preparation of High-Purity Fucoxanthinol by SpyTag-Tailored Active Cholesterol Esterase Aggregates
by Wenhui Jin, Ting Yang, Hui Chen, Hua Fang, Weizhu Chen, Quanling Xie, Qian Liu, Yiping Zhang, Zhuan Hong and Guangya Zhang
Mar. Drugs 2022, 20(11), 709; https://doi.org/10.3390/md20110709 - 12 Nov 2022
Viewed by 1268
Abstract
A novel approach to producing high-purity fucoxanthinol (FXOH) was exploited as a sustainable method to maximize fucoxanthin (FX) utilization. Through fusing the genes of cholesterol esterase and SpyTag and then expressing them in Escherichia coli, the fusion chimera was self-assembled into insoluble [...] Read more.
A novel approach to producing high-purity fucoxanthinol (FXOH) was exploited as a sustainable method to maximize fucoxanthin (FX) utilization. Through fusing the genes of cholesterol esterase and SpyTag and then expressing them in Escherichia coli, the fusion chimera was self-assembled into insoluble active aggregates by SpyTag, which could be regarded as carrier-free immobilization. The immobilization yield of the active cholesterol esterase aggregates could reach 60%. They have expressed good activity retention at 92.48% and 60.13% after 3 and 12 cycles, respectively, which is an exciting finding. The conversion ratio of FX to FXOH is 95.02%, which is remarkably higher than those realized via the conventional chemical reduction method (55.86%) and the enzymatic hydrolysis method by free cholesterol esterases (84.51%). The purity of FXOH obtained by this method is as high as 98%, which is much higher than those obtained by other methods. Thus, a promising method for simultaneously purifying and immobilizing active cholesterol esterase aggregates is demonstrated in this study by SpyTag tailoring. In addition, this study provides an eco-friendly method for producing high-purity FXOH from FX in a highly efficient manner. Full article
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45 pages, 3301 KiB  
Review
Marine Natural Products from the Russian Pacific as Sources of Drugs for Neurodegenerative Diseases
by Yuri S. Khotimchenko, Denis N. Silachev and Vladimir L. Katanaev
Mar. Drugs 2022, 20(11), 708; https://doi.org/10.3390/md20110708 - 11 Nov 2022
Cited by 8 | Viewed by 2952
Abstract
Neurodegenerative diseases are growing to become one of humanity’s biggest health problems, given the number of individuals affected by them. They cause enough mortalities and severe economic impact to rival cancers and infections. With the current diversity of pathophysiological mechanisms involved in neurodegenerative [...] Read more.
Neurodegenerative diseases are growing to become one of humanity’s biggest health problems, given the number of individuals affected by them. They cause enough mortalities and severe economic impact to rival cancers and infections. With the current diversity of pathophysiological mechanisms involved in neurodegenerative diseases, on the one hand, and scarcity of efficient prevention and treatment strategies, on the other, all possible sources for novel drug discovery must be employed. Marine pharmacology represents a relatively uncharted territory to seek promising compounds, despite the enormous chemodiversity it offers. The current work discusses one vast marine region—the Northwestern or Russian Pacific—as the treasure chest for marine-based drug discovery targeting neurodegenerative diseases. We overview the natural products of neurological properties already discovered from its waters and survey the existing molecular and cellular targets for pharmacological modulation of the disease. We further provide a general assessment of the drug discovery potential of the Russian Pacific in case of its systematic development to tackle neurodegenerative diseases. Full article
(This article belongs to the Special Issue Marine Drugs Research in Russia)
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16 pages, 3301 KiB  
Article
Ethyl Acetate Extract of Marine Algae, Halymenia durvillei, Provides Photoprotection against UV-Exposure in L929 and HaCaT Cells
by Pichnaree Kraokaew, Preeyanuch Manohong, Prachayaporn Prasertsuksri, Prapaporn Jattujan, Nakhon Niamnont, Montakan Tamtin, Prasert Sobhon and Krai Meemon
Mar. Drugs 2022, 20(11), 707; https://doi.org/10.3390/md20110707 - 11 Nov 2022
Cited by 4 | Viewed by 2757
Abstract
Halymenia durvillei is a red alga distributed along the coasts of Southeast Asian countries including Thailand. Previous studies have shown that an ethyl acetate fraction of H. durvillei (HDEA), containing major compounds including n-hexadecanoic acid, 2-butyl-5-hexyloctahydro-1H-indene, 3-(hydroxyacetyl) indole and indole-3-carboxylic acid, possesses high [...] Read more.
Halymenia durvillei is a red alga distributed along the coasts of Southeast Asian countries including Thailand. Previous studies have shown that an ethyl acetate fraction of H. durvillei (HDEA), containing major compounds including n-hexadecanoic acid, 2-butyl-5-hexyloctahydro-1H-indene, 3-(hydroxyacetyl) indole and indole-3-carboxylic acid, possesses high antioxidant and anti-lung cancer activities. The present study demonstrated that HDEA could protect mouse skin fibroblasts (L929) and human immortalized keratinocytes (HaCaT) against photoaging due to ultraviolet A and B (UVA and UVB) by reducing intracellular reactive oxygen species (ROS) and expressions of matrix metalloproteinases (MMP1 and MMP3), as well as increasing Nrf2 nuclear translocation, upregulations of mRNA transcripts of antioxidant enzymes, including superoxide dismutase (SOD), heme oxygenase (HMOX) and glutathione S-transferase pi1 (GSTP1), and procollagen synthesis. The results indicate that HDEA has the potential to protect skin cells from UV irradiation through the activation of the Nrf2 pathway, which leads to decreasing intracellular ROS and MMP production, along with the restoration of skin collagen. Full article
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18 pages, 2331 KiB  
Article
Influence of Oxidation and Dialysis of Phlorotannins on Bioactivity and Composition of Ultrasound-Assisted Extracts from Ascophyllum nodosum
by Mauro Gisbert, Jorge Sineiro and Ramón Moreira
Mar. Drugs 2022, 20(11), 706; https://doi.org/10.3390/md20110706 - 11 Nov 2022
Cited by 1 | Viewed by 1492
Abstract
The isolation and chemical characterization of phlorotannins has gained special attention in recent years due to their specific health-promoting benefits. Flow-cell ultrasound-assisted extraction (90 W/cm2 of sonication power, 2 min of retention time and 20 g solvent/g algae of liquid–solid ratio) was [...] Read more.
The isolation and chemical characterization of phlorotannins has gained special attention in recent years due to their specific health-promoting benefits. Flow-cell ultrasound-assisted extraction (90 W/cm2 of sonication power, 2 min of retention time and 20 g solvent/g algae of liquid–solid ratio) was carried out by using double-distilled water (WE) and acetone:water mixture (AWE) as extraction solvents. The AWE showed a higher total polyphenols content (TPC), carbohydrates (CHOs) and antioxidant activities than WE. However, when the WE was purified by using Amberlite XAD16 column, the purified WE (PWE) showed similar a TPC, decreased CHOs and increased antioxidant activity compared to WE. The oxidation of the PWE extract was evaluated under natural, forced and severe oxidation condition for 120 h. Only severe oxidation conditions were able to significantly reduce TPC and antioxidant activities. PWE was dialyzed (20, 10, 3.5 and 2 kDa). The main bioactive fraction of phlorotannins was obtained from 10 to 20 kDa. CHOs were distributed in fractions below 20 kDa. MALDI-TOF analysis was performed for PWE, PD20 and PD2 extracts to analyze the degree of polymerization of phlorotannins, which ranged from 4 to 17 phloroglucinol units/molecule. Fragmentation patterns allowed the proximate identification of several phlorotannins in Ascophyllum nodosum extracts. Full article
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13 pages, 1232 KiB  
Review
Application of Gene Knockout and Heterologous Expression Strategy in Fungal Secondary Metabolites Biosynthesis
by Yaodong Ning, Yao Xu, Binghua Jiao and Xiaoling Lu
Mar. Drugs 2022, 20(11), 705; https://doi.org/10.3390/md20110705 - 10 Nov 2022
Cited by 10 | Viewed by 2653
Abstract
The in-depth study of fungal secondary metabolites (SMs) over the past few years has led to the discovery of a vast number of novel fungal SMs, some of which possess good biological activity. However, because of the limitations of the traditional natural product [...] Read more.
The in-depth study of fungal secondary metabolites (SMs) over the past few years has led to the discovery of a vast number of novel fungal SMs, some of which possess good biological activity. However, because of the limitations of the traditional natural product mining methods, the discovery of new SMs has become increasingly difficult. In recent years, with the rapid development of gene sequencing technology and bioinformatics, new breakthroughs have been made in the study of fungal SMs, and more fungal biosynthetic gene clusters of SMs have been discovered, which shows that the fungi still have a considerable potential to produce SMs. How to study these gene clusters to obtain a large number of unknown SMs has been a research hotspot. With the continuous breakthrough of molecular biology technology, gene manipulation has reached a mature stage. Methods such as gene knockout and heterologous expression techniques have been widely used in the study of fungal SM biosynthesis and have achieved good effects. In this review, the representative studies on the biosynthesis of fungal SMs by gene knockout and heterologous expression under the fungal genome mining in the last three years were summarized. The techniques and methods used in these studies were also briefly discussed. In addition, the prospect of synthetic biology in the future under this research background was proposed. Full article
(This article belongs to the Special Issue Diversity of Marine Fungi as a Source of Bioactive Natural Products)
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15 pages, 2358 KiB  
Article
Laminaria japonica Peptides Suppress Liver Cancer by Inducing Apoptosis: Possible Signaling Pathways and Mechanism
by Yingzi Wu, Yuanhui Li, Wenhai Guo, Jie Liu, Weiguo Lao, Penghui Hu, Yiguang Lin and Hongjie Chen
Mar. Drugs 2022, 20(11), 704; https://doi.org/10.3390/md20110704 - 10 Nov 2022
Cited by 2 | Viewed by 2085
Abstract
The anticancer properties of Laminaria japonica peptides (LJPs) have never been studied. Here, we extracted LJPs from fresh seaweed and explored their anti-liver cancer activity (in vivo and in vitro). LJPs were isolated/purified by HPLC-ESI-MS. HepG2 cell apoptosis and cell cycle were evaluated. [...] Read more.
The anticancer properties of Laminaria japonica peptides (LJPs) have never been studied. Here, we extracted LJPs from fresh seaweed and explored their anti-liver cancer activity (in vivo and in vitro). LJPs were isolated/purified by HPLC-ESI-MS. HepG2 cell apoptosis and cell cycle were evaluated. MTT assays were used to examine the cytotoxicity of LJPs. Caspase activation of caspases 3 and 9, cleaved caspases 3 and 9, and cleaved PARP was examined by Western blotting. The PI3K/AKT pathway and the phosphorylation states of MAPKs (p38 and JNK) were examined. We found that the LJP-1 peptide had the most antiproliferative activity in H22 cells in vitro. LJP-1 blocked H22 cells in the G0/G1 phase, accompanied by inhibition of cyclin expression. LJP-1 induced apoptosis through caspase activation and regulation of the ASK1/MAPK pathway. Concurrent in vivo studies demonstrated that LJP-1 significantly inhibited tumor growth and induced tumor cell apoptosis/necrosis. In conclusion, LJPs, particularly LJP-1, exert strong inhibitory effects on liver cancer growth in vivo and in vitro. LJP-1 induces HCC cell apoptosis through the caspase-dependent pathway and G0/G1 arrest. LJP-1 induces caspase-dependent apoptosis, in part by inhibiting PI3K, MAPK signaling pathways, and cell cycle proteins. LJP-1 has the potential to be a novel candidate for human liver cancer therapeutics. Full article
(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents 2.0)
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16 pages, 4078 KiB  
Article
Sea Cucumber Saponins Derivatives Alleviate Hepatic Lipid Accumulation Effectively in Fatty Acids-Induced HepG2 Cells and Orotic Acid-Induced Rats
by Xiaoyue Li, Beibei Zeng, Lu Wen, Yingcai Zhao, Zhaojie Li, Changhu Xue, Tiantian Zhang and Yuming Wang
Mar. Drugs 2022, 20(11), 703; https://doi.org/10.3390/md20110703 - 10 Nov 2022
Cited by 3 | Viewed by 1769
Abstract
The sulfated echinoside A (EA) and holothurin A (HA) are two prominent saponins in sea cucumber with high hemolytic activity but also superior lipid-lowering activity. Deglycosylated derivatives EA2 and HA2 exhibit low hemolysis compared to EA and HA, but their efficacies on lipid [...] Read more.
The sulfated echinoside A (EA) and holothurin A (HA) are two prominent saponins in sea cucumber with high hemolytic activity but also superior lipid-lowering activity. Deglycosylated derivatives EA2 and HA2 exhibit low hemolysis compared to EA and HA, but their efficacies on lipid metabolism regulation remains unknown. In this study, fatty acids-treated HepG2 cells and orotic acid-treated rats were used to investigate the lipid-lowering effects of sea cucumber saponin derivatives. Both the saponin and derivatives could effectively alleviate lipid accumulation in HepG2 model, especially EA and EA2. Moreover, though the lipid-lowering effect of EA2 was not equal with EA at the same dosage of 0.05% in diet, 0.15% dosage of EA2 significantly reduced hepatic steatosis rate, liver TC and TG contents by 76%, 41.5%, and 63.7%, respectively, compared to control and reversed liver histopathological features to normal degree according to H&E stained sections. Possible mechanisms mainly included enhancement of fatty acids β-oxidation and cholesterol catabolism through bile acids synthesis and excretion, suppression of lipogenesis and cholesterol uptake. It revealed that the efficacy of EA2 on lipid metabolism regulation was dose-dependent, and 0.15% dosage of EA2 possessed better efficacy with lower toxicity compared to 0.05% dosage of EA. Full article
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14 pages, 2214 KiB  
Article
Antibacterial Mechanism of Chitosan–Gentamicin and Its Effect on the Intestinal Flora of Litopenaeus vannamei Infected with Vibrio parahaemolyticus
by Lefan Li, Fengyan Liang, Chengpeng Li, Tingting Hou and Dong-an Xu
Mar. Drugs 2022, 20(11), 702; https://doi.org/10.3390/md20110702 - 9 Nov 2022
Cited by 3 | Viewed by 1723
Abstract
To explore the application of chitosan–gentamicin conjugate (CS-GT) in inhibiting Vibrio parahaemolyticus (V. parahaemolyticus), which is an important pathogen in aquatic animals worldwide, the antimicrobial activity of CS-GT and the effects of a CS-GT dose on the intestine histopathology and intestinal [...] Read more.
To explore the application of chitosan–gentamicin conjugate (CS-GT) in inhibiting Vibrio parahaemolyticus (V. parahaemolyticus), which is an important pathogen in aquatic animals worldwide, the antimicrobial activity of CS-GT and the effects of a CS-GT dose on the intestine histopathology and intestinal flora of V. parahaemolyticus-infected shrimps were explored. The results showed that CS-GT possessed broad-spectrum antibacterial activity, with minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and half inhibitory concentration (IC50) of 20.00 ± 0.01, 75.00 ± 0.02 and 18.72 ± 3.17 μg/mL for V. parahaemolyticus, respectively. Further scanning electron microscope and cell membrane damage analyses displayed that the electrostatic interaction of CS-GT with cell membrane strengthened after CS grafted GT, resulting in leakage of nucleic acid and electrolytes of V. parahaemolyticus. On the other hand, histopathology investigation indicated that high (100 mg/kg) and medium (50 mg/kg) doses of CS-GT could alleviate the injury of a shrimp’s intestine caused by V. parahaemolyticus. Further 16S rRNA gene sequencing analysis found high and medium dose of CS-GT could effectively inhabit V. parahaemolyticus invasion and reduce intestinal dysfunction. In conclusion, CS-GT possesses good antibacterial activity and could protect shrimps from pathogenic bacteria infection. Full article
(This article belongs to the Special Issue Antimicrobial and Antiviral Agents from Marine Sources)
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17 pages, 2921 KiB  
Review
Structures and Biological Activities of Secondary Metabolites from Trichoderma harzianum
by Rui Guo, Gang Li, Zhao Zhang and Xiaoping Peng
Mar. Drugs 2022, 20(11), 701; https://doi.org/10.3390/md20110701 - 9 Nov 2022
Cited by 15 | Viewed by 3189
Abstract
The biocontrol fungus Trichoderma harzianum, from both marine and terrestrial environments, has attracted considerable attention. T. harzianum has a tremendous potential to produce a variety of bioactive secondary metabolites (SMs), which are an important source of new herbicides and antibiotics. This review [...] Read more.
The biocontrol fungus Trichoderma harzianum, from both marine and terrestrial environments, has attracted considerable attention. T. harzianum has a tremendous potential to produce a variety of bioactive secondary metabolites (SMs), which are an important source of new herbicides and antibiotics. This review prioritizes the SMs of T. harzianum from 1988 to June 2022, and their relevant biological activities. Marine-derived SMs, especially terpenoids, polyketides, and macrolides compounds, occupy a significant proportion of natural products from T. harzianum, deserving more of our attention. Full article
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15 pages, 3887 KiB  
Article
Structure of the Lipooligosaccharide from the Deep-Sea Marine Bacterium Idiomarina zobellii KMM 231T, Isolated at a Depth of 4000 Meters
by Maxim S. Kokoulin, Pavel S. Dmitrenok and Lyudmila A. Romanenko
Mar. Drugs 2022, 20(11), 700; https://doi.org/10.3390/md20110700 - 9 Nov 2022
Cited by 2 | Viewed by 1605
Abstract
The structural characterization of lipopolysaccharides has critical implications for some biomedical applications, and marine bacteria are an inimitable source of new glyco-structures potentially usable in medicinal chemistry. On the other hand, lipopolysaccharides of marine Gram-negative bacteria present certain structural features that can help [...] Read more.
The structural characterization of lipopolysaccharides has critical implications for some biomedical applications, and marine bacteria are an inimitable source of new glyco-structures potentially usable in medicinal chemistry. On the other hand, lipopolysaccharides of marine Gram-negative bacteria present certain structural features that can help the understanding of the adaptation processes. The deep-sea marine Gram-negative bacterium Idiomarina zobellii KMM 231T, isolated from a seawater sample taken at a depth of 4000 m, represents an engaging microorganism to investigate in terms of its cell wall components. Here, we report the structural study of the R-type lipopolysaccharide isolated from I. zobellii KMM 231T that was achieved through a multidisciplinary approach comprising chemical analyses, NMR spectroscopy, and MALDI mass spectrometry. The lipooligosaccharide turned out to be characterized by a novel and unique pentasaccharide skeleton containing a very short mono-phosphorylated core region and comprising terminal neuraminic acid. The lipid A was revealed to be composed of a classical disaccharide backbone decorated by two phosphate groups and acylated by i13:0(3-OH) in amide linkage, i11:0 (3-OH) as primary ester-linked fatty acids, and i11:0 as a secondary acyl chain. Full article
(This article belongs to the Special Issue Carbohydrate-Containing Marine Compounds of Mixed Biogenesis II)
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12 pages, 3349 KiB  
Article
May the Force (Field) Be with You: On the Importance of Conformational Searches in the Prediction of NMR Chemical Shifts
by Cristina Cuadrado, Antonio Hernández Daranas and Ariel M. Sarotti
Mar. Drugs 2022, 20(11), 699; https://doi.org/10.3390/md20110699 - 8 Nov 2022
Cited by 7 | Viewed by 3167
Abstract
NMR data prediction is increasingly important in structure elucidation. The impact of force field selection was assessed, along with geometry and energy cutoffs. Based on the conclusions, we propose a new approach named mix-J-DP4, which provides a remarkable increase in the [...] Read more.
NMR data prediction is increasingly important in structure elucidation. The impact of force field selection was assessed, along with geometry and energy cutoffs. Based on the conclusions, we propose a new approach named mix-J-DP4, which provides a remarkable increase in the confidence level of complex stereochemical assignments—100% in our molecular test set—with a very modest increment in computational cost. Full article
(This article belongs to the Section Structural Studies on Marine Natural Products)
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