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Mar. Drugs, Volume 20, Issue 9 (September 2022) – 46 articles

Cover Story (view full-size image): Many targeted natural product isolation approaches rely on the use of pre-existing bioactivity information to inform the strategy used for the isolation of new bioactive compounds. Bioactivity information can be available either in the form of prior assay data or via structure–activity relationship (SAR) information, which can indicate a potential chemotype that exhibits a desired bioactivity. The work described herein utilizes a unique method of targeted isolation using structure-based virtual screening to identify potential antibacterial compounds within the marine sponge order Verongiida active, against MRSA. This is coupled with molecular networking-guided, targeted isolation to provide a novel drug discovery procedure. View this paper
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38 pages, 7970 KiB  
Article
Marine Alga Ulva fasciata-Derived Molecules for the Potential Treatment of SARS-CoV-2: An In Silico Approach
by Haresh S. Kalasariya, Nikunj B. Patel, Amel Gacem, Taghreed Alsufyani, Lisa M. Reece, Virendra Kumar Yadav, Nasser S. Awwad, Hala A. Ibrahium, Yongtae Ahn, Krishna Kumar Yadav and Byong-Hun Jeon
Mar. Drugs 2022, 20(9), 586; https://doi.org/10.3390/md20090586 - 19 Sep 2022
Cited by 9 | Viewed by 3595
Abstract
SARS-CoV-2 is the causative agent of the COVID-19 pandemic. This in silico study aimed to elucidate therapeutic efficacies against SARS-CoV-2 of phyco-compounds from the seaweed, Ulva fasciata. Twelve phyco-compounds were isolated and toxicity was analyzed by VEGA QSAR. Five compounds were found [...] Read more.
SARS-CoV-2 is the causative agent of the COVID-19 pandemic. This in silico study aimed to elucidate therapeutic efficacies against SARS-CoV-2 of phyco-compounds from the seaweed, Ulva fasciata. Twelve phyco-compounds were isolated and toxicity was analyzed by VEGA QSAR. Five compounds were found to be nonmutagenic, noncarcinogenic and nontoxic. Moreover, antiviral activity was evaluated by PASS. Binding affinities of five of these therapeutic compounds were predicted to possess probable biological activity. Fifteen SARS-CoV-2 target proteins were analyzed by the AutoDock Vina program for molecular docking binding energy analysis and the 6Y84 protein was determined to possess optimal binding affinities. The Desmond program from Schrödinger’s suite was used to study high performance molecular dynamic simulation properties for 3,7,11,15-Tetramethyl-2-hexadecen-1-ol—6Y84 for better drug evaluation. The ligand with 6Y84 had stronger binding affinities (−5.9 kcal/mol) over two standard drugs, Chloroquine (−5.6 kcal/mol) and Interferon α-2b (−3.8 kcal/mol). Swiss ADME calculated physicochemical/lipophilicity/water solubility/pharmacokinetic properties for 3,7,11,15-Tetramethyl-2-hexadecen-1-ol, showing that this therapeutic agent may be effective against SARS-CoV-2. Full article
(This article belongs to the Special Issue Pharmacological Activity of Marine Algae Compounds)
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16 pages, 1847 KiB  
Article
Novel Natural Compounds and Their Anatomical Distribution in the Stinging Fireworm Hermodice carunculata (Annelida)
by Sara Righi, Luca Forti, Roberto Simonini, Valentina Ferrari, Daniela Prevedelli and Adele Mucci
Mar. Drugs 2022, 20(9), 585; https://doi.org/10.3390/md20090585 - 19 Sep 2022
Cited by 4 | Viewed by 1723
Abstract
Increasing evidence in the field of bioprospection fosters the necessity of studying poorly investigated poisonous marine invertebrates to expand knowledge on animal venom biology. Among marine annelids, amphinomid fireworms are notorious for their bearded trunk equipped with a powerful stinging capacity. Here, a [...] Read more.
Increasing evidence in the field of bioprospection fosters the necessity of studying poorly investigated poisonous marine invertebrates to expand knowledge on animal venom biology. Among marine annelids, amphinomid fireworms are notorious for their bearded trunk equipped with a powerful stinging capacity. Here, a methodological workflow based on analytical chemistry techniques (compound isolation followed by mass spectrometry and spectroscopy analyses) was applied to gain new insights, leading to the identification and structural elucidation of an array of natural products from Mediterranean specimens of Hermodice carunculata. Eight betaine-derived unprecedented compounds, named “carunculines”, were detected, bearing two terminal ammonium groups tri-and disubstituted at the Cα (A, B) and a series of different alkyl chains (I–VIII). The mixture of chemicals was found in all the body parts of H. carunculata, supporting a mechanism of action triggered by their vehiculation inside the dorsal chaetae, and subsequent injection when chaetae break off on contact. Preliminary investigations to understand adaptive features were also performed, showing a trend in carunculine abundance that fits into the evolutionary history of these worms. These findings shed light on the chemical ecology of amphinomids, giving reasons for the success of H. carunculata in benthic environments and providing promising novel metabolites for biotechnological implications. Full article
(This article belongs to the Section Structural Studies on Marine Natural Products)
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17 pages, 2969 KiB  
Article
Cytotoxic Drimane-Type Sesquiterpenes from Co-Culture of the Marine-Derived Fungi Aspergillus carneus KMM 4638 and Beauveria felina (=Isaria felina) KMM 4639
by Olesya I. Zhuravleva, Elena B. Belousova, Galina K. Oleinikova, Alexandr S. Antonov, Yuliya V. Khudyakova, Anton B. Rasin, Roman S. Popov, Ekaterina S. Menchinskaya, Phan Thi Hoai Trinh, Anton N. Yurchenko and Ekaterina A. Yurchenko
Mar. Drugs 2022, 20(9), 584; https://doi.org/10.3390/md20090584 - 19 Sep 2022
Cited by 9 | Viewed by 1939
Abstract
Chemical investigation of a coculture of the marine-derived fungi Beauveria felina KMM 4639 and Aspergillus carneus KMM 4638 led to the identification of three new drimane-type sesquiterpenes, asperflavinoids B, D and E (2, 4, 5), and nine previously reported [...] Read more.
Chemical investigation of a coculture of the marine-derived fungi Beauveria felina KMM 4639 and Aspergillus carneus KMM 4638 led to the identification of three new drimane-type sesquiterpenes, asperflavinoids B, D and E (2, 4, 5), and nine previously reported related compounds. The structures of these compounds were established using spectroscopic methods and by comparison with known analogues. We also investigated the cytotoxic activity of the isolated compounds against several cancer and normal cell lines. Asperflavinoid C (3) and ustusolate E (9) exerted a significant effect on human breast cancer MCF-7 cell viability, with IC50 values of 10 µM, and induced in caspase-dependent apoptosis and arrest of the MCF-7 cell cycle in the G2/M phase in these cells. Full article
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13 pages, 2612 KiB  
Article
New Polyketides from Mangrove Endophytic Fungus Penicillium sp. BJR-P2 and Their Anti-Inflammatory Activity
by Chen Chen, Geting Ye, Jing Tang, Jialin Li, Wenbin Liu, Li Wu and Yuhua Long
Mar. Drugs 2022, 20(9), 583; https://doi.org/10.3390/md20090583 - 18 Sep 2022
Cited by 5 | Viewed by 2049
Abstract
Four new polyketide compounds, including two new unique isocoumarins penicillol A (1) and penicillol B (2) featuring with spiroketal rings, two new citreoviridin derivatives citreoviridin H (3) and citreoviridin I (4), along with four known [...] Read more.
Four new polyketide compounds, including two new unique isocoumarins penicillol A (1) and penicillol B (2) featuring with spiroketal rings, two new citreoviridin derivatives citreoviridin H (3) and citreoviridin I (4), along with four known analogues were isolated from the mangrove endophytic fungus Penicillium sp. BJR-P2. Their structures were elucidated by extensive spectroscopic methods. The absolute configurations of compounds 14 based on electronic circular dichroism (ECD) calculations, DP4+ analysis, and single-crystal X-ray diffraction are presented. All the new compounds were evaluated for anti-inflammatory activity. An anti-inflammatory assay indicated that compound 2 inhibited lipopolysaccharide (LPS)-induced NO production in RAW 264.7 cells, with half-maximal inhibitory concentration (IC50) values of 12 μM, being more potent than the positive control, indomethacin (IC50 = 35.8 ± 5.7 μM). Docking study showed that compound 2 was perfectly docking into the active site of murine inducible nitric oxide oxygenase (iNOS) via forming multiple typical hydrogen bonds. Full article
(This article belongs to the Special Issue Diversity of Marine Fungi as a Source of Bioactive Natural Products)
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21 pages, 5132 KiB  
Article
Ilimaquinone (Marine Sponge Metabolite) Induces Apoptosis in HCT-116 Human Colorectal Carcinoma Cells via Mitochondrial-Mediated Apoptosis Pathway
by Malvi Surti, Mitesh Patel, Alya Redhwan, Lamya Ahmed Al-Keridis, Mohd Adnan, Nawaf Alshammari and Mandadi Narsimha Reddy
Mar. Drugs 2022, 20(9), 582; https://doi.org/10.3390/md20090582 - 18 Sep 2022
Cited by 7 | Viewed by 2074
Abstract
Ilimaquinone (IQ), a metabolite found in marine sponges, has been reported to have a number of biological properties, including potential anticancer activity against colon cancer. However, no clear understanding of the precise mechanism involved is known. The aim of this study was to [...] Read more.
Ilimaquinone (IQ), a metabolite found in marine sponges, has been reported to have a number of biological properties, including potential anticancer activity against colon cancer. However, no clear understanding of the precise mechanism involved is known. The aim of this study was to examine the molecular mechanism by which IQ acts on HCT-116 cells. The anticancer activity of IQ was investigated by means of a cell viability assay followed by the determination of induction of apoptosis by means of the use of acridine orange–ethidium bromide (AO/EB) staining, Annexin V/PI double staining, DNA fragmentation assays, and TUNEL assays. The mitochondrial membrane potential (ΔΨm) was detected using the JC-1 staining technique, and the apoptosis-associated proteins were analyzed using real-time qRT-PCR. A molecular docking study of IQ with apoptosis-associated proteins was also conducted in order to assess the interaction between IQ and them. Our results suggest that IQ significantly suppressed the viability of HCT-116 cells in a dose-dependent manner. Fluorescent microscopy, flow cytometry, DNA fragmentation and the TUNEL assay in treated cells demonstrated apoptotic death mode. As an additional confirmation of apoptosis, the increased level of caspase-3 and caspase-9 expression and the downregulation of Bcl-2 and mitochondrial dysfunction were observed in HCT-116 cells after treatment with IQ, which was accompanied by a decrease in mitochondrial membrane potential (ΔΨm). Overall, the results of our studies demonstrate that IQ could trigger mitochondria-mediated apoptosis as demonstrated by a decrease in ΔΨm, activation of caspase-9/-3, damage of DNA and a decrease in the proportion of Bcl-2 through the mitochondrial-mediated apoptosis pathway. Full article
(This article belongs to the Special Issue Development and Application of Marine-Derived Anti-cancer Agents)
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19 pages, 5611 KiB  
Article
A Comparison of Dinoflagellate Thiolation Domain Binding Proteins Using In Vitro and Molecular Methods
by Ernest Williams, Tsvetan Bachvaroff and Allen Place
Mar. Drugs 2022, 20(9), 581; https://doi.org/10.3390/md20090581 - 18 Sep 2022
Cited by 1 | Viewed by 1424
Abstract
Dinoflagellates play important roles in ecosystems as primary producers and consumers making natural products that can benefit or harm environmental and human health but are also potential therapeutics with unique chemistries. Annotations of dinoflagellate genes have been hampered by large genomes with many [...] Read more.
Dinoflagellates play important roles in ecosystems as primary producers and consumers making natural products that can benefit or harm environmental and human health but are also potential therapeutics with unique chemistries. Annotations of dinoflagellate genes have been hampered by large genomes with many gene copies that reduce the reliability of transcriptomics, quantitative PCR, and targeted knockouts. This study aimed to functionally characterize dinoflagellate proteins by testing their interactions through in vitro assays. Specifically, nine Amphidinium carterae thiolation domains that scaffold natural product synthesis were substituted into an indigoidine synthesizing gene from the bacterium Streptomyces lavendulae and exposed to three A. carterae phosphopantetheinyl transferases that activate synthesis. Unsurprisingly, several of the dinoflagellate versions inhibited the ability to synthesize indigoidine despite being successfully phosphopantetheinated. However, all the transferases were able to phosphopantetheinate all the thiolation domains nearly equally, defying the canon that transferases participate in segregated processes via binding specificity. Moreover, two of the transferases were expressed during growth in alternating patterns while the final transferase was only observed as a breakdown product common to all three. The broad substrate recognition and compensatory expression shown here help explain why phosphopantetheinyl transferases are lost throughout dinoflagellate evolution without a loss in a biochemical process. Full article
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18 pages, 3029 KiB  
Article
High Molecular Weight Fucoidan Restores Intestinal Integrity by Regulating Inflammation and Tight Junction Loss Induced by Methylglyoxal-Derived Hydroimidazolone-1
by Jae-Min Lim, Hee Joon Yoo and Kwang-Won Lee
Mar. Drugs 2022, 20(9), 580; https://doi.org/10.3390/md20090580 - 17 Sep 2022
Cited by 6 | Viewed by 2228
Abstract
Fucoidan from brown seaweeds has several biological effects, including preserving intestinal integrity. To investigate the intestinal protective properties of high molecular weight fucoidan (HMWF) from Undaria pinnatifida on intestinal integrity dysfunction caused by methylglyoxal-derived hydroimidazolone-1 (MG-H1), one of the dietary advanced-glycation end products [...] Read more.
Fucoidan from brown seaweeds has several biological effects, including preserving intestinal integrity. To investigate the intestinal protective properties of high molecular weight fucoidan (HMWF) from Undaria pinnatifida on intestinal integrity dysfunction caused by methylglyoxal-derived hydroimidazolone-1 (MG-H1), one of the dietary advanced-glycation end products (dAGEs) in the human-colon carcinoma-cell line (Caco-2) cells and ICR mice. According to research, dAGEs may damage the intestinal barrier by increasing gut permeability. The findings of the study showed that HMWF + MG-H1 treatment reduced by 16.8% the amount of reactive oxygen species generated by MG-H1 treatment alone. Furthermore, HMWF + MGH-1 treatment reduced MG-H1-induced monolayer integrity disruption, as measured by alterations in transepithelial electrical resistance (135% vs. 75.5%) and fluorescein isothiocyanate incorporation (1.40 × 10−6 cm/s vs. 3.80 cm/s). HMWF treatment prevented the MG-H1-induced expression of tight junction markers, including zonula occludens-1, occludin, and claudin-1 in Caco-2 cells and mouse colon tissues at the mRNA and protein level. Also, in Caco-2 and MG-H1-treated mice, HMWF plays an important role in preventing receptor for AGEs (RAGE)-mediated intestinal damage. In addition, HMWF inhibited the nuclear factor kappa B activation and its target genes leading to intestinal inflammation. These findings suggest that HMWF with price competitiveness could play an important role in preventing AGEs-induced intestinal barrier dysfunction. Full article
(This article belongs to the Special Issue Fucoidans: Structures-Based Bioactivities)
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45 pages, 6879 KiB  
Review
Fused Tricyclic Guanidine Alkaloids: Insights into Their Structure, Synthesis and Bioactivity
by Nur Zahirah Abd Rani, Yean Kee Lee, Sarfraz Ahmad, Ramu Meesala and Iskandar Abdullah
Mar. Drugs 2022, 20(9), 579; https://doi.org/10.3390/md20090579 - 17 Sep 2022
Cited by 3 | Viewed by 1792
Abstract
A marine natural product possesses a diverse and unique scaffold that contributes to a vast array of bioactivities. Tricyclic guanidine alkaloids are a type of scaffold found only in marine natural products. These rare skeletons exhibit a wide range of biological applications, but [...] Read more.
A marine natural product possesses a diverse and unique scaffold that contributes to a vast array of bioactivities. Tricyclic guanidine alkaloids are a type of scaffold found only in marine natural products. These rare skeletons exhibit a wide range of biological applications, but their synthetic approaches are still limited. Various stereochemical assignments of the compounds remain unresolved. Batzelladine and ptilocaulins are an area of high interest in research on tricyclic guanidine alkaloids. In addition, mirabilins and netamines are among the other tricyclic guanidine alkaloids that contain the ptilocaulin skeleton. Due to the different structural configurations of batzelladine and ptilocaulin, these two main skeletons are afforded attention in many reports. These two main skeletons exhibit different kinds of compounds by varying their ester chain and sidechain. The synthetic approaches to tricyclic guanidine alkaloids, especially the batzelladine and ptilocaulin skeletons, are discussed. Moreover, this review compiles the first and latest research on the synthesis of these compounds and their bioactivities, dating from the 1980s to 2022. Full article
(This article belongs to the Section Synthesis and Medicinal Chemistry of Marine Natural Products)
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11 pages, 1114 KiB  
Article
The Phospholipid Molecular Species Profile of Apostichopus japonicus Tissues Modifies through Exposure to n-3 Polyunsaturated Fatty Acid-Deficient Diet
by Ekaterina V. Ermolenko, Tatyana V. Sikorskaya and Valeria P. Grigorchuk
Mar. Drugs 2022, 20(9), 578; https://doi.org/10.3390/md20090578 - 15 Sep 2022
Cited by 3 | Viewed by 1321
Abstract
The sea cucumber Apostichopus japonicus, being a target species of commercial fisheries and aquaculture, is also used as a source of biologically active compounds with high pharmacological potential. By the methods of high-performance liquid chromatography with high resolution mass spectrometry, we analyzed [...] Read more.
The sea cucumber Apostichopus japonicus, being a target species of commercial fisheries and aquaculture, is also used as a source of biologically active compounds with high pharmacological potential. By the methods of high-performance liquid chromatography with high resolution mass spectrometry, we analyzed the major structural phospholipids (PL)—glycerophosphoethanolamines (PE), glycerophosphocholines (PC), glycerophosphoserines (PS), and glycerophosphoinositols (PI)—in tissues of wild and cultured sea cucumbers. The intestines of the wild and cultured animals differed from the other tissues by an elevated content of molecular species of PE, PC, and PS with 22:6n-3 fatty acid. The respiratory trees of the studied animals contained a high level of odd-chain PI and PI with 20:4n-6. The exposure to n-3 PUFA-deficient diet resulted in substantial changes in the molecular species profile of PL of the wild and cultured animals. The cultured sea cucumbers showed a significant decrease in the 20:5n-3 content in all four studied PL classes. A replacement of 20:5n-3 by 20:4n-6 occurred in PE, PC, and PI. The decrease in the level of molecular species of PS with 20:5n-3 was compensated by an increase in the level of monounsaturated long-chain PS. The diet of cultured sea cucumbers is a crucial factor for enhancing the nutritional properties of the product obtained from them. Full article
(This article belongs to the Special Issue Bioactive Compounds from Sea Cucumbers)
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19 pages, 1970 KiB  
Article
Metabolic Engineering of the Isopentenol Utilization Pathway Enhanced the Production of Terpenoids in Chlamydomonas reinhardtii
by Mei-Li Zhao, Wen-Sheng Cai, Si-Qi Zheng, Jia-Lin Zhao, Jun-Liang Zhang, Ying Huang, Zhang-Li Hu and Bin Jia
Mar. Drugs 2022, 20(9), 577; https://doi.org/10.3390/md20090577 - 15 Sep 2022
Cited by 5 | Viewed by 2137
Abstract
Eukaryotic green microalgae show considerable promise for the sustainable light-driven biosynthesis of high-value fine chemicals, especially terpenoids because of their fast and inexpensive phototrophic growth. Here, the novel isopentenol utilization pathway (IUP) was introduced into Chlamydomonas reinhardtii to enhance the hemiterpene (isopentenyl pyrophosphate, [...] Read more.
Eukaryotic green microalgae show considerable promise for the sustainable light-driven biosynthesis of high-value fine chemicals, especially terpenoids because of their fast and inexpensive phototrophic growth. Here, the novel isopentenol utilization pathway (IUP) was introduced into Chlamydomonas reinhardtii to enhance the hemiterpene (isopentenyl pyrophosphate, IPP) titers. Then, diphosphate isomerase (IDI) and limonene synthase (MsLS) were further inserted for limonene production. Transgenic algae showed 8.6-fold increase in IPP compared with the wild type, and 23-fold increase in limonene production compared with a single MsLS expressing strain. Following the culture optimization, the highest limonene production reached 117 µg/L, when the strain was cultured in a opt2 medium supplemented with 10 mM isoprenol under a light: dark regimen. This demonstrates that transgenic algae expressing the IUP represent an ideal chassis for the high-value terpenoid production. The IUP will facilitate further the metabolic and enzyme engineering to enhance the terpenoid titers by significantly reducing the number of enzyme steps required for an optimal biosynthesis. Full article
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12 pages, 1435 KiB  
Article
Chemistry and Bioactivity of the Deep-Water Antarctic Octocoral Alcyonium sp.
by Anne-Claire D. Limon, Hiran M. L. W. Patabendige, Ala Azhari, Xingmin Sun, Dennis E. Kyle, Nerida G. Wilson and Bill J. Baker
Mar. Drugs 2022, 20(9), 576; https://doi.org/10.3390/md20090576 - 14 Sep 2022
Cited by 2 | Viewed by 1689
Abstract
Chemical investigation of an Antarctic deep-water octocoral has led to the isolation of four new compounds, including three illudalane sesquiterpenoids (13) related to the alcyopterosins, a highly oxidized steroid, alcyosterone (5), and five known alcyopterosins (4 [...] Read more.
Chemical investigation of an Antarctic deep-water octocoral has led to the isolation of four new compounds, including three illudalane sesquiterpenoids (13) related to the alcyopterosins, a highly oxidized steroid, alcyosterone (5), and five known alcyopterosins (4, 69). The structures were established by extensive 1D and 2D NMR analyses, while 9 was verified by XRD. Alcyopterosins are unusual for their nitrate ester functionalization and have been characterized with cytotoxicity related to their DNA binding properties. Alcyopterosins V (3) and E (4) demonstrated single-digit micromolar activity against Clostridium difficile, an intestinal bacterium capable of causing severe diarrhea that is increasingly associated with drug resistance. Alcyosterone (5) and several alcyopterosins were similarly potent against the protist Leishmania donovani, the causative agent of leishmaniasis, a disfiguring disease that can be fatal if not treated. While the alcyopterosin family of sesquiterpenes is known for mild cytotoxicity, the observed activity against C. difficile and L. donovani is selective for the infectious agents. Full article
(This article belongs to the Section Structural Studies on Marine Natural Products)
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11 pages, 2616 KiB  
Article
Phenolic Metabolites from a Deep-Sea-Derived Fungus Aspergillus puniceus A2 and Their Nrf2-Dependent Anti-Inflammatory Effects
by Jianlin He, Xin Wu, Shuhuan Huang, Juan Wang, Siwen Niu, Meixiang Chen, Gaiyun Zhang, Songyan Cai, Jingna Wu and Bihong Hong
Mar. Drugs 2022, 20(9), 575; https://doi.org/10.3390/md20090575 - 13 Sep 2022
Cited by 2 | Viewed by 1758
Abstract
Four undescribed phenolic compounds, namely asperpropanols A–D (14), along with two known congeners 5 and 6, were isolated from Aspergillus puniceus A2, a deep-sea-derived fungus. The gross structures of the compounds were established by detailed analyses of the [...] Read more.
Four undescribed phenolic compounds, namely asperpropanols A–D (14), along with two known congeners 5 and 6, were isolated from Aspergillus puniceus A2, a deep-sea-derived fungus. The gross structures of the compounds were established by detailed analyses of the HRESIMS and NMR data, and their absolute configurations were resolved by modified Mosher’s method and calculations of ECD data. Compounds 16 were found to have excellent anti-inflammatory effect on lipopolysaccharide (LPS)-induced RAW264.7 cells at 20 μM, evidenced by the reduced nitric oxide (NO), tumor necrosis factor α, and interleukin 6 production. Among them, 5 and 6 showed inhibitory effects on NO production comparable with the positive control (BAY11-7083 at 10 μM). Additionally, the LPS-induced mRNA expressions of inducible nitric oxide synthase and cyclooxygenase-2 were also decreased. Interestingly, mRNA expression of nuclear factor erythroid 2–related factor 2 (Nrf2) was downregulated by LPS and recovered by 16, suggesting a vital role of Nrf2 in their effect. We further found that pharmacological inhibition of Nrf2 by ML385 largely abrogated the effects of 16 on RAW264.7 cells. Therefore, 16 may share a common anti-inflammatory mechanism via Nrf2 upregulation and activation. Full article
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10 pages, 2542 KiB  
Article
Sarcoeleganolides C–G, Five New Cembranes from the South China Sea Soft Coral Sarcophyton elegans
by Cili Wang, Jiarui Zhang, Xing Shi, Kai Li, Fengling Li, Xuli Tang, Guoqiang Li and Pinglin Li
Mar. Drugs 2022, 20(9), 574; https://doi.org/10.3390/md20090574 - 10 Sep 2022
Cited by 7 | Viewed by 1459
Abstract
Five new cembranes, named sarcoeleganolides C–G (15), along with three known analogs (68) were isolated from soft coral Sarcophyton elegans collected from the Yagong Island, South China Sea. Their structures and absolute configurations were determined [...] Read more.
Five new cembranes, named sarcoeleganolides C–G (15), along with three known analogs (68) were isolated from soft coral Sarcophyton elegans collected from the Yagong Island, South China Sea. Their structures and absolute configurations were determined by extensive spectroscopic analysis, QM-NMR, and TDDFT-ECD calculations. In addition, compound 3 exhibited better anti-inflammation activity compared to the indomethacin as a positive control in zebrafish at 20 μM. Full article
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25 pages, 2902 KiB  
Article
Gut and Gill-Associated Microbiota of the Flatfish European Plaice (Pleuronectes platessa): Diversity, Metabolome and Bioactivity against Human and Aquaculture Pathogens
by Marjan Ghotbi, Ole Kelting, Martina Blümel and Deniz Tasdemir
Mar. Drugs 2022, 20(9), 573; https://doi.org/10.3390/md20090573 - 09 Sep 2022
Cited by 6 | Viewed by 2490
Abstract
Similar to other marine holobionts, fish are colonized by complex microbial communities that promote their health and growth. Fish-associated microbiota is emerging as a promising source of bioactive metabolites. Pleuronectes platessa (European plaice, plaice), a flatfish with commercial importance, is common in the [...] Read more.
Similar to other marine holobionts, fish are colonized by complex microbial communities that promote their health and growth. Fish-associated microbiota is emerging as a promising source of bioactive metabolites. Pleuronectes platessa (European plaice, plaice), a flatfish with commercial importance, is common in the Baltic Sea. Here we used a culture-dependent survey followed by molecular identification to identify microbiota associated with the gills and the gastrointestinal tract (GIT) of P. platessa, then profiled their antimicrobial activity and metabolome. Altogether, 66 strains (59 bacteria and 7 fungi) were isolated, with Proteobacteria being the most abundant phylum. Gill-associated microbiota accounted for higher number of isolates and was dominated by the Proteobacteria (family Moraxellaceae) and Actinobacteria (family Nocardiaceae), whereas Gram-negative bacterial families Vibrionaceae and Shewanellaceae represented the largest group associated with the GIT. The EtOAc extracts of the solid and liquid media cultures of 21 bacteria and 2 fungi representing the diversity of cultivable plaice-associated microbiota was profiled for their antimicrobial activity against three fish pathogens, human bacterial pathogen panel (ESKAPE) and two human fungal pathogens. More than half of all tested microorganisms, particularly those originating from the GIT epithelium, exhibited antagonistic effect against fish pathogens (Lactococcus garvieae, Vibrio ichthyoenteri) and/or human pathogens (Enterococcus faecium, methicillin-resistant Staphylococcus aureus). Proteobacteria represented the most active isolates. Notably, the solid media extracts displayed higher activity against fish pathogens, while liquid culture extracts were more active against human pathogens. Untargeted metabolomics approach using feature-based molecular networking showed the high chemical diversity of the liquid extracts that contained undescribed clusters. This study highlights plaice-associated microbiota as a potential source of antimicrobials for the control of human and the aquaculture-associated infections. This is the first study reporting diversity, bioactivity and chemical profile of culture-dependent microbiota of plaice. Full article
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17 pages, 4358 KiB  
Article
A Nutraceutical Formulation Containing Brown Algae Reduces Hepatic Lipid Accumulation by Modulating Lipid Metabolism and Inflammation in Experimental Models of NAFLD and NASH
by Daniela Gabbia, Marco Roverso, Ilaria Zanotto, Martina Colognesi, Katia Sayaf, Samantha Sarcognato, Diletta Arcidiacono, Alice Zaramella, Stefano Realdon, Nicola Ferri, Maria Guido, Francesco Paolo Russo, Sara Bogialli, Maria Carrara and Sara De Martin
Mar. Drugs 2022, 20(9), 572; https://doi.org/10.3390/md20090572 - 08 Sep 2022
Cited by 4 | Viewed by 2358
Abstract
Recently, some preclinical and clinical studies have demonstrated the ability of brown seaweeds in reducing the risk factors for metabolic syndrome. Here, we analyzed the beneficial effect of a nutraceutical formulation containing a phytocomplex extracted from seaweeds and chromium picolinate in animal models [...] Read more.
Recently, some preclinical and clinical studies have demonstrated the ability of brown seaweeds in reducing the risk factors for metabolic syndrome. Here, we analyzed the beneficial effect of a nutraceutical formulation containing a phytocomplex extracted from seaweeds and chromium picolinate in animal models of liver steatosis of differing severities (rats with non-alcoholic fatty liver disease (NAFLD) and its complication, non-alcoholic steatohepatitis (NASH)). This treatment led to a significant drop in hepatic fat deposition in both models (p < 0.01 vs. untreated animals), accompanied by a reduction in plasma inflammatory cytokines, such as interleukin 6, tumor necrosis factor α, and C reactive protein, and myeloperoxidase expression in liver tissue. Furthermore, a modulation of the molecular pathways involved in lipid metabolism and storage was demonstrated, since we observed the significant reduction of the mRNA levels of fatty acid synthase, diacylglycerol acyltransferases, the sterol-binding protein SREBP-1, and the lipid transporter perilipin-2, in both treated NAFLD and NASH rats in comparison to untreated ones. In conclusion, this nutraceutical product was effective in reducing liver steatosis and showed further beneficial effects on hepatic inflammation and glycemic control, which were particularly evident in rats characterized by a more severe condition, thus representing a therapeutic option for the treatment of NAFLD and NASH patients. Full article
(This article belongs to the Collection Marine Drugs in the Management of Metabolic Diseases)
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16 pages, 1943 KiB  
Article
Inhibition of Nematocyst Discharge from Pelagia noctiluca (Cnidaria: Scyphozoa)—Prevention Measures against Jellyfish Stings
by Ainara Ballesteros, Carles Trullas, Eric Jourdan and Josep-Maria Gili
Mar. Drugs 2022, 20(9), 571; https://doi.org/10.3390/md20090571 - 08 Sep 2022
Cited by 2 | Viewed by 2263
Abstract
Pelagia noctiluca stings are common in Mediterranean coastal areas and, although the venom is non-lethal, they are painful. Due to its high toxicity and abundance, P. noctiluca is considered a target species for the focus of research on active ingredients to reduce the [...] Read more.
Pelagia noctiluca stings are common in Mediterranean coastal areas and, although the venom is non-lethal, they are painful. Due to its high toxicity and abundance, P. noctiluca is considered a target species for the focus of research on active ingredients to reduce the symptoms of its sting. To determine the effect of 31 substances and formulations on nematocyst discharge, we performed three tests: (1) screening of per se discharge activator solutions, (2) inhibitory test with nematocyst chemical stimulation (5% acetic acid) and (3) inhibitory test quantifying the hemolytic area. Ammonia, barium chloride, bleach, scented ammonia, carbonated cola, lemon juice, sodium chloride and papain triggered nematocyst discharge. All of them were ruled out as potential inhibitors. Butylene glycol showed a reduction in nematocyst discharge, while the formulations of 10% lidocaine in ethanol, 1.5% hydroxyacetophenone in distilled water + butylene glycol, and 3% Symsitive® in butylene glycol inhibited nematocyst discharge. These last results were subsequently correlated with a significant decrease in hemolytic area in the venom assays versus seawater, a neutral solution. The presented data represent a first step in research to develop preventive products for jellyfish stings while at the same time attempting to clarify some uncertainties about the role of various topical solutions in P. noctiluca first-aid protocols. Full article
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16 pages, 4902 KiB  
Article
Saquayamycin B1 Suppresses Proliferation, Invasion, and Migration by Inhibiting PI3K/AKT Signaling Pathway in Human Colorectal Cancer Cells
by Jianjiang Li, Ningning Han, Hao Zhang, Xiaoyu Xie, Yaoyao Zhu, E Zhang, Jiahui Ma, Chuangeng Shang, Mengxiong Yin, Weidong Xie and Xia Li
Mar. Drugs 2022, 20(9), 570; https://doi.org/10.3390/md20090570 - 07 Sep 2022
Cited by 4 | Viewed by 1740
Abstract
Moromycin B (Mor B), saquayamycin B1 (Saq B1), saquayamycin B (Saq B), and landomycin N (Lan N), four angucyclines produced by the marine-derived actinomycete Streptomyces sp., are a class of polyketone compounds containing benzanthracene. Here, the structure–activity relationship of these [...] Read more.
Moromycin B (Mor B), saquayamycin B1 (Saq B1), saquayamycin B (Saq B), and landomycin N (Lan N), four angucyclines produced by the marine-derived actinomycete Streptomyces sp., are a class of polyketone compounds containing benzanthracene. Here, the structure–activity relationship of these four compounds was analyzed in human colorectal cancer (CRC) cells. Saq B1, which showed the strongest cytotoxicity with an IC50 of 0.18–0.84 µM for CRC cells in MTT assays, was employed to test underlying mechanisms of action in SW480 and SW620 cells (two invasive CRC cell lines). Our results showed that Saq B1 inhibited CRC cell proliferation in a dose- and time-dependent manner. Notably, lower cytotoxicity was measured in normal human hepatocyte cells (QSG-7701). Furthermore, we observed proapoptosis, antimigration, and anti-invasion activities of Saq B1 in CRC cells. At the same time, the protein and mRNA expression of important markers related to the epithelial–mesenchymal transition (EMT) and apoptosis changed, including N-cadherin, E-cadherin, and Bcl-2, in Saq B1-treated CRC cells. Surprisingly, the PI3K/AKT signaling pathway was shown to be involved in Saq B1-induced apoptosis, and in inhibiting invasion and migration. Computer docking models also suggested that Saq B1 might bind to PI3Kα. Collectively, these results indicate that Saq B1 effectively inhibited growth and decreased the motor ability of CRC cells by regulating the PI3K/AKT signaling pathway, which provides more possibilities for the development of drugs in the treatment of CRC. Full article
(This article belongs to the Special Issue Bioactive Compounds from Marine Streptomyces (2nd Edition))
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12 pages, 1829 KiB  
Article
Extracellular Metabolites of Heterotrophic Auxenochlorella protothecoides: A New Source of Bio-Stimulants for Higher Plants
by Yujiao Qu, Xinxiang Chen, Beibei Ma, Huachang Zhu, Xuan Zheng, Jiazhen Yu, Qinghui Wu, Rong Li, Ziqiang Wang and Yibo Xiao
Mar. Drugs 2022, 20(9), 569; https://doi.org/10.3390/md20090569 - 07 Sep 2022
Cited by 1 | Viewed by 2007
Abstract
The biodiversity of microalgal species is enormous, and their versatile metabolism produces a wide diversity of compounds that can be used in food, healthcare, and other applications. Microalgae are also a potential source of bio-stimulants that enhance nutrition efficiency, abiotic stress tolerance, and/or [...] Read more.
The biodiversity of microalgal species is enormous, and their versatile metabolism produces a wide diversity of compounds that can be used in food, healthcare, and other applications. Microalgae are also a potential source of bio-stimulants that enhance nutrition efficiency, abiotic stress tolerance, and/or crop quality traits. In this study, the extracellular metabolites of Auxenochlorella protothecoides (EAp) were prepared using three different culture strategies, and their effects on plant growth were examined. Furthermore, the composition of EAp was analyzed by GC-MS. The elongation of lateral roots and the cold-tolerance of Arabidopsis thaliana and Nicotiana benthamiana were promoted by EAp. Moreover, EAp from high-cell-density fermentation stimulated the growth of the leafy vegetables Brassica rapa and Lactuca sativa at dilutions as high as 500- and 1000-fold. Three major groups of compounds were identified by GC-MS, including organic acids or organic acid esters, phenols, and saccharides. Some of these compounds have known plant–stimulating effects, while the rest requires further investigation in the future. Our study demonstrates that EAp is a potential bio-stimulant, while also providing an environmentally friendly and economical microalgae fermentation process. Full article
(This article belongs to the Special Issue Novel Biotechnology of Microalgae)
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12 pages, 2483 KiB  
Article
Characterization and Expression Analysis of Regeneration-Associated Protein (Aj-Orpin) during Intestinal Regeneration in the Sea Cucumber Apostichopus japonicus
by Fang Su, Lina Sun, Xiaoni Li, Wei Cui and Hongsheng Yang
Mar. Drugs 2022, 20(9), 568; https://doi.org/10.3390/md20090568 - 06 Sep 2022
Cited by 2 | Viewed by 1683
Abstract
Apostichopus japonicus achieves intestinal regeneration in a short period after evisceration, and multiple genes are involved in this process. The transcriptome of A. japonicus was screened for regeneration-associated protein (Aj-Orpin), a gene that is specifically upregulated during intestinal regeneration. The expression and function [...] Read more.
Apostichopus japonicus achieves intestinal regeneration in a short period after evisceration, and multiple genes are involved in this process. The transcriptome of A. japonicus was screened for regeneration-associated protein (Aj-Orpin), a gene that is specifically upregulated during intestinal regeneration. The expression and function of Aj-Orpin were identified and investigated in this study. The 5′ and 3′ RACE polymerase chain reaction (PCR) was used to clone the full-length cDNA of Aj-Orpin. The open reading frame codes for a 164 amino-acid protein with an EF-hand_7 domain and overlapping signal peptides and transmembrane regions. Moreover, Aj-Orpin mRNA and protein expression during intestinal regeneration was investigated using real-time quantitative PCR and Western blot. The expression pattern of Aj-Orpin in the regenerating intestine was investigated using immunohistochemistry. The results showed that Aj-Orpin is an exocrine protein with two EF-hand-like calcium-binding domains. Expression levels were higher in the regenerating intestine than in the normal intestine, but protein expression changes lagged behind mRNA expression changes. Aj-Orpin was found to play a role in the formation of blastema and lumen. It was primarily expressed in the serosal layer and submucosa, suggesting that it might be involved in proliferation. These observations lay the foundation for understanding the role of Orpin-like in echinoderm intestinal regeneration. Full article
(This article belongs to the Special Issue Bioactive Compounds from Sea Cucumbers)
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31 pages, 3735 KiB  
Review
Secondary Metabolites from Marine-Derived Bacillus: A Comprehensive Review of Origins, Structures, and Bioactivities
by Shaoyujia Xiao, Nan Chen, Zixue Chai, Mengdie Zhou, Chenghaotian Xiao, Shiqin Zhao and Xiliang Yang
Mar. Drugs 2022, 20(9), 567; https://doi.org/10.3390/md20090567 - 06 Sep 2022
Cited by 13 | Viewed by 2473
Abstract
The marine is a highly complex ecosystem including various microorganisms. Bacillus species is a predominant microbialflora widely distributed in marine ecosystems. This review aims to provide a systematic summary of the newly reported metabolites produced by marine-derived Bacillus species over recent years covering [...] Read more.
The marine is a highly complex ecosystem including various microorganisms. Bacillus species is a predominant microbialflora widely distributed in marine ecosystems. This review aims to provide a systematic summary of the newly reported metabolites produced by marine-derived Bacillus species over recent years covering the literature from 2014 to 2021. It describes the structural diversity and biological activities of the reported compounds. Herein, a total of 87 newly reported metabolites are included in this article, among which 49 compounds originated from marine sediments, indicating that marine sediments are majority sources of productive strains of Bacillus species Therefore, marine-derived Bacillus species are a potentially promising source for the discovery of new metabolites. Full article
(This article belongs to the Special Issue Bioactive Compounds from the Deep-Sea-Derived Microorganisms)
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10 pages, 2381 KiB  
Article
Mililatensols A–C, New Records of Sarsolenane and Capnosane Diterpenes from Soft Coral Sarcophyton mililatensis
by Qing Bu, Min Yang, Xian-Yun Yan, Song-Wei Li, Zeng-Yue Ge, Ling Zhang, Li-Gong Yao, Yue-Wei Guo and Lin-Fu Liang
Mar. Drugs 2022, 20(9), 566; https://doi.org/10.3390/md20090566 - 06 Sep 2022
Cited by 9 | Viewed by 1650
Abstract
Three unusual diterpenes with rare sarsolenane and capnosane skeletons, namely mililatensols A–C (13), were isolated from the South China Sea soft coral Sarcophyton mililatensis, leading to the first record of sarsolenane and capnosane diterpenes from the title animal. [...] Read more.
Three unusual diterpenes with rare sarsolenane and capnosane skeletons, namely mililatensols A–C (13), were isolated from the South China Sea soft coral Sarcophyton mililatensis, leading to the first record of sarsolenane and capnosane diterpenes from the title animal. The structures of compounds 13 were established by extensive spectroscopic analysis and comparison with the literature data. Moreover, the absolute configuration of 2 was determined by TDDFT ECD calculations. In an in vitro bioassay, none of the isolated compounds showed obvious anti-inflammatory activity on LPS-induced TNF-α release in RAW264.7 macrophages. In the preliminary virtual screening of inhibitory potential against SARS-CoV-2 by molecular docking, the results showed these three diterpenes were potential SARS-CoV-2 Mpro inhibitors. Full article
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10 pages, 1384 KiB  
Article
Actinoflavosides B–D, Flavonoid Type Glycosides from Tidal Mudflat-Derived Actinomyces
by Hyeongju Jeong, Se Jin Jo, Munhyung Bae, Young Ran Kim and Kyuho Moon
Mar. Drugs 2022, 20(9), 565; https://doi.org/10.3390/md20090565 - 05 Sep 2022
Cited by 3 | Viewed by 1699
Abstract
Three new secondary metabolites, actinoflavosides B–D (13), were discovered in the culture broth of two actinomycete strains (JML48 and JMS33) that were isolated from tidal mudflat sediment in Muan, Republic of Korea. The planar structures of the actinoflavosides were [...] Read more.
Three new secondary metabolites, actinoflavosides B–D (13), were discovered in the culture broth of two actinomycete strains (JML48 and JMS33) that were isolated from tidal mudflat sediment in Muan, Republic of Korea. The planar structures of the actinoflavosides were elucidated by MS, UV, and NMR analyses. The stereochemistry of an aminosugar, 2,3,6-trideoxy-3-amino-ribopyranoside in the actinoflavosides was determined by J-based configuration analysis using values obtained from DQF-COSY experiments and modified Mosher’s method. Actinoflavosides B–D (13) displayed antibacterial activity against Pseudomonas aeruginosa, and actinoflavoside D (3) significantly increased IL-2 production in mouse splenocytes. Full article
(This article belongs to the Special Issue Glycosylated Metabolites from Marine Bacteria)
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15 pages, 747 KiB  
Review
Potential Food and Nutraceutical Applications of Alginate: A Review
by Decheng Bi, Xu Yang, Lijun Yao, Zhangli Hu, Hui Li, Xu Xu and Jun Lu
Mar. Drugs 2022, 20(9), 564; https://doi.org/10.3390/md20090564 - 04 Sep 2022
Cited by 31 | Viewed by 3655
Abstract
Alginate is an acidic polysaccharide mainly extracted from kelp or sargassum, which comprises 40% of the dry weight of algae. It is a linear polymer consisting of β-D-mannuronic acid (M) and α-L-guluronic acid (G) with 1,4-glycosidic linkages, possessing various applications in the food [...] Read more.
Alginate is an acidic polysaccharide mainly extracted from kelp or sargassum, which comprises 40% of the dry weight of algae. It is a linear polymer consisting of β-D-mannuronic acid (M) and α-L-guluronic acid (G) with 1,4-glycosidic linkages, possessing various applications in the food and nutraceutical industries due to its unique physicochemical properties and health benefits. Additionally, alginate is able to form a gel matrix in the presence of Ca2+ ions. Alginate properties also affect its gelation, including its structure and experimental conditions such as pH, temperature, crosslinker concentration, residence time and ionic strength. These features of this polysaccharide have been widely used in the food industry, including in food gels, controlled-release systems and film packaging. This review comprehensively covers the analysis of alginate and discussed the potential applications of alginate in the food industry and nutraceuticals. Full article
(This article belongs to the Special Issue Pre-clinical Marine Drug Discovery Ⅱ)
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14 pages, 2531 KiB  
Article
3-Bromo-4,5-dihydroxybenzaldehyde Isolated from Polysiphonia morrowii Suppresses TNF-α/IFN-γ-Stimulated Inflammation and Deterioration of Skin Barrier in HaCaT Keratinocytes
by Arachchige Maheshika Kumari Jayasinghe, Eui-Jeong Han, Kirinde Gedara Isuru Sandanuwan Kirindage, Ilekuttige Priyan Shanura Fernando, Eun-A Kim, Junseong Kim, Kyungsook Jung, Kil-Nam Kim, Soo-Jin Heo and Ginnae Ahn
Mar. Drugs 2022, 20(9), 563; https://doi.org/10.3390/md20090563 - 31 Aug 2022
Cited by 9 | Viewed by 2635
Abstract
Polysiphonia morrowii is a well-known red alga that has promising pharmacological characteristics. The current study evaluates the protective effect of 3-bromo-4,5-dihydroxybenzaldehyde (BDB) isolated from P. morrowii on tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated inflammation and skin barrier deterioration in HaCaT keratinocytes. The anti-inflammatory effect [...] Read more.
Polysiphonia morrowii is a well-known red alga that has promising pharmacological characteristics. The current study evaluates the protective effect of 3-bromo-4,5-dihydroxybenzaldehyde (BDB) isolated from P. morrowii on tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated inflammation and skin barrier deterioration in HaCaT keratinocytes. The anti-inflammatory effect of BDB in TNF-α/IFN-γ-stimulated HaCaT keratinocytes is evaluated by investigating nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, inflammatory cytokines, and chemokines. Further, the interaction between BDB and the skin barrier functions in stimulated HaCaT keratinocytes is investigated. The findings of the study reveal that BDB dose-dependently increases cell viability while decreasing intracellular reactive oxygen species (ROS) production. BDB downregulates the expression of inflammatory cytokines, interleukin (IL)-6, -8, -13, IFN-γ, TNF-α, and chemokines, Eotaxin, macrophage-derived chemokine (MDC), regulated on activation, normal T cells expressed and secreted (RANTES), and thymus and activation-regulated chemokine (TARC) by modulating the MAPK and NF-κB signaling pathways in TNF-α/IFN-γ-stimulated HaCaT keratinocytes. Furthermore, BDB increases the production of skin hydration proteins and tight junction proteins in stimulated HaCaT keratinocytes by preserving skin moisturization and tight junction stability. These findings imply that BDB exhibits a protective ability against inflammation and deterioration of skin barrier via suppressing the expression of inflammatory signaling in TNF-α/IFN-γ-stimulated HaCaT keratinocytes. Full article
(This article belongs to the Special Issue Pharmacological Activity of Marine Algae Compounds)
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16 pages, 4006 KiB  
Article
Antarctic Marine Algae Extracts as a Potential Natural Resource to Protect Epithelial Barrier Integrity
by Seong-Hee Ko, YoonHee Lim, Eun Jae Kim, Young Wook Ko, In-Sun Hong, Sanghee Kim and YunJae Jung
Mar. Drugs 2022, 20(9), 562; https://doi.org/10.3390/md20090562 - 31 Aug 2022
Cited by 7 | Viewed by 2011
Abstract
The intestine and skin provide crucial protection against the external environment. Strengthening the epithelial barrier function of these organs is critical for maintaining homeostasis against inflammatory stimuli. Recent studies suggest that polar marine algae are a promising bioactive resource because of their adaptation [...] Read more.
The intestine and skin provide crucial protection against the external environment. Strengthening the epithelial barrier function of these organs is critical for maintaining homeostasis against inflammatory stimuli. Recent studies suggest that polar marine algae are a promising bioactive resource because of their adaptation to extreme environments. To investigate the bioactive properties of polar marine algae on epithelial cells of the intestine and skin, we created extracts of the Antarctic macroalgae Himantothallus grandifolius, Plocamium cartilagineum, Phaeurus antarcticus, and Kallymenia antarctica, analyzed the compound profiles of the extracts using gas chromatography-mass spectrometry, and tested the protective activities of the extracts on human intestinal and keratinocyte cell lines by measuring cell viability and reactive oxygen species scavenging. In addition, we assessed immune responses modulated by the extracts by real-time polymerase chain reaction, and we monitored the barrier-protective activities of the extracts on intestinal and keratinocyte cell lines by measuring transepithelial electrical resistance and fluorescence-labeled dextran flux, respectively. We identified bioactive compounds, including several fatty acids and lipid compounds, in the extracts, and found that the extracts perform antioxidant activities that remove intracellular reactive oxygen species and scavenge specific radicals. Furthermore, the Antarctic marine algae extracts increased cell viability, protected cells against inflammatory stimulation, and increased the barrier integrity of cells damaged by lipopolysaccharide or ultraviolet radiation. These results suggest that Antarctic marine algae have optimized their composition for polar environments, and furthermore, that the bioactive properties of compounds produced by Antarctic marine algae can potentially be used to develop therapeutics to promote the protective barrier function of the intestine and skin. Full article
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11 pages, 2394 KiB  
Article
Potential Use of 3D CORAGRAF-Loaded PDGF-BB in PLGA Microsphere Seeded Mesenchymal Stromal Cells in Enhancing the Repair of Calvaria Critical-Size Bone Defect in Rat Model
by Saktiswaren Mohan, Puvanan Karunanithi, Malliga Raman Murali, Khairul Anwar Ayob, Jayaraman Megala, Krishnamurithy Genasan, Tunku Kamarul and Hanumantha Rao Balaji Raghavendran
Mar. Drugs 2022, 20(9), 561; https://doi.org/10.3390/md20090561 - 31 Aug 2022
Cited by 1 | Viewed by 1793
Abstract
Our previous study evidenced that the 3D CORAGRAF loaded with PLGA microsphere constitutes PDGF-BB can support cell attachment and proliferation and can induce an osteogenic commitment of mesenchymal stromal cells in the in vitro condition. However, how this construct can perform in pathophysiological [...] Read more.
Our previous study evidenced that the 3D CORAGRAF loaded with PLGA microsphere constitutes PDGF-BB can support cell attachment and proliferation and can induce an osteogenic commitment of mesenchymal stromal cells in the in vitro condition. However, how this construct can perform in pathophysiological conditions in terms of repairing critical bone defects is yet to be understood. A study was therefore conducted to investigate the regeneration potential of calvaria critical-size defects using CORAGRAF + PLGA with PDGF-BB + mesenchymal stromal cells (MSCs) in a rat model. A 5 mm critical bone defect was created on calvaria of 40 male Sprague-Dawley rats. CORAGRAF incorporated either with or without PDGF-BB and seeded with rat bone-marrow-derived MSCs was implanted at the defect region. The bone regeneration potential of implanted constructs was assessed using micro-CT imaging and histological staining in weeks 4 and 8. The micro-CT images indicated a significant closure of defects in the cranial bone of the rats treated with 3D CORAGRAF + PLGA with PDGF-BB + MSCs on week 4 and 8 post-implantation. This finding, further supported with the histology outcome where the rat cranial defect treated with CORAGRAF + PLGA with PDGF-BB + MSCs indicated neo-bony ingrowth with organized and mature bone-like morphology as compared with other groups. The previous in vitro results substantiated with our pre-clinical findings demonstrate that the combination of CORAGRAF + PLGA with PDGF-BB + MSCs could be an ideal construct to support bone regeneration in critical bone defects. Hence, this construct can be further investigated for its safety and efficacy in large animal models, or it can be skipped to human trial prior for commercialization. Full article
(This article belongs to the Section Biomaterials of Marine Origin)
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14 pages, 5699 KiB  
Article
Immunoenhancing Effects of Cyclina sinensis Pentadecapeptide through Modulation of Signaling Pathways in Mice with Cyclophosphamide-Induced Immunosuppression
by Rui Zhao, Xiao-Xia Jiang, Qiao-Ling Zhao, Han-Wei Ye, Yi Lin, Ju Huang and Yun-Ping Tang
Mar. Drugs 2022, 20(9), 560; https://doi.org/10.3390/md20090560 - 31 Aug 2022
Cited by 3 | Viewed by 1850
Abstract
Our study aimed to investigate the immune-enhancing mechanism of the pentadecapeptide (RVAPEEHPVEGRYLV) from Cyclina sinensis (SCSP) in a cyclophosphamide (CTX)-induced murine model of immunosuppression. Our results showed that SCSP treatment significantly increased mouse body weight, immune organ indices, and the production of serum [...] Read more.
Our study aimed to investigate the immune-enhancing mechanism of the pentadecapeptide (RVAPEEHPVEGRYLV) from Cyclina sinensis (SCSP) in a cyclophosphamide (CTX)-induced murine model of immunosuppression. Our results showed that SCSP treatment significantly increased mouse body weight, immune organ indices, and the production of serum IL-6, IL-1β, and tumor necrosis factor (TNF)-α in CTX-treated mice. In addition, SCSP treatment enhanced the proliferation of splenic lymphocytes and peritoneal macrophages, as well as phagocytosis of the latter in a dose-dependent manner. Moreover, SCSP elevated the phosphorylation levels of p38, ERK, JNK, PI3K and Akt, and up-regulated IKKα, IKKβ, p50 NF-κB and p65 NF-κB protein levels, while down-regulating IκBα protein levels. Our results indicate that SCSP has immune-enhancing activities, and that it can activate the MAPK/NF-κB and PI3K/Akt pathways to enhance immunity in CTX-induced immunosuppressed mice. Full article
(This article belongs to the Special Issue Marine Bioactive Peptides—Structure, Function, and Application)
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23 pages, 4955 KiB  
Article
Stimulation of Neurite Outgrowth in Cerebrocortical Neurons by Sodium Channel Activator Brevetoxin-2 Requires Both N-Methyl-D-aspartate Receptor 2B (GluN2B) and p21 Protein (Cdc42/Rac)-Activated Kinase 1 (PAK1)
by Suneet Mehrotra, Marsha L. Pierce, Shashank M. Dravid and Thomas F. Murray
Mar. Drugs 2022, 20(9), 559; https://doi.org/10.3390/md20090559 - 31 Aug 2022
Viewed by 2573
Abstract
N-methyl-D-aspartate (NMDA) receptors play a critical role in activity-dependent dendritic arborization, spinogenesis, and synapse formation by stimulating calcium-dependent signaling pathways. Previously, we have shown that brevetoxin 2 (PbTx-2), a voltage-gated sodium channel (VGSC) activator, produces a concentration-dependent increase in intracellular sodium [Na+ [...] Read more.
N-methyl-D-aspartate (NMDA) receptors play a critical role in activity-dependent dendritic arborization, spinogenesis, and synapse formation by stimulating calcium-dependent signaling pathways. Previously, we have shown that brevetoxin 2 (PbTx-2), a voltage-gated sodium channel (VGSC) activator, produces a concentration-dependent increase in intracellular sodium [Na+]I and increases NMDA receptor (NMDAR) open probabilities and NMDA-induced calcium (Ca2+) influxes. The objective of this study is to elucidate the downstream signaling mechanisms by which the sodium channel activator PbTx-2 influences neuronal morphology in murine cerebrocortical neurons. PbTx-2 and NMDA triggered distinct Ca2+-influx pathways, both of which involved the NMDA receptor 2B (GluN2B). PbTx-2-induced neurite outgrowth in day in vitro 1 (DIV-1) neurons required the small Rho GTPase Rac1 and was inhibited by both a PAK1 inhibitor and a PAK1 siRNA. PbTx-2 exposure increased the phosphorylation of PAK1 at Thr-212. At DIV-5, PbTx-2 induced increases in dendritic protrusion density, p-cofilin levels, and F-actin throughout the dendritic arbor and soma. Moreover, PbTx-2 increased miniature excitatory post-synaptic currents (mEPSCs). These data suggest that the stimulation of neurite outgrowth, spinogenesis, and synapse formation produced by PbTx-2 are mediated by GluN2B and PAK1 signaling. Full article
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13 pages, 4271 KiB  
Article
Synthesis of Bioactive Silver Nanoparticles Using New Bacterial Strains from an Antarctic Consortium
by Maria Sindhura John, Joseph Amruthraj Nagoth, Kesava Priyan Ramasamy, Alessio Mancini, Gabriele Giuli, Cristina Miceli and Sandra Pucciarelli
Mar. Drugs 2022, 20(9), 558; https://doi.org/10.3390/md20090558 - 31 Aug 2022
Cited by 13 | Viewed by 1842
Abstract
In this study, we report on the synthesis of silver nanoparticles (AgNPs) achieved by using three bacterial strains Rhodococcus, Brevundimonas and Bacillus as reducing and capping agents, newly isolated from a consortium associated with the Antarctic marine ciliate Euplotes focardii. After [...] Read more.
In this study, we report on the synthesis of silver nanoparticles (AgNPs) achieved by using three bacterial strains Rhodococcus, Brevundimonas and Bacillus as reducing and capping agents, newly isolated from a consortium associated with the Antarctic marine ciliate Euplotes focardii. After incubation of these bacteria with a 1 mM solution of AgNO3 at 22 °C, AgNPs were synthesized within 24 h. Unlike Rhodococcus and Bacillus, the reduction of Ag+ from AgNO3 into Ag0 has never been reported for a Brevundimonas strain. The maximum absorbances of these AgNPs in the UV-Vis spectra were in the range of 404 nm and 406 nm. EDAX spectra showed strong signals from the Ag atom and medium signals from C, N and O due to capping protein emissions. TEM analysis showed that the NPs were spherical and rod-shaped, with sizes in the range of 20 to 50 nm, and they were clustered, even though not in contact with one another. Besides aggregation, all the AgNPs showed significant antimicrobial activity. This biosynthesis may play a dual role: detoxification of AgNO3 and pathogen protection against both the bacterium and ciliate. Biosynthetic AgNPs also represent a promising alternative to conventional antibiotics against common nosocomial pathogens. Full article
(This article belongs to the Section Synthesis and Medicinal Chemistry of Marine Natural Products)
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8 pages, 1751 KiB  
Article
Anti-Melanogenesis and Photoprotective Effects of Ecklonia maxima Extract Containing Dieckol and Eckmaxol
by Lei Wang, Jun-Geon Je, Hyun-Soo Kim, Kaiqiang Wang, Xiaoting Fu, Jiachao Xu, Xin Gao and You-Jin Jeon
Mar. Drugs 2022, 20(9), 557; https://doi.org/10.3390/md20090557 - 30 Aug 2022
Cited by 2 | Viewed by 1574
Abstract
Seaweeds are potential ingredients in the cosmeceutical industry. Our previous study demonstrates that the phlorotannin-enriched extract of Ecklonia maxima (EME-EA) containing dieckol and eckmaxol possesses strong anti-inflammatory activity and suggests the cosmeceutical potential of EME-EA. In order to evaluate the cosmeceutical potential of [...] Read more.
Seaweeds are potential ingredients in the cosmeceutical industry. Our previous study demonstrates that the phlorotannin-enriched extract of Ecklonia maxima (EME-EA) containing dieckol and eckmaxol possesses strong anti-inflammatory activity and suggests the cosmeceutical potential of EME-EA. In order to evaluate the cosmeceutical potential of EME-EA, the anti-melanogenesis and photoprotective effects of EME-EA were investigated in this study. EME-EA remarkably inhibited mushroom tyrosinase and melanogenesis in alpha-melanocyte-stimulating hormone-stimulated B16F10 cells. In addition, EME-EA significantly suppressed UVB-induced HaCaT cell death that was consistent with inhibition of apoptosis and reduction in scavenging intracellular reactive oxygen species. Furthermore, EME-EA significantly inhibited collagen degradation and matrix metalloproteinases expression in UVB-irradiated HDF cells in a concentration-dependent manner. These results indicate that EME-EA possesses strong anti-melanogenesis and photoprotective activities and suggest EME-EA is an ideal ingredient in the pharmaceutical and cosmeceutical industries. Full article
(This article belongs to the Special Issue Advances in Medicinal Research of Phlorotannins)
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