Marine Drugs

9 pages, 1606 KiB

Open AccessArticle

Ximaoornatins A–C, Polyoxygenated Diterpenoids from the Hainan Soft Coral Sinularia ornata

by Li-Li Sun, Xu-Wen Li and Yue-Wei Guo

Mar. Drugs 2022, 20(3), 218; https://doi.org/10.3390/md20030218 - 20 Mar 2022

Cited by 4 | Viewed by 2484

Three complex polyoxygenated diterpenoids possessing uncommon tetradecahydro-2,13:6,9-diepoxybenzo[10]annulene scaffold, namely ximaoornatins A–C (1–3), one new eunicellin-type diterpene, litophynin K (4), and a related known compound, litophynol B (5) were isolated from the South China Sea soft [...] Read more.

Three complex polyoxygenated diterpenoids possessing uncommon tetradecahydro-2,13:6,9-diepoxybenzo[10]annulene scaffold, namely ximaoornatins A–C (1–3), one new eunicellin-type diterpene, litophynin K (4), and a related known compound, litophynol B (5) were isolated from the South China Sea soft coral Sinularia ornata. The structures and absolute configurations of 1–4 were established by extensive spectroscopic analysis, X-ray diffraction analysis, and/or modified Mosher’s method. A plausible biosynthetic relationship of 1 and its potential precursor 4 was proposed. In a bioassay, none of the isolated compounds showed obvious anti-inflammatory activity on LPS-induced TNF-α release in RAW264.7 macrophages and PTP1B inhibitory effects. Full article

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8 pages, 907 KiB

Open AccessArticle

Nitrogen-Containing Secondary Metabolites from a Deep-Sea Fungus Aspergillus unguis and Their Anti-Inflammatory Activity

by Cao Van Anh, Yeo Dae Yoon, Jong Soon Kang, Hwa-Sun Lee, Chang-Su Heo and Hee Jae Shin

Mar. Drugs 2022, 20(3), 217; https://doi.org/10.3390/md20030217 - 20 Mar 2022

Cited by 7 | Viewed by 2827

Abstract

Aspergillus is well-known as the second-largest contributor of fungal natural products. Based on NMR guided isolation, three nitrogen-containing secondary metabolites, including two new compounds, variotin B (1) and coniosulfide E (2), together with a known compound, unguisin A ( [...] Read more.

Aspergillus is well-known as the second-largest contributor of fungal natural products. Based on NMR guided isolation, three nitrogen-containing secondary metabolites, including two new compounds, variotin B (1) and coniosulfide E (2), together with a known compound, unguisin A (3), were isolated from the ethyl acetate (EtOAc) extract of the deep-sea fungus Aspergillus unguis IV17-109. The planar structures of 1 and 2 were elucidated by an extensive analysis of their spectroscopic data (HRESIMS, 1D and 2D NMR). The absolute configuration of 2 was determined by comparison of its optical rotation value with those of the synthesized analogs. Compound 2 is a rare, naturally occurring substance with an unusual cysteinol moiety. Furthermore, 1 showed moderate anti-inflammatory activity with an IC₅₀ value of 20.0 µM. These results revealed that Aspergillus unguis could produce structurally diverse nitrogenous secondary metabolites, which can be used for further studies to find anti-inflammatory leads. Full article

(This article belongs to the Special Issue Marine Anti-inflammatory and Antioxidant Agents 2.0)

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24 pages, 2535 KiB

Open AccessArticle

In Vitro Anticancer and Cancer-Preventive Activity of New Triterpene Glycosides from the Far Eastern Starfish Solaster pacificus

by Timofey V. Malyarenko, Olesya S. Malyarenko, Alla A. Kicha, Anatoly I. Kalinovsky, Pavel S. Dmitrenok and Natalia V. Ivanchina

Mar. Drugs 2022, 20(3), 216; https://doi.org/10.3390/md20030216 - 20 Mar 2022

Cited by 4 | Viewed by 2421

Abstract

Sea stars or starfish (class Asteroidea) and holothurians or sea cucumbers (class Holothuroidea), belonging to the phylum Echinodermata (echinoderms), are characterized by different sets of glycosidic metabolites: the steroid type in starfish and the triterpene type in holothurians. However, herein we report the [...] Read more.

Sea stars or starfish (class Asteroidea) and holothurians or sea cucumbers (class Holothuroidea), belonging to the phylum Echinodermata (echinoderms), are characterized by different sets of glycosidic metabolites: the steroid type in starfish and the triterpene type in holothurians. However, herein we report the isolation of eight new triterpene glycosides, pacificusosides D–K (1–3, 5–9) along with the known cucumarioside D (4), from the alcoholic extract of the Far Eastern starfish Solaster pacificus. The isolated new compounds are closely related to the metabolites of sea cucumbers, and their structures of 1–3 and 5–9 were determined by extensive NMR and ESIMS techniques. Compounds 2, 5, and 8 have a new type of tetrasaccharide chain with a terminal non-methylated monosaccharide unit. Compounds 3, 6, and 9 contain another new type of tetrasaccharide chain, having 6-O-SO₃-Glc as one of the sugar units. The cytotoxic activity of 1–9 against non-cancerous mouse epidermal cells JB6 Cl41 and human melanoma cell lines SK-MEL-2, SK-MEL-28, and RPMI-7951 was determined by MTS assay. Compounds 1, 3, 4, 6, and 9 showed potent cytotoxicity against these cell lines, but the cancer selectivity (SI > 9) was observed only against the SK-MEL-2 cell line. Compounds 1, 3, 4, 6, and 9 at the non-toxic concentration of 0.1 μM significantly inhibited neoplastic cell transformation of JB6 Cl41 cells induced by chemical carcinogens (EGF, TPA) or ionizing radiation (X-rays and UVB). Moreover, compounds 1 and 4 at the non-toxic concentration of 0.1 µM possessed the highest inhibiting activity on colony formation among the investigated compounds and decreased the colonies number of SK-MEL-2 cells by 64% and 70%, respectively. Thus, triterpene glycosides 1 and 4 can be considered as prospective cancer-preventive and anticancer-compound leaders. Full article

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45 pages, 12098 KiB

Open AccessArticle

In Silico Evaluation of Antifungal Compounds from Marine Sponges against COVID-19-Associated Mucormycosis

by Omkar Pokharkar, Hariharan Lakshmanan, Grigory Zyryanov and Mikhail Tsurkan

Mar. Drugs 2022, 20(3), 215; https://doi.org/10.3390/md20030215 - 20 Mar 2022

Cited by 19 | Viewed by 5265

Abstract

The world is already facing the devastating effects of the SARS-CoV-2 pandemic. A disseminated mucormycosis epidemic emerged to worsen this situation, causing havoc, especially in India. This research aimed to perform a multitargeted docking study of marine-sponge-origin bioactive compounds against mucormycosis. Information on [...] Read more.

The world is already facing the devastating effects of the SARS-CoV-2 pandemic. A disseminated mucormycosis epidemic emerged to worsen this situation, causing havoc, especially in India. This research aimed to perform a multitargeted docking study of marine-sponge-origin bioactive compounds against mucormycosis. Information on proven drug targets and marine sponge compounds was obtained via a literature search. A total of seven different targets were selected. Thirty-five compounds were chosen using the PASS online program. For homology modeling and molecular docking, FASTA sequences and 3D structures for protein targets were retrieved from NCBI and PDB databases. Autodock Vina in PyRx 0.8 was used for docking studies. Further, molecular dynamics simulations were performed using the IMODS server for top-ranked docked complexes. Moreover, the drug-like properties and toxicity analyses were performed using Lipinski parameters in Swiss-ADME, OSIRIS, ProTox-II, pkCSM, and StopTox servers. The results indicated that naamine D, latrunculin A and S, (+)-curcudiol, (+)-curcuphenol, aurantoside I, and hyrtimomine A had the highest binding affinity values of −8.8, −8.6, −9.8, −11.4, −8.0, −11.4, and −9.0 kcal/mol, respectively. In sum, all MNPs included in this study are good candidates against mucormycosis. (+)-curcudiol and (+)-curcuphenol are promising compounds due to their broad-spectrum target inhibition potential. Full article

(This article belongs to the Special Issue Marine Natural Products against Coronaviruses)

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9 pages, 1916 KiB

Open AccessCommunication

Unique Cyclized Thiolopyrrolones from the Marine-Derived Streptomyces sp. BTBU20218885

by Fuhang Song, Jiansen Hu, Xinwan Zhang, Wei Xu, Jinpeng Yang, Shaoyong Li and Xiuli Xu

Mar. Drugs 2022, 20(3), 214; https://doi.org/10.3390/md20030214 - 18 Mar 2022

Cited by 5 | Viewed by 2250

Abstract

Two new cyclized thiolopyrrolone derivatives, namely, thiolopyrrolone A (1) and 2,2-dioxidothiolutin (2), together with the kn own compound, thiolutin (3) were identified from a marine-derived Streptomyces sp. BTBU20218885, which was isolated from a mud sample collected from [...] Read more.

Two new cyclized thiolopyrrolone derivatives, namely, thiolopyrrolone A (1) and 2,2-dioxidothiolutin (2), together with the kn own compound, thiolutin (3) were identified from a marine-derived Streptomyces sp. BTBU20218885, which was isolated from a mud sample collected from the coastal region of Xiamen, China. Their chemical structures were determined using spectroscopic data, including HRESIMS, 1D and 2D NMR techniques. 1 possessed a unique unsymmetrical sulfur-containing thiolopyrrolone structure. All the compounds were tested for bioactivities against Staphylococcus aureus, Escherichia coli, Bacille Calmette–Guérin (BCG), Mycobacterium tuberculosis, and Candida albicans. 1 displayed antibacterial activities against BCG, M. tuberculosis, and S. aureus with minimum inhibitory concentration (MIC) values of 10, 10, and 100 μg/mL, respectively. Thiolutin (3) showed antibacterial activities against E. coli, BCG, M. tuberculosis, and S. aureus with MIC values of 6.25, 0.3125, 0.625, and 3.125 μg/mL, respectively. Full article

(This article belongs to the Special Issue Heterocyclic Compounds from Marine Organisms)

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12 pages, 1706 KiB

Open AccessArticle

New Sorbicillinoids with Tea Pathogenic Fungus Inhibitory Effect from Marine-Derived Fungus Hypocrea jecorina H8

by Shun-Zhi Liu, Guang-Xin Xu, Feng-Ming He, Wei-Bo Zhang, Zhen Wu, Ming-Yu Li, Xi-Xiang Tang and Ying-Kun Qiu

Mar. Drugs 2022, 20(3), 213; https://doi.org/10.3390/md20030213 - 17 Mar 2022

Cited by 7 | Viewed by 2503

Abstract

Four new dimeric sorbicillinoids (1–3 and 5) and a new monomeric sorbicillinoid (4) as well as six known analogs (6–11) were purified from the fungal strain Hypocrea jecorina H8, which was obtained from [...] Read more.

Four new dimeric sorbicillinoids (1–3 and 5) and a new monomeric sorbicillinoid (4) as well as six known analogs (6–11) were purified from the fungal strain Hypocrea jecorina H8, which was obtained from mangrove sediment, and showed potent inhibitory activity against the tea pathogenic fungus Pestalotiopsis theae (P. theae). The planar structures of 1–5 were assigned by analyses of their UV, IR, HR-ESI-MS, and NMR spectroscopic data. All the compounds were evaluated for growth inhibition of tea pathogenic fungus P. theae. Compounds 5, 6, 8, 9, and 10 exhibited more potent inhibitory activities compared with the positive control hexaconazole with an ED₅₀ of 24.25 ± 1.57 µg/mL. The ED₅₀ values of compounds 5, 6, 8, 9, and 10 were 9.13 ± 1.25, 2.04 ± 1.24, 18.22 ± 1.29, 1.83 ± 1.37, and 4.68 ± 1.44 µg/mL, respectively. Additionally, the effects of these compounds on zebrafish embryo development were also evaluated. Except for compounds 5 and 8, which imparted toxic effects on zebrafish even at 0.625 μM, the other isolated compounds did not exhibit significant toxicity to zebrafish eggs, embryos, or larvae. Taken together, sorbicillinoid derivatives (6, 9, and 10) from H. jecorina H8 displayed low toxicity and high anti-tea pathogenic fungus potential. Full article

(This article belongs to the Special Issue Heterocyclic Compounds from Marine Organisms)

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11 pages, 2199 KiB

Open AccessArticle

Butenolides from the Coral-Derived Fungus Aspergillius terreus SCSIO41404

by Qingyun Peng, Weihao Chen, Xiuping Lin, Jiao Xiao, Yonghong Liu and Xuefeng Zhou

Mar. Drugs 2022, 20(3), 212; https://doi.org/10.3390/md20030212 - 17 Mar 2022

Cited by 14 | Viewed by 2529

Abstract

Five undescribed butenolides including two pairs of enantiomers, (+)-asperteretal G (1a), (−)-asperteretal G (1b), (+)-asperteretal H (2a), (−)-asperteretal H (2b), asperteretal I (3), and para-hydroxybenzaldehyde derivative, (S)-3-(2,3-dihydroxy-3-methylbutyl)-4-hydroxybenzaldehyde (14), [...] Read more.

Five undescribed butenolides including two pairs of enantiomers, (+)-asperteretal G (1a), (−)-asperteretal G (1b), (+)-asperteretal H (2a), (−)-asperteretal H (2b), asperteretal I (3), and para-hydroxybenzaldehyde derivative, (S)-3-(2,3-dihydroxy-3-methylbutyl)-4-hydroxybenzaldehyde (14), were isolated together with ten previously reported butenolides 4–13, from the coral-derived fungus Aspergillus terreus SCSIO41404. Enantiomers 1a/1b and 2a/2b were successfully purified by high performance liquid chromatography (HPLC) using a chiral column, and the enantiomers 1a and 1b were new natural products. Structures of the unreported compounds, including the absolute configurations, were elucidated by NMR and MS data, optical rotation, experimental and calculated electronic circular dichroism, induced circular dichroism, and X-ray crystal data. The isolated butenolides were evaluated for antibacterial, cytotoxic, and enzyme inhibitory activities. Compounds 7 and 12 displayed weak antibacterial activity, against Enterococcus faecalis (IC₅₀ = 25 μg/mL) and Klebsiella pneumoniae (IC₅₀ = 50 μg/mL), respectively, whereas 6 showed weak inhibitory effect on acetylcholinesterase. Nevertheless, most of the butenolides showed inhibition against pancreatic lipase (PL) with an inhibition rate of 21.2–73.0% at a concentration of 50 μg/mL. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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15 pages, 3819 KiB

Open AccessArticle

Pyranodipyran Derivatives with Tyrosyl DNA Phosphodiesterase 1 Inhibitory Activities and Fluorescent Properties from Aspergillus sp. EGF 15-0-3

by Xia Wei, Fang-Ting Wang, Mei-Xia Si-Tu, Hao Fan, Jin-Shan Hu, Hao Yang, Shan-Yue Guan, Lin-Kun An and Cui-Xian Zhang

Mar. Drugs 2022, 20(3), 211; https://doi.org/10.3390/md20030211 - 17 Mar 2022

Cited by 7 | Viewed by 1950

Abstract

Four new benzodipyran racemates, namely (±)-aspergiletals A–D (3–6), representing a rare pyrano[4,3-h]chromene scaffold were isolated together with eurotiumide G (1) and eurotiumide F (2) from the soft-coral-derived fungus Aspergillus sp. EGF 15-0-3. All [...] Read more.

Four new benzodipyran racemates, namely (±)-aspergiletals A–D (3–6), representing a rare pyrano[4,3-h]chromene scaffold were isolated together with eurotiumide G (1) and eurotiumide F (2) from the soft-coral-derived fungus Aspergillus sp. EGF 15-0-3. All the corresponding optically pure enantiomers were successfully separated by a chiral HPLC column. The structures and configurations of all the compounds were elucidated based on the combination of NMR and HRESIMS data, chiral separation, single-crystal X-ray diffraction, quantum chemical ¹³C NMR, and electronic circular dichroism calculations. Meanwhile, the structure of eurotiumide G was also revised. The TDP1 inhibitor activities and photophysical properties of the obtained compounds were evaluated. In the TDP1 inhibition assay, as a result of synergy between (+)-6 and (−)-6, (±)-6 displayed strong inhibitory activity to TDP1 with IC₅₀ values of 6.50 ± 0.73 μM. All compounds had a large Stokes shift and could be utilized for elucidating the mode of bioactivities by fluorescence imaging. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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16 pages, 1593 KiB

Open AccessArticle

Application of Feature-Based Molecular Networking for Comparative Metabolomics and Targeted Isolation of Stereoisomers from Algicolous Fungi

by Bicheng Fan, Laura Grauso, Fengjie Li, Silvia Scarpato, Alfonso Mangoni and Deniz Tasdemir

Mar. Drugs 2022, 20(3), 210; https://doi.org/10.3390/md20030210 - 16 Mar 2022

Cited by 4 | Viewed by 2889

Abstract

Seaweed endophytic (algicolous) fungi are talented producers of bioactive natural products. We have previously isolated two strains of the endophytic fungus, Pyrenochaetopsis sp. FVE-001 and FVE-087, from the thalli of the brown alga Fucus vesiculosus. Initial chemical studies yielded four new decalinoylspirotetramic [...] Read more.

Seaweed endophytic (algicolous) fungi are talented producers of bioactive natural products. We have previously isolated two strains of the endophytic fungus, Pyrenochaetopsis sp. FVE-001 and FVE-087, from the thalli of the brown alga Fucus vesiculosus. Initial chemical studies yielded four new decalinoylspirotetramic acid derivatives with antimelanoma activity, namely pyrenosetins A–C (1–3) from Pyrenochaetopsis sp. strain FVE-001, and pyrenosetin D (4) from strain FVE-087. In this study, we applied a comparative metabolomics study employing HRMS/MS based feature-based molecular networking (FB MN) on both Pyrenochaetopsis strains. A higher chemical capacity in production of decalin derivatives was observed in Pyrenochaetopsis sp. FVE-087. Notably, several decalins showed different retention times despite the same MS data and MS/MS fragmentation pattern with the previously isolated pyrenosetins, indicating they may be their stereoisomers. FB MN-based targeted isolation studies coupled with antimelanoma activity testing on the strain FVE-087 afforded two new stereoisomers, pyrenosetins E (5) and F (6). Extensive NMR spectroscopy including DFT computational studies, HR-ESIMS, and Mosher’s ester method were used in the structure elucidation of compounds 5 and 6. The 3’R,5’R stereochemistry determined for compound 6 was identical to that previously reported for pyrenosetin C (3), whose stereochemistry was revised as 3’S,5’R in this study. Pyrenosetin E (5) inhibited the growth of human malignant melanoma cells (A-375) with an IC₅₀ value of 40.9 μM, while 6 was inactive. This study points out significant variations in the chemical repertoire of two closely related fungal strains and the versatility of FB MN in identification and targeted isolation of stereoisomers. It also confirms that the little-known fungal genus Pyrenochaetopsis is a prolific source of complex decalinoylspirotetramic acid derivatives. Full article

(This article belongs to the Special Issue Fungal Natural Products: An Ongoing Source for New Drug Leads)

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17 pages, 4001 KiB

Open AccessArticle

Comparative Venomics of C. flavidus and C. frigidus and Closely Related Vermivorous Cone Snails

by S. W. A. Himaya, Alexander Arkhipov, Wai Ying Yum and Richard J. Lewis

Mar. Drugs 2022, 20(3), 209; https://doi.org/10.3390/md20030209 - 15 Mar 2022

Cited by 1 | Viewed by 2126

Abstract

Cone snail venom biodiversity reflects dietary preference and predatory and defensive envenomation strategies across the ≈900 species of Conidae. To better understand the mechanisms of adaptive radiations in closely related species, we investigated the venom of two phylogenetically and spatially related species, [...] Read more.

Cone snail venom biodiversity reflects dietary preference and predatory and defensive envenomation strategies across the ≈900 species of Conidae. To better understand the mechanisms of adaptive radiations in closely related species, we investigated the venom of two phylogenetically and spatially related species, C. flavidus and C. frigidus of the Virgiconus clade. Transcriptomic analysis revealed that the major superfamily profiles were conserved between the two species, including 68 shared conotoxin transcripts. These shared transcripts contributed 90% of the conotoxin expression in C. frigidus and only 49% in C. flavidus, which showed greater toxin diversification in the dominant O1, I2, A, O2, O3, and M superfamilies compared to C. frigidus. On the basis of morphology, two additional sub-groups closely resembling C. flavidus were also identified from One Tree Island Reef. Despite the morphological resemblance, the venom duct proteomes of these cryptic sub-groups were distinct from C. flavidus. We suggest rapid conotoxin sequence divergence may have facilitated adaptive radiation and the establishment of new species and the regulatory mechanisms facilitating species-specific venom evolution. Full article

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18 pages, 5261 KiB

Open AccessReview

Exploring Marine as a Rich Source of Bioactive Peptides: Challenges and Opportunities from Marine Pharmacology

by Ishtiaq Ahmed, Muhammad Asgher, Farooq Sher, Syed Makhdoom Hussain, Nadia Nazish, Navneet Joshi, Ashutosh Sharma, Roberto Parra-Saldívar, Muhammad Bilal and Hafiz M. N. Iqbal

Mar. Drugs 2022, 20(3), 208; https://doi.org/10.3390/md20030208 - 13 Mar 2022

Cited by 13 | Viewed by 4367

Abstract

This review highlights the underexplored potential and promises of marine bioactive peptides (MBPs) with unique structural, physicochemical, and biological activities to fight against the current and future human pathologies. A particular focus is given to the marine environment as a significant source to [...] Read more.

This review highlights the underexplored potential and promises of marine bioactive peptides (MBPs) with unique structural, physicochemical, and biological activities to fight against the current and future human pathologies. A particular focus is given to the marine environment as a significant source to obtain or extract high-value MBPs from touched/untouched sources. For instance, marine microorganisms, including microalgae, bacteria, fungi, and marine polysaccharides, are considered prolific sources of amino acids at large, and peptides/polypeptides in particular, with fundamental structural sequence and functional entities of a carboxyl group, amine, hydrogen, and a variety of R groups. Thus, MBPs with tunable features, both structural and functional entities, along with bioactive traits of clinical and therapeutic value, are of ultimate interest to reinforce biomedical settings in the 21st century. On the other front, as the largest biome globally, the marine biome is the so-called “epitome of untouched or underexploited natural resources” and a considerable source with significant potentialities. Therefore, considering their biological and biomedical importance, researchers around the globe are redirecting and/or regaining their interests in valorizing the marine biome-based MBPs. This review focuses on the widespread bioactivities of MBPs, FDA-approved MBPs in the market, sustainable development goals (SDGs), and legislation to valorize marine biome to underlying the impact role of bioactive elements with the related pathways. Finally, a detailed overview of current challenges, conclusions, and future perspectives is also given to satisfy the stimulating demands of the pharmaceutical sector of the modern world. Full article

(This article belongs to the Special Issue Novel Applications and Technologies for the Industrial Exploitation of Algal Derived Marine Bioactives as Nutraceuticals or Pharmaceuticals)

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17 pages, 2179 KiB

Open AccessArticle

Total Phenolic Levels, In Vitro Antioxidant Properties, and Fatty Acid Profile of Two Microalgae, Tetraselmis marina Strain IMA043 and Naviculoid Diatom Strain IMA053, Isolated from the North Adriatic Sea

by Riccardo Trentin, Luísa Custódio, Maria João Rodrigues, Emanuela Moschin, Katia Sciuto, José Paulo da Silva and Isabella Moro

Mar. Drugs 2022, 20(3), 207; https://doi.org/10.3390/md20030207 - 12 Mar 2022

Cited by 8 | Viewed by 2711

Abstract

This work studied the potential biotechnological applications of a naviculoid diatom (IMA053) and a green microalga (Tetraselmis marina IMA043) isolated from the North Adriatic Sea. Water, methanol, and dichloromethane (DCM) extracts were prepared from microalgae biomass and evaluated for total phenolic content [...] Read more.

This work studied the potential biotechnological applications of a naviculoid diatom (IMA053) and a green microalga (Tetraselmis marina IMA043) isolated from the North Adriatic Sea. Water, methanol, and dichloromethane (DCM) extracts were prepared from microalgae biomass and evaluated for total phenolic content (TPC) and in vitro antioxidant properties. Biomass was profiled for fatty acid methyl esters (FAME) composition. The DCM extracts had the highest levels of total phenolics, with values of 40.58 and 86.14 mg GAE/g dry weight (DW in IMA053 and IMA043, respectively). The DCM extracts had a higher radical scavenging activity (RSA) than the water and methanol ones, especially those from IMA043, with RSAs of 99.65% toward 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)diammonium salt (ABTS) at 10 mg/mL, and of 103.43% against 2,2-diphenyl-1-picrylhydrazyl (DPPH) at 5 mg/mL. The DCM extract of IMA053 displayed relevant copper chelating properties (67.48% at 10 mg/mL), while the highest iron chelating activity was observed in the water extract of the same species (92.05% at 10 mg/mL). Both strains presented a high proportion of saturated (SFA) and monounsaturated (MUFA) fatty acids. The results suggested that these microalgae could be further explored as sources of natural antioxidants for the pharmaceutical and food industry and as feedstock for biofuel production. Full article

(This article belongs to the Special Issue Biotechnology Applications of Microalgae)

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22 pages, 1536 KiB

Open AccessReview

Astaxanthin from Crustaceans and Their Byproducts: A Bioactive Metabolite Candidate for Therapeutic Application

by Vida Šimat, Nikheel Bhojraj Rathod, Martina Čagalj, Imen Hamed and Ivana Generalić Mekinić

Mar. Drugs 2022, 20(3), 206; https://doi.org/10.3390/md20030206 - 12 Mar 2022

Cited by 24 | Viewed by 5587

Abstract

In recent years, the food, pharma, and cosmetic industries have shown considerable interest in bioactive molecules of marine origin that show high potential for application as nutraceuticals and therapeutic agents. Astaxanthin, a lipid-soluble and orange-reddish-colored carotenoid pigment, is one of the most investigated [...] Read more.

In recent years, the food, pharma, and cosmetic industries have shown considerable interest in bioactive molecules of marine origin that show high potential for application as nutraceuticals and therapeutic agents. Astaxanthin, a lipid-soluble and orange-reddish-colored carotenoid pigment, is one of the most investigated pigments. Natural astaxanthin is mainly produced from microalgae, and it shows much stronger antioxidant properties than its synthetic counterpart. This paper aims to summarize and discuss the important aspects and recent findings associated with the possible use of crustacean byproducts as a source of astaxanthin. In the last five years of research on the crustaceans and their byproducts as a source of natural astaxanthin, there are many new findings regarding the astaxanthin content in different species and new green extraction protocols for its extraction. However, there is a lack of information on the amounts of astaxanthin currently obtained from the byproducts as well as on the cost-effectiveness of the astaxanthin production from the byproducts. Improvement in these areas would most certainly contribute to the reduction of waste and reuse in the crustacean processing industry. Successful exploitation of byproducts for recovery of this valuable compound would have both environmental and social benefits. Finally, astaxanthin’s strong biological activity and prominent health benefits have been discussed in the paper. Full article

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14 pages, 2531 KiB

Open AccessArticle

Investigations on the Wound Healing Potential of Tilapia Piscidin (TP)2-5 and TP2-6

by Chia-Wen Liu, Chu-Yi Hsieh and Jyh-Yih Chen

Mar. Drugs 2022, 20(3), 205; https://doi.org/10.3390/md20030205 - 10 Mar 2022

Cited by 3 | Viewed by 2434

Abstract

Wound healing is a highly orchestrated process involving many cell types, such as keratinocytes, fibroblasts and endothelial cells. This study aimed to evaluate the potential application of synthetic peptides derived from tilapia piscidin (TP)2, TP2-5 and TP2-6 in skin wound healing. The treatment [...] Read more.

Wound healing is a highly orchestrated process involving many cell types, such as keratinocytes, fibroblasts and endothelial cells. This study aimed to evaluate the potential application of synthetic peptides derived from tilapia piscidin (TP)2, TP2-5 and TP2-6 in skin wound healing. The treatment of HaCaT keratinocytes with TP2-5 and TP2-6 did not cause cytotoxicity, but did enhance cell proliferation and migration, which could be attributed to the activation of epidermal growth factor receptor signaling. In CCD-966SK fibroblasts, although TP2-5 (31.25 μg/mL) and TP2-6 (125 μg/mL) showed cytotoxic effects, we observed the significant promotion of cell proliferation and migration at low concentrations. In addition, collagen I, collagen III, and keratinocyte growth factor were upregulated by the peptides. We further found that TP2-5 and TP2-6 showed pro-angiogenic properties, including the enhancement of human umbilical vein endothelial cell (HUVEC) migration and the promotion of neovascularization. In a murine model, wounds treated topically with TP2-5 and TP2-6 were reduced by day 2 post-injury and healed significantly faster than untreated wounds. Taken together, these findings demonstrate that both TP2-5 and TP2-6 have multifaceted effects when used as topical agents for accelerating wound healing. Full article

(This article belongs to the Special Issue Advances in Marine Antimicrobial Peptides)

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11 pages, 1771 KiB

Open AccessArticle

Evaluation of the Preservation and Digestion of Seal Meat Processed with Heating and Antioxidant Seal Meat Hydrolysates

by Yi Zhang, Lea Spitzer, Xin Rui, Susana C. M. Fernandes, Romy Vaugeois and Benjamin K. Simpson

Mar. Drugs 2022, 20(3), 204; https://doi.org/10.3390/md20030204 - 10 Mar 2022

Viewed by 2821

Abstract

Seal meat is of high nutritive value but is not highly exploited for human food due to ethical issues, undesirable flavors, and loss of nutrients during the processing/cooking step. In this work, commercially available processed seal meat was treated with its hydrolysates as [...] Read more.

Seal meat is of high nutritive value but is not highly exploited for human food due to ethical issues, undesirable flavors, and loss of nutrients during the processing/cooking step. In this work, commercially available processed seal meat was treated with its hydrolysates as preservatives with the aim of improving nutrient bioavailability. The contents of the nutrients were analyzed after digestion using a simulated dynamic digestion model, and the effects of different processing conditions, i.e., low-temperature processing and storage (25 °C) and high-temperature cooking (100 °C), of seal meat were investigated. Hydrolysates with antioxidant activity decreased the amounts of the less desirable Fe³⁺ ions in the seal meat digests. After treatment with hydrolysates at room temperature, a much higher total Fe content of 781.99 mg/kg was observed compared to other treatment conditions. The release of amino acids increased with temperature and was 520.54 mg/g for the hydrolysate-treated sample versus 413.12 mg/g for the control seal meat sample treated in buffer. Overall, this study provides useful data on the potential use of seal meat as a food product with high nutritive value and seal meat hydrolysates with antioxidant activity as preservatives to control oxidation in food. Full article

(This article belongs to the Special Issue Bioactive Peptides from Marine By-Products and Underused Marine Organisms)

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14 pages, 4147 KiB

Open AccessArticle

A New Fungal Triterpene from the Fungus Aspergillus flavus Stimulates Glucose Uptake without Fat Accumulation

by Dan-dan Li, Ying Wang, Eun La Kim, Jongki Hong and Jee H. Jung

Mar. Drugs 2022, 20(3), 203; https://doi.org/10.3390/md20030203 - 10 Mar 2022

Cited by 2 | Viewed by 2104

Abstract

Through activity-guided fractionation, a new triterpene (asperflagin, 1) was isolated as a PPAR-γ agonist from the jellyfish-derived fungus Aspergillus flavus. Asperflagin displayed selective and moderate transactivation effects on PPAR-γ in Ac2F rat liver cells. Based on further biological evaluation and molecular [...] Read more.

Through activity-guided fractionation, a new triterpene (asperflagin, 1) was isolated as a PPAR-γ agonist from the jellyfish-derived fungus Aspergillus flavus. Asperflagin displayed selective and moderate transactivation effects on PPAR-γ in Ac2F rat liver cells. Based on further biological evaluation and molecular docking analysis, we postulated that asperflagin might function as a PPAR-γ partial agonist. This compound was calculated to display a typical PPAR-γ ligand–receptor interaction that is distinct from that of full agonistic antidiabetics such as rosiglitazone, and may retain the antidiabetic effect without accompanying weight gain. Weight gain and obesity are typical side effects of the PPAR-γ full agonist rosiglitazone, and lead to suboptimal outcomes in diabetic patients. Compared to rosiglitazone, asperflagin showed higher glucose uptake in HepG2 human liver cells at concentrations of 20 and 40 μM but induced markedly lower adipogenesis and lipid accumulation in 3T3-L1 preadipocytes. These results suggest that asperflagin may be utilized for further study on advanced antidiabetic leads. Full article

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17 pages, 2256 KiB

Open AccessReview

Ulva (Enteromorpha) Polysaccharides and Oligosaccharides: A Potential Functional Food Source from Green-Tide-Forming Macroalgae

by Limin Ning, Zhong Yao and Benwei Zhu

Mar. Drugs 2022, 20(3), 202; https://doi.org/10.3390/md20030202 - 10 Mar 2022

Cited by 17 | Viewed by 4901

Abstract

The high-valued utilization of Ulva (previously known as Enteromorpha) bioresources has drawn increasing attention due to the periodic blooms of world-wide green tide. The polysaccharide is the main functional component of Ulva and exhibits various physiological activities. The Ulva oligosaccharide as the [...] Read more.

The high-valued utilization of Ulva (previously known as Enteromorpha) bioresources has drawn increasing attention due to the periodic blooms of world-wide green tide. The polysaccharide is the main functional component of Ulva and exhibits various physiological activities. The Ulva oligosaccharide as the degradation product of polysaccharide not only possesses some obvious activities, but also possesses excellent solubility and bioavailability. Both Ulva polysaccharides and oligosaccharides hold promising potential in the food industry as new functional foods or food additives. Studies on Ulva polysaccharides and oligosaccharides are increasing and have been the focus of the marine bioresources field. However, the comprehensive review of this topic is still rare and do not cover the recent advances of the structure, isolation, preparation, activity and applications of Ulva polysaccharides and oligosaccharides. This review systematically summarizes and discusses the recent advances of chemical composition, extraction, purification, structure, and activity of Ulva polysaccharides as well as oligosaccharides. In addition, the potential applications as new functional food and food additives have also been considered, and these will definitely expand the applications of Ulva oligosaccharides in the food and medical fields. Full article

(This article belongs to the Special Issue Advances in Oligosaccharides and Polysaccharide Modifications in Marine Bioresources)

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18 pages, 2839 KiB

Open AccessArticle

Stimulating the Hematopoietic Effect of Simulated Digestive Product of Fucoidan from Sargassum fusiforme on Cyclophosphamide-Induced Hematopoietic Damage in Mice and Its Protective Mechanisms Based on Serum Lipidomics

by Wei-Ping Ma, Shi-Ning Yin, Jia-Peng Chen, Xi-Cheng Geng, Ming-Fei Liu, Hai-Hua Li, Ming Liu and Hong-Bing Liu

Mar. Drugs 2022, 20(3), 201; https://doi.org/10.3390/md20030201 - 09 Mar 2022

Cited by 6 | Viewed by 2539

Abstract

Hematopoietic damage is a serious side effect of cytotoxic drugs, and agents promoting hematopoiesis are quite important for decreasing the death rate in cancer patients. In our previous work, we prepared the simulated digestive product of fucoidan from Sargassum fusiforme, DSFF, and [...] Read more.

Hematopoietic damage is a serious side effect of cytotoxic drugs, and agents promoting hematopoiesis are quite important for decreasing the death rate in cancer patients. In our previous work, we prepared the simulated digestive product of fucoidan from Sargassum fusiforme, DSFF, and found that DSFF could activate macrophages. However, more investigations are needed to further evaluate whether DSFF could promote hematopoiesis in the chemotherapy process. In this study, the protective effect of DSFF (1.8–7.2 mg/kg, i.p.) on cyclophosphamide-induced hematopoietic damage in mice and the underlying mechanisms were investigated. Our results show that DSFF could restore the numbers of white blood cells, neutrophils, and platelets in the peripheral blood, and could also retard bone marrow cell decrease in mice with cyclophosphamide-induced hematopoietic damage. UPLC/Q-Extraction Orbitrap/MS/MS-based lipidomics results reveal 16 potential lipid biomarkers in a serum that responded to hematopoietic damage in mice. Among them, PC (20:1/14:0) and SM (18:0/22:0) were the key lipid molecules through which DSFF exerted protective actions. In a validation experiment, DSFF (6.25–100 μg/mL) could also promote K562 cell proliferation and differentiation in vitro. The current findings indicated that DSFF could affect the blood cells and bone marrow cells in vivo and thus showed good potential and application value in alleviating the hematopoietic damage caused by cyclophosphamide. Full article

(This article belongs to the Collection Marine Polysaccharides)

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18 pages, 4780 KiB

Open AccessArticle

Inflammation Regulation via an Agonist and Antagonists of α7 Nicotinic Acetylcholine Receptors in RAW264.7 Macrophages

by Yao Tan, Zhaoli Chu, Hongyu Shan, Dongting Zhangsun, Xiaopeng Zhu and Sulan Luo

Mar. Drugs 2022, 20(3), 200; https://doi.org/10.3390/md20030200 - 09 Mar 2022

Cited by 5 | Viewed by 3268

Abstract

The α7 nicotinic acetylcholine receptor (nAChR) is widely distributed in the central and peripheral nervous systems and is closely related to a variety of nervous system diseases and inflammatory responses. The α7 nAChR subtype plays a vital role in the cholinergic anti-inflammatory pathway. [...] Read more.

The α7 nicotinic acetylcholine receptor (nAChR) is widely distributed in the central and peripheral nervous systems and is closely related to a variety of nervous system diseases and inflammatory responses. The α7 nAChR subtype plays a vital role in the cholinergic anti-inflammatory pathway. In vivo, ACh released from nerve endings stimulates α7 nAChR on macrophages to regulate the NF-κB and JAK2/STAT3 signaling pathways, thereby inhibiting the production and release of downstream proinflammatory cytokines and chemokines. Despite a considerable level of recent research on α7 nAChR-mediated immune responses, much is still unknown. In this study, we used an agonist (PNU282987) and antagonists (MLA and α-conotoxin [A10L]PnIA) of α7 nAChR as pharmacological tools to identify the molecular mechanism of the α7 nAChR-mediated cholinergic anti-inflammatory pathway in RAW264.7 mouse macrophages. The results of quantitative PCR, ELISAs, and transcriptome analysis were combined to clarify the function of α7 nAChR regulation in the inflammatory response. Our findings indicate that the agonist PNU282987 significantly reduced the expression of the IL-6 gene and protein in inflammatory macrophages to attenuate the inflammatory response, but the antagonists MLA and α-conotoxin [A10L]PnIA had the opposite effects. Neither the agonist nor antagonists of α7 nAChR changed the expression level of the α7 nAChR subunit gene; they only regulated receptor function. This study provides a reference and scientific basis for the discovery of novel α7 nAChR agonists and their anti-inflammatory applications in the future. Full article

(This article belongs to the Special Issue Conotoxins II)

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25 pages, 1367 KiB

Open AccessReview

Emerging Marine Biotoxins in European Waters: Potential Risks and Analytical Challenges

by Paz Otero and Marisa Silva

Mar. Drugs 2022, 20(3), 199; https://doi.org/10.3390/md20030199 - 08 Mar 2022

Cited by 15 | Viewed by 3839

Abstract

Harmful algal blooms pose a challenge regarding food safety due to their erratic nature and forming circumstances which are yet to be disclosed. The best strategy to protect human consumers is through legislation and monitoring strategies. Global warming and anthropological intervention aided the [...] Read more.

Harmful algal blooms pose a challenge regarding food safety due to their erratic nature and forming circumstances which are yet to be disclosed. The best strategy to protect human consumers is through legislation and monitoring strategies. Global warming and anthropological intervention aided the migration and establishment of emerging toxin producers into Europe’s temperate waters, creating a new threat to human public health. The lack of information, standards, and reference materials delay effective solutions, being a matter of urgent resolution. In this work, the recent findings of the presence of emerging azaspiracids, spirolildes, pinnatoxins, gymnodimines, palitoxins, ciguatoxins, brevetoxins, and tetrodotoxins on European Coasts are addressed. The information concerning emerging toxins such as new matrices, locations, and toxicity assays is paramount to set the risk assessment guidelines, regulatory levels, and analytical methodology that would protect the consumers. Full article

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56 pages, 18737 KiB

Open AccessReview

Current Trends and New Challenges in Marine Phycotoxins

by Maria Carmen Louzao, Natalia Vilariño, Carmen Vale, Celia Costas, Alejandro Cao, Sandra Raposo-Garcia, Mercedes R. Vieytes and Luis M. Botana

Mar. Drugs 2022, 20(3), 198; https://doi.org/10.3390/md20030198 - 08 Mar 2022

Cited by 19 | Viewed by 4354

Abstract

Marine phycotoxins are a multiplicity of bioactive compounds which are produced by microalgae and bioaccumulate in the marine food web. Phycotoxins affect the ecosystem, pose a threat to human health, and have important economic effects on aquaculture and tourism worldwide. However, human health [...] Read more.

Marine phycotoxins are a multiplicity of bioactive compounds which are produced by microalgae and bioaccumulate in the marine food web. Phycotoxins affect the ecosystem, pose a threat to human health, and have important economic effects on aquaculture and tourism worldwide. However, human health and food safety have been the primary concerns when considering the impacts of phycotoxins. Phycotoxins toxicity information, often used to set regulatory limits for these toxins in shellfish, lacks traceability of toxicity values highlighting the need for predefined toxicological criteria. Toxicity data together with adequate detection methods for monitoring procedures are crucial to protect human health. However, despite technological advances, there are still methodological uncertainties and high demand for universal phycotoxin detectors. This review focuses on these topics, including uncertainties of climate change, providing an overview of the current information as well as future perspectives. Full article

(This article belongs to the Special Issue Marine Phycotoxins)

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16 pages, 3486 KiB

Open AccessArticle

In Vitro and In Vivo Dendritic Cell Immune Stimulation Effect of Low Molecular Weight Fucoidan from New Zealand Undaria pinnatifida

by Litong Liu, Xu Yang, Pengfei Yuan, Shanshan Cai, Jing Bao, Yanan Zhao, Alimu Aimaier, Adila Aipire, Jun Lu and Jinyao Li

Mar. Drugs 2022, 20(3), 197; https://doi.org/10.3390/md20030197 - 08 Mar 2022

Cited by 9 | Viewed by 3071

Abstract

Low molecular weight fucoidan (LMWF) has been reported to have immunomodulation effects through the increase of the activation and function of macrophages. In this study, the regulating effect of LMWF from Undaria pinnatifida grown in New Zealand on dendritic cells (DCs) was investigated. [...] Read more.

Low molecular weight fucoidan (LMWF) has been reported to have immunomodulation effects through the increase of the activation and function of macrophages. In this study, the regulating effect of LMWF from Undaria pinnatifida grown in New Zealand on dendritic cells (DCs) was investigated. We discovered that LMWF could stimulate DCs’ maturation and migration, as well as CD4+ and CD8+ T cells’ proliferation in vitro. We proved that this immune promoting activity is activated through TLR4 and its downstream MAPK and NF–κB signaling pathways. Further in vivo (mouse model) investigation showed that LMWF has a strong immunological boosting effect, such as facilitating the proliferation of immune cells and increasing the index of immune organs. These findings suggest that LMWF has a positive immunomodulatory effect and is a promising candidate to supplement cancer immunotherapy. Full article

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11 pages, 1378 KiB

Open AccessArticle

Australindolones, New Aminopyrimidine Substituted Indolone Alkaloids from an Antarctic Tunicate Synoicum sp.

by Sofia Kokkaliari, Kim Pham, Nargess Shahbazi, Laurent Calcul, Lukasz Wojtas, Nerida G. Wilson, Alexander D. Crawford and Bill J. Baker

Mar. Drugs 2022, 20(3), 196; https://doi.org/10.3390/md20030196 - 08 Mar 2022

Cited by 5 | Viewed by 2440

Abstract

Five new alkaloids have been isolated from the lipophilic extract of the Antarctic tunicate Synoicum sp. Deep-sea specimens of Synoicum sp. were collected during a 2011 cruise of the R/V Nathanial B. Palmer to the southern Scotia Arc, Antarctica. Crude extracts from the [...] Read more.

Five new alkaloids have been isolated from the lipophilic extract of the Antarctic tunicate Synoicum sp. Deep-sea specimens of Synoicum sp. were collected during a 2011 cruise of the R/V Nathanial B. Palmer to the southern Scotia Arc, Antarctica. Crude extracts from the invertebrates obtained during the cruise were screened in a zebrafish-based phenotypic assay. The Synoicum sp. extract induced embryonic dysmorphology characterized by axis truncation, leading to the isolation of aminopyrimidine substituted indolone (1–4) and indole (5–12) alkaloids. While the primary bioactivity tracked with previously reported meridianins A–G (5–11), further investigation resulted in the isolation and characterization of australindolones A–D (1–4) and the previously unreported meridianin H (12). Full article

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15 pages, 1488 KiB

Open AccessArticle

Rare β-Resorcylic Acid Derivatives from a Halophyte-Associated Fungus Colletotrichum gloeosporioides JS0419 and Their Antifungal Activities

by Sunghee Bang, Jaekyeong Kim, Jiwon Oh, Ji-Seok Kim, Seong-Ryong Yu, Stephen Deyrup, Yong-Sun Bahn and Sang Hee Shim

Mar. Drugs 2022, 20(3), 195; https://doi.org/10.3390/md20030195 - 07 Mar 2022

Cited by 6 | Viewed by 2587

Abstract

Six new β-resorcylic acid derivatives (1–5 and 7) were isolated from a halophyte-associated fungus, Colletotrichum gloeosporioides JS0419, together with four previously reported β-resorcylic acid lactones (RALs). The relative and absolute stereochemistry of 1 was completely established by a combination [...] Read more.

Six new β-resorcylic acid derivatives (1–5 and 7) were isolated from a halophyte-associated fungus, Colletotrichum gloeosporioides JS0419, together with four previously reported β-resorcylic acid lactones (RALs). The relative and absolute stereochemistry of 1 was completely established by a combination of spectroscopic data and chemical reactions. The structures of the isolated compounds were elucidated by analysis of HRMS and NMR data. Notably, compounds 1–3 had a β-resorcylic acid harboring a long unesterified aliphatic side chain, whereas the long aliphatic chains were esterified to form macrolactones in 4–9. Among the isolated compounds, monocillin I and radicicol showed potent antifungal activities against Cryptococcus neoformans, comparable to clinically available antifungal agents and radicicol showed weak antifungal activity against Candida albicans. These findings provide insight into the chemical diversity of fungal RAL-type compounds and their pharmacological potential. Full article

(This article belongs to the Topic Advances in Natural Products from Plants and Associated Microbes)

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13 pages, 4162 KiB

Open AccessArticle

Developing a Chromochloris zofingiensis Mutant for Enhanced Production of Lutein under CO₂ Aeration

by Yuanyuan Ren, Jinquan Deng, Yan Lin, Junchao Huang and Feng Chen

Mar. Drugs 2022, 20(3), 194; https://doi.org/10.3390/md20030194 - 07 Mar 2022

Cited by 4 | Viewed by 2377

Abstract

Microalgae are competitive and commercial sources for health-benefit carotenoids. In this study, a Chromochloris zofingiensis mutant (Cz-pkg), which does not shut off its photosystem and stays green upon glucose treatment, was generated and characterized. Cz-pkg was developed by treating the algal [...] Read more.

Microalgae are competitive and commercial sources for health-benefit carotenoids. In this study, a Chromochloris zofingiensis mutant (Cz-pkg), which does not shut off its photosystem and stays green upon glucose treatment, was generated and characterized. Cz-pkg was developed by treating the algal cells with a chemical mutagen as N-methyl-N’-nitro-N-nitrosoguanidine and followed by a color-based colony screening approach. Cz-pkg was found to contain a dysfunctional cGMP-dependent protein kinase (PKG). By cultivated with CO₂ aeration under mixotrophy, the mutant accumulated lutein up to 31.93 ± 1.91 mg L⁻¹ with a productivity of 10.57 ± 0.73 mg L⁻¹ day⁻¹, which were about 2.5- and 8.5-fold of its mother strain. Besides, the lutein content of Cz-pkg could reach 7.73 ± 0.52 mg g⁻¹ of dry weight, which is much higher than that of marigold flower, the most common commercial source of lutein. Transcriptomic analysis revealed that in the mutant Cz-pkg, most of the genes involved in the biosynthesis of lutein and chlorophylls were not down-regulated upon glucose addition, suggesting that PKG may regulate the metabolisms of photosynthetic pigments. This study demonstrated that Cz-pkg could serve as a promising strain for both lutein production and glucose sensing study. Full article

(This article belongs to the Special Issue Biotechnology Applications of Microalgae)

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19 pages, 2528 KiB

Open AccessArticle

The Biochemical Composition and Antioxidant Properties of Fucus vesiculosus from the Arctic Region

by Ekaterina D. Obluchinskaya, Olga N. Pozharitskaya, Denis V. Zakharov, Elena V. Flisyuk, Inna I. Terninko, Yulia E. Generalova, Irina E. Smekhova and Alexander N. Shikov

Mar. Drugs 2022, 20(3), 193; https://doi.org/10.3390/md20030193 - 06 Mar 2022

Cited by 32 | Viewed by 3922

Abstract

Fucus vesiculosus is one of the most prominent brown algae in the shallow waters of the seas of the Arctic region (Barents (BS), White (WS), Norwegian (NS), and Irminger (IS)). The aim of this study was to determine the biochemical composition of F. [...] Read more.

Fucus vesiculosus is one of the most prominent brown algae in the shallow waters of the seas of the Arctic region (Barents (BS), White (WS), Norwegian (NS), and Irminger (IS)). The aim of this study was to determine the biochemical composition of F. vesiculosus from the Arctic at different reproductive phases, and to evaluate the antioxidant properties of F. vesiculosus extracts. The amounts of monosaccharides, phlorotannins, flavonoids, and ash and the mineral composition significantly varied in the algae. A strong correlation was established between monosaccharide, phlorotannin, and flavonoid accumulation and water salinity (Pearson’s correlation coefficients r = −0.58, 0.83, and 0.44, respectively; p < 0.05). We noted a negative correlation between the antioxidant activity and the amount of the structural monosaccharides of fucoidan (r = −0.64). A positive correlation of phlorotannins and flavonoids with antioxidant power was confirmed for all samples. The ash accumulation was relatively lower in the sterile phase for the algae from the BS and WS. The correlation between the Metal Pollution Index (MPI) and the reproductive phases was medium with high fluctuation. Meanwhile, the MPI strongly correlated with the salinity and sampling site. The gradient of the MPI values across the sea was in the following ranking order: BS < WS < NS < IS. Taken together, and based on our data on the elemental contents of F. vesiculosus, we believe that this alga does not accumulate toxic doses of elements. Therefore, the Arctic F. vesiculosus could be safely used in food and drug development as a source of active biochemical compounds and as a source of dietary elements to cover the daily nutritional requirements of humans. Full article

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16 pages, 38481 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Discovery of Marine Natural Products as Promising Antibiotics against Pseudomonas aeruginosa

by Haoran Li, Mireguli Maimaitiming, Yue Zhou, Huaxuan Li, Pingyuan Wang, Yang Liu, Till F. Schäberle, Zhiqing Liu and Chang-Yun Wang

Mar. Drugs 2022, 20(3), 192; https://doi.org/10.3390/md20030192 - 04 Mar 2022

Cited by 8 | Viewed by 5108

Abstract

Pseudomonas aeruginosa, one of the most intractable Gram-negative bacteria, has become a public health threat due to its outer polysaccharide layer, efflux transporter system, and high level of biofilm formation, all of which contribute to multi-drug resistance. Even though it is a [...] Read more.

Pseudomonas aeruginosa, one of the most intractable Gram-negative bacteria, has become a public health threat due to its outer polysaccharide layer, efflux transporter system, and high level of biofilm formation, all of which contribute to multi-drug resistance. Even though it is a pathogen of the highest concern, the status of the antibiotic development pipeline is unsatisfactory. In this review, we summarize marine natural products (MNPs) isolated from marine plants, animals, and microorganisms which possess unique structures and promising antibiotic activities against P. aeruginosa. In the last decade, nearly 80 such MNPs, ranging from polyketides to alkaloids, peptides, and terpenoids, have been discovered. Representative compounds exhibited impressive in vitro anti-P. aeruginosa activities with MIC values in the single-digit nanomolar range and in vivo efficacy in infectious mouse models. For some of the compounds, the preliminary structure-activity-relationship (SAR) and anti-bacterial mechanisms of selected compounds were introduced. Compounds that can disrupt biofilm formation or membrane integrity displayed potent inhibition of multi-resistant clinical P. aeruginosa isolates and could be considered as lead compounds for future development. Challenges on how to translate hits into useful candidates for clinical development are also proposed and discussed. Full article

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15 pages, 2776 KiB

Open AccessArticle

Novel Prenylated Indole Alkaloids with Neuroprotection on SH-SY5Y Cells against Oxidative Stress Targeting Keap1–Nrf2

by Xueyang Xiao, Zhou Tong, Yuexing Zhang, Hui Zhou, Mengying Luo, Tianhui Hu, Ping Hu, Luqi Kong, Zeqin Liu, Chan Yu, Zhiyong Huang and Linzhen Hu

Mar. Drugs 2022, 20(3), 191; https://doi.org/10.3390/md20030191 - 04 Mar 2022

Cited by 8 | Viewed by 3028

Abstract

Oxidative stress has been implicated in the etiology of Parkinson’s disease (PD). Molecules non-covalently binding to the Keap1–Nrf2 complex could be a promising therapeutic approach for PD. Herein, two novel prenylated indole alkaloids asperpenazine (1), and asperpendoline (2) with [...] Read more.

Oxidative stress has been implicated in the etiology of Parkinson’s disease (PD). Molecules non-covalently binding to the Keap1–Nrf2 complex could be a promising therapeutic approach for PD. Herein, two novel prenylated indole alkaloids asperpenazine (1), and asperpendoline (2) with a scarce skeleton of pyrimido[1,6-a]indole were discovered from the co-cultivated fungi of Aspergillus ochraceus MCCC 3A00521 and Penicillium sp. HUBU 0120. Compound 2 exhibited potential neuroprotective activity on SH-SY5Y cells against oxidative stress. Molecular mechanism research demonstrated that 2 inhibited Keap1 expression, resulting in the translocation of Nrf2 from the cytoplasm to the nucleus, activating the downstream genes expression of HO-1 and NQO1, leading to the reduction in reactive oxygen species (ROS) and the augment of glutathione. Molecular docking and dynamic simulation analyses manifested that 2 interacted with Keap1 (PDB ID: 1X2R) via forming typical hydrogen and hydrophobic bonds with residues and presented less fluctuation of RMSD and RMSF during a natural physiological condition. Full article

(This article belongs to the Special Issue Neuroprotective Effects of Marine Natural Products 2022)

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20 pages, 1675 KiB

Open AccessArticle

Good Practices in Sponge Natural Product Studies: Revising Vouchers with Isomalabaricane Triterpenes

by Paco Cárdenas, Jayani Gamage, Chamari M. Hettiarachchi and Sunithi Gunasekera

Mar. Drugs 2022, 20(3), 190; https://doi.org/10.3390/md20030190 - 04 Mar 2022

Cited by 6 | Viewed by 3753

Abstract

Species misidentification in the field of natural products is an acknowledged problem. These errors are especially widespread in sponge studies, albeit rarely assessed and documented. As a case study, we aim to revisit reports of isomalabaricane triterpenes, isolated from four demosponge genera: Jaspis [...] Read more.

Species misidentification in the field of natural products is an acknowledged problem. These errors are especially widespread in sponge studies, albeit rarely assessed and documented. As a case study, we aim to revisit reports of isomalabaricane triterpenes, isolated from four demosponge genera: Jaspis, Geodia, Stelletta and Rhabdastrella. From a total of 44 articles (1981–2022), 27 unique vouchers were listed, 21 of which were accessed and re-examined here: 11 (52.4%) of these were misidentified. Overall, 65.9% of the studies published an incorrect species name: previously identified Jaspis and Stelletta species were all in fact Rhabdastrella globostellata. We conclude that isomalabaricane triterpenes were isolated from only two Rhabdastrella species and possibly one Geodia species. In addition to shedding a new light on the distribution of isomalabaricane triterpenes, this study is an opportunity to highlight the crucial importance of vouchers in natural product studies. Doing so, we discuss the impact of species misidentification and poor accessibility of vouchers in the field of sponge natural products. We advocate for stricter voucher guidelines in natural product journals and propose a common protocol of good practice, in the hope of reducing misidentifications in sponge studies, ensure reproducibility of studies, and facilitate follow-up work on the original material. Full article

(This article belongs to the Special Issue Marine Sponge Biotechnology)

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14 pages, 1798 KiB

Open AccessArticle

Rapid Mining of Novel α-Glucosidase and Lipase Inhibitors from Streptomyces sp. HO1518 Using UPLC-QTOF-MS/MS

by Jianlin Xu, Zhifeng Liu, Zhanguang Feng, Yuhong Ren, Haili Liu and Yong Wang

Mar. Drugs 2022, 20(3), 189; https://doi.org/10.3390/md20030189 - 04 Mar 2022

Cited by 2 | Viewed by 2383

Abstract

A rapid and sensitive method using ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) was applied for the analysis of the metabolic profile of acarviostatin-containing aminooligosaccharides derived from Streptomyces sp. HO1518. A total of ninety-eight aminooligosaccharides, including eighty potential new compounds, were detected [...] Read more.

A rapid and sensitive method using ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) was applied for the analysis of the metabolic profile of acarviostatin-containing aminooligosaccharides derived from Streptomyces sp. HO1518. A total of ninety-eight aminooligosaccharides, including eighty potential new compounds, were detected mainly based on the characteristic fragment ions originating from quinovosidic bond cleavages in their molecules. Following an LC-MS-guided separation technique, seven new aminooligosaccharides (10–16) along with four known related compounds (17–20) were obtained directly from the crude extract of strain HO1518. Compounds 10–13 represent the first examples of aminooligosaccharides with a rare acarviostatin II02-type structure. In addition, all isolates displayed considerable inhibitory effects on three digestive enzymes, which revealed that the number of the pseudo-trisaccharide core(s), the feasible length of the oligosaccharides, and acyl side chain exerted a crucial influence on their bioactivities. These results demonstrated that the UPLC-QTOF-MS/MS-based metabolomics approach could be applied for the rapid identification of aminooligosaccharides and other similar structures in complex samples. Furthermore, this study highlights the potential of acylated aminooligosaccharides with conspicuous α-glucosidase and lipase inhibition for the future development of multi-target anti-diabetic drugs. Full article

(This article belongs to the Special Issue Enzyme Inhibitors from Marine Resources)

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Mar. Drugs, Volume 20, Issue 3 (March 2022) – 63 articles

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