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Marine Anti-Inflammatory and Antioxidant Agents, 4th Edition

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A special issue of Marine Drugs (ISSN 1660-3397). This special issue belongs to the section "Marine Pharmacology".

Deadline for manuscript submissions: 30 April 2025 | Viewed by 10788

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Prof. Dr. Donatella Degl'Innocenti

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Guest Editor

Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy
Interests: bioactive natural products; inflammation; oxidative stress; polyphenols; cell migration; autophagy
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Dr. Marzia Vasarri

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Guest Editor

Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence, Italy
Interests: bioactive natural products; inflammation; oxidative stress; polyphenols; cell migration; autophagy
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Special Issue Information

Dear Colleagues,

Inflammation is a physiological reaction triggered by various factors, such as pathogens or injuries. Environmental factors, including food choices, can also lead to so-called "lifestyle diseases", in which chronic inflammation is a key factor.

Cardiovascular diseases, cancer, diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease, neurodegenerative diseases, autoimmune diseases, and others are classified as inflammation-related diseases. The process of chronic inflammation often creates the ideal conditions for triggering a state of oxidative stress, and vice versa. Oxidative stress is caused by an imbalance between the production of oxidants and antioxidant defenses. An excessive production of reactive oxygen species (ROS) and nitrogen species (RNS) or the stimulation of pro-inflammatory agents (including toxic or pathogenic substances) triggers inflammation.

The uncontrolled increase in chronic inflammatory diseases in the last decade has led to an increasingly urgent search for natural compounds with dual antioxidant and anti-inflammatory activity in an attempt to develop new, safe, and effective agents as alternatives to conventional drugs. In this regard, marine organisms and their metabolites are at the center of international research aimed toward the discovery of new and biologically active products as the foundation of the future bioeconomy and, above all, promising drugs. Among marine organisms, marine algae, sea cucumbers, fish, marine invertebrates (such as sponges and marine soft corals), crustaceans, and microorganisms (microalgae, fungi, archaea, protozoa, and yeasts) are known producers of natural antioxidants.

Given the widespread and current interest in this topic, we decided to propose Version 4.0 of this Special Issue to continue to collect the most innovative findings regarding antioxidant and anti-inflammatory products from the sea.

This Special Issue aims to provide an overview of the latest experimental in vitro and/or in vivo research highlighting the role of bioactive compounds of marine origin as modulators of inflammation and/or oxidative stress. Articles describing the mechanisms of action and molecular interactions of compounds isolated from marine organisms are particularly encouraged. Papers on individual molecules, as well as crude extracts of marine organisms, will be evaluated. In addition, comprehensive review articles summarizing the literature on marine anti-inflammatory and/or antioxidant agents in support of human health will also be considered.

Prof. Dr. Donatella Degl'Innocenti
Dr. Marzia Vasarri
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Marine Drugs is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

marine organisms
inflammation
cytokines
antioxidant agents
anti-inflammatory gents
oxidative stress
ROS/RNS
NF-κB
mitochondrial oxidative
drug delivery

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Published Papers (8 papers)

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Research

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13 pages, 1677 KiB

Open AccessArticle

Pilot-Scale Enzymatic Conversion of Low Stability, High Free Fatty, Squid Oil to an Oxidatively Stable Astaxanthin-Rich Acylglyceride Oil Suitable for Nutritional Applications

by Asavari Joshi, Brendan Holland, Moninder Sachar and Colin J. Barrow

Mar. Drugs 2025, 23(1), 21; https://doi.org/10.3390/md23010021 - 2 Jan 2025

Viewed by 580

Abstract

Squid viscera, a byproduct of squid processing, contains oil rich in omega-3 fatty acids (up to 10% by mass) and the antioxidant astaxanthin. However, its high free fatty acid (FFA) content compromises stability. To address this, pilot-scale (200 L) enzymatic re-esterification of squid oil using immobilized lipase (Lipozyme RMIM) was demonstrated, resulting in high acylglyceride yields. The processed oil was analyzed for oxidation kinetics and thermodynamics using Rancimat, fatty acid composition using GC, omega-3 fatty acid positional distribution in the acylglyceride product using ¹³C NMR, and astaxanthin content. Lipase treatment reduced FFA levels from 44% to 4% and increased acylglycerides to 93% in squid oil. This reduction in FFA was accompanied by significantly increased stability (0.06 to 18.9 h by Rancimat). The treated oil showed no loss in astaxanthin (194.1 µg/g) or omega-3 fatty acids, including docosahexaenoic acid (DHA). DHA remaining predominantly at sn-2 indicated that the naturally occurring positional distribution of this omega-3 FFA was retained in the product. Lipase treatment significantly enhanced oxidative stability, evidenced by improved thermodynamic parameters (E_a 94.15 kJ/mol, ΔH 91.09 kJ/mol, ΔS −12.6 J/mol K) and extended shelf life (IP₂₅ 74.42 days) compared to starting squid oil and commercial fish/squid oils lacking astaxanthin. Thus, lipase treatment offers an effective strategy for reducing FFA levels and producing oxidatively stable, astaxanthin-rich acylglyceride squid oil with DHA retained at the nutritionally favored sn-2 position. Full article

(This article belongs to the Special Issue Marine Anti-Inflammatory and Antioxidant Agents, 4th Edition)

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22 pages, 3596 KiB

Open AccessArticle

Chondroitin Sulfate Nanovectorized by LC-PUFAs Nanocarriers Extracted from Salmon (Salmo salar) by Green Process with Decreased Inflammatory Marker Expression in Interleukin-1β-Stimulated Primary Human Chondrocytes In Vitro Culture

by Louis Pruvost, Maureen Gerlei, Cédric Paris, Émilie Velot, Cyril J.-F. Kahn, Arnaud Bianchi and Michel Linder

Mar. Drugs 2024, 22(12), 571; https://doi.org/10.3390/md22120571 - 20 Dec 2024

Viewed by 786

Abstract

Chondroitin sulfate (CS), a glycosaminoglycan, supports health through various physiological functions, including tissue protection, bone growth, and skin aging prevention. It also contributes to anticoagulant or anti-inflammatory processes, with its primary clinical use being osteoarthritis treatment. This study presents the results of the valorization of lipids and CS, both extracted from salmon co-products through enzymatic processes. The polar lipids, naturally rich in long-chain fatty acids (docosahexaenoic acid DHA C22:6 n-3 and eicosapentaenoic acid EPA C20:5 n-3), and the CS, primarily located in the nasal cartilage, were separated and concentrated before being characterized using various techniques to determine functional and lipid composition. These compounds were then used to formulate liposomes of 63 to 95 nm in size composed of 19.38% of DHA and 7.44% of EPA and encapsulating CS extract with a Δdi-4S/Δdi-6S ratio of 0.53 at 2 weight masses (10–30 kDa and >30 kDa) or CS standard all at two different concentrations. Liposomes were tested on human chondrocytes in inflamed conditions. Thus, compatibility tests, the expression of various inflammation markers at transcriptional and molecular levels, nitrites, and the amount of collagenase produced were analyzed. The results showed that CS, in synergy with the liposomes, played a positive role in combating chondrocyte inflammation even at a low concentration. Full article

(This article belongs to the Special Issue Marine Anti-Inflammatory and Antioxidant Agents, 4th Edition)

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20 pages, 8399 KiB

Open AccessArticle

Butyrolactone-I from Marine Fungal Metabolites Mitigates Heat-Stress-Induced Apoptosis in IPEC-J2 Cells and Mice Through the ROS/PERK/CHOP Signaling Pathway

by Xueting Niu, Shengwei Chen, Xinchen Wang, Jiaying Wen, Xiaoxi Liu, Yanhong Yong, Zhichao Yu, Xingbing Ma, A. M. Abd El-Aty and Xianghong Ju

Mar. Drugs 2024, 22(12), 564; https://doi.org/10.3390/md22120564 - 17 Dec 2024

Viewed by 761

Abstract

Heat stress poses a significant challenge to animal husbandry, contributing to oxidative stress, intestinal mucosal injury, and apoptosis, which severely impact animal health, growth, and production efficiency. The development of safe, sustainable, and naturally derived solutions to mitigate these effects is critical for advancing sustainable agricultural practices. Butyrolactone-I (BTL-I), a bioactive compound derived from deep-sea fungi (Aspergillus), shows promise as a functional feed additive to combat heat stress in animals. This study explored the protective effects of BTL-I against heat-stress-induced oxidative stress and apoptosis in IPEC-J2 cells and mice. Our findings demonstrated that BTL-I effectively inhibited the heat-stress-induced upregulation of HSP70 and HSP90, alleviating intestinal heat stress. Both in vitro and in vivo experiments revealed that heat stress increased intestinal cell apoptosis, with a significant upregulation of Bax/Bcl-2 expression, while BTL-I pretreatment significantly reduced apoptosis-related protein levels, showcasing its protective effects. Furthermore, BTL-I suppressed oxidative stress markers (ROS and MDA) while enhancing antioxidant activity (SOD levels). BTL-I also reduced the expression of p-PERK, p-eIF2α, ATF4, and CHOP, mitigating oxidative and endoplasmic reticulum stress in intestinal cells. In conclusion, BTL-I demonstrates the potential to improve animal resilience to heat stress, supporting sustainable livestock production systems. Its application as a natural, eco-friendly feed additive will contribute to the development of sustainable agricultural practices. Full article

(This article belongs to the Special Issue Marine Anti-Inflammatory and Antioxidant Agents, 4th Edition)

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14 pages, 1782 KiB

Open AccessArticle

Alginate from Ericaria crinita Possesses Antioxidant Activity and Attenuates Systemic Inflammation via Downregulation of Pro-Inflammatory Cytokines

by Paolina Lukova, Vesela Kokova, Alexandra Baldzhieva, Marianna Murdjeva, Plamen Katsarov, Cédric Delattre and Elisaveta Apostolova

Mar. Drugs 2024, 22(11), 482; https://doi.org/10.3390/md22110482 - 25 Oct 2024

Viewed by 1100

Abstract

Alginates are anionic polysaccharides present in the cell walls of brown seaweeds. Various biological activities of alginate and its derivatives have been described. In this study, we assessed the potential of alginate obtained from Ericaria crinita (formerly Cystoseira crinita) to scavenge free radicals and function as a ferric ion reductor. The anti-inflammatory effect on the serum levels of TNF-α, IL-1β, IL-6, and IL-10 of rats with LPS-induced systemic inflammation after 14 days of treatment was also examined. Ericaria crinita alginate showed antioxidant activities of IC₅₀ = 505 µg/mL (DPPH) and OD₇₀₀ > 2 (ferric reducing power). A significant decrease in serum levels of IL-1β was observed only in animals treated with the polysaccharide at a dose of 100 mg/kg bw. Both doses of E. crinita alginate (25 and 100 mg/kg bw) significantly reduced the serum concentrations of pro-inflammatory cytokines TNF-α and IL-6, but no statistical significance was observed in the levels of the anti-inflammatory cytokine IL-10. Our findings show the potential of E. crinita alginate to act as an antioxidant and anti-inflammatory agent. It is likely that the exhibited antioxidant ability of the polysaccharide contributes to its antiphlogistic effects. More in-depth studies are needed to fully understand the specific mechanisms and the molecular pathways involved in these activities. Full article

(This article belongs to the Special Issue Marine Anti-Inflammatory and Antioxidant Agents, 4th Edition)

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12 pages, 5458 KiB

Open AccessArticle

Anti-Photoaging Effects of Antioxidant Peptide from Seahorse (Hippocampus abdominalis) in In Vivo and In Vitro Models

by Fengqi Yang, Yang Yang, Dandan Xiao, Poongho Kim, Jihee Lee, You-Jin Jeon and Lei Wang

Mar. Drugs 2024, 22(10), 471; https://doi.org/10.3390/md22100471 - 14 Oct 2024

Viewed by 1817

Abstract

Overexposure to ultraviolet (UV) radiation can lead to photoaging, which contributes to skin damage. The objective of this study was to evaluate the effects of an antioxidant peptide (SHP2) purified from seahorse (Hippocampus abdominalis) alcalase hydrolysate on UVB-irradiated skin damage in human keratinocyte (HaCaT) and human dermal fibroblast (HDF) cells and a zebrafish model. The data revealed that SHP2 significantly enhanced cell viability by attenuating apoptosis through the reduction of intracellular reactive oxygen species (ROS) levels in UVB-stimulated HaCaT cells. Moreover, SHP2 effectively inhibited ROS, improved collagen synthesis, and suppressed the secretion of matrix metalloproteinases (MMPs) in UVB-irradiated HDF cells. SHP2 restored the protein levels of HO-1, Nrf2, and SOD, while decreasing Keap1 expression in UVB-treated HDF, indicating stimulation of the Keap1/Nrf2/HO-1 signaling pathway. Furthermore, an in vivo study conducted in zebrafish confirmed that SHP2 inhibited photoaging by reducing cell death through the suppression of ROS generation and lipid peroxidation. Particularly, 200 µg/mL of SHP2 exerted a remarkable anti-photoaging effect on both in vitro and in vivo models. These results demonstrate that SHP2 possesses antioxidant properties and regulates skin photoaging activities, suggesting that SHP2 may have the potential for use in the development of cosmetic products. Full article

(This article belongs to the Special Issue Marine Anti-Inflammatory and Antioxidant Agents, 4th Edition)

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17 pages, 3897 KiB

Open AccessArticle

Blue Mussel-Derived Bioactive Peptides PIISVYWK (P1) and FSVVPSPK (P2): Promising Agents for Inhibiting Foam Cell Formation and Inflammation in Cardiovascular Diseases

by Chathuri Kaushalya Marasinghe and Jae-Young Je

Mar. Drugs 2024, 22(10), 466; https://doi.org/10.3390/md22100466 - 10 Oct 2024

Cited by 1 | Viewed by 1458

Abstract

Atherosclerosis is a key etiological event in the development of cardiovascular diseases (CVDs), strongly linked to the formation of foam cells. This study explored the effects of two blue mussel-derived bioactive peptides (BAPs), PIISVYWK (P1) and FSVVPSPK (P2), on inhibiting foam cell formation and mitigating inflammation in oxLDL-treated RAW264.7 macrophages. Both peptides significantly suppressed intracellular lipid accumulation and cholesterol levels while promoting cholesterol efflux by downregulating cluster of differentiation 36 (CD36) and class A1 scavenger receptors (SR-A1) and upregulating ATP binding cassette subfamily A member 1 (ABCA-1) and ATP binding cassette subfamily G member 1 (ABCG-1) expressions. The increased expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and liver X receptor-alpha (LXR-α) further validated their role in enhancing cholesterol efflux. Additionally, P1 and P2 inhibited foam cell formation in oxLDL-treated human aortic smooth muscle cells and exerted anti-inflammatory effects by reducing pro-inflammatory cytokines, nitric oxide (NO), prostaglandin E₂ (PGE₂), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), primarily through inhibiting NF-κB activation. Furthermore, P1 and P2 alleviated oxidative stress by activating the Nrf2/HO-1 pathway. Our findings demonstrate that P1 and P2 have significant potential in reducing foam cell formation and inflammation, both critical factors in atherosclerosis development. These peptides may serve as promising therapeutic agents for the prevention and treatment of CVDs associated with oxidative stress and inflammation. Full article

(This article belongs to the Special Issue Marine Anti-Inflammatory and Antioxidant Agents, 4th Edition)

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21 pages, 6595 KiB

Open AccessArticle

Proteomics Analysis of the Protective Effect of Polydeoxyribonucleotide Extracted from Sea Cucumber (Apostichopus japonicus) Sperm in a Hydrogen Peroxide-Induced RAW264.7 Cell Injury Model

by Zhiqiang Shu, Yizhi Ji, Fang Liu, Yuexin Jing, Chunna Jiao, Yue Li, Yunping Zhao, Gongming Wang and Jian Zhang

Mar. Drugs 2024, 22(7), 325; https://doi.org/10.3390/md22070325 - 21 Jul 2024

Cited by 3 | Viewed by 1795

Abstract

Sea cucumber viscera contain various naturally occurring active substances, but they are often underutilized during sea cucumber processing. Polydeoxyribonucleotide (PDRN) is an adenosine A_2A receptor agonist that activates the A_2A receptor to produce various biological effects. Currently, most studies on the activity of PDRN have focused on its anti-inflammatory, anti-apoptotic, and tissue repair properties, yet relatively few studies have investigated its antioxidant activity. In this study, we reported for the first time that PDRN was extracted from the sperm of Apostichopus japonicus (AJS-PDRN), and we evaluated its antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS), and hydroxyl radical scavenging assays. An in vitro injury model was established using H₂O₂-induced oxidative damage in RAW264.7 cells, and we investigated the protective effect of AJS-PDRN on these cells. Additionally, we explored the potential mechanism by which AJS-PDRN protects RAW264.7 cells from damage using iTRAQ proteomics analysis. The results showed that AJS-PDRN possessed excellent antioxidant activity and could significantly scavenge DPPH, ABTS, and hydroxyl radicals. In vitro antioxidant assays demonstrated that AJS-PDRN was cytoprotective and significantly enhanced the antioxidant capacity of RAW264.7 cells. The results of GO enrichment and KEGG pathway analysis indicate that the protective effects of AJS-PDRN pretreatment on RAW264.7 cells are primarily achieved through the regulation of immune and inflammatory responses, modulation of the extracellular matrix and signal transduction pathways, promotion of membrane repair, and enhancement of cellular antioxidant capacity. The results of a protein–protein interaction (PPI) network analysis indicate that AJS-PDRN reduces cellular oxidative damage by upregulating the expression of intracellular selenoprotein family members. In summary, our findings reveal that AJS-PDRN mitigates H₂O₂-induced oxidative damage through multiple pathways, underscoring its significant potential in the prevention and treatment of diseases caused by oxidative stress. Full article

(This article belongs to the Special Issue Marine Anti-Inflammatory and Antioxidant Agents, 4th Edition)

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Review

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27 pages, 7852 KiB

Open AccessReview

Recent Advances in Anti-Inflammatory Compounds from Marine Microorganisms

by Guihua Yang, Miaoping Lin, Kumaravel Kaliaperumal, Yaqi Lu, Xin Qi, Xiaodong Jiang, Xinya Xu, Chenghai Gao, Yonghong Liu and Xiaowei Luo

Mar. Drugs 2024, 22(9), 424; https://doi.org/10.3390/md22090424 - 18 Sep 2024

Cited by 1 | Viewed by 1918

Abstract

Marine microbial secondary metabolites with diversified structures have been found as promising sources of anti-inflammatory lead compounds. This review summarizes the sources, chemical structures, and pharmacological properties of anti-inflammatory natural products reported from marine microorganisms in the past three years (2021–2023). Approximately 252 anti-inflammatory compounds, including 129 new ones, were predominantly obtained from marine fungi and they are structurally divided into polyketides (51.2%), terpenoids (21.0%), alkaloids (18.7%), amides or peptides (4.8%), and steroids (4.3%). This review will shed light on the development of marine microbial secondary metabolites as potential anti-inflammatory lead compounds with promising clinical applications in human health. Full article

(This article belongs to the Special Issue Marine Anti-Inflammatory and Antioxidant Agents, 4th Edition)

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