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Marine Anti-inflammatory and Antioxidant Agents 3.0

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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: closed (31 March 2024) | Viewed by 17111

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Prof. Dr. Donatella Degl'Innocenti

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Dipartimento di Scienze Biomediche, Sperimentali e Cliniche “Mario Serio”, Università degli Studi di Firenze, viale Morgagni 50, 50134 Firenze, Italy
Interests: bioactive natural products; inflammation; oxidative stress; polyphenols; cell migration; autophagy
Special Issues, Collections and Topics in MDPI journals

Dr. Marzia Vasarri

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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
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Several chronic diseases are related to uncontrolled oxidative stress and inflammation. Oxidative stress results from an imbalance between oxidant production and antioxidant defense. Under pathological or stressful conditions, reactive oxygen species (ROS) and nitrogen species (RNS) overload antioxidant systems, leading to an imbalance that in turn causes oxidative stress, with consequential structural damage to nucleic acids, as well as structural changes in cellular proteins and alterations in their functions, and irreversible damage to cellular structures. Excessive production of ROS/RNS or stimulation of pro-inflammatory agents (including toxic or pathogenic substances) triggers inflammation. During the inflammatory process, the activation of intracellular signaling pathways, such as the nuclear factor kappa light-chain-enhancer of activated B cells (NF-κB) signaling pathway, leads to the release of a number of pro-inflammatory mediators (e.g., cytokines and chemokines) and the production of ROS/RNS by recruited inflammatory cells. In recent decades, the use of natural products with anti-inflammatory and antioxidant activities has become increasingly popular in an effort to meet the challenge of developing new, safe, and effective alternative agents to conventional drugs. In this regard, the marine environment is an invaluable source for molecules with potential antioxidant and anti-inflammatory power.

This Special Issue aims to provide an overview of the latest in vitro and/or in vivo experimental research highlighting the role of marine-derived bioactive compounds 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. Work on both single molecules and crude extracts of marine organisms will be evaluated. In addition, comprehensive review articles summarizing knowledge 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

Related Special Issues

Marine Anti-inflammatory Agents 2020 in Marine Drugs (6 articles)
Marine Anti-inflammatory and Antioxidant Agents 2021 in Marine Drugs (11 articles)
Marine Anti-inflammatory and Antioxidant Agents 2.0 in Marine Drugs (11 articles)

Published Papers (10 papers)

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Research

Jump to: Review

15 pages, 3281 KiB

Open AccessArticle

Zeaxanthin epoxidase 3 Knockout Mutants of the Model Diatom Phaeodactylum tricornutum Enable Commercial Production of the Bioactive Carotenoid Diatoxanthin

by Cecilie Græsholt, Tore Brembu, Charlotte Volpe, Zdenka Bartosova, Manuel Serif, Per Winge and Marianne Nymark

Mar. Drugs 2024, 22(4), 185; https://doi.org/10.3390/md22040185 - 19 Apr 2024

Viewed by 519

Abstract

Carotenoids are pigments that have a range of functions in human health. The carotenoid diatoxanthin is suggested to have antioxidant, anti-inflammatory and chemo-preventive properties. Diatoxanthin is only produced by a few groups of microalgae, where it functions in photoprotection. Its large-scale production in microalgae is currently not feasible. In fact, rapid conversion into the inactive pigment diadinoxanthin is triggered when cells are removed from a high-intensity light source, which is the case during large-scale harvesting of microalgae biomass. Zeaxanthin epoxidase (ZEP) 2 and/or ZEP3 have been suggested to be responsible for the back-conversion of high-light accumulated diatoxanthin to diadinoxanthin in low-light in diatoms. Using CRISPR/Cas9 gene editing technology, we knocked out the ZEP2 and ZEP3 genes in the marine diatom Phaeodactylum tricornutum to investigate their role in the diadinoxanthin–diatoxanthin cycle and determine if one of the mutant strains could function as a diatoxanthin production line. Light-shift experiments proved that ZEP3 encodes the enzyme converting diatoxanthin to diadinoxanthin in low light. Loss of ZEP3 caused the high-light-accumulated diatoxanthin to be stable for several hours after the cultures had been returned to low light, suggesting that zep3 mutant strains could be suitable as commercial production lines of diatoxanthin. Full article

(This article belongs to the Special Issue Marine Anti-inflammatory and Antioxidant Agents 3.0)

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16 pages, 2989 KiB

Open AccessArticle

The Role of Sargahydroquinoic Acid and Sargachromenol in the Anti-Inflammatory Effect of Sargassum yezoense

by Yena Park, Lei Cao, Suhyeon Baek, Seungjin Jeong, Hyun Jung Yun, Mi-Bo Kim and Sang Gil Lee

Mar. Drugs 2024, 22(3), 107; https://doi.org/10.3390/md22030107 - 26 Feb 2024

Viewed by 1112

Abstract

The anti-inflammatory effect of the ethanol extract of Sargassum yezoense and its fractions were investigated in this study. The ethanol extract exhibited a strong anti-inflammatory effect on lipopolysaccharide-stimulated RAW 264.7 macrophages and effectively suppressed the M1 polarization of murine bone-marrow-derived macrophages stimulated by lipopolysaccharides and IFN-γ (interferon-gamma). Through a liquid–liquid extraction process, five fractions (n-hexane, chloroform, ethyl acetate, butanol, and aqueous) were acquired. Among these fractions, the chloroform fraction (SYCF) was found to contain the highest concentration of phenolic compounds, along with two primary meroterpenoids, sargahydroquinoic acid (SHQA) and sargachromenol (SCM), and exhibit significant antioxidant capacity. It also demonstrated a robust anti-inflammatory effect. A direct comparison was conducted to assess the relative contribution of SHQA and SCM to the anti-inflammatory properties of SYCF. The concentrations of SHQA and SCM tested were determined based on their relative abundance in SYCF. SHQA contributed to a significant portion of the anti-inflammatory property of SYCF, while SCM played a limited role. These findings not only highlight the potential of the chloroform–ethanol fractionation approach for concentrating meroterpenoids in S. yezoense but also demonstrate that SHQA and other bioactive compounds work additively or synergistically to produce the potent anti-inflammatory effect of SYCF. Full article

(This article belongs to the Special Issue Marine Anti-inflammatory and Antioxidant Agents 3.0)

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20 pages, 4802 KiB

Open AccessArticle

Discovery and Anti-Inflammatory Activity of a Cyanobacterial Fatty Acid Targeting the Keap1/Nrf2 Pathway

by Fatma H. Al-Awadhi, Emily F. Simon, Na Liu, Ranjala Ratnayake, Valerie J. Paul and Hendrik Luesch

Mar. Drugs 2023, 21(11), 553; https://doi.org/10.3390/md21110553 - 25 Oct 2023

Viewed by 2032

Abstract

The monounsaturated fatty acid 7(E)-9-keto-hexadec-7-enoic acid (1) and three structurally related analogues with different oxidation states and degrees of unsaturation (2–4) were discovered from a marine benthic cyanobacterial mat collected from Delta Shoal, Florida Keys. Their structures were elucidated using NMR spectroscopy and mass spectrometry. The structure of 1 contained an α,β-unsaturated carbonyl system, a key motif required for the activation of the Keap1/Nrf2−ARE pathway that is involved in the activation of antioxidant and phase II detoxification enzymes. Compounds 1–4 were screened in ARE-luciferase reporter gene assay using stably transfected HEK293 cells, and only 1 significantly induced Nrf2 activity at 32 and 10 µM, whereas 2–4 were inactive. As there is crosstalk between inflammation and oxidative stress, subsequent biological studies were focused on 1 to investigate its anti-inflammatory potential. Compound 1 induced Nqo1, a well-known target gene of Nrf2, and suppressed iNos transcript levels, which translated into reduced levels of nitric oxide in LPS-activated mouse macrophage RAW264.7 cells, a more relevant model for inflammation. RNA sequencing was performed to capture the effects of 1 on a global level and identified additional canonical pathways and upstream regulators involved in inflammation and immune response, particularly those related to multiple sclerosis. A targeted survey of marine cyanobacterial samples from other geographic locations, including Guam, suggested the widespread occurrence of 1. Furthermore, the previous isolation of 1 from marine diatoms and green algae implied a potentially important ecological role across marine algal eukaryotes and prokaryotes. The previous isolation from sea lettuce raises the possibility of dietary intervention to attenuate inflammation and related disease progression. Full article

(This article belongs to the Special Issue Marine Anti-inflammatory and Antioxidant Agents 3.0)

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14 pages, 1750 KiB

Open AccessArticle

Extraction and Purification of Highly Active Astaxanthin from Corynebacterium glutamicum Fermentation Broth

by Jan Seeger, Volker F. Wendisch and Nadja A. Henke

Mar. Drugs 2023, 21(10), 530; https://doi.org/10.3390/md21100530 - 11 Oct 2023

Cited by 3 | Viewed by 1922

Abstract

The marine carotenoid astaxanthin is one of the strongest natural antioxidants and therefore is used in a broad range of applications such as cosmetics or nutraceuticals. To meet the growing market demand, the natural carotenoid producer Corynebacterium glutamicum has been engineered to produce astaxanthin by heterologous expression of genes from the marine bacterium Fulvimarina pelagi. To exploit this promising source of fermentative and natural astaxanthin, an efficient extraction process using ethanol was established in this study. Appropriate parameters for ethanol extraction were identified by screening ethanol concentration (62.5–97.5% v/v), temperature (30–70 °C) and biomass-to-solvent ratio (3.8–19.0 mg_CDW/mL_solvent). The results demonstrated that the optimal extraction conditions were: 90% ethanol, 60 °C, and a biomass-to-solvent ratio of 5.6 mg_CDW/mL_solvent. In total, 94% of the cellular astaxanthin was recovered and the oleoresin obtained contained 9.4 mg/g astaxanthin. With respect to other carotenoids, further purification of the oleoresin by column chromatography resulted in pure astaxanthin (100%, HPLC). In addition, a 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay showed similar activities compared to esterified astaxanthin from microalgae and a nine-fold higher antioxidative activity than synthetic astaxanthin. Full article

(This article belongs to the Special Issue Marine Anti-inflammatory and Antioxidant Agents 3.0)

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18 pages, 6564 KiB

Open AccessArticle

Mining Xanthine Oxidase Inhibitors from an Edible Seaweed Pterocladiella capillacea by Using In Vitro Bioassays, Affinity Ultrafiltration LC-MS/MS, Metabolomics Tools, and In Silico Prediction

by Yawen Wang, Longjian Zhou, Minqi Chen, Yayue Liu, Yu Yang, Tiantian Lu, Fangfang Ban, Xueqiong Hu, Zhongji Qian, Pengzhi Hong and Yi Zhang

Mar. Drugs 2023, 21(10), 502; https://doi.org/10.3390/md21100502 - 22 Sep 2023

Cited by 2 | Viewed by 1634

Abstract

The prevalence of gout and the adverse effects of current synthetic anti-gout drugs call for new natural and effective xanthine oxidase (XOD) inhibitors to target this disease. Based on our previous finding that an edible seaweed Pterocladiella capillacea extract inhibits XOD, XOD-inhibitory and anti-inflammatory activities were used to evaluate the anti-gout potential of different P. capillacea extract fractions. Through affinity ultrafiltration coupled with liquid chromatography tandem mass spectrometry (LC-MS/MS), feature-based molecular networking (FBMN), and database mining of multiple natural products, the extract’s bioactive components were traced and annotated. Through molecular docking and ADMET analysis, the possibility and drug-likeness of the annotated XOD inhibitors were predicted. The results showed that fractions F4, F6, F4-2, and F4-3 exhibited strong XOD inhibition activity, among which F4-3 reached an inhibition ratio of 77.96% ± 4.91% to XOD at a concentration of 0.14 mg/mL. In addition, the P. capillacea extract and fractions also displayed anti-inflammatory activity. Affinity ultrafiltration LC-MS/MS analysis and molecular networking showed that out of the 20 annotated compounds, 8 compounds have been previously directly or indirectly reported from seaweeds, and 4 compounds have been reported to exhibit anti-gout activity. Molecular docking and ADMET showed that six seaweed-derived compounds can dock with the XOD activity pocket and follow the Lipinski drug-like rule. These results support the value of further investigating P. capillacea as part of the development of anti-gout drugs or related functional foods. Full article

(This article belongs to the Special Issue Marine Anti-inflammatory and Antioxidant Agents 3.0)

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14 pages, 2519 KiB

Open AccessArticle

Fucoidan from Sargassum autumnale Inhibits Potential Inflammatory Responses via NF-κB and MAPK Pathway Suppression in Lipopolysaccharide-Induced RAW 264.7 Macrophages

by N. M. Liyanage, Hyo-Geun Lee, D. P. Nagahawatta, H. H. A. C. K. Jayawardhana, Kyung-Mo Song, Yun-Sang Choi, You-Jin Jeon and Min-Cheol Kang

Mar. Drugs 2023, 21(7), 374; https://doi.org/10.3390/md21070374 - 25 Jun 2023

Cited by 6 | Viewed by 1541

Abstract

Fucoidans are sulfate-rich polysaccharides with a wide variety of beneficial biological activities. The present study aimed to highlight the anti-inflammatory activity of fucoidan from the brown seaweed Sargassum autumnale (SA) against lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells. Among the isolated fucoidan fractions, the third fraction (SAF3) showed a superior protective effect on LPS-stimulated RAW 264.7 cells. SAF3 inhibits nitric oxide (NO) production and expression of prostaglandin E-2 (PGE2) via downregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) expression in LPS-induced RAW 26.7 cells. SAF3 treatment decreased pro-inflammatory cytokines IL-1β, TNF-α, and IL-6 expression in LPS-induced cells. LPS stimulation activated NF-κB and MAPK signaling cascades in RAW 264.7 cells, while treatment with SAF3 suppressed them in a concentration-dependent manner. Existing outcomes confirm that SAF3 from S. autumnale possesses potent anti-inflammatory activity and exhibits good potential for application as a functional food ingredient or for the treatment of inflammation-related disorders. Full article

(This article belongs to the Special Issue Marine Anti-inflammatory and Antioxidant Agents 3.0)

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29 pages, 5248 KiB

Open AccessArticle

Photoprotective and Anti-Aging Properties of the Apical Frond Extracts from the Mediterranean Seaweed Ericaria amentacea

by Serena Mirata, Valentina Asnaghi, Mariachiara Chiantore, Annalisa Salis, Mirko Benvenuti, Gianluca Damonte and Sonia Scarfì

Mar. Drugs 2023, 21(5), 306; https://doi.org/10.3390/md21050306 - 18 May 2023

Cited by 3 | Viewed by 2536

Abstract

There is a growing interest in using brown algal extracts thanks to the bioactive substances they produce for adaptation to the marine benthic environment. We evaluated the anti-aging and photoprotective properties of two types of extracts (50%-ethanol and DMSO) obtained from different portions, i.e., apices and thalli, of the brown seaweed, Ericaria amentacea. The apices of this alga, which grow and develop reproductive structures during summer when solar radiation is at its peak, were postulated to be rich in antioxidant compounds. We determined the chemical composition and pharmacological effects of their extracts and compared them to the thallus-derived extracts. All the extracts contained polyphenols, flavonoids and antioxidants and showed significant biological activities. The hydroalcoholic apices extracts demonstrated the highest pharmacological potential, likely due to the higher content of meroditerpene molecular species. They blocked toxicity in UV-exposed HaCaT keratinocytes and L929 fibroblasts and abated the oxidative stress and the production of pro-inflammatory cytokines, typically released after sunburns. Furthermore, the extracts showed anti-tyrosinase and anti-hydrolytic skin enzyme activity, counteracting the collagenase and hyaluronidase degrading activities and possibly slowing down the formation of uneven pigmentation and wrinkles in aging skin. In conclusion, the E. amentacea apices derivatives constitute ideal components for counteracting sunburn symptoms and for cosmetic anti-aging lotions. Full article

(This article belongs to the Special Issue Marine Anti-inflammatory and Antioxidant Agents 3.0)

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15 pages, 3868 KiB

Open AccessArticle

Tisochrysis lutea F&M-M36 Mitigates Risk Factors of Metabolic Syndrome and Promotes Visceral Fat Browning through β3-Adrenergic Receptor/UCP1 Signaling

by Mario D’Ambrosio, Elisabetta Bigagli, Lorenzo Cinci, Manuela Gencarelli, Sofia Chioccioli, Natascia Biondi, Liliana Rodolfi, Alberto Niccolai, Francesca Zambelli, Annunziatina Laurino, Laura Raimondi, Mario R. Tredici and Cristina Luceri

Mar. Drugs 2023, 21(5), 303; https://doi.org/10.3390/md21050303 - 17 May 2023

Cited by 2 | Viewed by 1622

Abstract

Pre-metabolic syndrome (pre-MetS) may represent the best transition phase to start treatments aimed at reducing cardiometabolic risk factors of MetS. In this study, we investigated the effects of the marine microalga Tisochrysis lutea F&M-M36 (T. lutea) on cardiometabolic components of pre-MetS and its underlying mechanisms. Rats were fed a standard (5% fat) or a high-fat diet (20% fat) supplemented or not with 5% of T. lutea or fenofibrate (100 mg/Kg) for 3 months. Like fenofibrate, T. lutea decreased blood triglycerides (p < 0.01) and glucose levels (p < 0.01), increased fecal lipid excretion (p < 0.05) and adiponectin (p < 0.001) without affecting weight gain. Unlike fenofibrate, T. lutea did not increase liver weight and steatosis, reduced renal fat (p < 0.05), diastolic (p < 0.05) and mean arterial pressure (p < 0.05). In visceral adipose tissue (VAT), T. lutea, but not fenofibrate, increased the β3-adrenergic receptor (β3ADR) (p < 0.05) and Uncoupling protein 1 (UCP-1) (p < 0.001) while both induced glucagon-like peptide-1 receptor (GLP1R) protein expression (p < 0.001) and decreased interleukin (IL)-6 and IL-1β gene expression (p < 0.05). Pathway analysis on VAT whole-gene expression profiles showed that T. lutea up-regulated energy-metabolism-related genes and down-regulated inflammatory and autophagy pathways. The multitarget activity of T. lutea suggests that this microalga could be useful in mitigating risk factors of MetS. Full article

(This article belongs to the Special Issue Marine Anti-inflammatory and Antioxidant Agents 3.0)

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Review

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25 pages, 4121 KiB

Open AccessReview

Anti-Inflammatory Effects of Bioactive Compounds from Seaweeds, Bryozoans, Jellyfish, Shellfish and Peanut Worms

by Md Khursheed, Hardik Ghelani, Reem K. Jan and Thomas E. Adrian

Mar. Drugs 2023, 21(10), 524; https://doi.org/10.3390/md21100524 - 30 Sep 2023

Cited by 1 | Viewed by 2122

Abstract

Inflammation is a defense mechanism of the body in response to harmful stimuli such as pathogens, damaged cells, toxic compounds or radiation. However, chronic inflammation plays an important role in the pathogenesis of a variety of diseases. Multiple anti-inflammatory drugs are currently available for the treatment of inflammation, but all exhibit less efficacy. This drives the search for new anti-inflammatory compounds focusing on natural resources. Marine organisms produce a broad spectrum of bioactive compounds with anti-inflammatory activities. Several are considered as lead compounds for development into drugs. Anti-inflammatory compounds have been extracted from algae, corals, seaweeds and other marine organisms. We previously reviewed anti-inflammatory compounds, as well as crude extracts isolated from echinoderms such as sea cucumbers, sea urchins and starfish. In the present review, we evaluate the anti-inflammatory effects of compounds from other marine organisms, including macroalgae (seaweeds), marine angiosperms (seagrasses), medusozoa (jellyfish), bryozoans (moss animals), mollusks (shellfish) and peanut worms. We also present a review of the molecular mechanisms of the anti-inflammatory activity of these compounds. Our objective in this review is to provide an overview of the current state of research on anti-inflammatory compounds from marine sources and the prospects for their translation into novel anti-inflammatory drugs. Full article

(This article belongs to the Special Issue Marine Anti-inflammatory and Antioxidant Agents 3.0)

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29 pages, 5855 KiB

Open AccessReview

Unlocking the Potential of Octocoral-Derived Secondary Metabolites against Neutrophilic Inflammatory Response

by Ngoc Bao An Nguyen, Mohamed El-Shazly, Po-Jen Chen, Bo-Rong Peng, Lo-Yun Chen, Tsong-Long Hwang and Kuei-Hung Lai

Mar. Drugs 2023, 21(8), 456; https://doi.org/10.3390/md21080456 - 18 Aug 2023

Viewed by 1165

Abstract

Inflammation is a critical defense mechanism that is utilized by the body to protect itself against pathogens and other noxious invaders. However, if the inflammatory response becomes exaggerated or uncontrollable, its original protective role is not only demolished but it also becomes detrimental to the affected tissues or even to the entire body. Thus, regulating the inflammatory process is crucial to ensure that it is resolved promptly to prevent any subsequent damage. The role of neutrophils in inflammation has been highlighted in recent decades by a plethora of studies focusing on neutrophilic inflammatory diseases as well as the mechanisms to regulate the activity of neutrophils during the overwhelmed inflammatory process. As natural products have demonstrated promising effects in a wide range of pharmacological activities, they have been investigated for the discovery of new anti-inflammatory therapeutics to overcome the drawbacks of current synthetic agents. Octocorals have attracted scientists as a plentiful source of novel and intriguing marine scaffolds that exhibit many pharmacological activities, including anti-inflammatory effects. In this review, we aim to provide a summary of the neutrophilic anti-inflammatory properties of these marine organisms that were demonstrated in 46 studies from 1995 to the present (April 2023). We hope the present work offers a comprehensive overview of the anti-inflammatory potential of octocorals and encourages researchers to identify promising leads among numerous compounds isolated from octocorals over the past few decades to be further developed into anti-inflammatory therapeutic agents. Full article

(This article belongs to the Special Issue Marine Anti-inflammatory and Antioxidant Agents 3.0)

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