Research

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19 pages, 4638 KiB

Open AccessArticle

Effects of Dermatan Sulfate from Marine Invertebrate Styela plicata in the Wound Healing Pathway: A Natural Resource Applied to Regenerative Therapy

by Vanessa S. Rizzo-Valente, Maria A. Fusco, Renata M. M. L. Cruz, Rachel A. Santos, Lucas S. Silva, Roberta C. Escaleira, Daniel F. Schulz, Shana P. C. Barroso, Bruno L. Miranda, Daniela Z. Santos, Marcelo L. Gregório, Rodrigo J. A. Guerra and Mauro S. G. Pavão

Mar. Drugs 2022, 20(11), 676; https://doi.org/10.3390/md20110676 - 28 Oct 2022

Cited by 2 | Viewed by 1772

Abstract

Acute and chronic dermatological injuries need rapid tissue repair due to the susceptibility to infections. To effectively promote cutaneous wound recovery, it is essential to develop safe, low-cost, and affordable regenerative tools. Therefore, we aimed to identify the biological mechanisms involved in the [...] Read more.

Acute and chronic dermatological injuries need rapid tissue repair due to the susceptibility to infections. To effectively promote cutaneous wound recovery, it is essential to develop safe, low-cost, and affordable regenerative tools. Therefore, we aimed to identify the biological mechanisms involved in the wound healing properties of the glycosaminoglycan dermatan sulfate (DS), obtained from ascidian Styela plicata, a marine invertebrate, which in preliminary work from our group showed no toxicity and promoted a remarkable fibroblast proliferation and migration. In this study, 2,4-DS (50 µg/mL)-treated and control groups had the relative gene expression of 84 genes participating in the healing pathway evaluated. The results showed that 57% of the genes were overexpressed during treatment, 16% were underexpressed, and 9.52% were not detected. In silico analysis of metabolic interactions exhibited overexpression of genes related to: extracellular matrix organization, hemostasis, secretion of inflammatory mediators, and regulation of insulin-like growth factor transport and uptake. Furthermore, in C57BL/6 mice subjected to experimental wounds treated with 0.25% 2,4-DS, the histological parameters demonstrated a great capacity for vascular recovery. Additionally, this study confirmed that DS is a potent inducer of wound-healing cellular pathways and a promoter of neovascularization, being a natural ally in the tissue regeneration strategy. Full article

(This article belongs to the Special Issue The Mechanisms of Action of Bioactive Marine Natural Products)

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27 pages, 6372 KiB

Open AccessArticle

Nanoformulation of Seaweed Eisenia bicyclis in Albumin Nanoparticles Targeting Cardiovascular Diseases: In Vitro and In Vivo Evaluation

by Sofia Pinto, Maria Manuela Gaspar, Lia Ascensão, Pedro Faísca, Catarina Pinto Reis and Rita Pacheco

Mar. Drugs 2022, 20(10), 608; https://doi.org/10.3390/md20100608 - 27 Sep 2022

Cited by 3 | Viewed by 2266

Abstract

Natural products, especially those derived from seaweeds, are starting to be seen as effective against various diseases, such as cardiovascular diseases (CVDs). This study aimed to design a novel oral formulation of bovine albumin serum nanoparticles (BSA NPs) loaded with an extract of [...] Read more.

Natural products, especially those derived from seaweeds, are starting to be seen as effective against various diseases, such as cardiovascular diseases (CVDs). This study aimed to design a novel oral formulation of bovine albumin serum nanoparticles (BSA NPs) loaded with an extract of Eisenia bicyclis and to validate its beneficial health effects, particularly targeting hypercholesterolemia and CVD prevention. Small and well-defined BSA NPs loaded with Eisenia bicyclis extract were successfully prepared exhibiting high encapsulation efficiency. Antioxidant activity and cholesterol biosynthesis enzyme 3-hydroxy-3 methylutaryl coenzyme A reductase (HMGR) inhibition, as well as reduction of cholesterol permeation in intestinal lining model cells, were assessed for the extract both in free and nanoformulated forms. The nanoformulation was more efficient than the free extract, particularly in terms of HMGR inhibition and cholesterol permeation reduction. In vitro cytotoxicity and in vivo assays in Wistar rats were performed to evaluate its safety and overall effects on metabolism. The results demonstrated that the Eisenia bicyclis extract and BSA NPs were not cytotoxic against human intestinal Caco-2 and liver HepG2 cells and were also safe after oral administration in the rat model. In addition, an innovative approach was adopted to compare the metabolomic profile of the serum from the animals involved in the in vivo assay, which showed the extract and nanoformulation’s impact on CVD-associated key metabolites. Altogether, these preliminary results revealed that the seaweed extract and the nanoformulation may constitute an alternative natural dosage form which is safe and simple to produce, capable of reducing cholesterol levels, and consequently helpful in preventing hypercholesterolemia, the main risk factor of CVDs. Full article

(This article belongs to the Special Issue The Mechanisms of Action of Bioactive Marine Natural Products)

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14 pages, 2013 KiB

Open AccessArticle

The Sponge-Derived Brominated Compound Aeroplysinin-1 Impairs the Endothelial Inflammatory Response through Inhibition of the NF-κB Pathway

by Isabel Vidal, Laura Castilla, Ana Dácil Marrero, Inés Bravo-Ruiz, Manuel Bernal, Inmaculada Manrique, Ana R. Quesada, Miguel Ángel Medina and Beatriz Martínez-Poveda

Mar. Drugs 2022, 20(10), 605; https://doi.org/10.3390/md20100605 - 26 Sep 2022

Cited by 3 | Viewed by 1779

Abstract

(+)-Aeroplysinin-1 (Apl-1) is a brominated compound isolated from the marine sponge Aplysina aerophoba that exhibits pleiotropic bioactive effects, impairing cell growth in cancer cells, inhibiting angiogenesis in vitro and in vivo and modulating the redox status of different cell types, among other reported [...] Read more.

(+)-Aeroplysinin-1 (Apl-1) is a brominated compound isolated from the marine sponge Aplysina aerophoba that exhibits pleiotropic bioactive effects, impairing cell growth in cancer cells, inhibiting angiogenesis in vitro and in vivo and modulating the redox status of different cell types, among other reported activities. In addition to the aforementioned effects, the anti-inflammatory potential of this natural compound was explored in previous work of our laboratory, but the mechanism of action underlying this effect was not described. In this work, we delve into the anti-inflammatory effect of Apl-1 in the context of vascular endothelial cells in vitro, providing new data regarding the molecular mechanism underlying this activity. The characterization of the mechanism of action points to an inhibitory effect of Apl-1 on the NF-κB pathway, one of the main axes involved in endothelial response during inflammatory events. Our results show that Apl-1 can inhibit the expression of pro-inflammatory genes in tumor necrosis factor alpha (TNF-α)- and lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs), targeting the nuclear factor kappa B subunit (NF-κB) pathway through a mechanism of action involving the inhibition of I kappa B kinase (IKK) complex phosphorylation and RelA/p65 nuclear import. In addition, Apl-1 prevented the phosphorylation of Akt induced by TNF-α in HUVECs, probably supporting the inhibitory effect of this compound in the NF-κB pathway. Experimental evidence reported in this work opens the door to the potential pharmacological use of this compound as an anti-inflammatory agent in diseases that course with a pathological endothelial response to inflammation, such as atherosclerosis. Full article

(This article belongs to the Special Issue The Mechanisms of Action of Bioactive Marine Natural Products)

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18 pages, 3911 KiB

Open AccessArticle

Antitumor Properties of Epitope-Specific Engineered Vaccine in Murine Model of Melanoma

by Emiliya Stoyanova, Nikolina Mihaylova, Nikola Ralchev, Petya Ganova, Silviya Bradyanova, Iliyan Manoylov, Yuliana Raynova, Krassimira Idakieva and Andrey Tchorbanov

Mar. Drugs 2022, 20(6), 392; https://doi.org/10.3390/md20060392 - 14 Jun 2022

Viewed by 3022

Abstract

Finding new effective compounds of natural origin for composing anti-tumor vaccines is one of the main goals of antitumor research. Promising anti-cancer agents are the gastropodan hemocyanins–multimeric copper-containing glycoproteins used so far for therapy of different tumors. The properties of hemocyanins isolated from [...] Read more.

Finding new effective compounds of natural origin for composing anti-tumor vaccines is one of the main goals of antitumor research. Promising anti-cancer agents are the gastropodan hemocyanins–multimeric copper-containing glycoproteins used so far for therapy of different tumors. The properties of hemocyanins isolated from the marine snail Rapana thomasiana (RtH) and the terrestrial snail Helix aspersa (HaH) upon their use as carrier-proteins in conjugated vaccines, containing ganglioside mimotope GD3P4 peptide, were studied in the developed murine melanoma model. Murine melanoma cell line B16F10 was used for solid tumor establishment in C57BL/6 mice using various schemes of therapy. Protein engineering, flow cytometry, and cytotoxicity assays were also performed. The administration of the protein-engineered vaccines RtH-GD3P4 or HaH-GD3P4 under the three different regimens of therapy in the B16F10 murine melanoma model suppressed tumor growth, decreased tumor incidence, and prolonged the survival of treated animals. The immunization of experimental mice induced an infiltration of immunocompetent cells into the tumors and generated cytotoxic tumor-specific T cells in the spleen. The treatment also generates significantly higher levels of tumor-infiltrated M1 macrophages, compared to untreated tumor-bearing control mice. This study demonstrated a promising approach for cancer therapy having potential applications for cancer vaccine research. Full article

(This article belongs to the Special Issue The Mechanisms of Action of Bioactive Marine Natural Products)

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13 pages, 2591 KiB

Open AccessArticle

Dieckol Ameliorates Aβ Production via PI3K/Akt/GSK-3β Regulated APP Processing in SweAPP N2a Cell

by Jeong-Hyun Yoon, Nayoung Lee, Kumju Youn, Mi Ra Jo, Hyeung-Rak Kim, Dong-Seok Lee, Chi-Tang Ho and Mira Jun

Mar. Drugs 2021, 19(3), 152; https://doi.org/10.3390/md19030152 - 15 Mar 2021

Cited by 16 | Viewed by 3089

Abstract

The proteolytic processing of amyloid precursor protein (APP) by β-secretase (BACE1) and γ-secretase releases amyloid-β peptide (Aβ), which deposits in amyloid plaques and contributes to the initial causative events of Alzheimer’s disease (AD). In the present study, the regulatory mechanism of APP processing [...] Read more.

The proteolytic processing of amyloid precursor protein (APP) by β-secretase (BACE1) and γ-secretase releases amyloid-β peptide (Aβ), which deposits in amyloid plaques and contributes to the initial causative events of Alzheimer’s disease (AD). In the present study, the regulatory mechanism of APP processing of three phlorotannins was elucidated in Swedish mutant APP overexpressed N2a (SweAPP N2a) cells. Among the tested compounds, dieckol exhibited the highest inhibitory effect on both intra- and extracellular Aβ accumulation. In addition, dieckol regulated the APP processing enzymes, such as α-secretase (ADAM10), β-secretase, and γ-secretase, presenilin-1 (PS1), and their proteolytic products, sAPPα and sAPPβ, implying that the compound acts on both the amyloidogenic and non-amyloidogenic pathways. In addition, dieckol increased the phosphorylation of protein kinase B (Akt) at Ser473 and GSK-3β at Ser9, suggesting dieckol induced the activation of Akt, which phosphorylated GSK-3β. The specific phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 triggered GSK-3β activation and Aβ expression. In addition, co-treatment with LY294002 noticeably blocked the effect of dieckol on Aβ production, demonstrating that dieckol promoted the PI3K/Akt signaling pathway, which in turn inactivated GSK-3β, resulting in the reduction in Aβ levels. Full article

(This article belongs to the Special Issue The Mechanisms of Action of Bioactive Marine Natural Products)

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Review

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17 pages, 1055 KiB

Open AccessReview

Immunomodulatory, Antioxidant, Anticancer, and Pharmacokinetic Activity of Ulvan, a Seaweed-Derived Sulfated Polysaccharide: An Updated Comprehensive Review

by Biswajita Pradhan, Prajna Paramita Bhuyan and Jang-Seu Ki

Mar. Drugs 2023, 21(5), 300; https://doi.org/10.3390/md21050300 - 16 May 2023

Cited by 13 | Viewed by 2731

Abstract

Cancer is one of the most worldwide spread diseases and causes maximum death. Treatment of cancer depends on the host immune system and the type of drugs. The inefficiency of conventional cancer treatments as a result of drug resistance, nontargeted delivery, and chemotherapy-related [...] Read more.

Cancer is one of the most worldwide spread diseases and causes maximum death. Treatment of cancer depends on the host immune system and the type of drugs. The inefficiency of conventional cancer treatments as a result of drug resistance, nontargeted delivery, and chemotherapy-related negative side effects has caused bioactive phytochemicals to come into focus. As a result, recent years have seen an increase in research into screening and identifying natural compounds with anticancer properties. Recent studies on the isolation and use of polysaccharides derived from various marine algal species have revealed a variety of biological activities, including antioxidant and anticancer properties. Ulvan is a polysaccharide derived from various green seaweeds of the Ulva species in the family Ulvaceae. It has been demonstrated to have potent anticancer and anti-inflammatory properties through the modulation of antioxidants. It is vital to understand the mechanisms underlying the biotherapeutic activities of Ulvan in cancer and its role in immunomodulation. In this context, we reviewed the anticancer effects of ulvan based on its apoptotic effects and immunomodulatory activity. Additionally, we also focused on its pharmacokinetic studies in this review. Ulvan is the most conceivable candidate for use as a cancer therapeutic agent and could be used to boost immunity. Moreover, it may be established as an anticancer drug once its mechanisms of action are understood. Due to its high food and nutritive values, it can be used as a possible dietary supplement for cancer patients in the near future. This review may provide fresh perspectives on the potential novel role of ulvan, reveal a brand-new cancer-prevention strategy, and improve human health. Full article

(This article belongs to the Special Issue The Mechanisms of Action of Bioactive Marine Natural Products)

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13 pages, 1201 KiB

Open AccessReview

Marine Polyphenol Phlorotannins as a Natural Sleep Aid for Treatment of Insomnia: A Review of Sedative–Hypnotic Effects and Mechanism of Action

by Seonghui Kim, Duhyeon Kim, Min Young Um, Minseok Yoon, Jae-Suk Choi, Yung Hyun Choi and Suengmok Cho

Mar. Drugs 2022, 20(12), 774; https://doi.org/10.3390/md20120774 - 10 Dec 2022

Cited by 2 | Viewed by 2310

Abstract

Insomnia is a common sleep disorder. Natural sleep aids are gaining worldwide popularity as alternatives to prescription drugs for improving sleep. Recently, numerous studies have investigated the sedative–hypnotic effects of the polyphenols of terrestrial plants. The hypnotic effects of marine polyphenols have also [...] Read more.

Insomnia is a common sleep disorder. Natural sleep aids are gaining worldwide popularity as alternatives to prescription drugs for improving sleep. Recently, numerous studies have investigated the sedative–hypnotic effects of the polyphenols of terrestrial plants. The hypnotic effects of marine polyphenols have also been studied in recent years. Phlorotannins are marine polyphenols that are found only in brown algae. Phlorotannins exert sedative–hypnotic effects via the gamma-aminobutyric acid type A-benzodiazepine receptor. In addition, the brown seaweed Ecklonia cava supplement containing phlorotannins has been approved by the Ministry of Food and Drug Safety as a health-functional ingredient that helps improve sleep quality. Currently, it is meaningful to deal with the sedative–hypnotic effects of phlorotannins as natural sleep aids. The current review comprehensively presents the sedative–hypnotic effects in animal models and human clinical trials as well as their mechanism of action, extraction, purification, and safety. Full article

(This article belongs to the Special Issue The Mechanisms of Action of Bioactive Marine Natural Products)

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13 pages, 3854 KiB

Open AccessReview

Carbonic Anhydrase Inhibitors from Marine Natural Products

by Claudiu T. Supuran

Mar. Drugs 2022, 20(11), 721; https://doi.org/10.3390/md20110721 - 17 Nov 2022

Cited by 8 | Viewed by 1833

Abstract

Carbonic anhydrases (CAs, EC 4.2.1.1) are widespread metalloenzymes in organisms in all life kingdoms, being involved in pH regulation, metabolic processes and many other physiological and pathological conditions. CA inhibitors and activators thus possess applications as pharmacological agents in the management of a [...] Read more.

Carbonic anhydrases (CAs, EC 4.2.1.1) are widespread metalloenzymes in organisms in all life kingdoms, being involved in pH regulation, metabolic processes and many other physiological and pathological conditions. CA inhibitors and activators thus possess applications as pharmacological agents in the management of a range of diseases. Marine natural products have allowed the identification of some highly interesting CA inhibitors, among which are sulfonamides, phenols, polyamines, coumarins and several other miscellaneous inhibitors, which are reviewed here. Psammaplin C and some bromophenols were the most investigated classes of such marine-based inhibitors and have been used as lead molecules for developing interesting types of potent and, in some cases, isoform-selective inhibitors, with applications as antitumor agents by inhibiting human CA XII and P-glycoprotein activities. Some phenols have shown interesting bacterial and fungal β-CA inhibitory effects. Marine natural products thus constitute a gold mine for identifying novel CA inhibitors, some of which may lead to the development of novel types of pharmacological agents. Full article

(This article belongs to the Special Issue The Mechanisms of Action of Bioactive Marine Natural Products)

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22 pages, 980 KiB

Open AccessReview

Call the Eckols: Present and Future Potential Cancer Therapies

by Pedro Monteiro, Silvia Lomartire, João Cotas, João C. Marques, Leonel Pereira and Ana M. M. Gonçalves

Mar. Drugs 2022, 20(6), 387; https://doi.org/10.3390/md20060387 - 09 Jun 2022

Cited by 9 | Viewed by 2608

Abstract

In recent years, an increased interest in marine macroalgae bioactive compounds has been recorded due to their benefits to human health and welfare. Several of their bioactivities have been demonstrated, such as anti-inflammatory, antioxidant, anticarcinogenic, antibacterial and antiviral behavior. However, there still lacks [...] Read more.

In recent years, an increased interest in marine macroalgae bioactive compounds has been recorded due to their benefits to human health and welfare. Several of their bioactivities have been demonstrated, such as anti-inflammatory, antioxidant, anticarcinogenic, antibacterial and antiviral behavior. However, there still lacks a clear definition regarding how these compounds exert their bioactive properties. Of all the bioactive compounds derived from marine macroalgae, attention has been focused on phenolic compounds, specifically in phlorotannins, due to their potential for biomedical applications. Phlorotannins are a diverse and wide group of phenolic compounds, with several structural variations based on the monomer phloroglucinol. Among the diverse phlorotannin structures, the eckol-family of phlorotannins demonstrates remarkable bioactivity, notably their anti-tumoral properties. However, the molecular mechanisms by which this activity is achieved remain elusive and sparse. This review focuses on the described molecular mechanisms of anti-tumoral effects by the eckol family of compounds and the future prospects of these molecules for potential application in oncology therapies. Full article

(This article belongs to the Special Issue The Mechanisms of Action of Bioactive Marine Natural Products)

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30 pages, 1069 KiB

Open AccessReview

Antiviral Activity and Mechanisms of Seaweeds Bioactive Compounds on Enveloped Viruses—A Review

by Silvia Lomartire and Ana M. M. Gonçalves

Mar. Drugs 2022, 20(6), 385; https://doi.org/10.3390/md20060385 - 08 Jun 2022

Cited by 19 | Viewed by 2971

Abstract

In the last decades, the interest in seaweed has significantly increased. Bioactive compounds from seaweed’s currently receive major attention from pharmaceutical companies as they express several interesting biological activities which are beneficial for humans. The structural diversity of seaweed metabolites provides diverse biological [...] Read more.

In the last decades, the interest in seaweed has significantly increased. Bioactive compounds from seaweed’s currently receive major attention from pharmaceutical companies as they express several interesting biological activities which are beneficial for humans. The structural diversity of seaweed metabolites provides diverse biological activities which are expressed through diverse mechanisms of actions. This review mainly focuses on the antiviral activity of seaweed’s extracts, highlighting the mechanisms of actions of some seaweed molecules against infection caused by different types of enveloped viruses: influenza, Lentivirus (HIV-1), Herpes viruses, and coronaviruses. Seaweed metabolites with antiviral properties can act trough different pathways by increasing the host’s defense system or through targeting and blocking virus replication before it enters host cells. Several studies have already established the large antiviral spectrum of seaweed’s bioactive compounds. Throughout this review, antiviral mechanisms and medical applications of seaweed’s bioactive compounds are analyzed, suggesting seaweed’s potential source of antiviral compounds for the formulation of novel and natural antiviral drugs. Full article

(This article belongs to the Special Issue The Mechanisms of Action of Bioactive Marine Natural Products)

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