Comparative investigation into the anticancer activity of analogs of marine coelenterazine and coelenteramine.

Cancer is still one of the most challenging diseases to treat, making the pursuit for novel molecules with potential anticancer activity an important research topic. Herein, we have performed a comparative investigation into the anticancer activity of analogs of marine coelenterazine and coelenteramine. The former is a well-known bioluminescent substrate, while the latter is a metabolic product of the resulting bioluminescent reaction. While both types of analogs showed anticancer activity toward lung and gastric cancer cell lines, we have obtained data that highlight relevant differences between the activity of these two types of compounds. More specifically, we observed relevant differences in structure-activity relationships between these types of compounds. Also, coelenteramine analogs showed time-dependent activity, while coelenterazine-based compounds usually present time-independent activity. Coelenterazine analogs also appear to be relatively safer toward noncancer cells than coelenteramine analogs. There was also seen a correlation between the activity of the coelenterazine-based compounds and their light-emission properties. Thus, these results further indicate the potential of the marine coelenterazine chemi-/bioluminescent system as a source of new molecules with anticancer activity, while providing more insight into their modes of action.

Synchrotron-based FTIR evaluation of biochemical changes in cancer and noncancer cells induced by brominated marine coelenteramine.

The mode of action toward gastric cancer cells of brominated Coelenteramine, an analogue of a metabolic product of a marine bioluminescent reaction, was investigated by synchrotron radiation-based Fourier Transform Infrared spectrocopy (FTIR). This method revealed that the anticancer activity of brominated Coelenteramine is closely connected with cellular lipids, by affecting their organization and composition. More specifically, there is an increasing extent of oxidative stress, which results in changes in membrane polarity, lipid chain packing and lipid composition. However, this effect was not observed in a noncancer cell line, helping to explain its selectivity profile. Thus, synchrotron radiation-based FTIR helped to identify the potential of this Coelenteramine analogue in targeting membrane lipids, while proving to be a powerful technique to probe the mechanism of anticancer drugs.

Examination of the Antioxidant Activity of Psoralidin: Computational Mechanistic Study and Impact on the ROS Level in Human Keratinocytes.

Psoralidin (Pso) is a coumestan-type compound found in Psoralea corylifolia L. that exhibits a broad spectrum of pharmacological properties. The current work aimed to study, for the first time, the antioxidant capacities of Pso under physiological circumstances. Tandem experimental and computational approaches were used to fully understand the interaction of Pso with ROS (reactive oxygen species) at the molecular level as well as its impact on the basal ROS level in cells. Pso has been found to be a potent radical scavenger in physiological polar media, acting via the single electron-transfer mechanism rather than the hydrogen-transfer mechanism. In contrast, Pso is a moderate radical scavenger in lipid media, and its reaction is determined by hydrogen transfer from the 7OH group. The in vitro assays revealed that Pso moderately reduces the basal ROS level in human keratinocytes at non-toxic concentrations, which is in agreement with the computational study. These findings indicate that Pso is a promising antioxidant, but in its natural form it has no significant effects on basal cell conditions.

Anti-inflammatory effects of naringenin 8-sulphonate from Parinari excelsa Sabine stem bark and its semi-synthetic derivatives.

The inflammatory response is a vital mechanism for repairing damage induced by aberrant health states or external insults; however, persistent activation can be linked to numerous chronic diseases. The nuclear factor kappa ß (NF-κB) inflammatory pathway and its associated mediators have emerged as critical targets for therapeutic interventions aimed at modulating inflammation, necessitating ongoing drug development. Previous studies have reported the inhibitory effect of a hydroethanol extract derived from Parinari excelsa Sabine (Chrysobalanaceae) on tumour necrosis factor-alpha (TNF-α), but the phytoconstituents and mechanisms of action remained elusive. The primary objective of this study was to elucidate the phytochemical composition of P. excelsa stem bark and its role in the mechanisms underpinning its biological activity. Two compounds were detected via HPLC-DAD-ESI(Ion Trap)-MS2 analysis. The predominant compound was isolated and identified as naringenin-8-sulphonate (1), while the identity of the second compound (compound 2) could not be determined. Both compound 1 and the extract were assessed for anti-inflammatory properties using a cell-based inflammation model, in which THP-1-derived macrophages were stimulated with LPS to examine the treatments' effects on various stages of the NF-κB pathway. Compound 1, whose biological activity is reported here for the first time, demonstrated inhibition of NF-κB activity, reduction in interleukin 6 (IL-6), TNF-α, and interleukin 1 beta (IL-1ß) production, as well as a decrease in p65 nuclear translocation in THP-1 cells, thus highlighting the potential role of sulphur substituents in the activity of naringenin (3). To explore the influence of sulphation on the anti-inflammatory properties of naringenin derivatives, we synthesized naringenin-4'-O-sulphate (4) and naringenin-7-O-sulphate (5) and evaluated their anti-inflammatory effects. Naringenin derivatives 4 and 5 did not display potent anti-inflammatory activities; however, compound 4 reduced IL-1ß production, and compound 5 diminished p65 translocation, with both exhibiting the capacity to inhibit TNF-α and IL-6 production. Collectively, the findings demonstrated that the P. excelsa extract was more efficacious than all tested compounds, while providing insights into the role of sulphation in the anti-inflammatory activity of naringenin derivatives.

Burden of disease among older adults in Europe-trends in mortality and disability, 1990-2019.

BACKGROUND: It is important to understand the effects of population ageing on disease burden and explore conditions that drive poor health in later life to prevent or manage these. We examined the development of disease burden and its components for major disease groups among older adults in Europe over the last 30 years. METHODS: Using data from the Global Burden of Disease 2019 Study, we analyzed burden of disease trends between 1990 and 2019 measured by years of life lost (YLL), years lived with disability (YLD) and disability-adjusted life years (DALYs) among older adults (65+ years) in Western, Central and Eastern Europe using cause groups for diseases and injuries. RESULTS: Between 1990 and 2019, the crude numbers of DALYs for all causes increased substantially among older Western Europeans. In Eastern Europe, the absolute DALYs also increased from 1990 to 2005 but then decreased between 2006 and 2013. However, DALY rates declined for all European regions over time, with large differences in the magnitude by region and gender. Changes in the YLL rate were mainly driven by the contribution of cardiovascular diseases. CONCLUSIONS: This study found an increased overall absolute disease burden among older Europeans between 1990 and 2019. The demographic change that has taken place in Eastern European countries implies a potential problem of directed resource allocation to the health care sector. Furthermore, the findings highlight the potential health gains through directing resources to health promotion and treatment to reduce YLDs and to prevent YLLs, primarily from cardiovascular diseases.

Inula viscosa (L.) Aiton Ethanolic Extract Inhibits the Growth of Human AGS and A549 Cancer Cell Lines.

The present study shows the chemical profile and cytotoxic properties of the ethanolic extracts of Inula viscosa from Northeast Algeria. The extract was obtained by maceration using ethanol. Its phenolic profile was determined using ultra-high-performance liquid chromatography coupled with a diode array detector and an electrospray mass spectrometer (UHPLC-DAD-ESI/MS), which allowed the identification and quantification of 17 compounds, 1,5-O-caffeoylquinic acid being the most abundant. The cytotoxic activity was assessed against human gastric cancer (AGS) and human non-small-cell lung cancer (A549) cell lines, whereas ethanolic extract elicited nearly 60 % and 40 % viability loss toward AGS and A549 cancer cells, respectively. Results also showed that cell death is caspase-independent and confirmed the involvement of RIPK1 and the necroptosis pathway in the toxicity induced by the I. viscosa extract. In addition, the ethanolic extract would not provoke morphological traits in the cancer cells. These findings suggest that I. viscosa can be a source of new antiproliferative drugs or used in preparation plant-derived pharmaceuticals.

Structural modification of naturally occurring phenolics as a strategy for developing cytotoxic molecules towards cancer cells.

Natural products belonging to different chemical classes have been established as a promising source of novel anticancer drugs. Several low-molecular-weight compounds from the classes of monoterpenes, phenylpropanoids, and flavonoids were shown to possess anticancer activities in previous studies. In this work, over 20 semisynthetic derivatives of molecules belonging to these classes, namely thymol, eugenol, and 6-hydroxyflavanone were synthesized and tested for their cytotoxicity against two human cancer cell lines, namely AGS cells (gastric adenocarcinoma) and A549 cells (human lung carcinoma). An initial screening based on viability assessment was performed to identify the most cytotoxic compounds at 100 µM. The results evidenced that two 6-hydroxyflavanone derivatives were the most cytotoxic among the compounds tested, being selected for further studies. These derivatives displayed enhanced toxicity when compared with their natural counterparts. Moreover, the lactate dehydrogenase (LDH) assay showed that the loss of cell viability was not accompanied by a loss of membrane integrity, thus ruling out a necrotic process. Morphological studies with AGS cells demonstrated chromatin condensation compatible with apoptosis, confirmed by the activation of caspase 3/7. Furthermore, a viability assay on a noncancer human embryonic lung fibroblast cell line (MRC-5) confirmed that these two derivatives possess selective anticancer activity.

Phytochemical Analysis and Antiproliferative Activity of Ulex gallii Planch. (Fabaceae), a Medicinal Plant from Galicia (Spain).

The genus Ulex comprises thirteen accepted species of perennial shrubs in the family Fabaceae. In Galicia (Spain) many of these are considered spontaneous colonizing species, which are easy to establish and maintain. Among them, Ulex gallii Planch. is used in traditional medicine for the same anti-infective, hypotensive and diuretic purposes as Ulex europaeus L., which is the most studied species. Likewise, some studies have described the antitumoral properties of several species. However, there are few scientific studies that justify the use of Ulex gallii Planch. and nothing has been reported about its composition to date. In our study, the entire plant was extracted with methanol and the crude extract was subjected to liquid phase extraction with distinct solvents, yielding three fractions: hexane (H), dichloromethane (D) and methanol (M), which were subsequently fractionated. The dichloromethane (D5, D7 and D8) and methanol (M4) sub-fractions showed antiproliferative activity on A549 (lung cancer) and AGS (stomach cancer) cell lines, and caspase 3/7 activity assessment and DNA quantification were also performed. Targeted analysis via UHPLC-QToF, in combination with untargeted analysis via MS-Dial, MS-Finder and Global Natural Products Social Molecular Networking (GNPS), allowed us to tentatively identify different metabolites in these sub-fractions, mostly flavonoids, that might be involved in their antiproliferative activity.

An injectable, naproxen-conjugated, supramolecular hydrogel with ultra-low critical gelation concentration-prepared from a known folate receptor ligand.

Short peptides capped on the N-terminus with aromatic groups are often able to form supramolecular hydrogels-self-assembled networks of fibrils able to trap water molecules. Typically, these hydrogelators can form stiff gels at concentrations of 0.1 to 1.0 wt%-i.e. they consist of mainly water. The properties of these soft materials mimic those of the extracellular matrix (ECM) of biological tissue and therefore they have found many biomedical uses in tissue engineering, wound healing, drug delivery, biosensing and bioprinting applications. In drug delivery strategies related to cancer therapy, injectable hydrogels can serve as a depot formulation, where a sustained release of the chemotherapeutic from near the tumour site allows reduced doses and, therefore, decreased side effects. To further target cancer cells, folic acid-conjugated hydrogels and nanostructures are often sought, to exploit the overexpression of folate receptors on cancer cells-an approach which can allow the selective cellular uptake of an encapsulated drug. In this present study, two known dipeptide folate receptor ligands (1 and 2) recently identified from a screen of a DNA-encoded compound library, were synthesised and investigated for their hydrogelation ability and cytotoxicity. Compound 1, containing a naproxen capping group, rapidly forms hydrogels at concentrations as low as 0.03 wt%-one of the lowest critical gelation concentrations (CGCs) known for a supramolecular hydrogelator. In contrast, compound 2, which contains a 3-indolepropionic acid capping group, was unable to form hydrogels under a range of conditions and concentrations, instead forming nanospheres with diameters of 0.5 µm. Hydrogels of 1 were characterised by STEM microscopy, rheology, fluorescence spectroscopy and circular dichroism. Both compounds 1 and 2 had no impact on the proliferation of kerotinocytes (HaCaT cells) at concentrations up to 100 µM. Compound 1, containing the NSAID, was tested for anti-inflammatory activity in a human cyclooxygenase-1/2 model. The rate of the release of model drug compounds from within hydrogels of 1 was also investigated.

Plasmonic lipogels: driving co-assembly of composites with peptide-based gels for controlled drug release.

Supramolecular short peptide-based gels are promising materials for the controlled release of drugs (e.g. chemotherapeutic drugs) owing to the biocompatibility and similarity to cell matrix. However, the drug encapsulation and control over its release, mainly the hydrophilic drugs, can be a cumbersome task. This can be overcome through encapsulation/compartmentalization of drugs in liposomes, which can also enable spatiotemporal control and enhanced drug release through a trigger, such as photothermia. Having this in mind, we explored the assembly of silica-coated gold nanoparticles and liposomes (storage units) with dehydropeptide-based hydrogels as a proof-of-concept to afford peptide-based NIR light-responsive lipogels. Several liposomes compositions were assessed that displayed influence on the final assembly properties by combining with silica-coated gold nanorods (∼106 nm). Gold nanospheres (∼11 nm) were used to study the preparation method, which revealed the importance of initially combine liposomes with nanoparticles and then the gelator solution to achieve a closer proximity of the nanoparticles to the liposomes. The control over a hydrophilic model drug, 5(6)-carboxyfluorescein, was only achieved by its encapsulation in liposomes, in which the presence of silica-coated nanorods further enabled the use of photothermia to induce the liposomes phase transition and stimulate the drug release. Further, both composites, the liposomes and silica-coated gold nanorods, induced a lower elastic modulus, but also provided an enhanced gelation kinetics. Hereby, this work advances fabrication strategies for the development of short peptide-based hydrogels towards on-demand, sustained and controlled release of hydrophilic drugs through photothermia under NIR light irradiation.

Eugenol ß-Amino/ß-Alkoxy Alcohols with Selective Anticancer Activity.

Eugenol, 4-allyl-2-methoxyphenol, is the main constituent of clove essential oil and has demonstrated relevant biological activity, namely anticancer activity. Aiming to increase this activity, we synthesized a series of eugenol ß-amino alcohol and ß-alkoxy alcohol derivatives, which were then tested against two human cancer cell lines, namely gastric adenocarcinoma cells (AGS) and lung adenocarcinoma cells (A549). An initial screening was performed to identify the most cytotoxic compounds. The results demonstrated that three ß-amino alcohol derivatives had anticancer activity that justified subsequent studies, having been shown to trigger apoptosis. Importantly, the most potent molecules displayed no appreciable toxicity towards human noncancer cells. Structure-activity relationships show that changes in eugenol structure led to enhanced cytotoxic activity and can contribute to the future design of more potent and selective drugs.

Aryl-Capped Lysine-Dehydroamino Acid Dipeptide Supergelators as Potential Drug Release Systems.

Employing amino acids and peptides as molecular building blocks provides unique opportunities for generating supramolecular hydrogels, owing to their inherent biological origin, bioactivity, biocompatibility, and biodegradability. However, they can suffer from proteolytic degradation. Short peptides (<8 amino acids) attached to an aromatic capping group are particularly attractive alternatives for minimalistic low molecular weight hydrogelators. Peptides with low critical gelation concentrations (CGCs) are especially desirable, as the low weight percentage required for gelation makes them more cost-effective and reduces toxicity. In this work, three dehydrodipeptides were studied for their self-assembly properties. The results showed that all three dehydrodipeptides can form self-standing hydrogels with very low critical gelation concentrations (0.05−0.20 wt%) using a pH trigger. Hydrogels of all three dehydrodipeptides were characterised by scanning tunnelling emission microscopy (STEM), rheology, fluorescence spectroscopy, and circular dichroism (CD) spectroscopy. Molecular modelling was performed to probe the structural patterns and interactions. The cytotoxicity of the new compounds was tested using human keratinocytes (HaCaT cell line). In general, the results suggest that all three compounds are non-cytotoxic, although one of the peptides shows a small impact on cell viability. In sustained release assays, the effect of the charge of the model drug compounds on the rate of cargo release from the hydrogel network was evaluated. The hydrogels provide a sustained release of methyl orange (anionic) and ciprofloxacin (neutral), while methylene blue (cationic) was retained by the network.

Discovery of the Anticancer Activity for Lung and Gastric Cancer of a Brominated Coelenteramine Analog.

Cancer is still a challenging disease to treat, both in terms of harmful side effects and therapeutic efficiency of the available treatments. Herein, to develop new therapeutic molecules, we have investigated the anticancer activity of halogenated derivatives of different components of the bioluminescent system of marine Coelenterazine: Coelenterazine (Clz) itself, Coelenteramide (Clmd), and Coelenteramine (Clm). We have found that Clz derivatives possess variable anticancer activity toward gastric and lung cancer. Interestingly, we also found that both brominated Clmd (Br-Clmd) and Clm (Br-Clm) were the most potent anticancer compounds toward these cell lines, with this being the first report of the anticancer potential of these types of molecules. Interestingly, Br-Clm possessed some safety profile towards noncancer cells. Further evaluation revealed that the latter compound induced cell death via apoptosis, with evidence for crosstalk between intrinsic and extrinsic pathways. Finally, a thorough exploration of the chemical space of the studied Br-Clm helped identify the structural features responsible for its observed anticancer activity. In conclusion, a new type of compounds with anticancer activity toward gastric and lung cancer was reported and characterized, which showed interesting properties to be considered as a starting point for future optimizations towards obtaining suitable chemotherapeutic agents.

Essential Oil Stabilisation by Response Surface Methodology (RSM): Nanoemulsion Formulation, Physicochemical, Microbiological, and Sensory Investigations.

This manuscript aimed to optimise the encapsulation of Thymus capitatus essential oil into nanoemulsion. Response Surface Methodology results were best fitted into polynomial models with regression coefficient values of more than 0.95. The optimal nanoemulsion showed nanometer-sized droplets (380 nm), a polydispersity index less than 0.5, and a suitable Zeta potential (-10.3 mV). Stability results showed that nanoemulsions stored at 4 °C were stable with the lowest d3,2, PolyDispersity Index (PDI), and pH (day 11). Significant ameliorations in the capacity to neutralise DPPH radical after the encapsulation of the antimicrobial efficacy of thyme essential oil were recorded. S. typhimurium growth inhibition generated by nanoencapsulated thyme essential oil was 17 times higher than by bulk essential oil. The sensory analysis highlighted that the encapsulation of thyme essential oil improved enriched milk's sensory appreciation. Indeed, 20% of the total population attributed a score of 4 and 5 on the scale used for milk enriched with nanoemulsion. In comparison, only 11% attributed the same score to milk enriched with bulk essential oil. The novel nanometric delivery system presents significant interest for agroalimentary industries.

Amino Alcohols from Eugenol as Potential Semisynthetic Insecticides: Chemical, Biological, and Computational Insights.

A series of ß-amino alcohols were prepared by the reaction of eugenol epoxide with aliphatic and aromatic amine nucleophiles. The synthesized compounds were fully characterized and evaluated as potential insecticides through the assessment of their biological activity against Sf9 insect cells, compared with a commercial synthetic pesticide (chlorpyrifos, CHPY). Three derivatives bearing a terminal benzene ring, either substituted or unsubstituted, were identified as the most potent molecules, two of them displaying higher toxicity to insect cells than CHPY. In addition, the most promising molecules were able to increase the activity of serine proteases (caspases) pivotal to apoptosis and were more toxic to insect cells than human cells. Structure-based inverted virtual screening and molecular dynamics simulations demonstrate that these molecules likely target acetylcholinesterase and/or the insect odorant-binding proteins and are able to form stable complexes with these proteins. Encapsulation assays in liposomes of DMPG and DPPC/DMPG (1:1) were performed for the most active compound, and high encapsulation efficiencies were obtained. A thermosensitive formulation was achieved with the compound release being more efficient at higher temperatures.

Endoplasmic reticulum stress signaling in cancer and neurodegenerative disorders: Tools and strategies to understand its complexity.

The endoplasmic reticulum (ER) comprises a network of tubules and vesicles that constitutes the largest organelle of the eukaryotic cell. Being the location where most proteins are synthesized and folded, it is crucial for the upkeep of cellular homeostasis. Disturbed ER homeostasis triggers the activation of a conserved molecular machinery, termed the unfolded protein response (UPR), that comprises three major signaling branches, initiated by the protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE1) and the activating transcription factor 6 (ATF6). Given the impact of this intricate signaling network upon an extensive list of cellular processes, including protein turnover and autophagy, ER stress is involved in the onset and progression of multiple diseases, including cancer and neurodegenerative disorders. There is, for this reason, an increasing number of publications focused on characterizing and/or modulating ER stress, which have resulted in a wide array of techniques employed to study ER-related molecular events. This review aims to sum up the essentials on the current knowledge of the molecular biology of endoplasmic reticulum stress, while highlighting the available tools used in studies of this nature.

New Eugenol Derivatives with Enhanced Insecticidal Activity.

Eugenol, the generic name of 4-allyl-2-methoxyphenol, is the major component of clove essential oil, and has demonstrated relevant biological potential with well-known antimicrobial and antioxidant actions. New O-alkylated eugenol derivatives, bearing a propyl chain with terminals like hydrogen, hydroxyl, ester, chlorine, and carboxylic acid, were synthesized in the present work. These compounds were later subjected to epoxidation conditions to give the corresponding oxiranes. All derivatives were evaluated against their effect upon the viability of insect cell line Sf9 (Spodoptera frugiperda), demonstrating that structural changes elicit marked effects in terms of potency. In addition, the most promising molecules were evaluated for their impact in cell morphology, caspase-like activity, and potential toxicity towards human cells. Some molecules stood out in terms of toxicity towards insect cells, with morphological assessment of treated cells showing chromatin condensation and fragmentation, which are compatible with the occurrence of programmed cell death, later confirmed by evaluation of caspase-like activity. These findings point out the potential use of eugenol derivatives as semisynthetic insecticides from plant natural products.

Cytotoxic Plant Extracts towards Insect Cells: Bioactivity and Nanoencapsulation Studies for Application as Biopesticides.

The potential of plant extracts as bioinsecticides has been described as a promising field of agricultural development. In this work, the extracts of Punica granatum (pomegranate), Phytolacca americana (American pokeweed), Glandora prostrata (shrubby gromwell), Ulex europaeus (gorce), Tagetes patula (French marigold), Camellia japonica red (camellia), Ruta graveolens (rue or herb-of-grace) were obtained, purified, and their activity against Spodoptera frugiperda (Sf9) insect cells was investigated. From the pool of over twenty extracts obtained, comprising different polarities and vegetable materials, less polar samples were shown to be more toxic towards the insect cell line Sf9. Among these, a dichloromethane extract of R. graveolens was capable of causing a loss of viability of over 50%, exceeding the effect of the commercial insecticide chlorpyrifos. This extract elicited chromatin condensation and the fragmentation in treated cells. Nanoencapsulation assays of the cytotoxic plant extracts in soybean liposomes and chitosan nanostructures were carried out. The nanosystems exhibited sizes lower or around 200 nm, low polydispersity, and generally high encapsulation efficiencies. Release assays showed that chitosan nanoemulsions provide a fast and total extract release, while liposome-based systems are suitable for a more delayed release. These results represent a proof-of-concept for the future development of bioinsecticide nanoformulations based on the cytotoxic plant extracts.

Application of Natural Pigments in Ordinary Cooked Ham.

The possibility of obtaining a carmine or pink color on ordinary cooked ham by applying natural dyes from three plant species, namely red radish (Raphanus sativus L.), hibiscus (Roselle sabdariffa L.) and red beetroot (Beta vulgaris L.), was investigated. The extracts were evaluated for the stability at physical-chemical parameters and subjected to cytotoxicity assays in the gastric cell line AGS Encapsulation of the extracts in soybean lecithin liposomes and maltodextrin microcapsules was performed. Lyophilized extracts before and after encapsulation in maltodextrin were applied in the formulation of ordinary cooked ham and used in a pilot scale of production. The color of cooked ham samples from different assays was evaluated visually and by colorimetry. The results suggest that the coloration of ordinary cooked ham obtained with extracts of red beetroot is very promising for future applications in this type of meat product.

Anti-Inflammatory Effects of 5α,8α-Epidioxycholest-6-en-3ß-ol, a Steroidal Endoperoxide Isolated from Aplysia depilans, Based on Bioguided Fractionation and NMR Analysis.

Sea hares of Aplysia genus are recognized as a source of a diverse range of metabolites. 5α,8α-Endoperoxides belong to a group of oxidized sterols commonly found in marine organisms and display several bioactivities, including antimicrobial, anti-tumor, and immunomodulatory properties. Herein we report the isolation of 5α,8α-epidioxycholest-6-en-3ß-ol (EnP(5,8)) from Aplysia depilans Gmelin, based on bioguided fractionation and nuclear magnetic resonance (NMR) analysis, as well as the first disclosure of its anti-inflammatory properties. EnP(5,8) revealed capacity to decrease cellular nitric oxide (NO) levels in RAW 264.7 macrophages treated with lipopolysaccharide (LPS) by downregulation of the Nos2 (inducible nitric oxide synthase, iNOS) gene. Moreover, EnP(5,8) also inhibited the LPS-induced expression of cyclooxygenase-2 (COX-2), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) at the mRNA and protein levels. Mild selective inhibition of COX-2 enzyme activity was also evidenced. Our findings provide evidence of EnP(5,8) as a potential lead drug molecule for the development of new anti-inflammatory agents.