Marine Anti-inflammatory Agents

Acute inflammation is a highly regulated process, and its dysregulation can lead to the development of a chronic inflammatory state which is believed to play a main role in the pathogenesis of many diseases, including cancer. In recent years, the need to find new anti-inflammatory molecules has raised the scientific community´s interest for marine natural products. In this regard, the marine environment represents a source for isolating a wealth of bioactive compounds. In this Special Issue, the reported products have been obtained from microalgae, sea cucumber, octopus, squid, red alga-derived fungus, cnidarians, hard-shelled mussel, and sponges

Fucoxanthin and Rosmarinic Acid Combination Has Anti-Inflammatory Effects through Regulation of NLRP3 Inflammasome in UVB-Exposed HaCaT Keratinocytes

Excessive exposure to ultraviolet (UV) radiation is the main risk factor to develop skin pathologies or cancer because it encourages oxidative condition and skin inflammation. In this sense, strategies for its prevention are currently being evaluated. Natural products such as carotenoids or polyphenols, which are abundant in the marine environment, have been used in the prevention of oxidative stress due to their demonstrated antioxidant activities. Nevertheless, the anti-inflammatory activity and its implication in photo-prevention have not been extensively studied. Thus, we aimed to evaluate the combination of fucoxanthin (FX) and rosmarinic acid (RA) on cell viability, apoptosis induction, inflammasome regulation, and anti-oxidative response activation in UVB-irradiated HaCaT keratinocytes. We demonstrated for the first time that the combination of FX and RA (5 µM RA plus 5 µM FX, designated as M2) improved antioxidant and anti-inflammatory profiles in comparison to compounds assayed individually, by reducing UVB-induced apoptosis and the consequent ROS production. Furthermore, the M2 combination modulated the inflammatory response through down-regulation of inflammasome components such as NLRP3, ASC, and Caspase-1, and the interleukin (IL)-1β production. In addition, Nrf2 and HO-1 antioxidant genes expression increased in UVB-exposed HaCaT cells pre-treated with M2. These results suggest that this combination of natural products exerts photo-protective effects by down-regulating NRLP3-inflammasome and increasing Nrf2 signalling pathway.Junta de Andalucía, Consejería de Innovación, Ciencia y Empresa-POLFANAT-P12-AGR-430Portugal, Fundação para a Ciência e a Tecnologia (FCT)-CESAM-UID/AMB/50017/2019Portugal, Fundação para a Ciência e a Tecnologia (FCT)-CEECIND/04050/2017Universidad de Sevilla "V Plan Propio US-PPI2015-1.5"

New Eunicellin-Type Diterpenes from the Panamanian Octocoral Briareum Asbestinum

Gorgonian octocorals are considered a prolific source of secondary metabolites with a wide range of biological activities, including anti-inflammatory activity. In particular, the genus Briareum is known for producing a wealth of diterpenes with complex chemical structures. The chemical study of the methanolic extract of Briareum asbestinum collected in Bocas del Toro, on the Caribbean side of Panama, led to the isolation of three new eunicellin-type diterpenes: briarellin T (1), asbestinin 27 (2), asbestinin 28 (3) and the previously described asbestinin 17 (4). The structures of the new compounds were determined by extensive NMR analyses and HRMS. Anti-inflammatory activity assays showed a significant reduction of the pro-inflammatory cytokines TNF-α, IL-6, IL-1β and IL-8 as well as a downregulation of COX-2 expression in LPS-stimulated THP-1 macrophages. These findings support the potential use of these marine compounds as therapeutic agents in the treatment of inflammatory diseases

The Algal Meroterpene 11-Hydroxy-11-O-Methylamentadione Ameloriates Dextran Sulfate Sodium-Induced Colitis in Mice

Inflammatory bowel disease (IBD) is a complex class of immune disorders. Unfortunately, a treatment for total remission has not yet been found, while the use of natural product-based therapies has emerged as a promising intervention. The present study was aimed to investigate the anti-inflammatory effects of the algal meroterpene 11-hydroxy-11-O-methylamentadione (AMT-E) in a murine model of dextran sodium sulphate (DSS)-induced colitis. AMT-E was orally administered daily (1, 10, and 20 mg/kg animal) to DSS treated mice (3% w/v) for 7 days. AMT-E prevented body weight loss and colon shortening and effectively attenuated the extent of the colonic damage. Similarly, AMT-E increased mucus production and reduced myeloperoxidase activity (marker for anti-inflammatory activity). Moreover, the algal meroterpene decreased the tumor necrosis factor (TNF)- , interleukin (IL)-1 , and IL-10 levels, and caused a significant reduction of the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Our results demonstrate the protective effects of AMT-E on experimental colitis, provide an insight of the underlying mechanisms of this compound, and suggest that this class of marine natural products might be an interesting candidate for further studies on the prevention/treatment of IBD

Anti-Inflammatory Effects of Adrenomedullin on Acute Lung Injury Induced by Carrageenan in Mice

Adrenomedullin (AM) is a 52 amino acid peptide that has shown predominant anti-inflammatory activities. In the present study, we evaluated the possible therapeutic effect of this peptide in an experimental model of acute inflammation, the carrageenan- (CAR-) induced pleurisy. Pleurisy was induced by injection of CAR into the pleural cavity of mice. AM (200 ng/kg) was administered by intraperitoneal route 1 h after CAR, and the animals were sacrificed 4 h after that. AM treatment attenuated the recruitment of leucocytes in the lung tissue and the generation and/or the expression of the proinflammatory cytokines as well as the expression of the intercellular cell adhesion molecules. Moreover, AM inhibited the induction of inducible nitric oxide synthase (iNOS), thereby abating the generation of nitric oxide (NO) and prevented the oxidative and nitroxidative lung tissue injury, as shown by the reduction of nitrotyrosine, malondialdehyde (MDA), and poly (ADP-ribose) polymerase (PARP) levels. Finally, we demonstrated that these anti-inflammatory effects of AM were associated with the inhibition of nuclear factor-κB (NF-κB) activation. All these parameters were markedly increased by intrapleural CAR in the absence of any treatment. We report that treatment with AM significantly reduces the development of acute lung injury by downregulating a broad spectrum of inflammatory factors

Analysis of the implementation of GESIDA quality indicators in the HIV+ cohort PSITAR

Objective: To determine the compliance of quality care indicators (GESIDA) for adult patients living with HIV infection in PSITAR cohort. Methods: Multi-center, prospective observational study. All adult naive patients, that began treatment during 2011 belonging to the PSITAR cohort, were selected. We recorded demographic data, virological parameters at baseline and 48 weeks of treatment and pharmacotherapy variables. The selected indicators were: The compliance of initial antiretroviral therapy with the Spanish national treatment guidelines (GESIDA) for treatment-naive HIV-infected patient (95%), undetectable viral load at 48 weeks (80%), treatment initiation with Abacavir without screening for HLA-B*5701 (0%), treatment modifications within the first year (<30%), adherence treatment measure (95%), study of resistance in the virologic failure (90%) and average expenditure per patient in the first treatment (GESIDA median). Results: In total 108 HIV+ naive patients were included, 83.3% men. The median age was 40.5 years (21-75). The most frequent combination was tenofovir-emtricitabineefavirenz with 61.0%. 28 patients (29.7%) modified their treatment during the first year. Focusing on indicators compliance, starting of treatment with a recommended regimen had 95.4% of compliance, undetectable viral load indicator 74.1%, treatment initiation without Abacavir test 0%, treatment modifications within the first year 25.9%, adherence treatment measure 86.3%, study of resistance in the virologic failure 80% and average expenditure per patient was 8,846 euros. Conclusion: Quality care follow up indicators were fulfilled in their vast majority. The worst accomplished indicators such as undetectable viral load at 48 weeks, evaluation of adherence and study of resistance must be study to examine the possible improvement points.Objetivos: Determinar el cumplimiento de los indicadores de calidad de la actividad asistencial GESIDA en la cohorte de pacientes VIH+ PSITAR. Método: Estudio multicéntrico prospectivo. Se seleccionaron aquellos pacientes VIH naive adulto que iniciaron tratamiento en 2011. Se recogieron variables demográficas, analíticas y farmacoterapéuticas. Los indicadores seleccionados fueron: adecuación de las pautas iniciales de TAR a las guías españolas (95%), carga viral indetectable al año de tratamiento (80%), tratamiento con abacavir sin HLA-B*5701 previo (0%), cambios de tratamiento durante el primer año (<30%), registro de la adherencia al tratamiento (95%), estudio de resistencias en el fracaso virológico (90%) y gasto medio por paciente en primer tratamiento (mediana GESIDA). Resultados: Se incluyeron 108 pacientes, de ellos el 83,3% hombres. La mediana de edad fue de 40,5 años (21-75). La combinación de inicio más frecuente fue emtricitabina-tenofovir-efavirenz (61%). El 95,4% de los pacientes iniciaron con un tratamiento considerado preferente. El 74,1% presentó carga viral plasmática indetectable a las 48 semanas. Ningún paciente inicio tratamiento con abacavir sin la determinación del HLA-B*5701. El 25,9% discontinuó el TAR en el primer año, registrándose una valoración de la adherencia en el 86,3% de los casos. El estudio de las resistencias en fallo virológico se realizó en el 80,0% de los pacientes y el gasto medio fue de 8.846 euros. Conclusiones: Los indicadores de calidad de la actividad asistencial se cumplen ampliamente. La carga viral plasmática indetectable, la valoración de la adherencia y el estudio de resistencia requieren de un mayor estudio para detectar puntos de mejora

Biological activity studies on marine natural products as therapeutic strategies in in vitro models of inflammation and colon cancer

Motivation: The inflammatory response is a highly regulated process, and its dysregulation can lead to the establishment of chronic inflammation and, in some cases, it is the cause of several diseases, including cancer. Marine invertebrates are exceptional sources of new natural products, such as terpenoids, which are secondary metabolites that can exhibit anti-inflammatory and anticancerogenic activities. Colon cancer is a disease with a high genetic factor in which inflammation, and therefore its mediators, play an important role.This study focuses on the analysis of the biological activity of various natural terpenoids isolated from marine corals.Methods:HT-29 cells (human adenocarcinoma colon cell line) were grown in McCoy´s 5A and THP-1 cells (human monocytic leukemia cell line) in RPMI1640, both supplemented with 10% FBS and Strep/Pen (37ºC in 5% CO2 atmosphere). Cytotoxic activity was evaluated with the sulforhodamine (SRB) assay. The anti-inflammatory activity was tested on THP-1 through quantification of TNF-alpha, IL-6, IL-8, IL-1B and IL-10 by ELISA and COX-2 and iNOS levels by western-blot. Adherent macrophages were treated with terpenoids (10, 20 and 50 µM) for 1h, followed by stimulation of 1μg/mL LPS for 24h in both assays. Antioxidant activity was measured by ABTS assay.Results: Terpenes showed a moderate cytotoxic activity in both HT-29 and THP-1 macrophages after 48 and 72h. Pre-treatment with these compounds significantly reduced LPS-stimulated cytokines production in THP-1 cells as well as attenuated LPS-induced COX-2 and iNOS protein expression after 24 h. In addition, ABTS assay showed a low antioxidant activity.Conclusions: The five terpenes present a moderate antioxidant and cytotoxic activity as well as a potent anti-inflammatory effect in vitro. This kind of marine natural products may represent an interesting alternative for the treatment of inflammation-related diseases or cancer

Fucoxanthin-Containing Cream Prevents Epidermal Hyperplasia and UVB-Induced Skin Erythema in Mice

Microalgae represent a source of bio-active compounds such as carotenoids with potent anti-inflammatory and antioxidant properties. We aimed to investigate the effects of fucoxanthin (FX) in both in vitro and in vivo skin models. Firstly, its anti-inflammatory activity was evaluated in LPS-stimulated THP-1 macrophages and TNF-α-stimulated HaCaT keratinocytes, and its antioxidant activity in UVB-irradiated HaCaT cells. Next, in vitro and ex vivo permeation studies were developed to determine the most suitable formulation for in vivo FX topical application. Then, we evaluated the effects of a FX-containing cream on TPA-induced epidermal hyperplasia in mice, as well as on UVB-induced acute erythema in hairless mice. Our results confirmed the in vitro reduction of TNF-α, IL-6, ROS and LDH production. Since the permeation results showed that cream was the most favourable vehicle, FX-cream was elaborated. This formulation effectively ameliorated TPA-induced hyperplasia, by reducing skin edema, epidermal thickness, MPO activity and COX-2 expression. Moreover, FX-cream reduced UVB-induced erythema through down-regulation of COX-2 and iNOS as well as up-regulation of HO-1 protein via Nrf-2 pathway. In conclusion, FX, administered in a topical formulation, could be a novel natural adjuvant for preventing exacerbations associated with skin inflammatory pathologies as well as protecting skin against UV radiation

Adrenomedullin in inflammatory process associated with experimental pulmonary fibrosis

<p>Abstract</p> <p>Background</p> <p>Adrenomedullin (AM), a 52-amino acid ringed-structure peptide with C-terminal amidation, was originally isolated from human pheochromocytoma. AM are widely distributed in various tissues and acts as a local vasoactive hormone in various conditions.</p> <p>Methods</p> <p>In the present study, we investigated the efficacy of AM on the animal model of bleomycin (BLM)-induced lung injury. Mice were subjected to intratracheal administration of BLM and were assigned to receive AM daily by an intraperitoneal injection of 200 ngr/kg.</p> <p>Results and Discussion</p> <p>Myeloperoxidase activity, lung histology, immunohistochemical analyses for cytokines and adhesion molecules expression, inducible nitric oxide synthase (iNOS), nitrotyrosine, and poly (ADP-ribose) polymerase (PARP) were performed one week after fibrosis induction. Lung histology and transforming growth factor beta (TGF-β) were performed 14 and 21 days after treatments. After bleomycin administration, AM-treated mice exhibited a reduced degree of lung damage and inflammation compared with BLM-treated mice, as shown by the reduction of (1) myeloperoxidase activity (MPO), (2) cytokines and adhesion molecules expression, (3) nitric oxide synthase expression, (4) the nitration of tyrosine residues, (5) poly (ADP-ribose) (PAR) formation, a product of the nuclear enzyme poly (ADP-ribose) polymerase (PARP) (6) transforming growth factor beta (TGF-β) (7)and the degree of lung injury.</p> <p>Conclusions</p> <p>Our results indicate that AM administration is able to prevent bleomycin induced lung injury through the down regulation of proinflammatory factors.</p

Anti-inflammatory effects of an oxylipin-containing lyophilised biomass from a microalga in a murine recurrent colitis model

Diet and nutritional factors have emerged as possible interventions for inflammatory bowel diseases (IBD), which are characterised by chronic uncontrolled inflammation of the intestinal mucosa. Microalgal species are a promising source of n-3 PUFA and derived oxylipins, which are lipid mediators with a key role in the resolution of inflammation. The aim of the present study was to investigate the effects of an oxylipin-containing lyophilised biomass from Chlamydomonas debaryana on a recurrent 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis mice model. Moderate chronic inflammation of the colon was induced in BALB/c mice by weekly intracolonic instillations of low dose of TNBS. Administration of the lyophilised microalgal biomass started 2 weeks before colitis induction and was continued throughout colitis development. Mice were killed 48 h after the last TNBS challenge. Oral administration of the microalgal biomass reduced TNBS-induced intestinal inflammation, evidenced by an inhibition of body weight loss, an improvement in colon morphology and a decrease in pro-inflammatory cytokines TNF-α, IL-1β, IL-6 and IL-17. This product also down-regulated colonic expressions of inducible nitric oxide, cyclo-oxygenase 2 and NF-κB, as well as increased PPAR-γ. In addition, lyophilised microalgal biomass up-regulated the expressions of the antioxidant transcription factor nuclear factor E2-related factor 2 and the target gene heme oxygenase 1. This study describes for the first time the prophylactic effects of an oxylipin-containing lyophilised microalgae biomass from C. debaryana in the acute phase of a recurrent TNBS-induced colitis model in mice. These findings suggest the potential use of this microalga, or derived oxylipins, as a nutraceutical in the treatment of IBD.España Ministerio de Economía y Competitividad MICIIN PSE-0632/0151España MICIIN INNPACTO-IPT-2012-1370-060000