Antioxidant, antitumor, and anti-inflammatory activity of natural products obtained from the brown alga Cystoseira usneoides

Macroalgae are an inexhaustible source of natural products that display a variety of pharmacological and biological activities. Among marine algae, the genus Cystoseira has proven to produce a wide variety of secondary metabolites that could benefit human health. However, studies on the natural products of the species Cystoseira usneoides and their respective biological properties are scarce. Hence, in this thesis, the extract of the brown alga Cystoseira usneoides and the natural products isolated therefrom were tested for antioxidant, anticancer, and antiinflammatory activities. The extract of C. usneoides exhibited potent radical-scavenging and inhibited the proliferation of HT-29 cancer cells by inducing apoptotis and G2/M arrest of the cell cycle. The extract was also found to inhibit the production of TNF-α in LPS-stimulated THP-1 human macrophages. The chemical study of the extract yielded six known algal meroterpenoids (AMTs): usneoidone Z (1), 11-hydroxy-1´-O-methylamentadione (2), cystomexicone B (3), cystomexicone A (4), 6-cis-amentadione-1′-methyl ether (5), and amentadione-1′-methyl ether (6), together with six new compounds: cystodiones A-F (7-12). AMTs 1-10 showed radical-scavenging activity in the ABTS assay. The most active were compounds 5, 6, 7, and 8, which exhibited antioxidant capacity equal or superior to that of the Trolox standard. AMTs 1-8 displayed significant cytotoxic activity against HT-29 human colon cancer cells, whereas lower cytotoxicity was observed against non-tumor cells CCD 841 CoN. Flow cytometry analysis revealed that AMTs 2, 3, and 5 caused apoptosis in HT-29 cells and compounds 1, 2, 3, 4, 5, and 7 induced cell cycle arrest in G2/M phase. Furthermore, AMTs 1-8 also inhibited the migration and invasion of colon cancer cells. Interestingly, exposure of HT-29 cells to different concentrations of AMTs 1-8 correlated with the down-regulation of p-ERK, p-JNK, and p-AKT pathways. Regarding to the anticancer effect of AMTs 1-8 against A549 human lung cancer cells, the cytotoxicity of all compounds was selective for A549 cells when compared to the non-tumor MRC-5 cells. Moreover, treatment of A549 cancer cells with AMTs 1-8 also led to cell cycle arrest in S and G2/M phases. In the in vitro anti-inflammatory assays, AMTs 1-8 showed significant activity as inhibitors of the production of the pro-inflammatory mediators TNF-α, IL-1β, IL-6, COX-2 and iNOS in LPSstimulated THP-1 human macrophages. The in vivo study clearly demonstrated that the compound 11-hydroxy-1´-O-methylamentadione (AMT-E, 2) significantly ameliorated DSS colitis (seven days), including the reduction of weight loss, disease activity, macroscopic and microscopic colonic injury. The levels of TNF-α, IL-1β, IL-10, COX-2 and iNOS expression were also significantly decreased in AMT-E treated DSS colitis. Taken together, these findings strengthen the potential of the natural products isolated from C. usneoides as leads for novel antioxidant, anticancer, and anti-inflammatory agents

Anticancer Activities of Meroterpenoids Isolated from the Brown Alga Cystoseira usneoides against the Human Colon Cancer Cells HT-29

Colorectal cancer (CRC) is one of the most common types of cancers and a leading cause of cancer death worldwide. The current treatment for CRC mainly involves surgery, radiotherapy, and chemotherapy. However, due to the side effects and the emergence of drug resistance, the search for new anticancer agents, pharmacologically safe and effective, is needed. In the present study, we have investigated the anticancer effects of eight algal meroterpenoids (AMTs, 1-8) isolated from the brown seaweed Cystoseira usneoides and their underlying mechanisms of action using HT-29, a highly metastatic human colon cancer cell line. All the tested meroterpenoids inhibited the growth of HT-29 malignant cells and were less toxic towards non-cancer colon cells, with the AMTs 1 and 5 exhibiting selectivity indexes of 5.26 and 5.23, respectively. Treatment of HT-29 cells with the AMTs 1, 2, 3, 4, 5, and 7 induced cell cycle arrest in G2/M phase and, in some instances, apoptosis (compounds 2, 3, and 5). Compounds 1-8 also exhibited significant inhibitory effects on the migration and/or invasion of colon cancer cells. Mechanistic analysis demonstrated that the AMTs 1, 2, 5, 6, 7, and 8 reduced phosphorylation levels of extracellular signal-regulated kinase (ERK) and the AMTs 2, 3, 4, 5, 7, and 8 decreased phosphorylation of c-JUN N-terminal kinase (JNK). Moreover, the AMTs 1, 2, 3, 4, 7, and 8 inhibited phosphorylation levels of protein kinase B (AKT) in colon carcinoma cells. These results provide new insights into the mechanisms and functions of the meroterpenoids of C. usneoides, which exhibit an anticancer effect on HT-29 colon cancer cells by inducing cell cycle arrest and apoptosis via the downregulation of ERK/JNK/AKT signaling pathways

Meroterpenoids from the Brown Alga Cystoseira usneoides as Potential Anti-Inflammatory and Lung Anticancer Agents

The anti-inflammatory and anticancer properties of eight meroterpenoids isolated from the brown seaweed Cystoseira usneoides have been evaluated. The algal meroterpenoids (AMTs) 1-8 were tested for their inhibitory effects on the production of the pro-inflammatory cytokines tumor necrosis factor (TNF-alpha), interleukin-6 (IL-6), and interleukin-1 beta (IL-1 beta), and the expression of cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) in LPS-stimulated THP-1 human macrophages. The anticancer effects were assessed by cytotoxicity assays against human lung adenocarcinoma A549 cells and normal lung fibroblastic MRC-5 cells, together with flow cytometry analysis of the effects of these AMTs on different phases of the cell cycle. The AMTs 1-8 significantly reduced the production of TNF-alpha, IL-6, and IL-1 beta, and suppressed the COX-2 and iNOS expression, in LPS-stimulated cells (p < 0.05). The AMTs 1-8 displayed higher cytotoxic activities against A549 cancer cells than against MRC-5 normal lung cells. Cell cycle analyses indicated that most of the AMTs caused the arrest of A549 cells at the G2/M and S phases. The AMTs 2 and 5 stand out by combining significant anti-inflammatory and anticancer activities, while 3 and 4 showed interesting selective anticancer effects. These findings suggest that the AMTs produced by C. usneoides may have therapeutic potential in inflammatory diseases and lung cancer

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

Repurposing anticancer drugs for the management of COVID-19

Since its outbreak in the last December, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has rapidly spread worldwide at a pandemic proportion and thus is regarded as a global public health emergency. The existing therapeutic options for COVID-19 beyond the intensive supportive care are limited, with an undefined or modest efficacy reported so far. Drug repurposing represents an enthusiastic mechanism to use approved drugs outside the scope of their original indication and accelerate the discovery of new therapeutic options. With the emergence of COVID-19, drug repurposing has been largely applied for early clinical testing. In this review, we discuss some repurposed anticancer drugs for the treatment of COVID-19, which are under investigation in clinical trials or proposed for the clinical testing.info:eu-repo/semantics/publishedVersio

The Algal Meroterpene 11-Hydroxy-1′-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-1′-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)-α, interleukin (IL)-1β, 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

Lista de algas marinas del Parque Nacional de Alhucemas en Marruecos (Área Marina Protegida del Mediterráneo)

The Mediterranean basin is a marine biodiversity hot spot. Despite this, the macroalgal diversity of the Mediterranean Sea is still not fully known, especially in the Mediterranean Marine Protected Areas (MPAs) including, Al-Hoceima National Park of Morocco (PNAH). This paper provides the first comprehensive checklist of the seaweeds of PNAH, based chiefly on our own original collections, and complimented by literature records. Using present-day taxonomy, the total number of taxa at both specific and infraspecific levels currently accepted is 306 taxa with 207 Rhodophyta (39 families), 51 Ochrophyta (13 families) and 48 Chlorophyta (12 families). Ninety five of these species were not found in our samples, 93 were new to the PNAH, and the taxonomic identity of 26 taxa was amended. From the totality of taxa, ten species were reported for the first time from Morocco: 9 Rhodophyta and one green alga. Furthermore, 12 others species (10 red, 1 brown and 1 green alga) are new records for the Mediterranean coast of Morocco. Besides this, confirmed records are mentioned for 20 species, whether in Africa, in Morocco or in the Moroccan Mediterranean coast. This accessible checklist to the international community could serve as an infrastructure for future algal investigations of the taxa in this Specially Protected Area of Mediterranean Importance

Checklist of seaweeds of Al-Hoceima National Park of Morocco (Mediterranean Marine Protected Area)

Abstract The Mediterranean basin is a marine biodiversity hot spot. Despite this, the macroalgal diversity of the Mediterranean Sea is still not fully known, especially in the Mediterranean Marine Protected Areas (MPAs) including, Al-Hoceima National Park of Morocco (PNAH). This paper provides the first comprehensive checklist of the seaweeds of PNAH, based chiefly on our own original collections, and complimented by literature records. Using present-day taxonomy, the total number of taxa at both specific and infraspecific levels currently accepted   is 306 taxa with 207 Rhodophyta (39 families), 51 Ochrophyta (13 families) and 48 Chlorophyta (12 families). Ninety five of these species were not found in our samples, 93 were new to the PNAH, and the taxonomic identity of 26 taxa was amended. From the totality of taxa, ten species were reported for the first time from Morocco: 9 Rhodophyta and one green alga. Furthermore, 12 others species (10 red, 1 brown and 1 green alga) are new records for the Mediterranean coast of Morocco. Besides this, confirmed records are mentioned for 20 species, whether in Africa, in Morocco or in the Moroccan Mediterranean coast. This accessible checklist to the international community could serve as an infrastructure for future algal investigations of the taxa in this Specially Protected Area of Mediterranean Importance. Key words: Al-Hoceima National Park, Checklist, Mediterranean Marine Protected Areas, Morocco, Seaweeds. Resumen Lista de algas marinas del Parque Nacional de Alhucemas en Marruecos (Área Marina Protegida del Mediterráneo) La cuenca del Mediterráneo es un Hot Spot de biodiversidad marina. Aún así, la diversidad de macroalgas del Mediterráneo no está plenamente conocida, especialmente en las Áreas Marinas Protegidas del Mediterráneo (AMP) incluido el Parque Nacional de Alhucemas en Marruecos (PNAH). Este documento proporciona la primera lista exhaustiva de las algas marinas del PNAH. Usando la taxonomía actual, el número total de taxones a niveles específicos y infraespecíficos actualmente aceptados es de 306 taxones con 207 Rhodophyta (39 familias), 51 Ochrophyta (13 familias) y 48 Chlorophyta (12 familias). Noventa y cinco de estas especies no se encontraron en nuestras muestras, 93 eran nuevas en el PNAH y se modificó la identidad taxonómica de 26 taxones. De la totalidad de las macroalgas, 10 especies (9 Rhodophyta y 1 Ulvophyceae) fueron registradas por primera vez desde Marruecos. Además, 12 otras especies (10 Rhodophyta, 1 Phaeophyceae y 1 Ulvophyceae) son nuevos registros para la costa mediterránea de Marruecos. También, se mencionan los registros confirmados de 20 especies, ya sea en África, en Marruecos o en la costa mediterránea marroquí. Esta lista de algas accesibles a la comunidad internacional podría servir como una infraestructura para futuras investigaciones algales de los taxones en esta zona especialmente protegida de importancia para el Mediterráneo. Palabras clave: Parque Nacional de Alhucemas, Lista de algas, Áreas Marinas Protegidas del Mediterráneo, Marruecos, Algas marinas.

New records of benthic marine algae from Morocco (eastern Atlantic Ocean): morphology, taxonomy and distribution

AbstractWe report new records and corological data for three Moroccan marine macroalgae that complete their distribution information. Radicilingua thysanorhizans is new record for Morocco; Champia compressa is recorded for the first time from the eastern coast of the Atlantic Ocean. Diplothamnion jolyi is widely distributed in the western coast of the Atlantic coast and Pacific Islands, and recently reported from the Mediterranean Sea; this new record from Moroccan Atlantic coast extends their distribution range.Key words: Algae, Atlantic Ocean, Champia compressa, Diplothamnion jolyi, Radicilingua thysanorhizans.ResumenSe aportan nuevos registros y datos corológicos para tres macroalgas marinas de Marruecos, que completan la información sobre su distribución. Radicilingua thysanorhizans es cita nueva para Marruecos. Champia compressa se registra por la primera vez en la costa oriental del Océano Atlántico. Diplothamnion jolyi se distribuye ampliamente en la costa occidental de la costa atlántica y las islas del Pacífico y ha sido recientemente citada en el mar Mediterráneo; esta nueva cita para costa Atlántica Marroquí amplia su rango de distribución.Palabras clave: Algae, Océano Atlántico, Champia compressa, Diplothamnion jolyi, Radicilingua thysanorhizans