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Naturally occurring peptides, such as rubiscolins derived from spinach leaves, have been shown to possess some interesting activities. They exerted central effects, such as antinociception, memory consolidation and anxiolytic-like activity. The fact that rubiscolins are potent even when given orally makes them very promising drug candidates. The present work tested whether rubiscolin-6 (R-6, Tyr-Pro-Leu-Asp-Leu-Phe) analogs have neuroprotective and anti-inflammatory effects. These hypotheses were tested in the 6-hydroxydopamine (6-OHDA) injury model of human neuroblastoma SH-SY5Y and lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The determination of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), Caspase-3 activity, lipid peroxidation and nitric oxide (NO) production allowed us to determine the effects of peptides on hallmarks related to Parkinson's Disease (PD) and inflammation. Additionally, we investigated the impact of R-6 analogs on serine-threonine kinase (also known as protein kinase B, AKT) and mammalian target of rapamycin (mTOR) activation. The treatment with analogs 3 (Tyr-Inp-Leu-Asp-Leu-Phe-OH), 5 (Dmt-Inp-Leu-Asp-Leu-Phe-OH) and 7 (Tyr-Inp-Leu-Asp-Leu-Phe-NH2) most effectively prevented neuronal death via attenuation of ROS, mitochondrial dysfunction and Caspase-3 activity. Peptides 5 and 7 significantly increased the protein expression of the phosphorylated-AKT (p-AKT) and phosphorylated-mTOR (p-mTOR). Additionally, selected analogs could also ameliorate LPS-mediated inflammation in macrophages via inhibition of intracellular generation of ROS and NO production. Our findings suggest that R-6 analogs exert protective effects, possibly related to an anti-oxidation mechanism in in vitro model of PD. The data shows that the most potent peptides can inhibit 6-OHDA injury by activating the PI3-K/AKT/mTOR pathway, thus playing a neuroprotective role and may provide a rational and robust approach in the design of new therapeutics or even functional foods.
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Neuroblastoma , Fármacos Neuroprotectores , Enfermedad de Parkinson , Fragmentos de Péptidos , Ribulosa-Bifosfato Carboxilasa , Humanos , Apoptosis , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Oxidopamina/toxicidad , Caspasa 3/metabolismo , Lipopolisacáridos/farmacología , Línea Celular Tumoral , Neuroblastoma/metabolismo , Enfermedad de Parkinson/tratamiento farmacológico , Serina-Treonina Quinasas TOR/metabolismo , Péptidos/uso terapéutico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Inflamación/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéuticoRESUMEN
Wounds or chronic injuries are associated with high medical costs so, develop healing-oriented drugs is a challenge for modern medicine. The identification of new therapeutic alternatives focuses on the use of natural products. Therefore, the main goal of this study was to evaluate the healing potential and anti-inflammatory mechanism of action of extracts and the main compounds derived from Myrciaria plinioides D. Legrand leaves. The antimicrobial activity of leaf extracts was analyzed. Cell viability, cytotoxicity and genotoxicity of plant extracts and compounds were also assessed. Release of pro- and anti-inflammatory cytokines and TGF-ß by ELISA, and protein expression was determined by Western Blot. The cell migration and cell proliferation of ethanol and aqueous leaf extracts and p-coumaric acid, quercetin and caffeic acid compounds were also evaluated. The aqueous extract exhibited antibacterial activity and, after determining the safety concentrations in three assays, we showed that this extract induced p38-α MAPK phosphorylation and the same extract and the p-coumaric acid decreased COX-2 and caspase-3, -8 expression, as well as reduced the TNF-α release and stimulated the IL-10 in RAW 264.7 cells. In L929 cells, the extract and p-coumaric acid induced TGF-ß release, besides increasing the process of cell migration and proliferation. These results suggested that the healing properties of Myrciaria plinioides aqueous extract can be associated to the presence of phenolic compounds, especially p-coumaric acid, and/or glycosylated metabolites.
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The increase in the life expectancy average has led to a growing elderly population, thus leading to a prevalence of neurodegenerative disorders, such as Parkinson's disease (PD). PD is the second most common neurodegenerative disorder and is characterized by a progressive degeneration of the dopaminergic neurons in the substantia nigra pars compacta (SNpc). The marine environment has proven to be a source of unique and diverse chemical structures with great therapeutic potential to be used in the treatment of several pathologies, including neurodegenerative impairments. This review is focused on compounds isolated from marine organisms with neuroprotective activities on in vitro and in vivo models based on their chemical structures, taxonomy, neuroprotective effects, and their possible mechanism of action in PD. About 60 compounds isolated from marine bacteria, fungi, mollusk, sea cucumber, seaweed, soft coral, sponge, and starfish with neuroprotective potential on PD therapy are reported. Peptides, alkaloids, quinones, terpenes, polysaccharides, polyphenols, lipids, pigments, and mycotoxins were isolated from those marine organisms. They can act in several PD hallmarks, reducing oxidative stress, preventing mitochondrial dysfunction, α-synuclein aggregation, and blocking inflammatory pathways through the inhibition translocation of NF-kB factor, reduction of human tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6). This review gathers the marine natural products that have shown pharmacological activities acting on targets belonging to different intracellular signaling pathways related to PD development, which should be considered for future pre-clinical studies.
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Antozoos , Productos Biológicos , Enfermedad de Parkinson , Anciano , Humanos , Animales , Enfermedad de Parkinson/tratamiento farmacológico , Vendajes , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Neuronas DopaminérgicasRESUMEN
The formulation of magnetic ionic liquids (MILs) or organic salts based on lanthanides as anions has been explored. In this work, a set of choline-family-based salts, and two other, different cation families, were combined with Gadolinium(III) and Terbium(III) anions. Synthetic methodologies were previously optimized, and all organic salts were obtained as solids with melting temperatures higher than 100 °C. The magnetic moments obtained for the Gd(III) salts were, as expected, smaller than those obtained for the Tb(III)-based compounds. The values for Gd(III) and Tb(III) magnetic salts are in the range of 6.55-7.30 MB and 8.22-9.34 MB, respectively. It is important to note a correlation between the magnetic moments obtained for lanthanides, and the structural features of the cation. The cytotoxicity of lanthanide-based salts was also evaluated using 3T3, 293T, Caco2, and HepG2 cells, and it was revealed that most of the prepared compounds are not toxic.
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Elementos de la Serie de los Lantanoides , Humanos , Elementos de la Serie de los Lantanoides/farmacología , Elementos de la Serie de los Lantanoides/química , Sales (Química) , Células CACO-2 , Aniones , CationesRESUMEN
Seaweeds are a great source of compounds with cytotoxic properties with the potential to be used as anticancer agents. This study evaluated the cytotoxic and proteasome inhibitory activities of 12R-hydroxy-bromosphaerol, 12S-hydroxy-bromosphaerol, and bromosphaerol isolated from Sphaerococcus coronopifolius. The cytotoxicity was evaluated on malignant cell lines (A549, CACO-2, HCT-15, MCF-7, NCI-H226, PC-3, SH-SY5Y, and SK-MEL-28) using the MTT and LDH assays. The ability of compounds to stimulate the production of hydrogen peroxide (H2O2) and to induce mitochondrial dysfunction, the externalization of phosphatidylserine, Caspase-9 activity, and changes in nuclear morphology was also studied on MCF-7 cells. The ability to induce DNA damage was also studied on L929 fibroblasts. The proteasome inhibitory activity was estimated through molecular docking studies. The compounds exhibited IC50 values between 15.35 and 53.34 µM. 12R-hydroxy-bromosphaerol and 12S-hydroxy-bromosphaerol increased the H2O2 levels on MCF-7 cells, and bromosphaerol induced DNA damage on fibroblasts. All compounds promoted a depolarization of mitochondrial membrane potential, Caspase-9 activity, and nuclear condensation and fragmentation. The compounds have been shown to interact with the chymotrypsin-like catalytic site through molecular docking studies; however, only 12S-hydroxy-bromosphaerol evidenced interaction with ALA20 and SER169, key residues of the proteasome catalytic mechanism. Further studies should be outlined to deeply characterize and understand the potential of those bromoditerpenes for anticancer therapeutics.
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Antineoplásicos , Neuroblastoma , Rhodophyta , Algas Marinas , Humanos , Inhibidores de Proteasoma/farmacología , Peróxido de Hidrógeno/farmacología , Citotoxinas/farmacología , Línea Celular Tumoral , Simulación del Acoplamiento Molecular , Fosfatidilserinas/farmacología , Complejo de la Endopetidasa Proteasomal , Células CACO-2 , Caspasa 9 , Quimotripsina/farmacología , Rhodophyta/química , Antineoplásicos/farmacología , Antineoplásicos/química , ApoptosisRESUMEN
Peptides have revealed a large range of biological activities with high selectivity and efficiency for the development of new drugs, including neuroprotective agents. Therefore, this work investigates the neuroprotective properties of naturally occurring peptides, endomorphin-1 (EM-1), endomorphin-2 (EM-2), rubiscolin-5 (R-5), and rubiscolin-6 (R-6). We aimed at answering the question of whether well-known opioid peptides can counteract cell injury in a common in vitro model of Parkinson's disease (PD). Antioxidant activity of these four peptides was evaluated by the 2-diphenyl-1-picrylhydrazyl radical (DPPH) scavenging activity, oxygen radical absorbance capacity (ORAC), and ferric-reducing antioxidant power (FRAP) assays, while neuroprotective effects were assessed in a neurotoxic model induced by 6-hydroxydopamine (6-OHDA) in a human neuroblastoma cell line (SH-SY5Y). The mechanisms associated with neuroprotection were investigated by the determination of mitochondrial membrane potential (MMP), reactive oxygen species (ROS) production, and Caspase-3 activity. Among the tested peptides, endomorphins significantly prevented neuronal death induced by 6-OHDA treatment, decreasing MMP (EM-1) or Caspase-3 activity (EM-2). Meanwhile, R-6 showed antioxidant potential by FRAP assay and exhibited the highest capacity to recover the neurotoxicity induced by 6-OHDA via attenuation of ROS levels and mitochondrial dysfunction. Generally, we hypothesize that peptides' ability to suppress the toxic effect induced by 6-OHDA may be mediated by different cellular mechanisms. The protective effect caused by endomorphins results in an antiapoptotic effect (mitochondrial protection and decrease in Caspase-3 activity), while R-6 potency to increase a cell's viability seems to be mediated by reducing oxidative stress. Our results may provide new insight into neurodegeneration and support the short peptides as a potent drug candidate to treat PD. However, further studies should be conducted on the detailed mechanisms of how tested peptides could suppress neuronal injuries.
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Neuroblastoma , Fármacos Neuroprotectores , Síndromes de Neurotoxicidad , Enfermedad de Parkinson , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Apoptosis , Caspasa 3/metabolismo , Línea Celular Tumoral , Supervivencia Celular , Humanos , Neuroblastoma/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Péptidos Opioides/farmacología , Oxidopamina/farmacología , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Luteolin is one of the most common flavonoids present in edible plants and its potential benefits to the central nervous system include decrease of microglia activation, neuronal damage and high antioxidant properties. The aim of this research was to evaluate the neuroprotective, antioxidant and anti-inflammatory activities of luteolin-7-O-glucoside (Lut7). Undifferentiated and retinoic acid (RA)-differentiated SH-SY5Y cells were pretreated with Lut7 and incubated with 6-hydroxydopamine (6-OHDA). Cytotoxic and neuroprotective effects were determined by MTT assay. Antioxidant capacity was determined by DPPH, FRAP, and ORAC assays. ROS production, mitochondrial membrane potential (ΔΨm), Caspase-3 activity, acetylcholinesterase inhibition (AChEI) and nuclear damage were also determined in SH-SY5Y cells. TNF-α, IL-6 and IL-10 release were evaluated in LPS-induced RAW264.7 cells by ELISA. In undifferentiated SH-SY5Y cells, Lut7 increased cell viability after 24 h, while in RA-differentiated SH-SY5Y cells, Lut7 increased cell viability after 24 and 48 h. Lut7 showed a high antioxidant activity when compared with synthetic antioxidants. In undifferentiated cells, Lut7 prevented mitochondrial membrane depolarization induced by 6-OHDA treatment, decreased Caspase-3 and AChE activity, and inhibited nuclear condensation and fragmentation. In LPS-stimulated RAW264.7 cells, Lut7 treatment reduced TNF-α levels and increased IL-10 levels after 3 and 24 h, respectively. In summary, the results suggest that Lut7 has neuroprotective effects, thus, further studies should be considered to validate its pharmacological potential in more complex models, aiming the treatment of neurodegenerative diseases.
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Neuroblastoma , Fármacos Neuroprotectores , Acetilcolinesterasa/metabolismo , Antioxidantes/metabolismo , Apoptosis , Caspasa 3/metabolismo , Línea Celular Tumoral , Supervivencia Celular , Flavonas , Glucósidos , Humanos , Interleucina-10/metabolismo , Lipopolisacáridos/farmacología , Potencial de la Membrana Mitocondrial , Neuroblastoma/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Oxidopamina/toxicidad , Tretinoina/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Gastrointestinal diseases, such as peptic ulcers, are caused by a damage in the gastric mucosa provoked by several factors. This stomach injury is regulated by many inflammatory mediators and is commonly treated with proton-pump inhibitors, histamine H2 receptor blockers and antacids. However, various medicinal plants have demonstrated positive effects on gastric ulcer treatment, including plants of the Ceiba genus. The aim of this study was to evaluate the antiulcer and anti-inflammatory activities of the stem bark ethanolic extract of Ceiba speciosa (A. St.-Hil.) Ravenna. We performed a preliminary quantification of phenolic compounds by high-performance liquid chromatography-diode array detection (HPLC-DAD), followed by the prospection of other chemical groups through nuclear magnetic resonance (NMR) spectroscopy. A set of in vitro assays was used to evaluate the extract potential regarding its antioxidant activity (DPPH: 19.83 ± 0.34 µg/mL; TPC: 307.20 ± 6.20 mg GAE/g of extract), effects on cell viability and on the release of TNF-α in whole human blood. Additionally, in vivo assays were performed to evaluate the leukocyte accumulation and total protein quantification in carrageenan-induced air pouch, as well as the antiulcerogenic effect of the extract on an ethanol-induced ulcer in rats. The extract contains flavonoids and phenolic compounds, as well as sugars and quinic acid derivatives exhibiting potent antioxidant activity and low toxicity. The extract reduced the release of TNF-α in human blood and inhibited the activity of p38α (1.66 µg/mL), JAK3 (5.25 µg/mL), and JNK3 (8.34 µg/mL). Moreover, it reduced the leukocyte recruitment on the pouch exudate and the formation of edema, reverting the effects caused by carrageenan. The extract presented a significant prevention of ulcer formation and a higher reduction than the reference drug, Omeprazole. Therefore, C. speciosa extract has demonstrated relevant therapeutic potential for the treatment of gastric diseases, deserving the continuation of further studies to unveil the mechanisms of action of plant bioactive ingredients.
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Antiulcerosos , Ceiba , Extractos Vegetales , Úlcera Gástrica , Animales , Humanos , Ratas , Antiulcerosos/farmacología , Antioxidantes/farmacología , Carragenina/efectos adversos , Ceiba/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/metabolismo , ÚlceraRESUMEN
The growing knowledge about the harmful effects caused by some synthetic ingredients present in skincare products has led to an extensive search for natural bioactives. Thus, this study aimed to investigate the dermatological potential of five fractions (F1-F5), obtained by a sequential extraction procedure, from the brown seaweed Saccorhiza polyschides. The antioxidant (DPPH, FRAP, ORAC and TPC), anti-enzymatic (collagenase, elastase, hyaluronidase and tyrosinase), antimicrobial (Staphylococcus epidermidis, Cutibacterium acnes and Malassezia furfur), anti-inflammatory (nitric oxide, tumor necrosis factor-α, interleukin-6 and interleukin-10) and photoprotective (reactive oxygen species) properties of all fractions were evaluated. The ethyl acetate fraction (F3) displayed the highest antioxidant and photoprotective capacity, reducing ROS levels in UVA/B-exposed 3T3 fibroblasts, and the highest anti-enzymatic capacity against tyrosinase (IC50 value: 89.1 µg/mL). The solid water-insoluble fraction (F5) revealed the greatest antimicrobial activity against C. acnes growth (IC50 value: 12.4 µg/mL). Furthermore, all fractions demonstrated anti-inflammatory potential, reducing TNF-α and IL-6 levels in RAW 264.7 macrophages induced with lipopolysaccharides. Chemical analysis of the S. polyschides fractions by NMR revealed the presence of different classes of compounds, including lipids, polyphenols and sugars. The results highlight the potential of S. polyschides to be incorporated into new nature-based skincare products.
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Antiinfecciosos , Phaeophyceae , Antiinfecciosos/farmacología , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Colagenasas , Hialuronoglucosaminidasa , Interleucina-10 , Interleucina-6 , Lipopolisacáridos , Monofenol Monooxigenasa , Óxido Nítrico , Elastasa Pancreática , Extractos Vegetales/química , Especies Reactivas de Oxígeno , Azúcares , Factor de Necrosis Tumoral alfa , AguaRESUMEN
BACKGROUD: In recent years, research on the bioactive properties of macroalgae has increased, due to the great interest in exploring new products that can contribute to improve human health and wellbeing. In the present study, the antioxidant and antimicrobial potential of six different brown algae of the Fucales order were evaluated, namely Ericaria selaginoides, Ericaria amentacea, Gongolaria baccata, Gongolaria usneoides, Cystoseira compressa and Sargassum vulgare (collected along the Mediterranean and Atlantic coasts). The antioxidant capacity was measured by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, the oxygen radical absorbent capacity (ORAC) and the ferric reducing antioxidant power (FRAP) and were related to the total phenolic content (TPC). The antimicrobial activity was evaluated measuring the growth inhibition of Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans. RESULTS: The highest antioxidant capacity was obtained for Ericaria selaginoides revealing the highest capacity to scavenge DPPH radical [half maximal effective concentration (EC50 ) = 27.02 µg mL-1 ], highest FRAP (1761.19 µmol FeSO4 equivalents g-1 extract), high ORAC (138.92 µmol TE g-1 extract), alongside to its high TPC (121.5 GAE g-1 extract). This species also reported the highest antimicrobial capacity against Staphylococcus aureus [half maximal inhibitory concentration (IC50 ) = 268 µg mL-1 ]. CONCLUSIONS: Among all studied seaweed, Ericaria selaginoides reveals the highest antioxidant and antimicrobial activities, and thus should be explored as a natural food additive and/or functional ingredient. © 2022 Society of Chemical Industry.
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Antiinfecciosos , Phaeophyceae , Algas Marinas , Antibacterianos/farmacología , Antiinfecciosos/química , Antiinfecciosos/farmacología , Antioxidantes/química , Humanos , Mar Mediterráneo , Fenoles/química , Extractos Vegetales/química , Algas Marinas/química , Staphylococcus aureusRESUMEN
The treatment of Parkinson´s disease (PD) has benefited from significant advances resulting from the increasing research efforts focused on new therapeutics. However, the current treatments for PD are mostly symptomatic, alleviating disease symptoms without reversing or retarding disease progression. Thus, it is critical to find new molecules that can result in more effective treatments. Within this framework, this study aims to evaluate the neuroprotective and anti-inflammatory effects of three compounds (eleganolone, eleganonal and fucosterol) isolated from the brown seaweed Bifurcaria bifurcata. In vitro neuroprotective effects were evaluated on a PD cellular model induced by the neurotoxin 6-hydroxydopamine (6-OHDA) on SH-SY5Y human cells, while lipopolysaccharide (LPS) - stimulated RAW 264.7 macrophages were used to evaluate the anti-inflammatory potential. Additionally, the underlying mechanisms of action were also investigated. Compounds were isolated by preparative chromatographic methods and their structural elucidation attained by NMR spectroscopy. Among the tested compounds, eleganolone (0.1-1 µM; 24 h) reverted the neurotoxicity induced by 6-OHDA in about 20%. The neuroprotective effects were mediated by mitochondrial protection, reduction of oxidative stress, inflammation and apoptosis, and inhibition of NF-kB pathway. The results suggest that eleganolone may provide advantages in the treatment of neurodegenerative conditions and, therefore, should be considered for future preclinical studies.
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Antiinflamatorios/farmacología , Diterpenos/farmacología , Fármacos Neuroprotectores/farmacología , Enfermedad de Parkinson/tratamiento farmacológico , Animales , Línea Celular Tumoral , Citocinas/análisis , Diterpenos/uso terapéutico , Humanos , Ratones , Óxido Nítrico/biosíntesis , Células RAW 264.7 , Algas Marinas/química , Factor de Transcripción ReIA/metabolismoRESUMEN
Inflammation is a double-edged sword, as it can have both protective effects and harmful consequences, which, combined with oxidative stress (OS), can lead to the development of deathly chronic inflammatory conditions. Over the years, research has evidenced the potential of marine sponges as a source of effective anti-inflammatory therapeutic agents. Within this framework, the purpose of this study was to evaluate the antioxidant and the anti-inflammatory potential of the marine sponge Cliona celata. For this purpose, their organic extracts (C1-C5) and fractions were evaluated concerning their radical scavenging activity through 2,2-diphenyl-1-picrylhydrazyl radical (DPPH), ferric reducing antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC), and anti-inflammatory activity through a (lipopolysaccharides (LPS)-induced inflammation on RAW 264.7 cells) model. Compounds present in the two most active fractions (F5 and F13) of C4 were tentatively identified by gas chromatography coupled to mass spectrometry (GC-MS). Even though samples displayed low antioxidant activity, they presented a high anti-inflammatory capacity in the studied cellular inflammatory model when compared to the anti-inflammatory standard, dexamethasone. GC-MS analysis led to the identification of n-hexadecanoic acid, cis-9-hexadecenal, and 13-octadecenal in fraction F5, while two major compounds, octadecanoic acid and cholesterol, were identified in fraction F13. The developed studies demonstrated the high anti-inflammatory activity of the marine sponge C. celata extracts and fractions, highlighting its potential for further therapeutic applications.
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Antineoplásicos/farmacología , Poríferos , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antineoplásicos/química , Antioxidantes/química , Antioxidantes/farmacología , Organismos Acuáticos , Línea Celular Tumoral/efectos de los fármacos , Células HT29/efectos de los fármacos , Humanos , Lipopolisacáridos , Ratones , Portugal , Células RAW 264.7/efectos de los fármacosRESUMEN
The ever-increasing interest in keeping a young appearance and healthy skin has leveraged the skincare industry. This, coupled together with the increased concern regarding the safety of synthetic products, has boosted the demand for new and safer natural ingredients. Accordingly, the aim of this study was to evaluate the dermatological potential of the brown seaweed Carpomitra costata. The antioxidant, anti-enzymatic, antimicrobial, photoprotective and anti-inflammatory properties of five C. costata fractions (F1-F5) were evaluated. The ethyl acetate fraction (F3) demonstrated the most promising results, with the best ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals (EC50 of 140.1 µg/mL) and the capacity to reduce reactive oxygen species (ROS) production promoted by UVA and UVB radiation in 3T3 cells, revealing its antioxidant and photoprotective potential. This fraction also exhibited the highest anti-enzymatic capacity, inhibiting the activities of collagenase, elastase and tyrosinase (IC50 of 7.2, 4.8 and 85.9 µg/mL, respectively). Moreover, F3 showed anti-inflammatory potential, reducing TNF-α and IL-6 release induced by LPS treatment in RAW 264.7 cells. These bioactivities may be related to the presence of phenolic compounds, such as phlorotannins, as demonstrated by NMR analysis. The results highlight the potential of C. costata as a source of bioactive ingredients for further dermatological applications.
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Antiinflamatorios/farmacología , Antioxidantes/farmacología , Fármacos Dermatológicos/aislamiento & purificación , Phaeophyceae/química , Células 3T3 , Animales , Antiinflamatorios/aislamiento & purificación , Antioxidantes/aislamiento & purificación , Fármacos Dermatológicos/farmacología , Depuradores de Radicales Libres/aislamiento & purificación , Depuradores de Radicales Libres/farmacología , Concentración 50 Inhibidora , Ratones , Fenoles/aislamiento & purificación , Fenoles/farmacología , Células RAW 264.7 , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Parkinsons Disease (PD) is the second most common neurodegenerative disease worldwide, and is characterized by a progressive degeneration of dopaminergic neurons. Without an effective treatment, it is crucial to find new therapeutic options to fight the neurodegenerative process, which may arise from marine resources. Accordingly, the goal of the present work was to evaluate the ability of the monoterpenoid lactone Loliolide, isolated from the green seaweed Codium tomentosum, to prevent neurological cell death mediated by the neurotoxin 6-hydroxydopamine (6-OHDA) on SH-SY5Y cells and their anti-inflammatory effects in RAW 264.7 macrophages. Loliolide was obtained from the diethyl ether extract, purified through column chromatography and identified by NMR spectroscopy. The neuroprotective effects were evaluated by the MTT method. Cells' exposure to 6-OHDA in the presence of Loliolide led to an increase of cells' viability in 40%, and this effect was mediated by mitochondrial protection, reduction of oxidative stress condition and apoptosis, and inhibition of the NF-kB pathway. Additionally, Loliolide also suppressed nitric oxide production and inhibited the production of TNF-α and IL-6 pro-inflammatory cytokines. The results suggest that Loliolide can inspire the development of new neuroprotective therapeutic agents and thus, more detailed studies should be considered to validate its pharmacological potential.
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Antiinflamatorios/farmacología , Benzofuranos/farmacología , Chlorophyta/química , Lactonas/farmacología , Monoterpenos/farmacología , Enfermedades Neurodegenerativas/tratamiento farmacológico , Animales , Antiinflamatorios/química , Benzofuranos/química , Línea Celular Tumoral , Citocinas/metabolismo , Fragmentación del ADN/efectos de los fármacos , Humanos , Lactonas/química , Macrófagos/citología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Estructura Molecular , Monoterpenos/química , FN-kappa B/metabolismo , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacología , Óxido Nítrico/metabolismo , Células RAW 264.7 , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Marine natural products have exhibited uncommon chemical structures with relevant antitumor properties highlighting their potential to inspire the development of new anticancer agents. The goal of this work was to study the antitumor activities of the brominated diterpene sphaerodactylomelol, a rare example of the dactylomelane family. Cytotoxicity (10-100 µM; 24 h) was evaluated on tumor cells (A549, CACO-2, HCT-15, MCF-7, NCI-H226, PC-3, SH-SY5Y, SK-ML-28) and the effects estimated by MTT assay. Hydrogen peroxide (H2O2) levels and apoptosis biomarkers (membrane translocation of phosphatidylserine, depolarization of mitochondrial membrane potential, Caspase-9 activity, and DNA condensation and/or fragmentation) were studied in the breast adenocarcinoma cellular model (MCF-7) and its genotoxicity on mouse fibroblasts (L929). Sphaerodactylomelol displayed an IC50 range between 33.04 and 89.41 µM without selective activity for a specific tumor tissue. The cells' viability decrease was accompanied by an increase on H2O2 production, a depolarization of mitochondrial membrane potential and an increase of Caspase-9 activity and DNA fragmentation. However, the DNA damage studies in L929 non-malignant cell line suggested that this compound is not genotoxic for normal fibroblasts. Overall, the results suggest that the cytotoxicity of sphaerodactylomelol seems to be mediated by an increase of H2O2 levels and downstream apoptosis.
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Antineoplásicos/farmacología , Apoptosis , Neoplasias de la Mama/tratamiento farmacológico , Diterpenos/farmacología , Fibroblastos/efectos de los fármacos , Rhodophyta/química , Animales , Antineoplásicos/química , Neoplasias de la Mama/patología , Proliferación Celular , Células Cultivadas , Daño del ADN , Diterpenos/química , Femenino , Humanos , Peróxido de Hidrógeno/química , Potencial de la Membrana Mitocondrial/efectos de los fármacos , RatonesRESUMEN
Neurodegenerative diseases, such as Parkinson's disease, represent a biggest challenge for medicine, imposing high social and economic impacts. As a result, it is of utmost importance to develop new therapeutic strategies. The present work evaluated the neuroprotective potential of seaweeds extracts on an in vitro dopamine (DA)-induced neurotoxicity cellular model. The neuroprotective effects on SH-SY5Y cells' viability were estimated by the MTT assay. Changes in mitochondrial membrane potential (MMP), caspase-3 activity, and hydrogen peroxide (H2O2) production were determined. DA (30-3000 µM; 24 h) treatment decreased SH-SY5Y cells' viability in concentration and time-dependent manner, increasing the H2O2 production, MMP depolarization, and caspase-3 activity. On the other hand, DA (1000 µM; 24 h) toxicity was reduced (10-15%) with Sargassum muticum and Codium tomentosum extracts (1000 µg/mL; 24 h). The highest neuroprotective activity was exhibited by a methanolic extract obtained from Saccorhiza polyschides, which completely blunted DA effects. Results show that the marine seaweed S. polyschides contain substances with high neuroprotective potential against the toxicity induced by DA, exhibiting anti-apoptotic effects associated with both mitochondrial protection and caspase-3 inhibition. S. polyschides reveals, therefore, to be an excellent source of bioactive molecules, for new drugs development aiming PD therapeutics.
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Mezclas Complejas , Fármacos Neuroprotectores , Estrés Oxidativo/efectos de los fármacos , Enfermedad de Parkinson , Sargassum/química , Algas Marinas/química , Línea Celular Tumoral , Mezclas Complejas/química , Mezclas Complejas/farmacología , Humanos , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacología , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patologíaRESUMEN
Natural products are still a promising source of bioactive molecules. Food and Drug Administration data showed that approximately 49% of the approved molecules originate naturally or chemically-resemble these substances, of which more than 70% are being used in anticancer therapy. It is noteworthy that at present there are no scientific studies to prove the effectiveness and safety of a number of plants used in folk medicine such as in the case of Calyptranthes grandifolia O. Berg (Myrtaceae) originally from South America. The aim of the present study was to determine the biological potential and toxicological effects of the aqueous leaf extract of C. grandifolia. The main detected phytoconstituents were condensed tannins and flavonoids and a high quantity of polyphenols. Regarding the antimicrobial potential, the extract exerted inhibitory activity against Pseudomonas aeruginosa. The results also revealed the extract induced DNA damage in a concentration-dependent manner in RAW 264.7 cells. In addition, C. grandifolia produced cytotoxicity in leukemia cell lines (HL60 and Kasumi-1) without affecting isolated human lymphocytes but significantly inhibited JAK3 and p38α enzyme activity. Taken together, these findings add important information on the biological and toxicological effects of C. grandifolia, indicating that aqueous extract may be a source of natural antimicrobial and antileukemic constituents.
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Antibacterianos/farmacología , Antineoplásicos Fitogénicos/farmacología , Antioxidantes/farmacología , Myrtaceae/química , Extractos Vegetales/farmacología , Hojas de la Planta/química , Animales , Antibacterianos/química , Antineoplásicos Fitogénicos/química , Antioxidantes/química , Compuestos de Bifenilo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Humanos , Ratones , Picratos , Extractos Vegetales/química , Pseudomonas aeruginosa/efectos de los fármacos , Células RAW 264.7RESUMEN
The International Symposium on Marine Natural Products (MaNaPro) happened for the first time in 1975 in the city of Aberdeen, Scotland, organized by Professor Ronald H [...].
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Organismos Acuáticos , Productos Biológicos , Descubrimiento de Drogas/tendencias , Animales , Europa (Continente) , HumanosRESUMEN
Parkinson's disease (PD) is the second most common neurodegenerative disorder, and is characterized by a progressive degeneration of the dopaminergic neurons in the substantianigra. Although not completely understood, several abnormal cellular events are known to be related with PD progression, such as oxidative stress, mitochondrial dysfunction and apoptosis. Accordingly, the aim of this study was to evaluate the neuroprotective effects of Codium tomentosum enriched fractions in a neurotoxicity model mediated by 6-hydroxydopamine (6-OHDA) on SH-SY5Y human cells, and the disclosure of their mechanisms of action. Additionally, a preliminary chemical screening of the most promising bioactive fractions of C. tomentosum was carried out by GC-MS analysis. Among the tested fractions, four samples exhibited the capacity to revert the neurotoxicity induced by 6-OHDA to values higher or similar to the vitamin E (90.11 ± 3.74% of viable cells). The neuroprotective effects were mediated by the mitigation of reactive oxygen species (ROS) generation, mitochondrial dysfunctions and DNA damage, together with the reduction of Caspase-3 activity. Compounds belonging to different chemical classes, such as terpenes, alcohols, carboxylic acids, aldehydes, esters, ketones, saturated and unsaturated hydrocarbons were tentatively identified by GC-MS. The results show that C. tomentosum is a relevant source of neuroprotective agents, with particular interest for preventive therapeutics.
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Productos Biológicos/farmacología , Chlorophyta/química , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Animales , Antioxidantes , Apoptosis/efectos de los fármacos , Productos Biológicos/química , Productos Biológicos/aislamiento & purificación , Productos Biológicos/uso terapéutico , Línea Celular Tumoral , Fraccionamiento Químico , Humanos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Enfermedades del Sistema Nervioso/diagnóstico , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/metabolismo , Neuroprotección/efectos de los fármacos , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/aislamiento & purificación , Fármacos Neuroprotectores/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Enfermedad de Parkinson , Fenoles/química , Especies Reactivas de Oxígeno/metabolismo , Algas Marinas/químicaRESUMEN
Neurodegenerative diseases are multifactorial debilitating disorders of the nervous system affecting approximately 30 million individuals worldwide. Mitochondrial dysfunction and oxidative stress have also been implicated in causing neurodegeneration. As life expectancy is increasing, neurodegenerative disorders are becoming a major social issue. None of the drugs currently available for treatment are capable of healing the patient. This means that new molecules should be explored. Plants have been used for treatment of countless medical conditions and extensive research is being carried out on species of the Myrtaceae family, widely used in traditional medicine. To date, Myrciaria plinioides D. Legrand has not been studied for its therapeutic use. To evaluate the neuroprotective effect of aqueous and ethanol extracts of this plant, we investigated the protective effects in human neuroblastoma cells (SH-SY5Y). High-performance liquid chromatography fingerprinting of extracts revealed the presence of phenolic compounds and flavonoids. Extracts showed antioxidant activity in the ORAC, DPPH, FRAP and GAE methods. Ethanol extract presented a strong inhibitory activity toward p38 and JNK3 MAPKs and AChE activity and also toward TNF-α release in human whole blood. None of the extracts significantly affected cell viability; the ethanol extract, however, reversed 6-OHDA-induced toxicity. Particularly the ethanol extract suggests neuroprotective effects by preventing membrane depolarization and by significantly decreasing H2O2 production and caspase-3 activity. The present results indicate that the ethanol extract protects SH-SY5Y cells against oxidative damage and apoptosis, as shown by the antioxidative activity of the extract as well as by the inhibition of important proteins such as caspase-3, p38 and JNK3 and the cytokine TNF-α.