The unicellular green microalga Dunaliella is a potential source of a wide range of nutritionally important compounds applicable to the food industry. The aim of this study was to assess the effect of Dunaliella salina dried biomass on the growth and adherence of 10 strains of Lactobacillus, Lacticaseibacillus, and Bifidobacterium. The immunomodulatory, antioxidant, and cytotoxic effects of D. salina on human peripheral mononuclear cells and simulated intestinal epithelial cell lines Caco-2 and HT-29 were evaluated. Furthermore, the hypocholesterolemic effects of the microalgae on lipid metabolism in rats fed a high-fat diet were analyzed. The addition of D. salina biomass had a positive effect on the growth of nine out of 10 probiotics and promoted the adherence of three bifidobacteria strains to human cell lines. The antioxidant and immunomodulatory properties of D. salina were concentration-dependent. The inflammatory cytokines (TNF-α and IL-6) were significantly increased following Dunaliella stimulation at the lowest concentration (0.5% w/v). Eight week supplementation of D. salina to the diet of hypercholesteromic rats significantly decreased the serum concentrations of LDL-C, VLDL, IDL-B, and IDL-C. D. salina is not cytotoxic in intestinal cell models; it promotes adherence of selected bifidobacteria, it affords immunomodulatory and antioxidant effects, and its addition to diets may help decrease atherosclerosis risk factors.
- MeSH
- antioxidancia farmakologie metabolismus MeSH
- biomasa MeSH
- Caco-2 buňky MeSH
- Chlorophyceae * MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- mikrořasy * metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Alginates have been widely explored due to their salient advantages of hydrophilicity, biocompatibility, mucoadhesive features, bioavailability, environmentally-benign properties, and cost-effectiveness. They are applied for designing micro- and nanosystems for controlled and targeted drug delivery and cancer therapy as alginate biopolymers find usage in encapsulating anticancer drugs to improve their bioavailability, sustained release, pharmacokinetics, and bio-clearance. Notably, these nanomaterials can be applied for photothermal, photodynamic, and chemodynamic therapy of cancers/tumors. Future explorations ought to be conducted to find novel alginate-based (nano)systems for targeted cancer therapy using advanced drug delivery techniques with benefits of non-invasiveness, patient compliance, and convenience of drug administration. Thus, some critical parameters such as mucosal permeability, stability in the gastrointestinal tract environment, and drug solubility ought to be considered. In addition, the comprehensive clinical translational studies along with the optimization of synthesis techniques still need to be addressed. Herein, we present an overview of the current state of knowledge and recent developments pertaining to the applications of alginate-based micro- and nanosystems for targeted cancer therapy based on controlled drug delivery, photothermal therapy, and chemodynamic/photodynamic therapy approaches, focusing on important challenges and future directions.
- MeSH
- algináty * MeSH
- biologická dostupnost MeSH
- léky s prodlouženým účinkem MeSH
- lidé MeSH
- nádory * farmakoterapie MeSH
- rozpustnost MeSH
- systémy cílené aplikace léků metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Six new (1, 2, 6, 8, 13, and 20) and twenty previously isolated (3-5, 7, 9-12, 14-19, and 21-26) steroids featuring thirteen different carbocycle motifs were isolated from the organic extract of the soft coral Sinularia polydactyla collected from the Hurghada reef in the Red Sea. The structures and the relative configurations of the isolated natural products have been determined based on extensive analysis of their NMR and MS data. The cytotoxic, anti-inflammatory, anti-angiogenic, and neuroprotective activity of compounds 3-7, 9-12, 14-20, and 22-26, as well as their effect on androgen receptor-regulated transcription was evaluated in vitro in human tumor and non-cancerous cells. Steroids 22 and 23 showed significant cytotoxicity in the low micromolar range against the HeLa and MCF7 cancer cell lines, while migration of endothelial cells was inhibited by compounds 11, 12, 22, and 23 at 20 µM. The results of the androgen receptor (AR) reporter assay showed that compound 11 exhibited the strongest inhibition of AR at 10 µM, while it is noteworthy that steroids 10, 16, and 20 displayed increased inhibition of AR with decreasing concentrations. Additionally, compounds 11 and 23 showed neuroprotective activity on neuron-like SH-SY5Y cells.
- MeSH
- antiflogistika izolace a purifikace farmakologie MeSH
- antitumorózní látky izolace a purifikace farmakologie MeSH
- endoteliální buňky pupečníkové žíly (lidské) účinky léků metabolismus MeSH
- fyziologická neovaskularizace účinky léků MeSH
- HeLa buňky MeSH
- inhibitory angiogeneze izolace a purifikace farmakologie MeSH
- korálnatci chemie MeSH
- lidé MeSH
- MFC-7 buňky MeSH
- molekulární struktura MeSH
- nádory farmakoterapie metabolismus patologie MeSH
- neurony účinky léků metabolismus patologie MeSH
- neuroprotektivní látky izolace a purifikace farmakologie MeSH
- steroidy izolace a purifikace farmakologie MeSH
- viabilita buněk účinky léků MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Geografické názvy
- Indický oceán MeSH
Seaweeds have been exploited as both food products and therapeutics to manage human ailments for centuries. This study investigated the metabolite profile of five seaweeds (Halimeda spp., Spyridia hypnoides (Bory de Saint-Vincent) Papenfuss, Valoniopsis pachynema (G. Martens) Børgesen, Gracilaria fergusonii J. Agardh and Amphiroa anceps (Lamarck) Decaisne using ultra-high-performance liquid chromatography coupled with electrospray ionization mass spectrometry (UHPLC-ESI-MS/MS). Furthermore, these seaweeds were assessed for antioxidant and inhibitory effects against α-amylase, α-glucosidase, acetyl-cholinesterase (AChE), butyryl-cholinesterase (BChE) and tyrosinase. Valoniopsis pachynema and A. anceps yielded the highest flavonoid (4.30 ± 0.29 mg RE/g) and phenolic content (7.83 ± 0.08 mg RE/g), respectively. Additionally, A. anceps exhibited significant antioxidant properties with all assays and significantly depressed BChE (IC50 = 6.68 ± 0.83 mg/mL) and α-amylase activities (IC50 = 5.34 ± 0.14 mg/mL). Interestingly, the five seaweeds revealed potent inhibitory effects against tyrosinase activity. In conclusion, A. anceps might be considered as a key source of phytoantioxidants and a potential candidate to develop nutritional supplements. Besides, the five tested seaweeds warrant further study and may be exploited as promising natural sources for managing hyperpigmentation.
Marine sponges, a well-documented prolific source of natural products, harbor highly diverse microbial communities. Their extracts were previously shown to contain quorum sensing (QS) signal molecules of the N-acyl homoserine lactone (AHL) type, known to orchestrate bacterial gene regulation. Some bacteria and eukaryotic organisms are known to produce molecules that can interfere with QS signaling, thus affecting microbial genetic regulation and function. In the present study, we established the production of both QS signal molecules as well as QS inhibitory (QSI) molecules in the sponge species Sarcotragus spinosulus. A total of eighteen saturated acyl chain AHLs were identified along with six unsaturated acyl chain AHLs. Bioassay-guided purification led to the isolation of two brominated metabolites with QSI activity. The structures of these compounds were elucidated by comparative spectral analysis of 1HNMR and HR-MS data and were identified as 3-bromo-4-methoxyphenethylamine (1) and 5,6-dibromo-N,N-dimethyltryptamine (2). The QSI activity of compounds 1 and 2 was evaluated using reporter gene assays for long- and short-chain AHL signals (Escherichia coli pSB1075 and E. coli pSB401, respectively). QSI activity was further confirmed by measuring dose-dependent inhibition of proteolytic activity and pyocyanin production in Pseudomonas aeruginosa PAO1. The obtained results show the coexistence of QS and QSI in S. spinosulus, a complex signal network that may mediate the orchestrated function of the microbiome within the sponge holobiont.
- MeSH
- Escherichia coli účinky léků fyziologie MeSH
- faktory virulence MeSH
- fylogeneze MeSH
- luminiscenční měření MeSH
- Porifera genetika metabolismus mikrobiologie MeSH
- proteasy chemie farmakologie MeSH
- pyokyanin chemie farmakologie MeSH
- quorum sensing účinky léků MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
This study explored the antitubercular properties of fucoxanthin, a marine carotenoid, against clinical isolates of Mycobacterium tuberculosis (Mtb). Two vital enzymes involved in Mtb cell wall biosynthesis, UDP-galactopyranose mutase (UGM) and arylamine-N-acetyltransferase (TBNAT), were selected as drug targets to reveal the mechanism underlying the antitubercular effect of fucoxanthin. The obtained results showed that fucoxanthin showed a clear bacteriostatic action against the all Mtb strains tested, with minimum inhibitory concentrations (MIC) ranging from 2.8 to 4.1 µM, along with a good degree of selectivity index (ranging from 6.1 to 8.9) based on cellular toxicity evaluation compared with standard drug isoniazid (INH). The potent inhibitory actions of fucoxanthin and standard uridine-5'-diphosphate against UGM were recorded to be 98.2% and 99.2%, respectively. TBNAT was potently inactivated by fucoxanthin (half maximal inhibitory concentration (IC50) = 4.8 µM; 99.1% inhibition) as compared to INH (IC50 = 5.9 µM; 97.4% inhibition). Further, molecular docking approaches were achieved to endorse and rationalize the biological findings along with envisaging structure-activity relationships. Since the clinical evidence of the last decade has confirmed the correlation between bacterial infections and autoimmune diseases, in this study we have discussed the linkage between infection with Mtb and autoimmune diseases based on previous clinical observations and animal studies. In conclusion, we propose that fucoxanthin could demonstrate great therapeutic value for the treatment of tuberculosis by acting on multiple targets through a bacteriostatic effect as well as by inhibiting UGM and TBNAT. Such outcomes may lead to avoiding or decreasing the susceptibility to autoimmune diseases associated with Mtb infection in a genetically susceptible host.
- MeSH
- antituberkulotika farmakologie MeSH
- arylamin-N-acetyltransferasa metabolismus MeSH
- autoimunitní nemoci farmakoterapie MeSH
- buněčná stěna účinky léků enzymologie MeSH
- buněčné linie MeSH
- intramolekulární transferasy metabolismus MeSH
- izoenzymy metabolismus MeSH
- karotenoidy farmakologie MeSH
- lidé MeSH
- mikrobiální testy citlivosti metody MeSH
- Mycobacterium tuberculosis účinky léků enzymologie MeSH
- simulace molekulového dockingu metody MeSH
- tuberkulóza farmakoterapie MeSH
- xanthofyly farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Pregnane X Receptor (PXR) is a ligand-activated transcription factor which binds many structurally different molecules. The receptor is able to regulate the expression of a wide array of genes and is involved in cancer and different key physiological processes such as the metabolism of drugs/xenobiotics and endogenous compounds including lipids and carbohydrates, and inflammation. Algae, sponges, sea squirts, and other marine organisms are some of the species from which structurally new molecules have been isolated that have been subsequently identified in recent decades as ligands for PXR. The therapeutic potential of these natural compounds is promising in different areas and has recently resulted in the registration of trabectedin by the FDA as a novel antineoplastic drug. Apart from being potentially novel drugs, these compounds can also serve as models for the development of new molecules with improved activity. The aim of this review is to succinctly summarize the currently known natural molecules isolated from marine organisms with a proven ability to interact with PXR.
- MeSH
- biologické přípravky chemie izolace a purifikace farmakologie MeSH
- lidé MeSH
- ligandy MeSH
- molekulární struktura MeSH
- Porifera chemie MeSH
- pregnanový X receptor metabolismus MeSH
- regulace genové exprese účinky léků MeSH
- Urochordata chemie MeSH
- vodní organismy chemie MeSH
- vyvíjení léků * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
We found previously that white adipose tissue (WAT) hyperplasia in obese mice was limited by dietary omega-3 polyunsaturated fatty acids (omega-3 PUFA). Here we aimed to characterize the underlying mechanism. C57BL/6N mice were fed a high-fat diet supplemented or not with omega-3 PUFA for one week or eight weeks; mice fed a standard chow diet were also used. In epididymal WAT (eWAT), DNA content was quantified, immunohistochemical analysis was used to reveal the size of adipocytes and macrophage content, and lipidomic analysis and a gene expression screen were performed to assess inflammatory status. The stromal-vascular fraction of eWAT, which contained most of the eWAT cells, except for adipocytes, was characterized using flow cytometry. Omega-3 PUFA supplementation limited the high-fat diet-induced increase in eWAT weight, cell number (DNA content), inflammation, and adipocyte growth. eWAT hyperplasia was compromised due to the limited increase in the number of preadipocytes and a decrease in the number of endothelial cells. The number of leukocytes and macrophages was unaffected, but a shift in macrophage polarization towards a less inflammatory phenotype was observed. Our results document that the counteraction of eWAT hyperplasia by omega-3 PUFA in dietary-obese mice reflects an effect on the number of adipose lineage and endothelial cells.
- MeSH
- bílá tuková tkáň účinky léků MeSH
- dieta s vysokým obsahem tuků MeSH
- endoteliální buňky účinky léků MeSH
- kyseliny mastné omega-3 aplikace a dávkování MeSH
- makrofágy účinky léků patologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- proliferace buněk účinky léků MeSH
- tukové buňky cytologie účinky léků MeSH
- zánět patologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Ciguatoxins (CTXs) are marine toxins that cause ciguatera fish poisoning, a debilitating disease dominated by sensory and neurological disturbances that include cold allodynia and various painful symptoms as well as long-lasting pruritus. Although CTXs are known as the most potent mammalian sodium channel activator toxins, the etiology of many of its neurosensory symptoms remains unresolved. We recently described that local application of 1 nM Pacific Ciguatoxin-1 (P-CTX-1) into the skin of human subjects induces a long-lasting, painful axon reflex flare and that CTXs are particularly effective in releasing calcitonin-gene related peptide (CGRP) from nerve terminals. In this study, we used mouse and rat skin preparations and enzyme-linked immunosorbent assays (ELISA) to study the molecular mechanism by which P-CTX-1 induces CGRP release. We show that P-CTX-1 induces CGRP release more effectively in mouse as compared to rat skin, exhibiting EC50 concentrations in the low nanomolar range. P-CTX-1-induced CGRP release from skin is dependent on extracellular calcium and sodium, but independent from the activation of various thermosensory transient receptor potential (TRP) ion channels. In contrast, lidocaine and tetrodotoxin (TTX) reduce CGRP release by 53-75%, with the remaining fraction involving L-type and T-type voltage-gated calcium channels (VGCC). Using transgenic mice, we revealed that the TTX-resistant voltage-gated sodium channel (VGSC) NaV1.9, but not NaV1.8 or NaV1.7 alone and the combined activation of the TTX-sensitive VGSC subtypes NaV1.7 and NaV1.1 carry the largest part of the P-CTX-1-caused CGRP release of 42% and 34%, respectively. Given the contribution of CGRP to nociceptive and itch sensing pathways, our findings contribute to a better understanding of sensory symptoms of acute and chronic ciguatera that may help in the identification of potential therapeutics.
- MeSH
- ciguatera metabolismus MeSH
- ciguatoxiny chemie farmakologie MeSH
- ELISA MeSH
- hyperalgezie chemicky indukované MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- lidokain farmakologie MeSH
- membránové potenciály účinky léků MeSH
- mořské toxiny farmakologie MeSH
- myši transgenní MeSH
- myši MeSH
- napětím řízený sodíkový kanál, typ 1 účinky léků MeSH
- napětově řízený sodíkový kanál typ 11 účinky léků MeSH
- napěťově řízený sodíkový kanál, typ 9 účinky léků MeSH
- peptid spojený s genem pro kalcitonin účinky léků MeSH
- receptory peptidu se vztahem ke genu kalcitoninu účinky léků MeSH
- tetrodotoxin farmakologie MeSH
- vápník metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Exposure to β-N-methylamino-l-alanine (BMAA) might be linked to the incidence of amyotrophic lateral sclerosis, Alzheimer's disease and Parkinson's disease. Analytical chemistry plays a crucial role in determining human BMAA exposure and the associated health risk, but the performance of various analytical methods currently employed is rarely compared. A CYANOCOST initiated workshop was organized aimed at training scientists in BMAA analysis, creating mutual understanding and paving the way towards interlaboratory comparison exercises. During this workshop, we tested different methods (extraction followed by derivatization and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) analysis, or directly followed by LC-MS/MS analysis) for trueness and intermediate precision. We adapted three workup methods for the underivatized analysis of animal, brain and cyanobacterial samples. Based on recovery of the internal standard D₃BMAA, the underivatized methods were accurate (mean recovery 80%) and precise (mean relative standard deviation 10%), except for the cyanobacterium Leptolyngbya. However, total BMAA concentrations in the positive controls (cycad seeds) showed higher variation (relative standard deviation 21%-32%), implying that D₃BMAA was not a good indicator for the release of BMAA from bound forms. Significant losses occurred during workup for the derivatized method, resulting in low recovery (<10%). Most BMAA was found in a trichloroacetic acid soluble, bound form and we recommend including this fraction during analysis.
- MeSH
- aminokyseliny diaminové analýza metabolismus MeSH
- chromatografie kapalinová metody MeSH
- Daphnia MeSH
- kyselina trichloroctová chemie MeSH
- mozek metabolismus MeSH
- neurotoxiny analýza metabolismus MeSH
- reprodukovatelnost výsledků MeSH
- sinice metabolismus MeSH
- tandemová hmotnostní spektrometrie metody MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
