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Biomedicine & Pharmacotherapy =... Aug 2023Vitamin A (retinol) is a lipid-soluble vitamin that acts as a precursor for several bioactive compounds, such as retinaldehyde (retinal) and isomers of retinoic acid....
Vitamin A (retinol) is a lipid-soluble vitamin that acts as a precursor for several bioactive compounds, such as retinaldehyde (retinal) and isomers of retinoic acid. Retinol and all-trans-retinoic acid (atRA) penetrate the blood-brain barrier and are reported to be neuroprotective in several animal models. We characterised the impact of retinol and its metabolites, all-trans-retinal (atRAL) and atRA, on ferroptosis-a programmed cell death caused by iron-dependent phospholipid peroxidation. Ferroptosis was induced by erastin, buthionine sulfoximine or RSL3 in neuronal and non-neuronal cell lines. We found that retinol, atRAL and atRA inhibited ferroptosis with a potency superior to α-tocopherol, the canonical anti-ferroptotic vitamin. In contrast, we found that antagonism of endogenous retinol with anhydroretinol sensitises ferroptosis induced in neuronal and non-neuronal cell lines. Retinol and its metabolites atRAL and atRA directly interdict lipid radicals in ferroptosis since these compounds displayed radical trapping properties in a cell-free assay. Vitamin A, therefore, complements other anti-ferroptotic vitamins, E and K; metabolites of vitamin A, or agents that alter their levels, may be potential therapeutics for diseases where ferroptosis is implicated.
Topics: Animals; Vitamin A; Ferroptosis; Lipid Peroxidation; Tretinoin; Vitamins; Retinaldehyde; Lipids
PubMed: 37236031
DOI: 10.1016/j.biopha.2023.114930 -
Molecules (Basel, Switzerland) Jul 2020Bioactive compounds with diverse chemical structures play a significant role in disease prevention and maintenance of physiological functions. Due to the increase in... (Review)
Review
Bioactive compounds with diverse chemical structures play a significant role in disease prevention and maintenance of physiological functions. Due to the increase in industrial demand for new biosourced molecules, several types of biomasses are being exploited for the identification of bioactive metabolites and techno-functional biomolecules that are suitable for the subsequent uses in cosmetic, food and pharmaceutical fields. Among the various biomasses available, macroalgae are gaining popularity because of their potential nutraceutical and health benefits. Such health effects are delivered by specific diterpenes, pigments (fucoxanthin, phycocyanin, and carotenoids), bioactive peptides and polysaccharides. Abundant and recent studies have identified valuable biological activities of native algae polysaccharides, but also of their derivatives, including oligosaccharides and (bio)chemically modified polysaccharides. However, only a few of them can be industrially developed and open up new markets of active molecules, extracts or ingredients. In this respect, the health and nutraceutical claims associated with marine algal bioactive polysaccharides are summarized and comprehensively discussed in this review.
Topics: Carotenoids; Dietary Supplements; Humans; Peptides; Polysaccharides; Seaweed; Xanthophylls
PubMed: 32660153
DOI: 10.3390/molecules25143152 -
Molecules (Basel, Switzerland) Feb 2022Carotenoids represent a class of pigmented terpenoids. They are distributed in all taxonomic groups of fungi. Most of the fungal carotenoids differ in their chemical... (Review)
Review
Carotenoids represent a class of pigmented terpenoids. They are distributed in all taxonomic groups of fungi. Most of the fungal carotenoids differ in their chemical structures to those from other organisms. The general function of carotenoids in heterotrophic organisms is protection as antioxidants against reactive oxygen species generated by photosensitized reactions. Furthermore, carotenoids are metabolized to apocarotenoids by oxidative cleavage. This review presents the current knowledge on fungal-specific carotenoids, their occurrence in different taxonomic groups, and their biosynthesis and conversion into trisporic acids. The outline of the different pathways was focused on the reactions and genes involved in not only the known pathways, but also suggested the possible mechanisms of reactions, which may occur in several non-characterized pathways in different fungi. Finally, efforts and strategies for genetic engineering to enhance or establish pathways for the production of various carotenoids in carotenogenic or non-carotenogenic yeasts were highlighted, addressing the most-advanced producers of each engineered yeast, which offered the highest biotechnological potentials as production systems.
Topics: Biological Evolution; Biological Transport; Biosynthetic Pathways; Carotenoids; Fatty Acids, Unsaturated; Fungi; Gene Expression Regulation, Fungal; Genetic Engineering; Mutagenesis; beta Carotene
PubMed: 35209220
DOI: 10.3390/molecules27041431 -
Roczniki Panstwowego Zakladu Higieny 2023Lutein and zeaxanthin are naturally occurring xanthophylls, mainly present in green, leafy vegetables and egg's yolk. Their presence is connected with blue spectrum...
Lutein and zeaxanthin are naturally occurring xanthophylls, mainly present in green, leafy vegetables and egg's yolk. Their presence is connected with blue spectrum light absorbance, including UV. This property, and fact, that these xanthophylls are accumulated by human eye's macula, leads to eye's protective functions of them including protection from age-related macular degeneration (AMD). Also, antioxidative features of lutein and zeaxanthin are boosting overall health of human body. Numerous studies proves anti-inflammatory and protective attributes of these compounds, based on many, different mechanisms. One of them is regulating redox potential in cells, and impact on expression of linked genes. In preventing of eye diseases, an important gene that is regulated by lutein and zeaxanthin is the Nrf2 gene, whose increased activity leads to optimizing the cellular response to reactive oxygen species (ROS) and preventing related diseases. Other research confirms antiproliferative properties of mentioned compounds in case of certain human cancer cell lines. There are e.g.: HepG2 (hepatitis cancer), MCF-7 (breast cancer), which treated in vitro with lutein solution showed reduction of cell growth. Lutein alone, during in vivo studies conducted on mice, exhibited also radioprotective properties, positively affecting the vitality of animals. Lutein provides also increasing of tolerance to UV radiation, reducing inflammatory processes in the skin and preventing oncogenesis. Low intake of lutein and zeaxanthin, associated with "western diet", rich in simple carbohydrates and processed food, common in developed countries, including Poland, is linked with diabetes and obesity incidence. Assuming, lutein and zeaxanthin significantly affect the well-being of the human body, and their appropriate amount in diet can help reduce risk of many diseases. For supplementation, the optimized dosage of these xanthophylls includes doses of 10 mg for lutein and 2 mg for zeaxanthin, and it is recommended to consume along with fats or meals rich in fats.
Topics: Humans; Animals; Mice; Lutein; Zeaxanthins; Xanthophylls; Macular Degeneration; Diet; Neoplasms
PubMed: 37577931
DOI: 10.32394/rpzh.2023.0266 -
Molecules (Basel, Switzerland) Mar 2021In synthetic organic chemistry, there are very useful basic compounds known as building blocks. One of the main reactions wherein they are applied for the synthesis of... (Review)
Review
In synthetic organic chemistry, there are very useful basic compounds known as building blocks. One of the main reactions wherein they are applied for the synthesis of complex molecules is the Diels-Alder cycloaddition. This reaction is between a diene and a dienophile. Among the most important dienes are the cyclic dienes, as they facilitate the reaction. This review considers the synthesis and reactivity of one of these dienes with special characteristics-it is cyclic and has an electron withdrawing group. This building block has been used for the synthesis of biologically active compounds and is present in natural compounds with interesting properties.
Topics: Cycloaddition Reaction; Molecular Structure; Polyenes; Stereoisomerism
PubMed: 33809941
DOI: 10.3390/molecules26061772 -
Angewandte Chemie (International Ed. in... Mar 2020The combination of electrocyclizations and cycloadditions accounts for the formation of a range of fascinating natural products. Cascades consisting of 8π...
The combination of electrocyclizations and cycloadditions accounts for the formation of a range of fascinating natural products. Cascades consisting of 8π electrocyclizations followed by a 6π electrocyclization and a cycloaddition are relatively common. We now report the synthesis of the tetramic acid PF-1018 through an 8π electrocyclization, the product of which is immediately intercepted by a Diels-Alder cycloaddition. The success of this pericyclic cascade was critically dependent on the substitution pattern of the starting polyene and could be rationalized through DFT calculations. The completion of the synthesis required the instalment of a trisubstituted double bond by radical deoxygenation. An unexpected side product formed through 4-exo-trig radical cyclization could be recycled through an unprecedented triflation/fragmentation.
Topics: Biological Products; Cyclization; Cycloaddition Reaction; Density Functional Theory; Electrochemical Techniques; Models, Molecular; Polyenes; Pyrrolidinones; Pyrrolizidine Alkaloids; Stereoisomerism
PubMed: 31788926
DOI: 10.1002/anie.201912452 -
Nutrients Jan 2021Animal studies as early as the 1920s suggested that vitamin A deficiency leads to squamous cell metaplasia in numerous epithelial tissues including the skin. However,... (Review)
Review
Animal studies as early as the 1920s suggested that vitamin A deficiency leads to squamous cell metaplasia in numerous epithelial tissues including the skin. However, humans usually die from vitamin A deficiency before cancers have time to develop. A recent long-term cohort study found that high dietary vitamin A reduced the risk of cutaneous squamous cell carcinoma (cSCC). cSCC is a form of nonmelanoma skin cancer that primarily occurs from excess exposure to ultraviolet light B (UVB). These cancers are expensive to treat and can lead to metastasis and death. Oral synthetic retinoids prevent the reoccurrence of cSCC, but side effects limit their use in chemoprevention. Several proteins involved in vitamin A metabolism and signaling are altered in cSCC, which may lead to retinoid resistance. The expression of vitamin A metabolism proteins may also have prognostic value. This article reviews what is known about natural and synthetic retinoids and their metabolism in cSCC.
Topics: Animals; Antineoplastic Agents; Biological Products; Carcinoma, Squamous Cell; Clinical Studies as Topic; Disease Management; Drug Evaluation, Preclinical; Drug Resistance; Humans; Metabolic Networks and Pathways; Retinoids; Skin Neoplasms; Treatment Outcome; Vitamin A
PubMed: 33466372
DOI: 10.3390/nu13010153 -
Marine Drugs May 2022Over the past few decades (covering 1972 to 2022), astounding progress has been made in the elucidation of structures, bioactivities and biosynthesis of polyene... (Review)
Review
Over the past few decades (covering 1972 to 2022), astounding progress has been made in the elucidation of structures, bioactivities and biosynthesis of polyene macrolactams (PMLs), but they have only been partially summarized. PMLs possess a wide range of biological activities, particularly distinctive fungal inhibitory abilities, which render them a promising drug candidate. Moreover, the unique biosynthetic pathways including β-amino acid initiation and pericyclic reactions were presented in PMLs, leading to more attention from inside and outside the natural products community. According to current summation, in this review, the chem- and bio-diversity of PMLs from marine and terrestrial sources are considerably rich. A systematic, critical and comprehensive overview is in great need. This review described the PMLs' general structural features, production strategies, biosynthetic pathways and the mechanisms of bioactivities. The challenges and opportunities for the research of PMLs are also discussed.
Topics: Biological Products; Biosynthetic Pathways; Polyenes
PubMed: 35736163
DOI: 10.3390/md20060360 -
Marine Drugs Dec 2023Crocin is one of the most valuable components of the Chinese medicinal plant and is widely used in the food, cosmetics, and pharmaceutical industries. Traditional... (Review)
Review
Crocin is one of the most valuable components of the Chinese medicinal plant and is widely used in the food, cosmetics, and pharmaceutical industries. Traditional planting of is unable to fulfill the increasing demand for crocin in the global market, however, such that researchers have turned their attention to the heterologous production of crocin in a variety of hosts. At present, there are reports of successful heterologous production of crocin in , , microalgae, and plants that do not naturally produce crocin. Of these, the microalga , which produces high levels of -carotene, the substrate for crocin biosynthesis, is worthy of attention. This article describes the biosynthesis of crocin, compares the features of each heterologous host, and clarifies the requirements for efficient production of crocin in microalgae.
Topics: Carotenoids; beta Carotene; Chlorophyceae; Drug Industry; Escherichia coli; Microalgae; Saccharomyces cerevisiae
PubMed: 38248646
DOI: 10.3390/md22010022 -
Methods in Enzymology 2022Carotenoids constitute an essential dietary component of animals and other non-carotenogenic species which use these pigments in both their modified and unmodified...
Carotenoids constitute an essential dietary component of animals and other non-carotenogenic species which use these pigments in both their modified and unmodified forms. Animals utilize uncleaved carotenoids to mitigate light damage and oxidative stress and to signal fitness and health. Carotenoids also serve as precursors of apocarotenoids including retinol, and its retinoid metabolites, which carry out essential functions in animals by forming the visual chromophore 11-cis-retinaldehyde. Retinoids, such as all-trans-retinoic acid, can also act as ligands of nuclear hormone receptors. The fact that enzymes and biochemical pathways responsible for the metabolism of carotenoids in animals bear resemblance to the ones in plants and other carotenogenic species suggests an evolutionary relationship. We will explore some of the modes of transmission of carotenoid genes from carotenogenic species to metazoans. This apparent relationship has been successfully exploited in the past to identify and characterize new carotenoid and retinoid modifying enzymes. We will review approaches used to identify putative animal carotenoid enzymes, and we will describe methods used to functionally validate and analyze the biochemistry of carotenoid modifying enzymes encoded by animals.
Topics: Animals; Carotenoids; Plants; Retinaldehyde; Retinoids
PubMed: 36008015
DOI: 10.1016/bs.mie.2022.05.005