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Science Advances Jun 2024Withanolides are a group of naturally occurring C steroids based on an ergostane skeleton. They have a high degree of polyoxygenation, and the abundance of -functional...
Withanolides are a group of naturally occurring C steroids based on an ergostane skeleton. They have a high degree of polyoxygenation, and the abundance of -functional groups has enabled various natural alterations to both the carbocyclic skeleton and the side chain. Consequently, these molecules have intricate structural features that lead to their highly varied display of biological activities including anticancer, anti-inflammatory, and immunomodulating properties. Despite being intriguing leads for further discovery research, synthetic access to the withanolides remains highly challenging-compounds for current biological research are mainly isolated from plants, often inefficiently. Here, we report the divergent synthesis of 11 withanolides in 12 to 20 steps, enabled by a gram-scale route and a series of late-stage functionalizations, most notably a bioinspired photooxygenation-allylic hydroperoxide rearrangement sequence. This approach enables further biological research disconnected from a reliance on minute quantities of the parent natural products or their simple derivatives.
Topics: Withanolides; Chemistry Techniques, Synthetic; Molecular Structure; Biological Products
PubMed: 38941454
DOI: 10.1126/sciadv.adp9375 -
AAPS PharmSciTech Jun 2024Oleogels is a novel semi-solid system, focusing on its composition, formulation, characterization, and diverse pharmaceutical applications. Due to their stability,... (Review)
Review
Oleogels is a novel semi-solid system, focusing on its composition, formulation, characterization, and diverse pharmaceutical applications. Due to their stability, smoothness, and controlled release qualities, oleogels are frequently utilized in food, cosmetics, and medicinal products. Oleogels are meticulously formulated by combining oleogelators like waxes, fatty acids, ethyl cellulose, and phytosterols with edible oils, leading to a nuanced understanding of their impact on rheological characteristics. They can be characterized by methods like visual inspection, texture analysis, rheological measurements, gelation tests, and microscopy. The applications of oleogels are explored in diverse fields such as nutraceuticals, cosmetics, food, lubricants, and pharmaceutics. Oleogels have applications in topical, transdermal, and ocular drug delivery, showcasing their potential for revolutionizing drug administration. This review aims to enhance the understanding of oleogels, contributing to the evolving landscape of pharmaceutical formulations. Oleogels emerge as a versatile and promising solution, offering substantial potential for innovation in drug delivery and formulation practices.
Topics: Organic Chemicals; Drug Delivery Systems; Chemistry, Pharmaceutical; Rheology; Pharmaceutical Preparations; Drug Compounding
PubMed: 38937416
DOI: 10.1208/s12249-024-02854-2 -
AAPS PharmSciTech Jun 2024Our study aimed to explore the potential of using nanostructured lipid carriers (NLCs) to enhance the topical administration of β-sitosterol, a bioactive that is poorly...
Our study aimed to explore the potential of using nanostructured lipid carriers (NLCs) to enhance the topical administration of β-sitosterol, a bioactive that is poorly soluble in water. Here, we have taken advantage of the unique characteristics that cubosomes have to provide as a drug delivery system. These characteristics include a large surface area, thermal stability, and the capacity to encapsulate molecules that are hydrophobic, amphiphilic, and hydrophilic. The cubosomal formulation was optimized by building a central composite design. The optimum dispersion exhibited a particle size of 88.3 nm, a zeta potential of -43, a polydispersity index of 0.358, and drug entrapment of 95.6%. It was composed of 15% w/w oleic acid and 5% w/w pluronic F127. The optimized cubosome dispersion was incorporated into a sponge formulation. The optimized cubosome sponge achieved a higher drug release compared with the cubosome dispersion. The SEM micrograph of the selected sponge showed that it has an interwoven irregular fibrous lamellar structure with low density and high porosity. The in-vivo data revealed that topical application of the β-sitosterol cubosomal sponge showed significant higher wound closure percentage relative to the β-sitosterol product (Mebo)®.
Topics: Sitosterols; Animals; Chitosan; Drug Carriers; Particle Size; Burns; Drug Liberation; Wound Healing; Male; Drug Delivery Systems; Rats; Poloxamer; Hydrophobic and Hydrophilic Interactions; Nanostructures; Administration, Topical
PubMed: 38937387
DOI: 10.1208/s12249-024-02852-4 -
Journal of Food and Drug Analysis Jun 2024Nutraceuticals, that include food ingredients and bioactives from natural products, confer physiological health benefits and protection against chronic diseases. Annatto... (Comparative Study)
Comparative Study
Nutraceuticals, that include food ingredients and bioactives from natural products, confer physiological health benefits and protection against chronic diseases. Annatto is a tropical shrub grown in Central and South America and parts of India. Its seeds are rich in the edible carotenoid-derived apocarotenoid pigment, bixin, which is used as a natural colorant in food, textiles, and cosmetics, and is now gaining attention for its potential health-promoting attributes. Here, we compared a green solvent (ethyl lactate) based extraction of bixin and associated metabolites in annatto seeds (crushed and seed coat) with two other conventional solvents (acetone and acid-base). Bixin was characterized in the extracts using UV-visible- and FTIR-spectroscopy and thin-layer chromatography. The bixin-containing solvent extracts were then profiled for other co-existing metabolites using GC-MS analysis, which were found to be sesquiterpenes, terpenes, terpenoids, phytosterols, and tocotrienols. Their bioactivity was evaluated based on antioxidant and wound-healing efficacies and compared with pure bixin, using NIH-3T3 fibroblast cells in-vitro. Pure bixin, as well as the annatto solvent extracts, showed strong antioxidant and wound healing properties, wherein pure bixin and green solvent extract (ethyl lactate coat) exhibited higher levels of antioxidant activity, achieving 46.00% and 44.60% reduction in MDA levels, respectively, as well as enhanced wound-healing activity, with 54.09% and 53.60% wound closure within 24 h. The green solvent extracts of annatto seeds revealed: (a) differential bioactive profiles in annatto seeds (crushed and seed coat) in comparison with other solvents, and (b) strong antioxidant and wound healing properties. Thus, ethyl lactate extraction shows strong potential for sustainable environmental friendly production of functional foods/nutraceuticals from annatto seeds.
Topics: Bixaceae; Seeds; Carotenoids; Mice; Animals; Plant Extracts; Phytochemicals; Antioxidants; Solvents; NIH 3T3 Cells; Green Chemistry Technology
PubMed: 38934695
DOI: 10.38212/2224-6614.3500 -
Frontiers in Veterinary Science 2024Feline chronic enteropathies (FCE) are common causes of chronic gastrointestinal signs in cats and include different diseases such as food-responsive enteropathy (FRE),...
Feline chronic enteropathies (FCE) are common causes of chronic gastrointestinal signs in cats and include different diseases such as food-responsive enteropathy (FRE), inflammatory bowel diseases (IBD), and low-grade intestinal T-cell lymphoma (LGITL). Although changes in intestinal microbiota and fecal metabolites have been reported in dogs and humans with chronic enteropathy, research in cats has been limited. Therefore, this study aimed to evaluate the fecal microbiota and lipid-related fecal metabolites in cats with FCE to a clinically healthy comparison group (CG). A total of 34 cats with FCE (13 FRE, 15 IBD, and 6 LGITL) and 27 cats in the CG were enrolled in this study. The fecal microbiota was evaluated by the qPCR-based feline Dysbiosis Index (DI). The feline DI in cats with CE (median: 1.3, range: -2.4 to 3.8) was significantly higher ( < 0.0001) compared to CG (median: - 2.3, Range: -4.3 to 2.3), with no difference found among the FCE subgroups. The fecal abundances of Faecalibacterium ( < 0.0001), ( < 0.0001), ( = 0.0398), Bifidobacterium ( = 0.0004), and total bacteria ( = 0.0337) significantly decreased in cats with FCE. Twenty-seven targeted metabolites were measured by gas chromatography-mass spectrometry, including long-chain fatty acids (LCFAs), sterols, and bile acids (BAs). Fecal concentrations of 5 of 12 LCFAs were significantly increased in cats with FCE compared to CG. Fecal concentrations of zoosterol ( = 0.0109), such as cholesterol ( < 0.001) were also significantly increased in cats with FCE, but those of phytosterols were significantly decreased in this group. No differences in fecal BAs were found between the groups. Although no differences were found between the four groups, the fecal metabolomic pattern of cats with FRE was more similar to that of the CG than to those with IBD or LGITL. This could be explained by the mild changes associated with FRE compared to IBD and LGITL. The study showed changes in intestinal microbiota and alteration of fecal metabolites in FCE cats compared to the CG. Changes in fecal lipids metabolites suggest a dysmetabolism of lipids, including LCFAs, sterols, and unconjugated BAs in cats with CE.
PubMed: 38933703
DOI: 10.3389/fvets.2024.1401592 -
Plants (Basel, Switzerland) Jun 2024Species belonging to the genus (Apiaceae) have been used by humanity since ancient times as flavoring agents, preservatives, and medicines for the treatment of a broad... (Review)
Review
Species belonging to the genus (Apiaceae) have been used by humanity since ancient times as flavoring agents, preservatives, and medicines for the treatment of a broad spectrum of conditions, including respiratory, digestive and kidney disorders, fungi infections, wounds, and gastric ulcers. Phytochemical studies on this botanical genus mainly investigate the essential oil composition and reveal the species as a rich source of volatile compounds, including monoterpenes and phenylpropanoids. Among the non-volatile secondary metabolites, flavonoids, coumarins, phenolic acids, phytosterols, and polyacetylenes have been identified. Pharmacological studies revealed extracts and essential oils exhibit different biological properties, including antibacterial, antifungal, anticancer, insecticidal, anti-inflammatory, and hepatoprotective activities. However, compared to other genera, the biological activity and chemical diversity of this genus are not well studied. In future decades, it is highly likely that the small genus will play an important role in drug discovery and drug development.
PubMed: 38931031
DOI: 10.3390/plants13121599 -
Foods (Basel, Switzerland) Jun 2024This article provides an overview of the literature data on the role of liposomal structures and encapsulated substances in food technology and human nutrition. The... (Review)
Review
This article provides an overview of the literature data on the role of liposomal structures and encapsulated substances in food technology and human nutrition. The paper briefly describes how liposomes are created and how they encapsulate food ingredients, which can either be individual compounds or plant extracts. Another very interesting application of liposomes is their use as antimicrobial carriers to protect food products from spoilage during storage. The encapsulation of food ingredients in liposomes can increase their bioavailability, which is particularly important for compounds with health-promoting properties but low bioavailability. Particular attention was paid to compounds such as phytosterols, which lower blood cholesterol levels but have very low absorption in the human body. In addition, consumer expectations and regulations for liposomes in food are discussed. To date, no in vivo human studies have been conducted to indicate which encapsulation methods give the best results for gastrointestinal effects and which food-added substances are most stable during food storage and processing. The paper identifies further lines of research that are needed before liposomes can be introduced into food.
PubMed: 38928757
DOI: 10.3390/foods13121814 -
Plant Signaling & Behavior Dec 2024One of the main signal transduction pathways that modulate plant growth and stress responses, including drought, is the action of phytohormones. Recent advances in omics...
One of the main signal transduction pathways that modulate plant growth and stress responses, including drought, is the action of phytohormones. Recent advances in omics approaches have facilitated the exploration of plant genomes. However, the molecular mechanisms underlying the response in the crown of barley, which plays an essential role in plant performance under stress conditions and regeneration after stress treatment, remain largely unclear. The objective of the present study was the elucidation of drought-induced molecular reactions in the crowns of different barley phytohormone mutants. We verified the hypothesis that defects of gibberellins, brassinosteroids, and strigolactones action affect the transcriptomic, proteomic, and hormonal response of barley crown to the transitory drought influencing plant development under stress. Moreover, we assumed that due to the strong connection between strigolactones and branching the mutant, with dysfunctional receptor of strigolactones, manifests the most abundant alternations in crowns and phenotype under drought. Finally, we expected to identify components underlying the core response to drought which are independent of the genetic background. Large-scale analyses were conducted using gibberellins-biosynthesis, brassinosteroids-signaling, and strigolactones-signaling mutants, as well as reference genotypes. Detailed phenotypic evaluation was also conducted. The obtained results clearly demonstrated that hormonal disorders caused by mutations in the , , and genes affected the multifaceted reaction of crowns to drought, although the expression of these genes was not induced by stress. The study further detected not only genes and proteins that were involved in the drought response and reacted specifically in mutants compared to the reaction of reference genotypes and , but also the candidates that may underlie the genotype-universal stress response. Furthermore, candidate genes involved in phytohormonal interactions during the drought response were identified. We also found that the interplay between hormones, especially gibberellins and auxins, as well as strigolactones and cytokinins may be associated with the regulation of branching in crowns exposed to drought. Overall, the present study provides novel insights into the molecular drought-induced responses that occur in barley crowns.
Topics: Hordeum; Plant Growth Regulators; Droughts; Mutation; Gibberellins; Gene Expression Regulation, Plant; Brassinosteroids; Plant Proteins; Stress, Physiological; Lactones
PubMed: 38923879
DOI: 10.1080/15592324.2024.2371693 -
Chemistry & Biodiversity Jun 2024Pereskia aculeata has been widely investigated due to its anti-inflammatory potential. Among the metabolites found in this species are the phytosterols beta-sitosterol...
Pereskia aculeata has been widely investigated due to its anti-inflammatory potential. Among the metabolites found in this species are the phytosterols beta-sitosterol (β-SIT) and stigmasterol (STIG). The objective of the study was to evaluate the anti-inflammatory and toxicity activities of the hexane partition of P. aculeata (PHEX), as well as β-SIT and STIG. PHEX was prepared and the phytosterols were quantified. In terms of toxicity against L929 fibroblast cells, PHEX showed toxicity up to 200 µg/mL; STIG and β-SIT showed toxicity up to 25 µg/mL. PHEX inhibited 66% of nitric oxide radicals, while STIG and β-SIT inhibited 33.73% and 34.94%, respectively. In an anti-inflammatory test against Zophobas morio larvae, all samples significantly reduced hemocyte levels. Additionally, the LD50 values were calculated: 229.6 mg/kg for PHEX, 101.5 mg/kg for STIG, and 103.8 mg/kg for β-SIT. In conclusion, the study indicates that the phytosterols present in PHEX may contribute to its anti-inflammatory activity.
PubMed: 38923804
DOI: 10.1002/cbdv.202400686 -
Plant Cell Reports Jun 2024Two significant studies have unveiled the pivotal role of BR regulation in shaping distinct features: the clustered-spikelet architecture in rice and the superior...
Two significant studies have unveiled the pivotal role of BR regulation in shaping distinct features: the clustered-spikelet architecture in rice and the superior semi-dwarf stature in wheat.
Topics: Brassinosteroids; Oryza; Crops, Agricultural; Triticum; Plant Growth Regulators; Gene Expression Regulation, Plant
PubMed: 38922346
DOI: 10.1007/s00299-024-03270-3