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1.
Food Chem ; 452: 139520, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38723573

ABSTRACT

The current study addresses the growing demand for sustainable plant-based cheese alternatives by employing molecular docking and deep learning algorithms to optimize protein-ligand interactions. Focusing on key proteins (zein, soy, and almond protein) along with tocopherol and retinol, the goal was to improve texture, nutritional value, and flavor characteristics via dynamic simulations. The findings demonstrated that the docking analysis presented high accuracy in predicting conformational changes. Flexible docking algorithms provided insights into dynamic interactions, while analysis of energetics revealed variations in binding strengths. Tocopherol exhibited stronger affinity (-5.8Kcal/mol) to zein compared to retinol (-4.1Kcal/mol). Molecular dynamics simulations offered comprehensive insights into stability and behavior over time. The integration of machine learning algorithms improved the classification and the prediction accuracy, achieving a rate of 71.59%. This study underscores the significance of molecular understanding in driving innovation in the plant-based cheese industry, facilitating the development of sustainable alternatives to traditional dairy products.


Subject(s)
Cheese , Molecular Docking Simulation , Plant Proteins , Prunus dulcis , Tocopherols , Vitamin A , Zein , Plant Proteins/chemistry , Plant Proteins/metabolism , Cheese/analysis , Prunus dulcis/chemistry , Vitamin A/chemistry , Vitamin A/metabolism , Tocopherols/chemistry , Tocopherols/metabolism , Zein/chemistry , Zein/metabolism , Molecular Dynamics Simulation , Machine Learning , Glycine max/chemistry , Glycine max/metabolism , Support Vector Machine
2.
ACS Appl Mater Interfaces ; 16(20): 25740-25756, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38722759

ABSTRACT

Micro- and nano-plastics (NPs) are found in human milk, blood, tissues, and organs and associate with aberrant health outcomes including inflammation, genotoxicity, developmental disorders, onset of chronic diseases, and autoimmune disorders. Yet, interfacial interactions between plastics and biomolecular systems remain underexplored. Here, we have examined experimentally, in vitro, in vivo, and by computation, the impact of polystyrene (PS) NPs on a host of biomolecular systems and assemblies. Our results reveal that PS NPs essentially abolished the helix-content of the milk protein ß-lactoglobulin (BLG) in a dose-dependent manner. Helix loss is corelated with the near stoichiometric formation of ß-sheet elements in the protein. Structural alterations in BLG are also likely responsible for the nanoparticle-dependent attrition in binding affinity and weaker on-rate constant of retinol, its physiological ligand (compromising its nutritional role). PS NP-driven helix-to-sheet conversion was also observed in the amyloid-forming trajectory of hen egg-white lysozyme (accelerated fibril formation and reduced helical content in fibrils). Caenorhabditis elegans exposed to PS NPs exhibited a decrease in the fluorescence of green fluorescent protein-tagged dopaminergic neurons and locomotory deficits (akin to the neurotoxin paraquat exposure). Finally, in silico analyses revealed that the most favorable PS/BLG docking score and binding energies corresponded to a pose near the hydrophobic ligand binding pocket (calyx) of the protein where the NP fragment was found to make nonpolar contacts with side-chain residues via the hydrophobic effect and van der Waals forces, compromising side chain/retinol contacts. Binding energetics indicate that PS/BLG interactions destabilize the binding of retinol to the protein and can potentially displace retinol from the calyx region of BLG, thereby impairing its biological function. Collectively, the experimental and high-resolution in silico data provide new insights into the mechanism(s) by which PS NPs corrupt the bimolecular structure and function, induce amyloidosis and onset neuronal injury, and drive aberrant physiological and behavioral outcomes.


Subject(s)
Caenorhabditis elegans , Lactoglobulins , Muramidase , Animals , Muramidase/chemistry , Muramidase/metabolism , Lactoglobulins/chemistry , Lactoglobulins/metabolism , Caenorhabditis elegans/metabolism , Polystyrenes/chemistry , Nanoparticles/chemistry , Vitamin A/chemistry , Vitamin A/metabolism , Humans , Homeostasis/drug effects , Plastics/chemistry
3.
Int J Pharm ; 659: 124279, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38806096

ABSTRACT

Controlled release drug delivery systems of eye drops are a promising ophthalmic therapy with advantages of good patient compliance and low irritation. However, the lack of a suitable drug carrier for ophthalmic use limits the development of the aforementioned system. Herein, the crosslinked cyclodextrin organic framework (COF) with a cubic porous structure and a uniform particle size was synthesized and applied to solidify vitamin A palmitate (VAP) by using the solvent-free method. The VAP@COF suspension eye drops were formulated by screening co-solvents, suspending agents, and stabilizing agents to achieve a homogeneous state and improve stability. According to the in vitro release study, the VAP@COF suspension exhibited a controlled release of VAP within 12 h. Both the ex vivo corneal contact angle and in vivo fluorescence tracking indicated that the VAP@COF suspension prolonged the VAP residence time on the ocular surface. This suspension accelerated the recovery of the dry eye disease (DED) model in New Zealand rabbits. Furthermore, the suspension was non-cytotoxic to human corneal epithelial cells and non-irritation to rabbit eyes. In summary, the particulate COF is an eye-acceptable novel carrier that sustains release and prolongs the VAP residence time on the ocular surface for DED treatment.


Subject(s)
Delayed-Action Preparations , Drug Carriers , Drug Liberation , Dry Eye Syndromes , Retinyl Esters , Vitamin A , Animals , Rabbits , Vitamin A/administration & dosage , Vitamin A/chemistry , Vitamin A/analogs & derivatives , Dry Eye Syndromes/drug therapy , Humans , Drug Carriers/chemistry , Cyclodextrins/chemistry , Ophthalmic Solutions/administration & dosage , Particle Size , Male , Cell Line , Cross-Linking Reagents/chemistry , Administration, Ophthalmic , Disease Models, Animal , Drug Delivery Systems/methods , Diterpenes
4.
Biomacromolecules ; 25(6): 3831-3839, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38728153

ABSTRACT

This study utilizes mechanochemistry to prepare retinol acetate (RA) solid dispersion (RA-sodium starch octenyl succinate (SSOS)), resulting in improved solubility, stability, and bioavailability compared with raw RA and commercial RA microcapsules. RA, poloxamer 188, SSOS, and milling beads (8 mm) were mixed in a ratio of 2:1:8:220 (w/w) and ball-milled at 100 rpm for 3 h. RA-SSOS exhibited a solubility of 1020.35 µL/mL and a 98.09% retention rate after aging at 30 °C. Rats fed with RA-SSOS showed an ∼30% increase in organ RA content. Characterization analysis attributed the solubility and stabilization of RA-SSOS to hydrogen bonding between RA and SSOS, along with an amorphous state. RA-SSOS offers significant advantages for the pharmaceutical and food industries, leveraging mechanochemistry to enhance solid dispersions for hydrophobic compounds and optimize drug delivery.


Subject(s)
Biological Availability , Retinyl Esters , Solubility , Vitamin A , Animals , Rats , Vitamin A/chemistry , Vitamin A/pharmacokinetics , Retinyl Esters/chemistry , Male , Rats, Sprague-Dawley , Drug Stability , Starch/chemistry , Diterpenes
5.
Ultrason Sonochem ; 107: 106929, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38820933

ABSTRACT

A novel approach to ultrasound-assisted Pickering interfacial biocatalysis (PIB) has been proposed and implemented for the efficient enzymatic transesterification production of vitamin A fatty acid esters. This is the first instance of exploiting the synergistic effect of ultrasound and the bifunctional modification of enzyme supports to accelerate biocatalytic performance in PIB systems. The optimal conditions were determined to be ultrasound power of 70 W, on/off time of 5 s/5 s, substrate molar ratio of 1:1, enzyme addition of 2 %, and a volume ratio of n-hexane to PBS of 3:1, a temperature of 40 °C, and a time of 30 min. The application of ultrasound technology not only improved lipase activity but also allowed for a reduction in emulsion droplet size to enhance interfacial mass transfer.Bifunctional modification of silica-based supports enhanced stability of immobilized enzymes by increasing hydrogen bonding while maintaining the active interface microenvironment. Compared with a non-ultrasound-assisted PIB system stabilized by mono-modified immobilized enzyme particles, the catalytic efficacy (CE) of the novel system reached 8.18 mmol g-1 min-1, which was enhanced by 3.33-fold, while the interfacial area was found to have increased by 17.5-fold. The results facilitated the conversion of vitamin A palmitate (VAP), vitamin A oleate (VAO), vitamin A linoleate (VAL), and vitamin A linolenate (VALn), with conversion rates of approximately 98.2 %, 97.4 %, 96.1 %, and 94.7 %, respectively. This represents the most efficient example that has been reported to our knowledge. Furthermore, the system demonstrated improved reusability, with a conversion rate of 62.1 % maintained even after 10 cycles. The findings presented in this paper provide valuable insights into an efficient and conveniently promising protocol for the development of PIB systems.


Subject(s)
Biocatalysis , Enzymes, Immobilized , Esters , Lipase , Ultrasonic Waves , Vitamin A , Vitamin A/chemistry , Esters/chemistry , Lipase/metabolism , Lipase/chemistry , Enzymes, Immobilized/chemistry , Enzymes, Immobilized/metabolism , Esterification , Temperature , Silicon Dioxide/chemistry
6.
Food Chem ; 449: 139158, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38608602

ABSTRACT

This work presents a novel use of fibrous egg white protein (FEWP) in food preservation and nutraceutical applications. In this study, food-grade FEWP was used as an encapsulating material, along with chitosan (CS), to stabilize emulsions. The emulsion system was then used as a delivery system to improve the stability of retinyl acetate (RA). The structural and functional properties, as well as the stability and rheological behavior of the FEWP/CS copolymer, was investigated. The stability of RA-enriched emulsions was also evaluated. FEWP and CS stabilized emulsions exhibited smaller particle size and enhanced stability against different ionic strengths and storage periods. Additionally, RA-encapsulated emulsions stabilized by FEWP:CS (25:1 w/w) effectively inhibited apple browning. This study provides a promising strategy for delivering antioxidant components, highlighting its potential in food preservation and nutraceutical applications.


Subject(s)
Diterpenes , Egg White , Emulsions , Retinyl Esters , Vitamin A , Emulsions/chemistry , Diterpenes/chemistry , Retinyl Esters/chemistry , Egg White/chemistry , Vitamin A/chemistry , Particle Size , Food Preservation/methods , Egg Proteins/chemistry , Malus/chemistry , Chitosan/chemistry , Rheology , Chickens
7.
Chem Asian J ; 19(10): e202400198, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38558255

ABSTRACT

The ideal and highly anticipated dressing for skin wounds should provide a moist environment, possess antibacterial properties, and ensure sustained drug release. In the present work, a hyaluronic acid-based hydrogel was formed by cross-linking crocetin and CaCO3@polyelectrolyte materials (CaCO3@PEM) microspheres with HA hydrogels via hydrogen bond and amido bonding (CaCO3@PEM@Cro@HA hydrogel, CPC@HA hydrogel). Moreover, the CPC@HA hydrogel had the capability of sustained, controlled release of calcium ions and crocetin via pH-sensitive and accelerated skin wound healing. The experiment results showed that the CPC@HA hydrogel exhibited porous network structures, stable physical properties, and had antibacterial properties and biocompatibility in vitro. In addition, the CPC@HA hydrogel covering on the skin wound could reduce inflammation and promote wound healing. The high expression of angiogenic cytokines (CD31) and epidermal terminal differentiation markers (Loricrin) of wound healing tissue suggested the CPC@HA hydrogel also had the function of promoting the remodeling of regenerated skin. Overall, CPC@HA hydrogel has promising potential for clinical applications in accelerating skin wound repair.


Subject(s)
Calcium , Carotenoids , Hydrogels , Vitamin A , Wound Healing , Wound Healing/drug effects , Vitamin A/analogs & derivatives , Vitamin A/pharmacology , Vitamin A/chemistry , Hydrogels/chemistry , Hydrogels/pharmacology , Hydrogels/chemical synthesis , Hydrogen-Ion Concentration , Calcium/metabolism , Animals , Carotenoids/chemistry , Carotenoids/pharmacology , Skin/drug effects , Skin/pathology , Skin/metabolism , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Drug Liberation , Mice , Ions/chemistry , Calcium Carbonate/chemistry , Calcium Carbonate/pharmacology , Humans , Microbial Sensitivity Tests , Staphylococcus aureus/drug effects
8.
Drug Deliv Transl Res ; 14(7): 1923-1939, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38117406

ABSTRACT

The most promising active ingredient of Crocus sativus L., crocetin (CCT), has been demonstrated to possess many biological activities. However, only a few studies have been conducted on CCT formulation, especially in oral formulation, mainly due to its insolubility in water, which limits its application for oral administration. This article reports an equilibrium saturation solubility and single-pass intestinal perfusion studies conducted to classify the biopharmaceutics classification system (BCS) of CCT. To enhance in vitro dissolution and in vivo oral bioavailability, ternary solid dispersions of CCT (CCT-SDs) with soluplus (SOL) as hydrophilic carrier and meglumine (MEG) as alkalizer were optimized using response surface methodology (RSM) with central composite design (CCD) experiments. Four different preparation methods were evaluated using the optimal formulation, including solvent evaporation, ball milling, spray drying, and freeze-drying. Prepared formulations were characterized by TG-DSC, FTIR, X-RPD, and SEM; the pharmacokinetic studies were performed in rats after oral administration. The cumulative dissolution rate of CCT-SDs containing SOL and MEG prepared by the ball milling method was 97.1% at 15 min and remained at 95.6% at 480 min, which was significantly higher than that of untreated CCT. The lower crystallinity, smaller particle size, and higher microenvironment pH (pHM) were observed in CCT-SDs prepared by the ball milling method. In vivo absorption of CCT-SDs (Cmax = 52.789 ± 12.441 µg/mL and AUC0-12 = 191.748 ± 35.043 µg/mL·h) was greater than untreated CCT (Cmax = 5.918 ± 1.388 µg/mL and AUC0-12 = 44.309 ± 7.264 µg/mL·h). In conclusion, the current study provides ternary solid dispersion formulation of CCT to increase the in vitro dissolution and in vivo bioavailability, which will benefit the commercial production and future clinical applications of CCT.


Subject(s)
Biological Availability , Carotenoids , Rats, Sprague-Dawley , Solubility , Vitamin A , Animals , Carotenoids/pharmacokinetics , Carotenoids/chemistry , Carotenoids/administration & dosage , Administration, Oral , Vitamin A/pharmacokinetics , Vitamin A/analogs & derivatives , Vitamin A/administration & dosage , Vitamin A/chemistry , Hydrogen-Ion Concentration , Male , Rats , Drug Liberation , Polyethylene Glycols/chemistry , Polyethylene Glycols/pharmacokinetics , Polyethylene Glycols/administration & dosage
9.
Food Chem ; 377: 132040, 2022 May 30.
Article in English | MEDLINE | ID: mdl-34999454

ABSTRACT

To date there are no methods in the literature leading to crocetin selective concentration from saffron powder aqueous solutions. To this aim, we decided to test the performance of its heterogeneous extraction by means of a panel of 21 synthetic clays, 4 of which demonstrated to selectively retain crocetin in the solid phase after hydrolysis of its digentiobyosil ester (crocin) (and its isomers) and to its chemical stabilization (e.g., oxidation) over time. The best adsorption yield was obtained with zinc hydroxy chloride (66.18 ± 0.06 µg/g dry powder). This phenomenon was assessed by HPLC-DAD analyses after desorption of crocetin from the respective support and assessing its degradation along a period of 30 days. The method we established could represent a good mean to provide pure crocetin from saffron powder, preserving in the meantime its chemical properties for a concrete future exploitation for food pharmaceutical, and cosmetic purposes.


Subject(s)
Carotenoids/chemistry , Crocus , Vitamin A/chemistry , Hydrolysis , Powders , Vitamin A/analogs & derivatives
10.
Oxid Med Cell Longev ; 2021: 6631929, 2021.
Article in English | MEDLINE | ID: mdl-34545298

ABSTRACT

Crocetin is a main bioactive component with a carotenoid skeleton in Gardenia jasminoides, a typical traditional Chinese medicine with a long history in Southeast Asia. Crocetin is being commonly consumed as spices, dyes, and food colorants. Recent pharmacological studies had implied that crocetin may possess potent anti-inflammatory properties; however, the underlying molecular mechanism is not fully elucidated. In the present study, the regulatory effect of crocetin on redox balance was systematically investigated in lipopolysaccharide- (LPS-) stimulated RAW264.7 cells. The results showed that crocetin dose-dependently inhibited LPS-induced nitric oxide production and inducible nitric oxide synthase (iNOS) expression in RAW264.7 cells. Molecular data revealed that crocetin exerted its anti-inflammatory property by inhibiting the MEK1/JNK/NF-κB/iNOS pathway and activating the Nrf2/HO-1 pathway. The shRNA-knockdown (KD) of MEK1 and ERK1 confirmed that the activation of MEK1 and inhibition of JNK mediated the anti-inflammatory effect of crocetin. Moreover, the pull-down assay and computational molecule docking showed that crocetin could directly bind to MEK1 and JNK1/2. It is noticed that both KD and knockout (KO) of HO-1 gene blocked this action. More detailed data have shown that HO-1-KO blocked the inhibition of p-IκB-α by crocetin. These data indicated that crocetin exerted its anti-inflammatory property via modulating the crosstalk between the MEK1/JNK/NF-κB/iNOS pathway and the Nrf2/HO-1 pathway, highlighting HO-1 as a major player. Therefore, the present study reveals that crocetin can act as a potential candidate for redox-balancing modulation in charge of its anti-inflammatory and chemopreventive effect, which strengthens its potency in the subsequent clinic application in the near future.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Carotenoids/pharmacology , Signal Transduction/drug effects , Vitamin A/analogs & derivatives , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/metabolism , Binding Sites , Carotenoids/chemistry , Carotenoids/metabolism , Heme Oxygenase-1/metabolism , JNK Mitogen-Activated Protein Kinases/metabolism , Lipopolysaccharides/pharmacology , MAP Kinase Kinase 1/antagonists & inhibitors , MAP Kinase Kinase 1/genetics , MAP Kinase Kinase 1/metabolism , Macrophages/cytology , Macrophages/drug effects , Macrophages/metabolism , Mice , Molecular Docking Simulation , NF-E2-Related Factor 2/metabolism , NF-KappaB Inhibitor alpha/antagonists & inhibitors , NF-KappaB Inhibitor alpha/metabolism , NF-kappa B/antagonists & inhibitors , NF-kappa B/metabolism , Nitric Oxide Synthase Type II/metabolism , Phosphorylation/drug effects , RAW 264.7 Cells , RNA Interference , RNA, Small Interfering/metabolism , Vitamin A/chemistry , Vitamin A/metabolism , Vitamin A/pharmacology
11.
Molecules ; 26(15)2021 Jul 21.
Article in English | MEDLINE | ID: mdl-34361546

ABSTRACT

The adsorption of retinol, niacinamide and glycolic acid active ingredients on the internal surface of halloysite in an aqueous environment was explored at the molecular level by means of calculations based on quantum mechanics and force fields from empirical interatomic potentials. These active ingredients are stably adsorbed on the internal surface of halloysite forming hydrogen bonds between the hydrogen, oxygen and nitrogen atoms with the hydroxyl groups of the inner surface of the halloysite. In addition, electrostatic interaction between these active ingredients with the water molecules was observed. Therefore, the theoretical results indicate that the adsorption of these active principles is favourable in the halloysite nanotube, which allows directing future experimental investigations for the development and design of retinol, niacinamide and glycolic acid with halloysite nanotubes systems, which may be topical formulations for skincare.


Subject(s)
Clay/chemistry , Glycolates , Niacinamide , Skin Care , Vitamin A , Administration, Topical , Glycolates/chemistry , Glycolates/pharmacology , Humans , Niacinamide/chemistry , Niacinamide/pharmacology , Vitamin A/chemistry , Vitamin A/pharmacology
12.
Cells ; 10(8)2021 08 03.
Article in English | MEDLINE | ID: mdl-34440735

ABSTRACT

Knowledge regarding complex radiation responses in biological systems can be enhanced using genetically amenable model organisms. In this manuscript, we reviewed the use of the nematode, Caenorhabditis elegans (C. elegans), as a model organism to investigate radiation's biological effects. Diverse types of experiments were conducted on C. elegans, using acute and chronic exposure to different ionizing radiation types, and to assess various biological responses. These responses differed based on the type and dose of radiation and the chemical substances in which the worms were grown or maintained. A few studies compared responses to various radiation types and doses as well as other environmental exposures. Therefore, this paper focused on the effect of irradiation on C. elegans, based on the intensity of the radiation dose and the length of exposure and ways to decrease the effects of ionizing radiation. Moreover, we discussed several studies showing that dietary components such as vitamin A, polyunsaturated fatty acids, and polyphenol-rich food source may promote the resistance of C. elegans to ionizing radiation and increase their life span after irradiation.


Subject(s)
Caenorhabditis elegans/radiation effects , Radiation, Ionizing , Animals , Caenorhabditis elegans/genetics , Caenorhabditis elegans/growth & development , Caenorhabditis elegans/metabolism , Caenorhabditis elegans Proteins/metabolism , DNA Damage/drug effects , DNA Damage/radiation effects , Fatty Acids, Unsaturated/chemistry , Fatty Acids, Unsaturated/pharmacology , Glucosides/pharmacology , Lignans/pharmacology , Longevity/radiation effects , Reproduction/drug effects , Reproduction/radiation effects , Vitamin A/chemistry , Vitamin A/pharmacology
13.
Front Immunol ; 12: 671283, 2021.
Article in English | MEDLINE | ID: mdl-34305901

ABSTRACT

The vitamin A derivative, retinoid acid (RA) is key player in guiding adaptive mucosal immune responses. However, data on the uptake and metabolism of vitamin A within human immune cells has remained largely elusive because retinoids are small, lipophilic molecules which are difficult to detect. To overcome this problem and to be able to study the effect of vitamin A metabolism in human immune cell subsets, we have synthesized novel bio-orthogonal retinoid-based probes (clickable probes), which are structurally and functionally indistinguishable from vitamin A. The probes contain a functional group (an alkyne) to conjugate to a fluorogenic dye to monitor retinoid molecules in real-time in immune cells. We demonstrate, by using flow cytometry and microscopy, that multiple immune cells have the capacity to internalize retinoids to varying degrees, including human monocyte-derived dendritic cells (DCs) and naïve B lymphocytes. We observed that naïve B cells lack the enzymatic machinery to produce RA, but use exogenous retinoic acid to enhance CD38 expression. Furthermore, we showed that human DCs metabolize retinal into retinoic acid, which in co-culture with naïve B cells led to of the induction of CD38 expression. These data demonstrate that in humans, DCs can serve as an exogenous source of RA for naïve B cells. Taken together, through the use of clickable vitamins our data provide valuable insight in the mechanism of vitamin A metabolism and its importance for human adaptive immunity.


Subject(s)
B-Lymphocytes/immunology , Click Chemistry/methods , Dendritic Cells/immunology , Vitamin A/metabolism , ADP-ribosyl Cyclase 1/metabolism , Adaptive Immunity , Cells, Cultured , Coculture Techniques , Copper/metabolism , Flow Cytometry , Fluorescent Dyes , Humans , Tretinoin/chemistry , Tretinoin/metabolism , Up-Regulation , Vitamin A/chemistry
14.
Pak J Pharm Sci ; 34(2): 537-544, 2021 Mar.
Article in English | MEDLINE | ID: mdl-34275827

ABSTRACT

Saffron has been applied in depression treatment, but its antidepressant compounds and mechanisms are unclear. In this research, a network pharmacology-based method was proposed to screen the active compounds and the potential mechanisms of saffron for depression treatment. Firstly, the chemical compounds of saffron were collected from literature and filtered by drug-like prediction. Secondly, common targets, by comparing the targets of saffron predicted by Pharm Mapper server with targets associated with depression collected from Genecards, were regarded as the antidepressant targets of saffron. Thirdly, common targets were mapped to KEGG pathways, considered as the pathways related with the antidepressant effects of saffron. Finally, the network of compounds-targets-pathways was constructed and analyzed by cytoscape 3.4.0. Ten compounds including crocetin, picrocrocin, (1R, 5S, 6R)-5-(hydroxymethyl)- 4, 4, 6-trimethyl-7-Oxabicyclo[4.1.0]heptan-2-one and its glycoside were screened as the main antidepressant compounds, some of which were reported for the first time. They might have effective treatment for depression by acting on targets, such as MAP2K1, MAPK1, HRAS, PIK3R1, ALB and AKT1 and pathways related with immune system, signal transduction and so on. This study provided a new insight into the antidepressant mechanism and active compounds of saffron, which also had a guiding effect on later experiments.


Subject(s)
Antidepressive Agents/pharmacology , Crocus/chemistry , Flowers , Network Pharmacology , Albumins/drug effects , Albumins/metabolism , Carotenoids/chemistry , Class Ia Phosphatidylinositol 3-Kinase/drug effects , Class Ia Phosphatidylinositol 3-Kinase/metabolism , Cyclohexenes/chemistry , Glucosides/chemistry , Humans , MAP Kinase Kinase 1/drug effects , MAP Kinase Kinase 1/metabolism , Mitogen-Activated Protein Kinase 1/drug effects , Mitogen-Activated Protein Kinase 1/metabolism , Proto-Oncogene Proteins c-akt/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins p21(ras)/drug effects , Proto-Oncogene Proteins p21(ras)/metabolism , Signal Transduction/drug effects , Terpenes/chemistry , Vitamin A/analogs & derivatives , Vitamin A/chemistry
15.
Cell Mol Life Sci ; 78(17-18): 6105-6117, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34297165

ABSTRACT

Transthyretin (TTR) is an extracellular protein mainly produced in the liver and choroid plexus, with a well-stablished role in the transport of thyroxin and retinol throughout the body and brain. TTR is prone to aggregation, as both wild-type and mutated forms of the protein can lead to the accumulation of amyloid deposits, resulting in a disease called TTR amyloidosis. Recently, novel activities for TTR in cell biology have emerged, ranging from neuronal health preservation in both central and peripheral nervous systems, to cellular fate determination, regulation of proliferation and metabolism. Here, we review the novel literature regarding TTR new cellular effects. We pinpoint TTR as major player on brain health and nerve biology, activities that might impact on nervous systems pathologies, and assign a new link between TTR and angiogenesis and cancer. We also explore the molecular mechanisms underlying TTR activities at the cellular level, and suggest that these might go beyond its most acknowledged carrier functions and include interaction with receptors and activation of intracellular signaling pathways.


Subject(s)
Amyloidosis/etiology , Prealbumin/metabolism , Amyloidosis/metabolism , Central Nervous System/metabolism , Humans , Neurons/cytology , Neurons/metabolism , Prealbumin/chemistry , Prealbumin/genetics , Protein Aggregates/physiology , Reactive Oxygen Species/metabolism , Thyroxine/chemistry , Thyroxine/metabolism , Vitamin A/chemistry , Vitamin A/metabolism
16.
Food Chem ; 362: 130199, 2021 Nov 15.
Article in English | MEDLINE | ID: mdl-34091167

ABSTRACT

Crocins in commercial liquid saffron extracts (Saffr'activ®) were identified using high-performance liquid chromatography (HPLC) with a diode array detector (DAD) and mass spectrometry (MS). The impact of storage on the qualities of the saffron extract were studied with HPLC-DAD-MS by exposing trans-4-GG crocin to environmental factors. Light and temperature induced degradation after only one week. Trans-4-GG crocin was totally hydrolyzed when stored at 60 °C and exposed to light. A quick and reliable method using HPLC-DAD was then developed to improve quantification of crocins in commercial liquid saffron extracts. An internal standard quantification method that uses a response factor, corrected with the molecular weight of each crocin, improved results for old saffron extracts.


Subject(s)
Carotenoids/analysis , Chromatography, High Pressure Liquid/methods , Crocus/chemistry , Mass Spectrometry/methods , Plant Extracts/analysis , Air , Carotenoids/chemistry , Food Analysis/methods , Food Storage/methods , Light , Plant Extracts/chemistry , Vitamin A/analogs & derivatives , Vitamin A/chemistry
17.
Yakugaku Zasshi ; 141(4): 557-577, 2021.
Article in Japanese | MEDLINE | ID: mdl-33790122

ABSTRACT

"Retinoid" is the general term for vitamin A derivatives and chemical compounds that act like vitamin A. Vitamin A are composed of four isoprene units and are named according to their terminal functional group, such as retinol (OH, 1), retinal (CHO, 2), and retinoic acid (CO2H, 3). Vitamin A usually refers to retinol. In the past few decades, major advances in research on vitamin A have improved our understanding of its fundamental roles and physiological significance in living cells. In this review, three types of chemical biology studies using vitamin A analogs are described: (1) conformational studies of the chromophore in retinal proteins (rhodopsin, phoborhodopsin, and retinochrome), especially the conformation around the cyclohexene ring; (2) structure-activity relationship studies of retinoic acid analogs to create new signaling molecules for activating nuclear receptors; and (3) development of a new channelrhodopsin with an absorption maximum at longer wavelength to overcome the various demerits of channelrhodopsins used in optogenetics, as well as the stereoselective synthesis of retinoid isomers and their analogs using a diene-tricarbonyliron complex or a palladium-catalyzed cross-coupling reaction between vinyl triflates and stannyl olefins.


Subject(s)
Vitamin A/analogs & derivatives , Vitamin A/chemistry , Alkenes/chemistry , Catalysis , Channelrhodopsins , Cyclohexenes/chemistry , Eye Proteins/chemistry , Isomerism , Mesylates/chemistry , Molecular Conformation , Nuclear Reactors , Palladium/chemistry , Retinoids/chemical synthesis , Retinoids/chemistry , Stereoisomerism , Structure-Activity Relationship , Vinyl Compounds/chemistry , Vitamin A/pharmacology , Vitamin A/physiology
18.
Am J Clin Nutr ; 113(5): 1209-1220, 2021 05 08.
Article in English | MEDLINE | ID: mdl-33693468

ABSTRACT

BACKGROUND: Replacement of conventional staples with biofortified or industrially fortified staples in household diets may increase maternal breast milk retinol content and vitamin A intakes from complementary foods, improving infant total body stores (TBS) of vitamin A. OBJECTIVES: To determine whether biofortified or industrially fortified maize consumption by Zambian women and their breastfeeding infants could improve milk retinol concentration and infant TBS. METHODS: We randomly assigned 255 lactating women and their 9-mo-old infants to a 90-d intervention providing 0 µg retinol equivalents (RE)/d as conventional maize or ∼315 µg RE/d to mothers and ∼55 µg RE/d to infants as provitamin A carotenoid-biofortified maize or retinyl palmitate-fortified maize. Outcomes were TBS, measured by retinol isotope dilution in infants (primary), and breast milk retinol, measured by HPLC in women (secondary). RESULTS: The intervention groups were comparable at baseline. Loss to follow-up was 10% (n = 230 mother-infant pairs). Women consumed 92% of the intended 287 g/d and infants consumed 82% of the intended 50 g/d maize. The baseline geometric mean (GM) milk retinol concentration was 1.57 µmol/L (95% CI: 1.45, 1.69 µmol/L), and 24% of women had milk retinol <1.05 µmol/L. While mean milk retinol did not change in the biofortified arm (ß: 0.11; 95% CI: -0.02, 0.24), the intervention reduced low milk retinol (RR: 0.42; 95% CI: 0.21, 0.85). Fortified maize increased mean milk retinol (ß: 0.17; 95% CI: 0.04, 0.30) and reduced the prevalence of low milk retinol (RR: 0.46; 95% CI: 0.25, 0.82). The baseline GM TBS was 178 µmol (95% CI: 166, 191 µmol). This increased by 24 µmol (± 136) over the 90-d intervention period, irrespective of treatment group. CONCLUSIONS: Both biofortified and fortified maize consumption improved milk retinol concentration. This did not translate into greater infant TBS, most likely due to adequate TBS at baseline. This trial was registered at clinicaltrials.gov as NCT02804490.


Subject(s)
Biofortification , Diterpenes/administration & dosage , Milk, Human/chemistry , Retinyl Esters/administration & dosage , Vitamin A/administration & dosage , Vitamin A/chemistry , Zea mays/genetics , Adult , Breast Feeding , Cohort Studies , Female , Food, Fortified , Humans , Infant , Vitamin A/metabolism , Zambia
19.
ACS Chem Biol ; 16(3): 480-490, 2021 03 19.
Article in English | MEDLINE | ID: mdl-33600157

ABSTRACT

In mammals, carotenoids are converted by two carotenoid cleavage oxygenases into apocarotenoids, including vitamin A. Although knowledge about ß-carotene oxygenase-1 (BCO1) and vitamin A metabolism has tremendously increased, the function of ß-carotene oxygenase-2 (BCO2) remains less well-defined. We here studied the role of BCO2 in the metabolism of long chain ß-apocarotenoids, which recently emerged as putative regulatory molecules in mammalian biology. We showed that recombinant murine BCO2 converted the alcohol, aldehyde, and carboxylic acid of a ß-apocarotenoid substrate by oxidative cleavage at position C9,C10 into a ß-ionone and a diapocarotenoid product. Chain length variation (C20 to C40) and ionone ring site modifications of the apocarotenoid substrate did not impede catalytic activity or alter the regioselectivity of the double bond cleavage by BCO2. Isotope labeling experiments revealed that the double bond cleavage of an apocarotenoid followed a dioxygenase reaction mechanism. Structural modeling and site directed mutagenesis identified amino acid residues in the substrate tunnel of BCO2 that are critical for apocarotenoid binding and catalytic processing. Mice deficient for BCO2 accumulated apocarotenoids in their livers, indicating that the enzyme engages in apocarotenoid metabolism. Together, our study provides novel structural and functional insights into BCO2 catalysis and establishes the enzyme as a key component of apocarotenoid homeostasis in mice.


Subject(s)
Carotenoids/metabolism , Dioxygenases/metabolism , Vitamin A/metabolism , Alcohols/chemistry , Aldehydes/chemistry , Carboxylic Acids/chemistry , Carotenoids/chemistry , Catalysis , Cloning, Molecular , Dioxygenases/genetics , Escherichia coli/chemistry , Escherichia coli/genetics , Isotope Labeling , Lipid Metabolism , Models, Molecular , Molecular Structure , Oxidative Stress , Oxygen Isotopes/chemistry , Oxygenases/metabolism , Structure-Activity Relationship , Vitamin A/chemistry , beta Carotene/metabolism
20.
Food Chem ; 338: 128004, 2021 Feb 15.
Article in English | MEDLINE | ID: mdl-32950868

ABSTRACT

The aim was to enhance provitamin A carotenoid (proVA CAR) concentrations and bioaccessibility in carrots by manipulating post-harvest factors. To that end, we assessed the effects of Ultraviolet-C light, pulsed light, storage temperature, and storage duration. We also measured CAR bioaccessibility by using an in vitro model. Pulsed light, but not Ultraviolet-C, treatment increased proVA CAR concentrations in the cortex tissue (p < 0.05). Longer storage times and higher temperatures also increased concentrations (p < 0.05). The maximal increase induced by pulsed light was obtained after treatment with 20 kJ/m2 and 3-days of storage at 20 °C. However, the positive effect induced by pulsed light decreased considerably over the next seven days. ProVA CAR in carrots with the highest concentrations also proved to be more bioaccessible (p < 0.05). Thus, proVA CAR concentrations in stored carrots can be increased significantly through storage times and temperatures. Pulsed light can also significantly increase proVA CAR concentrations, but only temporarily.


Subject(s)
Carotenoids/analysis , Daucus carota/chemistry , Food Storage/methods , Provitamins/analysis , Biological Availability , Carotenoids/chemistry , Digestion , Light , Provitamins/chemistry , Provitamins/pharmacokinetics , Temperature , Time Factors , Ultraviolet Rays , Vitamin A/chemistry
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