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1.
J Hazard Mater ; 470: 134116, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38547753

RESUMEN

Microplastic (MP), as a new pollutant, not only affects the growth and development of plants but also may affect the secondary metabolites of plants. The anti-tumor role of Pinellia ternata is related to secondary metabolites. The role of brassinolide (BR) in regulating plant resistance is currently one of the research hotspots. The paper mainly explores the regulation of BR on growth and physiology of Pinellia ternata under MP stress. The experimental design includes two levels of MP (0, 1%) and two levels of BR (0, 0.1 mg/L). MP led to a marked reduction in plant height (15.0%), Fv/Fm (3.2%), SOD and APX activity (15.0%, 5.1%), whereas induced an evident raise in the rate of O2·- production (29.6%) and GSH content (4.4%), as well as flavonoids (6.8%), alkaloids (75%), and ß-sitosterol (26.5%) contents. Under MP addition, BR supply significantly increased plant height (15.7%), aboveground and underground biomass (16.1%, 10.3%), carotenoid and GSH content (11.8%, 4.2%), Fv/Fm (2.9%), and activities of SOD, GR, and MDHAR (32.2%, 21.08%, 20.9%). These results indicate that MP suppresses the growth of P. ternata, although it promotes secondary metabolism. BR can alleviate the inhibitory effect of MP on growth by improving photosynthesis, redox homeostasis, and the AsA-GSH cycle.


Asunto(s)
Brasinoesteroides , Glutatión , Homeostasis , Oxidación-Reducción , Fotosíntesis , Pinellia , Esteroides Heterocíclicos , Fotosíntesis/efectos de los fármacos , Homeostasis/efectos de los fármacos , Glutatión/metabolismo , Brasinoesteroides/metabolismo , Pinellia/metabolismo , Pinellia/efectos de los fármacos , Pinellia/crecimiento & desarrollo , Esteroides Heterocíclicos/farmacología , Plásticos/metabolismo , Sitoesteroles/metabolismo , Flavonoides/metabolismo
2.
Am J Clin Nutr ; 119(4): 969-980, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38278364

RESUMEN

BACKGROUND: People with overweight/obesity generally have impaired immune responses, resulting among others in increased risk of severe complaints and hospitalization after infections with severe acute respiratory syndrome coronavirus 2 (COVID-19), as well as decreased antibody production after vaccinations. Plant stanol ester previously increased the combined IgM/IgG antibody titers toward a hepatitis A vaccination in patients with allergic asthma, but the underlying mechanism is unknown. OBJECTIVES: We evaluated whether plant stanol ester consumption improved the immune response in subjects with overweight/obesity after a COVID-19 vaccination. METHODS: A double-blind, randomized, placebo-controlled trial was performed. Thirty-two subjects with overweight/obesity consumed products with added plant stanols (4 g/d; provided as plant stanol ester) or control ≥2 wk before receiving their COVID-19 vaccination until 4 wk after vaccination. Antibody titers were analyzed weekly and statistically analyzed using mixed models. Serum metabolic markers and cytokine profiles were also analyzed. RESULTS: IgM concentrations against the COVID-19 Spike protein were increased in the plant stanol ester group compared with the control group, with the largest difference observed 2 wk after vaccination [31.2 (0.43, 62.1) BAU/mL, or +139%; Group × Time: P = 0.031]. Subjects that produced very low IgM antibodies produced, as expected, hardly any IgG antibodies. In those with IgG seroconversion, IgG Spike concentrations were also increased in the plant stanol ester group compared with the control group [71.3 (2.51, 140.1) BAU/mL; Group P = 0.043]. Stimulated cytokine concentrations decreased in the plant stanol ester group compared with the control group in all 3 cytokine domains (that is, proinflammatory, T helper [Th1]/Th17, and Th2/regulatory T cells). Between-group differences in serum LDL cholesterol or other metabolic markers were not observed. CONCLUSIONS: Consuming plant stanols (4 g/d) affects immune responses to COVID-19 vaccinations, translating into increased serum anti-COVID-19 IgM concentrations in subjects with overweight/obesity. Only in IgG seroconverted subjects, serum anti-COVID-19 IgG concentrations also increase. These effects are independent of reductions in LDL cholesterol. These results suggest that this high-risk group for COVID-19 complications could benefit from plant stanol consumption. This trial was registered at clinicaltrials.gov as NCT04844346.


Asunto(s)
COVID-19 , Fitosteroles , Humanos , LDL-Colesterol , Sobrepeso , Formación de Anticuerpos , Vacunas contra la COVID-19 , Sitoesteroles/metabolismo , Citocinas , Obesidad , Inmunoglobulina G , Inmunoglobulina M , Método Doble Ciego
3.
Chem Commun (Camb) ; 59(61): 9392-9395, 2023 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-37435674

RESUMEN

Cholesterol catabolism is an important survival mechanism for the pathogenic Mycobacterium tuberculosis. Various other mycobacteria degrade not only cholesterol but plant sterols such as sitosterol and campesterol. In this work we demonstrate that the cytochrome P450 (CYP) CYP125 enzyme family is capable of sitosterol and campesterol side-chain oxidation and activation in these bacteria. We also show that the CYP142 and CYP124 cholesterol hydroxylating enzyme families are significantly less active for sitosterol hydroxylation compared to CYP125 enzymes.


Asunto(s)
Mycobacterium tuberculosis , Sitoesteroles , Sitoesteroles/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Colesterol/metabolismo , Oxidación-Reducción
4.
Science ; 380(6644): 520-526, 2023 05 05.
Artículo en Inglés | MEDLINE | ID: mdl-37141360

RESUMEN

Sterols are vital for nearly all eukaryotes. Their distribution differs in plants and animals, with phytosterols commonly found in plants whereas most animals are dominated by cholesterol. We show that sitosterol, a common sterol of plants, is the most abundant sterol in gutless marine annelids. Using multiomics, metabolite imaging, heterologous gene expression, and enzyme assays, we show that these animals synthesize sitosterol de novo using a noncanonical C-24 sterol methyltransferase (C24-SMT). This enzyme is essential for sitosterol synthesis in plants, but not known from most bilaterian animals. Our phylogenetic analyses revealed that C24-SMTs are present in representatives of at least five animal phyla, indicating that the synthesis of sterols common to plants is more widespread in animals than currently known.


Asunto(s)
Anélidos , Colesterol , Sitoesteroles , Animales , Colesterol/metabolismo , Filogenia , Plantas/metabolismo , Sitoesteroles/metabolismo , Anélidos/metabolismo
5.
Int J Mol Sci ; 23(20)2022 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-36293029

RESUMEN

The interplay between steroids and triterpenoids, compounds sharing the same biosynthetic pathway but exerting distinctive functions, is an important part of the defense strategy of plants, and includes metabolic modifications triggered by stress hormones such as jasmonic acid. Two experimental models, Calendula officinalis hairy root cultures and greenhouse cultivated plants (pot plants), were applied for the investigation of the effects of exogenously applied jasmonic acid on the biosynthesis and accumulation of steroids and triterpenoids, characterized by targeted GC-MS (gas chromatography-mass spectroscopy) metabolomic profiling. Jasmonic acid elicitation strongly increased triterpenoid saponin production in hairy root cultures (up to 86-fold) and their release to the medium (up to 533-fold), whereas the effect observed in pot plants was less remarkable (two-fold enhancement of saponin biosynthesis after a single foliar application). In both models, the increase of triterpenoid biosynthesis was coupled with hampering the biomass formation and modifying the sterol content, involving stigmasterol-to-sitosterol ratio, and the proportions between ester and glycoside conjugates. The study revealed that various organs in the same plant can react differently to jasmonic acid elicitation; hairy root cultures are a useful in vitro model to track metabolic changes, and enhanced glycosylation (of both triterpenoids and sterols) seems to be important strategy in plant defense response.


Asunto(s)
Calendula , Saponinas , Triterpenos , Triterpenos/farmacología , Triterpenos/metabolismo , Sitoesteroles/metabolismo , Sitoesteroles/farmacología , Estigmasterol/metabolismo , Raíces de Plantas/metabolismo , Saponinas/farmacología , Saponinas/metabolismo , Glicósidos/farmacología , Esteroides/metabolismo , Ésteres/metabolismo , Hormonas/metabolismo
6.
Am J Dermatopathol ; 44(10): 753-755, 2022 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-36122334

RESUMEN

ABSTRACT: We report a noteworthy case of a 10-year-old girl who presented with papular and nodular lesions on the skin that were clinically and histologically mistaken for progressive nodular histiocytosis. During the clinical management of the patient, the high lipid levels raised the suspicion of lipid metabolism disease and helped us to make the correct diagnosis of sitosterolemia. In sitosterolemia, proper management such as restriction of plant sterol intake and administration of cholesterol absorption inhibitor can improve prognosis.


Asunto(s)
Histiocitosis , Fitosteroles , Enfermedades de la Piel , Xantomatosis , Niño , Colesterol , Femenino , Histiocitosis/diagnóstico , Humanos , Hipercolesterolemia , Enfermedades Intestinales , Errores Innatos del Metabolismo Lipídico , Fitosteroles/efectos adversos , Sitoesteroles/metabolismo , Enfermedades de la Piel/diagnóstico , Xantomatosis/diagnóstico , Xantomatosis/metabolismo
7.
Proc Natl Acad Sci U S A ; 119(7)2022 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-35131946

RESUMEN

Tomato (Solanum lycopersicum) produces a wide range of volatile chemicals during fruit ripening, generating a distinct aroma and contributing to the overall flavor. Among these volatiles are several aromatic and aliphatic nitrogen-containing compounds for which the biosynthetic pathways are not known. While nitrogenous volatiles are abundant in tomato fruit, their content in fruits of the closely related species of the tomato clade is highly variable. For example, the green-fruited species Solanum pennellii are nearly devoid, while the red-fruited species S. lycopersicum and Solanum pimpinellifolium accumulate high amounts. Using an introgression population derived from S. pennellii, we identified a locus essential for the production of all the detectable nitrogenous volatiles in tomato fruit. Silencing of the underlying gene (SlTNH1;Solyc12g013690) in transgenic plants abolished production of aliphatic and aromatic nitrogenous volatiles in ripe fruit, and metabolomic analysis of these fruit revealed the accumulation of 2-isobutyl-tetrahydrothiazolidine-4-carboxylic acid, a known conjugate of cysteine and 3-methylbutanal. Biosynthetic incorporation of stable isotope-labeled precursors into 2-isobutylthiazole and 2-phenylacetonitrile confirmed that cysteine provides the nitrogen atom for all nitrogenous volatiles in tomato fruit. Nicotiana benthamiana plants expressing SlTNH1 readily transformed synthetic 2-substituted tetrahydrothiazolidine-4-carboxylic acid substrates into a mixture of the corresponding 2-substituted oxime, nitro, and nitrile volatiles. Distinct from other known flavin-dependent monooxygenase enzymes in plants, this tetrahydrothiazolidine-4-carboxylic acid N-hydroxylase catalyzes sequential hydroxylations. Elucidation of this pathway is a major step forward in understanding and ultimately improving tomato flavor quality.


Asunto(s)
Frutas/química , Oxigenasas de Función Mixta/metabolismo , Nitrógeno/metabolismo , Odorantes/análisis , Sitoesteroles/metabolismo , Solanum lycopersicum/metabolismo , Frutas/metabolismo , Oxigenasas de Función Mixta/genética , Nitrógeno/química , Compuestos Orgánicos Volátiles
8.
J Steroid Biochem Mol Biol ; 216: 106039, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34861389

RESUMEN

We evaluated oxyphytosterol (OPS) concentrations in plasma and various tissues of two genetically modified mouse models with either increased cholesterol (apoE KO mice) or increased cholesterol and plant sterol (PS) concentrations (apoExABCG8 dKO mice). Sixteen female apoE KO and 16 dKO mice followed the same standard, low OPS-chow diet. Animals were euthanized at 36 weeks to measure PS and OPS concentrations in plasma, brain, liver and aortic tissue. Cholesterol and oxysterol (OS) concentrations were analyzed as reference for sterol oxidation in general. Plasma campesterol (24.1 ± 4.3 vs. 11.8 ± 3.0 mg/dL) and sitosterol (67.4 ± 12.7 vs. 4.9 ± 1.1 mg/dL) concentrations were severely elevated in the dKO compared to the apoE KO mice (p < 0.001). Also, in aortic and brain tissue, PS levels were significantly elevated in dKO. However, plasma, aortic and brain OPS concentrations were comparable or even lower in the dKO mice. In contrast, in liver tissue, both PS and OPS concentrations were severely elevated in the dKO compared to apoE KO mice (sum OPS: 7.4 ± 1.6 vs. 4.1 ± 0.8 ng/mg, p < 0.001). OS concentrations followed cholesterol concentrations in plasma and all tissues suggesting ubiquitous oxidation. Despite severely elevated PS concentrations, OPS concentrations were only elevated in liver tissue, suggesting that OPS are primarily formed in the liver and plasma concentrations originate from hepatic spill-over into the circulation.


Asunto(s)
Hígado/metabolismo , Oxiesteroles/sangre , Fitosteroles/sangre , Transportador de Casete de Unión a ATP, Subfamilia G, Miembro 8/genética , Animales , Apolipoproteínas E/genética , Colesterol/análogos & derivados , Colesterol/sangre , Colesterol/metabolismo , Femenino , Metabolismo de los Lípidos/genética , Lipoproteínas/genética , Ratones , Ratones Noqueados , Oxidación-Reducción , Oxiesteroles/metabolismo , Fitosteroles/metabolismo , Sitoesteroles/sangre , Sitoesteroles/metabolismo
9.
Biomed Res Int ; 2021: 8141075, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34873575

RESUMEN

OBJECTIVE: Nephrotic syndrome (NS) is a common glomerular disease caused by a variety of causes and is the second most common kidney disease. Guizhi is the key drug of Wulingsan in the treatment of NS. However, the action mechanism remains unclear. In this study, network pharmacology and molecular docking were used to explore the underlying molecular mechanism of Guizhi in treating NS. METHODS: The active components and targets of Guizhi were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Hitpick, SEA, and Swiss Target Prediction database. The targets related to NS were obtained from the DisGeNET, GeneCards, and OMIM database, and the intersected targets were obtained by Venny2.1.0. Then, active component-target network was constructed using Cytoscape software. And the protein-protein interaction (PPI) network was drawn through the String database and Cytoscape software. Next, Gene Ontology (GO) and pathway enrichment analyses of Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by DAVID database. And overall network was constructed through Cytoscape. Finally, molecular docking was conducted using Autodock Vina. RESULTS: According to the screening criteria, a total of 8 active compounds and 317 potential targets of Guizhi were chosen. Through the online database, 2125 NS-related targets were identified, and 93 overlapping targets were obtained. In active component-target network, beta-sitosterol, sitosterol, cinnamaldehyde, and peroxyergosterol were the important active components. In PPI network, VEGFA, MAPK3, SRC, PTGS2, and MAPK8 were the core targets. GO and KEGG analyses showed that the main pathways of Guizhi in treating NS involved VEGF, Toll-like receptor, and MAPK signaling pathway. In molecular docking, the active compounds of Guizhi had good affinity with the core targets. CONCLUSIONS: In this study, we preliminarily predicted the main active components, targets, and signaling pathways of Guizhi to treat NS, which could provide new ideas for further research on the protective mechanism and clinical application of Guizhi against NS.


Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Síndrome Nefrótico/tratamiento farmacológico , Acroleína/análogos & derivados , Acroleína/metabolismo , Ontología de Genes , Humanos , Medicina Tradicional China/métodos , Simulación del Acoplamiento Molecular/métodos , Síndrome Nefrótico/metabolismo , Farmacología en Red/métodos , Mapas de Interacción de Proteínas/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Sitoesteroles/metabolismo , Programas Informáticos , Tecnología/métodos
10.
Sci Rep ; 11(1): 21618, 2021 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-34732753

RESUMEN

The properties of biomembranes depend on the presence, local structure and relative distribution assumed by the thousands of components it is made of. As for animal cells, plant membranes have been demonstrated to be organized in subdomains with different persistence lengths and times. In plant cells, sitosterol has been demonstrated to confer to phospholipid membranes a more ordered structure while among lipids, glycosphingolipids are claimed to form rafts where they tightly pack with sterols. Glucosylceramides are glycosphingolipids involved in plant signalling and are essential for viability of cells and whole plant. The glucosylceramide-sitosterol structural coupling within PLPC membranes is here investigated by Langmuir films, in silico simulations and neutron reflectometry, unveiling that a strong direct interaction between the two molecules exists and governs their lateral and transversal distribution within membrane leaflets. The understanding of the driving forces governing specific molecules clustering and segregation in subdomains, such as glucosylceramide and sitosterol, have an impact on the mechanical properties of biomembranes and could reflect in the other membrane molecules partitioning and activity.


Asunto(s)
Membrana Celular/metabolismo , Glucosilceramidas/metabolismo , Membrana Dobles de Lípidos/metabolismo , Células Vegetales/metabolismo , Sitoesteroles/metabolismo
11.
Oxid Med Cell Longev ; 2021: 4883398, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34603597

RESUMEN

Many traditional Chinese medicines (TCMs) with skin-whitening properties have been recorded in the Ben-Cao-Gang-Mu and in folk prescriptions, and some literature confirms that their extracts do have the potential to inhibit pigmentation. However, no systematic studies have identified the specific regulatory mechanisms of the potential active ingredients. The aim of this study was to screen the ingredients in TCMs that inhibit skin pigmentation through a network pharmacology system and to explore underlying mechanisms. We identified 148 potential active ingredients from 14 TCMs, and based on the average "degree" of the topological parameters, the top five TCMs (Fructus Ligustri Lucidi, Hedysarum multijugum Maxim., Ampelopsis japonica, Pseudobulbus Cremastrae Seu Pleiones, and Paeoniae Radix Alba) that were most likely to cause skin-whitening through anti-inflammatory processes were selected. Sitogluside, the most common ingredient in the top five TCMs, inhibits melanogenesis in human melanoma cells (MNT1) and murine melanoma cells (B16F0) and decreases skin pigmentation in zebrafish. Furthermore, mechanistic research revealed that sitogluside is capable of downregulating tyrosinase (TYR) expression by inhibiting the ERK and p38 pathways and inhibiting TYR activity. These results demonstrate that network pharmacology is an effective tool for the discovery of natural compounds with skin-whitening properties and determination of their possible mechanisms. Sitogluside is a novel skin-whitening active ingredient with dual regulatory effects that inhibit TYR expression and activity.


Asunto(s)
Farmacología en Red/métodos , Sitoesteroles/farmacología , Pigmentación de la Piel/efectos de los fármacos , Animales , Arbutina/química , Arbutina/metabolismo , Sitios de Unión , Productos Biológicos/química , Productos Biológicos/metabolismo , Productos Biológicos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Bases de Datos de Compuestos Químicos , Regulación hacia Abajo/efectos de los fármacos , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Medicina Tradicional China , Melaninas/metabolismo , Ratones , Simulación del Acoplamiento Molecular , Monofenol Monooxigenasa/antagonistas & inhibidores , Monofenol Monooxigenasa/genética , Monofenol Monooxigenasa/metabolismo , Sitoesteroles/química , Sitoesteroles/metabolismo
12.
J Biol Chem ; 297(4): 101105, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34425106

RESUMEN

The degradation of cholesterol and related steroids by microbes follows fundamentally different strategies in aerobic and anaerobic environments. In anaerobic bacteria, the primary C26 of the isoprenoid side chain is hydroxylated without oxygen via a three-step cascade: (i) water-dependent hydroxylation at the tertiary C25, (ii) ATP-dependent dehydration to form a subterminal alkene, and (iii) water-dependent hydroxylation at the primary C26 to form an allylic alcohol. However, the enzymes involved in the ATP-dependent dehydration have remained unknown. Here, we isolated an ATP-dependent 25-hydroxy-steroid kinase (25-HSK) from the anaerobic bacterium Sterolibacterium denitrificans. This highly active enzyme preferentially phosphorylated the tertiary C25 of steroid alcohols, including metabolites of cholesterol and sitosterol degradation or 25-OH-vitamin D3. Kinetic data were in agreement with a sequential mechanism via a ternary complex. Remarkably, 25-HSK readily catalyzed the formation of γ-(18O)2-ATP from ADP and the C25-(18O)2-phosphoester. The observed full reversibility of 25-HSK with an equilibrium constant below one can be rationalized by an unusual high phosphoryl transfer potential of tertiary steroid C25-phosphoesters, which is ≈20 kJ mol-1 higher than that of standard sugar phosphoesters and even slightly greater than the ß,γ-phosphoanhydride of ATP. In summary, 25-HSK plays an essential role in anaerobic bacterial degradation of zoo- and phytosterols and shows only little similarity to known phosphotransferases.


Asunto(s)
Proteínas Bacterianas/química , Betaproteobacteria/enzimología , Colesterol/química , Fosfotransferasas/química , Sitoesteroles/química , Proteínas Bacterianas/metabolismo , Colesterol/metabolismo , Oxidación-Reducción , Fosfotransferasas/metabolismo , Sitoesteroles/metabolismo
13.
J Oleo Sci ; 70(8): 1093-1101, 2021 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-34248096

RESUMEN

The size, dispersibility, and fluidity of DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine), POPC (1-palmitoy-2-oleoyl-sn-glycero-3-phosphocholine), and DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine) liposomes doped with ß-sitosteryl sulfate (PSO4) were comparatively studied. In all three types of liposomes, PSO4 reduced sizes and enhanced the negative values of the ζ-potential. However, the effect on sizes quantitatively differed in the three cases in a manner dependent on their phase behaviors. PSO4 rigidified each type of membrane in its liquid crystalline phase and fluidized the gel phase. It enhanced the glucose trapping efficiency (TE) of both DPPC and DOPC liposomes. The TE of DPPC first increased with the increasing concentration of PSO4, then decreased gradually. On the other hand, in the case of DOPC, the TE increased significantly upon addition of PSO4, then remained nearly constant. Though the exact dependence of TE on the PSO4 concentration differed in the two cases, its effect, in each case, was more than the effect of ß-sitosterol (POH). The ability of PSO4 for reducing the size and enhancing dispersibility and TE of liposomes can be useful for preparing cosmetics and pharmaceutical formulations.


Asunto(s)
1,2-Dipalmitoilfosfatidilcolina/química , Liposomas/química , Fosfatidilcolinas/química , Sitoesteroles/química , 1,2-Dipalmitoilfosfatidilcolina/metabolismo , Glucosa/metabolismo , Liposomas/metabolismo , Fluidez de la Membrana , Estructura Molecular , Tamaño de la Partícula , Fosfatidilcolinas/metabolismo , Sitoesteroles/metabolismo , Electricidad Estática
14.
Protein Pept Lett ; 28(3): 276-281, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32798371

RESUMEN

BACKGROUND: Although glucocorticoids (GCs) are characterized as powerful agents to treat inflammatory afflictions, they are accompanied by metabolic side effects which limit their usage. ß-Sitosterol, as a minor component found in extraction of vegetable oil, was reported to have anti-inflammatory effects in RAW 264.7 cells. OBJECTIVE: To test whether ß-sitosterol has an effect to dissociate transrepression from transactivation as a selective novel GR binder, this work evaluated the dissociated characteristics of ß-sitosterol. METHODS: The probable binding interaction between ß-sitosterol and GR was explored by molecular docking. The GR transcriptional activity of ß-sitosterol was assessed in the reporter gene assay. The ability of ß-sitosterol to modulate the transactivation and transrepression of GR was evaluated by real-time quantitative PCR analysis. RESULTS AND DISCUSSION: In the present study, ß-sitosterol treatment cannot induce GR-mediated transactivation. ß-Sitosterol exerted a potential to inhibited the expression of GR target transrepressed gene without activating the expression of GR transactivation dependent gene. Molecular docking demonstrated that ß-Sitosterol was able to bind the ligand binding domain of GR but unable to induce GR activation. CONCLUSION: This work offers evidence that ß-sitosterol may serve as a selective GR modulator.


Asunto(s)
Simulación del Acoplamiento Molecular , Receptores de Glucocorticoides/química , Sitoesteroles/química , Animales , Células HeLa , Células Hep G2 , Humanos , Ratones , Células RAW 264.7 , Receptores de Glucocorticoides/metabolismo , Sitoesteroles/metabolismo
15.
Biomed Pharmacother ; 131: 110702, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32882583

RESUMEN

Phytosterols are bioactive compounds that are naturally present in plant cell membranes with chemical structure similar to the mammalian cell- derived cholesterol. They are highly present in lipid-rich plant foods such as nuts, seed, legumes and olive oil. Among various phytosterols, ß-sitosterol (SIT) is the major compound, found plentiful in plants. It has been evidenced in many in-vitro and in-vivo studies that SIT possesses various biological actions such as anxiolytic & sedative effects, analgesic, immunomodulatory, antimicrobial, anticancer, anti - inflammatory, lipid lowering effect, hepatoprotective, protective effect against NAFLD and respiratory diseases, wound healing effect, antioxidant and anti-diabetic activities. In this review, in order to compile the sources, characterization, biosynthesis, pharmacokinetics, antioxidant and anti-diabetic activities of SIT, classical and online-literature were studied which includes the electronic search (Sci Finder, Pubmed, Google Scholar, Scopus, and Web of Science etc) and books on photochemistry. The experimental studies on SIT gives a clear evidence that the potential phytosterol can be used as supplements to fight against life threatening diseases. High potential of this compound, classifies it as the notable drug of the future. Therefore, immense researches regarding its action at molecular level on life threatening diseases in humans are highly endorsed.


Asunto(s)
Diabetes Mellitus/tratamiento farmacológico , Suplementos Dietéticos , Sitoesteroles/administración & dosificación , Animales , Antioxidantes/farmacología , Humanos , Sitoesteroles/química , Sitoesteroles/metabolismo , Sitoesteroles/farmacología
16.
Arch Biochem Biophys ; 689: 108472, 2020 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-32590065

RESUMEN

ß-Sitosterol (ßSito) is the most abundant phytosterol found in elevated concentrations in vegetable oils, nuts, seeds, cereals, fruits, and in many phytosterol-enriched foods. Although the benefits, there is a concern in terms of food quality and health due to the increasing consumption of phytosterols and the possible adverse side effects of their oxidation products, oxyphytosterols. ßSito has a similar structure to cholesterol, with an unsaturated double bond at C5-C6, which is susceptible to oxidation by reactive oxygen species like ozone, generating oxyphytosterols. In this work we propose a mechanism of formation of three oxyphytosterols 2-[(7aR)-5-[(1R,4S)-4-hydroxy-1-methyl-2-oxocyclohexyl]-1,7a-dimethyl-1,2,3,3a,4,5,6,7- octahydroinden-4-yl] acetaldehyde (ßSec), (2-[(7aR)-5-[(2R,5S)-5-hydroxy-2-methyl-7-oxo-oxepan- 2-yl]-1,7a-dimethyl-1,2,3,3a,4,5,6,7-octahydroinden-4- yl] acetaldehyde (ßLac) and 2-((7aR)-5-((1R,4S)-4-hydroxy-1-methyl-2- oxocyclohexyl)-1,7a-dimethyloctahydro-1Hinden-4-yl) acetic acid (ßCOOH) generated by ozonization of ßSito, through their synthesis and molecular characterization. The cytotoxic effect of ßSito and its main oxyphytosterol ßSec was evaluated and both reduced the HepG2 cell viability.


Asunto(s)
Ozono/metabolismo , Fitosteroles/metabolismo , Sitoesteroles/metabolismo , Supervivencia Celular/efectos de los fármacos , Células Hep G2 , Humanos , Oxidación-Reducción , Fitosteroles/química , Fitosteroles/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Sitoesteroles/química , Sitoesteroles/toxicidad
17.
Biosci Rep ; 40(7)2020 07 31.
Artículo en Inglés | MEDLINE | ID: mdl-32579186

RESUMEN

It is controversial whether atherosclerosis is linked to increased intestinal cholesterol absorption or synthesis in humans. The aim of the present study was to relate atherosclerosis to the measurements of plasma markers of cholesterol synthesis (desmosterol, lathosterol) and absorption (campesterol, sitosterol). In healthy male (n=344), non-obese, non-diabetics, belonging to the city of São Paulo branch of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), we measured in plasma these non-cholesterol sterol markers, together with their anthropometric, dietary parameters, traditional atherosclerotic risk factors, and blood chemistry, coronary arterial calcium score (CAC), and ultrasonographically measured common carotid artery intima-media thickness (CCA-IMT). Cases with CAC>zero had the following parameters higher than cases with CAC = zero: age, waist circumference (WC), plasma total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and non-high density lipoprotein-cholesterol (non HDL-C). Plasma desmosterol and campesterol, duly corrected for TC, age, body mass index (BMI), waist circumference (WC), hypertension, smoking, and the homeostasis model assessment-insulin resistance (HOMA-IR) correlated with CAC, but not with CCA-IMT. The latter related to increased age, BMI, waist circumference (WC), and systolic blood pressure (SBP). Plasma HDL-C concentrations did not define CAC or CCA-IMT degrees, although in relation to the lower tertile of HDL-C in plasma the higher tertile of HDL-C had lower HOMA-IR and concentration of a cholesterol synthesis marker (desmosterol). Present work indicated that increased cholesterol synthesis and absorption represent primary causes of CAD, but not of the common carotid artery atherosclerosis.


Asunto(s)
Aterosclerosis/diagnóstico , Calcio/análisis , Vasos Coronarios/química , Adulto , Anciano , Aterosclerosis/sangre , Biomarcadores/sangre , Biomarcadores/metabolismo , Índice de Masa Corporal , Brasil , Arteria Carótida Común/diagnóstico por imagen , Grosor Intima-Media Carotídeo , Colesterol/análogos & derivados , Colesterol/sangre , Colesterol/metabolismo , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Vasos Coronarios/diagnóstico por imagen , Estudios Transversales , Desmosterol/sangre , Desmosterol/metabolismo , Femenino , Humanos , Absorción Intestinal , Mucosa Intestinal/metabolismo , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Fitosteroles/sangre , Fitosteroles/metabolismo , Estudios Prospectivos , Sitoesteroles/sangre , Sitoesteroles/metabolismo , Tomografía Computarizada por Rayos X , Ultrasonografía
18.
J Insect Physiol ; 123: 104054, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32275907

RESUMEN

Sterols are essential membrane components and are critical for many physiological processes in all eukaryotes. Insects and other arthropods are sterol auxotrophs that typically rely on a dietary source of sterols. Herbivorous insects generally obtain sterols from plants and then metabolize them into cholesterol, the dominant sterol in most insects. However, there is significant variation in phytosterol structure, and not all phytosterols are equally suitable for insects. In the current study, we used seven Arabidopsis thaliana lines that display altered sterol profiles due to mutations in the sterol biosynthetic pathway or to overexpression of key enzymes of the pathway, and investigated how plant sterol profiles affected green peach aphid (Myzus persicae) growth and reproduction. We also characterized the sterol profile of aphids reared on these Arabidopsis genotypes. Aphids on two mutant lines (14R/fk and ste1-1) that accumulated biosynthetic sterol intermediates (Δ8,14-sterols, and Δ7-sterols, respectively) all showed significantly reduced growth and reproduction. Aphids on SMT2COSUP plants (which have decreased ß-sitosterol but increased campesterol) also displayed significantly reduced growth and reproduction. However, aphids on SMT2OE plants (which have increased ß-sitosterol but decreased campesterol) performed similarly to aphids on wild-type plants. Finally, Arabidopsis plants that had an overproduction of sterols (CD-HMGROE) or decreased sterol esters (psat1-2) had no impact on aphid performance. Two noteworthy results come from the aphid sterol profile study. First, ß-sitosterol, cholesterol and stigmasterol were recovered in all aphids. Second, we did not detect Δ8,14-sterols in aphids reared on 14R/fk plants. We discuss the implications of our findings, including how aphid sterol content does not appear to reflect plant leaf sterol profiles. We also discuss the potential of modifying plant sterol profiles to control insect herbivore pests, including aphids.


Asunto(s)
Áfidos/fisiología , Arabidopsis/química , Colesterol/análogos & derivados , Fitosteroles/metabolismo , Sitoesteroles/metabolismo , Animales , Áfidos/crecimiento & desarrollo , Arabidopsis/genética , Colesterol/química , Colesterol/metabolismo , Cadena Alimentaria , Regulación de la Expresión Génica de las Plantas , Fitosteroles/química , Plantas Modificadas Genéticamente/química , Plantas Modificadas Genéticamente/genética , Sitoesteroles/química
19.
Biosci Biotechnol Biochem ; 84(7): 1521-1528, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32183612

RESUMEN

Sterols are verified to be able to produce polycyclic aromatic hydrocarbons during its pyrolysis. In this study, a kind of Aspergillus fumigatus (LSD-1) was isolated from cigar leaves, and the biosorption effects on the stigmasterol, ß-sitosterol, campesterol, cholesterol, and ergosterol by using living and dead biomass of LSD-1 were investigated. The results showed that both living and dead biomass could efficiently remove these sterols in aqueous solution and tobacco waste extract (TWE). Interestingly, compared with the living biomass of LSD-1, the dead biomass of LSD-1 not only kept a high adsorption efficiency but also did not produce ergosterol. Overall, dead biomass of LSD-1 was a more suitable biosorbent to sterols in TWE. Furthermore, Brunner-Emmet-Teller (BET), Fourier transformed infrared spectrometer (FTIR) and scanning electron microscope (SEM) analysis were used to explore the biosorption process of living and dead biomass and their differences, suggesting that the biosorption of sterols was a physical process.


Asunto(s)
Absorción Fisiológica , Aspergillus fumigatus/metabolismo , Colesterol/análogos & derivados , Ergosterol/metabolismo , Nicotiana/química , Nicotiana/microbiología , Fitosteroles/metabolismo , Extractos Vegetales/metabolismo , Sitoesteroles/metabolismo , Estigmasterol/metabolismo , Biodegradación Ambiental , Biomasa , Colesterol/metabolismo , Concentración de Iones de Hidrógeno , Microscopía Electrónica de Rastreo , Hojas de la Planta/química , Hojas de la Planta/microbiología , Espectroscopía Infrarroja por Transformada de Fourier , Contaminantes Químicos del Agua/metabolismo
20.
Poult Sci ; 99(3): 1400-1408, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32111314

RESUMEN

This research investigated effects of dietary ß-sitosterol addition at different levels on serum lipid levels, immune function, oxidative status, and intestinal morphology in broilers. One-day-old broiler chicks were allocated to 5 groups of 6 replicates. Chickens in the 5 groups were fed a basal diet supplemented with 0 (control group), 40, 60, 80, and 100 mg/kg of ß-sitosterol for 42 D, respectively. ß-Sitosterol linearly decreased (P < 0.05) concentrations of serum total cholesterol, jejunal tumor necrosis factor α (TNF-α), and ileal interleukin 1ß (IL-1ß) and mRNA relative expressions levels of jejunal TLR4 and ileal MyD88, whereas it linearly increased (P < 0.05) contents of jejunal immunoglobulin G (IgG), ileal secreted IgA and glutathione, jejunal catalase activity and Nrf2 mRNA relative expression level, villus height (VH), and VH-to-crypt depth (CD) ratio (VH:CD) in the jejunum and ileum. Linear and quadratic increases (P < 0.05) in absolute and relative spleen weight were observed by dietary ß-sitosterol, whereas malondialdehyde (MDA) concentration in the jejunum and ileum followed the opposite trend (P < 0.05). Compared with the control group, dietary ß-sitosterol at higher than or equal to 60 mg/kg level decreased (P < 0.05) contents of serum total cholesterol, ileal MDA, and jejunal TLR4 mRNA relative expression level, whereas it increased (P < 0.05) absolute spleen weight and ileal glutathione content. Higher than or equal to 80 mg/kg level of ß-sitosterol enhanced (P < 0.05) jejunal IgG concentration, VH, catalase activity, and Nrf2 relative expression level and ileal secreted IgA content, but reduced (P < 0.05) ileal IL-1ß content and MyD88 mRNA relative expression level. ß-Sitosterol addition at 60 and 80 mg/kg levels increased (P < 0.05) relative spleen weight, whereas it decreased (P < 0.05) jejunal MDA accumulation. Moreover, 100 mg/kg level of ß-sitosterol reduced (P < 0.05) jejunal TNF-α level, but it increased (P < 0.05) VH in the jejunum and VH:CD in the jejunum and ileum. Accordingly, dietary ß-sitosterol supplementation could regulate serum cholesterol level, promote immune function, and improve intestinal oxidative status and morphology in broilers.


Asunto(s)
Pollos/fisiología , Inmunidad Innata/efectos de los fármacos , Intestinos/efectos de los fármacos , Lípidos/sangre , Estrés Oxidativo/efectos de los fármacos , Sitoesteroles/metabolismo , Alimentación Animal/análisis , Animales , Pollos/sangre , Dieta/veterinaria , Suplementos Dietéticos/análisis , Relación Dosis-Respuesta a Droga , Intestinos/anatomía & histología , Distribución Aleatoria , Sitoesteroles/administración & dosificación
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