-
Food Chemistry Oct 2022The study investigated the thermo-oxidative stability of distigmasterol-modified acylglycerols as a new structured acylglycerols. Samples were heated at 60 and 180 °C...
The study investigated the thermo-oxidative stability of distigmasterol-modified acylglycerols as a new structured acylglycerols. Samples were heated at 60 and 180 °C for 8 h. Their percentage degradation and products formed during heating were compared with free stigmasterol and stigmasteryl esters. The remaining of stigmasterol and fatty acid parts, the formation of stigmasterol oxidation products and the composition of polar and non-polar fractions were analysed using chromatographic methods. The cytotoxicity and genotoxicity were determined with the use of an MTT test and a comet assay, respectively. The highest stability during heating was observed for 2,3-distigmasterylsuccinoyl-1-oleoyl-sn-glycerol (dStigS-OA) and the lowest for 2,3-distigmasterylcarbonoyl-1-oleoyl-sn-glycerol (dStigC-OA). Data showed that the formation of thermo-oxidative degradation products is affected by the temperature and chemical structure of lipids present in the molecule. The dStigMAs bonded by a succinate linker and products formed during their thermo-oxidation showed no cytotoxic or genotoxic activity to normal human cells.
Topics: Glycerides; Glycerol; Humans; Oxidative Stress; Phytosterols; Stigmasterol
PubMed: 35551028
DOI: 10.1016/j.foodchem.2022.133150 -
Molecular and Cellular Endocrinology Feb 2017Foods and botanical supplements can interfere with the endocrine system through the presence of phytosteroids - chemicals that interact with steroids receptors.... (Review)
Review
Foods and botanical supplements can interfere with the endocrine system through the presence of phytosteroids - chemicals that interact with steroids receptors. Phytoestrogens are well studied, but compounds such as kaempferol, apigenin, genistein, ginsenoside Rf, and glycyrrhetinic acid have been shown to interact with non-estrogen nuclear receptors. These compounds can have agonist, antagonist, or mixed agonist/antagonist activity depending on compound, receptor, cell line or tissue, and concentration. Some phytosteroids have also been shown to inhibit steroid metabolizing enzymes, resulting in biological effects through altered endogenous steroid concentrations. An interesting example, compound A (4-[1-chloro-2-(methylamino)ethyl]phenyl acetate hydrochloride (1:1)) is a promising selective glucocorticoid receptor modulator (SGRM) based on a phytosteroid isolated from Salsola tuberculatiformis Botschantzev. Given that $6.9 billion of herbal supplements are sold each year, is clear that further identification and characterization of phytosteroids is needed to ensure the safe and effective use of botanical supplements.
Topics: Animals; Biological Products; Endocrine System; Estrogens; Humans; Phytosterols; Reproduction
PubMed: 27986590
DOI: 10.1016/j.mce.2016.12.013 -
Biochimie Dec 2019Microalgae are photosynthetic microorganisms that produce numerous bioactive molecules that can be used as food supplement to prevent chronic disease installation.... (Review)
Review
Microalgae are photosynthetic microorganisms that produce numerous bioactive molecules that can be used as food supplement to prevent chronic disease installation. Indeed, they produce phycobiliproteins, polysaccharides, lipids, carotenoids and sterolic compounds. The use of microalgae in human nutrition provide a mixture of these molecules with synergistic effect. The aim of this review is to present the specific roles played by the xanthophylls, and specifically astaxanthin and fucoxanthin, two high added value carotenoids, and by microalgal phytosterols such as β-sitosterol, campesterol and stigmasterol on several cell mechanisms involved in the prevention of cardiometabolic diseases and cancers. This review explains how these microalgal molecules modulate cell signaling pathways involved in carbohydrate and lipid metabolisms, inflammation, apoptosis, invasion and metastasis. Xanthophylls and phytosterols are involved in the reduction of inflammatory markers in relation with the regulation of the c-Jun N-terminal kinases and nuclear factor-kappa B signaling pathways, and suppression of production of pro-inflammatory mediators. Xanthophylls act on glucose and lipid metabolisms via both the upregulation of peroxisome proliferator-activated receptors (PPARs) and glucose transporters and its effects on the expression of enzymes involved in fatty acid synthesis and cholesterol metabolism. Their anti-cancer effects are related to the induction of intrinsic apoptosis due to down-regulation of key regulatory kinases. The anti-angiogenesis, anti-proliferative and anti-invasive effects are correlated with decreased production of endothelial growth factors and of matrix metalloproteinases. Phytosterols have a major role on cholesterol absorption via modification of the activities of Niemann-Pick C1 like 1 and ATP-binding cassette transporters and on cholesterol esterification. Their action are also related with the modulation of PPARs and sterol regulatory element-binding protein-1 activities.
Topics: Apoptosis; Carbohydrate Metabolism; Cardiovascular Diseases; Cholesterol; Dietary Supplements; Humans; Lipid Metabolism; Metabolic Diseases; Microalgae; Neoplasms; Phytosterols; Signal Transduction; Sitosterols; Xanthophylls
PubMed: 31545993
DOI: 10.1016/j.biochi.2019.09.012 -
Molecular Plant Nov 2013The plant steroid hormones, brassinosteroids (BRs), and their precursors, phytosterols, play major roles in plant growth, development, and stress tolerance. Here, we... (Review)
Review
The plant steroid hormones, brassinosteroids (BRs), and their precursors, phytosterols, play major roles in plant growth, development, and stress tolerance. Here, we review the impressive progress made during recent years in elucidating the components of the sterol and BR metabolic and signaling pathways, and in understanding their mechanism of action in both model plants and crops, such as Arabidopsis and rice. We also discuss emerging insights into the regulations of these pathways, their interactions with other hormonal pathways and multiple environmental signals, and the putative nature of sterols as signaling molecules.
Topics: Biological Transport; Brassinosteroids; Phytosterols; Plants; Signal Transduction; Squalene; Steroids, Heterocyclic
PubMed: 23761349
DOI: 10.1093/mp/sst096 -
Applied Microbiology and Biotechnology Feb 2024Steroid-based drugs are now mainly produced by the microbial transformation of phytosterol, and a two-step bioprocess is adopted to reach high space-time yields, but...
Steroid-based drugs are now mainly produced by the microbial transformation of phytosterol, and a two-step bioprocess is adopted to reach high space-time yields, but byproducts are frequently observed during the bioprocessing. In this study, the catabolic switch between the C19- and C22-steroidal subpathways was investigated in resting cells of Mycobacterium neoaurum NRRL B-3805, and a dose-dependent transcriptional response toward the induction of phytosterol with increased concentrations was found in the putative node enzymes including ChoM2, KstD1, OpccR, Sal, and Hsd4A. Aldolase Sal presented a dominant role in the C22 steroidal side-chain cleavage, and the byproduct was eliminated after sequential deletion of opccR and sal. Meanwhile, the molar yield of androst-1,4-diene-3,17-dione (ADD) was increased from 59.4 to 71.3%. With the regard of insufficient activity of rate-limiting enzymes may also cause byproduct accumulation, a chromosomal integration platform for target gene overexpression was established supported by a strong promoter L2 combined with site-specific recombination in the engineered cell. Rate-limiting steps of ADD bioconversion were further characterized and overcome. Overexpression of the kstD1 gene further strengthened the bioconversion from AD to ADD. After subsequential optimization of the bioconversion system, the directed biotransformation route was developed and allowed up to 82.0% molar yield with a space-time yield of 4.22 g·L·day. The catabolic diversion elements and the genetic overexpression tools as confirmed and developed in present study offer new ideas of M. neoaurum cell factory development for directed biotransformation for C19- and C22-steroidal drug intermediates from phytosterol. KEY POINTS: • Resting cells exhibited a catabolic switch between the C19- and C22-steroidal subpathways. • The C22-steroidal byproduct was eliminated after sequential deletion of opccR and sal. • Rate-limiting steps were overcome by promoter engineering and chromosomal integration.
Topics: Aldehyde-Lyases; Androstadienes; Cell Differentiation; Phytosterols; Polyenes
PubMed: 38300290
DOI: 10.1007/s00253-023-12847-z -
The Journal of Biological Chemistry Jun 2023Cholesterol is the precursor of bioactive plant metabolites such as steroidal saponins. An Australian plant, Dioscorea transversa, produces only two steroidal saponins:...
Cholesterol is the precursor of bioactive plant metabolites such as steroidal saponins. An Australian plant, Dioscorea transversa, produces only two steroidal saponins: 1β-hydroxyprotoneogracillin and protoneogracillin. Here, we used D. transversa as a model in which to elucidate the biosynthetic pathway to cholesterol, a precursor to these compounds. Preliminary transcriptomes of D. transversa rhizome and leaves were constructed, annotated, and analyzed. We identified a novel sterol side-chain reductase as a key initiator of cholesterol biosynthesis in this plant. By complementation in yeast, we determine that this sterol side-chain reductase reduces Δ double bonds required for phytosterol biogenesis as well as Δ double bonds. The latter function is believed to initiate cholesterogenesis by reducing cycloartenol to cycloartanol. Through heterologous expression, purification, and enzymatic reconstitution, we also demonstrate that the D. transversa sterol demethylase (CYP51) effectively demethylates obtusifoliol, an intermediate of phytosterol biosynthesis and 4-desmethyl-24,25-dihydrolanosterol, a postulated downstream intermediate of cholesterol biosynthesis. In summary, we investigated specific steps of the cholesterol biosynthetic pathway, providing further insight into the downstream production of bioactive steroidal saponin metabolites.
Topics: Australia; Cholesterol; Cytochrome P450 Family 51; Dioscorea; Oxidoreductases; Phytosterols; Saccharomyces cerevisiae; Saponins; Transcriptome
PubMed: 37142228
DOI: 10.1016/j.jbc.2023.104768 -
Nutrients Jul 2019(1) Background: Modern dietary patterns with a high intake of fat and fructose, as well as refined carbohydrates, closely relate to lipid/glucose metabolic disorders....
(1) Background: Modern dietary patterns with a high intake of fat and fructose, as well as refined carbohydrates, closely relate to lipid/glucose metabolic disorders. The main objective of this study is to provide new thoughts in designing functional food with some lipid/glucose metabolism regulating effects for obese people. (2) Methods: The alleviating abilities of γ-oryzanol, phytosterol or ferulic acid-enriched wheat flour on lipid/glucose metabolic dysfunction were evaluated in male SD rats induced by a high-fat-fructose diet. The underlying mechanisms were clarified using western blot. (3) Results: In an in vitro cell model, γ-oryzanol, phytosterol and ferulic acid regulate lipid/glucose metabolism by increasing the phosphorylation of AMPK and Akt, and PI3K expression, as well as decreasing expressions of DGAT1 and SCD. The in vivo study shows that ferulic acid and γ-oryzanol-enriched flours are beneficial for managing body weight, improving glucose metabolism, hyperlipidemia and hepatic lipid accumulation. Phytosterol-enriched flour exerted remarkable effects in regulating hyperinsulinemia, insulin resistance and hyperuricemia. Western blot analysis of proteins from liver samples reveals that these enriched flours alleviated hepatic lipid accumulation and insulin resistance through their elevation in the phosphorylation of AMPK and Akt. (4) Conclusions: Our study indicates that these enriched flours can serve as a health-promoting functional food to regulate obesity-related lipid/glucose metabolic dysfunction in rats.
Topics: Animal Feed; Animals; Biomarkers; Blood Glucose; Coumaric Acids; Dietary Sugars; Disease Models, Animal; Flour; Food, Fortified; Fructose; Hep G2 Cells; Humans; Lipids; Male; Metabolic Diseases; Obesity; Phenylpropionates; Phytosterols; Rats, Sprague-Dawley; Signal Transduction; Triticum
PubMed: 31340583
DOI: 10.3390/nu11071697 -
Scientific Reports May 2024Phytosterols are natural components of plant-based foods used as supplements because of their known cholesterol-lowering effect. However, their effects on lipoprotein... (Randomized Controlled Trial)
Randomized Controlled Trial
Phytosterols are natural components of plant-based foods used as supplements because of their known cholesterol-lowering effect. However, their effects on lipoprotein subfractions and the quality of the LDL particle have not been studied in greater detail. We aimed to evaluate the effects of phytosterols supplements on lipids, lipoproteins subfractions, and on the quality of LDL. A prospective, pilot-type, open label, cross-over study, randomized 23 males in primary prevention of hypercholesterolemia to receive diet or diet plus phytosterol (2.6 g in 2 doses, with meals) for 12 weeks, when treatments were switched for another 12 weeks. Lipoprotein subfractions were analyzed by electrophoresis in polyacrylamide gel (Lipoprint System®). The Sampson equation estimated the small and dense (sd) and large and buoyant (lb) LDL subfractions from the lipid profile. Quality of LDL particle was analyzed by Z-scan and UV-vis spectroscopy. Primary outcome was the comparison of diet vs. diet plus phytosterols. Secondary outcomes assessed differences between baseline, diet and diet plus phytosterol. Non-parametric statistics were performed with p < 0.05. There was a trend to reduction on HDL-7 (p = 0.05) in diet plus phytosterol arm, with no effects on the quality of LDL particles. Heatmap showed strong correlations (ρ > 0.7) between particle size by different methods with both interventions. Diet plus phytosterol reduced TC, increased HDL-c, and reduced IDL-B, whereas diet increased HDL7, and reduced IDL-B vs. baseline (p < 0.05, for all). Phytosterol supplementation demonstrated small beneficial effects on HDL-7 subfraction, compared with diet alone, without effects on the quality of LDL particles.This trial is registered in Clinical Trials (NCT06127732) and can be accessed at https://clinicaltrials.gov .
Topics: Phytosterols; Humans; Male; Dietary Supplements; Middle Aged; Hypercholesterolemia; Cross-Over Studies; Lipoproteins, LDL; Prospective Studies; Adult; Cholesterol, LDL; Pilot Projects; Lipoproteins
PubMed: 38750162
DOI: 10.1038/s41598-024-61897-4 -
ELife Feb 2024Sterol lipids are widely present in eukaryotes and play essential roles in signaling and modulating membrane fluidity. Although rare, some bacteria also produce sterols,...
Sterol lipids are widely present in eukaryotes and play essential roles in signaling and modulating membrane fluidity. Although rare, some bacteria also produce sterols, but their function in bacteria is not known. Moreover, many more species, including pathogens and commensal microbes, acquire or modify sterols from eukaryotic hosts through poorly understood molecular mechanisms. The aerobic methanotroph was the first bacterium shown to synthesize sterols, producing a mixture of C-4 methylated sterols that are distinct from those observed in eukaryotes. C-4 methylated sterols are synthesized in the cytosol and localized to the outer membrane, suggesting that a bacterial sterol transport machinery exists. Until now, the identity of such machinery remained a mystery. In this study, we identified three novel proteins that may be the first examples of transporters for bacterial sterol lipids. The proteins, which all belong to well-studied families of bacterial metabolite transporters, are predicted to reside in the inner membrane, periplasm, and outer membrane of and may work as a conduit to move modified sterols to the outer membrane. Quantitative analysis of ligand binding revealed their remarkable specificity for 4-methylsterols, and crystallographic structures coupled with docking and molecular dynamics simulations revealed the structural bases for substrate binding by two of the putative transporters. Their striking structural divergence from eukaryotic sterol transporters signals that they form a distinct sterol transport system within the bacterial domain. Finally, bioinformatics revealed the widespread presence of similar transporters in bacterial genomes, including in some pathogens that use host sterol lipids to construct their cell envelopes. The unique folds of these bacterial sterol binding proteins should now guide the discovery of other proteins that handle this essential metabolite.
Topics: Sterols; Bacteria; Bacterial Proteins; Biological Transport; Phytosterols
PubMed: 38329015
DOI: 10.7554/eLife.90696 -
Current Opinion in Endocrinology,... Apr 2009This review summarizes recent developments in the activity, regulation, and physiology of the ABCG5 ABCG8 (G5G8) transporter and the use of its xenobiotic substrates,... (Review)
Review
PURPOSE OF REVIEW
This review summarizes recent developments in the activity, regulation, and physiology of the ABCG5 ABCG8 (G5G8) transporter and the use of its xenobiotic substrates, phytosterols, as cholesterol lowering agents in the treatment of cardiovascular disease. Recent progress has significant implications for the role of G5G8 and its substrates in complications associated with features of the metabolic syndrome.
RECENT FINDINGS
Recent reports expand the clinical presentation of sitosterolemia to include platelet and adrenal dysfunction. The G5G8 sterol transporter is critical to hepatobiliary excretion of cholesterol under nonpathological conditions and has been linked to the cholesterol gallstone susceptibility. Finally, the cardiovascular benefits of cholesterol lowering through the use of phytosterol supplements were offset by vascular dysfunction, suggesting that alternative strategies to reduced cholesterol absorption offer greater benefit.
SUMMARY
Insulin resistance elevates G5G8 and increases susceptibility to cholesterol gallstones. However, this transporter is critical for the exclusion of phytosterols from the absorptive pathways in the intestine. Challenging the limits of this protective mechanism through phytosterol supplementation diminishes the cardioprotective benefits of cholesterol lowering in mouse models of cardiovascular disease.
Topics: ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; ATP-Binding Cassette Transporters; Animals; Heart Diseases; Humans; Lipoproteins; Metabolic Diseases; Phytosterols; Sterols
PubMed: 19306529
DOI: 10.1097/med.0b013e3283292312