-
Phytochemistry Jul 2019Diatoms are abundant unicellular marine photosynthetic algae that have genetically diversified their physiology and metabolism while adapting to numerous environments.... (Review)
Review
Diatoms are abundant unicellular marine photosynthetic algae that have genetically diversified their physiology and metabolism while adapting to numerous environments. The metabolic repertoire of diatoms presents opportunities to characterise the biosynthesis and production of new and potentially valuable microalgal compounds, including sterols. Sterols of plant origin, known as phytosterols, have been studied for health benefits including demonstrated cholesterol-lowering properties. In this review we summarise sterol diversity, the unique metabolic features of sterol biosynthesis in diatoms, and prospects for the extraction of diatom phytosterols in comparison to existing sources. We also review biotechnological efforts to manipulate diatom biosynthesis, including culture conditions and avenues for the rational engineering of metabolism and cellular regulation.
Topics: Diatoms; Molecular Structure; Phytosterols
PubMed: 31005802
DOI: 10.1016/j.phytochem.2019.03.018 -
Journal of Experimental Botany Feb 2021Plants stand out among eukaryotes due to the large variety of sterols and sterol derivatives that they can produce. These metabolites not only serve as critical... (Review)
Review
Plants stand out among eukaryotes due to the large variety of sterols and sterol derivatives that they can produce. These metabolites not only serve as critical determinants of membrane structures, but also act as signaling molecules, as growth-regulating hormones, or as modulators of enzyme activities. Therefore, it is critical to understand the wiring of the biosynthetic pathways by which plants generate these distinct sterols, to allow their manipulation and to dissect their precise physiological roles. Here, we review the complexity and variation of the biosynthetic routes of the most abundant phytosterols and cholesterol in the green lineage and how different enzymes in these pathways are conserved and diverged from humans, yeast, and even bacteria. Many enzymatic steps show a deep evolutionary conservation, while others are executed by completely different enzymes. This has important implications for the use and specificity of available human and yeast sterol biosynthesis inhibitors in plants, and argues for the development of plant-tailored inhibitors of sterol biosynthesis.
Topics: Biosynthetic Pathways; Cholesterol; Phytosterols; Plants; Sterols
PubMed: 32929492
DOI: 10.1093/jxb/eraa429 -
Phytotherapy Research : PTR Oct 2022α-Spinasterol is a phytosterol found in various edible and non-edible plant sources. The edible plant materials containing α-spinasterol include spinach leaves,... (Review)
Review
α-Spinasterol is a phytosterol found in various edible and non-edible plant sources. The edible plant materials containing α-spinasterol include spinach leaves, cucumber fruits, seeds of pumpkin and watermelon, argan seed oil, cactus pear seed oil and Amaranthus sp. It is a bioavailable nutraceutical, and it can cross the blood-brain barrier. It possesses several important pharmacological properties such as anti-diabetes mellitus, antiinflammation, hypolipidemic, antiulcer, neuroprotection, anti-pain and antitumour activities. For this review, literature search was made focusing on the pharmacological properties of α-spinasterol using PubMed and Google Scholar data bases. Recent studies show the promising antidiabetic properties of α-spinasterol. Its anti-diabetic mechanisms include enhancement of insulin secretion, reduction in insulin resistance, anti-diabetic nephropathy, increase in glucose uptake in muscle cells and inhibition of glucose absorption from intestine. Besides, it is a safe antiinflammatory agent, and its antiinflammatory mechanisms include inhibition of cyclooxygenases, antagonism of TRPV1 receptor and attenuation of proinflammatory cytokines and mediators. It is a promising and safe nutraceutical molecule for human health care. Food supplements, value-added products and nutraceutical formulations can be developed with α-spinasterol for the management of diabetes, chronic inflammatory diseases and improving general health. This review provides all scattered pharmacological studies on α-spinasterol in one place and highlights its immense value for human health care.
Topics: Anti-Inflammatory Agents; Cytokines; Dietary Supplements; Glucose; Humans; Hypoglycemic Agents; Phytosterols; Plant Oils; Prostaglandin-Endoperoxide Synthases; Stigmasterol
PubMed: 35802356
DOI: 10.1002/ptr.7560 -
The British Journal of Nutrition Mar 2024Phytosterols/phytostanols are bioactive compounds found in vegetable oils, nuts and seeds and added to a range of commercial food products. Consumption of... (Review)
Review
Phytosterols/phytostanols are bioactive compounds found in vegetable oils, nuts and seeds and added to a range of commercial food products. Consumption of phytosterols/phytostanols reduces levels of circulating LDL-cholesterol, a causative biomarker of CVD, and is linked to a reduced risk of some cancers. Individuals who consume phytosterols/phytostanols in their diet may do so for many years as part of a non-pharmacological route to lower cholesterol or as part of a healthy diet. However, the impact of long term or high intakes of dietary phytosterols/phytostanols has not been on whole-body epigenetic changes before. The aim of this systematic review was to identify all publications that have evaluated changes to epigenetic mechanisms (post-translation modification of histones, DNA methylation and miRNA expression) in response to phytosterols/phytostanols. A systematic search was performed that returned 226 records, of which eleven were eligible for full-text analysis. Multiple phytosterols were found to inhibit expression of histone deacetylase (HDAC) enzymes and were also predicted to directly bind and impair HDAC activity. Phytosterols were found to inhibit the expression and activity of DNA methyl transferase enzyme 1 and reverse cancer-associated gene silencing. Finally, phytosterols have been shown to regulate over 200 miRNA, although only five of these were reported in multiple publications. Five tissue types (breast, prostate, macrophage, aortic epithelia and lung) were represented across the studies, and although phytosterols/phytostanols alter the molecular mechanisms of epigenetic inheritance in these mammalian cells, studies exploring meiotic or transgenerational inheritance were not found.
Topics: Male; Animals; Humans; Phytosterols; Noncommunicable Diseases; Cholesterol; Epigenesis, Genetic; Neoplasms; MicroRNAs; Mammals
PubMed: 37955052
DOI: 10.1017/S0007114523002532 -
Journal of Food Science Feb 2022Coffee silverskin is a byproduct of the coffee roasting process contributing to organic waste burdens in urban areas. Silverskin is a potential source of dietary fiber,...
Coffee silverskin is a byproduct of the coffee roasting process contributing to organic waste burdens in urban areas. Silverskin is a potential source of dietary fiber, protein, carbohydrates, caffeine as well as vitamins and minerals. However, phytosterols present in the plant are susceptible to thermal oxidation resulting in the formation of phytosterol oxidation products (POPs) in the silverskin during roasting. In collaboration with a small roastery, the formation of POPs in three coffee varieties with roasting time was monitored by GC-MS. The objective was to evaluate the safety and potential benefits of incorporating coffee silverskin into value-added products. The qualitative profile of POPs in the silverskin from the three varieties was similar. Average total POPs were 0.32 g POPs/kg silverskin. POPs from the dominant plant sterol, sitosterol, were present at the highest concentrations. Caffeine, total antioxidant capacity, and total flavonoids were measured in the silverskin of the three coffees. Average values were 1.3 g caffeine/100 g silverskin, TEAC of 11 mmol Trolox/kg silverskin, and 1.94 to 8.60 mg catechin equivalent (CE)/g silverskin, respectively. An analysis of the impact of consuming teas and baked goods containing silverskin was also performed. Using published formulations, a tea or cookie containing silverskin would contribute approximately 1 and 0.3 mg POP per day, respectively. Consumption of these products would not substantially increase dietary exposure to POPs, while increasing fiber and antioxidants while reducing organic waste. PRACTICAL APPLICATION: Coffee silverskin has been studied as a possible source of fiber, antioxidants, and caffeine when incorporated in snack foods and used to make teas. To assess possible concerns about increasing dietary oxidized phytosterols, the formation of phytosterol oxidation products (POPs) was investigated in the silverskin fraction during the roasting process in three coffee varieties. In addition, caffeine, antioxidant capacity, and total flavonoids were determined. We found that silverskin can be safely used for value-added products including caffeinated teas, cookies, and bars with minimal impact on dietary POP exposures.
Topics: Antioxidants; Coffea; Coffee; Oxidation-Reduction; Phytosterols; Plant Extracts
PubMed: 35067916
DOI: 10.1111/1750-3841.16042 -
Diabetes & Metabolic Syndrome 2020Several commercially available phytosterol supplements are promoted for their cholesterol-lowering effects. However, limited information is available about their...
BACKGROUND AND AIMS
Several commercially available phytosterol supplements are promoted for their cholesterol-lowering effects. However, limited information is available about their potential anti-hyperglycaemic effects. This study aimed to evaluate the dipeptidyl peptidase-4 (DPP-4) inhibitory effects of phytosterol supplements in silico and in vitro to determine their potential for anti-diabetic activity.
METHODS
Docking studies were carried out in silico to evaluate the potential for interactions between three major phytosterol compounds (stigmasterol, β-sitosterol, campesterol) and the DPP-4 enzyme, the enzyme that is inhibited by the anti-diabetic gliptins. Gas chromatography-tandem mass spectrometry (GC-MS/MS) was used to analyse three different supplements for phytosterol content. DPP-4 inhibitory activity was tested in vitro for these phytosterol supplements and two major phytosterol standards.
RESULTS
In silico calculations predicted free binding energies for DPP-4 with the phytosterols to be: stigmasterol -8.78 kcal/mol; β-sitosterol -8.70 kcal/mol; campesterol -8.40 kcal/mol. These binding energies indicated a potential for significant DPP-4 inhibition. However, these results were not supported by the in vitro studies. Stigmasterol and β-sitosterol had an IC > 50 mg/ml (maximum tested concentration) and the Thompson's Cholesterol Manager® and Mega Strength Beta Sitosterol® supplements gave an IC > 100 mg/ml (maximum tested concentration). Blackmores Cholesterol Health® gave an IC value of 40 mg/ml which was attributed to β-carotene content.
CONCLUSIONS
Phytosterol supplements do not appear to offer any anti-diabetic activity potential via pathways that involve the inhibition of DPP-4.
Topics: Dietary Supplements; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Humans; In Vitro Techniques; Molecular Docking Simulation; Phytosterols
PubMed: 32771921
DOI: 10.1016/j.dsx.2020.07.019 -
Molecular Nutrition & Food Research Jul 2015Hypercholesterolemia is an important risk factor for the development of cardiovascular diseases. Dietary intake of phytosterols/phytostanols and their fatty acid esters... (Review)
Review
Hypercholesterolemia is an important risk factor for the development of cardiovascular diseases. Dietary intake of phytosterols/phytostanols and their fatty acid esters results in a reduction of the LDL and total plasma cholesterol levels. Therefore, these constituents are added to a broad spectrum of foods. As in the case of cholesterol, thermo-oxidative treatment of phytosterols may result in the formation of phytosterol oxidation products (POPs), i.e. keto-, hydroxy-, and epoxy-derivatives. This review summarizes and evaluates the current knowledge regarding POPs in the light of the potentially increasing dietary exposure to these constituents via the consumption of foods enriched with phytosterols/phytostanols and their esters. Data on the occurrence of POPs and approaches to assess the potential intake of POPs resulting from the consumption of enriched foods are described. The knowledge on the uptake of POPs and the presently available data on the impact of the consumption of enriched foods on the levels of POPs in humans are discussed. Biological effects of POPs, such as potential proatherogenic properties or the loss of the cholesterol-lowering effects compared to nonoxidized phytosterols, are discussed. Finally, knowledge gaps are outlined and recommendations for further research needed for a safety assessment of POPs are presented.
Topics: Animals; Cholesterol; Diet; Food; Food Analysis; Food, Fortified; Humans; Mutagenicity Tests; Oxidation-Reduction; Phytosterols; Toxicity Tests, Subchronic
PubMed: 25787244
DOI: 10.1002/mnfr.201400922 -
Phytotherapy Research : PTR Feb 2024Despite multiple investigations assessing the impact of phytosterol supplementation on serum lipid levels, there is still a great deal of debate regarding the benefits... (Meta-Analysis)
Meta-Analysis Review
Despite multiple investigations assessing the impact of phytosterol supplementation on serum lipid levels, there is still a great deal of debate regarding the benefits of this intervention in the management of dyslipidemia. Therefore, we aimed at clarifying this dilemma by conducting the present umbrella review of interventional meta-analyses. Scopus, PubMed, Web of Science, and EMBASE were used to search for pertinent publications on the effect of phytosterol supplementation on the lipid profile in humans up to June 2023. To compute the overall effect size (ES) and confidence intervals (CI), the random-effects model was used. The I statistic and Cochrane's Q-test were applied to estimate the heterogeneity among the studies. Seventeen meta-analyses with 23 study arms were included in the umbrella meta-analysis. Data pooled from the 23 eligible arms revealed that phytosterol supplementation reduces low-density lipoprotein cholesterol (LDL-C) (ES = -11.47 mg/dL; 95% CI: -12.76, -10.17, p < 0.001), total cholesterol (TC) (ES = -13.02 mg/dL; 95% CI: -15.68, -10.37, p < 0.001), and triglyceride (TG) (ES = -3.77 mg/dL; 95% CI: -6.04, -1.51, p = 0.001). Subgroup analyses showed that phytosterol administration with dosage ≥2 g/day and duration over 8 weeks and in hypercholesterolemic subjects was more likely to decrease LDL-C, TC, and TG. Phytosterol administration did not significantly modify HDL-C (ES = 0.18 mg/dL; 95% CI: -0.13, -0.51, p = 258) levels when compared to controls. The present umbrella meta-analysis confirms that phytosterol administration significantly reduces LDL-C, TC, and TG, with a greater effect with doses of ≥2 g/day and treatment duration >8 weeks, suggesting its possible application as a complementary therapy for cardiovascular risk reduction. Further studies are needed to determine the efficacy of phytosterols in patients with specific health conditions, as well as to ascertain the adverse effects, the maximum tolerable dose, and the maximum recommended duration of phytosterol administration.
Topics: Humans; Phytosterols; Cholesterol, LDL; Cholesterol, HDL; Triglycerides; Dietary Supplements
PubMed: 37905579
DOI: 10.1002/ptr.8052 -
Current Medicinal Chemistry 2019Phytosterol measurement has gained a lot of interest during the last two decades after foods and supplements with added 4-desmethyl phytosterols were recognized and used... (Review)
Review
Phytosterol measurement has gained a lot of interest during the last two decades after foods and supplements with added 4-desmethyl phytosterols were recognized and used as effective and safe non-pharmacologic hypocholesterolemic agents, and also after the mechanisms of intestinal absorption and hepatic excretion of sterols were unraveled. In addition, the wide use of serum phytosterols as biomarkers of cholesterol absorption has increased the interest in their measurement. In this review, the basic methods are discussed without going into details of the practical operations. The analysis includes first lipid extraction and saponification from various biologic matrices such as serum/plasma, feces, or tissues, after which the individual sterols are separated by adsorption chromatography (gas-liquid or liquid or high performance liquid chromatography) based on the polarity of the various sterols. We also deal with some specific aspects of phytosterol measurements in biological samples such as the need of harmonization of their analysis in biological samples, the discrepancies in the results of sitosterol and campesterol concentrations between different studies, and what is known about their biological day-to-day fluctuation. Phytosterols have a remarkable role in human health, so that their complicated and time consuming measurements call attention to routine ways of standardization between the sterol research laboratories.
Topics: Body Fluids; Humans; Phytosterols
PubMed: 30009697
DOI: 10.2174/0929867325666180713160330 -
Biochemical and Biophysical Research... Apr 2014Phytosterols and their oxidation products have become increasingly investigated in recent years with respect to their roles in diet and nutrition. We present a... (Review)
Review
Phytosterols and their oxidation products have become increasingly investigated in recent years with respect to their roles in diet and nutrition. We present a comprehensive review of recent literature on Phytosterol Oxidation Products (POP) identifying critical areas for future investigation. It is evident that POP are formed on food storage/preparation; are absorbed and found in human serum; do not directly affect cholesterol absorption; have evidence of atherogenicity and inflammation; have distinct levels of cytotoxicity; are implicated with high levels of oxidative stress, glutathione depletion, mitochondrial dysfunction and elevated caspase activity.
Topics: Atherosclerosis; Caspases; Cholesterol; Food; Glutathione; Humans; Inflammation; Mitochondria; Oxidation-Reduction; Oxidative Stress; Phytosterols
PubMed: 24491535
DOI: 10.1016/j.bbrc.2014.01.148