-
Molecules (Basel, Switzerland) Dec 2020This study investigated how the physicochemical characteristics of phytosterol esters are influenced by the chain length and degree of unsaturation of the fatty acid...
This study investigated how the physicochemical characteristics of phytosterol esters are influenced by the chain length and degree of unsaturation of the fatty acid ester moiety. Saturated and unsaturated phytosterol esters (PEs) were synthesized by the esterification of different types of fatty acids (stearic, palmitic, lauric, oleic, and linoleic acid) to β-sitosterol. The non-isothermal crystallization and melting behavior of the pure PEs were analyzed. It was proven by X-ray diffraction that saturated β-sitosteryl esters and β-sitosteryl oleate formed a bilayer crystal structure. The lamellar spacings of the bilayer structure decreased with decreasing fatty acid chain length and with an increasing degree in unsaturation. The degree of unsaturation of the fatty acid chain of the β-sitosteryl esters also influenced the type of subcell packing of the fatty acid moieties in the bilayer structure, whether or not a metastable or stable liquid crystalline phase was formed during cooling. Furthermore, it was found that the melting temperature and enthalpy of the β-sitosteryl esters increased with an increasing fatty acid chain length while they decreased with an increasing degree of unsaturation. The microscopic analyses demonstrated that β-sitosteryl oleate formed much smaller spherulites than their saturated β-sitosteryl analogues.
Topics: Crystallization; Esters; Fatty Acids; Phytosterols; Sitosterols; Temperature; X-Ray Diffraction
PubMed: 33291641
DOI: 10.3390/molecules25235727 -
Critical Reviews in Food Science and... 2022Phytosterols and phytostanols are natural products present in vegetable oils, nuts, and seeds, or added to consumer food products whose intake is inversely associated... (Meta-Analysis)
Meta-Analysis
Phytosterols and phytostanols are natural products present in vegetable oils, nuts, and seeds, or added to consumer food products whose intake is inversely associated with incidence and prognosis of several cancers. Randomized cancer prevention trials in humans are unfeasible due to time and cost yet the cellular processes and signaling cascades that underpin anti-cancer effects of these phytochemicals have been explored extensively in vitro and in preclinical in vivo models. Here we have performed an original systematic review, meta-analysis, and qualitative interpretation of literature published up to June 2020. MEDLINE, Scopus, and hand-searching identified 408 unique records that were screened leading to 32 original articles that had investigated the effects of phytosterols or phytostanols on cancer biology in preclinical models. Data was extracted from 22 publications for meta-analysis. Phytosterols were most commonly studied and found to reduce primary and metastatic tumor burden in all cancer sites evaluated. Expression of pAKT, and markers of metastasis (alkaline phosphatase, matrix metalloproteases, epithelial to mesenchymal transcription factors, lung and brain colonization), angiogenesis (vascular endothelial growth factor, CD31), and proliferation (Ki67, proliferating cell nuclear antigen) were consistently reduced by phytosterol treatment in breast and colorectal cancer. Very high dose treatment (equivalent to 0.2-1 g/kg body weight not easily achievable through diet or supplementation in humans) was associated with adverse events including poor gut health and intestinal adenoma development. Phytosterols and phytostanols are already clinically recommended for cardiovascular disease risk reduction, and represent promising anti-cancer agents that could be delivered in clinic and to the general population at low cost, with a well understood safety profile, and now with a robust understanding of mechanism-of-action.
Topics: Animals; Drug Evaluation, Preclinical; Neoplasms; Phytosterols
PubMed: 33238719
DOI: 10.1080/10408398.2020.1835820 -
Molecules (Basel, Switzerland) Jan 2022Phytosterols are natural sterols widely found in plants that have a variety of physiological functions, and their role in reducing cholesterol absorption has garnered... (Review)
Review
Phytosterols are natural sterols widely found in plants that have a variety of physiological functions, and their role in reducing cholesterol absorption has garnered much attention. Although the bioavailability of phytosterols is only 0.5-2%, they can still promote cholesterol balance in the body. A mechanism of phytosterols for lowering cholesterol has now been proposed. They not only reduce the uptake of cholesterol in the intestinal lumen and affect its transport, but also regulate the metabolism of cholesterol in the liver. In addition, phytosterols can significantly reduce the plasma concentration of total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C), with a dose-response relationship. Ingestion of 3 g of phytosterols per day can reach the platform period, and this dose can reduce LDL-C by about 10.7%. On the other hand, phytosterols can also activate the liver X receptor α-CPY7A1 mediated bile acids excretion pathway and accelerate the transformation and metabolism of cholesterol. This article reviews the research progress of phytosterols as a molecular regulator of cholesterol and the mechanism of action for this pharmacological effect.
Topics: Anticholesteremic Agents; Bile Acids and Salts; Cholesterol; Cholesterol, LDL; Humans; Intestinal Absorption; Phytosterols
PubMed: 35056839
DOI: 10.3390/molecules27020523 -
Nutrients May 2022Nonalcoholic fatty liver disease is now recognized as the most common cause of chronic liver disease with an increasing prevalence in both adults and children. Although... (Review)
Review
Nonalcoholic fatty liver disease is now recognized as the most common cause of chronic liver disease with an increasing prevalence in both adults and children. Although the symptoms are absent or poorly expressed in most cases, some patients may progress to end-stage liver disease. The pathogenesis of NAFLD is known to be multifactorial. Current therapeutic recommendations focus on lifestyle changes in order to reduce the incidence of risk factors and drugs targeting major molecular pathways potentially involved in the development of this disease. Given that a pharmacological treatment, completely safe and effective, is not currently known in recent years more research has been done on the effects that some bio-active natural compounds, derived from plants, have in preventing the onset and progression of NAFLD. Numerous studies, in animals and humans, have shown that phytosterols (PSs) play an important role in this pathology. Phytosterols are natural products that are found naturally in plant. More than 250 phytosterols have been identified, but the most common in the diet are stigmasterol, β-sitosterol, and campesterol. Consumption of dietary PSs can reduce serum cholesterol levels. Due to these properties, most studies have focused on their action on lipid metabolism and the evolution of NAFLD. PSs may reduce steatosis, cytotoxicity oxidative stress, inflammation, and apoptosis. The purpose of this review is to provide an overview of the importance of dietary phytosterols, which are a window of opportunity in the therapeutic management of NAFLD.
Topics: Animals; Diet; Humans; Lipid Metabolism; Non-alcoholic Fatty Liver Disease; Phytosterols; Stigmasterol
PubMed: 35683987
DOI: 10.3390/nu14112187 -
Atherosclerosis Jan 2022Dietary approaches to lowering cholesterol appear to be common knowledge. However, the marketing of phytosterol-enriched products and their recommendation by guidelines...
BACKGROUND AND AIMS
Dietary approaches to lowering cholesterol appear to be common knowledge. However, the marketing of phytosterol-enriched products and their recommendation by guidelines for individuals at increased risk of cardiovascular disease have given rise to concern, since phytosterols may be atherogenic and inappropriately used by healthy individuals of higher social status at low cardiovascular risk. Hence, we have investigated awareness of cholesterol lowering lifestyle measures and attitudes towards consumption of phytosterol-enriched foods.
METHODS
Data from validated questionnaires supplemented by queries on cholesterol lowering and phytosterol-enriched products were analyzed using data of 7223 participants of the Hamburg City Health Study, an ongoing cohort study of the general population aged 45-74 years.
RESULTS
95.9% of the participants agreed that lifestyle may lower cholesterol and 76.6% claimed knowledge of measures that lower plasma cholesterol. As to effective approaches, 80.2% suggested physical activity, 67.8% reducing dietary fat, followed by sugar-sweetened beverages or stress, increasing water consumption, or dietary fiber and only 16.2% stated statins and 9.3% phytosterol-enriched products. Compared to nonusers, the 2.0% female and 2.8% male individuals regularly using phytosterol-enriched products had a lower educational status, higher cardiovascular risk, but no difference in income and were characterized by adverse dietary habits. The study has been registered in ClinicalTrial.gov (NCT03934957).
CONCLUSIONS
In the general population awareness of hypercholesterolemia is high but knowledge on how to lower plasma cholesterol does not necessarily follow scientific evidence. There is a trend towards the use of phytosterol-enriched products by individuals at increased cardiovascular risk independent of income.
Topics: Cholesterol; Cohort Studies; Female; Food, Fortified; Humans; Male; Phytosterols; Social Status
PubMed: 34922192
DOI: 10.1016/j.atherosclerosis.2021.12.004 -
Applied and Environmental Microbiology Jul 2020Androst-4-ene-3,17-dione (AD) and androst-1,4-diene-3,17-dione (ADD) are valuable steroid pharmaceutical intermediates obtained by soybean phytosterol biotransformation...
Androst-4-ene-3,17-dione (AD) and androst-1,4-diene-3,17-dione (ADD) are valuable steroid pharmaceutical intermediates obtained by soybean phytosterol biotransformation by Cyclodextrins (CDs) are generally believed to be carriers for phytosterol delivery and can improve the production of AD and ADD due to their effects on steroid solubilization and alteration in cell wall permeability for steroids. To better understand the mechanisms of CD promotion, we performed proteomic quantification of the effects of hydroxypropyl-β-CD (HP-β-CD) on phytosterol metabolism in TCCC 11978 C2. Perturbations are observed in steroid catabolism and glucose metabolism by adding HP-β-CD in a phytosterol bioconversion system. AD and ADD, as metabolic products of phytosterol, are toxic to cells, with inhibited cell growth and biocatalytic activity. Treatment of mycobacteria with HP-β-CD relieves the inhibitory effect of AD(D) on the electron transfer chain and cell growth. These results demonstrate the positive relationship between HP-β-CD and phytosterol metabolism and give insight into the complex functions of CDs as mediators of the regulation of sterol metabolism. Phytosterols from soybean are low-cost by-products of soybean oil production and, owing to their good bioavailability in mycobacteria, are preferred as the substrates for steroid drug production via biotransformation by However, the low level of production of steroid hormone drugs due to the low aqueous solubility (below 0.1 mmol/liter) of phytosterols limits the commercial use of sterol-transformed strains. To improve the bioconversion of steroids, cyclodextrins (CDs) are generally used as an effective carrier for the delivery of hydrophobic steroids to the bacterium. CDs improve the biotransformation of steroids due to their effects on steroid solubilization and alterations in cell wall permeability for steroids. However, studies have rarely reported the effects of CDs on cell metabolic pathways related to sterols. In this study, the effects of hydroxypropyl-β-CD (HP-β-CD) on the expression of enzymes related to steroid catabolic pathways in were systematically investigated. These findings will improve our understanding of the complex functions of CDs in the regulation of sterol metabolism and guide the application of CDs to sterol production.
Topics: 2-Hydroxypropyl-beta-cyclodextrin; Bacterial Proteins; Excipients; Mycobacteriaceae; Phytosterols; Proteomics
PubMed: 32414803
DOI: 10.1128/AEM.00441-20 -
The Journal of Steroid Biochemistry and... May 2017Dietary sterols are nutritionally interesting compounds which can suffer oxidation reactions. In the case of plant sterols, they are being widely used for food... (Review)
Review
Dietary sterols are nutritionally interesting compounds which can suffer oxidation reactions. In the case of plant sterols, they are being widely used for food enrichment due to their hypocholesterolemic properties. Besides, cholesterol and plant sterols oxidation products are associated with the development of cardiovascular and neurodegenerative diseases, among others. Therefore, the evaluation of the particular factors affecting sterol degradation and oxysterols formation in foods is of major importance. The present work summarizes the main results obtained in experiments which aimed to study four aspects in this context: the effect of the heating treatment, the unsaturation degree of the surrounding lipids, the presence of antioxidants on sterols degradation, and at last, oxides formation. The use of model systems allowed the isolation of some of these effects resulting in more accurate data. Thus, these results could be applied in real conditions.
Topics: Animals; Antioxidants; Cholesterol; Hot Temperature; Humans; Kinetics; Models, Theoretical; Oxygen; Oxysterols; Phytosterols; Sitosterols; Stigmasterol
PubMed: 26921766
DOI: 10.1016/j.jsbmb.2016.02.027 -
Journal of Natural Products Oct 2018Fifteen new multifunctional conjugates were designed and synthesized by chemically linking the steroidal framework of natural occurring γ-oryzanol and...
Fifteen new multifunctional conjugates were designed and synthesized by chemically linking the steroidal framework of natural occurring γ-oryzanol and γ-oryzanol-derived phytosterols to a wide range of bioactive natural compounds (fatty acids, phenolic acids, amino acids, lipoic acid, retinoic acid, curcumin, and resveratrol). Starting from γ-oryzanol, which is the main component of rice bran oil, this study was aimed at assessing if the conjugation strategy might enhance some γ-oryzanol bioactivities. The antioxidant activity was evaluated through three different mechanisms, namely, DPPH-scavenging activity, metal-chelating activity, and β-carotene-bleaching inhibition. Measurement of the in vitro cell growth inhibitory effects on three different human cancer cellular lines was also carried out, and the potential hypocholesterolemic effect was studied. Compounds 10 and 15 displayed an improved antioxidant activity, with respect to that of γ-oryzanol. Compounds 2, 6, and 12 exerted an antiproliferative activity in the low micromolar range against HeLa and DAOY cells (GI < 10 μM). As for the claimed hypocholesterolemic effect of γ-oryzanol, none of the synthesized compounds inhibited the 3-hydroxy-3-methylglutaryl-coenzyme A reductase, a key enzyme in cholesterol biosynthesis.
Topics: Anticholesteremic Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Cell Line, Tumor; Cell Proliferation; Chelating Agents; Free Radical Scavengers; Humans; Molecular Structure; Oryza; Phenylpropionates; Phytosterols; Plant Oils; beta Carotene
PubMed: 30360625
DOI: 10.1021/acs.jnatprod.8b00465 -
International Journal of Molecular... Jun 2023Phytosterols are natural active substances widely found in plants and play an important role in hypolipidemia, antioxidants, antitumor, immunomodulation, plant growth,...
Phytosterols are natural active substances widely found in plants and play an important role in hypolipidemia, antioxidants, antitumor, immunomodulation, plant growth, and development. In this study, phytosterols were extracted and identified from the seed embryos of 244 maize inbred lines. Based on this, a genome-wide association study (GWAS) was used to predict the possible candidate genes responsible for phytosterol content; 9 SNPs and 32 candidate genes were detected, and was identified to be associated with phytosterol accumulation. We initially confirmed its functions in transgenic and found that mutation of resulted in slow plant growth and a significant reduction in sterol content, while overexpression of accelerated plant growth and significantly increased sterol content. These results were further confirmed in transgenic tobacco and suggest that was closely related to plant growth; overexpression of not only facilitated plant growth and development but also promoted the accumulation of phytosterols.
Topics: Phytosterols; Genome-Wide Association Study; Sterols; Seeds; Arabidopsis
PubMed: 37373558
DOI: 10.3390/ijms241210411 -
Molecules (Basel, Switzerland) Apr 2019The preservation of active constituents in fresh herbs is affected by drying methods. An effective drying method for which is increasingly marketed as an important...
The preservation of active constituents in fresh herbs is affected by drying methods. An effective drying method for which is increasingly marketed as an important herbal tea remains to be reported. This study evaluated the effects of conventional and new drying technologies, namely vacuum microwave drying methods, on the antioxidant activity and yield of essential oil volatiles and phytosterols. These drying methods included convective drying (CD) at 40 °C, 50 °C, and 60 °C; vacuum microwave drying (VMD) at 6, 9, and 12 W/g; convective pre-drying and vacuum microwave finish drying (CPD-VMFD) at 50 °C and 9 W/g; and freeze-drying (FD). GC–MS revealed 33 volatiles, and 2-hexen-1-ol, 2-hexenal, 1-octen-3-ol, linalool, and benzaldehyde were major constituents. The compounds β-sitosterol and α-linolenic acid were the most abundant phytosterol and fatty acid, respectively, in fresh . The highest phenolic content was achieved with CD at 60 °C. The highest antioxidant activity was obtained with CD at 40 °C and VMD at 9 W/g. On the contrary, the highest total volatiles and phytosterols were detected with CD at 50 °C and VMD at 9 W/g, respectively. This study showed that CD and VMD were effective in producing highly bioactive . A suitable drying parameter level, irrespective of the drying method used, was an important influencing factor.
Topics: Acanthaceae; Antioxidants; Freeze Drying; Microwaves; Phytosterols; Vacuum
PubMed: 30970652
DOI: 10.3390/molecules24071397