stigmasterol and fucosterol

Fucosterol (24-ethylidene cholesterol) is a bioactive compound belonging to the sterol group that can be isolated from marine algae. Fucosterol of marine algae exhibits various biological activities including anti-osteoarthritic, anticancer, anti-inflammatory, anti-photoaging, immunomodulatory, hepatoprotective, anti-neurological, antioxidant, algicidal, anti-obesity, and antimicrobial. Numerous studies on fucosterol, mainly focusing on the quantification and characterization of the chemical structure, bioactivities, and health benefits of fucosterol, have been published. However, there is no comprehensive review on safety and toxicity levels of fucosterol of marine algae. This review aims to discuss the bioactivities, safety, and toxicity of fucosterol comprehensively, which is important for the application and development of fucosterol as a bioactive compound in nutraceutical and pharmaceutical industries. We used four online databases to search for literature on fucosterol published between 2002 and 2020. We identified, screened, selected, and analyzed the literature using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method and identified 43 studies for review. Despite the potential applications of fucosterol, we identified the need to fill certain related research gaps. Fucosterol exhibited low toxicity in animal cell lines, human cell lines, and animals. However, studies on the safety and toxicity of fucosterol at the clinical stage, which are required before fucosterol is developed for the industry, are lacking.

Topics: Animals; Antioxidants; Aquatic Organisms; Biological Products; Microalgae; Stigmasterol; Structure-Activity Relationship

Marine algae are rich in some unique biologically active secondary metabolites having diverse pharmacological benefits. Of these, sterols comprise a group of functional lipid compounds that have attracted much attention to natural product scientists.. This review was aimed to update information on the health effects of algae-derived phytosterols and their molecular interactions in various aspects of human health and diseases and to address some future perspectives that may open up a new dimension of pharmacological potentials of algal sterols.. A literature-based search was carried out to retrieve published research information on the potential health effects of algal phytosterols with their pharmacological mechanisms from accessible online databases, such as Pubmed, Google Scholar, Web of Science, and Scopus, using the key search terms of 'marine algae sterol' and 'health potentials such as antioxidant or anti-inflammatory or anti-Alzheimer's or anti-obesity or cholesterol homeostasis or hepatoprotective, antiproliferative, etc.'. Phytosterols of marine algae, particularly fucosterol, have been investigated for a plethora of health benefits, including anti-diabetes, anti-obesity, anti-Alzheimer's, antiaging, anticancer, and hepatoprotection, among many others, which are attributed to their antioxidant, anti-inflammatory, immunomodulatory and cholesterol-lowering properties, indicating their potentiality as therapeutic leads. These sterols interact with enzymes and various other proteins that are actively participating in different cellular pathways, including antioxidant defense system, apoptosis and cell survival, metabolism, and homeostasis.. In this review, we briefly overview the chemistry, pharmacokinetics, and distribution of algal sterols, and provide critical insights into their potential health effects and the underlying pharmacological mechanisms, beyond the well-known cholesterol-lowering paradigm.

Topics: Anti-Inflammatory Agents; Antioxidants; Aquatic Organisms; Cholesterol; Humans; Phaeophyceae; Phytosterols; Rhodophyta; Seaweed; Stigmasterol; Tissue Distribution

Macroalgae are increasingly viewed as a source of secondary metabolites with great potential for the development of new drugs. In this development, in vitro studies are only the first step in a long process, while in vivo studies and clinical trials are the most revealing stages of the true potential and limitations that a given metabolite may have as a new drug. This literature review aims to give a critical overview of the secondary metabolites that reveal the most interesting results in these two steps. Phlorotannins show great pharmaceutical potential in in vivo models and, among the several examples, the anti-dyslipidemia activity of dieckol must be highlighted because it was more effective than lovastatin in an in vivo model. The IRLIIVLMPILMA tridecapeptide that exhibits an in vivo level of activity similar to the hypotensive clinical drug captopril should still be stressed, as well as griffithsin which showed such stunning results over a variety of animal models and which will probably move onto clinical trials soon. Regarding clinical trials, studies with pure algal metabolites are scarce, limited to those carried out with kahalalide F and fucoxanthin. The majority of clinical trials currently aim to ascertain the effect of algae consumption, as extracts or fractions, on obesity and diabetes.

Topics: Animals; Anti-Obesity Agents; Antihypertensive Agents; Antioxidants; Benzofurans; Humans; Peptides; Phenols; Seaweed; Stigmasterol; Xanthophylls

Seaweeds belong to a group of marine plants known as algae, which are consumed as sea vegetables in several Asian countries. Recent studies have focused on the biological and pharmacological activities of seaweeds and their highly bioactive secondary metabolites because of their potential in the development of new pharmaceutical agents. Although several varieties of bioactive novel compounds such as phlorotannins, diterpenes and polysaccharides from seaweeds have already been well scrutinized, fucosterol as a phytosterol still needs to reinvent itself. Fucosterol (24-ethylidene cholesterol) is a sterol that can be isolated from algae, seaweed and diatoms. Fucosterol exhibits various biological therapeutics, including anticancer, antidiabetic, antioxidant, hepatoprotective, antihyperlipidemic, antifungal, antihistaminic, anticholinergic, antiadipogenic, antiphotodamaging, anti-osteoporotic, blood cholesterol reducing, blood vessel thrombosis preventive and butyrylcholinesterase inhibitory activities. In this review, we address some potential approaches for arbitrating novel fucosterol biologics in the medical field, focusing on the selection of personalized drug candidates and highlighting the challenges and opportunities regarding medical breakthroughs. We also highlight recent advances made in the design of this novel compound, as the significant health benefits from using these optimized applications apply to the nutraceutical and pharmaceutical fields.

Topics: Aquatic Organisms; Humans; Molecular Structure; Seaweed; Stigmasterol

The number of patients diagnosed with Alzheimer's disease (AD) increases each year, and there are currently few treatment strategies to decrease the symptoms of AD; furthermore, these strategies are not sufficient to reduce memory loss in AD patients. In this work

Topics: Alzheimer Disease; Amyloid beta-Peptides; Humans; Peptide Fragments; Sargassum; Stigmasterol

This paper provides a method for the quantification of sterols in different types of calf feedstuffs based on soy, sunflower, hay, calf feed and a mixture of all of them. The free fraction and the total sterolic fraction, after saponification and acidic hydrolysis of the samples, are extracted by solvent and the sterols are identified/quantified by reversed phase HPLC coupled to tandem mass spectrometry by atmospheric pressure chemical ionization. After the recovery evaluation, the method is validated in terms of linearity (coefficient of determination R

Topics: Animal Feed; Animals; Atmospheric Pressure; Cattle; Cholesterol; Chromatography, High Pressure Liquid; Ergosterol; Glycine max; Helianthus; Phytosterols; Sitosterols; Stigmasterol; Tandem Mass Spectrometry

Alterations of monoamine transmission in mesocorticolimbic regions have been suggested in the pathophysiology of attention deficit/hyperactivity disorder (ADHD). The habenula is an important brain area in regulation of monoamine transmission. In this study, we investigated behavioral and electrophysiological alterations induced by neonatal habenula lesion (NHL) in rats. In NHL rats, age-dependent behavioral alterations relevant to the ADHD symptoms, such as hyperlocomotion, impulsivity, and attention deficit, were observed. Local field potentials (LFPs) in mesocorticolimbic regions of anesthetized rats were examined with in vivo electrophysiological recordings. Abnormally enhanced synchronization of slow (delta) and fast (gamma) LFP oscillations between the amygdala (AMY) and prefrontal cortex (PFC) was found in juvenile, but not in adult, NHL rats. We further examined the effects of an extract and the active compound from the perennial large brown algae Ecklonia stolonifera (ES), which have previously been demonstrated to modulate monoamine transmission, on these NHL-induced alterations. One week of ES extract treatments normalized the NHL-induced behavioral alterations, whereas the active compound fucosterol improved attention deficit and impulsivity, but not hyperlocomotion, in NHL rats. Consistent with the behavioral effects, ES extract treatments also normalized augmented AMY-PFC coupling. These results suggest that altered limbic-cortical information processing may be involved in ADHD-like behavioral alterations induced by NHL, which could be ameliorated by the natural substance, such as ES that affects monoamine transmission.

Topics: Animals; Animals, Newborn; Attention; Attention Deficit Disorder with Hyperactivity; Biogenic Monoamines; Disease Models, Animal; Electrophysiological Phenomena; Habenula; Impulsive Behavior; Phaeophyceae; Phytochemicals; Plant Extracts; Rats; Stigmasterol; Synaptic Transmission

Fucosterol, a sterol isolated from brown algae, has been demonstrated to have anti-cancer properties. However, the effects and underlying molecular mechanism of fucosterol on non-small cell lung cancer remain to be elucidated. In this study, the corresponding targets of fucosterol were obtained from PharmMapper, and NSCLC related targets were gathered from the GeneCards database, and the candidate targets of fucosterol-treated NSCLC were predicted. The mechanism of fucosterol against NSCLC was identified in DAVID6.8 by enrichment analysis of GO and KEGG, and protein-protein interaction data were collected from STRING database. The hub gene GRB2 was further screened out and verified by molecular docking. Moreover, the relationship of GRB2 expression and immune infiltrates were analyzed by the TIMER database. The results of network pharmacology suggest that fucosterol acts against candidate targets, such as MAPK1, EGFR, GRB2, IGF2, MAPK8, and SRC, which regulate biological processes including negative regulation of the apoptotic process, peptidyl-tyrosine phosphorylation, positive regulation of cell proliferation. The Raf/MEK/ERK signaling pathway initiated by GRB2 showed to be significant in treating NSCLC. In conclusion, our study indicates that fucosterol may suppress NSCLC progression by targeting GRB2 activated the Raf/MEK/ERK signaling pathway, which laying a theoretical foundation for further research and providing scientific support for the development of new drugs.

Topics: Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; GRB2 Adaptor Protein; Humans; Lung Neoplasms; MAP Kinase Signaling System; Molecular Docking Simulation; Network Pharmacology; Signal Transduction; Stigmasterol

Enhancing the cholesterol turnover in the brain via activation of liver x receptors can restore memory in a mouse model for Alzheimer's disease. The edible Asian brown alga Sargassum fusiforme (Hijiki) contains high amounts of oxysterols such as (3β, 24ξ)-stigmasta-5, 28-dien-3, 24-diol (24[R, S]-saringosterol) that are a potent liver x receptor agonists. We aimed to find native European seaweed species with contents of 24(R, S)-saringosterol that are comparable to those found in Sargassum fusiforme. Additionally, we hypothesize that seasonal variations modify the amount of 24(R, S)-saringosterol in seaweeds. Sterols and oxysterols were extracted with chloroform/methanol from various seaweed species harvested in the Eastern Scheldt in different seasons between October 2016 and September 2017. Identification and quantification of the lipids was performed by gas chromatography- mass spectrometry and gas chromatography- flame ionization detection. We confirmed that brown algae Undaria pinnatifida harvested in February and Sargassum muticum harvested in October contained the highest amounts of 24(R, S)-saringosterol (32.4 ± 15.25 μg/g, mean ± S.D. and 32.95 ± 2.91 μg/g, respectively) and its precursor fucosterol (1.48 ± 0.11 mg/g), higher than Sargassum fusiforme (20.94 ± 3.00 μg/g, mean ± S.D.), while Ascophyllum nodosum and Fucus vesiculosus and Fucus serratus contained amounts of 24(R, S)-saringosterol (22.09 ± 3.45 μg/g, 18.04 ± 0.52 μg/g and 19.47 ± 9.01 μg/g, mean ± S.D., respectively) comparable to Sargassum fusiforme. In other algae only minor amounts of these sterols were observed. The green algae Ulva lactuca contained only 0.29 mg/g fucosterol and 10.3 μg/g 24 (R, S)-saringosterol, while all investigated red algae did not contain any 24(R, S)-saringosterol or fucosterol. In the Eastern Scheldt algae harvested in September/October delivered the highest yield for 24(R, S)-saringosterol, with the exception of Undaria pinnatifida that showed the highest levels in February. We showed that exposure of lipid extracts of Ulva lactuca to sunlight at room temperature or in the presence of oxygen to UV-C light lead to the quantitative conversion of fucosterol into 24(R, S)-saringosterol. Exposing pure fucosterol to UV-light did not convert any fucosterol into 24(R, S)-saringosterol underscoring the requirement of seaweed constituents in the conversion of fucosterol into 24(R, S)-saringosterol. In conclusion, we showed that brown seaweeds harvested from the Ea

Topics: Artifacts; Biological Factors; Chlorophyll; Isomerism; Phaeophyceae; Seaweed; Stigmasterol; Ultraviolet Rays; Ulva

Ovarian cancer is difficult to diagnose early and has high rates of relapse and mortality. Therefore, the treatment of ovarian cancer needs to be improved. Recently, several studies have been conducted in an attempt to develop anticancer drugs from naturally derived ingredients. Compared to traditional chemotherapy, natural compounds can overcome drug resistance with lower side effects. Fucosterol, a phytosterol present in brown algae, reportedly possesses many bioactive effects, including anticancer properties. However, the anticancer effects of fucosterol in ovarian cancer remain unexplored. Therefore, we investigated the effects of fucosterol on progression in human ovarian cancer cells. Fucosterol inhibited cell proliferation and cell-cycle progression in ovarian cancer cells. Additionally, fucosterol regulated the proliferation-related signaling pathways, the production of reactive oxygen species, mitochondrial function, endoplasmic reticulum stress, angiogenesis, and calcium homeostasis. Moreover, it decreased tumor formation in a zebrafish xenograft model. These results indicate that fucosterol could be used as a potential therapeutic agent in ovarian cancer.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Disease Models, Animal; Endoplasmic Reticulum Stress; Female; Humans; Mitochondria; Oceans and Seas; Ovarian Neoplasms; Phaeophyceae; Stigmasterol; Zebrafish

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cytokines; Heme Oxygenase-1; Inflammation Mediators; Macrophages; Membrane Proteins; Mice; Mitogen-Activated Protein Kinases; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Particulate Matter; Phaeophyceae; Phosphorylation; RAW 264.7 Cells; Signal Transduction; Stigmasterol

Alzheimer's disease (AD) is a neurodegenerative disease that leads to progressive loss of neurons which often results in deterioration of memory and cognitive function. The development of AD is highly associated with the formation of senile plaques and neurofibrillary tangles. Amyloid β (Aβ) induces neurotoxicity and contributes to the development of AD. Recent evidences also highlighted the importance of neuroglobin (Ngb) in ameliorating AD. This study assessed the ability of fucosterol, a phytosterol found in brown alga, in protecting SH-SY5Y cells against Aβ-induced neurotoxicity. Its effects on the mRNA levels of APP and Ngb as well as the intracellular Aβ levels were also determined in Aβ-induced SH-SY5Y cells. SH-SY5Y cells were exposed to fucosterol prior to Aβ treatment. The effect on apoptosis was determined using Annexin V FITC staining and mRNA expression was studied using RT-PCR. Flow cytometry confirmed the protective effects of fucosterol on SH-SY5Y cells against Aβ-induced apoptosis. Pretreatment with fucosterol increased the Ngb mRNA levels but reduced the levels of APP mRNA and intracellular Aβ in Aβ-induced SH-SY5Y cells. These observations demonstrated the protective properties of fucosterol against Aβ-induced neurotoxicity in neuronal cells.

Topics: Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Apoptosis; Cell Line, Tumor; Cell Survival; Gene Expression Regulation; Humans; Intracellular Space; Neuroglobin; Neurons; Neuroprotective Agents; Neurotoxins; RNA, Messenger; Stigmasterol

Particulate matter (PM) air pollution has gradually become a widespread problem in East Asia. PM may cause unfamiliar inflammatory responses, oxidative stress, and pulmonary tissue damage, and a comprehensive understanding of the underlying mechanisms is required in order to develop effective anti-inflammatory agents. In this study, fine dust collected from Beijing, China (CPM) (size < PM13 with majority < PM2.5) was evaluated for its oxidative stress- and inflammation-inducing effects, which cause cell damage, in A459 human lung epithelial cells. Oxidative stress was marked by an increase in intracellular ROS levels and the production of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and heme oxygenase-1 (HO-1). Upon induction of oxidative stress, a marked increase was observed in the expression of key inflammatory mediators such as COX-2 and PGE

Topics: A549 Cells; Air Pollutants; Anti-Inflammatory Agents; Beijing; China; Epithelial Cells; Humans; Inflammation; Lung; Lung Diseases; Lung Injury; Oxidative Stress; Particulate Matter; Sargassum; Stigmasterol

Colorectal cancer (CRC) is one of the most frequently occurring carcinomas which require effective therapies. Fucosterol is a sterol present in marine brown seaweeds with several biological activities. However, the influence of fucosterol in CRC remains to be determined. Thus, the aim of this study was to examine the anticancer activity of fucosterol alone and in combination with 5-fluorouracil (5-Fu) on two human CRC cell lines (HCT116 and HT29) and compared with cytotoxicity in one normal colon fibroblast cell line (CCD-18co) in monolayer (2D). The effect of fucosterol alone or in combination with 5-Fu was further assessed using HT29 multicellular spheroids (3D). Data demonstrated that fucosterol alone or combined with 5-Fu decreased cell viability in HT29 cells in 2D cultures without inducing cytotoxic in normal colon cells. The combination, fucosterol, and 5-Fu, also inhibited cell proliferation, clonogenic potential and cell migration without producing cell death in 2D. In multicellular spheroids, the combination fucosterol plus 5-Fu at the same concentrations used in 2D was not effective demonstrating that under the tested conditions the 3D model was more resistant than the 2D model. Taken together, these findings suggest that fucosterol might be a promising alternative to enhance the cytotoxic and anti-invasive actions of 5-Fu in colon cancer cells without consequent major adverse effects in normal cells. Our results also reinforce the need to include more complex 3D culture models in the initial stages of drug screening.

Topics: Antineoplastic Agents; Cell Proliferation; Cell Survival; Colonic Neoplasms; Fibroblasts; Fluorouracil; HCT116 Cells; HT29 Cells; Humans; Seaweed; Spheroids, Cellular; Stigmasterol

Increased levels of particulate matter (PM) air pollutants in East Asia have resulted in detrimental health impacts increasing morbidity and mortality. Epidemiological studies suggest a possible relation between the cutaneous exposure of PM and increased oxidative stress and inflammation which lead to skin lesions. The present study utilizes an integrated cell culture model of keratinocytes and fibroblasts to mimic viable skin layers and investigate the possible effects of PM exposure after penetration through corneocytes. The skin perfection is upheld by homeostatic functionality of epidermal cells and the integrity of connective tissues. Exposure to xenobiotics could alter the skin cell homeostasis aggravating premature skin aging. Stimulation of HaCaT keratinocytes by PM collected from Beijing, China (CPM) increased the intracellular ROS levels triggering a cascade of events aggravating inflammatory responses and connective tissue degradation. In HDF fibroblasts, treatment with preconditioned keratinocyte culture media augmented inflammatory responses, cellular differentiation, and connective tissue degradation. Above events were marked by the increased intracellular ROS, inflammatory mediators, pro-inflammatory cytokines, matrix metalloproteinases (MMP)-1 and -2 levels, collagenase, and elastase activity. Fucosterol treatment of keratinocytes dose-dependently attenuated the detrimental effects both in keratinocytes and fibroblasts restoring the conditions near to physiological levels. Further evaluations could be advanced on developing fucosterol, in forms such as rejuvenating cosmeceuticals which could attenuate detrimental responses of CPM exposure.

Topics: Air Pollutants; Cells, Cultured; Coculture Techniques; Cytokines; Fibroblasts; Humans; Inflammation; Keratinocytes; NF-kappa B; Oxidative Stress; Particulate Matter; Reactive Oxygen Species; Skin; Skin Diseases; Stigmasterol

Topics: Animals; Antimalarials; Chloroquine; Drug Evaluation, Preclinical; Erythrocytes; India; Inhibitory Concentration 50; Parasitemia; Plant Extracts; Plasmodium falciparum; Sargassum; Seaweed; Stigmasterol

A new steroid, 20-hydroxyisofucosterol (stigmasta-5,24(28)-diene-3β,20β-diol) (7), along with six known compounds 1 - 6 were isolated from the MeOH extract of the leaves of Sauropus androgynus L. Merr. (Euphorbiaceae). The structure of new steroid was determined by HR-APCI-MS and various NMR techniques in combination with literature data. Subsequently, their anti-inflammatory, cytotoxic activities against five human cell lines, as well as inhibitory activities against the α-MSH induced melanogenesis on the B16 cell line were evaluated. As the results, steroid compounds, 6 and 7 exhibited moderate cytotoxic to HL60, AZ521, SKBR3, and A549 tumor cell lines (IC

Topics: alpha-MSH; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Euphorbiaceae; Humans; Melanins; Melanoma, Experimental; Mice; Molecular Structure; Plant Leaves; Stigmasterol; Structure-Activity Relationship

The functional chemical substances and the antioxidant activity of lipids in 21 marine algae along the Japanese coast were investigated. Principal component analysis was performed to detect any correlation between the chemical substances and algae phylum. Chlorophyta contained a high level of β-carotene. Rhodophyta contained high amounts of cholesterol, β-sitosterol, and saturated fatty acids. Phaeophyta were rich in fucosterol, α-tocopherol, fucoxanthin, and polyphenol. Phaeophyta algae also showed the highest antioxidant activity compared with other phylum. This suggests that Phaeophyta has the greatest potential to be used as a functional food. Consumption of the beneficial Phaeophyta species, such as Eisenia arborea Areschoug and Ecklonia cava Kjellman should be encouraged as not only as food products but also as nutraceuticals and dietary supplements. These beneficial ingredients should be encouraged to be studied in depth with the possibility to develop specific formulated products target to special consumer's population with added nutritional value.

Topics: Antioxidants; Carotenoids; Chlorophyta; Dietary Supplements; Fatty Acids; Free Radical Scavengers; Functional Food; Japan; Phaeophyceae; Polyphenols; Principal Component Analysis; Rhodophyta; Stigmasterol; Tocopherols; Xanthophylls

Several feeding trials with Atlantic salmon fed naturally high phytosterol concentrations due to dietary rapeseed oil inclusion have shown changes in lipid metabolism and increased hepatic lipid storage in the fish. An in vitro trial with Atlantic salmon hepatocytes was, therefore, performed to study the possible direct effects of phytosterols on lipid storage and metabolism. The isolated hepatocytes were exposed to seven different sterol treatments and gene expression, as well as lipid accumulation by Oil Red O dyeing, was assessed. Fucosterol, a sterol found in many algae species, had an effect on the size of individual lipid droplets, leading to smaller lipid droplets than in the control without added sterols. A sterol extract from soybean/rapeseed led to an increase in the percentage of hepatocytes with visible lipid droplets at 20× magnification, while hepatocytes of both the sterol extract-treated groups and fucosterol-treated groups had a larger proportion of their area covered with lipids compared to control cells. Brassicasterol, a sterol characteristic of rapeseed oil, was the only sterol treatment leading to a change in gene expression, affecting the expression of the nuclear receptors, peroxisome proliferator-activated receptor gamma (pparg) and retinoid X receptor (rxr). The current study thus shows that phytosterols can have direct, although subtle, effects on both hepatic lipid storage and gene expression of Atlantic salmon in vitro.

Topics: Animals; Cholestadienols; Hepatocytes; Lipid Metabolism; Lipids; Phytosterols; Salmon; Stigmasterol

Higher sterols are universally present in large amounts (20-30%) in the plasma membranes of all eukaryotes whereas they are universally absent in prokaryotes. It is remarkable that each kingdom of the eukaryotes has chosen, during the course of evolution, its preferred sterol: cholesterol in animals, ergosterol in fungi and yeast, phytosterols in higher plants, and e.g., fucosterol and desmosterol in algae. The question arises as to which specific properties do sterols impart to membranes and to which extent do these properties differ among the different sterols. Using a range of biophysical techniques, including calorimetry, fluorescence microscopy, vesicle-fluctuation analysis, and atomic force microscopy, we have found that fucosterol and desmosterol, found in red and brown macroalgae (seaweeds), similar to cholesterol support liquid-ordered membrane phases and induce coexistence between liquid-ordered and liquid-disordered domains in lipid bilayers. Fucosterol and desmosterol induce acyl-chain order in liquid membranes, but less effectively than cholesterol and ergosterol in the order: cholesterol>ergosterol>desmosterol>fucosterol, possibly reflecting the different molecular structure of the sterols at the hydrocarbon tail.

Topics: Calorimetry, Differential Scanning; Cell Membrane; Desmosterol; Lipid Bilayers; Mechanical Phenomena; Microscopy, Atomic Force; Microscopy, Fluorescence; Molecular Structure; Seaweed; Stigmasterol

Chicories produce a wide range of vegetables with important nutritional value. We determined the variation of sterol, total polyphenol, nitrate contents and antioxidant capacity (SC, TPC, NC, AC) in endive leaves and stem-chicory novel vegetables, cultivated in two Italian regions. Within a given area, the SC was similar in smooth- and curly leafed endives (106.3-176.0 mg/kg FW); sitosterol and stigmasterol were major fractions (45-56 versus 38-43%). The stem SC was independent of landrace (101.5-118.6 mg/kg FW); sitosterol prevailed on stigmasterol and fucosterol (73-76 versus 12-14% versus 8-9%); the latter reached 15.7 mg/kg FW, conferring value as potential antidiabetes food. The planting site affected the AC and TPC of endives (893.1-1571.4 μmTE/100 g FW, 30.8-76.1 GAE100/g FW) and chicory stems (729.8-1152.5 μmTE/100 g FW; 56.2-124.4 GAE100/g FW), while the NC was recurrently below dangerous thresholds. PCA showed that environment was the major cause of variation, though it modestly affected these parameters.

Topics: Antioxidants; Asteraceae; Cichorium intybus; Crop Production; Crops, Agricultural; Food Contamination; Functional Food; Humans; Italy; Nitrates; Nutritive Value; Oxygen Radical Absorbance Capacity; Phenols; Phytosterols; Plant Leaves; Plant Stems; Principal Component Analysis; Sitosterols; Spatio-Temporal Analysis; Species Specificity; Stigmasterol

The purpose of this study was to investigate the effects of fucosterol on adipogenesis of 3T3-L1 preadipocytes and its underlying mechanisms.. Fucosterol, isolated from brown algae, Ecklonia stolonifera. We investigated the levels of lipid accumulation using Oil Red O staining. We conducted Western blot analysis to investigate regulatory effects of fucosterol on expression of phosphoinositide 3-kinase (PI3K), Akt, extracellular signal-regulated kinase (ERK), forkhead box protein O 1 (FoxO1) in 3T3-L1 adipocytes.. Fucosterol significantly reduced intracellular lipid accumulation of 3T3-L1 adipocytes at concentrations of 25 and 50 μm. Fucosterol downregulated insulin-triggered PI3K/Akt, and ERK pathways. It subsequently decreased expression of adipogenic transcription factors, including PPARγ, C/EBPα and SREBP-1. In addition, fucosterol enhanced SirT1 expression while decreased phospho-FoxO1 expression which resulted in the activation of FoxO1.. We revealed that fucosterol inhibited adipogenesis of 3T3-L1 preadipocytes through modulation of FoxO signalling pathway. Therefore, our results suggest that fucosterol may be used for novel agents for the treatment of obesity.

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Animals; Anti-Obesity Agents; CCAAT-Enhancer-Binding Protein-alpha; Cell Line; Down-Regulation; Extracellular Signal-Regulated MAP Kinases; Forkhead Box Protein O1; Lipid Metabolism; Mice; Obesity; Phaeophyceae; Phosphatidylinositol 3-Kinases; Plant Extracts; PPAR gamma; Proto-Oncogene Proteins c-akt; Signal Transduction; Stigmasterol

Hizikia fusiforme, a brown seaweed, has been utilized as a health food and in traditional medicine. In this study, we investigated whether enzyme-modified H. fusiforme extracts (EH) have immunological effects compared with normal H. fusiforme extracts (NH). The effects of NH and EH on immune responses were investigated by assessing nitric oxide (NO) production, phagocytosis, and cytokine secretion in RAW 264.7 murine macrophages and mice. Also, fucosterol was evaluated to find the active component of NH and EH by addressing cytotoxicity test and NO production. Both of NH and EH significantly increased cell viability and NO synthesis. Tumor necrosis factor-α (TNF-α) expression was more induced by EH with LPS treatment. Phagocytic activity, as the primary function of macrophages, was markedly induced by EH treatment. Additionally, EH encouraged splenocyte proliferation and recovered the levels of cytokines IL-1β, IL-6, and TNF-α in mice. Finally, fucosterol increased NO production with no cytotoxicity, which means that fucosterol is an active component of EH. In conclusion, EH has the potential to modulate immune function and could offer positive therapeutic effect for immune system diseases.

Topics: Animals; Cell Line; Cell Survival; Gene Expression; Immunologic Factors; Interleukin-1beta; Interleukin-6; Lipopolysaccharides; Lymphocytes; Macrophages; Mice; Nitric Oxide; Phaeophyceae; Phagocytosis; Primary Cell Culture; Seaweed; Stigmasterol; Tumor Necrosis Factor-alpha

Since the action of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is strongly correlated with the onset of Alzheimer's disease (AD), the development of BACE1 inhibitors as therapeutic agents is being vigorously pursued. In our ongoing research aimed at identifying anti-AD remedies derived from maritime plants, we evaluated the BACE1 inhibitory activities of fucosterol and fucoxanthin from Ecklonia stolonifera and Undaria pinnatifida. In vitro anti-AD activities were performed via BACE1 inhibition assays, as well as enzyme kinetic and molecular docking predictions. Based on enzyme-based assays, fucosterol and fucoxanthin showed noncompetitive and mixed-type inhibition, respectively, against BACE1. In addition, docking simulation results demonstrated that the Lys224 residue of BACE1 interacted with one hydroxyl group of fucosterol, while two additional BACE1 residues (Gly11 and Ala127) interacted with two hydroxyl groups of fucoxanthin. Moreover, the binding energy of fucosterol and fucoxanthin was negative (-10.1 and -7.0 kcal/mol), indicating that hydrogen bonding may stabilize the open form of the enzyme and potentiate tight binding of the active site of BACE1, resulting in more effective BACE1 inhibition. The results suggest that fucosterol and fucoxanthin may be used beneficially in the treatment of AD and provide potential guidelines for the design of new BACE1 inhibitors.

Topics: Amyloid Precursor Protein Secretases; Aspartic Acid Endopeptidases; Hydrogen Bonding; Kinetics; Molecular Docking Simulation; Phaeophyceae; Stigmasterol; Xanthophylls

Exposure to environmental contaminants has been linked to developmental and reproductive abnormalities leading to infertility, spontaneous abortion, reduced number of offspring, and metabolic disorders. In addition, there is evidence linking environmental contaminants and endocrine disruption to abnormal developmental rate, defects in heart and eye morphology, and alterations in behavior. Notably, these effects could not be explained by interaction with a single hormone receptor. Here, using a whole-organism approach, we investigated morphological changes to developing zebrafish caused by exposure to a number of environmental contaminants, including bisphenol A (BPA), di(2-ethylhexyl)phthalate (DEHP), nonylphenol, and fucosterol at concentrations measured in a local water body (Oldman River, AB), individually and in mixture. Exposure to nanomolar contaminant concentrations resulted in abnormal morphological development, including changes to body length, pericardia (heart), and the head. We also characterize the spatiotemporal expression profiles of estrogen, androgen, and thyroid hormone receptors to demonstrate that localization of these receptors might be mediating contaminant effects on development. Finally, we examined the effects of contaminants singly and in mixture. Combined, our results support the hypothesis that adverse effects of contaminants are not mediated by single hormone receptor signaling, and adversity of contaminants in mixture could not be predicted by simple additive effect of contaminants. The findings provide a framework for better understanding of developmental toxicity of environmental contaminants in zebrafish and other vertebrate species.

Topics: Animals; Benzhydryl Compounds; Body Size; Diethylhexyl Phthalate; Embryo, Nonmammalian; Embryonic Development; Endocrine Disruptors; Head; In Situ Hybridization; Phenols; Stigmasterol; Water Pollutants, Chemical; Zebrafish

Insulin resistance is a characteristic feature of type 2 diabetes mellitus (T2DM) and is characterized by defects in insulin signaling. This study investigated the modulatory effects of fucosterol on the insulin signaling pathway in insulin-resistant HepG2 cells by inhibiting protein tyrosine phosphatase 1B (PTP1B). In addition, molecular docking simulation studies were performed to predict binding energies, the specific binding site of fucosterol to PTP1B, and to identify interacting residues using Autodock 4.2 software. Glucose uptake was determined using a fluorescent D-glucose analogue and the glucose tracer 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxyglucose, and the signaling pathway was detected by Western blot analysis. We found that fucosterol enhanced insulin-provoked glucose uptake and conjointly decreased PTP1B expression level in insulin-resistant HepG2 cells. Moreover, fucosterol significantly reduced insulin-stimulated serine (Ser307) phosphorylation of insulin receptor substrate 1 (IRS1) and increased phosphorylation of Akt, phosphatidylinositol-3-kinase, and extracellular signal- regulated kinase 1 at concentrations of 12.5, 25, and 50 µM in insulin-resistant HepG2 cells. Fucosterol inhibited caspase-3 activation and nuclear factor kappa B in insulin-resistant hepatocytes. These results suggest that fucosterol stimulates glucose uptake and improves insulin resistance by downregulating expression of PTP1B and activating the insulin signaling pathway. Thus, fucosterol has potential for development as an anti-diabetic agent.

Topics: Cell Survival; Dose-Response Relationship, Drug; Hep G2 Cells; Humans; Insulin; Insulin Resistance; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Signal Transduction; Stigmasterol

Structures of some bioactive phytochemicals in bran extract of the black rice cv. Riceberry that had demonstrated anti-cancer activity in leukemic cell line were investigated. After saponification with potassium hydroxide, separation of the unsaponified fraction by reversed-phase high performance liquid chromatography (HPLC) resulted in four sub-fractions that had a certain degree of anti-proliferation against a mouse leukemic cell line (WEHI-3 cell), this being IC50 at 24 h ranging between 2.80-467.11 μg/mL. Further purification of the bioactive substances contained in these four sub-fractions was performed by normal-phase HPLC. Structural characterization by gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance spectroscopy (NMR) resulted in, overall, the structures of seven phytosterols and four triterpenoids. Four phytosterols, 24-methylene-ergosta-5-en-3β-ol, 24-methylene-ergosta-7-en-3β-ol, fucosterol, and gramisterol, along with three triterpenoids, cycloeucalenol, lupenone, and lupeol, were found in the two sub-fractions that showed strong anti-leukemic cell proliferation (IC50 = 2.80 and 32.89 μg/mL). The other sterols and triterpenoids were campesterol, stigmasterol, β-sitosterol and 24-methylenecycloartanol. Together with the data from in vitro biological analysis, we suggest that gramisterol is a significant anti-cancer lead compound in Riceberry bran extract.

Topics: Animals; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cholesterol; Chromatography, High Pressure Liquid; Gas Chromatography-Mass Spectrometry; Leukemia; Mass Spectrometry; Mice; Molecular Structure; Oryza; Pentacyclic Triterpenes; Phytosterols; Phytotherapy; Plant Extracts; Seeds; Sitosterols; Stigmasterol; Triterpenes

Fucosterol is the primary sterol found in brown algae. Recently, considerable interest has been generated regarding fucosterol due to its potential antioxidant, anti-inflammatory and antidiabetic effects. The aim of this study was to investigate the protective effects of fucosterol on tert-butyl hydroperoxide (t-BHP)- and tacrine-induced oxidative stress in HepG2 cells.. Fucosterol by itself exhibited no cytotoxicity at concentrations below 100 μm by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The increased intracellular reactive oxygen species (ROS) and decreased glutathione levels observed in t-BHP- and tacrine-treated HepG2 cells were ameliorated by fucosterol pretreatment, indicating that the protective effects of fucosterol are mediated by the induction of cellular defence mechanisms against oxidative stress. Moreover, elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in tacrine-treated mice were significantly reduced after oral administration of fucosterol.. The hepatoprotective effects of fucosterol may occur via an increase in the hepatic level of glutathione and a decrease in ROS production, thereby preventing hepatic damage and the resultant increases in ALT and AST activity.. These results suggest that fucosterol may be an effective hepatoprotective agent that could be useful for preventive therapies against oxidative stress-related hepatotoxicity.

Topics: Animals; Cell Survival; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Dose-Response Relationship, Drug; Glutathione; Hep G2 Cells; Humans; Male; Mice; Oxidative Stress; Phaeophyceae; Protective Agents; Reactive Oxygen Species; Stigmasterol; Tacrine; tert-Butylhydroperoxide

Fucosterol has been reported to have antioxidant, antidiabetic, and anti-inflammatory effects. In this study, we investigated the protective effect and the possible mechanism of fucosterol on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.. Lung injury was assessed by a histologic study, pulmonary edema, and inflammatory cytokines production in bronchoalveolar lavage fluid. Alveolar macrophages were stimulated with LPS in the presence or absence of fucosterol. The expressions of inflammatory cytokines were determined by enzyme-linked immunosorbant assay. Nuclear factor-kappa B (NF-κB) expression was detected by Western blotting.. The results showed that fucosterol attenuated lung histopathologic changes, wet-to-dry ratio, and tumor necrosis factor-α, interleukin (IL)-6 and IL-1β production in LPS-induced ALI in mice. Meanwhile, fucosterol inhibited NF-κB activation and tumor necrosis factor-α, IL-6, and IL-1β production in LPS-stimulated alveolar macrophages.. In conclusion, the present study demonstrated that fucosterol exhibited a protective effect on LPS-induced acute lung injury, and the possible mechanism is involved in inhibiting NF-κB activation, thereby inhibiting LPS-induced inflammatory response.

Topics: Acute Lung Injury; Animals; Cells, Cultured; Cytokines; Lipopolysaccharides; Lung; Male; Mice; Mice, Inbred BALB C; NF-kappa B; Stigmasterol

Fucosterol is a phytosterol commonly extracted from algae. It has been proved that fucosterol possesses antioxidant activity that is capable of scavenging the free radicals causing skin damages. In this study, we investigated the protective mechanisms of fucosterol on cobalt chloride (CoCl2) induced hypoxia damages to keratinocytes (HaCaT). We found that fucosterol inhibited CoCl2 induced cytotoxicity and inflammation in a dose-dependent manner. Furthermore, fucosterol attenuated CoCl2 induced excess expression of IL-6, IL-1β and TNF-α in HaCaT cells. In addition, fucosterol surpressed the phosphorylation of PI3K and Akt and accumulation of HIF1-α simulated by CoCl2. Taken together, these results suggested that fucosterol executed its protective effects against CoCl2 induced cytotoxicity and inflammation by the inhibition of hypoxia inducible factor through PI3K/Akt pathway.

Topics: Cell Line; Chromones; Cobalt; Cytokines; Gene Expression Regulation; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation; Keratinocytes; Morpholines; Phosphatidylinositol 3-Kinases; Phosphorylation; Proto-Oncogene Proteins c-akt; Stigmasterol

We previously showed that extracts of Sargassum fusiforme significantly reduce immobility time in the forced swim test and tail suspension test, suggesting that these extracts possess antidepressant-like effects. Here, fucosterol extracted from S. fusiforme was evaluated for antidepressant and anticonvulsant activities in mice. Fucosterol (10, 20, 30 and 40mg/kg) significantly shortened immobility time in the forced swim test and tail suspension test for30min after treatment but had no effect on locomotor activity in the open field test. Fucosterol significantly increased serotonin, norepinephrine and the metabolite 5-hydroxyindoleacetic acid in mouse brain, suggesting that the effects of fucosterol may be mediated through these neurotransmitters. As assessed using maximal electroshock, fucosterol (20, 40, 100mg/kg) possessed anticonvulsant activity, whereas rotarod toxicity test results indicated that fucosterol did not induce neurotoxicity at the same dose levels in mice. Thus, fucosterol may be a useful antidepressant adjunct candidate for treating depression in patients with epilepsy. A significant increase in hippocampal brain-derived neurotrophic factor (BDNF) levels was found in the fucosterol 20mg/kg group (P<0.05). Our findings suggested that fucosterol may possess an antidepressant-like effect, which may be mediated by increasing central BDNF levels.

Topics: Animals; Anticonvulsants; Antidepressive Agents; Biogenic Monoamines; Brain; Depression; Male; Mice; Mice, Inbred BALB C; Motor Activity; Neurotransmitter Agents; Sargassum; Seizures; Stigmasterol; Swimming

Fucosterol is a sterol metabolite of brown algae and regulates genes involved with cholesterol homeostasis. As a part of our continuous search for anti-obesity agents from natural marine sources, the anti-adipogenic activities of Ecklonia stolonifera and its sterol, fucosterol, were evaluated for the inhibition of adipocyte differentiation and lipid formation. Oil Red O staining was used to evaluate triglyceride contents in 3T3-L1 pre-adipocytes primed by differentiation medium (DM) I and DM II. The methanolic extract of E. stolonifera showed strong anti-adipogenic activity, and was thus fractionated with several solvents. Among the tested fractions, the dichloromethane (CH2Cl2) fraction was found to be the most active fraction, with significant inhibition (40.5 %) of intracellular lipid accumulation at a non-toxic concentration, followed by the ethyl acetate fraction (30.2 %) at the same concentration, while the n-butanol and water fractions did not show inhibitory activity within the tested concentrations. The strong anti-adipogenic CH2Cl2-soluble fraction was further purified by a repeated chromatography to yield fucosterol. Fucosterol reduced lipid contents in a concentration-dependent manner without showing any cytotoxicity. Fucosterol treatment also yielded a decrease in the expression of the adipocyte marker proteins peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα) in a concentration-dependent manner. Taken together, these results suggest that fucosterol inhibits expression of PPARγ and C/EBPα, resulting in a decrease of lipid accumulation in 3T3-L1 pre-adipocytes, indicating that the potential use of E. stolonifera and its bioactive fucosterol as an anti-obesity agent.

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Animals; Anti-Obesity Agents; Cell Survival; Dose-Response Relationship, Drug; Mice; Phaeophyceae; Stigmasterol

Exposure to ultraviolet (UV) light causes matrix metalloproteinase (MMP) overexpression and extracellular matrix depletion, leading to skin photoaging. The activation of MMP is related to increased interlukin-6 (IL-6) and type I procollagen production, which is regulated by transforming growth factor-β1 (TGF-β1). Activator protein-1 (AP-1) activation induces MMP-1 production and reduces type I procollagen secretion. Fucosterol, which is extracted and purified from the brown algae Hizikia fusiformis, is a phytosterol. We assessed the effects of fucosterol on photodamage and investigated its molecular mechanism of action in UVB-irradiated normal human dermal fibroblasts by using enzyme-linked immunosorbent assay, Western blot analysis, and reverse transcription-polymerase chain reaction. Our results showed that fucosterol significantly decreased the UVB-induced expression of MMP-1, IL-6, p-c-Jun, and p-c-Fos. Additionally, fucosterol markedly increased the UVB-induced production of type I procollagen and TGF-β1. Our results indicate that fucosterol regulates MMP-1 and type I procollagen expression by modulating AP-1 and TGF-β1 signaling and that MMP-1 activation is correlated with IL-6. These data suggest that fucosterol is a promising botanical agent to protect against skin photodamage.

Topics: Blotting, Western; Dermis; Enzyme-Linked Immunosorbent Assay; Fibroblasts; Humans; Interleukin-6; Matrix Metalloproteinase 1; Radiation Injuries; Reverse Transcriptase Polymerase Chain Reaction; Stigmasterol; Ultraviolet Rays

In this study, we investigated the effect of fucosterol on HL-60 and the molecular mechanism. HL-60 Cells were treated with fucosterol, and 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) method was used to study fucosterol anti-tumor activity. Morphology of HL-60 cells was observed. Flow cytometry (FCM) was employed to detect the cell cycle. Laser scanning confocal microscope (LSCM) was used to analyze mitochondrial membrane potential (MMP) and the expressions of Fas, FasL, Fadd and Caspase-8. Western blot was performed to analyze the expressions of Cyt-C, Pro-Caspase-9 and Pro-Caspase-3. Caspase activity kits were used to determine the activity of Caspase-9, Caspase-8 and Caspase-3. The results showed fucosterol could inhibit the growth of HL-60 cells, and the cell cycle was arrested at G2/M phase. HL-60 cells showed obvious apoptosis morphology. After being treated with fucosterol for 24 h, HL-60 cells decreased MMP, induced Cyt-C release and Caspase-9, Caspase-3 activation. Fucosterol also increased the protein expression of Fas, FasL, Fadd and Caspase-8. Moreover, the activity of Caspase-9, Caspase-8 and Caspase-3 was increased significantly. In conclusion, Fucosterol can induce HL-60 cells apoptosis, suggesting that it may be a potent agent for cancer prevention and treatment.

Topics: Apoptosis; Caspase 3; Caspase 8; Caspase 9; Cell Cycle; Fas Ligand Protein; fas Receptor; Fas-Associated Death Domain Protein; Gene Expression Regulation, Leukemic; HL-60 Cells; Humans; Leukemia, Promyelocytic, Acute; Membrane Potential, Mitochondrial; Microscopy, Confocal; Microscopy, Fluorescence; Stigmasterol

New and sustainable sources of long-chain (LC, ≥C₂₀) omega-3 oils containing DHA (docosahexaenoic acid, 22:6ω3) are required to meet increasing demands. The lipid content of the oilseed of a novel transgenic, DHA-producing land plant, Camelina sativa, containing microalgal genes able to produce LC omega-3 oils, contained 36% lipid by weight with triacylglycerols (TAG) as the major lipid class in hexane extracts (96% of total lipid). Subsequent chloroform-methanol (CM) extraction recovered further lipid (~50% polar lipid, comprising glycolipids and phospholipids) and residual TAG. The main phospholipid species were phosphatidyl choline and phosphatidyl ethanolamine. The % DHA was: 6.8% (of total fatty acids) in the TAG-rich hexane extract and 4.2% in the polar lipid-rich CM extract. The relative level of ALA (α-linolenic acid, 18:3ω3) in DHA-camelina seed was higher than the control. Major sterols in both DHA- and control camelina seeds were: sitosterol, campesterol, cholesterol, brassicasterol and isofucosterol. C₁₆-C₂₂ fatty alcohols, including iso-branched and odd-chain alcohols were present, including high levels of iso-17:0, 17:0 and 19:0. Other alcohols present were: 16:0, iso-18:0, 18:0 and 18:1 and the proportions varied between the hexane and CM extracts. These iso-branched odd-chain fatty alcohols, to our knowledge, have not been previously reported. These components may be derived from wax esters, or free fatty alcohols.

Topics: Brassicaceae; Cholestadienols; Cholesterol; Fatty Acids, Omega-3; Gas Chromatography-Mass Spectrometry; Phospholipids; Phytosterols; Plant Oils; Plants, Genetically Modified; Seeds; Sitosterols; Stigmasterol; Triglycerides

The aim of this study was to investigate the bone regenerative effects of fucosterol in estrogen-deficient ovariectomized (OVX) rats.. Bone regeneration was assessed in fucosterol-treated MG63 cells in vitro via assays for osteoblast proliferation, alkaline phosphatase, and osteoclast differentiation. Osteoblast proliferation rates, alkaline phosphatase activity, and mineralization were increased in the fucosterol-treated group. Moreover, differentiation of osteoclasts was decreased in the fucosterol-treated group. In the in vivo assay, female rats were OVX. Twelve weeks after ovariectomy, rats were divided into seven groups, each oral administrate everyday for 7 weeks. The bone mineral density of femoral bones was higher in fucosterol groups than in OVX control, and body weight was lower in fucosterol groups. Among bone-quality parameters, bone volume/total volume increased and trabecular separation decreased in fucosterol groups relative to the OVX control. Bone formation and resorption were evaluated using the serum biomarkers osteocalcin and CTx. Fucosterol tripled the level of serum osteocalcin relative to the OVX group and reduced the serum level of CTx.. These results suggest that fucosterol has the dual potentials to activate osteoblasts to stimulate bone formation and suppress differentiation of osteoclasts so as to reduce bone resorption.

Topics: Administration, Oral; Alkaline Phosphatase; Animals; Bone Density; Bone Regeneration; Bone Resorption; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Collagen Type I; Disease Models, Animal; Female; Femur; Humans; Osteoblasts; Osteocalcin; Osteoclasts; Osteogenesis; Osteoporosis, Postmenopausal; Ovariectomy; Peptides; Rats; Rats, Sprague-Dawley; Stigmasterol

Three compounds (chlorophyll a, isofucosterol and saringosterol) were isolated from chloroform fraction of Sargassum thunbergii extract. The three compounds had two- to fourfold lower lipase inhibitory activity than that of the CHCl3:MeOH (C:M) (100:1) fraction (fraction I, 83.78% at 1 mg/mL). These results suggested that the high lipase inhibitory activity of fraction I was attributable to the actions of the three compounds. Therefore, S. thunbergii has potential for application as an anti-obesity agent.

Topics: Anti-Obesity Agents; Chloroform; Chlorophyll; Chlorophyll A; Lipase; Molecular Structure; Sargassum; Stigmasterol

Although individual phlorotannins contained in the edible brown algae have been reported to possess strong anti-inflammatory activity, the responsible components of Eisenia bicyclis have yet to be fully studied. Thus, we evaluated their anti-inflammatory activity via inhibition against production of lipopolysaccharide (LPS)-induced nitric oxide (NO) and tert-butylhydroperoxide (t-BHP)-induced reactive oxygen species (ROS), along with suppression against expression of inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), in RAW 264.7 cells. The anti-inflammatory activity potential of the methanolic extract and its fractions of E. bicyclis was in the order of dichloromethane>methanol>ethyl acetate>n-butanol. The strong anti-inflammatory dichloromethane fraction was further purified to yield fucosterol. From the ethyl acetate fraction, six known phlorotannins were isolated: phloroglucinol, eckol, dieckol, 7-phloroeckol, phlorofucofuroeckol A and dioxinodehydroeckol. We found that these compounds, at non-toxic concentrations, dose-dependently inhibited LPS-induced NO production. Fucosterol also inhibited t-BHP-induced ROS generation and suppressed the expression of iNOS and COX-2. These results indicate that E. bicyclis and its constituents exhibited anti-inflammatory activity which might attribute to inhibition of NO and ROS generation and suppression of the NF-κB pathway and can therefore be considered as a useful therapeutic and preventive approach to various inflammatory and oxidative stress-related diseases.

Topics: Animals; Anti-Inflammatory Agents; Cell Line, Transformed; Cell Survival; Cyclooxygenase 2; Dioxanes; Down-Regulation; Functional Food; Kelp; Macrophages; Mice; Nitric Oxide; Nitric Oxide Synthase Type II; Osmolar Concentration; Oxidative Stress; Phloroglucinol; Plant Extracts; Plant Leaves; Reactive Oxygen Species; Republic of Korea; Solvents; Stigmasterol

In the present study, we investigated the anti-diabetic potential of fucosterol by evaluating the ability of this compound to inhibit rat lens aldose reductase (RLAR), human recombinant aldose reductase (HRAR), protein tyrosine phosphatase 1B (PTP1B), and α-glucosidase. Fucosterol displayed moderate inhibitory activity against RLAR, HRAR, and PTP1B. However, it showed weak or no activity against AGE formation and α-glucosidase. In addition, our kinetic study revealed that fucosterol showed a mixed type inhibition against RLAR and HRAR, while it noncompetitively inhibited PTP1B. Since fucosterol inhibited aldose reductase (AR), it holds great promise for use in the treatment of diabetic complications. Therefore, we predicted the 3D structure of AR in rat and human using the Autodock program to simulate binding between AR and fucosterol and evaluate the binding site-directed inhibition of AR by fucosterol. Results of the docking simulations of fucosterol demonstrated negative binding energies (-8.2 kcal/mol for RLAR and -8.5 kcal/mol for HRAR), which indicated a higher affinity and tighter binding capacity of fucosterol for the active site of the enzyme. In particular, the hydrophobic ring system and the aliphatic side chain of fucosterol were found to be tightly bound in a specificity pocket through apolar amino acid residues on AR, while the anion binding site on AR interacts with the 3-hydroxyl group and the double bond on the side chain of fucosterol. The results of the present study clearly demonstrated the potential of using fucosterol for the management and treatment of diabetes and diabetes-associated complications.

Topics: Aldehyde Reductase; alpha-Glucosidases; Animals; Dose-Response Relationship, Drug; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Kinetics; Lens, Crystalline; Models, Molecular; Molecular Conformation; Plants, Edible; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Stigmasterol; Structure-Activity Relationship

It has been reported that fucosterol has anti-diabetic, anti-oxidant, and anti-osteoporotic effects. We investigated the anti-inflammatory effects and the underlying molecular mechanism of fucosterol in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Fucosterol suppressed the expressions of inducible nitric oxide synthase (iNOS), tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6) by downregulating their transcriptions, and subsequently inhibited the productions of nitric oxide, TNF-α, and IL-6. In addition, fucosterol attenuated LPS-induced DNA binding and the transcriptional activity of nuclear factor-κB (NF-κB). These reductions were accompanied by parallel reductions in the phosphorylation and nuclear translocation of NF-κB. Furthermore, fucosterol attenuated the phosphorylations of mitogen-activated protein kinase kinases 3/6 (MKK3/6) and mitogen-activated protein kinase-activated protein kinase 2 (MK2), which are both involved in the p38 MAPK pathway. These results suggest that the anti-inflammatory effects of fucosterol are associated with the suppression of the NF-κB and p38 MAPK pathways.

Topics: Animals; Cell Line; Cytokines; Down-Regulation; Gene Expression Regulation; Inflammation Mediators; Lipopolysaccharides; Macrophages; Mice; NF-kappa B; Nitric Oxide; p38 Mitogen-Activated Protein Kinases; Stigmasterol; Undaria

Fucosterol, a sterol that is abundant in marine algae, has hypocholesterolemic activity, but the mechanism underlying its effect is not clearly understood. Because data suggest that fucosterol can increase plasma high-density lipoprotein concentrations, we investigated whether it could activate liver X receptors (LXRs), critical transcription factors in reverse cholesterol transport. Fucosterol dose-dependently stimulated the transcriptional activity of both LXR-α and -β in a reporter gene assay, responses that were attenuated by the LXR antagonist As(2)O(3). Fucosterol also activated co-activator recruitment in cell-free time-resolved fluorescence resonance energy transfer analysis. In THP-1-derived macrophages, it induced the transcriptional activation of ABCA1, ABCG1, and ApoE, key genes in reverse cholesterol transport, and thereby significantly increased the efflux of cholesterol. Fucosterol also regulated intestinal NPC1L1 and ABCA1 in Caco-2 cells. Notably, fucosterol did not induce cellular triglyceride accumulation in HepG2 cells, primarily because of its upregulation of Insig-2a, which delays nuclear translocation of SREBP-1c, a key hepatic lipogenic transcription factor. These results suggest that fucosterol is a dual-LXR agonist that regulates the expression of key genes in cholesterol homeostasis in multiple cell lines without inducing hepatic triglyceride accumulation.

Topics: Cell Line; Cholesterol; Gene Expression; Hepatocytes; Humans; Intestinal Mucosa; Liver; Liver X Receptors; Macrophages; Orphan Nuclear Receptors; Stigmasterol; Transcriptional Activation

Sterols are isoprenoid-derived molecules that have essential functions in eukaryotes but whose metabolism remains largely unknown in a large number of organisms. Oomycetes are fungus-like microorganisms that are evolutionarily related to stramenopile algae, a large group of organisms for which no sterol metabolic pathway has been reported. Here, we present data that support a model of sterol biosynthesis in Aphanomyces euteiches, an oomycete species causing devastating diseases in legume crops. In silico analyses were performed to identify genes encoding enzymes involved in the conversion of the isoprenoid precursor 3-hydroxy-3-methylglutaryl coenzyme A to isoprenoids. Several metabolic intermediates and two major sterol end-products were identified by gas chromatography-mass spectroscopy. We show that A. euteiches is able to produce fucosterol (a sterol initially identified in brown algae) and cholesterol (the major animal sterol). Mycelium development is inhibited by two sterol demethylase inhibitors used as fungicides, namely tebuconazole and epoxiconazole. We propose the first sterol biosynthetic pathway identified in a stramenopile species. Phylogenetic analyses revealed close relationships between A. euteiches enzyme sequences and those found in stramenopile algae, suggesting that part of this pathway could be conserved in the Stramenopila kingdom.

Topics: Aphanomyces; Cholesterol; Fabaceae; Gas Chromatography-Mass Spectrometry; Lanosterol; Phylogeny; Plant Roots; Sterols; Stigmasterol

To study the chemical constituents of Fructus Broussonetiae.. Column chromatography with silic gel was employed to isolate and purify the 80% alcohol extract of Fructus Broussonetia, and the constituents were identified by spectral methods.. Six compounds were isolated from 80% ethanol extract. Their structures were identified as Isoterihanine (1), Chelerythrine (2), Trillin (3), Sucrose (4), beta-sitosterol (5) and Fucosterol (6).. These compounds are isolated from Fructus Broussonetiae for the first time.

Topics: Benzophenanthridines; Broussonetia; Fruit; Molecular Structure; Plants, Medicinal; Sitosterols; Spectrophotometry, Ultraviolet; Stigmasterol; Sucrose

To investigate the chemical constituents of the brown alga D. divaricata, and to test cytotoxicities of the purified compounds.. Compounds were isolated by normal phase silica gel, Sephadex LH-20 chromatography and reverse phase HPLC techniques. Their structures were elucidated by spectroscopic methods including IR, MS and NMR. Cytotoxicities were tested by MTT method.. Eight compounds were isolated from ethanolic extract of the brown alga D. divaricata and their structures were identified as (-)-torreyol (I), 4beta, 5alpha-dihydroxycubenol (II), 3-farnesyl-p-hydroxybenzioc acid (III), chromazonarol (IV), fucosterol (V), phenyl acetylamine (VI), 4-hydroxybenzoic acid (VII) and n-hexadecanoic acid (VIII).. Compound II and IV were obtained from this alga for the first time. The others were isolated from the Dictyotaceae algae for the first time. All compounds were inactive (IC50 > 10 microg x mL(-1)) against human tumor cell lines KB, Bel-7402, PC-3M, Ketr 3 and MCF-7.

Topics: Cell Line, Tumor; Humans; Parabens; Phaeophyceae; Stigmasterol; Terpenes; Xanthenes

The incorporation of [1-13C]-labeled glucose into the irregular monoterpene artemisia ketone, the regular monoterpenes camphor and beta-thujone, the sesquiterpene germacrene D, the diterpene trans-phytol and beta-sitosterol and isofucosterol has been studied in axenic cultures of Tanacetum vulgare L. (Asteraceae). Quantitative 13C NMR spectroscopic analysis of the resulting labeling patterns showed that the isoprene units of the monoterpenes and the diterpene are formed via the methylerythritol phosphate (MEP) pathway, whereas the isoprene building blocks of the sesquiterpene and the sterols originate from the mevalonic acid (MVA) pathway.

Topics: Bicyclic Monoterpenes; Camphor; Diterpenes; Magnetic Resonance Spectroscopy; Monoterpenes; Sesquiterpenes, Germacrane; Sitosterols; Stigmasterol; Tanacetum; Terpenes

Fucosterol isolated from Pelvetia siliquosa was tested for its anti-diabetic activity in vivo. Fucosterol, when administered orally at 30 mg/kg in streptozotocin-induced diabetic rats, was caused a significant decrease in serum glucose concentrations, and exhibited an inhibition of sorbitol accumulations in the lenses. Fucosterol, when administered orally at 300 mg/kg in epinephrine-induced diabetic rats, was also caused an inhibition of blood glucose level and glycogen degradation. These results demonstrated that fucosterol is a main anti-diabetic principle from the marine algae P. siliquosa.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Experimental; Dose-Response Relationship, Drug; Liver; Liver Glycogen; Male; Mice; Phaeophyceae; Rats; Rats, Sprague-Dawley; Rhodanine; Stigmasterol; Thiazolidines

The anti-oxidant activities of fucosterol isolated from the marine algae Pelvetia siliquosa were investigated. Fucosterol exhibited a significant decrease in serum transaminase activities elevated by hepatic damage induced by CCl4-intoxication in rats. Fucosterol inhibited the sGOT and sGPT activities by 25.57 and 63.16%, respectively. Fucosterol showed the increase in the anti-oxidant enzymes such as hepatic cytosolic superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-px) activities by 33.89, 21.56 and 39.24%, respectively, in CCl4-intoxicated rats. These results suggest that fucosterol possess not only the anti-oxidant, but also the hepatoprotective activities in rats.

Topics: Administration, Oral; Animals; Antioxidants; Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Catalase; Chemical and Drug Induced Liver Injury; Clinical Enzyme Tests; Drug Administration Schedule; Eukaryota; Glutathione Peroxidase; Hexanes; Injections, Intraperitoneal; Korea; Liver; Male; Plant Extracts; Premedication; Rats; Rats, Sprague-Dawley; Silymarin; Stigmasterol; Superoxide Dismutase; Transaminases

The first committed step in the conversion of cycloartenol into Delta(5) C24-alkyl sterols in plants is catalyzed by an S-adenosyl-methionine-dependent sterol-C24-methyltransferase type 1 (SMT1). We report the consequences of overexpressing SMT1 in tobacco (Nicotiana tabacum), under control of either the constitutive carnation etched ring virus promoter or the seed-specific Brassica napus acyl-carrier protein promoter, on sterol biosynthesis in seed tissue. Overexpression of SMT1 with either promoter increased the amount of total sterols in seed tissue by up to 44%. The sterol composition was also perturbed with levels of sitosterol increased by up to 50% and levels of isofucosterol and campesterol increased by up to 80%, whereas levels of cycloartenol and cholesterol were decreased by up to 53% and 34%, respectively. Concomitant with the enhanced SMT1 activity was an increase in endogenous 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, from which one can speculate that reduced levels of cycloartenol feed back to up-regulate 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and thereby control the carbon flux into sterol biosynthesis. This potential regulatory role of SMT1 in seed sterol biosynthesis is discussed.

Topics: Biological Transport; Carbon; Cholesterol; Cloning, Molecular; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Plant; Hydroxymethylglutaryl CoA Reductases; Methyltransferases; Nicotiana; Phytosterols; Plant Leaves; Plants, Genetically Modified; Seeds; Sitosterols; Stigmasterol; Triterpenes

Assay-guided fractionation of an antitubercular extract obtained from Lessonia nigrescens yielded the phytosterol saringosterol as its active component. No appreciable toxicity against Vero cells was observed for this compound. Saringosterol was also synthesized by oxidation of fucosterol. The MIC values for antitubercular activity of saringosterol and its 24S and 24R epimers were determined as 0.25, 1, and 0.125 microg/mL.

Topics: Animals; Antitubercular Agents; Cells, Cultured; Chile; Chlorocebus aethiops; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Dose-Response Relationship, Drug; Molecular Structure; Mycobacterium tuberculosis; Nuclear Magnetic Resonance, Biomolecular; Oxidation-Reduction; Phaeophyceae; Stereoisomerism; Stigmasterol; Vero Cells

Fucosterol (1), 24xi-hydroperoxy-24-vinylcholesterol (2), 29-hydroperoxystigmasta-5,24(28)-dien-3beta-ol (3), 24-ethylcholesta-4,24(28)-dien-3-one (4), 24xi-hydroperoxy-24-ethylcholesta-4,28(29)-dien-3-one (5), 24-ethylcholesta-4,24(28)-dien-3,6-dione (6), 24xi-hydroperoxy-24-ethylcholesta-4,28(29)-dien-3,6-di one (7), 6beta-hydroxy-24-ethylcholesta-4,24(28)-dien-3-one (8), and 24xi-hydroperoxy-6beta-hydroxy-24-ethylcholesta-4,28(2 9)-dien-3-one (9) were isolated from the marine brown alga Turbinaria conoides. The structures of these compounds were established by spectral analysis. Isolated for the first time from a natural source, the oxygenated fucosterols 4-9 exhibit cytotoxicity against various cancer cell lines.

Topics: Antineoplastic Agents, Phytogenic; Drug Screening Assays, Antitumor; Oxygen; Phaeophyceae; Spectrum Analysis; Stigmasterol; Tumor Cells, Cultured

We have identified the function of the Arabidopsis DIMINUTO/DWARF1 (DIM/DWF1) gene by analyzing the dim mutant, a severe dwarf with greatly reduced fertility. Both the mutant phenotype and gene expression could be rescued by the addition of exogenous brassinolide. Analysis of endogenous sterols demonstrated that dim accumulates 24-methylenecholesterol but is deficient in campesterol, an early precursor of brassinolide. In addition, we show that dim is deficient in brassinosteroids as well. Feeding experiments using deuterium-labeled 24-methylenecholesterol and 24-methyldesmosterol confirmed that DIM/DWF1 is involved in both the isomerization and reduction of the Delta24(28) bond. This conversion is not required in cholesterol biosynthesis in animals but is a key step in the biosynthesis of plant sterols. Transient expression of a green fluorescent protein-DIM/DWF1 fusion protein and biochemical experiments showed that DIM/DWF1 is an integral membrane protein that most probably is associated with the endoplasmic reticulum.

Topics: Amino Acid Sequence; Arabidopsis; Arabidopsis Proteins; Base Sequence; Brassinosteroids; Cholestanols; Cholesterol; DNA, Plant; Gene Expression Regulation, Plant; Genes, Plant; Membrane Proteins; Molecular Sequence Data; Mutation; Phenotype; Phytosterols; Plant Growth Regulators; Plant Proteins; RNA, Messenger; RNA, Plant; Sequence Homology, Amino Acid; Steroids; Steroids, Heterocyclic; Stigmasterol

This work shows that fucosterol, delta5-avenasterol, and similar ethylidene-side chain sterols can undergo acid-catalyzed isomerization to give a mixture of five isomers. Four isomers formed from fucosterol were analyzed, using gas chromatography-mass spectrometry, and were characterized as delta5-avenasterol, two delta5,23-stigmastadienols, and delta5,24(25)-stigmastadienol. When the unsaponifiables fraction from oat oil was subjected to acid hydrolysis, the two delta5,23-stigmastadienol isomers and delta5,24(25)-stigmastadienol were detected while fucosterol coeluted with sitosterol. Interisomerization of ethylidene-side chain sterols represents a limitation to the use of the acid hydrolysis method in the determination of sterols in food and other plant materials rich in these sterols, e.g., oat lipids.

Topics: Anticholesteremic Agents; Avena; Gas Chromatography-Mass Spectrometry; Hydrolysis; Isomerism; Seeds; Stigmasterol

Methyl 2-[propanamide-2'-methoxycarbonyl] benzoate, fucosterol, trans-phytol and p-formylphenol were isolated for the first time from a methanolic extract of Jolyna laminarioides. Methyl 2-[propanamide-2'-methoxycarbonyl]-benzoate exhibited chymotrypsin inhibitory activity and also found to be active against Escherichia coli and Shigella boydii. Fucosterol exhibited antifungal activity against Curvularia lunata, Stachybotrys atra and Microsporum canis.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Bacteria; Benzaldehydes; Benzoates; Chymotrypsin; Escherichia coli; Fungi; Microbial Sensitivity Tests; Microsporum; Molecular Structure; Phaeophyceae; Phytol; Plant Extracts; Protease Inhibitors; Shigella boydii; Stigmasterol

The complexation of fucosterol with three kinds of beta-cyclodextrin (beta-CyD) was investigated in aqueous solution and in the solid state. The solubility of fucosterol increased significantly on its complexation with maltosyl-beta-CyD and heptakis(2,6-di-O-methyl)-beta-CyD (DM-beta-CyD), while no appreciable increase was observed when complexed with beta-CyD. The stability constant of complexation with beta-CyD estimated from solubility determinations was greater for a 1:2 complex than for a 1:1 complex. On the other hand, 1:1 complexation of fucosterol with maltosyl-beta-CyD or DM-beta-CyD was greater than 1:2 complexation. The solid complexes were obtained in molar ratios of 1:2 and 1:3 for beta-CyD and maltosyl-beta-CyD complexes, respectively. The inclusion behaviour of fucosterol with maltosyl-beta-CyD was compared with beta-CyD in the solid state using DSC, powder X-ray diffractometry and CP/MAS 13C NMR. Maltosyl-beta-CyD showed different inclusion behaviour compared with beta-CyD, and produced an amorphous structure of fucosterol on complex formation. The dissolution rate of fucosterol-maltosyl-beta-CyD complex was significantly faster than other complexes due to its high aqueous solubility and amorphous structure.

Topics: beta-Cyclodextrins; Chemistry, Pharmaceutical; Cyclodextrins; Solubility; Solutions; Stigmasterol; Water

The thermotropic behavior of multilamellar vesicles (MLV) composed of different mole fractions of various marine sterols and 1-stearoyl-2-oleoyl phosphatidylcholine (SOPC) was examined by differential scanning calorimetry (DSC), and was compared to pure SOPC as well as their mixtures with cholesterol. The marine sterols investigated were capable of interacting with the phospholipid bilayers. Upon addition of marine sterols, the apparent transition temperature (Tm) of SOPC decreased significantly. Desmosterol (cholesta-5,24-dien-3 beta-ol) had the least interaction with SOPC, as reflected by the larger delta H values of its mixtures with the phospholipid. Fucosterol (24-ethylcholesta-5,24(28)-dien-3 beta-ol) showed a non-linear trend as the mole percent of the sterol increased. Mixtures of sutinasterol (24R-24-ethyl-26,26-dimethylcholesta-7,25(27)-dien-3 beta-ol) with SOPC had similar enthalpy values to cholesterol. The shape of the SOPC/marine sterol endotherm and their delta H values were not identical when liposomes prepared by dialysis were compared to MLV.

Topics: Calorimetry, Differential Scanning; Cholestadienols; Desmosterol; Eukaryota; Lipid Bilayers; Liposomes; Membrane Fluidity; Phosphatidylcholines; Sterols; Stigmasterol

The sterol fraction of Gynostemma pentafillum contains beta-sito sterol and isofucosterol. The identification of these compounds has been carried out through NMR and MS data.

Topics: Phytosterols; Plants; Sitosterols; Stigmasterol

The extent and site(s) of inhibition of cholesterol absorption by plant sterols, sitosterol and fucosterol, were studied in rats. The intragastric administration of a single emulsified lipid meal containing 25 mg [3H]cholesterol and 25 mg of either sitosterol or fucosterol inhibited the lymphatic absorption of cholesterol by 57% and 41%, respectively, in 24 hr. Less than 2% of each plant sterol was absorbed in the 24-hr period. In contrast, neither plant sterol (50 microM) inhibited cholesterol absorption when co-administered with equimolar amounts of cholesterol in phospholipid-bile salt micelles nor was either absorbed from the micellar solution. A series of in vitro studies was conducted to identify the site(s) of plant sterol inhibition of cholesterol absorption and to account for the difference in inhibitory effectiveness of sitosterol and fucosterol. A comparison of the micellar solubility of each sterol alone and in equimolar binary mixtures (to 2.0 mM) revealed that the solubility of individual sterols decreased in the following order: cholesterol, fucosterol, sitosterol, and that in binary mixtures cholesterol solubility was decreased by sitosterol and, to a lesser extent, by fucosterol relative to its solubility alone. A comparison between micellar-solubilized cholesterol and either sitosterol or fucosterol for binding to isolated brush border membranes, intestinal mucin, or for esterification by either cholesterol esterase or acyl coenzyme A:cholesterol acyltransferase revealed moderate to no competition. The data suggest that plant sterols displace cholesterol from bile salt (taurocholate) micelles and that sitosterol is more effective than fucosterol in this capacity.

Topics: Absorption; Animals; Anticholesteremic Agents; Binding, Competitive; Cholesterol; Esterification; Gastric Mucins; In Vitro Techniques; Intestinal Absorption; Lymphatic System; Male; Micelles; Microvilli; Mucous Membrane; Phytosterols; Rats; Rats, Inbred Strains; Sitosterols; Solubility; Sterol Esterase; Stigmasterol

The modulation of angiotensin converting enzyme (ACE) levels was studied using fucosterol, one of phytosterols, in cultured bovine carotid endothelial cells. Addition of fucosterol to the culture medium resulted in the decrease of ACE activity of endothelial cells; however, fucosterol did not directly inhibit ACE activity. Dexamethasone elevated the levels of ACE in normal cells, but this effect was not seen in the fucosterol-treated cells. Receptor assays showed that the amount of glucocorticoid receptors in fucosterol-treated cells decreased to an undetectable level. These results indicate that fucosterol lowers the ACE levels on the endothelial cells by inhibiting the synthesis of glucocorticoid receptors involved in the regulation of ACE levels.

Topics: Cells, Cultured; Dexamethasone; Endothelium; Peptidyl-Dipeptidase A; Phytosterols; Receptors, Glucocorticoid; Sitosterols; Stigmasterol

We have succeeded in corroborating the enhancing effect of vitamin A, vitamin C, sitosterol and fucosterol on the fibrinolytic activity of endothelial cells. The assay system consisted of an in situ dissolution of a fibrin layer coated onto a culture dish, over which endothelial cells were grown in a culture medium containing 10% serum. The dissolution was enhanced by the addition of these vitamins and phytosterols to the culture medium.

Topics: Animals; Ascorbic Acid; Cattle; Cells, Cultured; Endothelium; Fibrin; Fibrinolysis; Phytosterols; Sitosterols; Stigmasterol; Vitamin A

The sterol fraction of Equisetum arvense L. contains, essentially, the following sterols: beta-sitosterol (60.0%), campesterol (32.9%), isofucosterol (5.9%) and cholesterol (trace amounts). The identification of the compounds has been carried out through NMR and MS, while the corresponding percentage have been desumed from the GLC and HPLC data.

Topics: Cholesterol; Chromatography, Gas; Chromatography, High Pressure Liquid; Magnetic Resonance Spectroscopy; Phytosterols; Plants, Medicinal; Sitosterols; Stigmasterol

In a previous study(1), it was demonstrated that one of phytosterols, sitosterol, has an ability to increase the intracellular and extracellular activities of plasminogen activator in cultured endothelial cells and that other steroids including cholesterol, 5-androsten-3 beta-ol, stigmasterol, 20(R)-propyl-5-pregnen-3 beta-ol and 20(R)-heptyl-5-pregnen-3 beta-ol have no ability. Once-stimulated cells went back to normal states by removal of sitosterol. The similar lines of research for plasminogen activators were reported by several groups which were cited in a previous paper(l). In the present communication, we found that fucosterol, which is present mainly in brown algae, Phaeophyta, enhances the production of plasminogen activator in endothelial cells, as well as sitosterol. A similar enhancement was not observed for other steroids and sex hormones including androsterone, testosterone, estrone and estradiol. Synthesis of plasminogen activator induced with fucosterol or sitosterol was inhibited by protein synthesis inhibitor, cycloheximide. The plasminogen activators produced in cells were, in the present study, classified into urokinase-type activators with molecular weights of 31,000 and 55,000 and tissue-type ones with molecular weights of 81,000 and 130,000, which were identified with respective antibodies. The synthesis of each type of plasminogen activator in endothelial cells was stimulated by sitosterol or by fucosterol.

Topics: Animals; Carotid Arteries; Cattle; Cells, Cultured; Endothelium; Molecular Weight; Phytosterols; Plasminogen Activators; Sitosterols; Stigmasterol

Studies have been conducted on the lymphatic absorption of sitosterol (24 alpha-ethyl cholesterol), stigmasterol (delta 22, 24 alpha-ethyl cholesterol), and fucosterol (24-ethylidine cholesterol) when administered intragastrically to rats. In addition, the effect of each sterol on absorption of endogenous cholesterol has been assessed by including tracer cholesterol in the administered test emulsion. Analysis of 24-h lymph collections by GLC-mass spectrometry demonstrated that all three sterols were poorly absorbed to the extent of only 3 to 4% of the administered dose of 50 mg. In contrast, cholesterol absorption under similar conditions was about 42% of the administered dose. Administration of either sitosterol or stigmasterol resulted in an equally effective inhibition of cholesterol absorption (54%). Under identical conditions fucosterol had no effect on absorption of luminal cholesterol. The data suggest that the mechanism(s) for intestinal discrimination of sterols for absorption may be independent of the mechanism for interference with efficient cholesterol uptake by the intestine.

Topics: Absorption; Animals; Cholesterol; Lymphatic System; Male; Rabbits; Rats; Sitosterols; Sterols; Stigmasterol; Structure-Activity Relationship

Anaerobically grown Saccharomyces cerevisiae retained the ability to transfer a C1-group to the C-24 position of a delta 24(25)-sterol and to reduce the delta 25(28)-bond of a 24-methylenesterol. Both desmosterol and 24-methylenecholesterol yielded 24 beta-methylcholesterol. However, when the substituent at C-24 was enlarged to a 24-ethylidene group (fucosterol), reduction of the delta 24(28)-bond did not occur. In no cases was a delta 7- or a delta 22-bond introduced. Because the delta 24(28)-bond was reduced in the absence of the delta 22-bond, the delta 22-bond is not an obligatory requirement for reduction.

Topics: Anaerobiosis; Cholesterol; Desmosterol; Models, Biological; Oxidation-Reduction; Saccharomyces cerevisiae; Stigmasterol

Two new sterols, (24E)-24-n-propylidenecholesterol and 24 epsilon-n-propylcholesterol, were isolated from a cultured marine Chrysophyte. Since most of the steroids found in marine invertebrates are unchanged or modified sterols of algal or symbiotic origin, the discovery of these two unusual sterols in a unicellular alga grown under well-defined conditions contributes to our knowledge of sterols in marine food chains and offers a potential substrate for biosynthetic labeling experiments.

Topics: Chemical Phenomena; Chemistry; Cholesterol; Eukaryota; Magnetic Resonance Spectroscopy; Stigmasterol

The sponge Calyx niceaensis metabolizes administered [7,7--(3)H2]-fucosterol to produce labelled calysterol, the principal sterol component of the sponge, possessing the unique feature of a cyclopropene ring bridging C23,24.

Topics: Animals; Cyclopropanes; Phytosterols; Porifera; Sterols; Stigmasterol

Topics: Steroids; Stigmasterol