Phytosterols: Potential Metabolic Modulators in Neurodegenerative Diseases.

Phytosterols constitute a class of natural products that are an important component of diet and have vast applications in foods, cosmetics, and herbal medicines. With many and diverse isolated structures in nature, they exhibit a broad range of biological and pharmacological activities. Among over 200 types of phytosterols, stigmasterol and ß-sitosterol were ubiquitous in many plant species, exhibiting important aspects of activities related to neurodegenerative diseases. Hence, this mini-review presented an overview of the reported studies on selected phytosterols related to neurodegenerative diseases. It covered the major phytosterols based on biosynthetic considerations, including other phytosterols with significant in vitro and in vivo biological activities.

Phytosterols of marine algae: Insights into the potential health benefits and molecular pharmacology.

BACKGROUND: 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. PURPOSE: 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. METHODS: 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.' RESULTS: 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. CONCLUSION: 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.

Comparison of pharmacokinetics of phytoecdysones and triterpenoid saponins of monomer, crude and processed Radix Achyranthis Bidentatae by UHPLC-MS/MS.

1. The aim of this study was to develop a selective, rapid, accurate and sensitive ultrahigh performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for pharmacokinetic (PK) studies of phytoecdysones and triterpenoid saponins after oral administration of five monomers, crude, wine-processed and salt-processed Radix Achyranthis bidentatae (RAB).2. A Thermo Hypersil GOLD C18 column (100 mm × 2.1 mm, 1.9 µm) coupled with a mobile phase of (A) acetonitrile and (B) water (both containing 0.3% acetic acid) was used for sample separation. The mass analysis was performed in a triple quadruple mass spectrometer using selected reaction monitoring (SRM) with negative scan mode.3. The results showed that this method exhibited desirable sensitivity, precision, stability and repeatability. The extraction recoveries of the compounds ranged from 94.2 to 99.8% and the matrix effects ranged from 93.3 to 100.5%. Comparing the Cmax and AUC of five analytes in those groups showed this tendency: salt-processed RAB > wine-processed RAB > crude RAB > monomer group. The results confirmed the feasibility of TCM theory to enhance the efficacy of processed RAB.

Half-life of plasma phytosterols in very low birth weight preterm infants on routine parenteral nutrition with vegetable oil-based lipid emulsions.

BACKGROUND: Phytosterols in vegetable oil (VO)-based lipid emulsions (LE) likely contribute to parenteral nutrition-associated cholestasis (PNAC) in preterm infants. No characterization of plasma phytosterol half-lives has been done in very low birth weight (VLBW) preterm infants receiving parenteral nutrition (PN) with LE. METHODS: In a prospective cohort study, 45 VLBW preterm infants who received PN underwent serial blood sample measurements of sitosterol (SITO), campesterol (CAMP), and stigmasterol (STIGM). Plasma phytosterol half-lives were calculated from the phytosterol concentrations-decay curves by using a single-compartment model. RESULTS: After the stop of the intravenous LE, study infants had significantly lower plasma total CAMP, STIGM and SITO concentrations. The decay of plasma phytosterol concentrations was monoexponential. Half-life of plasma total CAMP, STIGM and SITO was 13.5 ± 6.9, 10.3 ± 4.5 and 10.3 ± 4.0 days, respectively. Plasma phytosterol half-lives did not correlate with gestational age, birth weight, cumulative phytosterol intakes and plasma conjugated bilirubin. CONCLUSION: VLBW preterm infants on PN with LE had rather long plasma phytosterol half-lives similar to hypercholesterolemic adults and phytosterolemic homozygotes patients. We speculate that the accumulation of phytosterols could contribute to their vulnerability to PNAC. CLINICAL TRIAL REGISTRY: The Ethics Committee of Marche-Italy (DG/469); www.clinicaltrials.gov (identification number NCT02758834).

Plasma Creatine Kinetics After Ingestion of Microencapsulated Creatine Monohydrate with Enhanced Stability in Aqueous Solutions.

Creatine monohydrate represents one of the largest sports supplement markets. Enhancing creatine (CRE) stability in aqueous solutions, such as with microencapsulation, represents innovation potential. Ten physically active male volunteers were randomly assigned in a double-blind design to either placebo (PLA) (3-g maltodextrin; n = 5) or microencapsulated CRE (3-g creatine monohydrate; n = 5) conditions. Experimental conditions involved ingestion of the samples in a 70-mL ready-to-drink format. CRE was delivered in a novel microencapsulation matrix material consisting entirely of hydrolyzed milk protein. Three hours after ingestion, plasma creatine concentrations were unchanged during PLA, and averaged ∼45 µM. During CRE, plasma creatine concentration peaked after 30 min at 101.6 ± 14.9 µM (p < 0.05), representing a 2.3-fold increase over PLA. Thereafter, plasma creatine concentration gradually trended downwards but remained significantly elevated (∼50% above resting levels) 3 hr after ingestion. These results demonstrate that the microencapsulated form of creatine monohydrate reported herein remains bioavailable when delivered in aqueous conditions, and has potential utility in ready-to-drink formulations for creatine supplementation.

Efecto de esteroles vegetales en la reducción del colesterol plasmático: ensayo clínico, controlado, aleatorizado, cruzado y doble ciego / Effect of plant sterols in reducing plasma cholesterol: crossover double-blind randomized clinical trial

Introducción: la hipercolesterolemia es uno de los principales factores de riesgo en la enfermedad cardiovascular. Los esteroles vegetales se han postulado como agentes reguladores y beneficiosos para el control de esta. Objetivo: analizar el efecto de los esteroles vegetales añadidos en una leche en la reducción del colesterol plasmático en adultos jóvenes. Métodos: ensayo clínico, controlado, aleatorizado, doble ciego y cruzado. Los esteroles (2,24 g diarios) fueron administrados en dos tomas de 350 ml de una leche comercial desnatada, durante dos periodos de 3 semanas, separados por una ‘fase de lavado’ de 2 semanas, en el grupo experimental. Al grupo control se le administró la misma cantidad de leche desnatada, sin esteroles. Tanto al inicio como al final de cada periodo de intervención se extrajeron muestras sanguíneas. Se analizaron la composición corporal, hábitos de salud y los siguientes marcadores sanguíneos: perfil lipídico, hematológico, inflamación, etc. Resultados: se incluyeron 54 personas en el estudio con una edad media de 38,8 ± 7,3 años. La diferencia porcentual entre los marcadores basales y finales para el colesterol total, colesterol-LDL, colesterol-HDL, triglicéridos y colesterol no-HDL fueron del 9,73%, 12,5%, 1,9%, 3,15% y 13,2%, respectivamente. Se obtuvieron diferencias estadísticamente significativas entre el grupo experimental y el grupo control, para todos los marcadores analizados excepto para los triglicéridos. Conclusión: los esteroles vegetales suministrados en un alimento de consumo habitual, como la leche, pueden ser una estrategia terapéutica no farmacológica para el control de la hipercolesterolemia de alto interés sanitario (AU)

Introduction: Hypercholesterolemia is one of the most relevant risk factors in cardiovascular disease, and plant sterols have been postulated as beneficial regulator agents for the control of the disease. Objective: Analyze the effect of added plant sterols in milk in reducing plasma cholesterol in young adults. Methods: A randomized, clinical controlled trial, double-blind crossover study. Sterols (2.24 g per day) were administrated in two doses of 350 ml of commercial skimmed milk, during two phases of three weeks respectively separated by a washout period of 2 weeks, in the experimental group. The same amount of skimmed milk was administrated to the control group, but with no sterols. At the beginning and end of each phase blood draws were performed. Anthropometric data and health habits were analyzed and the following blood laboratory markers: lipid profile, hematology, inflammation, etc. were collected. Results: Fifty four people were included in the study with an average age of 38.8 ± 7.3 years. Differences between baseline and final scores percentage were 9.73 %, 12.5 %, 1.9 %, 3.15 % y 13.2 % for total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides and No HDL-cholesterol, respectively. Statistically significant differences were found between the experimental group and the control group for all biomarkers analyzed except for triglycerides. Conclusion: Plant sterols supplied in commonly consumed food, such as milk, may be a non- pharmacological therapeutic strategy of hypercholesterolemia with high health interest (AU)

Bioactive substances with preventive effect in cardiovascular diseases / Sustancias bioactivas con efecto preventivo en la enfermedad cardiovascular

The effect of diet on cardiovascular disease prevention has been widely studied for many years. Numerous studies have confirmed that diets rich in fruits and vegetables (Mediterranean diet) are beneficial to the cardiovascular system and various bioactive food components have preventive effect on chronic diseases such as cardiovascular disease. In this paper we review the effect of bioactive substances included in the group of flavonoids (catechins and proanthocyanidins, anthocyanins and isoflavones), stilbenes such as resveratrol, bioactive peptides, plant sterols and polyunsaturated fatty acids omega-3 on the cardiovascular system (AU)

El efecto de la dieta sobre la prevención de las enfermedades cardiovasculares ha sido ampliamente estudiado durante muchos años. Numerosos estudios han corroborado que las dietas ricas en frutas y hortalizas (dieta mediterránea) resultan cardiosaludables y que diversas sustancias bioactivas que componen los alimentos tienen un efecto preventivo en diversas enfermedades crónicas como son las enfermedades cardiovasculares. En esta revisión vamos a tratar ciertas sustancias bioactivas, como son algunas incluidas en el grupo de los flavonoides (catequinas y proantocianidinas, antocianinas e isoflavonas), estilbenos como el resveratrol, péptidos bioactivos, esteroles vegetales y ácidos grasos poliinsaturados omega-3 (AU)

Pharmacokinetic comparison of a generic coenzyme Q10 solubilizate and a formulation with soybean phytosterols.

Coenzyme Q10 (CoQ10) is essential for all cells, and deficiency has been implicated in cardiovascular disease. Plant phytosterols inhibit cholesterol absorption, and may thereby also reduce cardiovascular risk. This study compared the relative bioavailability of CoQ10 solubilized in low-dose soybean phytosterols (SterolQ10) with a generic CoQ10 solubilizate. In a randomized, cross-over design, 36 healthy males received a single 100 mg dose of CoQ10, as SterolQ10 or generic CoQ10, with a two-week washout between treatments. Plasma CoQ10 was analysed at baseline, and at 2, 4, 6, 8 and 10 h after supplement ingestion. Subjects were then administered either 100 mg/day of generic CoQ10 or SterolQ10 for 4 weeks. Fasting plasma CoQ10 levels were measured at baseline and following supplementation. The two preparations were bioequivalent in regard to the area under the curve (AUC(0-10h) ) and maximum increase in concentration (C(max) ), with geometric mean ratios of 0.89 (CI 0.81-0.98) and 0.88 (CI 0.80-0.96), respectively. Four-weeks of CoQ10 resulted in a comparable twofold increase in CoQ10 levels for both formulations (p < 0.001), which was similar between preparations (p = 0.74). The combined CoQ10 and phytosterol formulation, SterolQ10, showed bioequivalence to the generic CoQ10 following a single CoQ10 dose, and demonstrated comparable bioavailability following multiple dose administration.

Differential effects on inhibition of cholesterol absorption by plant stanol and plant sterol esters in apoE-/- mice.

AIMS: 'Functional foods' supplemented with plant sterol esters (PSE) and plant stanol esters (PSA) are therapeutic options for the management of hypercholesterolaemia. However, their effects on blood monocytes, endothelial function, atherogenesis, and sterol tissue concentrations are poorly understood. METHODS AND RESULTS: Male apoE-/- mice (n= 30) were randomized to three different diets for 6 weeks (n= 10 per group): high-cholesterol (1.25%) western-type diet (WTD), WTD + 2% PSE, and WTD + 2% PSA. Both supplements reduced serum cholesterol. WTD + PSE resulted in increased plant sterol serum concentrations and increased inflammatory Ly-6C(high) monocyte numbers. WTD + PSA increased plant stanol serum concentrations and Ly-6C-monocyte numbers, but decreased vascular superoxide release, lipid hydroperoxides, and inflammatory cytokines in aortic tissue, in plasma, and in circulating monocytes. Despite reduced serum cholesterol concentrations, both supplements impaired endothelial vasodilation compared with WTD. WTD + PSA reduced the development of atherosclerotic lesions compared with WTD alone (12.7 ± 3.7 vs. 28.3 ± 3.5%), and WTD + PSE was less effective (17.5 ± 3.7%). WTD + PSE and WTD + PSA reduced the cholesterol content in the liver, but not in the brain. However, WTD + PSE and WTD + PSA increased plant sterol and plant stanol concentrations in the liver as well as in the brain. CONCLUSION: PSE and PSA supplementation reduced serum cholesterol, but increased plant sterol and plant stanol concentrations. Elevated levels of PSE and PSA were associated with endothelial dysfunction and increased central nervous system depositions. Atherosclerotic lesion retardation was more pronounced in WTD + PSA, coinciding with higher regenerative monocyte numbers, decreased oxidative stress, and decreased inflammatory cytokines compared with WTD + PSE.

Anticarcinogenic compounds of olive oil and related biomarkers.

Olive oil, one of the oldest vegetable oils consumed without any refining, is associated with a reduced risk of a number of common cancers. Minor constituents of virgin olive oil have been suggested to be among the major chemopreventive components. A brief overview is presented of recent findings concerning the bioavailability of certain important olive oil minor components including efficient antioxidant polyphenols, the triterpene hydrocarbon squalene and beta-sitosterol, considered as putative nutritional biomarkers, in relation to the incidence of cancer.

Increased plant sterol and stanol levels in brain of Watanabe rabbits fed rapeseed oil derived plant sterol or stanol esters.

Foods containing plant sterol or stanol esters can be beneficial in lowering LDL-cholesterol concentration, a major risk factor for CVD. The present study examined whether high dietary intake of rapeseed oil (RSO) derived plant sterol and stanol esters is associated with increased levels of these components in brain tissue of homozygous and heterozygous Watanabe rabbits, an animal model for familial hypercholesterolemia. Homozygous animals received either a standard diet, RSO stanol or RSO sterol ester while heterozygous animals were additionally fed with 2 g cholesterol/kg to the respective diet form for 120 d (n 9 for each group). Concentrations of cholesterol, its precursor lathosterol, plant sterols and stanols in brain and additionally in liver and plasma were determined by highly sensitive GC-MS. High-dose intake of RSO derived plant sterols and stanols resulted in increased levels of these components in plasma and liver. In brain a limited uptake of plant sterols and stanols was proven, indicating that these compounds passed the blood-brain barrier and may be retained in the brain tissue of Watanabe rabbits. Plant stanol ester feeding lowered plant sterol levels in brain, liver, and plasma. Cholesterol synthesis in brain, indicated by lathosterol, a local surrogate cholesterol synthesis marker, does not seem to be affected by plant sterol or stanol ester feeding. We conclude that high dose intake of plant sterol and stanol esters in Watanabe rabbits results in elevated concentrations of these components not only in the periphery but also in the central nervous system.

Bioidentical hormones for menopausal hormone therapy: variation on a theme.

BACKGROUND: Progesterone creams and natural or bioidentical compounded estrogen preparations are being promoted to consumers as safe alternatives to conventional menopausal hormone therapy and as health-promoting tonics. No reliable data support these claims. SAFETY: Natural hormones, including estradiol, estriol, estrone, and progesterone, can be expected to have the same adverse event profile as conventional menopausal hormone regimens. SALIVARY HORMONE TESTS: Salivary tests may be used to persuade asymptomatic consumers to use hormones (or symptomatic patients to use higher doses than those needed to mitigate symptoms), a practice that can be expected to result in adverse events.

Fitoestrógenos –isoflavonas- y menopausia / Phytoestrogens –isoflavones- and menopause

En los últimos años, se ha producido un cambio radical en el interés y el estudio e investigación de las plantas medicinales. El aumento del consumo de productos fitoterápicos en Estados Unidos y algunos países europeos ha hecho que muchas de estas plantas se evalúen de modo mucho más científico y se compruebe si realmente existe una eficacia clínica mediante la realización de ensayos clínicos prospectivos y aleatorizados que confirmen estas observaciones. Se han revisado las publicaciones existentes sobre los efectos biológicos de los fitoestrógenos en seres humanos, incluidos sus efectos sobre los sofocos, el aparato cardiovascular, la osteoporosis, el cáncer y el aparato genitourinario; también se han incluido estudios epidemiológicos y estudios realizados en animales y líneas celulares. Al final, se llega a la conclusión de que los fitoestrógenos tienen una serie de efectos en los seres humanos, destacando la acción estrogénica débil sobre los sofocos en mujeres posmenopáusicas. Parece también que las isoflavonas tienen acción sobre los lípidos y las lipoproteínas

In recent years, there has been a radical change in the study, research and interest in medicinal plants. As a result of the increase in the consumption of phytotherapeutic products in the United States and some European countries, many of these plants are now being evaluated in a much more scientific way, and their possible clinical efficacy is being assessed through randomised, prospective clinical trials that confirm these observations. The existing literature concerning the biological effects of phytoestrogens in humans, including their effect on hot flashes, the cardiovascular system, osteoporosis, cancer and the genitourinary system has been reviewed. Epidemiological studies and studies performed in animals and cell lines have been also included. It has been concluded tha phytoestrogens have a series of effects on humans, particularly their weak estrogenic activity relative to hot flashes in postmenopausal women. Isoflavones also appear to have an effect on lipids and lipoproteins

Growth hormone selectively improves intestinal cholesterol absorption after jejunoileal autotransplantation in pigs.

BACKGROUND/PURPOSE: Small bowel transplantation impairs enteric function and causes malabsorption of cholesterol and bile acids. Growth hormone stimulates intestinal absorptive function. The authors hypothesized that long-term growth hormone therapy could improve absorption of bile acids and cholesterol after autotransplantation of the jejunoileum. METHODS: Sixteen pigs with similar food, cholesterol, and fat intake underwent either sham laparotomy or a model of jejunoileal autotransplantation, including extrinsic autonomic denervation, lymphatic interruption, and in situ cold ischemia. Five randomly chosen autotransplanted animals received daily growth hormone treatment for 8 weeks. Serum lipids, absorption, and excretion of cholesterol, bile acids, and fat were determined after 8 weeks. Mucosal morphometrics, proliferation, and enzyme activities were determined. Plasma cholesterol precursors and plant sterols, respective markers of cholesterol synthesis and absorption, were measured after 2 and 8 weeks. RESULTS: After jejunoileal autotransplantation, growth hormone treatment significantly increased body weight gain, cholesterol absorption efficiency from 45.1% to 62.1%, plasma campesterol to cholesterol proportions, and biliary secretion of cholesterol. With or without growth hormone treatment, autotransplantation significantly increased fecal bile acid excretion, plasma cholesterol precursors, fecal bacterially modified neutral sterols, mucosal thickness of the ileum (but not jejunum), and intestinal transit time when compared with sham-operated animals. Crypt cell proliferation, mucosal enzyme activities, and microvilli showed no differences between the groups. CONCLUSIONS: These findings suggest that growth hormone treatment selectively improves cholesterol, but not bile acid absorption, after autotransplantation of the jejunoileum.

Monograph. Plant sterols and sterolins.

Sterols and sterolins, also known as phytosterols, are fats present in all plants, including fruits and vegetables. Although they are chemically similar to the animal fat, cholesterol, they have been shown to exert significant unique biochemical effects in both animals and humans. Because they are bound to the fibers of the plant, they are difficult to absorb during the transit of digested food through the gut, particularly in individuals with impaired digestive function. For this reason, and because much of the modern diet is over-processed and low in fresh plant materials, sterols and sterolins appear in the serum and tissue of healthy humans at 800-1000 times lower concentrations than that of cholesterol. Beta-sitosterol (BSS) is the major phytosterol in higher plants along with its glycoside, beta-sitosterolin (BSSG). Animal studies have demonstrated BSS and BSSG possess anti-inflammatory, antipyretic, antineoplastic, and immune-modulating properties. In other in vitro, animal, and human studies, a proprietary BSS:BSSG mixture has shown promise in normalizing T-cell function, dampening overactive antibody responses, and normalizing DHEA:cortisol ratios. Research has shown plant oils contain the highest concentration of phytosterols, nuts and seeds contain moderate amounts, and fruits and vegetables generally contain the lowest phytosterol concentrations. Because only low levels of these substances are found in humans, increased dietary intake of unprocessed fruits and vegetables or supplementation with commercial phytosterols may be of benefit in re-establishing optimal immune parameters. Restoring balance to the immune system may be of therapeutic benefit in disease processes such as chronic viral infections, stress-induced immune suppression, tuberculosis, allergies, cancer, and rheumatoid arthritis and other autoimmune conditions.

Pharmacological properties of plant sterols in vivo and in vitro observations.

Plant sterols have been investigated as one of the safe potential alternative methods in lowering plasma cholesterol levels. Several human studies have shown that plant sterols/stanols significantly reduce plasma total and LDL cholesterol. In this article, pharmacological characteristics of plant sterols/stanols have been summarized and discussed. In particular, experimental data that demonstrate the effects of dietary phytosterols on lipid metabolism and development of atherosclerotic lesions have been critically reviewed. Despite their similar chemical structures, phytosterols and cholesterol differ markedly from each other in regard to their pharmacological characteristics including intestinal absorption and metabolic fate. Compared to cholesterol, plant sterols have poor intestinal absorption. The most and best studied effects of plant sterols are their inhibition of intestinal cholesterol absorption. Other biological activities of phytosterols such as effects on lecithin:cholesterol acyltransferase activity, bile acid synthesis, oxidation and uptake of lipoproteins, hepatic and lipoprotein lipase activities and coagulation system have been linked to their anti-atherogenic properties. Moreover, evidence for beneficial effects of plant sterols on disorders such as cutaneous xanthomatosis, colon cancer and prostate hyperplasia has been discussed. Finally, the potential adverse effects of plant sterols as well as pathophysiology of hereditary sitosterolemia are also reviewed. In conclusion, more pharmacokinetic data are needed to better understand metabolic fate of plant sterols/stanols and their fatty acid esters as well as their interactions with other nutraceutical/pharmaceutical agents.

Effect of dietary phytosterols on rat tissue lipids.

The present study was designed to examine the incorporation of phytosterols (PS) in membranes and tissues of rats fed a diet containing 2% PS in the presence of 0.2% cholic acid for 22 days. The control diet contained 12 mg PS/100 g compared with 2,012 mg/100 g. Liver, kidney, testis, and prostate microsomes, plasma, and epididymal fat pads were examined for sterols. Fatty acid composition and phospholipid pattern were also examined in some tissues. The PS diet resulted in a fivefold increase in plasma PS compared with controls. PS was found to accumulate in adipose tissue and liver microsomes in rats fed the PS-supplemented diet. There was no effect of PS incorporation on microsomal cholesterol content, except in the testes, in which dietary PS reduced cholesterol content by 25%. Dietary PS increased 20:4n-6 and 22:5n-3 fatty acids in membranes of the liver, testis, and prostate but decreased 16:1 in liver microsomes. PS incorporation had no effect on the phospholipid pattern of the liver and testis.