Lacticaseibacillus casei decrease long-chain fatty acids and most substances in an experimental model of intestinal mucositis.

PURPOSE: To evaluate the long-chain fatty acid and major compounds levels in the feces after prophylactic oral use of Lacticaseibacillus casei in an experimental model of intestinal mucositis. METHODS: Fifteen Swiss mice were randomly divided into three groups (n=5/group): The negative or positive control groups (n = 5) received saline orally for 18 days and an the intraperitoneal (i.p.) of saline or 5 Fluorouracil (450 mg/kg) in 15th day, respectability. L. casei group received oral concentration of L. casei (1x109 CFU/mL) for 18 days, the i.p. injection of 5-fluorouracil (450 mg/kg) in 15th days. Tissue samples from colon and each small intestine segment were collected for histopathological analysis. Stool samples were collected. Fecal composition of long-chain fatty acids and sterols were analysed by gas chromatography-mass spectrometry on the 15th and the 18th day. RESULTS: The mucosa layer of all small intestine segments of animals from L. casei showed well preserved epithelium and glands, without necrosis signs, but Goblet cells number decreased. Several long-chain fatty acids and sterols have been identified before and after in the groups. L. casei administration after 5-FU treatment reduced concentrations of linoleic acid (18:2) (p < 0.001) and oleic acid (18:1) (p < 0.001) in feces. CONCLUSIONS: L. casei prevented the mucosal damage associated with 5-FU-induced intestinal mucositis reduced long-chain fatty acid levels in the feces.

Diversity of Plant Sterols Metabolism: The Impact on Human Health, Sport, and Accumulation of Contaminating Sterols.

The way of plant sterols transformation and their benefits for humans is still a question under the massive continuing revision. In fact, there are no receptors for binding with sterols in mammalians. However, possible biotransformation to steroids that can be catalyzed by gastro-intestinal microflora, microbial cells in prebiotics or cytochromes system were repeatedly reported. Some products of sterols metabolization are capable to imitate resident human steroids and compete with them for the binding with corresponding receptors, thus affecting endocrine balance and entire physiology condition. There are also tremendous reports about the natural origination of mammalian steroid hormones in plants and corresponding receptors for their binding. Some investigations and reports warn about anabolic effect of sterols, however, there are many researchers who are reluctant to believe in and have strong opposing arguments. We encounter plant sterols everywhere: in food, in pharmacy, in cosmetics, but still know little about their diverse properties and, hence, their exact impact on our life. Most of our knowledge is limited to their cholesterol-lowering influence and protective effect against cardiovascular disease. However, the world of plant sterols is significantly wider if we consider the thousands of publications released over the past 10 years.

Antidiabetic activities of alkaloids isolated from medicinal plants

Diabetes mellitus is a metabolic disorder affecting a great part of population around the world. It is the fifth leading death causing disease in the world and its cases are increasing day by day. Traditional medicine is thought to have promising future in the treatment of diabetes mellitus. In contrast to synthetic drugs phytochemicals are considered to be free from side effects. As one of the main class of natural products, alkaloids and their derivatives have been widely used as sources of pharmacological agents against a variety of medical problems. Many studies confirmed the role of alkaloids in the management of diabetes and numerous alkaloids isolated from different medicinal plants were found active against diabetes. Like other natural products, alkaloids regulate glucose metabolism either by inhibiting or inducing multiple candidate proteins including AMP-activated protein kinase, glucose transporters, glycogen synthase kinase-3, sterol regulatory element-binding proteins 1, glucokinase, glucose-6-phosphatase, acetyl-CoA carboxylase among the others. A comprehensive review of alkaloids reported in the literature with anti-diabetic activities and their target enzymes is conducted, with the aim to help in exploring the use of alkaloids as anti-diabetic agents. Future work should focus on rigorous clinical studies of the alkaloids, their development and relevant drug targets.

A two-center, assessor-blinded, prospective trial evaluating the efficacy of a novel hypertonic draining cream for cellulite reduction: A Clinical and instrumental (Antera 3D CS) assessment.

INTRODUCTION: Gynoid lipodystrophy, also known as cellulite, is a very common skin alteration representing mainly a cosmetic problem rather than a real disease. An effective treatment of cellulite has not been well established. The initial phase of cellulite is characterized by subdermal tissue edema with interstitial fluids retention. A new hypertonic topical product with draining action (HTC) containing NaCl 13%, escine, caffeine, and beta-sitosterol has been recently developed. A 28-day double-blind placebo-controlled study has shown that this cream is able to reduce thigh circumference and the thickness of adipose tissue. No data so far are available regarding an objective evaluation of skin appearance for a longer application period. STUDY AIM: To evaluate the clinical efficacy of 2-month HCT treatment with clinical and instrumental assessments. SUBJECTS AND METHODS: In a prospective, 2-center, assessor-blinded trial 20 women (mean age 34 years) with cellulite of Grade I-III in severity were enrolled after their informed consent. HTC was applied once daily for 60 days. Primary outcomes of the trial were the evolution of thigh circumference measurements (assessed at baseline, after 1 and 2 months) and the computer-analysis of skin profilometry (ie, skin volumes) of a prespecified target area evaluated by means of Antera 3D CS digitalized images (assessed at baseline and at the end of the trial). Secondary outcome was the orange peel severity score (from 0 to 5) before and after pitch test. RESULTS: All subjects concluded the study period. Thigh circumference was reduced by -0.88 (right)/-1.2 cm (left) and by -1.8(right)/-2.1 (left) cm, after 30 and 60 days of treatment, respectively (P = .001, Wilcoxon test vs baseline). Antera 3D profilometry of the target zone showed a significant reduction in skin depression expressed in mm3 of -56% (from 59.7 to 26.73 mm3 ) after HTC application. Orange peel (no pitch test) mean (SD) score was 2.3 (1) at baseline, 2.0 (1) and 1.8 (0.8) after 1 and 2 months (P = .0031), respectively. After-pitch orange peel score was significantly reduced after treatment (from 3.3 to 2.2). CONCLUSION: Once daily application of HTC for 2 months has confirmed its efficacy in the improvement of objective and subjective assessments of cellulite parameters.(Trial Number registration: ISRCTN15111614).

Identification of sterols from the soft coral Dendronephthya gigantea and their anti-inflammatory potential.

Exploration of anti-inflammatory phytochemicals has received tremendous attention worldwide owing to the rapid increase in inflammatory diseases. Current study reveals the identification of eight 3ß-hydroxy-Δ5-steroidal congeners from a nonpolar column fraction of the ethanol solubles from the soft coral Dendronephthya gigantea collected from Jeju Island South Korea, using GC-MS/MS analysis. The sterol-rich fraction (DGEH21) showed a significant anti-inflammatory activity as exhibited by the inhibition of NO production (IC50 4.33±0.50µg/mL) and PGE2 production in LPS-stimulated RAW 264.7 macrophages. It also suppressed the expression levels of proinflammatory cytokines, TNF-α, IL-1ß, and IL-6 in a dose-dependent manner. Furthermore, DGEH21 effectively downregulated the expression levels of iNOS, and COX-2 and reduced NO and ROS production as well as cell death in LPS-stimulated in-vivo zebrafish embryo model. However, DGEH21 at relatively high concentrations indicated cytotoxicity in both RAW cells and zebrafish embryos with RAW cell viability being nearly 80% after treatment with 25µg/mL DGEH21. This study highlights the synergistic anti-inflammatory activity of several steroids found in D. gigantea. Their actions may be useful in the development of anti-inflammatory cosmeceuticals, pharmaceutical agents, and other consumer products.

The effects of Zanthoxylum bungeanum extract on lipid metabolism induced by sterols.

Variant pharmacological activities of Zanthoxylum bungeanum were determined before. The aim of this study was to assess whether Z. bungeanum could regulate lipid metabolism. The cholesterol overloading HepG2 cells induced by sterols were used as in vitro model to study lipid-lowering activities of the n-butanol (BuOH) fraction isolated from Z. bungeanum (ZBBu). Male apolipoprotein E knockout (apoE-KO) mice with high fat diet were used as in vivo model. We firstly demonstrated ZBBu had effects on reversed lipid accumulation, decreased apoB and enhanced apoA1 secretion. It increased the amount of low density lipoprotein receptor (LDLR) protein, also significantly inhibited the expression of SREBP-1 and SREBP-2's target molecule (hydroxy methylglutaryl coenzyme A reductase, HMGCR), which might be active in stimulation of RCT. And the expression of genes involved in RCT, such as CYP27A1, LXR-α, ABCG1, was promoted by ZBBu. Furthermore, ZBBu could reduce serum TC, TG levels in apoE-KO mice. Our study indicated that ZBBu could regulate the lipid metabolism through increasing the amount of low density lipoprotein receptor (LDLR) and inducing the expression of genes involved in RCT.

Smooth muscle cells isolated from thoracic aortic aneurysms exhibit increased genomic damage, but similar tendency for apoptosis.

Aortic aneurysms (AA) are characterized by structural deterioration leading to progressive dilation. During the development of AA, two key structural changes are pronounced, one being degradation of extracellular matrix and the other loss of smooth muscle cells (SMCs) through apoptosis. Reactive oxygen species (ROS) are produced above physiological levels in dilated (aneurismal) part of the aorta compared to the nondilated part and they are known to be associated with both the extracellular matrix degradation and the loss of SMCs. In this study, we hypothesized that aneurismal SMCs are more prone to apoptosis and that at least some cells undergo apoptosis due to elevated ROS in the aortic wall. To test this hypothesis, we first isolated SMCs from thoracic aneurismal tissue and compared their apoptotic tendency with normal SMCs in response to H(2)O(2), oxidized sterol, or UV treatment. Exposed cells exhibited morphological changes characteristic of apoptosis, such as cell shrinkage, membrane blebbing, chromatin condensation, and DNA fragmentation. Terminal deoxynucleotidyl transferased UTP nick end labeling (TUNEL) further confirmed the fragmentation of nuclear DNA in these cells. Vascular SMCs were analyzed for their micronuclei (MN) and binucleate (BN) frequency as indicators of genomic abnormality. These data were then compared to patient parameters, including age, gender, hypertension, or aortic diameter for existing correlations. While the tendency for apoptosis was not significantly different compared to normal cells, both the %MN and %BN were higher in aneurismal SMCs. The data suggest that there is increased DNA damage in TAA samples, which might play a pivotal role in disease development.

Oxysterols: A world to explore.

Oxysterols (oxidized derivatives of cholesterol and phytosterols) can be generated in the human organism through different oxidation processes, some requiring enzymes. Furthermore, oxysterols are also present in food due to lipid oxidation reactions caused by heating treatments, contact with oxygen, exposure to sunlight, etc., and they could be absorbed from the diet, at different rates depending on their side chain length. In the organism, oxysterols can follow different routes: secreted into the intestinal lumen, esterified and distributed by lipoproteins to different tissues or degraded, mainly in the liver. Cholesterol oxidation products (COPs) have shown cytotoxicity, apoptotic and pro-inflammatory effects and they have also been linked with chronic diseases including atherosclerotic and neurodegenerative processess. In the case of phytosterol oxidation products (POPs), more research is needed on toxic effects. Nevertheless, current knowledge suggests they may also cause cytotoxic and pro-apoptotic effects, although at higher concentrations than COPs. Recently, new beneficial biological activities of oxysterols are being investigated. Whereas COPs are associated with cholesterol homeostasis mediated by different mechanisms, the implication of POPs is not clear yet. Available literature on sources of oxysterols in the organism, metabolism, toxicity and potential beneficial effects of these compounds are reviewed in this paper.

Preliminary study on health-related lipid components of bakery products.

The purpose of this study was to evaluate the presence of health-related lipid components, in particular trans fatty acids and sterol oxidation products, in four bakery products. Both types of components are known for their adverse biological effects, especially the increase of atherogenic risk, and therefore it is advisable to monitor their presence in food products. Trans fatty acids were determined by silver-ion thin-layer chromatography-gas chromatography, whereas sterol oxidation was assessed by gas chromatography and gas chromatography-mass spectrometry determination of 7-keto derivatives (tracers of sterol oxidation). The amount of trans fatty acids (0.02 to 3.13 g/100 g of product), sterols (34.9 to 128.3 mg/100 g of product), and 7-keto derivatives of sterols (1.88 to 3.14 mg/kg of product) varied considerably among samples. The supply of phytosterols (22.5 to 64.0 mg/100 g of product) was not significant, and the extent of oxidation of most phytosterols to its corresponding 7-keto derivative was low (0.29 to 0.84%), except for that of brassicasterol (2.01 to 3.11%). The quality of ingredients and raw materials seems to have greatly influenced the fatty acid profile, stability, safety, and quality of the final product; these ingredients should be chosen with extreme care to decrease their potential negative health effects and to increase safety of these products.

Inhibition of cholesterol absorption by plant sterols for mass intervention.

Plant sterols and stanols lower serum cholesterol by inhibiting intestinal absorption of cholesterol. Because of their safety and efficacy, their application for mass intervention is promising. The use of fatty acid esters of stanols is particularly helpful because stanols readily mix with dietary fats in this form and their hypocholesterolemic efficacy is greater than in the free form.

Changes in synthesis of sterols and fatty acids associated with inhibition of growth of L-M cells at high cell density.

The relationship between cell density and de novo synthesis of sterols and fatty acids has been studied in monolayer cultures of L-M cells grown in serum-free medium. Incorporation of radioactivity from [14C] acetate or 3H2O into sterols and fatty acids declined sharply as cultures approached stationary phase. The activities of 3-hydroxy-3-methylglutaryl-CoA reductase and 3-hydroxy-3-methylglutaryl-CoA synthase declined in conjunction with the decrease in sterol synthesis; however, the activity of acetoacetyl-CoA thiolase did not decrease until after sterol synthesis had begun to decline. The magnitude of the initial decline in reductase activity was not diminished when activation of latent enzyme activity was prevented by addition of fluoride to cell homogenates. The diminution in the rate of fatty acid synthesis at high cell density was accompanied by a decrease in the activity of fatty acid synthetase, whereas the activity of acetyl-CoA carboxylase increased slightly. The data suggest that lipogenesis is regulated in coordination with the changes in the rate of cell proliferation that occur when L-M cells attain a high density in monolayer culture. Moreover, these studies establish the feasibility of using the L-M cell culture system to investigate the relationship between cell density and the enzymatic regulation of lipogenesis.