An update on ß-sitosterol: A potential herbal nutraceutical for diabetic management.

Phytosterols are bioactive compounds that are naturally present in plant cell membranes with chemical structure similar to the mammalian cell- derived cholesterol. They are highly present in lipid-rich plant foods such as nuts, seed, legumes and olive oil. Among various phytosterols, ß-sitosterol (SIT) is the major compound, found plentiful in plants. It has been evidenced in many in-vitro and in-vivo studies that SIT possesses various biological actions such as anxiolytic & sedative effects, analgesic, immunomodulatory, antimicrobial, anticancer, anti - inflammatory, lipid lowering effect, hepatoprotective, protective effect against NAFLD and respiratory diseases, wound healing effect, antioxidant and anti-diabetic activities. In this review, in order to compile the sources, characterization, biosynthesis, pharmacokinetics, antioxidant and anti-diabetic activities of SIT, classical and online-literature were studied which includes the electronic search (Sci Finder, Pubmed, Google Scholar, Scopus, and Web of Science etc) and books on photochemistry. The experimental studies on SIT gives a clear evidence that the potential phytosterol can be used as supplements to fight against life threatening diseases. High potential of this compound, classifies it as the notable drug of the future. Therefore, immense researches regarding its action at molecular level on life threatening diseases in humans are highly endorsed.

Prophylactic Intra-Uterine ß-Cyclodextrin Administration during Intra-Uterine Ureaplasma parvum Infection Partly Prevents Liver Inflammation without Interfering with the Enterohepatic Circulation of the Fetal Sheep.

Chorioamnionitis can lead to inflammation and injury of the liver and gut, thereby predisposing patients to adverse outcomes such as necrotizing enterocolitis (NEC). In addition, intestinal bile acids (BAs) accumulation is causally linked to NEC development. Plant sterols are a promising intervention to prevent NEC development, considering their anti-inflammatory properties in the liver. Therefore, we investigated whether an intra-amniotic (IA) Ureaplasma parvum (UP) infection affected the liver and enterohepatic circulation (EHC) and evaluated whether an IA administered plant sterol mixture dissolved in ß-cyclodextrin exerted prophylactic effects. An ovine chorioamnionitis model was used in which liver inflammation and the EHC were assessed following IA UP exposure in the presence or absence of IA prophylactic plant sterols (a mixture of ß-sitosterol and campesterol dissolved in ß-cyclodextrin (carrier)) or carrier alone. IA UP exposure caused an inflammatory reaction in the liver, histologically seen as clustered and conflated hepatic erythropoiesis in the parenchyma, which was partially prevented by IA administration of sterol + ß-cyclodextrin, or ß-cyclodextrin alone. In addition, IA administration of ß-cyclodextrin prior to UP caused changes in the expression of several hepatic BAs transporters, without causing alterations in other aspects of the EHC. Thereby, the addition of plant sterols to the carrier ß-cyclodextrin did not have additional effects.

Dietary ß-sitosterol regulates serum lipid level and improves immune function, antioxidant status, and intestinal morphology in broilers.

This research investigated effects of dietary ß-sitosterol addition at different levels on serum lipid levels, immune function, oxidative status, and intestinal morphology in broilers. One-day-old broiler chicks were allocated to 5 groups of 6 replicates. Chickens in the 5 groups were fed a basal diet supplemented with 0 (control group), 40, 60, 80, and 100 mg/kg of ß-sitosterol for 42 D, respectively. ß-Sitosterol linearly decreased (P < 0.05) concentrations of serum total cholesterol, jejunal tumor necrosis factor α (TNF-α), and ileal interleukin 1ß (IL-1ß) and mRNA relative expressions levels of jejunal TLR4 and ileal MyD88, whereas it linearly increased (P < 0.05) contents of jejunal immunoglobulin G (IgG), ileal secreted IgA and glutathione, jejunal catalase activity and Nrf2 mRNA relative expression level, villus height (VH), and VH-to-crypt depth (CD) ratio (VH:CD) in the jejunum and ileum. Linear and quadratic increases (P < 0.05) in absolute and relative spleen weight were observed by dietary ß-sitosterol, whereas malondialdehyde (MDA) concentration in the jejunum and ileum followed the opposite trend (P < 0.05). Compared with the control group, dietary ß-sitosterol at higher than or equal to 60 mg/kg level decreased (P < 0.05) contents of serum total cholesterol, ileal MDA, and jejunal TLR4 mRNA relative expression level, whereas it increased (P < 0.05) absolute spleen weight and ileal glutathione content. Higher than or equal to 80 mg/kg level of ß-sitosterol enhanced (P < 0.05) jejunal IgG concentration, VH, catalase activity, and Nrf2 relative expression level and ileal secreted IgA content, but reduced (P < 0.05) ileal IL-1ß content and MyD88 mRNA relative expression level. ß-Sitosterol addition at 60 and 80 mg/kg levels increased (P < 0.05) relative spleen weight, whereas it decreased (P < 0.05) jejunal MDA accumulation. Moreover, 100 mg/kg level of ß-sitosterol reduced (P < 0.05) jejunal TNF-α level, but it increased (P < 0.05) VH in the jejunum and VH:CD in the jejunum and ileum. Accordingly, dietary ß-sitosterol supplementation could regulate serum cholesterol level, promote immune function, and improve intestinal oxidative status and morphology in broilers.

Effects of Moist Exposed Burn Therapy and Ointment (MEBT/MEBO) on the autophagy mTOR signalling pathway in diabetic ulcer wounds.

Context: Burn therapy (MEBT)/moist exposed burn ointment (MEBO) is an effective traditional Chinese medicine method to treat diabetic wound, but the mechanism is unclear. Autophagy has been proved to be closely related with wound healing, so MEBO/MEBT is hypothesized to promote diabetic wound healing by regulating autophagy.Objective: To explore the mechanism of moist exposed MEBT/MEBO promoting diabetic wound repair.Materials and methods: Eighty male Wistar rats were randomly assigned to control (n = 20) and diabetic group induced by intraperitoneal injection of STZ (n = 60), which were further randomly assigned to MEBO, Kangfuxin and model groups (n = 20 each). All rats underwent full-thickness skin resection in the back. Wound healing was dynamically observed and wound tissues were collected at five time points for pathological examination, autophagosome and the expression of PI3K, Akt and mTOR.Results: The healing time in the control group was the shortest, no statistically significant difference was found between the MEBO and the Kangfuxin group (p = 0.76). The morphology of autophagosomes ranged large to small, which was the most obvious in the MEBO group. The mRNA and protein expression of PI3K, Akt and mTOR in each group reached the peak on Day 5, the levels in the MEBO group were the highest (F = 18.43, 19.97, 15.36, p < 0.05). On Day 11, the expression levels in each group began to decline.Discussion and conclusions: In this study, we discussed the molecular mechanism of MEBT/MEBO promoting the repair of diabetic ulcer wounds through autophagy and PI3K-Akt-mTOR signalling pathway, which provides a new way for drug design in the future.

An ultra high performance liquid chromatography with tandem mass spectrometry method for simultaneous determination of thirteen components extracted from Radix Puerariae in rat plasma and tissues: Application to pharmacokinetic and tissue distribution study.

A rapid and sensitive ultra high performance liquid chromatography with tandem mass spectrometry method was established and validated for simultaneous determination of thirteen bioactive components (gallic acid, protocatechuic acid, puerarin, p-hydroxycinnamic acid, daidzin, ononin, daidzein, naringenin, genistein, apigenin, formononetin, biochanin A, and ß-sitosterol) of Radix Puerariae extract in rat plasma and tissues. The plasma and tissues samples were pretreated by protein precipitation extraction, and umbelliferone and rutin were used as internal standards. Sample separation was performed on a ZORBAX RRHD Eclipse plus C18 column (2.1 mm × 50 mm, 1.8 µm, Agilent) with a mobile phase consisting of methanol-water (containing 0.1% formic acid). The mass spectrometry analysis was conducted in positive and negative ionization modes with multiple reaction monitoring. The lower limit of quantitation range for the 13 analytes was 0.2-35 ng/mL. The intra- and inter-day precision of all the analytes were less than 10.92%, with an accuracy ranging from -13.10 to 11.96%. Both the recovery and matrix effect were within acceptable limits. This method was successfully applied to pharmacokinetic and tissue distribution study of the 13 bioactive components in rats after oral administration of R. Puerariae extract.

A phytosterol-enriched saw palmetto supercritical CO2 extract ameliorates testosterone-induced benign prostatic hyperplasia by regulating the inflammatory and apoptotic proteins in a rat model.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a pathological condition affecting older men. BPH complications often lead to deterioration in the quality of life. Serenoa repens (Saw Palmetto) is used for treating lower urinary tract infections in traditional medicine. METHODS: This study was performed to compare the efficacy of ß-sitosterol enriched saw palmetto oil (VISPO) and conventional saw palmetto oil (SPO) extracted using supercritical fluid extraction, in alleviating the BPH complications using testosterone-induced BPH model rats. The animals received testosterone (5 mg/kg s.c.) with or without SPO and VISPO (200 and 400 mg/kg b.w.) or Finasteride (1 mg/kg b.w.) p.o. for 28 days. At the end of the experiment, overnight fasted animals were euthanized, blood samples collected for serum analysis of testosterone. Prostate tissue histomorphology was examined by hematoxylin and eosin (H&E) staining. Western blot analysis was performed using prostate tissue homogenates. RESULTS: VISPO exhibited superior efficacy compared to SPO as evident from the significant decrease in prostate weight to body weight ratio, serum testosterone level and increase in growth inhibition of prostate tissue compared to BPH group (p < 0.001). Histological examination of prostate tissue samples showed that VISPO treatment was comparatively better than SPO in improving the hyperplastic patterns. Further, VISPO significantly regulated the expression of inflammatory and apoptotic marker proteins in BPH rats. CONCLUSION: Our data provide experimental evidence that ß-sitosterol enriched saw palmetto oil could be higher efficacious in treating the BPH complications compared to the conventional saw palmetto oil preparations.

An Attempt of Using ß-Sitosterol-Corn Oil Oleogels to Improve Water Barrier Properties of Gelatin Film.

Oleogel with tailored viscoelasticity is a great interest for food structuring, while its potential benefits for edible film performance are not clear. In this study, ß-sitosterol (0, 5, 10, 15, and 20 wt%)-corn oil oleogel was developed and used in the formation of gelatin-based films. Importantly, adding oleogel significantly decreased water vapor permeability of the gelatin films, however, it had little negative influence on film strength. In addition, the results of this study demonstrated that increasing the sitosterol in oleogels led to an increasing number of ordered crystals formed in the oleogel, which contributed to compact and smooth surface of the film. Moreover, the incorporation of oleogel also caused some changes in molecule conformation and film barrier property. Therefore, the superior mechanical performance and moisture resistance properties of the film were obtained when 15% ß-sitosterol was used to prepare oleogel. PRACTICAL APPLICATION: Corn oil oleogels ß-sitosterol was incorporated with gelatin to prepare the gelatin film aiming to improve the water resistance of the films for its variety of practical production. The enhanced vapor permeability and accepted strength of the emulsion film indicated the potential application of it with a variety of edible packaging forms, such as films, pouch and sachet in medium and high humid condition.

Toward a Scientific Nutritional Supplement Combination for Prostatism and Erectile Dysfunction I: From Known Pharmacology to Clinical Testing.

Prostatism and erectile dysfunction (ED) are highly prevalent and closely comorbid. Prescription treatments are limitingly expensive but robust in mechanisms of action (MoA). Nutritional supplements (NS) are low-cost but inadequately supported by evidence. Do any NS use robust MoA? Could their efficacy be amplified via dosing, concentration of active principles, and/or use in combination? The goal is to develop an effective NS for prostatism and ED using the MoA of prescription treatments. Literature reviews were conducted on dietary supplements for prostatism or ED and MoA of relevant drugs. The most promising NS employing these MoA were chosen. A pilot study of a prototype combination was conducted. A protocol was created for an adequate dose-response trial to test the NS combination in men with ED and prostatism. The main measures were response rates, International Prostate Symptom Score, and International Index of Erectile Function. For drugs, the MoAs best proven for prostatism and ED were nitric oxide augmentation, mild androgen inhibition, and anti-inflammatory effects. The following NS best simulate these MoA and are best supported for efficacy; for prostatism: beta sitosterol; for ED: panax ginseng, arginine, and citrulline. Pilot clinical data provided support. A plan for a formal dose-response clinical trial was approved by a central institutional review board. NS using effective MoA might suffice for prostatism and ED. Pilot testing of a combination NS with the best-supported MoA supported further development. A dose-response trial should be conducted using adequate doses of L-citrulline, beta-sitosterol, ginseng, and vitamin D3.

Three Constituents of Moringa oleifera Seeds Regulate Expression of Th17-Relevant Cytokines and Ameliorate TPA-Induced Psoriasis-Like Skin Lesions in Mice.

As a folk medicine, Moringa oleifera L. is used effectively to treat inflammatory conditions and skin diseases. However, its mechanism of action is not well understood, limiting its medical use. We isolated and identified three compounds, namely niazirin, marumoside A and sitosterol-3-O-ß-d-glucoside, from the seeds of Moringa oleifera, and studied their effects on the expression of Th17-relevant cytokines (IL-12/IL-23 p40, IL-17A, IL-22 and IL-23 p19) using lipopolysaccharide-stimulated THP-1 cells. Additionally, as Th17 plays a critical role in the pathogenesis of psoriasis, we used a 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced psoriasis-like skin lesion mouse model to study their potential therapeutic application in vivo. The compounds suppressed the expression of IL-12/IL-23 p40, IL-17A, IL-22 and IL-23 p19 in vitro, and in vivo they ameliorated psoriasis-like skin lesions, decreased IL-17A mRNA expression, and increased the expression of keratinocyte differentiation markers. To our knowledge, this is the first report regarding the mechanism and therapeutic application of Moringa oleifera seeds to treat psoriasis-like lesions in vivo.

Anti-breast-Cancer Activity Exerted by ß-Sitosterol-d-glucoside from Sweet Potato via Upregulation of MicroRNA-10a and via the PI3K-Akt Signaling Pathway.

Breast cancer (BC) is a prominent source of cancer mortality in women throughout the world. ß-Sitosterol-d-glucoside (ß-SDG), a newly isolated phytosterol from sweet potato, possibly displays potent anticancer activity. However, the probable anticancer mechanisms involved are still unclear. This study sought to study how ß-SDG from sweet potato affects two BC cell lines (MCF7 and MDA-MB-231) and nude mice bearing MCF7-induced tumors. In addition, we assessed how ß-SDG affects tumor suppressor miR-10a and PI3K-Akt signaling in BC cells. Cell viability and proliferation were determined via MTT and colony-formation assays, and apoptosis was quantified by Hoechst staining and flow cytometry. In addition, miR-10a expression and apoptosis-related protein levels were measured. Our study indicated that ß-SDG exhibited cytotoxic activities on MCF7 and MDA-MB-231 cells via inducing apoptosis and activating caspase proteases in these cells. Furthermore, the experimental results in nude mice bearing MCF7-induced tumors demonstrated that oral ß-SDG administration at medium (60 mg/kg) or high (120 mg/kg) doses was sufficient to substantially impair the growth of tumors and to decrease the levels of CEA, CA125, and CA153 by 64.71, 74.64, and 85.32%, respectively, relative to those of the controls ( P < 0.01). ß-SDG was further found to regulate the expression of PI3K, p-Akt, Bcl-2-family members, and other factors involved in the PI3K-Akt-mediated mitochondrial signaling pathway via the tumor suppressor miR-10a. These findings indicated that ß-SDG suppresses tumor growth by upregulating miR-10a expression and inactivating the PI3K-Akt signaling pathway. Furthermore, ß-SDG could be developed as a potential therapeutic agent against MCF7-cell-related BC.

Role of Daucosterol Linoleate on Breast Cancer: Studies on Apoptosis and Metastasis.

The antitumor property of steroids in sweet potato ( Ipomoea batatas L.) remains poorly understood. Herein, we investigated the anticancer effect on breast carcinoma of daucosterol linoleate (DL), a steroid isolated from sweet potato. DL inhibited the cell viability of estrogen receptor (ER)-positive MCF-7 breast cancer cells at an IC50 value of 53.27 ± 9.02 µg/mL, while the effect was modest in ER-negative MDA-MB-231 breast cancer cells. Flow cytometry indicated that the DL-induced apoptosis in MCF-7 cells is dose-dependent. However, DL inhibited tumor growth and tumor weight at 100 mg/kg in MCF-7 xenograft nude mice. DL diminished the expression of Bcl-xl, Bcl-2, and XIAP, while increasing Bax, Bad, and activated caspase-dependent apoptosis in tumor tissues. Furthermore, DL inactivated the upstream Pi3k/Akt/NF-κB pathway. In the 4T1 spontaneous metastasis model, DL blocked metastasis progression, decreased the number of visible metastasis foci and inhibited metastasis size distribution in lung tissue. Further studies showed that DL suppressed VEGF, MMP 2, and MMP 9 expression in both tumor and lung tissues. From these results, we can assume that DL is a potential adjuvant therapy for ER-positive breast cancer patients.

Propolis wax nanostructured lipid carrier for delivery of ß sitosterol: Effect of formulation variables on physicochemical properties.

Preparation and characterization of novel functional nanostructured lipid carriers containing ß sitosterol has been studied. The nanostructured lipid carrires (NLCs) were formulated with propolis wax (PW) alone or in mixture (1:1 w/w) with glyceryl behenate (GB), and pomegranate seed oil (PSO) and produced by a hot melt emulsification method. Response surface methodology was used to optimize formulations with respect to ß sitosterol concentration, liquid lipid content and solid lipid composition. The NLCs formulated with less oil and higher drug content showed higher size and lower encapsulation efficiency. Solid state analysis exhibited lower crystallinity of optimal formulations compared to raw lipids and a drug amorphization into the NLC matrix. The compatibility between drug and encapsulating materials was confirmed by Fourier transform infrared spectroscopy. Transmission electron microscopy showed spherical particles ranged around 100 nm confirming the applicability of such formulations for the production of functional foods.

Buddleja thyrsoides Lam. crude extract presents antinociceptive effect on an arthritic pain model in mice.

Arthritis is a chronic inflammatory disease which reduces the life quality of affected individuals. Therapeutic tools used for treating inflammatory pain are associated with several undesirable effects. Buddleja thyrsoides Lam., known as 'Barbasco' or 'Cambara', is mostly used in several disorders and possesses antirheumatic, anti-inflammatory, and analgesic properties. Here, we investigated the antinociceptive and anti-inflammatory effects of the B. thyrsoides crude extract applied orally and topically in acute pain models and an arthritic pain model induced by complete Freund's adjuvant (CFA) paw injection in male mice (25-30 g). The high-performance liquid chromatography (HPLC) of the B. thyrsoides extract crude revealed the presence of the lupeol, stigmasterol, and ß-sitosterol. The stability study of the B. thyrsoides gel did not show relevant changes at low temperatures. The oral treatment with the B. thrysoides extract prevented the capsaicin-induced spontaneous nociception and the acetic acid-induced abdominal writhing, but did not alter the thermal threshold in the tail immersion test. The B. thyrsoides antinociceptive effect was not reversed by naloxone in the capsaicin test. The B. thyrsoides oral or topical treatment reversed the CFA-induced mechanical allodynia and thermal hyperalgesia with maximum inhibition (Imax) of 69 ± 6 and 68 ± 5% as well as 78 ± 15 and 87 ± 12%, respectively. Moreover, the topical but not oral treatment inhibited the CFA-induced cell infiltration, but did not reduce the paw edema significantly. The oral treatment with B. thyrsoides did not cause adverse effects. These findings suggest that the oral or topical treatment with B. thyrsoides presents antinociceptive actions in an arthritic pain model without causing adverse effects.

EVALUATION OF THE ANTI-INFLAMMATORY CAPACITY OF BETA-SITOSTEROL IN RODENT ASSAYS.

BACKGROUND: Beta-sitosterol (BS) is a compound discovered to be present in numerous plants. A number of interesting biomedical properties have been attributed to BS, including immuno-modulating and anti-inflammatory activities. Therefore, the aim of this report was to evaluate its anti-inflammatory capacity by applying various rodent experimental tests. METHODS: To carry out the objective of the study we applied the methods indicated here. Two of the adopted methods were based on the passive reverse Arthus reaction: the rat paw edema test and the rat pleurisy assay. We also applied two methods related with the non-specific acute inflammation: the mouse ear edema test, and the mouse mieloperoxidase activity assay. RESULTS: The results obtained in all tests established a significant anti-inflammatory potential of BS. In the rat paw edema test we found an inhibitory effect which goes from 50-70%; in the rat pleurisy assay our findings with respect to the volume of pleural exuded showed a reduction of 46%, as well as a 20% low amount of neutrophils in comparison with the level of the control group. In the mouse ear edema test we found a mean inflammatory inhibition of 75%, and with respect to mieloproxidase activity the results showed a significant inhibition induced by the three doses of BS. CONCLUSIONS: In the present study we determined a potent anti-inflammatory capacity of BS in specific and non-specific types of acute inflammation in rodents.

Interindividual variability in the cholesterol-lowering effect of supplementation with plant sterols or stanols.

Low-density lipoprotein cholesterol (LDL-C) plays a causal role in atherosclerosis. One way to reduce LDL-C levels is to inhibit cholesterol absorption. Plant sterols and stanols compete with cholesterol for absorption in the intestine and induce an average decrease in LDL-C by 5% to 15% in a dose-dependent manner, but not in all individuals. This review focuses on the interindividual variability in response to dietary supplementation with plant sterols and stanols. Dietary plant sterols and stanols have no significant effects on LDL-C in substantial numbers of individuals. Higher responses, in absolute value and percentage of LDL-C, are observed in individuals with higher cholesterol absorption and a lower rate of cholesterol synthesis. Some data provide evidence of the influence of genetics on the response to plant sterols and stanols. Further studies in large populations are required to extend these conclusions about genetic influences.

The effect of a plant extract enriched in stigmasterol and ß-sitosterol on glycaemic status and glucose metabolism in alloxan-induced diabetic rats.

Banana is an extensively cultivated plant worldwide, mainly for its fruit, while its ancillary product, the banana pseudostem, is consumed as a vegetable and is highly recommended for diabetics in the traditional Indian medicine system. The present study was aimed at elucidating the mechanism of antihyperglycaemia exerted by the ethanol extract of banana pseudostem (EE) and its isolated compounds viz., stigmasterol (C1) and ß-sitosterol (C2), in an alloxan-induced diabetic rat model. Diabetic rats which were administered with C1, C2 and EE (100 and 200 mg per kg b. wt.) for 4 weeks showed reduced levels of fasting blood glucose and reversal of abnormalities in serum/urine protein, urea and creatinine in diabetic rats compared to the diabetic control group of rats. Diabetic symptoms such as polyphagia, polydipsia, polyuria, urine glucose and reduced body weight were ameliorated in the diabetic group of rats fed with EE, C1 and C2 (100 mg per kg b. wt., once daily) for 28 days. The levels of insulin and Hb were also increased, while the HbA1c level was reduced. The altered activities of hepatic marker enzymes viz., aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP); glycolytic enzyme (hexokinase); shunt enzyme (glucose-6-phosphate dehydrogenase); gluconeogenic enzymes (glucose-6-phosphatase, fructose-1,6-bisphosphatase and lactate dehydrogenase) and pyruvate kinase were significantly reverted to normal levels by the administration of EE, C1 and C2. In addition, increased levels of hepatic glycogen and glycogen synthase and the corresponding decrease of glycogen phosphorylase activity in diabetic rats illustrated the antihyperglycaemic potential of EE and its components. The histological observations revealed a marked regeneration of the ß-cells in the drug treated diabetic rats. These findings suggest that EE might exert its antidiabetic potential in the presence of C1 and C2, attributable to the enhanced glycolytic activity, besides increasing the hepatic glucose utilization in diabetic rats by stimulating insulin secretion from the remnant ß-cells.

Effects of Dietary Plant Sterols and Stanol Esters with Low- and High-Fat Diets in Chronic and Acute Models for Experimental Colitis.

In this study, we evaluated the effects of dietary plant sterols and stanols as their fatty acid esters on the development of experimental colitis. The effects were studied both in high- and low-fat diet conditions in two models, one acute and another chronic model of experimental colitis that resembles gene expression in human inflammatory bowel disease (IBD). In the first experiments in the high fat diet (HFD), we did not observe a beneficial effect of the addition of plant sterols and stanols on the development of acute dextran sulphate sodium (DSS) colitis. In the chronic CD4CD45RB T cell transfer colitis model, we mainly observed an effect of the presence of high fat on the development of colitis. In this HFD condition, the presence of plant sterol or stanol did not result in any additional effect. In the second experiments with low fat, we could clearly observe a beneficial effect of the addition of plant sterols on colitis parameters in the T cell transfer model, but not in the DSS model. This positive effect was related to the gender of the mice and on Treg presence in the colon. This suggests that especially dietary plant sterol esters may improve intestinal inflammation in a T cell dependent manner.

Beta-Sitosterol: A Promising but Orphan Nutraceutical to Fight Against Cancer.

All the currently available cancer therapeutic options are expensive but none of them are safe. However, traditional plant-derived medicines or compounds are relatively safe. One widely known such compound is beta-sitosterol (BS), a plant derived nutrient with anticancer properties against breast cancer, prostate cancer, colon cancer, lung cancer, stomach cancer, ovarian cancer, and leukemia. Studies have shown that BS interfere with multiple cell signaling pathways, including cell cycle, apoptosis, proliferation, survival, invasion, angiogenesis, metastasis and inflammation. Most of the studies are incomplete partly due to the fact that BS is relatively less potent. But the fact that it is generally considered as nontoxic, the opposite of all currently available cancer chemo-therapeutics, is missed by almost all research communities. To offset the lower efficacy of BS, designing BS delivery for "cancer cell specific" therapy hold huge potential. Delivery of BS through liposome is one of such demonstrations that has shown to be highly promising. But further research did not progress neither in the field of drug delivery of BS nor in the field on how BS mediated anticancer activities could be improved, thus making BS an orphan nutraceutical. Therefore, extensive research with BS as potent anticancer nutraceutical is highly recommended.

Plasma cholesterol-lowering activity of dietary dihydrocholesterol in hypercholesterolemia hamsters.

OBJECTIVE: Cholesterol analogs have been used to treat hypercholesterolemia. The present study was to examine the effect of dihydrocholesterol (DC) on plasma total cholesterol (TC) compared with that of ß-sitosterol (SI) in hamsters fed a high cholesterol diet. METHODS AND RESULTS: Forty-five male hamsters were randomly divided into 6 groups, fed either a non-cholesterol diet (NCD) or one of five high-cholesterol diets without addition of DC and SI (HCD) or with addition of 0.2% DC (DA), 0.3% DC (DB), 0.2% SI (SA), and 0.3% SI (SB), respectively, for 6 weeks. Results showed that DC added into diet at a dose of 0.2% could reduce plasma TC by 21%, comparable to that of SI (19%). At a higher dose of 0.3%, DC reduced plasma TC by 15%, less effective than SI (32%). Both DC and SI could increase the excretion of fecal sterols, however, DC was more effective in increasing the excretion of neutral sterols but it was less effective in increasing the excretion of acidic sterols compared with SI. Results on the incorporation of sterols in micellar solutions clearly demonstrated both DC and SI could displace the cholesterol from micelles with the former being more effective than the latter. CONCLUSION: DC was equally effective in reducing plasma cholesterol as SI at a low dose. Plasma TC-lowering activity of DC was mediated by inhibiting the cholesterol absorption and increasing the fecal sterol excretion.

Lecithin-linker formulations for self-emulsifying delivery of nutraceuticals.

Lecithin-linker microemulsions are formulations produced with soybean lecithin in combination with a highly lipophilic (lipophilic linker) and highly hydrophilic (hydrophilic linkers) surfactant-like additives. In this work, lecithin-linker systems were formulated to produce self-emulsifying delivery systems for ß-carotene and ß-sitosterol. The concentration of the lipophilic linker, sorbitan monooleate, was adjusted to minimize the formation of liquid crystals. The concentration of hydrophilic linkers, decaglyceryl caprylate/caprate and PEG-6-caprylic/capric glycerides, was gradually increased (scanned) until single phase clear microemulsions were obtained. For these scans, the oil (ethyl caprate) to water ratio was set to 1. The single phase, clear microemulsions were diluted with fed-state simulated intestinal fluid (FeSSIF) and produced stable emulsions, with drop sizes close to 200 nm. Using pseudo-ternary phase diagrams to evaluate the process of dilution of microemulsion preconcentrates (mixtures of oil, lecithin and linkers with little or no water) with FeSSIF, it was determined that self-emulsifying systems are obtained when the early stages of the dilution produce single phase microemulsions. If liquid crystals or multiple phase systems are obtained during those early stages, then the emulsification yields unstable emulsions with large drop sizes. An in vitro permeability study conducted using a Flow-Thru Dialyzer revealed that stable emulsions with drop sizes of 150-300 nm produce large and irreversible permeation of ß-carotene to sheep intestine. On the other hand, unstable emulsions produced without the linker combination separated in the dialyzer chamber.