Safety Of Dietary Supplements Research Articles

The National Center for Natural Products Research (NCNPR) at 30: A Legacy of Pioneering Research in Natural Products and Dietary Supplements

Since its establishment in 1994, the National Center for Natural Products Research (NCNPR) at the University of Mississippi has made notable contributions to the field of natural product research, coinciding with the passage of the Dietary Supplement Health and Education Act. Over the past three decades, the Center has focused on studying plants, herbs, and other natural materials for applications in medicine, agriculture, and nutraceuticals, particularly in the area of botanical dietary supplements. NCNPR scientists have been actively engaged in developing and improving quality control measures to help ensure the safety of dietary supplements in response to a growing market. The Center’s research efforts have led to its designation as a U.S. Food and Drug Administration Center of Excellence, reflecting its role in advancing scientific understanding of natural products. Through collaborations with various stakeholders and regulators, NCNPR has contributed to shaping the regulatory landscape for botanical dietary supplements, highlighting both their potential health benefits and associated risks, such as product adulteration. The Center’s influence is also evident internationally, as demonstrated by its annual International Conference on the Science of Botanicals, which will mark its 26th year in April 2025. This overview outlines NCNPR’s role in supporting research, regulation, and safety in the natural products field.

Functional Effects of Probiotic Lactiplantibacillus plantarum in Alleviation Multidrug-Resistant Escherichia coli-Associated Colitis in BALB/c Mice Model.

Multidrug-resistant Escherichia coli (MDR-E. coli) is a global health concern. Lactic acid bacteria (LAB) are important probiotics that have beneficial effects on health, and in recent years, their influences in preventing foodborne pathogens-induced colitis have attracted much attention. Therefore, this study aimed to investigate the oral administration of Lactiplantibacillus plantarum NWAFU-BIO-BS29 as an emerging approach to alleviate MDR-E. coli-induced colitis in BALB/c mice model. To illustrate the mode of action of NWAFU-BIO-BS29 interventions with the gut microbiota and immune responses, the changes on the colonic mucosal barrier, regulatory of the gene expressions of inflammatory cytokines, re-modulating the intestinal microflora, and changes in physiological parameters were studied. The results indicated that daily supplementation of 200 µL fresh bacteria for 7days had ameliorated the associated colitis and partially prevented the infection. The modes of action by ameliorating the inflammatory response, which destructed villous and then affected the intestinal barrier integrity, reducing the secretion of interleukins (6 and β) and tumor necrosis factor (TNF-α) in serum by 87.88-89.93%, 30.73-35.98%, and 19.14-22.32%, respectively, enhancing the expressions of some epithelial integrity-related proteins in the mouse mucous layer of mucins 2 and 3, Claudin-1, and Occludin by 130.00-661.85%, 27.64-57.35%, 75.52-162.51%, and 139.36-177.73%, respectively, and 56.09-73.58% for toll-like receptor (TLR4) in colon tissues. Notably, the mouse gut microbiota analysis showed an increase in the relative abundance of beneficial bacteria, including Lactobacillus, Bacteriodales bacterium, Candidatus Saccharimonas, Enterorhabdus, and Bacilli. Furthermore, the probiotic promoted the proliferation of epithelia and goblet cells by increasing short-chain fatty acids (SCFAs) levels by 19.23-31.39%. In conclusion, L. plantarum NWAFU-BIO-BS29 has potential applications and can be considered a safe dietary supplement to ameliorate the colitis inflammation symptoms of MDR-E. coli infection.

Cannabinoid Hyperemesis Syndrome Presumed Secondary to CBD Use: A Case Report.

Cannabinoid hyperemesis syndrome is characterized by recurrent episodes of severe nausea and vomiting, often associated with prolonged and excessive cannabis use. With the recent legalization and rising consumption of cannabidiol (CBD) in Europe and the United States, concerns have emerged about its potential role in triggering similar symptoms. A 32-year-old male with a history of cannabis, tobacco and alcohol use disorder experienced multiple cyclic vomiting episodes after switching from cannabis to CBD. Initially, the patient presented with abdominal pain and vomiting after ceasing cannabis use, with symptoms alleviated by hot showers. Three months later, similar symptoms reappeared despite abstinence from cannabis but regular CBD consumption. Over the next 6 months, recurrent episodes of abdominal pain and vomiting persisted with daily CBD use but no cannabis consumption. Clinical data, laboratory results, and treatment responses were analyzed to investigate the connection between CBD consumption and symptom onset. The pathophysiology of cannabis-induced cyclic vomiting is poorly understood. Hypotheses include tetrahydrocannabinol accumulation in adipose tissue, pyrolytic conversion of CBD into tetrahydrocannabinol, and CBD's intrinsic effects, particularly its interaction with transient receptor potential vanilloid 1 receptors. Our analysis suggests that high doses of CBD may activate transient receptor potential vanilloid 1 receptors, inducing proemetic effects. Although the connection between CBD and cyclic vomiting remains uncertain, it warrants further investigation. The increasing use of CBD, perceived as a safe dietary supplement, underscores the need to understand its potential health impacts better.

Xanthophyllomyces dendrorhous Is a Safe Dietary Supplement with Potent Antioxidant Defense Enhancing Activity.

Xanthophyllomyces dendrorhous (X. dendrorhous), previously known as Phaffia rhodozyma, is a red yeast that is widely recognized as a rich source of carotenoids, particularly astaxanthin, which exhibits potent antioxidant activity and other health-promoting functions. However, there is currently a lack of research on the safety of consuming X. dendrorhous. To address this, we conducted an acute toxicity study followed by a 90-day subchronic toxicity trial to evaluate the safety of X. dendrorhous and investigate its in vivo antioxidant activity. In the acute toxicity study, Sprague-Dawley rats were administered a maximum of 12 g/kg body weight of X. dendrorhous powder by gavage and survived without any adverse effects for 14 days. In the subsequent subchronic toxicity test, the rats were randomly divided into five groups, each with free access to their diet adulterated with 0% (control), 2.5% (low), 5% (middle), 10% (high), and 20% (extreme high) X. dendrorhous powder. The rats' behavior, body weight, and food intake were monitored during the 90-day experiment. At the end of the experiment, urine, blood, and organs were collected from the rats for biochemical testing. Additionally, the antioxidant activity in rat sera was evaluated. The results of the acute toxicity test demonstrated that the LD50 of X. dendrorhous was greater than 12 g/kg body weight, indicating that the substance was not toxic. Throughout the 90-day period of subchronic toxicity, the triglyceride levels of male rats fed with 10 and 20% X. dendrorhous increased to 1.54 ± 0.17 and 1.55 ± 0.25 mmol/L (P < 0.05), respectively. This may be attributed to the elevated fat content of the diet in the high-dose and extreme high-dose groups, which was 5.5 and 2.5% higher than that in the control, respectively. Additionally, the white pulp in the spleen exhibited an increase, and the number of white blood cells in the extreme high-dose group increased by 2.41 × 109/L (P < 0.05), which may contribute to enhanced immunity. Finally, the body weight, food intake, blood and urine indexes, and histopathological examination results of the organs of the rats did not demonstrate any regular toxic effects. With the adulteration of X. dendrorhous, the activity of GSH-Px in male rats increased by 16-36.32%. The activity of GSH-Px in female rats of the extreme high-dose group increased by 14.70% (P < 0.05). The free radical scavenging ability of ABTS in male rats in the two high-dose groups exhibited an increase of 6.5 and 11.41% (P < 0.05). In contrast, the MDA content of male rats in the extreme high-dose group demonstrated a reduction of 2.73 nmol/mL (P < 0.05). These findings indicate that X. dendrorhous has no toxic effects, can be taken in high doses, and has a beneficial antioxidant effect that may enhance the body's immunity.

Applications of Capillary Electrophoresis for the Detection of Adulterants in Dietary Supplements.

In recent years, the consumption of dietary supplements, particularly those incorporating plant-based ingredients, has increased greatly, driven by the perception of their natural origins and purported minimal health risks. However, one significant safety concern revolves around the adulteration of dietary supplements, wherein unscrupulous manufacturers may illegally incorporate pharmaceutical substances or their analogs into these products to achieve increased efficiency and bolster sales. This review assesses the role of capillary electrophoresis (CE) in ensuring the quality control of dietary supplement products over the past two decades. This study provides an overview of various applications of CE in analyzing dietary supplements, outlining the typical attributes of natural product analysis using CE. These analyses demonstrate the broad versatility of CE, exemplified by its diverse applications and detection modes. Moreover, the review highlights the growing prominence of CE as a separation technique in quality control, by comparison with more conventional methods like high-performance liquid chromatography (HPLC). Through this exploration, the review elucidates the pivotal role of CE in upholding the integrity and safety of dietary supplements, in connection with a landscape of evolving regulatory challenges and consumer demands.

Evaluation of 12-Week Standardized Beetroot Extract Supplementation in Older Participants: A Preliminary Study of Human Health Safety.

In recent years, there has been a notable surge in the popularity of beetroot-based dietary supplements, driven by their rich nitrate composition. Several types of beetroot-based dietary supplements can be found in markets worldwide; however, ensuring the safety of dietary supplements is a crucial consideration, as there is limited evidence on their safety, especially for older populations. Therefore, the purpose of the current study was to evaluate the safety and tolerability of a nitrate-rich beetroot extract in older participants taking supplements over 12 weeks. The participants were randomly assigned to receive 20 g daily of beetroot extract or a matching placebo. The safety and tolerability of the supplementation were evaluated as the occurrence of adverse events and anthropometric, biochemical, and hemodynamic parameters were measured. No serious adverse events were reported in any group. Anthropometric, biochemical, and hemodynamic parameter changes between the baseline and the end of the study were not statistically significant in either group. However, interestingly, the group receiving beetroot extract supplementation exhibited a notable increase in plasma nitrate levels (p = 0.076, f = 0.50) and showed a decrease in insulin levels (p = 0.026, f = 0.59). In conclusion, we found that 20 g of beetroot extract supplementation for 12 weeks was safe and well tolerated in older participants.

Prebiotics for Induction and Maintenance of Remission in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis.

Prebiotics are nondigestible carbohydrates fermented by gut bacteria into metabolites that confer health benefits. However, evidence on their role for inflammatory bowel disease (IBD) is unclear. This study systematically evaluated the research on prebiotics for treatment of IBD. A search was performed in PubMed, Embase, Cochrane, and Web of Science. Eligible articles included randomized controlled trials or prospective observational studies that compared a prebiotic with a placebo or lower-dose control in patients with IBD. Meta-analyses were performed using random-effects models for the outcomes of clinical remission, clinical relapse, and adverse events. Seventeen studies were included. For induction of clinical remission in ulcerative colitis (UC), the fructooligosaccharide (FOS) kestose was effective (relative risk, 2.75, 95% confidence interval, 1.05-7.20; n = 40), but oligofructose-enriched inulin (OF-IN) and lactulose were not. For maintenance of remission in UC, germinated barley foodstuff trended toward preventing clinical relapse (relative risk, 0.40; 95% confidence interval, 0.15-1.03; n = 59), but OF-IN, oat bran, and Plantago ovata did not. For Crohn's disease, OF-IN and lactulose were no different than controls for induction of remission, and FOS was no different than controls for maintenance of remission. Flatulence and bloating were more common with OF-IN; reported adverse events were otherwise similar to controls for other prebiotics. Prebiotics, particularly FOS and germinated barley foodstuff, show potential as effective and safe dietary supplements for induction and maintenance of remission in UC, respectively. The overall certainty of evidence was very low. There would be benefit in further investigation on the role of prebiotics as treatment adjuncts for IBD.

Ginseng-DF ameliorates intestinal mucosal barrier injury and enhances immunity in immunosuppressed mice by regulating MAPK/NF-κB signaling pathways.

Dietary fiber (DF) has a good application prospect in effectively restoring the integrity of the intestinal mucosal barrier. Ginseng-DF has good physicochemical properties and physiological activity and shows positive effects in enhancing immunity. The aim of this study was to investigate the protective effect of Ginseng-DF on intestinal mucosal barrier injury induced by cyclophosphamide (CTX) in immunosuppressed mice and its possible mechanism. The effects of Gginseng-DF on immune function in mice were studied by delayed-type hypersensitivy, lymphocyte proliferation assay and NK cytotoxicity assay, the T lymphocyte differentiation and intestinal barrier integrity were analyzed by flow cytometry and western blot. Ginseng-DF (2.5% and 5%) could attenuate the inhibition of DTH response by CTX, promote the transformation and proliferation of lymphocytes, and stimulate NK effector cell activity. At the same time, Ginseng-DF could restore the proportion of CD4+/CD8+ T lymphocytes induced by CTX to different extents, improved spleen tissue damage, promoted the secretion of immunoglobulin IgG, and enhanced body immunity. More importantly, Ginseng-DF could up-regulate the contents of TNF-α, IFN-γ, IL-6 and IL-1β in serum and intestine of immunosuppressed mice to maintain the balance between Th1/Th2 cytokines, and improve the permeability of intestinal mucosal barrier. Meanwhile, Ginseng-DF could reduce intestinal epithelial cell apoptosis and improve intestinal adaptive immunity in CTX-induced immunosuppressed mice by regulating MAPK/NF-κB signaling pathway. Ginseng-DF can be used as a safe dietary supplement to enhance body immunity and reduce intestinal mucosal injury caused by CTX.

Safety and Tolerability of Microbial Inulinase Supplementation in Healthy Adults: A Randomized, Placebo-Controlled Trial

BACKGROUND AND AIMSDietary fermentable oligo-, di-, monosaccharides and polyols (FODMAPs) contribute to gastrointestinal (GI) symptoms in individuals with FODMAP sensitivity and/or irritable bowel syndrome (IBS). Oral enzyme supplementation is a strategy to reduce dietary FODMAP exposure and limit FODMAP-associated GI distress. This clinical trial investigated the safety of dietary supplementation with a food-grade, microbial inulinase known to hydrolyze fructan-type or inulin-type FODMAPs and related fructo-oligosaccharides (FOS) in vitro. METHODSA randomized, double-blind, placebo-controlled, parallel design trial was conducted in 60 healthy adult participants of both sexes. Following a 2-week run-in placebo phase, participants were randomized to consume inulinase or placebo capsules twice daily with meals for 4 weeks. The total daily dose of inulinase was 2,000 inulinase activity units (INU). Safety measures included blood clinical chemistry, hematology, lipid profile, high-sensitivity C-reactive protein (hs-CRP), insulin, lactate, and uric acid. GI symptoms were recorded weekly using the 15-item Gastrointestinal Symptom Rating Scale (GSRS). RESULTSFifty-eight participants completed the study. There were no clinically meaningful between-group differences in blood biomarkers. During the 4-week intervention period, 5 (16.7%) of 30 participants reported 5 adverse events (AEs) in the inulinase group, and 8 (26.7%) of 30 participants reported 13 AEs in the placebo group. No statistically significant between-group differences were observed in the change from baseline to 1, 2, 3, or 4 weeks of supplementation with respect to GSRS overall or domain scores. CONCLUSIONSMicrobial inulinase supplementation demonstrated a favorable safety profile in healthy adults. Further investigation in a dose-ranging study in individuals with dietary FODMAP, fructan, or inulin sensitivity or IBS is warranted. ClinicalTrials.gov: NCT05744700.

Metabolic brain imaging with glucosamine CEST MRI: in vivo characterization and first insights

The utility of chemical exchange saturation transfer (CEST) MRI for monitoring the uptake of glucosamine (GlcN), a safe dietary supplement, has been previously demonstrated in detecting breast cancer in both murine and human subjects. Here, we studied and characterized the detectability of GlcN uptake and metabolism in the brain. Following intravenous GlcN administration in mice, CEST brain signals calculated by magnetization transfer ratio asymmetry (MTRasym) analysis, were significantly elevated, mainly in the cortex, hippocampus, and thalamus. The in vivo contrast remained stable during 40 min of examination, which can be attributed to GlcN uptake and its metabolic products accumulation as confirmed using 13C NMR spectroscopic studies of brain extracts. A Lorentzian multi-pool fitting analysis revealed an increase in the hydroxyl, amide, and relayed nuclear Overhauser effect (rNOE) signal components after GlcN treatment. With its ability to cross the blood-brain barrier (BBB), the GlcN CEST technique has the potential to serve as a metabolic biomarker for the diagnosis and monitoring various brain disorders.

The Development and Efficacy of a High School Athlete Education Program for Safe Nutritional Supplement Use

Many high school athletes report using nutritional supplements. Due to a lack of education at the high school level, the use of safe for sports third-party tested nutritional supplements may be limited. To determine the impact of a short online nutritional supplement education program on safe dietary supplement behavior a cross-sectional repeated measures design was used. Therefore, a convenience sample of 106 high school athletes (14–19 years old) was recruited to measure pre-post education difference for nutritional supplement use and third-party tested (TPT) supplements. Additionally, it was analyzed if nutritional supplement related Theory of Planned Behavior (TPB) constructs were associated with athlete choices. The most popular supplements included protein powder (65%), caffeine from beverages (45%), and different types of vitamins (ranging from 38–44%). Consistent use of (safe) third-party tested individual supplements was low, ranging from 35–77% for the most frequently reported supplements. The combined TPB determinants explained 26% of the variance of the intention to use safe supplements (F3, 102 = 13.03, p < 0.001, Adj R2 = 0.26). The self-reported intention to use third-party tested supplements increased significantly (+7%–36% per individual supplement) after following the education program (Z = −3.288, p = 0.001) resulting in an intentional use of 54–94% TPT supplements. In conclusion, education resulted in more high school athletes reporting future third-party tested supplements use, and TPB construct scores did not change over time but could explain a substantial part of the variance of safe supplement use intentions.

Preparation of astaxanthin-loaded composite micelles with coaxial electrospray technology for enhanced oral bioavailability and improved antioxidation capability.

Astaxanthin (AST) is approved by the US Food and Drug Administration (FDA) as a safe dietary supplement for humans. As a potent lipid-soluble keto-carotenoid, it is widely used in food, cosmetics, and the pharmaceutical industry. However, its low solubility limits its powerful biological activity and its application in these fields. This study aims to develop a delivery system to address the low solubility and bioavailability of AST and to enhance its antioxidant capacity. Astaxanthin-loaded composite micelles were successfully prepared via coaxial electrospray technology. Astaxanthin existed in the amorphous state in the electro-sprayed formulation with an approximate particle size of 186.28 nm and with a polydispersity index of 0.243. In this delivery system, Soluplus and copovidone (PVPVA 64) were the main polymeric matrix for AST, which then released the drug upon contact with aqueous media, resulting in an overall increase in drug solubility and a release rate of 94.08%. Meanwhile, lecithin, and Polyethylene glycol-grafted Chitosan (PEG-g-CS)could support the absorption of AST in the gastrointestinal tract, assisting transmembrane transport. The relative bioavailability reached about 308.33% and the reactive oxygen species (ROS) scavenging efficiency of the formulation was 44.10%, which was 1.57 times higher than that of free astaxanthin (28.10%) when both were at the same concentration level based on astaxanthin. Coaxial electrospray could be applied to prepare a composite micelles system for the delivery of poorly water-soluble active ingredients in functional food, cosmetics, and medicine. © 2023 Society of Chemical Industry.

P24-076-23 Forging a Way Forward for Safe Dietary Supplement Use: Development of a Mobile App

P24-076-23 Forging a Way Forward for Safe Dietary Supplement Use: Development of a Mobile App

Dietary Supplements for Weight Loss.

The Federal Drug Administration has approved, following rigorous testing, 6 pharmacologic agents and one drug in device form for the management of overweight and obesity. Myriad products that purport to act on physiological mechanisms leading to weight loss also pervade the market with minimal regulatory oversight. Systematic reviews and meta-analyses of these products and their ingredients fail to establish any as meaningfully effective at the clinical level. Moreover, safety concerns prevail with adulteration, hypersensitivity reactions, and recognized adverse reactions. Lifestyle, pharmacologic, and bariatric surgical treatments are increasingly available, effective, and safe management tools for practitioners who should council patients, many of whom are susceptible to misinformation, on the lack effective and safe dietary supplements for weight loss.

Can exercise prevent the age‐related decline in adaptive homeostasis? Evidence across organisms and tissues

Can exercise prevent the age‐related decline in adaptive homeostasis? Evidence across organisms and tissues

Narrative Review: The FDA's Perfunctory Approach of Dietary Supplement Regulations Giving Rise to Copious Reports of Adverse Events.

Background: The Food and Drug Administration (FDA) originated from the passage of the 1906 Pure Food and Drugs act aimed to rein in the long-standing abuse in the consumer product marketplace. The act was passed to prohibit interstate commerce of misbranded and adulterated foods, drinks, drugs. Thus, promoting the FDA's mission to protect the public health by regulating human and veterinary drugs, biological products, medical devices, food supply, cosmetics, and tobacco to ensure safety, efficacy, and security. Progressing further in 1994, the Dietary Supplement Health and Education Act (DSHEA) was established designating specific label requirements, providing regulatory framework, and authorizing the FDA to promulgate good manufacturing practices for dietary supplements. This act defined and classified "dietary supplements" and "dietary ingredients" as food requiring all over the counter products (OTC) products to consist of labeling that is easy to understand and meets the FDA quality, effectiveness, and safety standards. However, under the umbrella of OTC products, the FDA fell short in its regulation of the expansive dietary supplement market. The objective of this study is to discern how the lack of efficacy in the FDA's regulations of OTC dietary supplements inevitably inspired more harm than benefit. Methods: This review comprised of case studies including young adolescents and adult consumers who experienced adverse events from the use of dietary supplements. Products which showed highest prevalence in adverse event reports through the Food and Drug Administration CFSAN Adverse Event Reporting System (CAERS) included but not limited to; Vitamin E (vitamin derivative), Beta-sitosterol (plant sterol) Yohimbine, Kava Kava Kratom, Garcinia Cambogia, (herbal products) and OxyElite Pro (marketed weight loss product). The primary endpoint was evaluating the FDA's regulations on dietary supplement safety protocols. The secondary endpoint was assessing the actions of the FDA in response to these case events. Results: Overall, between 2004 to 2021, a total of 79,071 adverse events related to the use of dietary supplements were reported to the Center for Food Safety and Applied Nutrition. Vitamin E products for example, marketed for decades for their antioxidant benefits in turn have shown significant evidence of toxicity and an increased risk of bleeding outweighing its potential benefit. The FDA's response was simply implementing a label guideline update, yet this update had evidence of minimal effect as the number of cases gradually continued to increase. Likewise, herbal products such as Kava Kava, Yohimbine, Kratom, and Garcinia Cambogia, in addition to weight regulating products, such as OxyElite Pro and HydroxyCut, have been linked to organ failure, hepatic, renal, cardiac toxicity, and death respectively. The FDA merely responded through instating public consumer warnings of their effects with consumption and limited recalls of certain products. Conclusion: With the easy accessibility of these products, the general public is more inclined to its use without proper guidance and monitoring from their healthcare team, posing as a major concern for possible interactions, contraindications and unfavorable outcomes. With proper implementation of stringent regulations post findings from increased studies on efficacy and safety, cases of adverse events could have been reduced significantly or averted completely. The FDA's minimalistic efforts consisting of only post-marketing monitoring and retrospective actions of label modifying have time and time again shown flaws as seen in the growing series of reports. By emending the over-the-counter supplement review process to reflect that of prescription medication, the magnitude of adverse events can be diminished. The process should include preclinical research in addition to clinical research, FDA thorough examination of data prior approval and post marketing surveillance.

Screening of Spirulina Components for Anti-Parkinson's and Anti-Alzheimer's Activity byin Silico Methods and Docking Studies.

Spirulina platensis was first isolated from Lake Texcoco by Aztecs in the sixteenth century. In 2012, spirulina was considered to be safe dietary supplement by the Food and Drug Administration (FDA). Spirulina is a cyanophytic microalgae that is often considered as single cell protein. It contains many essential amino acids, proteins, fatty acids, antioxidant pigments, carotenoids, and cyanogenic pigments, that is, phycocyanobilins and phycocyanins (Eriksen, Appl Microbiol Biotechnol, 80(1):1-4, 2008). Components of spirulina are investigated for many health benefits and for pharmaceutical uses (Karkos et al., Spirulina in clinical practice: evidence-based human applications). Spirulina has been found to have a role in growth, immunity (Wu et al., Arch Toxicol, 90(8):1817-40, 2016), antioxidant (Wu et al., Arch Toxicol, 90(8):1817-40, 2016), antiviral (Ayehunie et al., J Acquir Immune Defic Syndr Hum Retrovirol, 18(1):7-12, 1998), antitoxicologic, anti-cancerogenic (Hirahashi et al., Int Immunopharmacol, 2(4):423-34, 2002), antidiabetic (Layam and Reddy, Diabetol Croat, 35(2):29-33, 2006), and neuroprotective properties. In this study, we focused on spirulina components in anti-Parkinson's and anti-Alzheimer's activity. Four potential targets, two for each activity, that is, structure of parkinE3 ligase (PDB ID:4I1H) and structure of BACE bound to 5-(3-(5-chloropyridin-3-yl)phenyl)-5-cyclopropyl-2-imino-3-methylimidazolidin-4one (PDBI D:4DJx) for anti-Parkinson's activity and structure of human MAO B in complex with selective inhibitor safinamide (PDB ID:2V5Z) and crystal structure of human BACE-1 in complex with CNP520(PDB ID:6EQM) for anti-Alzheimer's activity, have been selected. The in silico results and scoring of virtual screening, that is, molecular docking, were compared with commonly used marketed drugs such as levodopa for Parkinson's disease (PD) and rivastigmine (Rösler et al., BMJ, 318(7184):633-40, 1999) for Alzheimer's disease.

Processes in Doping System: Quantification Reports in Mixed Martial Arts Fighters

Mixed martial arts (MMA) has always been surrounded by controversy due to the unusual muscle development of its participants, so it is crucial to know the strategies that have been implemented to reduce doping cases. The main purpose of this paper is to describe the various cases of doping detected by USADA in UFC MMA participants. In addition, strategies that are being developed to reduce cases of positive doping are proposed. From the UFC USADA database, doping cases were extracted, obtaining the substance or substances involved; the formula, physiological effect and the athletes involved; the dates of the sampling; if it was out of competition or in-competition and the sanction time. The substances that were most involved were found to be Ostarine (22), Clomiphene (9), Diuretics (10) and Stanozolol (9). Some sanctions were diminished because they were treated with contamination of supplements (cases of Ostarine) and cases of contamination of meat (Clomiphene). When contaminated supplements were reported, they were added to the list of high-risk supplements maintained as part of USADA’s online dietary supplement safety education and awareness resource—Supplement 411. There were also cases in which positive doping could be avoided through the early report of therapeutic use exemptions. The methodology that the USADA has implemented allows us to register the athletes with positive doping, check the risk of the supplements before being bought and provide a teaching portal. These efforts are necessary to implement in all countries in which MMA is practiced, avoiding the participation of doped martial artists.

Soluble dietary fiber and cellulose from Saccharina japonica by-product ameliorate Loperamide-induced constipation via modulating enteric neurotransmitters, short-chain fatty acids and gut microbiota

The effects of soluble dietary fiber (SDF) and cellulose (IDF) from Saccharina japonica by-product and their differences in improving constipation were further clarified in the present study. We demonstrated that SDF was mainly made up of d-mannuronic acid and d-mannose while IDF consisted of d-glucose , which is different from other reported dietary fibers of terrestrial plants. In this research, both SDF and IDF improved fecal-related indicators, gastrointestinal transit rate and histological morphology in Lop-induced mice. Moreover, they could increase the level of antioxidant enzymes (SOD and GSH-Px), restore the expression of enteric neurotransmitters, and maintain the function of ZO-1, JAM-1 as well as Occludin. Interestingly, SDF and IDF had a significant up-regulated effect on the proportion of Muribaculacea, Prevotellaceaen and Lachnospiraceae, which are critical to preserving intestinal immune homeostasis. Besides, they promoted the biosynthesis of short-chain fatty acids (SCFAs). The overall index showed that SDF is more effective for constipation due to its better water retention capacity. Thus, they can be used as a safe dietary supplement for the treatment of chronic or occasional constipation in humans.

Evaluation of Effectiveness and Safety of Microcin C7 in Weaned Piglets.

The effects and safety of dietary supplementation with Microcin C7 (C7) were evaluated in 216 weaned piglets. The pigs were given a control corn−soybean meal basal diet or C7 diet (control diet supplemented with 250, 500, 750, 1000, or 5000 mg C7/kg diets). Compared with the control group, the 500 mg/kg C7 supplementation group had better intestinal morphological indicators (p < 0.05), which may help maintain intestinal epithelial function and increase the growth performance (p < 0.05) and apparent total tract digestibility (p < 0.05). The diarrhea indexes of the 250, 500, and 750 mg/kg groups were significantly lower than that of the control group at 0−28 d (p < 0.05), and the 500 mg/kg group had the lowest diarrhea indexes (linear and quadratic, p < 0.05). A comprehensive analysis showed that microbial structure was significantly correlated with the degree of diarrhea, and the diarrhea-alleviating effect of C7 may be related to its selective regulation of specific microbial taxa. The 250 and 500 mg/kg C7 supplementation also significantly improved several immune indices of piglets (p < 0.05). Compared with the control diet, 5000 mg/kg C7 supplementation had no significant adverse effect on all parameters. Overall, the 250−500 mg/kg dose had the best effect, and the highest dose (5000 mg/kg) posed no toxicity risk. Therefore, C7 appears safe for use as an alternative to antibiotic growth promoters in weaned piglets.