Porphyra haitanensis polysaccharide-functionalized selenium nanoparticles for effective alleviation of ulcerative colitis.

Exacerbated intestinal inflammation, oxidative stress imbalance, and damage to intestinal mucosal barrier are closely related to the pathogenesis and progression of ulcerative colitis (UC). Selenium nanoparticles (Se NPs) have demonstrated promising potential to alleviate UC symptoms, however, their poor solubility and stability leading to aggregation and large precipitates have significantly limit their clinical application. In this study, we aimed to enhance the performance of Se NPs by functionalizing them with Porphyra haitanensis polysaccharide, yielding PHP-Se NPs. As expected, these PHP-Se NPs exhibited reduced particle size (70.51 ± 2.92 nm), enhanced cellular uptake compared to native Se NPs, and preferential accumulation in the colonic tissue, providing targeted UC treatment. In vivo animal experiments revealed that PHP-Se NPs significantly improved weight loss, shortened colon length, and higher disease activity index (DAI) scores in DSS-induced UC mice. Moreover, PHP-Se NPs significantly inhibited the levels of inflammatory factors in colitis tissues and oxidative stress in serum of UC mice, improved histological damage in colitis tissues, and restored the intestinal mucosal barrier. Taken together, our study offers an innovative approach to augment the bioavailability of Se NPs, presenting a promising strategy for the effective prevention and management of UC.

Dendrobium offificinale polysaccharides prevents glucocorticoids-induced osteoporosis by destabilizing KEAP1-NRF2 interaction.

Glucocorticoid-induced osteoporosis (GIOP) represents the foremost cause of secondary osteoporosis and fragility fractures. Novel therapeutic strategies for GIOP are needed, with improved safety profiles and reduced costs compared to current options. Dendrobium officinale (D. officinale) is a traditional Chinese medicine that has been reported to have beneficial effects on bone metabolism. Here, we sought to investigate the impacts of D. officinale polysaccharides (DOP), the main active constituents of D. officinale, on GIOP in vivo models and dexamethasone (DEX)-treated osteoblast lineage cells. We found that low concentrations of DOP are relatively safe in vitro and in vivo, respectively. Importantly, we found that DOP treatment significantly inhibited DEX-induced osteoporosis in two in vivo models, zebrafish and mice, while boosting osteogenic differentiation of hBMSCs exposed to DEX. Futhermore, our data reveal that DOP elevates nuclear Nrf2 levels under DEX treatment, by suppressing of Nrf2 ubiquitination. Leveraging Keap1b knockout zebrafish and RNAi approach, we demonstrated that DOP disrupts the association of Nrf2/Keap1, resulting in the inhibition of Nrf2 ubiquitination. Taken together, these results illuminate that DOP stimulates osteogenesis in the presence of DEX by destabilizing the Nrf2/Keap1 interaction. These findings suggest that DOP may serve as a novel drug against osteoporosis caused by glucocorticoids.

Study of anti-fatigue activity of polysaccharide from fruiting bodies of Armillaria gallica.

Fatigue is a common physiological response that is closely related to energy metabolism. Polysaccharides, as excellent dietary supplements, have been proven to have a variety of pharmacological activities. In this study, A 23.007 kDa polysaccharide from Armillaria gallica (AGP) was purified and performed structural characterization, including analysis of homogeneity, molecular weight and monosaccharide composition. Methylation analysis is used to analyze the glycosidic bond composition of AGP. The mouse model of acute fatigue was used to evaluate the anti-fatigue effect of AGP. AGP-treatment improved exercise endurance in mice and reduced fatigue symptoms caused by acute exercise. AGP regulated the levels of adenosine triphosphate, lactic acid, blood urea nitrogen and lactate dehydrogenase, muscle glycogen and liver glycogen of acute fatigue mice. AGP affected the composition of intestinal microbiota, the changes of some intestinal microorganisms are correlated with fatigue and oxidative stress indicators. Meanwhile, AGP reduced oxidative stress levels, increased antioxidant enzyme activity and regulated the AMP-dependent protein kinase/nuclear factor erythroid 2-related factor 2 signaling pathway. AGP exerted an anti-fatigue effect through modulation of oxidative stress, which is related to intestinal microbiota.

Salvia miltiorrhiza polysaccharide and its related metabolite 5-methoxyindole-3-carboxaldehyde ameliorate experimental colitis by regulating Nrf2/Keap1 signaling pathway.

The roots of Salvia miltiorrhiza have been used in Traditional Chinese Medicine for thousands of years. However, tons of aerial parts of this plant are usually discarded in the production of roots preparation. To make better use of these plant resources, the polysaccharide isolated from the aerial part of S. miltiorrhiza was investigated for its potential protection against intestinal diseases. A pectic polysaccharide (SMAP-1) was isolated and characterized being composed of homogalacturonan as the main chain and rhamnogalacturonan type I as ramified region, with side chains including arabinans and possible arabinogalactan type I and II. SMAP-1 exhibited robust protective effects against dextran sodium sulfate (DSS)-induced colitis and restored colitis symptoms, colonic inflammation, and barrier functions. Anti-oxidative effects were also observed by up-regulating Nrf2/Keap1 signaling pathway. Additionally, the level of serum 5-methoxyindole-3-carboxaldehyde (5-MC) was restored by SMAP-1 identified in metabolomic analysis, being correlated with the aforementioned effects. Protection against oxidative stress on intestinal porcine enterocyte cells (IPEC-J2) by 5-MC was observed through the activation of Nrf2/Keap1 system, as also shown by SMAP-1. In conclusion, SMAP-1 could be a promising candidate for colitis prevention, and 5-MC could be the signal metabolite of SMAP-1 in protecting against oxidative stress in the intestine.

Protective effects of black onion polysaccharide on liver and kidney injury in T2DM rats through the synergistic impact of hypolipidemic and antioxidant abilities.

In this study, the synergistic effects of black onion on the hypolipidemic and antioxidant activities in T2DM rats induced by a high-fat-diet and alloxan were investigated. The results showed that the fasting blood glucose of diabetic rats was significantly decreased after treatment with black onion polysaccharide (p < 0.01). Blood lipid analysis indicated that black onion polysaccharide could significantly improve the abnormal metabolism of blood lipids caused by diabetes. In addition, the MDA and ROS of the diabetic rats treated with black onion polysaccharide were significantly reduced; moreover, SOD was increased, indicating the excellent antioxidant activity of black onion polysaccharide. A histological examination clearly showed that black onion polysaccharide could improve the histological morphology of the liver and kidney. Furthermore, the indices of liver and kidney function were restored. These results indicate that black onion polysaccharide can reduce blood glucose and simultaneously show synergistic effects of hypoglycemic and antioxidant activities in diabetic rats. Therefore, black onion polysaccharide may alleviate liver and kidney function injury by improving the "two-hit" mechanism and can thus be used as a potential functional food to prevent diabetes and its complications.

Pectic polysaccharides from Aconitum carmichaelii leaves protects against DSS-induced ulcerative colitis in mice through modulations of metabolism and microbiota composition.

The industrial processing of Aconitum carmichaelii roots for use in Traditional Chinese Medicine generates a high amount of waste material, especially leaves. An acidic polysaccharide fraction isolated from these unutilized leaves, AL-I, was in our previous work shown to contain pectic polysaccharides. This study aimed to investigate the protective effect of AL-I on ulcerative colitis for the possible application of A. carmichaelii leaves in the treatment of intestinal inflammatory diseases. AL-I was found to alleviate symptoms and colonic pathological injury in colitis mice, and ameliorate the levels of inflammatory indices in serum and colon. The production of short- and branched-chain fatty acids was also restored by AL-I. The observed protective effect could be due to the inhibition of NOD1 and TLR4 activation, the promotion of gene transcription of tight-junction proteins, and the modulation of gut microbiota composition like Bacteroides, Dubosiella, Alistipes and Prevotella,. A regulation of serum metabolomic profiles being relevant to the bacterial change, such as D-mannose 6-phosphate, D-erythrose 4-phosphate and uric acid, was also observed.

Polysaccharides derived from Shenling Baizhu San improve colitis via modulating tryptophan metabolism in mice.

Shenling Baizhu San has beneficial effects on the metabolism of the gut microbiota, however, the mechanisms underlying microbiota metabolites mediated anti-inflammation signaling are not well understood. Previously, we have demonstrated that supplementation with Shenling Baizhu San alleviated antibiotic-associated diarrhea (AAD). The current study intends to investigate the dynamic modulation of Shenling Baizhu San polysaccharides (SP) on colitis from the gut microbiota metabolites perspective. Administration of SP effectively relieved colitis induced by DSS in mice, including alleviating body weight loss, the downregulation of colon proinflammatory mediators, and the promotion of intestinal injury repair. Whereas, the efficacy was eliminated by antibiotics, which demonstrated that the efficacy of SP was dependent on the gut microbiota. Fecal microbiota transplantation (FMT) showed that the efficacy of SP can be transferred to gut microbiota. Serum metabolomics analysis showed that supplementation with SP significantly promoted tryptophan metabolism, which was consistent with the changed structure of the gut microbiota, including Bacteroides, Bifidobacterium and Ruminococcus regulated by SP. Especially, the tryptophan metabolites-kynurenine (KYN) activated the expression of amplifying aryl-hydrocarbon receptor (AhR) and Cyp1A1 to promote IL-10 expression in colon. These data suggested that SP positively affected colitis in mice by regulating tryptophan metabolic function of their gut microbiota.

Ginger polysaccharides relieve ulcerative colitis via maintaining intestinal barrier integrity and gut microbiota modulation.

Ulcerative colitis (UC) is an autoimmune disease afflicting an increasing number of patients and increasing demands towards the development of efficacious and safe drugs. Recently, with increasing interest in alternative medicines, natural resources have become a hotspot for drug discovery against UC. In addition to being consumed as a food and spice, ginger is also widely used as a well-recognized gastrointestinal herbal medicine. With a long history in the treatment of digestive disorders, the potential of ginger in alleviating UC has been documented in several experimental models and clinical trials. However, as a major active constituent of ginger, ginger polysaccharides (GP) and its effect on UC has yet to be reported. In this study, GP was firstly separated and characterized. In a dextran sulfate sodium (DSS)-induced colitis mouse model, GP alleviated UC symptoms by inhibiting pro-inflammatory cytokines levels to regulate intestinal inflammation, repairing the intestinal barrier as indicated by occludin-1 and ZO-1, as well as regulating gut microbiota. Taking these results together, we believe GP could be an innovative option in developing functional foods or therapeutic agents for UC management.

Effects of oxidation-based tea processing on the characteristics of the derived polysaccharide conjugates and their regulation of intestinal homeostasis in DSS-induced colitis mice.

Different cultivars and processing technologies involved in producing tea result in the high heterogeneity of derived polysaccharide conjugates, which limits the understanding of their composition and structure, and biological activity. Here, raw tea leaves from the same cultivar were used to produce dried fresh tea leaves, green tea, and black tea, and three polysaccharide conjugates derived from dried fresh tea leaves (FTPS), green tea (GTPS), and black tea (BTPS) were prepared accordingly. Their physiochemical characteristics and bioactivities were investigated. The results showed that the oxidation during tea processing increased the phenolics and proteins while decreasing the GalA in the derived TPS conjugates; meanwhile, it reduced the molecular weight and particle size of BTPS but enhanced their antioxidant activity in vitro. Furthermore, all three TPS conjugates improved intestinal homeostasis by reducing TJ protein loss and inflammation and alleviated DSS-induced colitis symptoms in mice. In addition, the three TPS conjugates showed differential regulation of the intestinal microbiome and altered the produced SCFAs, which contributed to the prevention of colitis. Our findings suggest that TPS conjugates could be applied in colitis prevention in association with the regulation of gut microbiota, and their efficacy could be optimized by employing suitable tea processing technologies.

Efficacy and safety of polysaccharide iron complex capsules compared with iron sucrose in hemodialysis patients: study protocol for a randomized, open-label, positive control, multicenter trial (IHOPE).

BACKGROUND: Anemia is one of the main complications of chronic kidney disease especially kidney failure, which includes treatment with erythropoiesis-stimulating agents and iron supplementation, including intravenous and oral iron. However, intravenous iron may pose limitations, such as potential infusion reactions. Oral iron is mainly composed of divalent iron, which can excessively stimulate the gastrointestinal tract. Iron polysaccharide complex capsules are a novel oral iron trivalent supplement with higher iron content and lower gastrointestinal irritation. However, since high-quality evidence-based medicinal support is lacking, it is necessary to conduct clinical studies to further evaluate the effectiveness and safety of oral iron polysaccharide complex in chronic kidney disease patients. METHODS: This randomized controlled trial uses an open-label, parallel group design, where the efficacy and safety of maintenance hemodialysis (MHD) participants is evaluated. The experimental group is assigned erythropoietins and iron polysaccharide complex (two capsules each time, bid), and the control group is assigned erythropoietin and sucrose iron (100mg, 2w) injection. Participants (aged 18-75 years) undergoing maintenance hemodialysis were considered for screening. Inclusion criteria included hemoglobin (Hb) ≥110g/L and < 130g/L, transferrin saturation (TSAT) > 20% and < 50%, and serum ferritin (SF) > 200µg/L and < 500µg/L. Exclusion criteria included acute or chronic bleeding, serum albumin < 35g/L, hypersensitive C-reactive protein (HsCRP) > 10 mg/L, and severe secondary hyperparathyroidism (iPTH ≥ 800 pg/mL). Full inclusion and exclusion criteria are described in the "Methods" section. The primary endpoint is TSAT of the participants at week 12. Secondary endpoints include Hb, SF, hematocrit (Hct), HsCRP, pharmacoeconomic evaluation, drug costs, quality of life, and indicators of oxidative stress. The treatment will last for 24 weeks with a follow-up visit at baseline (within 7 days prior to initial treatment) and weeks 4, 8, 12, 16, 20, and 24 after initial treatment. This clinical research includes 9 hemodialysis centers in mainland China and plans to enroll 186 participants. DISCUSSION: It is expected that it will provide strong evidence to reveal the clinical efficacy and safety of oral iron in the treatment of chronic CKD-related anemia in MHD patients through this clinical trial. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000031166 . Registered on March 23, 2020.

Anti-cerebral ischemia reperfusion injury of polysaccharides: A review of the mechanisms.

Cerebral ischemia-reperfusion injury can lead to a series of serious brain diseases and cause death or different degrees of disability. Polysaccharide is a kind of biological macromolecule with multiple pharmacological activities and has been proven that it may be used for the treatment of cerebral I/R injury in the future. By sorting out all relevant research from 2000 to 2020, we selected 74 references and identified 22 kinds of polysaccharides. Almost all of these polysaccharides are extracted from traditional Chinese medicine. Research shows that these polysaccharides can improve cerebral ischemia-reperfusion injury through anti-oxidative stress, inhibiting the neuroinflammation, glutamate neurotoxicity and neuronal apoptosis, and exerting neurotrophic effect. The specific mechanisms include clearing ROS and RNS, inhibiting the expression of inflammatory factors, maintaining mitochondrial homeostasis and blocking caspase cascade, regulating NMDA receptor and promoting angiogenesis. We hoped this review is instructive for researchers to design, research and develop polysaccharides.

Effects of Polysaccharide from Malus halliana Koehne Flowers in Cyclophosphamide-Induced Immunosuppression and Oxidative Stress on Mice.

The immunomodulatory effects of Malus halliana flower polysaccharide (MHFP) were investigated in this paper. The model of immunosuppressive mice was established by cyclophosphamide, which was treated with different dosages of MHFP (600, 400, and 200 mg/kg·d-1). The results showed that MHFP significantly increased the index of the spleen and thymus and improved the atrophy of immune organs. MHFP enhanced the ability of carbon clearance and phagocytosis of mononuclear phagocytes in mice. Meanwhile, MHFP promoted the proliferation of splenic lymphocytes. MHFP could enhance the content of serum hemolysin and improve the decrease of hemolysin induced by cyclophosphamide. The contents of ACP and LDH in the serum and spleen were determined, indicating that MHFP could enhance the activity of macrophages. MHFP promoted the content of cytokines (IL-2, IL-6, TNF-α, and IFN-γ) and mRNA expression. At the same time, the pathological changes of the spleen tissue also showed that MHFP could improve the immunosuppression induced by cyclophosphamide. In addition, MHFP increased the content of SOD, T-AOC, and CAT in the serum and spleen tissue, decreased the level of MDA, and improved the oxidative stress caused by cyclophosphamide. In conclusion, MHFP could effectively improve the immunosuppression and oxidative stress induced by cyclophosphamide and enhance the immune capacity of mice.

The 25(OH)Vitamin D Status Affected the Effectiveness of Oligo Fucoidan in Patients with Chronic Hepatitis B Virus Infection with Immune Tolerance Phase.

Chronic hepatitis B virus (HBV) infection is a serious public health issue. Vitamin D is involved in various pathophysiological mechanisms as an immune modulator and the deficiency rate of vitamin D is prevalent in chronic liver disease. Fucoidan exerts anti-inflammatory, anticoagulant, antitumor, antimetastatic, and antiangiogenetic effects; however, its effect on the immune responses of HBV patients is unclear. This study investigated how 25(OH)Vitamin D status affected the effectiveness of oligo fucoidan in patients with HBV infection in the immune tolerance phase. Fifty-one patients received oligo fucoidan 4400 mg/day for 48 weeks. Flow cytometry was used to detect T lymphocyte markers (CD3+CD4+, CD3+CD8+, CD4+CD45RO+, CD8+CD45RO+). The levels of white blood cell (WBC), platelets (PLT), and albumin were decreased after 48 weeks of supplementation (p < 0.05). Percentages of CD3+CD8+ and CD8+CD45RO+ cells were decreased after 12 weeks of supplementation (p < 0.05). In patients with adequate vitamin D, HBV-DNA concentrations decreased and the proportion of CD4+CD45RO+ and CD8+CD45RO+ cells increased upon oligo fucoidan supplementation. The HBeAg status of one vitamin D-adequate patient changed from positive to negative at the 12th week of supplementation. The oligo fucoidan may regulate immune effects in patients with HBV infection, and the 25(OH)Vitamin D status might have affected the effectiveness of oligo fucoidan.

High-level expression of an acidic thermostable xylanase in Pichia pastoris and its application in weaned piglets.

An acidic thermostable xylanase (AT-xynA) which was stable at low pH and high temperature was considered to have great potential in animal feed. For large-scale production, AT-xynA activity was enhanced about 1-fold in Pichia pastoris by constructing a double-copy expression strain in this study. Furthermore, impacts of different AT-xynA levels on growth performance, nutrient digestibility, short-chain fatty acids, and bacterial community in weaned piglets were determined. Compared with the control group, ADFI and ADG were higher for the pigs fed 4,000 or 6,000 U/kg AT-xynA (P < 0.05). AT-xynA supplementation also significantly increased the digestibility of OM, GE, and DM (P < 0.05). AT-xynA supplementation increased the concentrations of acetate in ileal (P < 0.01) and cecal digesta (P < 0.05). Isobutyrate (P < 0.05) and valerate (P < 0.05) concentrations in colonic digesta also significantly increased compared with the control group. AT-xynA supplementation increased the abundance of Lactobacillus in the ileal, cecal, and colonic digesta of weaned piglets (P < 0.05). AT-xynA alleviated anti-nutritional effects of nonstarch polysaccharides (NSP) by preventing the growth of Pateurella and Leptotrichia in the ileum (P < 0.05). AT-xynA increased the abundance of NSP-degrading bacteria, such as Ruminococcaceae, Prevotella in the cecum and colon (P < 0.05). In summary, AT-xynA addition could improve the growth performance of weaned piglets by altering gut microbiota.

Development, in vitro biocompatibility, and antitumor efficacy of acetic acid-modified Cordyceps sinensis polysaccharide nanoparticle drug delivery system

Docetaxel-loaded acetic acid conjugated Cordyceps sinensis polysaccharide (DTX-AA-CSP) nanoparticles were prepared through dialysis and their release rates in vitro, particle sizes, zeta potentials, drug loading capacities, and encapsulation efficiencies were characterized for the synthesis of AA-modified CSPs from traditional Chinese medicine Cordyceps sinensis (Berk.) Sacc. Then, the AA-modified CSPs were characterized by 1H-NMR and FT-IR. Furthermore, the biocompatibility of the delivery carrier (AA-CSP nanoparticles) was assessed on human umbilical vein endothelial cells. In vitro antitumor activity studies on DTX-AA-CSP nanoparticles were conducted on the human liver (HepG2) and colon cancer cells (SW480). The DTX-AA-CSP nanoparticles were spherical and had an average size of 98.91±0.29 nm and zeta potential within the −19.75±1.13 mV. The encapsulation efficiency and loading capacity were 80.95%±0.43% and 8.09%±0.04%, respectively. In vitro, DTX from the DTX-AA-CSP nanoparticles exhibited a sustained release, and the anticancer activities of DTX-AA-CSP nanoparticles against SW480 and HepG2 were significantly higher than those of marketed docetaxel injection (Taxotere®) in nearly all the tested concentrations. The AA-CSP nanoparticles showed good biocompatibility. This study provided a promising biocompatible delivery system for carrying antitumor drugs for cancer therapy

Effect of a Fucoidan Extract on Insulin Resistance and Cardiometabolic Markers in Obese, Nondiabetic Subjects: A Randomized, Controlled Trial.

OBJECTIVES: To determine whether a fucoidan extract reduced insulin resistance and/or altered other cardiometabolic markers in an obese, nondiabetic population. DESIGN: Single-site, double-blinded, placebo-controlled, randomized controlled trial. SETTING/LOCATION: Hobart, Tasmania, Australia. SUBJECTS: Eligible subjects were obese, with no history of diabetes, and ages between 18 and 65 years. INTERVENTIONS: Subjects were randomly assigned, in even blocks of 10, to either active fucoidan 500 mg or placebo capsules twice daily for 90 days, with identical measurements performed at baseline and follow-up. OUTCOME MEASURES: The primary outcome was insulin resistance, defined by the homeostasis model of assessment (HOMA) values. Secondary outcomes were lipid profile, glycosylated hemoglobin, urea electrolytes and creatinine, liver function tests, full/complete blood count, fasting insulin, fasting glucose, quantitative insulin sensitivity check index, glucose area under the curve, weight, body mass index, waist circumference, and systolic and diastolic blood pressure. The trial was registered with the Australian New Zealand Clinical Trial Registry (ACTRN12614000495628) and the Therapeutic Goods Administration (2014/0348), and was funded by Marinova Pty. Ltd. RESULTS: There were no differences in the 90-day outcome measures between placebo and active treatment in the intention-to-treat-analysis (n = 35 for active, n = 37 for placebo). The mean change in HOMA scores was 0 for the placebo and -0.1 for the active groups (p = 0.73). Self-reported adherence was high, consistent with capsule counting at the conclusion of the trial. CONCLUSIONS: Fucoidan taken twice daily for a period of 90 days did not markedly affect insulin resistance or other measured parameters of cardiometabolic health in an obese, nondiabetic cohort. This could be due to an intrinsic lack of efficacy, lower than measured adherence, or because longer therapy and/or higher baseline insulin resistance are required to exert a significant effect.

The Risk of Necrotizing Enterocolitis Differs Among Preterm Pigs Fed Formulas With Either Lactose or Maltodextrin.

OBJECTIVES: When breast milk is unavailable for preterm infants, formulas are needed that won't increase the risk of necrotizing enterocolitis (NEC). Adding novel ingredients to formula to reduce NEC has not been effective clinically. Instead, we tested the prediction that NEC can be reduced by removing the maltodextrin now included in preterm formulas. METHODS: The preterm pig model of spontaneous NEC was used to evaluate growth, health, and intestinal responses to 6 to 7 days of feeding formulas that were identical except for the source of carbohydrate; either 100% lactose or maltodextrin; colostrum was used as the control. RESULTS: Formula with maltodextrin resulted in a 50% incidence of NEC with 30% mortality. The lactose formula and colostrum resulted in a 0% incidence of NEC. Growth was highest for pigs fed the formula with lactose, intermediate with maltodextrin, and minimal when bovine colostrum was fed (P < 0.05). Although the small intestine was larger when colostrum was fed (P < 0.05), because rates of glucose uptake were lower (P < 0.05), total small intestine capacities to transport glucose were similar for healthy pigs in all 3 groups. CONCLUSIONS: If lactose-based formulas reduce NEC clinically, the transition of preterm infants to enteral feeding can be accelerated, improving growth and development, and shortening reliance on parenteral nutrition. Although colostrum protects against NEC, chronic feeding does not promote body weight gain after preterm birth. The preterm pig can be used for preclinical studies that evaluate the mechanisms by which carbohydrates and other ingredients influence growth, development, health, and risk of NEC.

Fructans Exacerbate Symptoms in a Subset of Children With Irritable Bowel Syndrome.

BACKGROUND & AIMS: Dietary fructans exacerbate symptoms in some, but not all, adults with irritable bowel syndrome (IBS). We sought to determine whether fructans worsen symptoms in children with IBS and whether clinical and psychosocial factors, and/or gas production, can identify those who are fructan sensitive. METHODS: We performed a double-blind placebo-controlled (maltodextrin) cross-over trial of 23 children with IBS, based on pediatric Rome III criteria, from September 2014 through December 2016. At baseline, participants completed 1-week pain and stool diaries and a 3-day food record and psychosocial factors (depression, anxiety, and somatization) were measured. Subjects were randomly assigned to groups that were provided meals for 72 hours containing either fructans or maltodextrin (0.5 g/kg; maximum, 19 g). Following a washout period of 10 days or more, the subjects received the meal they were not given during the first study period (crossed over). Gastrointestinal symptoms and breath hydrogen and methane production were captured during each meal period. Fructan sensitivity was defined as an increase of 30% or more in abdominal pain frequency following fructan ingestion. RESULTS: Subjects had more mean episodes of abdominal pain/day during the fructan-containing diet (3.4 ± 2.6) vs the maltodextrin-containing diet (2.4 ± 1.7) (P < .01), along with more severe bloating (P < .05) and flatulence (P = .01). Hydrogen (but not methane) production was greater while subjects were on the fructan-containing diet (617 ± 305 ppm∗h) than the maltodextrin-containing diet (136 ± 78 ppm*h) (P < .001). Eighteen subjects (78.2%) had more frequent abdominal pain while on the fructan-containing diet and 12 (52.2%) qualified as fructan sensitive. We found no difference between fructan-sensitive and fructan-insensitive subjects in baseline abdominal pain or bowel movement characteristics, dietary intake, psychosocial parameters, IBS subtype, or gas production. CONCLUSIONS: In a randomized controlled trial of children with IBS, we found fructans to exacerbate several symptoms. However, fructan sensitivity cannot be identified based on baseline gastrointestinal symptoms, dietary intake, psychosocial factors, or gas production. Clinicaltrials.gov no: NCT02842281.

Genotoxicity and 28-day oral toxicity studies of a functional food mixture containing maltodextrin, white kidney bean extract, mulberry leaf extract, and niacin-bound chromium complex.

Steady-fiber granule (SFG) is a functional food mixture that is composed of four major ingredients, resistant maltodextrin, white kidney bean (Phaseolus vulgaris) extract, mulberry leaf (Morus alba L.) extract, and niacin-bound chromium complex. This study focused on determining the safety of SFG. Genotoxicity and 28-day oral toxicity were evaluated. SFG did not induce mutagenicity in the bacterial reverse mutation assay using five Salmonella typhimurium strains (TA98, TA100, TA102, TA1535, and TA1537) in the presence or absence of metabolic activation (S9 system). SFG also did not induce clastogenic effects in Chinese hamster ovary cells with or without S9 treatment. Similarly, SFG did not induce genotoxicity in a micronucleus test conducted with mice. A dose-dependent 28-day oral toxicity assessment of SFG for rats revealed no significant effects on mortality, body weight, selected organ weights, and behavior. Evaluations of hematology, clinical biochemistry, and histopathology showed no adverse effects in rats treated with SFG. These results suggest that SFG has no significant mutagenic or toxic properties, and the no observed adverse effect level of SFG was defined as at least 5000 mg/kg/day orally for 28 days for male and female rats.

The Effect of Undaria pinnatifida Fucoidan on the Pharmacokinetics of Letrozole and Tamoxifen in Patients With Breast Cancer.

BACKGROUND: Although the use of complementary and alternative medicines is widespread in cancer patients, clinical evidence of their benefits is sparse. Furthermore, while they are often assumed to be safe with regard to concurrent use of anticancer therapies, few studies have been carried out to investigate possible interactions. Fucoidans are a group of sulfated carbohydrates, derived from marine brown algae, which have long been used as dietary supplements due to their reported medicinal properties, including anticancer activity. The aim of this study was to investigate the effect of co-administration of fucoidan, derived from Undaria pinnatifida, on the pharmacokinetics of 2 commonly used hormonal therapies, letrozole and tamoxifen, in patients with breast cancer. METHODS: This was an open label non-crossover study in patients with active malignancy taking letrozole or tamoxifen (n = 10 for each group). Patients took oral fucoidan, given in the form of Maritech extract, for a 3-week period (500 mg twice daily). Trough plasma concentrations of letrozole, tamoxifen, 4-hydroxytamoxifen, and endoxifen were measured using HPLC-CAD (high-performance liquid chromatography charged aerosol detector), at baseline and after concomitant administration with fucoidan. RESULTS: No significant changes in steady-state plasma concentrations of letrozole, tamoxifen, or tamoxifen metabolites were detected after co-administration with fucoidan. In addition, no adverse effects of fucoidan were reported, and toxicity monitoring showed no significant differences in all parameters measured over the study period. CONCLUSIONS: Administration of Undaria pinnatifida fucoidan had no significant effect on the steady-state trough concentrations of letrozole or tamoxifen and was well tolerated. These results suggest that fucoidan in the studied form and dosage could be taken concomitantly with letrozole and tamoxifen without the risk of clinically significant interactions.