Mannan oligosaccharides selenium ameliorates intestinal mucosal barrier, and regulate intestinal microbiota to prevent Enterotoxigenic Escherichia coli -induced diarrhea in weaned piglets.

Enterotoxigenic Escherichia coli (ETEC) is a common diarrheal pathogen in humans and animals. To prevent and treat ETEC induced diarrhea, we synthesized mannan oligosaccharide selenium (MOSS) and studied its beneficial effect on ETEC-induced diarrhea. A total of 32 healthy weaned piglets (6.69 ± 0.01 kg) were randomly divided into four groups: NC group (Basal diet), MOSS group (0.4 mg/kg MOSS supplemented diet), MOET group (0.4 mg/kg MOSS supplemented diet + ETEC treatment), ETEC group (ETEC treatment). NC and ETEC group fed with basal diet, MOSS and MOET group fed with the MOSS supplemented diet. On the 8th and 15th day of the experiment, MOET and ETEC group were gavaged with ETEC, and NC and MOSS group were gavaged with stroke-physiological saline solution. Our data showed that dietary MOSS supplementation increased average daily gain (ADG) and average daily feed intake (ADFI) and significantly decreased diarrhea index and frequency in ETEC-treated piglets. MOSS did not affect the α diversity and ß diversity of ileal microbial community, but it significantly decreased the proportion of lipopolysaccharide biosynthesis in ileal microbial community. MOSS supplementation regulated colonic microbiota community composition, which significantly increased carbohydrate metabolism, and inhibited lipopolysaccharide biosynthesis pathway in colonic microbial community. Moreover, MOSS significantly decreased inflammatory stress, and oxidative stress in ETEC treated piglets. Furthermore, dietary MOSS supplementation significantly decreased intestinal barrier permeability, and alleviated ETEC induced intestinal mucosa barrier irritation. In conclusion, our study showed that dietary MOSS supplementation ameliorated intestinal mucosa barrier, and regulated intestinal microbiota to prevent ETEC induced diarrhea in weaned piglets.

Development and characterization of a novel conjugated methamphetamine vaccine.

BACKGROUND: Methamphetamine (METH) addiction is a major public health concern globally with limited management options. The development of a METH vaccine through hapten design has received significant attention as a promising platform for the potential treatment of METH addiction and overdose, however there is yet to be a successful candidate in human trials. RESEARCH DESIGN AND METHODS: In this study, we developed a novel conjugated METH vaccine using oxidized mannan (a polymannose) as an immunogenic carrier. A METH hapten was synthesized by using amphetamine and conjugated to mannan with a (Lysine-Glycine-Lysine-Glycine-lysine-Glycine-Lysine-Glycine-Lysine-Glycine) (KG)5 peptide linker. RESULTS: The reaction between amphetamine and (KG)5, oxidation of mannan, and conjugation of amphetamine-(KG)5 with oxidized mannan were confirmed by color tests, Fourier-transform infrared spectroscopy, gas and liquid chromatography mass spectrometry, thin-layer chromatography, and ultraviolet spectrophotometer. Additionally, the ability of the vaccine to generate antibodies was confirmed in C57BL/6 mice. CONCLUSIONS: The successful development and characterization of the METH-mannan conjugate vaccine, provides a potential therapeutic intervention to curb METH substance use disorders. Each step of vaccine development was characterized to aid in future research on these vaccines, and the immunogenicity shown in the animal models supports future evaluation of the approach. Future studies of the conjugated METH vaccine should evaluate the efficacy in animal models of acute and chronic METH to pave the way for human studies.

Comparative effects of different enzymatic hydrolysates of konjac glucomannan on gut flora and constipation in rats.

This study aimed to compare the effects of different hydrolysates (named GKOS and MKOS) on constipated rats, which were obtained by degradation from konjac glucomannan by ß-glucanase and ß-mannanase, respectively. GKOS and MKOS were characterized and administered by gavage at 100 mg kg-1 to constipated rats. The variation of the gut flora, content of short-chain fatty acids (SCFAs), defecation function, gastrointestinal motility, and intestinal mucus secretion were determined to evaluate their regulatory effects on constipation. The results revealed the more prominent augmentation of species richness in MKOS than with GKOS. They also possessed diverse modulatory effects on different genera, such as Prevotella and Parabacteroides. Unexpectedly, there was no statistical divergence between GKOS and MKOS in defecation parameters, gastrointestinal transit, serum parameters, and mucous secretion. Overall, MKOS and GKOS exhibited differential regulatory function on gut microbiota in vivo, but with nearly consistent therapeutic effects on constipation.

Continuous partially hydrolyzed guar gum intake reduces cold-like symptoms: a randomized, placebo-controlled, double-blinded trial in healthy adults.

OBJECTIVE: Partially hydrolyzed guar gum (PHGG), a water-soluble dietary fiber produced by the controlled partial enzymatic hydrolysis of guar gum beans, has various physiological roles. PHGG is expected to influence the immune function and prevent infections. The objective of this study was to examine the effect of continuous ingestion of PHGG for 12 weeks on the development of cold-like symptoms. PATIENTS AND METHODS: A placebo-controlled, double blind, randomized, parallel-group comparative study was conducted. 96 healthy Japanese adults received 5.2 g PHGG or placebo daily for 12 weeks. Cold-like symptoms were assessed based on patient diary, and the levels of short-chain fatty acids (SCFAs) in stool and blood immune markers at baseline and at weeks 6 and 12. RESULTS: The cumulative number of "no symptoms" days for all symptoms was significantly larger in the PHGG than in the placebo group. The result of the analysis by severity of cold-like symptoms also showed significant differences, with the PHGG group having a lower severity of cold-like symptoms. Propionic acid at weeks 6 and 12 and n-butyric acid and total SCFAs at week 12 were significantly higher in the PHGG than in the placebo group. The Interferon-γ level was significantly lower at week 6 in the PHGG than in the placebo group. CONCLUSIONS: PHGG intake may affect immune function and suppress cold-like symptoms through the production of SCFAs in healthy adults.

Bacillus amyloliquefaciens BLCC1-0238 Alone or in Combination with Mannan-Oligosaccharides Alleviates Subclinical Necrotic Enteritis in Broilers.

Subclinical necrotic enteritis (SNE) is a severe intestinal disease in broilers which brings huge economic losses to poultry industry. Herein, the effects of Bacillus amyloliquefaciens BLCC1-0238 (B. amyloliquefaciens BLCC1-0238) alone or in combination with mannan-oligosaccharides (MOS) on the SNE challenge model in broilers were comprehensively explored. A total of 360 broilers were randomly divided into 4 groups, including an SNE infection control (IC), an antibiotic pretreatment control (AC), a B. amyloliquefaciens BLCC1-0238 pretreatment (BP), and a B. amyloliquefaciens BLCC1-0238 + MOS pretreatment (BMP). The results showed that compared with the IC, three pretreatment groups significantly improved the growth performance, lowered the overall mortality, and reduced intestinal mucosal lesions in broilers. Additionally, the expression levels of claudin-3 and peroxisome proliferator-activated receptor-gamma coactivator-1α in the BP and BMP groups and the levels of mucin-2 and mechanistic target of rapamycin in the BMP group were significantly upregulated compared with the IC. By contrast, the expression levels of interferon-γ, interleukin-10, and secretory immunoglobulin A in the BP and BMP groups were significantly downregulated. In conclusion, these findings show that B. amyloliquefaciens BLCC1-0238 in combination with MOS can exert synergetic effects by the interplay between them on improving growth performance and combating the SNE infection in broilers.

Anti-SARS-CoV-2 Activity of Rhamnan Sulfate from Monostroma nitidum.

The COVID-19 pandemic is a major human health concern. The pathogen responsible for COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), invades its host through the interaction of its spike (S) protein with a host cell receptor, angiotensin-converting enzyme 2 (ACE2). In addition to ACE2, heparan sulfate (HS) on the surface of host cells also plays a significant role as a co-receptor. Our previous studies demonstrated that sulfated glycans, such as heparin and fucoidans, show anti-COVID-19 activities. In the current study, rhamnan sulfate (RS), a polysaccharide with a rhamnose backbone from a green seaweed, Monostroma nitidum, was evaluated for binding to the S-protein from SARS-CoV-2 and inhibition of viral infectivity in vitro. The structural characteristics of RS were investigated by determining its monosaccharide composition and performing two-dimensional nuclear magnetic resonance. RS inhibition of the interaction of heparin, a highly sulfated HS, with the SARS-CoV-2 spike protein (from wild type and different mutant variants) was studied using surface plasmon resonance (SPR). In competitive binding studies, the IC50 of RS against the S-protein receptor binding domain (RBD) binding to immobilized heparin was 1.6 ng/mL, which is much lower than the IC50 for heparin (~750 ng/mL). RS showed stronger inhibition than heparin on the S-protein RBD or pseudoviral particles binding to immobilized heparin. Finally, in an in vitro cell-based assay, RS showed strong antiviral activities against wild type SARS-CoV-2 and the delta variant.

The edible Lactobacillus paracasei X11 with Konjac glucomannan promotes intestinal motility in zebrafish.

BACKGROUND: Constipation is a gastrointestinal symptom with high incidence rate and large number of patients. It is becoming one of the urgent medical problems. Poor intestinal motility is one of the important causes of constipation. Current drug treatments for constipation are associated with many side effects; thus, it is necessary to study more effective treatment methods and potential mechanism. METHODS: A zebrafish model of intestinal motility obstruction was established by loperamide hydrochloride to evaluate the effect of probiotic, food ingredients, and combination on intestinal peristalsis according to intestinal peristalsis frequency counts. The gastrointestinal survival ability of the best probiotics was evaluated by surface hydrophobicity, self-aggregation, acid and bile salt tolerance, and gastrointestinal transit tolerance. Interactions between probiotics and food ingredients were studied in vivo and in vitro. The expression of 5-HT was detected by ELISA and fluorescence immunoassay, and 5-HT related genes were detected by RT-PCR. KEY RESULTS: We obtained the probiotics, food ingredients, and combination that effectively promoted intestinal peristalsis, X11 and YRL577, P. persica and KGM, KGM + X11, respectively. Both KGM and P. persica promoted colonization of probiotics in vivo. KGM + X11 could effectively promote the increase in 5-HT synthesis in zebrafish via up-regulating gene expression of TPH-1, TPH-2, and 5-HTR and down-regulating gene expression of SERT. The specific in-depth mechanism needs further study. CONCLUSIONS AND INFERENCES: The combinations of KGM with X11 effectively promoted intestinal peristalsis. We provide a theoretical basis for new modalities that can promote intestinal peristalsis and alleviate constipation.

Heteropolysaccharides from S. cerevisiae show anti-adhesive properties against E. coli associated with Crohn's disease.

The Saccharomyces cerevisiae CNCM I-3856 was previously reported to strongly inhibit adherent-invasive Escherichia coli (AIEC) adhesion to intestinal epithelial cells in vitro and to favor AIEC elimination from the gut in a murine model of Crohn's disease in vivo. In order to identify which cell wall components of yeast are responsible for AIEC elimination, constituent polysaccharides of yeast were isolated and their anti-adhesive ability against AIEC adhesion in vitro was screened. A fraction containing mannan, ß-glucan and α-glucan extracted from yeast cell-walls was shown to inhibit 95% of AIEC adhesion in vitro and was thus identified as the strongest anti-adhesive yeast cell wall component. Furthermore, this mannan-glucan-containing fraction was shown to accelerate AIEC decolonization from gut in vivo. This fraction could be proposed as a treatment to eliminate AIEC bacteria in patients with Crohn's disease, a microbial trigger of intestinal inflammation.

Efficacy and tolerability of a novel galactomannan-based formulation for symptomatic treatment of gastroesophageal reflux disease: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: Proton Pump Inhibitors (PPIs) and traditional antacids are the common standard set of therapy for the management of gastroesophageal reflux disease (GERD) symptoms. The aim of the current study was to evaluate efficacy and safety of a novel galactomannan-based liquid formulation in reducing typical GERD symptoms in patients not taking PPIs. PATIENTS AND METHODS: This was a single-center, randomized, double-blind, placebo-controlled study. Sixty patients met the eligibility criteria and were treated either with the investigational product (RefluG™) or placebo, one sachet three times per day for 14 consecutive days. Symptom intensity/frequency and quality of life were assessed over the course of the study by Reflux Disease Questionnaire (RDQ) and GERD-Health related Quality of life (HRQL) Questionnaire, respectively. The primary endpoint was to determine the number of subjects with at least 30% symptoms reduction from baseline to day 14 compared to placebo. RESULTS: RefluG™ was statistically superior to placebo (p <0.001) as 100% of subjects experienced at least 30% symptoms reduction at the end of the study while none achieved a 30% reduction in the placebo group. For all domains both after 7 and 14 days of treatment, significant improvement in HRQL was seen in the active group in comparison to placebo. Tolerability and safety were good and comparable between groups. CONCLUSIONS: The investigational product was safe and effective as mono-therapy in providing early resolution of troublesome GERD symptoms as well as for improving quality of life.

Effect of konjac glucomannan on metabolites in the stomach, small intestine and large intestine of constipated mice and prediction of the KEGG pathway.

The occurrence of constipation involves the whole gastrointestinal tract. Konjac glucomannan (KGM) has been clinically proven to alleviate constipation, but its mechanism has not been fully understood. The present study aimed to investigate the excretion-promoting effect of KGM on constipated mice and the underlying molecular mechanism. In this study, the UHPLC-QE orbitrap/MS method was used to determine the metabolic phenotypes of total gastrointestinal segments (i.e., the stomach {St}, small intestine {S}, and large intestine {L}) in constipated mice treated with KGM. The results showed that KGM improved the fecal water content, body weight growth rate, and serum gastrointestinal regulation related peptide levels. The metabolomics results revealed the decreased levels of amino acids, cholines, deoxycholic acid, arachidonic acid, thiamine and the increased levels of indoxyl sulfate, histamine, linoelaidic acid etc. The KEGG pathway analysis indicated that the relaxation effect of KGM supplementation was most likely driven by modulating the expression levels of various key factors involved in biosynthesis of amino acid (i.e., phenylalanine, tyrosine and tryptophan), linoleic acid metabolism, biosynthesis of secondary metabolites, and arachidonic acid metabolism signalling pathways. The results indicated that KGM alleviates constipation by regulating potential metabolite markers and metabolic pathways in different gastrointestinal segments.

Fibers in pediatric functional gastrointestinal disorders. Practical considerations from clinical cases.

Introduction: Functional gastrointestinal disorders (FGIDs) are common in children and incur high direct and indirect social costs. Partially hydrolyzed guar gum (PHGG) is a natural and water-soluble dietary fiber that is derived from guar gum. It has been proposed as complementary therapy in pediatric FGIDs, especially in chronic functional constipation and irritable bowel syndrome.Areas covered: By focusing on four clinical cases, this article illustrates the use of PHGG fiber as sole supplement ingredient or as a formula component in orally- and tube-fed children suffering from malnutrition due to FGIDs, with or without special medical conditions such as neurological disability. The formula used was a whey peptide-based nutritionally complete formula containing PHGG as a source of soluble dietary fiber. It was offered under medical supervision and after full consideration of all feeding options.Expert opinion: Implementing appropriate feeding behaviors, adapted to age and potential comorbidities, is an essential requisite for therapeutic management of FGIDs. The use of a PHGG supplement or a nutritionally complete formula containing PHGG as a source of soluble dietary fiber can be helpful to manage pediatric FGIDs.

Galactomannan of Delonix regia seeds reduces nociception and morphological damage in the rat model of osteoarthritis induced by sodium monoiodoacetate.

This study investigated the effects of the protein-free galactomannan obtained from Delonix regia seeds (GM-DR) in an experimental osteoarthritis (OA) model. GM-DR was obtained from water-homogenized endosperms by collection of the supernatant and precipitation with ethanol. The remaining proteins in the galactomannan were removed by alkaline hydrolysis. Weight average molar mass (Mw) of the galactomannan was estimated in 5.8 × 105 g mol-1, presenting mannose:galactose ratio of 2.39:1. Rats received sodium monoiodoacetate (OA groups, 1 mg/25 µL) or saline (sham group) in the right tibio-tarsal joint. GM-DR (30-300 µg) was administered by intra-articular route at days 14 and 21 after OA induction. Hypernociception was evaluated daily by the measurement of the mechanical threshold required to cause joint flexion and paw withdrawal reflex. The 56-day animal groups were euthanized for joint histopahological analysis using the OARSI score system. Lower doses of GM-DR (30 and 100 µg) promoted antinociception from day 15 until the endpoint at day 56. Joint damage was reduced by GM-DR administration (100 µg) in OA-subjected animals, compared to the vehicle-treated OA group (5.9 ± 1.8 vs 19.0 ± 1.8, respectively, p < 0.05). Conclusion: Both antinociception and damage reduction suggest that Delonix regia galactomannan is a promising approach for osteoarthritis therapy.

Comparison of the Effect of Ceratonia siliqua L. (Carob) Syrup and Vitamin E on Sperm Parameters, Oxidative Stress Index, and Sex Hormones in Infertile Men: a Randomized Controlled Trial.

Herbal products with an antioxidant capacity can boost male reproductive functions. The empiric use of Ceratonia siliqua (carob) for its antioxidant properties is common among infertile men in Iran and Turkey. The objective of this study is to investigate the effects of C. siliqua (carob) on semen parameters, oxidative stress markers, and pregnancy rate in a parallel randomized, controlled study. A total of 60 infertile men with oligozoospermia, asthenospermia, and teratospermia were recruited from April 2018 to March 2019. Participants were divided randomly into the following two groups: carob syrup twice a day or vitamin E 100 mg twice a day for 3 months. Semen analysis was performed and hormonal levels and stress oxidative markers were measured in each treatment arm after 3 months. The quality of semen parameters improved in the carob group compared with Vit E semen count (p = 0.04 Cohen's d = .51), morphology (p = 0.001 Cohen's d = .93) and motility parameters (p = 0.002 Cohen's d = .90) were significantly higher in the carob group. No significant difference can be detected in post-treatment hormonal parameters and oxidative markers between groups, except for total antioxidant capacity(TAC) which was higher after post-treatment in carob group. A significantly higher pregnancy rate was found among the carob group. The administration of carob may be an effective agent for the improvement of semen parameters, probably related both to its involvement in the changing of testosterone level and to its antioxidant properties. Nevertheless, additional studies to evaluate the optimal dose and duration of treatment are needed. The trial has been registered in the Iranian Registry of Clinical Trials (Registration number: IRCT20171209037794N1.

Hypoglycemic effects and mechanism of different molecular weights of konjac glucomannans in type 2 diabetic rats.

Konjac glucomannan (KGM) is a hypoglycemic polysaccharide with a wide range of molecular weights. But study on hypoglycemic effects of KGMs relate to molecular weight is limited. In this study, KGMs with high and medium molecular weights, and the degraded KGMs were analyzed with physicochemical properties, hypoglycemic effects and mechanisms. Results showed that as the molecular weight KGMs decreased, the viscosity decreased, molecular flexibility increased, while chemical groups, crystal structures and main chains showed little change. KGMs with medium molecular weights (KGM-M1, KGM-M2) showed better effects on increasing body weight, decreasing levels of fasting blood glucose, insulin resistance, total cholesterol and low density lipoprotein cholesterol, and enhancing integrity of pancreas and colon, than KGMs with high or low molecular weights (KGM-H, KGM-L) in type 2 diabetic rats. Mechanism analysis suggested that KGM-M1 and KGM-M2 had higher antioxidant and anti-inflammatory activities on elevating superoxide dismutase, decreasing malondialdehyde and tumor necrosis factor-α levels. Moreover, KGM-M1 and KGM-M2 increased gut microbiota diversity, Bacteroidetes/Firmicutes ratio and Muribaculaceae, decreased Romboutsia and Klebsiella, and improved 6 diabetic related metabolites. Combined, KGM-M1 and KGM-M2 showed higher hypoglycemic effects, due to regulatory activities of antioxidant, anti-inflammatory, intestinal microbiota, and relieved metabolic disorders.

Research progress in galactomannan-based nanomaterials: Synthesis and application.

Galactomannans are naturally occurring biocompatible and biodegradable nonionic polysaccharides comprised of mannose and galactose residues. They are under investigation for the design of various drug delivery carriers such as matrix tablets, microparticles, nanoparticles/nanocomposites, polymeric micelles, hydrogels, as well as pharmaceutical excipients. Amongst galactomannans, guar gum, locust bean gum, and fenugreek gum are the biomaterials mostly investigated for their potential utility as nanocarriers for various purposes, either in their native or modified forms. The galactomannan-based nanomaterials have been fabricated by adopting various strategies. These galactomannan nanomaterials have been tested for oral vaccination, oral insulin delivery, cancer cell & macrophage targeting, controlled drug delivery, heavy metal extraction and wound dressing applications. The galactomannan has attracted the attention of researchers as reducing agents for the green synthesis of metal nanoparticles as well. These nanometals have shown improved antimicrobial, antioxidant and anticancer activities. In vitro toxicity of the nanomaterials is also assessed in some instances. Others such as cassia gum, tara gum, Delonix, Leucaena leucocephala, Punica granatum galactomannans are amongst the least studied materials for biological applications. This review describes various strategies adopted for the synthesis of galactomannan-based nanomaterials, their properties and applications, especially in the field of drug delivery.

Pharmacological interventions for treating intrahepatic cholestasis of pregnancy.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder that can develop in pregnancy. It occurs when there is a build-up of bile acids in the maternal blood. It has been linked to adverse maternal and fetal/neonatal outcomes. As the pathophysiology is poorly understood, therapies have been largely empiric. As ICP is an uncommon condition (incidence less than 2% a year), many trials have been small. Synthesis, including recent larger trials, will provide more evidence to guide clinical practice. This review is an update of a review first published in 2001 and last updated in 2013. OBJECTIVES: To assess the effects of pharmacological interventions to treat women with intrahepatic cholestasis of pregnancy, on maternal, fetal and neonatal outcomes. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (13 December 2019), and reference lists of retrieved studies. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials, including cluster-randomised trials and trials published in abstract form only, that compared any drug with placebo or no treatment, or two drug intervention strategies, for women with a clinical diagnosis of intrahepatic cholestasis of pregnancy. DATA COLLECTION AND ANALYSIS: The review authors independently assessed trials for eligibility and risks of bias. We independently extracted data and checked these for accuracy. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 26 trials involving 2007 women. They were mostly at unclear to high risk of bias. They assessed nine different pharmacological interventions, resulting in 14 different comparisons. We judged two placebo-controlled trials of ursodeoxycholic acid (UDCA) in 715 women to be at low risk of bias. The ten different pharmacological interventions were: agents believed to detoxify bile acids (UCDA) and S-adenosylmethionine (SAMe); agents used to bind bile acids in the intestine (activated charcoal, guar gum, cholestyramine); Chinese herbal medicines (yinchenghao decoction (YCHD), salvia, Yiganling and Danxioling pill (DXLP)), and agents aimed to reduce bile acid production (dexamethasone) Compared with placebo, UDCA probably results in a small improvement in pruritus score measured on a 100 mm visual analogue scale (VAS) (mean difference (MD) -7.64 points, 95% confidence interval (CI) -9.69 to -5.60 points; 2 trials, 715 women; GRADE moderate certainty), where a score of zero indicates no itch and a score of 100 indicates severe itching. The evidence for fetal distress and stillbirth were uncertain, due to serious limitations in study design and imprecision (risk ratio (RR) 0.70, 95% CI 0.35 to 1.40; 6 trials, 944 women; RR 0.33, 95% CI 0.08 to 1.37; 6 trials, 955 women; GRADE very low certainty). We found very few differences for the other comparisons included in this review. There is insufficient evidence to indicate if SAMe, guar gum, activated charcoal, dexamethasone, cholestyramine, Salvia, Yinchenghao decoction, Danxioling and Yiganling, or Yiganling alone or in combination are effective in treating women with intrahepatic cholestasis of pregnancy. AUTHORS' CONCLUSIONS: When compared with placebo, UDCA administered to women with ICP probably shows a reduction in pruritus. However the size of the effect is small and for most pregnant women and clinicians, the reduction may fall below the minimum clinically worthwhile effect. The evidence was unclear for other adverse fetal outcomes, due to very low-certainty evidence. There is insufficient evidence to indicate that SAMe, guar gum, activated charcoal, dexamethasone, cholestyramine, YCHD, DXLP, Salvia, Yiganling alone or in combination are effective in treating women with cholestasis of pregnancy. There are no trials of the efficacy of topical emollients. Further high-quality trials of other interventions are needed in order to identify effective treatments for maternal itching and preventing adverse perinatal outcomes. It would also be helpful to identify those women who are mostly likely to respond to UDCA (for example, whether bile acid concentrations affect how women with ICP respond to treatment with UDCA).

In vivo antioxidant and anti-inflammatory effects of soluble dietary fiber Konjac glucomannan in type-2 diabetic rats.

Although the anti-diabetic properties of Konjac glucomannan (KGM) have been reported previously; however, the molecular pathways of its anti-diabetic properties are not clear. The present study hypothesized that KGM could mitigate oxidative stress and inflammation. Three doses of KGM (40, 80, 120 mg/kg b.w.) decreased the levels of plasma glucose and insulin in type-2 diabetic rats induced by a high-fat diet and streptozotocin (STZ) after administration for 28 days. Besides, the C-reactive protein, antioxidants, and the pathways of the nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-kappa B (NF-κB) showed amelioration and positively regulation after treated with a medium dose of KGM (80 mg/kg b.w.). The results of the histological study indicated that the medium dose of KGM was able to reverse the structural impairment of kidney and liver caused by type-2 diabetes. In conclusion, our research demonstrated that KGM reduced the hyperglycemia, regulated the Nrf2 pathway and by which it prevented oxidative stress, besides, it reduced the inflammation via regulation of the NF-kB pathway.

Anti-Influenza A Virus Activity of Rhamnan Sulfate from Green Algae Monostroma nitidum in Mice with Normal and Compromised Immunity.

Influenza viruses cause a significant public health burden each year despite the availability of anti-influenza drugs and vaccines. Therefore, new anti-influenza virus agents are needed. Rhamnan sulfate (RS) is a sulfated polysaccharide derived from the green alga Monostroma nitidum. Here, we aimed to demonstrate the antiviral activity of RS, especially against influenza A virus (IFV) infection, in vitro and in vivo. RS showed inhibitory effects on viral proliferation of enveloped viruses in vitro. Evaluation of the anti-IFV activity of RS in vitro showed that it inhibited both virus adsorption and entry steps. The oral administration of RS in IFV-infected immunocompetent and immunocompromised mice suppressed viral proliferation in both mouse types. The oral administration of RS also had stimulatory effects on neutralizing antibody production. Fluorescent analysis showed that RS colocalized with M cells in Peyer's patches, suggesting that RS bound to the M cells and may be incorporated into the Peyer's patches, which are essential to intestinal immunity. In summary, RS inhibits influenza virus infection and promotes antibody production, suggesting that RS is a potential candidate for the treatment of influenza virus infections.

Hypolipidemic Effects of ß-Glucans, Mannans, and Fucoidans: Mechanism of Action and Their Prospects for Clinical Application.

The search for lipid-lowering drugs is important for clinical medicine. This review summarizes our research findings regarding the hypolipidemic activity of polysaccharides. There are several validated agents altering lipid levels which reduce the risk of atherosclerotic cardiovascular events. Nonetheless, for many people, the risk of such an event remains unacceptably high despite treatment with these agents. This situation has prompted the search for new therapies to reduce the residual cardiovascular risk. The lipid-lowering effect of ß-glucans consumed with food was demonstrated in patients with atherosclerosis. The mechanism of the protective effect of ß-glucans is poorly studied. The effects of ß-glucans are mediated by Toll-like receptors, by dectin-1, and possibly by other receptors. Nevertheless, the mechanism of the protective action of ß-glucan in lipemic mice has been studied insufficiently. This review will present up-to-date information regarding experimental hypolipidemic polysaccharide compounds that hold promise for medicine. Phagocyte-specific chitotriosidase in humans contributes to innate immune responses against chitin-containing fungi. This enzyme has been first described in patients with Gaucher disease and serves as an important diagnostic biomarker. It has been reported that, in mice, chitin particles of certain size are recognized by macrophages through Toll-like receptors, dectin-1, and to a lesser extent through mannose receptor.

Structural characterization and anti-lung cancer activity of a sulfated glucurono-xylo-rhamnan from Enteromorpha prolifera.

A sulfated glucurono-xylo-rhamnan (EP-3-H) was purified from a green alga, Enteromorpha prolifera. EP-3-H and its oligomers were characterized by high performance liquid chromatography, mass spectrometry and one and two-dimensional nuclear magnetic resource spectroscopy. The structural analysis showed EP-3-H has a backbone of glucurono-xylo-rhamnan, branches with glucuronic acid and sulfated at C3 of rhamnose and/or C2 of xylose. The inhibition of EP-3-H on human lung cancer A549 cell proliferation in vitro and its therapeutic effects in BALB/c-nu mice in vivo were determined to evaluate the anti-lung cancer activity of EP-3-H. The tumor inhibition level was 59 %, suggesting that EP-3-H might be a good candidate for the treatment of lung cancer. Surface plasmon resonance (SPR) studies revealed the IC50 on the binding of fibroblast growth factors, (FGF1 and FGF2), to heparin were 0.85 and 1.47 mg/mL, respectively. These results suggest that EP-3-H inhibits cancer proliferation by interacting with these growth factors.