An inulin-type fructan CP-A from Codonopsis pilosula attenuates experimental colitis in mice by promoting autophagy-mediated inactivation of NLRP3 inflammasome.

Inulin-type fructan CP-A, a predominant polysaccharide in Codonopsis pilosula, demonstrates regulatory effects on immune activity and anti-inflammation. The efficacy of CP-A in treating ulcerative colitis (UC) is, however, not well-established. This study employed an in vitro lipopolysaccharide (LPS)-induced colonic epithelial cell model (NCM460) and an in vivo dextran sulfate sodium (DSS)-induced colitis mouse model to explore CP-A's protective effects against experimental colitis and its underlying mechanisms. We monitored the clinical symptoms in mice using various parameters: body weight, disease activity index (DAI), colon length, spleen weight, and histopathological scores. Additionally, molecular markers were assessed through enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence (IF), immunohistochemistry (IHC), and Western blotting assays. Results showed that CP-A significantly reduced reactive oxygen species (ROS), tumor necrosis factor-alpha (TNF-α), and interleukins (IL-6, IL-1ß, IL-18) in LPS-induced cells while increasing IL-4 and IL-10 levels and enhancing the expression of Claudin-1, ZO-1, and occludin proteins in NCM460 cells. Correspondingly, in vivo findings revealed that CP-A administration markedly improved DAI, reduced colon shortening, and decreased the production of myeloperoxidase (MPO), malondialdehyde (MDA), ROS, IL-1ß, IL-18, and NOD-like receptor protein 3 (NLRP3) inflammasome-associated genes/proteins in UC mice. CP-A treatment also elevated glutathione (GSH) and superoxide dismutase (SOD) levels, stimulated autophagy (LC3B, P62, Beclin-1, and ATG5), and reinforced Claudin-1 and ZO-1 expression, thereby aiding in intestinal epithelial barrier repair in colitis mice. Notably, the inhibition of autophagy via chloroquine (CQ) diminished CP-A's protective impact against colitis in vivo. These findings elucidate that CP-A's therapeutic effect on experimental colitis possibly involves mitigating intestinal inflammation through autophagy-mediated NLRP3 inflammasome inactivation. Consequently, inulin-type fructan CP-A emerges as a promising drug candidate for UC treatment.

Structure characterization of an agavin-type fructan isolated from Polygonatum cyrtonema and its effect on the modulation of the gut microbiota in vitro.

The herbal medicine Polygonatum cyrtonema is highly regarded in China for its medicinal and dietary properties. However, further research is needed to elucidate the structure of its polysaccharide and understand how it promotes human health by modulating the gut microbiota. This study aims to investigate a homogeneous polysaccharide (PCP95-1-1) from Polygonatum cyrtonema and assess its susceptibility to digestion as well as its utilization by intestinal microbiota. The results confirmed that PCP95-1-1 is an agavin-type fructan, which possesses two fructose chains, namely ß-(2 â†’ 6) and ß-(2 â†’ 1) fructosyl-fructose, attached to the sucrose core, and has branches of ß-D-Fruf residues. Moreover, PCP95-1-1 demonstrated resistance to digestion and maintained its reducing sugar content throughout the digestive system, indicating it could reach the gut without being digested. In vitro fermentation of PCP95-1-1 significantly decreased the pH value (p < 0.05) while notably increasing the production of short-chain fatty acids (SCFAs), confirming its utilization by human gut microbiota. Additionally, PCP95-1-1 exhibited a significant ability (p < 0.05) to beneficial bacteria such as Megamonas and Bifidobacterium, while reducing the presence of facultative or conditional pathogens such as Escherichia-Shigella and Klebsiella at the genus level. Consequently, PCP95-1-1 has the potential to positively influence physical well-being by modulating the gut microbiota environment and can be developed as a functional food.

Structural characterization of an inulin neoseries-type fructan from Ophiopogonis Radix and the therapeutic effect on liver fibrosis in vivo.

Ophiopogonis Radix is a well-known Traditional Chinese Medicine and functional food that is rich in polysaccharides and has fructan as a characteristic component. In this study, an inulin neoseries-type fructan designated as OJP-W2 was obtained and characterized from Ophiopogonis Radix, and its potential therapeutic effect on liver fibrosis in vivo were investigated. Structural studies revealed that OJP-W2 had a molecular weight of 5.76 kDa and was composed of glucose and fructose with a molar ratio of 1.00:30.87. Further analysis revealed OJP-W2 has a predominantly lineal (1-2)-linked ß-D-fructosyl units linked to the glucose moiety of the sucrose molecule with (2-6)-linked ß-D-fructosyl side chains. Pharmacological studies revealed that OJP-W2 exerted a marked hepatoprotective effect against liver fibrosis, the mechanism of action was involved in regulating collagen deposition (α-SMA, COL1A1 and liver Hyp contents) and TGF-ß/Smads signaling pathway, alleviating liver inflammation (IL-1ß, IL-6, CCL5 and F4/80) and MAPK signaling pathway, and inhibiting hepatic apoptosis (Bax, Bcl-2, ATF4 and Caspase 3). These data provide evidence for expanding Ophiopogonis Radix-acquired fructan types and advancing our understanding of the specific role of inulin neoseries-type fructan in liver fibrosis therapy.

The Leap of Inulin Fructans from Food Industry to Medical Application.

As a dietary supplement, the efficacy of prebiotics has become a hot issue in recent years. Inulin is one of internationally recognized prebiotics and belongs to a group of non-digestible and fermentable carbohydrates. Currently, the food industry is increasingly using prebiotic inulin as a health-promoting substrate, not just as food supplement. In addition, inulin has also shown great promise in the treatment of various diseases. This article reviews the application of inulin in the food industry and summarizes physiological function of inulin. Through the review and prospect of the research on obesity, diabetes and mental illness, it provides the theoretical basis for the joint development of inulin in food industry and medical application.

Construction of inulin-based selenium nanoparticles to improve the antitumor activity of an inulin-type fructan from chicory.

Cancer has become one of the leading causes of death worldwide. It is urgent to develop new antitumor drugs with high efficiency and low toxicity. In this study, an inulin-type fructan CIP70-1 was purified and characterized from chicory and showed weak antitumor activity. To improve its antitumor effects, inulin-based selenium nanoparticles (CIP-SeNPs) were constructed and characterized. CIP-SeNPs were spherical nanoparticles (60 nm), which remained stable in water for more than 3 months. A cellular antitumor assay revealed that CIP-SeNPs had stronger inhibitory effects on cancer cells (MCF-7, A549, and HepG2) than CIP70-1 alone. Furthermore, the in vivo antitumor effects of CIP-SeNPs were confirmed using zebrafish models. The results showed that CIP-SeNPs significantly inhibited the proliferation and migration of tumors as well as the angiogenesis of transgenic zebrafish in the concentration range of 1-4 µg/mL.

Antimutagenic and Antiproliferative Activity of the Coccoloba uvifera L. Extract Loaded in Nanofibers of Gelatin/Agave Fructans Elaborated by Electrospinning.

BACKGROUND: The Coccoloba uvifera L. species is currently considered an important source of compounds of high biological value such as lupeol. This is related to different and important biological activities to human health. OBJECTIVE: The objective of this study was to encapsulate the C. uvifera extract in nanofibers made with the biopolymers gelatin (G)/high-grade polymerization agave fructans (HDPAF) in the proportions 1:0, 1:1, 1:2, 1:3 and 0:1, through the electrospinning process, in addition to evaluating the antimutagenic and antiproliferative properties of the encapsulated extract. METHODS: The physicochemical characteristics of the nanofibers were evaluated, as well as the antiproliferative and antimutagenic activities of the encapsulated and unencapsulated extract. SEM evaluation shows nanofibers of smooth, continuous morphology and nanometric size (50-250 nm). The TGA, FTIR-ATR, HPLC-MS analyses reveal the presence of the extract in the nanofibers. RESULTS: The extract did not show a mutagenic effect during the development of the Ames test, on the other hand, the MTT test showed the antiproliferative effect at the concentrations of 50 and 100 µg/mL of extract. CONCLUSION: The extract of C. uvifera loaded in nanofibers elaborated by electrospinning with the G/HDPAF biopolymers conserves its antimutagenic and antiproliferative properties.

Uniform and disperse selenium nanoparticles stabilized by inulin fructans from Codonopsis pilosula and their anti-hepatoma activities.

The present work reported the extraction, purification and characterization of an inulin fructan from Codonopsis pilosula (CPW1) and its application in stabilization of selenium nanoparticles (SeNPs). The morphology, stability, and stabilization mechanism of CPW1 stabilized SeNPs (CPW1-Se) were explored, and the results showed that the SeNPs were amorphous state, with size of 54-79 nm, and kept stable within 15 days due to the interaction between SeNPs and the hydroxyl groups on the surface of CPW1. Moreover, the effects on proliferation and apoptosis of CPW1-Se to both normal cells (293T) and liver cancer cells (Huh-7 and HepG2) were evaluated systematically by using the CCK8 assay, plate clone formation assay, flow cytometry and western blot. The results indicated that CPW1-Se possessed selective anti-hepatoma activities without side effects on normal cells, which exhibited strong potential application in liver cancer treatments.

In vitro and in silico anti-osteoporosis activities and underlying mechanisms of a fructan, ABW90-1, from Achyranthes bidentate.

Achyranthes bidentata is a traditional Chinese medicine used to treat osteoporosis. AB90, a crude saccharide from A. bidentata, showed excellent osteoprotective effects in ovariectomized rats, and ABW90-1, an oligosaccharide purified from AB90, stimulated significant differentiation of osteoblasts. However, the osteogenic effects and underlying mechanisms of ABW90-1 have remained unknown. In the present study, we found that ABW90-1 significantly promoted ALP activity, mineralization, and the expression of osteogenic markers in MC3T3-E1 cells. ABW90-1 showed strong binding with the WNT signaling complex and BMP2 based on number of interactions, hydrogen bond length, and binding energy in silico. ABW90-1 significantly increased the expression of active-ß-catenin, p-GSK-3ß, LEF-1, BMP2, and p-SMAD1. Importantly, the osteogenic effects of ABW90-1 were partially suppressed by DKK-1 and Noggin, which are specific inhibitors of the WNT and BMP signaling pathways, respectively. Collectively, these findings suggest that ABW90-1 has osteogenic effects through crosstalk between WNT/ß-catenin and BMP2/SMAD1 signaling pathways.

A dandelion polysaccharide and its selenium nanoparticles: Structure features and evaluation of anti-tumor activity in zebrafish models.

In this study, an inulin fructan (TMP50-2) with moderate anti-tumor activity was obtained from dandelion. To further improve the anti-tumor activity of TMP50-2, a monodisperse and stable spherical nanoparticle (Tw-TMP-SeNP, 50 nm) was fabricated. Physico-chemical analysis revealed that TMP50-2 and Tween 80 were tightly wrapped on the surface of SeNPs by forming CO⋯Se bonds or through hydrogen bonding interaction (OH⋯Se). In vitro anti-tumor assay showed that Tw-TMP-SeNP treatment could significantly inhibit the proliferation of cancer cells (HepG2, A549, and HeLa) in a dose-dependent manner, while HepG2 cells were more susceptible to Tw-TMP-SeNP with an IC50 value of 46.8 µg/mL. The apoptosis induction of HepG2 cells by Tw-TMP-SeNP was evidenced by increasing the proportion of apoptotic cells ranging from 12.5% to 27.4%. Furthermore, in vivo zebrafish model confirmed the anti-tumor activity of Tw-TMP-SeNP by inhibiting the proliferation and migration of tumor cells as well as the angiogenesis of zebrafish embryos.

Efficacy of dietary supplements containing isolated organic compounds for weight loss: a systematic review and meta-analysis of randomised placebo-controlled trials.

BACKGROUND/OBJECTIVES: A systematic review with meta-analysis was conducted to synthesise evidence on the efficacy of dietary supplements containing isolated organic compounds for weight loss. SUBJECTS/METHODS: Four electronic databases (Medline, Embase, Web of Science, Cinahl) were searched until December 2019. Sixty-seven randomised placebo-controlled trials of dietary supplements containing isolated organic compounds for weight loss were included. Meta-analyses were conducted for chitosan, glucomannan, conjugated linoleic acid and fructans, comparing mean weight difference post-intervention between participants receiving the dietary supplement or placebo. RESULTS: Statistically significant weight differences compared to placebo were observed for chitosan (-1.84 kg; 95% confidence interval [CI] -2.79, -0.88; p < 0.01), glucomannan (-1.27 kg; 95%CI -2.45, -0.09; p = 0.04), and conjugated linoleic acid (-1.08 kg; 95%CI -1.61, -0.55; p < 0.01). None met our threshold for clinical significance (≥2.5 kg). There was no statistically significant effect on weight for fructans compared to placebo (p = 0.24). For dietary supplements with an inadequate number of trials for meta-analysis, a statistically and borderline clinically significant weight difference compared to placebo was found for modified cellulose, manno-oligosaccharides (in males), blood orange juice extract, and three multiple-ingredient dietary supplements. These were only reported in one trial of each. Thus, more evidence is needed before recommending them for weight loss. CONCLUSIONS: While some dietary supplements containing isolated organic compounds warrant further investigation to determine efficacy and safety, there is currently insufficient evidence to recommend any of these dietary supplements for weight loss.

The Immunomodulatory Properties of ß-2,6 Fructans: A Comprehensive Review.

Polysaccharides such as ß-2,1-linked fructans including inulin or fructose oligosaccharides are well-known prebiotics with recognised immunomodulatory properties. In recent years, other fructan types covering ß-2,6-linked fructans, particularly microbial levans, have gained increasing interest in the field. ß-2,6-linked fructans of different degrees of polymerisation can be synthesised by plants or microbes including those that reside in the gastrointestinal tract. Accumulating evidence suggests a role for these ß-2,6 fructans in modulating immune function. Here, we provide an overview of the sources and structures of ß-2,6 fructans from plants and microbes and describe their ability to modulate immune function in vitro and in vivo along with the suggested mechanisms underpinning their immunomodulatory properties. Further, we discuss the limitations and perspectives pertinent to current studies and the potential applications of ß-2,6 fructans including in gut health.

Effect of inulin-type fructans and galactooligosaccharides on cultures of Lactobacillus strains isolated in Algeria from camel's milk and human colostrum.

Bacteria from the genus Lactobacillus are responsible for spontaneous food fermentations. Some species, such as Lactobacillus casei and Lactobacillus brevis, have the "Qualified Presumption of Safety" status recognized by the European Food Safety Authority. Several of their strains are used as probiotics in foods and sometimes are included in synbiotic combinations together with prebiotics. New microbial strains isolated from different sources represent an opportunity to use them for the production of traditional food products. The capacity of three selected strains (one isolated from Camel's milk and identified by partial 16 S rRNA gene sequencing as L. brevis, and two isolated from human colostrum and identified as L. paracasei/L. casei and L. brevis, respectively) was assessed in vitro for the ability to survive in gastrointestinal conditions (low pH and high bile salts concentrations). We also tested the capacity of growth and the production of organic acids and volatile compounds by high-performance liquid chromatography and gas chromatography, respectively, when these bacteria were incubated anaerobically in the presence of inulin, fructooligosaccharides, or galactooligosaccharides as the main carbon sources. The strains were able to survive in simulated gastrointestinal conditions and to grow in inulin, fructooligosaccharides, and galactooligosaccharides. However, they displayed different profiles of organic acids and volatile compounds, mainly depending on the microbial species and the prebiotic used. The influence that the combined use of strains and different prebiotics could exert on the organic acids and volatiles formed in food and in the gut should be assessed for each synbiotic combination and food product.

Characterization of inulin-type fructans from two species of Radix Codonopsis and their oxidative defense activation and prebiotic activities.

BACKGROUND: Codonopsis pilosula and C. tangshen are both plants widely used in traditional Chinese medicine. Polysaccharides, which are their primary active components, are thought to be important in their extensive use. In this study, two neutral polysaccharide fractions of C. pilosula (CPPN) and C. tangshen (CTPN) were obtained by fractionation on a DEAE-Sepharose column and characterized. RESULTS: It was confirmed that the neutral polymers CPPN and CTPN were ß-(2,1)-linked inulin-type fructans with non-reducing terminal glucose, and degree of polymerization (DP) of 19.6 and 25.2, respectively. The antioxidant and prebiotic activities in vitro were assayed based on IPEC-J2 cell lines and five strains of Lactobacillus. Results indicated that the effects of CPPN and CTPN were increased antioxidant defense in intestinal epithelial cells through enhanced cell viability, improved expression of total antioxidant capacity, glutathione peroxidase, superoxide dismutase and catalase, and reduced levels of malondialdehyde and lactic dehydrogenase. The prebiotic activity of CPPN and CTPN was demonstrated by the promoting effect on Lactobacillus proliferation in vitro. The different biological activities obtained between the two fractions are probably due to the different DP and thus molecular weights of CPPN and CTPN. CONCLUSION: The inulin fractions from C. pilosula and C. tangshen were natural sources of potential intestinal antioxidants as well as prebiotics, which will be valuable in further studies and new applications of inulin-containing health products. © 2020 Society of Chemical Industry.

A novel inulin-type fructan from Asparagus cochinchinensis and its beneficial impact on human intestinal microbiota.

A purified inulin-type fructan named ACNP (Asparagus cochinchinensis neutral polysaccharide) with apparent molecular weight of 2690 Da was obtained from Asparagus cochinchinensis (Lour.) Merr. by ion-exchange and gel-filtration column chromatography. Structural analyses reveal that ACNP has a linear backbone composed of 2,1-ß-D-Fruf residues, ending with a (1→2) bonded α-D-Glcp. The impacts of ACNP on gut microbiota were then investigated by in vitro fermentation with human fecal cultures. The results showed that ACNP was digested by gut microbiota, while the pH value in the fecal culture of ACNP was greatly decreased, and total short-chain fatty acids, acetic, propionic, i-valeric and n-valeric acids were significantly increased. Moreover, ACNP regulated the fecal microbiota composition by stimulating the growth of Prevotella, Megamonas, and Bifidobacterium while depleting Haemophilus. Collectively, these results indicated that ACNP beneficially regulates gut microbiota, which thus suggested that ACNP has the potential to be used as a dietary supplement or drug to improve health.

Comparative studies on characterization, saccharide mapping and antiglycation activity of polysaccharides from different Polygonatum ssp.

Multiple species of Polygonatum are used as "Huangjing" in China and polysaccharides are the main effective constituents of "Huangjing". However, there is a lack of systematic comparison of polysaccharides from Polygonatum spp., and little work concerning on the polysaccharides from unofficial species. This paper conducted a comparison study on the characterization, high-performance gel permeation chromatography (HPGPC) saccharide mapping and antiglycation assay of polysaccharides and their enzymatic hydrolysates from nine species of Polygonatum. The results showed that polysaccharides from P. macropodium were mainly composed of fructans (3.3 × 103 Da); while polysaccharides from other eight Polygonatum spp. contained both fructans (2.5 × 103-4.1 × 103 Da) and pectins (more than 4.1 × 105 Da). Antiglycation assay showed that polysaccharides from Polygonatum spp. could significantly inhibit the formation of AGEs, and degradation of pectins and fructans could result in loss of activity. The results are helpful to the rational usage and quality control of Polygonatum spp.

Levan production from sucrose using chicken feather peptone as a low cost supplemental nutrient source.

Chicken feather peptone (CFP) derived from poultry waste is a rich source of essential minerals and amino acids. This, along with suitable carbon source, can be used as a low cost complex supplemental nutrient source for microbial fermentation. In the present work, CFP blended with sucrose was evaluated for the production of levan using Bacillus subtilis MTCC 441. Amount of CFP added to the medium significantly influenced levan production and it was found that at a concentration 2 g/L, maximum levan yield of 0.26 ±â€¯0.04 g/g sucrose was obtained. The levan yield obtained with CFP as a low cost supplemental nutrient source was comparable with that obtained from commercial medium (0.31 ±â€¯0.02 g/g sucrose). Levan produced using CFP was tested on primary cell lines at various concentrations (100-1000 µM) and found to be non-toxic and bio-compatible in nature. This indicates that CFP could be used as low cost nutrient source for levan production.

Levan from Bacillus amyloliquefaciens JN4 acts as a prebiotic for enhancing the intestinal adhesion capacity of Lactobacillus reuteri JN101.

Improving intrinsic adhesion performance of the known probiotics facilitates their residence and colonization, and therefore exerts more beneficial effects on the human or animal host. In this study, through adaptive culture with levan, Lactobacillus reuteri JN101 achieved the same biomass and exhibited 2.6 times higher adhesion capacity to HT-29 cells than those grown with glucose. The mechanism study related to this adhesion enhancement showed that the elevated proportion of unsaturated fatty acids facilitated the bacterial cells to overcome repulsive forces to approach the intestinal epithelial cell. At the same time, and the greater amounts of cell membrane proteins, such as S-layer protein (3.2 folds), elongation factor Tu (2.6 folds) and phosphoglycerate kinase (2.4 folds) probably enhanced the complementary interactions to the receptor on the epithelial cell. These results presented here indicated levan could be used as a potential prebiotic to regulate the adhesion capacity of probiotics, and provide ground for developing the specific-probiotics oriented functional food.

Fructans as Immunomodulatory and Antiviral Agents: The Case of Echinacea.

Throughout history, medicinal purposes of plants have been studied, documented, and acknowledged as an integral part of human healthcare systems. The development of modern medicine still relies largely on this historical knowledge of the use and preparation of plants and their extracts. Further research into the human microbiome highlights the interaction between immunomodulatory responses and plant-derived, prebiotic compounds. One such group of compounds includes the inulin-type fructans (ITFs), which may also act as signaling molecules and antioxidants. These multifunctional compounds occur in a small proportion of plants, many of which have recognized medicinal properties. Echinacea is a well-known medicinal plant and products derived from it are sold globally for its cold- and flu-preventative and general health-promoting properties. Despite the well-documented phytochemical profile of Echinacea plants and products, little research has looked into the possible role of ITFs in these products. This review aims to highlight the occurrence of ITFs in Echinacea derived formulations and the potential role they play in immunomodulation.

Agave salmiana fructans as gut health promoters: Prebiotic activity and inflammatory response in Wistar healthy rats.

Prebiotic effects of Agave salmiana fructans at five different doses were evaluated by the growth of Bifidobacterium, Lactobacillus, and Clostridium strains and SCFA production in the cecum and proximal colon of healthy Wistar rats. Mucosal integrity, bacterial proliferation, and inflammatory response were also examined. Growth of Bifidobacterium and Lactobacillus strains was improved by 12.5% doses of fructans in both cecum and proximal colon tissues, and a significant decrease of Clostridium (P < 0.05) was observed. Increases in mucosal thickness, proliferation, and cell adhesion were mainly observed in the cecum. High concentration of butyric acid and total SCFA were contained in the 12.5% doses. This study provides direct evidence of the prebiotic effects of Agave salmiana fructans, demonstrating that a diet supplemented with a 12.5% dose of fructans promotes major growth of probiotic bacteria and could be used as a potential prebiotic ingredient under the conditions used in this study. Taken together, these results further indicate the significance of Agave salmiana fructans as a prebiotic ingredient in the regulation and prevention of gastrointestinal diseases, as well as for the design of functional foods.

Characterization of Inulin-Type Fructan from Platycodon grandiflorus and Study on Its Prebiotic and Immunomodulating Activity.

Platycodon grandiflorus is a plant widely used in traditional Chinese medicine, of which polysaccharides are reported to be the main components responsible for its bio-functions. In this work, the inulin-type fructan (PGF) was obtained by DEAE anion exchange chromatography from the water extracted from P. grandifloras. Characterization was performed with methanolysis, methylation, and NMR and the results showed that PGF is a ß-(2-1) linked fructan, with terminal glucose and with a degree of polymerization of 2⁻10. In order to study its biofunctions, the prebiotic and immunomodulation properties were assayed. We found that PGF exhibited good prebiotic activity, as shown by a promotion on six strains of lactobacillus proliferation. Additionally, the PGF also displayed direct immunomodulation on intestinal epithelial cells and stimulated the expressions of anti-inflammatory factors. These results indicated that the inulin from P. grandiflorus is a potential natural source of prebiotics as well as a potential intestinal immunomodulator, which will be valuable for further studies and new applications.