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Amyloid beta (Aß) aggregation is one of the distinctive pathological hallmarks of Alzheimer's disease (AD). Therefore, the development of effective inhibitors against Aß aggregate formation offers great promise for the treatment of AD. In this study, we designed a novel negatively charged functionalized conjugate aimed at inhibiting Aß42 aggregation and attenuating neurotoxicity by grafting polysialic acid with mannuronate oligosaccharide, a biocompatible glycan extracted from seaweeds, designated as polysialic acid-mannan conjugate (PSA-MOS). ThT, biological microscopy, TEM and CD confirmed the inhibition of Aß42 aggregation by PSA-MOS, as well as its ability to inhibit the conformational transition of Aß42 to ß-sheet. CCK-8 assay demonstrated that PSA-MOS was not cytotoxic to SH-SY5Y (p < 0.05) and promoted cell proliferation. In the Aß42-induced SH-SY5Y injury models, PSA-MOS dose-dependently ameliorated cytotoxicity (p < 0.0001) and significantly reduced the levels of inflammatory factors of IL-1ß (p < 0.0001), IL-6 (p < 0.0001) and TNF-α (p < 0.05). MD simulations demonstrated that PSA-MOS effectively impeded the α-helix to ß-sheet transition of the Aß42 monomer via electrostatic interactions with its CTR and NTR regions. These findings demonstrate the therapeutic potential of PSA-MOS as promising glycoconjugate for the treatment of AD.
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Peptídeos beta-Amiloides , Inflamação , Ácidos Siálicos , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/química , Humanos , Ácidos Siálicos/química , Ácidos Siálicos/farmacologia , Inflamação/tratamento farmacológico , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Linhagem Celular Tumoral , Mananas/farmacologia , Mananas/química , Proliferação de Células/efeitos dos fármacos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Simulação de Dinâmica Molecular , Ácidos HexurônicosRESUMO
Through adaptive laboratory evolution (ALE) of Sphingomonas sp. ATCC 31555, fermentation for production of low-molecular-weight welan gum (LMW-WG) was performed using glycerol as sole carbon source. During ALE, GPC-MALS analysis revealed a gradual decrease in WG molecular weight with the increase of adaptation cycles, accompanied by changes in solution conformation. LMW-WG was purified and structurally analyzed using GPC-MALS, monosaccharide composition analysis, infrared spectroscopy, NMR analysis, atomic force microscopy, and scanning electron microscopy. Subsequently, LMW-WG obtains hydration, transparency, antioxidant activity, and rheological properties. Finally, an in vitro simulation colon reactor was used to evaluate potential prebiotic properties of LMW-WG as dietary fiber. Compared with WG produced using sucrose as substrate, LMW-WG exhibited a fourfold reduction in molecular weight while maintaining moderate viscosity. Structurally, L-Rha nearly completely replaced L-Man. Furthermore, LMW-WG demonstrated excellent hydration, antioxidant activity, and high transparency. It also exhibited resistance to saliva and gastrointestinal digestion, showcasing a favorable colonization effect on Bifidobacterium, making it a promising symbiotic agent.
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Antioxidantes , Fermentação , Glicerol , Peso Molecular , Sphingomonas , Glicerol/química , Glicerol/metabolismo , Antioxidantes/química , Antioxidantes/farmacologia , Sphingomonas/metabolismo , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/farmacologia , Viscosidade , Prebióticos , Bifidobacterium/metabolismoRESUMO
Food-derived mucins are glycoproteins rich in sialic acid, but their digestive properties and potential health benefits for humans have been scarcely investigated. In this work, ovomucin (OVM, rich in N-acetylneuraminic acid, about 3 %), porcine small intestinal mucin (PSIM, rich in N-glycolylneuraminic acid, about 1 %), the desialylated OVM (AOVM) and the desialylated PSIM (APSIM) were selected to examine their digestion and their impact on the gut microbiota of elderly individuals. The results shown that, the proportion of low-molecular-weight proteins increased after simulated digestion of these four mucins, with concomitant comparable antioxidant activity observed. Desialylation markedly increased the degradation and digestion rate of mucins. In vitro fecal fermentation was conducted with these mucins using fecal samples from individuals of different age groups: young, low-age and high-age elderly. Fecal fermentation with mucin digestive solution stimulated the production of organic acids in the group with fecal sample of the elderly individuals. Among them, the OVM group demonstrated the most favorable outcomes. The OVM and APSIM groups elevated the relative abundance of beneficial bacteria such as Lactobacillus and Bifidobacterium, while diminishing the presence of pathogenic bacteria such as Klebsiella. Conversely, the probiotic effects of AOVM and PSIM were attenuated or even exhibited adverse effects. Hence, mucins originating from different sources and possessing distinct glycosylation patterns exhibit diverse biological functions. Our findings can offer valuable insights for developing a well-balanced and nutritious diet tailored to the elderly population.
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Microbioma Gastrointestinal , Mucinas , Humanos , Idoso , Animais , Suínos , Dieta , Alimentos , BifidobacteriumRESUMO
In this study, the curdlan-polyphenol complexes were constructed by a pH-driven method. The interaction between curdlan and various hydrophobic polyphenols (curcumin, quercetin, and chlorogenic acid) was investigated. Curdlan could self-assemble into particles for loading polyphenols through hydrogen bonding and hydrophobic interactions. The three polyphenols were embedded in curdlan in an amorphous state. The curdlan-curcumin complex showed the lowest viscoelasticity but exhibited the highest curcumin loading ability (34.04 ± 1.73 mg/g). However, the curdlan-chlorogenic acid complex emerged the opposite trend, indicating that the loading capacity was associated with the hydrophobicity of polyphenols. The antioxidant activity of curdlan significantly increased after combining with polyphenols, which could be maintained during in vitro simulated gastrointestinal digestion. In particular, the curdlan-quercetin complex exhibited the highest antioxidant activity and short-chain fatty acid concentration, which could influence gut microbiota composition by promoting the proliferation of Prevotella and inhibiting the growth of Escherichia_Shigella. In conclusion, the curdlan-polyphenol complexes prepared by an alcohol-free pH-driven method could effectively enhance the gastrointestinal stability of polyphenols as well as increase the antioxidant and prebiotic activities of curdlan, which could be applied as a functional ingredient to improve gut health.
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Antioxidantes , Polifenóis , Prebióticos , beta-Glucanas , beta-Glucanas/química , beta-Glucanas/farmacologia , Antioxidantes/farmacologia , Antioxidantes/química , Concentração de Íons de Hidrogênio , Polifenóis/química , Polifenóis/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Quercetina/química , Quercetina/farmacologia , Fenômenos QuímicosRESUMO
In vitro digestion models, as innovative assessment tools, possess advantages such as speed, high throughput, low cost, and high repeatability. They have been widely applied to the investigation of food digestion behavior and its potential impact on health. In recent years, research on edible polysaccharides in the field of intestinal health has been increasing. However, there is still a lack of systematic reviews on the application of microbial-derived edible polysaccharides in in vitro intestinal models. This review thoroughly discusses the limitations and challenges of static and dynamic in vitro digestion experiments, while providing an in-depth introduction to several typical in vitro digestion models. In light of this, we focus on the degradability of microbial polysaccharides and oligosaccharides, with a particular emphasis on edible microbial polysaccharides typically utilized in the food industry, such as xanthan gum and gellan gum, and their potential impacts on intestinal health. Through this review, a more comprehensive understanding of the latest developments in microbial polysaccharides, regarding probiotic delivery, immobilization, and probiotic potential, is expected, thus providing an expanded and deepened perspective for their application in functional foods.
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The influence of polysialic acid (PSA) and sialic acid (SA) on the gut microbial community composition and metabolites in healthy humans was investigated using a bionic gastrointestinal reactor. The results indicated that PSA and SA significantly changed the gut microbiota and metabolites to different degrees. PSA can increase the relative abundances of Faecalibacterium and Allisonella, whereas SA can increase those of Bifidobacterium and Megamonas. Both can significantly increase the content of short-chain fatty acids. The results of metabolome analysis showed that PSA can upregulate ergosterol peroxide and gallic acid and downregulate the harmful metabolite N-acetylputrescine. SA can upregulate 4-pyridoxic acid and lipoic acid. PSA and SA affect gut microbiota and metabolites in different ways and have positive effects on human health. These results will provide a reference for the further development of PSA- and SA-related functional foods and health products.
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Welan gum, a natural polysaccharide produced by Sphingomonas sp. ATCC 31555, has attracted considerable attention in the scientific community due to its desirable properties. However, challenges, such as high viscosity, residual bacterial cells, carotenoids, and protein complexation, hinder the widespread application of welan gum. In this study, we established a method for the extraction and purification of welan gum using a synergistic approach with lysozyme and alkaline protease. Lysozyme hydrolysis conditions were optimized by applying response surface methodology, and the best results for bacterial cell removal were achieved at 11 000 U/g, 44 °C, and pH 9 after 3 h of treatment. Subsequently, we evaluated protein hydrolysis through computer simulation and identified alkaline protease as the most suitable enzyme. Through experimental investigations, we found that the optimal conditions for alkaline protease hydrolysis were 7500 U/g, 50 °C, pH 10, and 600 rpm. These conditions resulted in a sugar recovery rate of 76.1%, carotenoid removal rate of 89.5%, bacterial removal rate of 95.2%, and protein removal rate of 87.3% after 3 h of hydrolysis. The purified welan gum exhibited high transparency and purity. Structural characterization and antioxidant activity evaluation revealed that enzymatically purified welan gum has potential application prospects. Our study provides valuable insights into the optimal method for the enzymatic extraction and purification of welan gum. Such a method is conducive to the development of the multiple potential applications of welan gum. KEY POINTS: ⢠A novel process for the synergistic purification of welan gum using lysozyme and alkaline protease was established. ⢠In silico virtual digestion was employed to select the purification enzyme. ⢠Welan gum with high transparency and purity was obtained.
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Proteínas de Bactérias , Muramidase , Simulação por Computador , CarotenoidesRESUMO
Cereals are one of the most important foods on which human beings rely to sustain basic life activities and are closely related to human health. This study investigated the effects of different steamed buns on intestinal microbiota. Three steamed buns were prepared using refined flour (RF), 1:1 mixed flour (MF), and whole wheat flour (WF). In vitro digestion simulations were conducted using a bionic gastrointestinal reactor (BGR) to examine their influence on intestinal microbiota. The results showed that at 0.5% addition, butyric acid and short-chain fatty acids in WF were significantly different from those in RF and MF (p < 0.05). WF also promoted the proliferation of beneficial microbiota, such as Megamonas and Subdoligranulum. At 0.5%, 1.0%, and 1.5% additions of WF, acetic acid and short-chain fatty acids at 1.5% WF increased by 1167.5% and 11.4% from 0.5% WF, respectively, and by 20.2% and 7.6% from 1.0% WF, respectively. WF also promoted the proliferation of Bifidobacterium, Lactobacillus, and Bacteroides and inhibited the growth of pathogenic microbiota, such as Streptococcus, Enterococcus, and Klebsiella. These findings support the consumption of whole cereals and offer insights into the development of new functional foods derived from wheat.
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In this work, a mannan-oligosaccharide conjugate with sialic acid capable of perturbing Aß42 aggregation was designed and synthesized. Mannan oligosaccharides with degree polymerization of 3-13 were obtained by stepwise hydrolysis of locust bean gum using ß-mannanase and α-galactosidase, named as LBOS. The activated LBOS was further chemically conjugated with sialic acid (Sia, N-acetylneuraminic acid) by fluoro-mercapto chemical coupling to synthesize a conjugate LBOS-Sia, and then phosphorylated to obtain pLBOS-Sia. The successful synthesis of pLBOS-Sia was confirmed by infrared1 chromatography, mass spectrometry, and 1H NMR. The soluble protein analysis, microscopic observation, thioflavin T-labeling, and circular dichroism spectroscopy revealed that both LBOS-Sia and pLBOS-Sia can inhibit Aß42 aggregation. MTT assay showed that LBOS-Sia and pLBOS-Sia had no cytotoxicity to BV-2 cells, and could substantially reduce the release of pro-inflammatory factor TNF-α induced by Aß42 in BV-2 cells, and inhibit the occurrence of neuroinflammation. In future, this novel structure of mannan oligosaccharide-sialic acid conjugate can be potentially used to for the development of glycoconjugates against AD targeting Aß.
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Mananas , Ácido N-Acetilneuramínico , Ácido N-Acetilneuramínico/química , Mananas/farmacologia , Peptídeos beta-Amiloides/química , Oligossacarídeos/farmacologia , Oligossacarídeos/químicaRESUMO
During curdlan production by Agrobacterium sp., the secreted exopolysaccharide (EPS) gradually encapsulated Agrobacterium sp., accompanied by cell aggregation, resulted in inhibited substrate uptake and curdlan synthesis. To relieve the EPS encapsulation effect, the shake-flask culture medium was quantitatively supplemented with 2 % to 10 % endo-ß-1,3-glucanase (BGN), while obtaining curdlan with a decreased weight-average molecular weight ranging from 18.99 × 104 Da to 3.20 × 104 Da. In a 7-L bioreactor, the 4 % BGN supplement substantially attenuated the EPS encapsulation, resulting in increased glucose consumption and curdlan yield to 66.41 g/L and 34.53 g/L after fermentation of 108 h, which improved 43 % and 67 %, respectively compared with the control. The disruption of EPS encapsulation with BGN treatment accelerated the regeneration of ATP and UTP, resulting in sufficient uridine diphosphate glucose for curdlan synthesis. The upregulation of related genes at the transcription level reveals that the respiratory metabolic intensity, the energy regeneration efficiency, and the curdlan synthetase activity were enhanced. This study presents a simple and novel strategy of relieving the effects of EPS encapsulation on the metabolism of Agrobacterium sp. for the high-yield and value-added production of curdlan, which could be potentially applied in producing other EPSs.
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Agrobacterium , beta-Glucanas , Agrobacterium/genética , Agrobacterium/metabolismo , beta-Glucanas/química , Transporte Biológico , FermentaçãoRESUMO
Sialic acids (Sias), a group of over 50 structurally distinct acidic saccharides on the surface of all vertebrate cells, are neuraminic acid derivatives. They serve as glycan chain terminators in extracellular glycolipids and glycoproteins. In particular, Sias have significant implications in cell-to-cell as well as host-to-pathogen interactions and participate in various biological processes, including neurodevelopment, neurodegeneration, fertilization, and tumor migration. However, Sia is also present in some of our daily diets, particularly in conjugated form (sialoglycans), such as those in edible bird's nest, red meats, breast milk, bovine milk, and eggs. Among them, breast milk, especially colostrum, contains a high concentration of sialylated oligosaccharides. Numerous reviews have concentrated on the physiological function of Sia as a cellular component of the body and its relationship with the occurrence of diseases. However, the consumption of Sias through dietary sources exerts significant influence on human health, possibly by modulating the gut microbiota's composition and metabolism. In this review, we summarize the distribution, structure, and biological function of particular Sia-rich diets, including human milk, bovine milk, red meat, and egg.
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On the basis of a novel two-stage pH combined with dissolved oxygen (DO) control strategy in fed-batch fermentation, this research addresses the influence of pH on cyclic ß-1,2-glucans (CßGs) biosynthesis and melanin accumulation during the production of CßGs by Rhizobium radiobacter ATCC 13,333. Under these optimal fermentation conditions, the maximum cell concentration and CßGs concentration in a 7-L stirred-tank fermenter were 7.94 g L-1 and 3.12 g L-1, which were the maximum production reported for R. radiobacter. The melanin concentration of the fermentation broth was maintained at a low level, which was beneficial to the subsequent separation and purification of the CßGs. In addition, a neutral extracellular oligosaccharide (COGs-1) purified by the two-stage pH combined with DO control strategy fermentation medium was structurally characterized. Structural analyses indicated that COGs-1 was a family of unbranched cyclic oligosaccharides composed of only ß-1,2-linked D-glucopyranose residues with degree of polymerization between 17 and 23, namely CßGs. This research provides a reliable source of CßGs and structural basis for further studies of biological activity and function. KEY POINTS: ⢠A two-stage pH combined with DO control strategy was proposed for CßGs production and melanin biosynthesis by Rhizobium radiobacter. ⢠The final extracellular CßGs production reached 3.12 g L-1, which was the highest achieved by Rhizobium radiobacter. ⢠The existence of CßGs could be detected by TLC quickly and accurately.
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Melaninas , Oxigênio , Fermentação , Glucanos , Agrobacterium tumefaciens , Concentração de Íons de HidrogênioRESUMO
Selenium nanoparticles (SeNPs) have attracted much recent interest as nutraceuticals, while they face great challenges, such as poor stability and low cellular uptake efficiency. This study introduced a facile approach to synthesizing protamine sulfate (PS) functionalized selenium nanoparticles (PS-SeNPs) by using PS as a surface decorator. The monodisperse spherical PS-SeNPs with a particle size of 130 nm and a ζ-potential of +31 mV were ligated with PS through Se-N, Se-O bonds, and physical adsorption, which exhibits excellent physical stability against pH, temperature, and storage time. The positive surface charge of PS-SeNPs contributed to the enhancement of cellular uptake efficiency by endocytosis, which was 3-times higher than bare SeNPs. Compared to SeNPs (IC50 = 17.675 µg/mL), PS-SeNPs could dramatically inhibit the proliferation of HepG2 cells with an IC50 value of 5.507 µg/mL, as reflected by the induction of apoptosis, S phase arresting, overproduction of intracellular ROS, and depolarization of mitochondria membrane. Overall, these results demonstrated the great potential of PS-SeNPs that can be applied as a functional ingredient in foods and nutraceuticals.
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Nanopartículas , Selênio , Selênio/farmacologia , Selênio/química , Linhagem Celular Tumoral , Nanopartículas/química , Apoptose , Protaminas/farmacologiaRESUMO
Textiles can be contaminated with pathogens during household laundering, potentially leading to human sickness. In this work, chitosan (CTS) was used as a substrate to prepare Ag/Cu-CTS composite, which was applied in laundering and showed a remarkable antibacterial effect on Escherichia coli and Staphylococcus aureus. The mechanical strength of Ag/Cu-CTS composite beads was higher than 400 MPa. The Ag/Cu-CTS composite were further characterized by scanning electron microscopy and energy dispersive spectroscopy. This composite had a strong inhibitory effect on several laundry pathogens, such as Acinetobacter sp., Pseudomonas aeruginosa, and Candida albicans. Using a standard laundering program and 15 g of Ag/Cu-CTS composite beads, the antibacterial rates reached 99.9%, and no silver emission was detected, thereby satisfying the Chinese requirement for washing machines. After 160 runs of laundering tests, this composite still has an excellent antibacterial effect. For the first time, chitosan is successfully applied as an antibacterial material on household electric appliances.
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Low-gluten rice is part of a special diet for chronic kidney disease patients, but its digestive mechanism in the gastrointestinal tract is unclear. In this study, low-gluten rice (LGR), common rice (CR), and rice starch (RS) were used as experimental samples, and their digestion and bacterial fermentation were simulated using an in vitro gastrointestinal reactor to investigate the mechanism of the effect of LGR on human health. The starch digestibility of CR was higher than that of LGR, with statistically significant differences. LGR has growth-promoting and metabolic effects on Akkermansia muciniphila. Among the beneficial metabolites, the concentration of short-chain fatty acids (SCFAs) from LGR reached 104.85 mmol/L, an increase of 44.94% (versus RS) and 25.33% (versus CR). Moreover, the concentration of lactic acid reached 18.19 mmol/L, an increase of 60.55% (versus RS) and 25.28% (versus CR). Among the harmful metabolites, the concentration of branched-chain fatty acids (BCFAs) in LGR was 0.29 mmol/L and the concentration of ammonia was 2.60 mmol/L, which was 79.31% and 16.15% lower than CR, respectively. A significant increase in the concentration of the beneficial intestinal bacteria Bacteroides and Bifidobacterium occurred from LGR. The 16s rDNA sequencing showed that the abundance of the Bacteroidetes and Firmicutes increased and the abundance of the Proteobacteria and Fusobacteria decreased. Thus, LGR has positive effects on digestion and gut microbiota structure and metabolism in humans.
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Profiling intestinal gases and their responses to dietary changes can reveal the products and functions of the gut microbiota and their influence on human health. High-fat foods (HFF) can alter the gut microbiota and its metabolites, posing a potential health risk. However, little is known about the effects of HFF on intestinal gas distribution. Therefore, in this study, we used human fecal microorganisms as strains, an in vitro three-chamber colon model and an intestinal gas array sensor as tools. We performed in vitro fermentation using HFF as the fermentation substrate to reveal the effects of HFF on the kinetics of intestinal gas production and changes in the gut microbiota and its metabolites. We found that dietary fatty acids stimulated the production of H2S and volatile organic compounds in the colon, promoted Firmicutes abundance, and decreased Bacteroidetes abundance. These results highlight the potential role of HFF in altering the gut microbiota and intestinal gas, which can lead to health hazards.
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Malto-oligosaccharides (MOS) are α-1,4 glycosidic linked linear oligosaccharides of glucose, which have a diverse range of functional applications in the food, pharmaceutical, and other industries. They can be used to modify the physicochemical properties of foods thereby improving their quality attributes, or they can be included as prebiotics to improve their nutritional attributes. The degree of polymerization of MOS can be controlled by using specific enzymes, which means their functionality can be tuned for specific applications. In this article, we review the chemical structure, physicochemical properties, preparation, and functional applications of MOS in the food, health care, and other industries. Besides, we offer an overview for this saccharide from the perspective of prospect functional ingredient, which we feel lacks in the current literature. MOS could be expected to provide a novel promising substitute for functional oligosaccharides.
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An amphiphilic polymer based on octenyl succinic anhydride-modified curdlan oligosaccharide (MCOS) was synthesized. The critical micelle concentration of MCOS was 3.91 µg·mL-1. MCOS could self-assemble into spherical micelles with a particle size of 230.1 nm and a zeta potential of - 37.9 mV. When used for polyphenol encapsulation, the loading capacity of curcumin and quercetin-co-encapsulated micelles was higher than that of single-polyphenol encapsulated micelles. In vitro gastrointestinal release test showed that the MCOS micelle presented a pH-dependent release, released a little polyphenol in simulated gastric fluid, but presented sustained release in the simulated intestinal fluid. The gastrointestinal-digested polyphenol-loaded micelles exhibited excellent antioxidant ability. In vitro human fecal fermentation indicated that the MCOS carrier could promote the production of short-chain fatty acids by gut microbiota and exhibited the highest relative abundance of Megamonas. In addition, the supplementation of curcumin and quercetin-co-loaded MCOS micelles increased the relative abundance of Bifidobacterium and inhibited the growth of Escherichia_Shigella. These findings indicated that the MCOS carrier can be potentially used for the colon-targeted delivery of hydrophobic polyphenols due to its pH-responsive property.
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Proteins from Bacillus thuringiensis are widely used as biopesticides but little is known about its exopolysaccharides. The exopolysaccharide BPS-2 was extracted from B. thuringiensis IX-01 after high-cell-density fermentation. BPS-2 is a heteropolysaccharide (molecular weight 29.36 kDa) composed of D-galactosamine, arabinose, glucosamine, glucose, and mannose in molar ratios 5.53: 1.77:4.74:3.24:1. In vitro upper gastrointestinal simulations showed that BPS-2 has strong anti-digestive capacity, with scavenging of DPPH, hydroxyl, ABTS, and superoxide anions radicals of 31.34 ± 1.67 %, 32.43 ± 3.01 %, 34.31 ± 2.12 %, and 48.53 ± 3.55 %, respectively, after BPS-2 entered the colon. It significantly inhibited production of lipopolysaccharide-induced nitric oxide and multiple pro-inflammatory cytokines and had proliferative effects on RAW 264.7 cells. BPS-2 inhibited malondialdehyde secretion and elevated activities of glutathione peroxidase, superoxide dismutase, and total antioxidants, significantly improving the antioxidant status of inflammation model cells. This first report of the in vitro anti-inflammation and antioxidant properties of BPS-2 from B. thuringiensis provides a basis for biopharmaceutical applications.