Alginate Oligosaccharides Research Articles

Improving thermostability of a PL 5 family alginate lyase with combination of rational design strategies

Alginate lyases with strict substrate specificity possess potential in directed production of alginate oligosaccharides with specific composition. However, their poor thermostability hampered their applications in industry. In this study, an efficient comprehensive strategy including sequence-based analysis, structure-based analysis, and computer-aid ΔΔGfold value calculation was proposed. It was successfully performed on alginate lyase (PMD) with strict poly-β-D-mannuronic acid substrate specificity. Four single-point variants A74V, G75V, A240V, and D250G with increased Tm of 3.94 °C, 5.21 °C, 2.56 °C, and 4.80 °C, respectively, were selected out. After ordered combined mutations, a four-point mutant (M4) was finally generated which displayed remarkable increase on thermostability. The Tm of M4 increased from 42.25 °C to 51.59 °C and its half-life at 50 °C was about 58.9-fold of PMD. Meanwhile, there was no obvious loss of enzyme activity (more than 90% retained). Molecular dynamics simulation analysis insisted that the improvement of thermostability might be attribute to the rigidified region A which might be caused by the newly formed hydrogen bonds and salt bridges introduced by mutations, the lower distance of original hydrogen bonds, and the more compact overall structures.

Preparation of Alginate Oligosaccharides from Laminaria japonica Biomass by a Novel Biofunctional Alginate Lyase with pH and Salt Tolerance

Enzymatic alginate oligosaccharides were proved with various biological activities. Developing robust alginate lyase with high production is essential for its industrial application. In this study, a novel alginate lyase gene, AL07, was successfully screened and expressed in Pichia pastoris, and its characteristics were characterized. The secreted alginate lyase has a molecular weight of approximately 40.0 kDa and an activity of 45.4 U/mL. AL07 exhibits superior biological activity at pH 7.0 and 40 °C, with a preference for polyG substrates. Notably, the enzyme exhibits more than 60% relative activity over a pH range of 5.0 to 10.0. AL07 is also independent of ions and exhibits salt tolerance properties. The main degradation product of AL07 is DP2 oligosaccharide. Using AL07-based enzyme cocktail, Laminaria japonica can be degraded within 120 min. Therefore, AL07 has been demonstrated to be an efficient tool for the preparation of alginate oligosaccharides and the degradation of L. japonica.

Synergistic depolymerisation of alginate and chitosan by high hydrostatic pressure (HHP) and pulsed electric fields (PEF) treatment in the presence of H2O2

Physically-induced depolymerisation procedures are often preferred for obtaining alginate and chitosan oligosaccharides as they either do not use or make minimal use of additional chemicals; therefore, separation of the final products is facile. In this work, solutions of three types of alginate with different mannuronic and guluronic acid residues ratio (M/G ratio) and molecular weights (Mw) and one type of chitosan were non-thermally processed by applying high hydrostatic pressures (HHP) up to 500 MPa (20 min) or pulsed electric fields (PEF) up to 25 kV cm−1 (4000 μm) in the absence or presence of 3 % hydrogen peroxide (H2O2). The impact on the physicochemical properties of alginate and chitosan was investigated by rheology, GPC, XRD, FTIR, and 1H NMR. In the rheological investigations, the apparent viscosities of all samples decreased with increasing shear rate, indicating a non-Newtonian shear-thinning behaviour. GPC results reported Mw reductions that ranged between 8 and 96 % for all treatments. NMR results revealed that HHP and PEF treatment predominantly reduced the M/G ratio of alginate and the degree of deacetylation (DDA) of chitosan, whilst H2O2 promoted an increase in the M/G ratio in alginate and DDA of chitosan. Overall, the present investigation has demonstrated the feasibility of HHP and PEF for rapidly producing alginate and chitosan oligosaccharides.

Alginate Oligosaccharides Enhance Autophagy to Rejuvenate H2O2-Induced Senescent IEC-6 Through the AMPK/mTOR Signaling Pathway.

Intestinal epithelial cellular senescence contributes to the physiological decline of intestine and induces age-associated intestinal diseases. Therefore, the intestine is a vital target to delay intestinal epithelial cellular senescence and extend healthy lifespan. Alginate oligosaccharides (AOSs) have a wide range of biological and pharmacological activities. However, there are no related reports of AOSs on intestinal epithelial cellular senescence. Our study aimed to investigate the effect of AOSs on hydrogen peroxide (H2O2)-induced senescent intestinal epithelial cells (IEC-6) and its antiaging mechanism. A senescent model was successfully constructed by H2O2 (200 μmol/L) treatment on IEC-6 for 4 hours. Different concentrations of AOSs (10, 50, 100 μg/mL) were used to intervene in H2O2-induced senescent IEC-6. The number of β-galactosidase staining-positive cells was significantly reduced by AOS intervention. The expression levels of p21 and p16, known as the senescent biomarkers, were also decreased. In addition, AOSs alleviated oxidative stress by reducing reactive oxygen species and improving antioxidative ability. To understand how AOSs rejuvenate H2O2-induced senescent IEC-6, we detected the expression level of genes in autophagy process. The results indicated that AOSs restored the expression level of Beclin 1, Atg7, and LC3 to enhance autophagy process by activating activated protein kinase (AMPK) and inhibiting mammalian target of rapamycin in H2O2-induced senescent IEC-6. Compound C, an AMPK inhibitor, abolished the effect of AOSs on activating autophagy and rejuvenating senescent IEC-6. Altogether, our study suggests that AOS is a promising drug for delaying intestinal epithelial cellular senescence.

Response of Salmonella enterica serovar Typhimurium to alginate oligosaccharides fermented with fecal inoculum: integrated transcriptomic and metabolomic analyses

Alginate oligosaccharides (AOS), extracted from marine brown algae, are a common functional feed additive; however, it remains unclear whether they modulate the gut microbiota and microbial metabolites. The response of Salmonella enterica serovar Typhimurium, a common poultry pathogen, to AOS fermented with chicken fecal inocula was investigated using metabolomic and transcriptomic analyses. Single-strain cultivation tests showed that AOS did not directly inhibit the growth of S. Typhimurium. However, when AOS were fermented by chicken fecal microbiota, the supernatant of fermented AOS (F-AOS) exhibited remarkable antibacterial activity against S. Typhimurium, decreasing the abundance ratio of S. Typhimurium in the fecal microbiota from 18.94 to 2.94%. Transcriptomic analyses showed that the 855 differentially expressed genes induced by F-AOS were mainly enriched in porphyrin and chlorophyll metabolism, oxidative phosphorylation, and Salmonella infection-related pathways. RT-qPCR confirmed that F-AOS downregulated key genes involved in flagellar assembly and the type III secretory system of S. Typhimurium, indicating metabolites in F-AOS can influence the growth and metabolism of S. Typhimurium. Metabolomic analyses showed that 205 microbial metabolites were significantly altered in F-AOS. Among them, the increase in indolelactic acid and 3-indolepropionic acid levels were further confirmed using HPLC. This study provides a new perspective for the application of AOS as a feed additive against pathogenic intestinal bacteria.

Efficient adsorption of alginate oligosaccharides by ion exchange resin based on molecular simulation and experiments

Alginate oligosaccharides (AOS) with low polymerization have gained considerable attention due to their unique physiological activities. However, the lack of understanding regarding the mechanism of action for resin selection and optimization of separation processes has impeded their precise chromatographic separation and large-scale production. Here, the adsorption–desorption characteristics of AOS on the resins with varying solid phase composition, including backbones, functional groups, crosslinking degrees, and counterions resin structures, were analyzed using simulations and experiments. The simulation results revealed that the structural differences of AOS are characterized by their electrostatic potential and lowest unoccupied molecular orbital energy level. Based on molecular simulations, we predicted that the basic anion resin with a styrene backbone would be suitable for AOS separation. Subsequently, we constructed SM-7Cl resin based on the simulation results and performed static adsorption experiments to verify the prediction. SM-7Cl resin demonstrated noteworthy adsorption–desorption performance for AOS, with an adsorption capacity of 471.2 mg/g and a desorption rate of 89.45%. The fitting adsorption isotherm was consistent with the Freundlich model, indicating that the adsorption proceeded spontaneously. The equilibrium times for AOS adsorption on the gel-type resin and the macroporous resin, which both followed a pseudo-second-order kinetic model, were 30 min and 60 min, respectively. This study provides optimized chromatographic media and separation processing that can be implemented for the amplification of chromatographic separation in AOS production.

Alginate oligosaccharide alleviates aging-related intestinal mucosal barrier dysfunction by blocking FGF1-mediated TLR4/NF-κB p65 pathway

BackgroundAlginate oligosaccharide (AOS) has been reported to exert a crucial role in maintaining the intestinal mucosal barrier (IMB) function. The current study aimed at ascertaining the protective effects of AOS on aging-induced IMB dysfunction and to elucidate the underlying molecular mechanisms. MethodsAn aging mouse model and a senescent NCM460 cell model were established using d-galactose. AOS was administered to aging mice and senescent cells, and IMB permeability, inflammatory response and tight junction proteins were assessed. In silico analysis was conducted to identify factors regulated by AOS. Using gain- and loss-of-function approaches, we evaluated the roles of FGF1, TLR4 and NF-κB p65 in the aging-induced IMB dysfunction and NCM460 cell senescence. ResultsAOS protected the IMB function of aging mice and NCM460 cells by reducing permeability and increasing tight junction proteins. In addition, AOS up-regulated FGF1, which blocked the TLR4/NF-κB p65 pathway, and identified as the mechanism responsible for the protective effect of AOS. ConclusionAOS blocks the TLR4/NF-κB p65 pathway via inducing FGF1, ultimately reducing the risk of IMB dysfunction in aging mice. This study highlights the potential of AOS as a protective agent against aging-induced IMB disorder and provides insight into the underlying molecular mechanisms.

Gut bacterial alginate degrading enzymes.

Alginates are abundant marine anionic polysaccharides consumed by humans. Thus, over the years some understanding has emerged about alginate utilization by human gut microbiota (HGM). However, insights have been obtained only recently at the molecular level with regard to structure and function of alginate degrading and metabolizing enzymes from HGM. Still, numerous studies report on effects of alginates on bacterial communities from digestive tracts of various, predominantly marine organisms feeding on alginate and some of the involved alginate lyases have been characterized. Other studies describe the beneficial impact on gut microbiota elicited by alginates in animal models, for example, high-fat-diet-fed mice addressing obesity or as feed supplements for livestock. Alginates are depolymerized by a β-elimination reaction catalyzed by polysaccharide lyases (PLs) referred to as alginate lyases (ALs). The ALs are found in 15 of the 42 PL families categorized in the CAZy database. While genome mining has led to prediction of ALs encoded by bacteria of the HGM; currently, only four enzymes from this niche have been characterized biochemically and two crystal structures are reported. Alginates are composed of mannuronate (M) and guluronate (G) residues organized in M-, G-, and MG-blocks, which calls for ALs of complementary specificity to effectively depolymerize alginate to alginate oligosaccharides (AOSs) and monosaccharides. Typically, ALs of different PL families are encoded by genes arranged in clusters denoted as polysaccharide utilization loci. Currently, biochemical and structural analyses of marine bacterial ALs contribute to depicting the mode of action of predicted enzymes from bacteria of the HGM.

Synergistic effects of alginate oligosaccharide and cyanidin-3-O-glucoside on the amelioration of intestinal barrier function in mice

Emerging evidence shows that dietary oligosaccharides are important prebiotics that can improve intestinal flora, while dietary polyphenols can act directly on intestinal cells. However, information about their synergistic effects on gut health is still limited. In this study, alginate oligosaccharide (AOS) and cyanidin-3-O-glucoside (C3G) were selected as a common marine plant oligosaccharide and terrestrial plant polyphenol, respectively, to study their effects on intestinal health. The results show that, in comparison to their individual applications, the combination of AOS and C3G (mass ratio, 3:1) displayed a stronger ability to up-regulate the expression of tight junction proteins, while enhanced intestinal epithelial barrier was also observed and levels of mucin-2 and β-defensins were simultaneously increased in the intestinal mucus. Interestingly, the secretion of immunoglobulin A and immune-related cytokines were approximately doubled by the AOS + C3G mixture. In addition, the AOS + C3G mixture was found to be more conducive to the positive transformation of intestinal flora, which stimulated the growth of beneficial bacteria Akkermansia, Lachnospiraceae and Feacalibaculum while inhibiting the growth of harmful bacteria Helicobacter and Turicibacter. The data generated herein thus suggests that dietary oligosaccharides and dietary polyphenols may be more beneficial to intestinal health when applied in combination than their individual effects alone.

Valorization of the pelagic Sargassum horneri for co-production of erythritol and alginate oligosaccharides

Pelagic Sargassum is invasive macroalgae with huge biomass. To produce bulk chemicals with profit from the biomass, innovative strategies need to be developed. In this study, maximum saccharification yield of Sargassum horneri biomass was obtained with the combined use of 3% alginate lyase and 3% cellulase, releasing 20.83 g/L glucose and 1.73 g/L mannitol at a 1:6 feed ratio. Subsequently, the crude S. horneri hydrolysate (pH 3.0) was proved most suitable for erythritol production of Yarrowia lipolytica strain. After 60 h fermentation in a 10-L fermenter, the erythritol concentration reached 18.42 g/L with a yield of 0.82 g/g; while the concentration of alginate oligosaccharides (AOS) was 37.56 g/L. Finally, AOS with a purity of 93.4% were obtained by ethanol precipitation, and erythritol was harvested via crystallization. This proposed strategy demonstrates the feasibility of transforming invasive Sargassum into two high-value chemicals for the first time.

Discontinuous low temperature stress and plant growth regulators during the germination period promote roots growth in alfalfa (Medicago sativa L.)

In high-cold regions, alfalfa is susceptible to cold damage during the seed germination. The effects of discontinuous low temperature stress and plant growth regulators (PGRs) on alfalfa were studied in response to the high day/night temperature differentials in the area. The experiments included seed germination, seedling cold tolerance and plant recovery. Variable temperatures (VT) of 0 °C/15 °C, 5 °C/20 °C and 10 °C/25 °C were set and seeds were soaked with alginate oligosaccharides (AOS), brassinolide (BR) and diethyl aminoethyl hexanoate (DA-6) during the germination period. Parameters such as seed germination and mean germination time (MGT), phenylalanine ammonia-lyase (PAL) activity and oligomeric proanthocyanidins (OPC) content of early seedlings, dry matter accumulation and root crown of the restored plants were analysed. The results showed that low variable-temperature (LVT) stress prolonged the MGT but had little inhibitory effect on germination percentage. Early seedlings adapted to LVT stress by regulating their own water and OPC content, PAL activity and other parameters. LVT induced early alfalfa seedlings to increase their underground biomass by shortening root length and increasing root diameter, and those that had accumulated more underground biomass had faster growth rates and higher total biomass when the ambient temperature rose. AOS also promoted an increase in root crown diameter and root dry weight. This research proved that LVT stress and AOS during the germination process can lead to better growth of alfalfa in high cold regions.

Efficient Degradation of Alginate and Preparation of Alginate Oligosaccharides by a Novel Biofunctional Alginate Lyase with High Activity and Excellent Thermophilic Features.

The enzymatic degradation of seaweed polysaccharides is gaining interest for its potential in the production of functional oligosaccharides and fermentable sugars. Herein, a novel alginate lyase, AlyRm3, was cloned from a marine strain, Rhodothermus marinus DSM 4252. The AlyRm3 showed optimal activity (37,315.08 U/mg) at 70 °C and pH 8.0, with the sodium alginate used as a substrate. Noticeably, AlyRm3 was stable at 65 °C and also exhibited 30% of maximal activity at 90 °C. These results indicated that AlyRm3 is a thermophilic alginate lyase that efficiently degrades alginate at high industrial temperatures (>60 °C). The FPLC and ESI-MS analyses suggested that AlyRm3 primarily released disaccharides and trisaccharides from the alginate, polyM, and polyG in an endolytic manner. In the saccharification process of sodium alginate (0.5%, w/v), the AlyRm3 yielded numerous reducing sugars (1.73 g/L) after 2 h of reaction. These results indicated that AlyRm3 has a high enzymatic capacity for saccharifying the alginate, and could be used to saccharify the alginate biomass before the main fermentation process for biofuels. These properties make AlyRm3 a valuable candidate for both fundamental research and industrial applications.

Alginate oligosaccharide structures differentially affect DSS-induced colitis in mice by modulating gut microbiota

Alginate oligosaccharides (AOS) are divided by their monomer sequences into three types: oligomannuronate (MAOS), oligoguluronate (GAOS), and heterogeneous AOS (HAOS). However, how these AOS structures differentially regulate health and modulate gut microbiota is unclear. We explored the structure-function relationship of AOS both in an in vivo colitis model and an in vitro enterotoxigenic Escherichia coli (ETEC)-challenged cell model. We found that MAOS administration significantly alleviated the symptom of experimental colitis and improved the gut barrier function in vivo and in vivo. Nevertheless, HAOS and GAOS were less effective than MAOS. The abundance and diversity of gut microbiota are obviously increased by MAOS intervention, but not by HAOS or GAOS. Importantly, microbiota from MAOS-dosed mice through FMT decreased the disease index level, alleviated histopathological changes, and improved gut barrier function in the colitis model. Super FMT donors induced by MAOS but not by HAOS or GAOS, seemed to exert potential in colitis bacteriotherapy. These findings may aid in establishing precise pharmaceutical applications based on the targeted production of AOS.

Characterization of a thermostable PL-31 family alginate lyase from Paenibacillus ehimensis and its application for alginate oligosaccharides bioproduction

Currently, people pay more attention to marine sugars, because of their unique physiological effects. Alginate oligosaccharides (AOS) are the degradation products of alginate and have been used in food, cosmetic, and medicine fields. AOS display good physical characteristics (low relative molecular weight, good solubility, high safety, and high stability) and excellent physiological functions (immunomodulatory, antioxidant, antidiabetic, and prebiotic activities). Alginate lyase plays a key role in the AOS bioproduction. In this study, a novel PL-31 family alginate lyase from Paenibacillus ehimensis (paeh-aly) was identified and characterized. It was extracellularly secreted in E. coli and exhibited a preference for the substrate poly β-D-mannuronate. Using sodium alginate as the substrate, it showed the maximum catalytic activity (125.7 U/mg) at pH 7.5 and 55 °C with 50 mM NaCl. Compared with other alginate lyases, paeh-aly exhibited good stability. About 86.6% and 61.0% residual activity could be maintained after 5 h incubation at 50 and 55 °C respectively, and its Tm value was 61.5 °C. The degradation products were AOS with DP 2–4. Paeh-aly demonstrated strong promise for AOS industrial production because of its excellent thermostability and efficiency.

Adsorption mechanisms of alginate oligosaccharides with specific degree of polymerizations on a novel ion-exchange resin: Experiments and simulations

Alginate oligosaccharides (AOS) with a specific degree of polymerization (DP) have unique physiological activity, but industrialization and high-value applications of AOS are restricted due to the paucity of study on its precise separation mechanism. In the process design of adsorption separation chromatography, the adsorption behaviors of the adsorbent are crucial. Herein, the adsorption properties of AOS with DPs 1–4 (AOS1-4) on novel SM-7 resin were clarified by combining adsorption experiments and theoretical calculations. The effect of various parameters on the adsorption process of AOS1-4 was investigated using a series of static adsorption tests. Molecular dynamics modeling was implemented to determine the interaction energy and diffusion between AOS1-4 and SM-7 resin. The results of the adsorption equilibrium demonstrated that the adsorption of AOS1-4 complied with the Langmuir model and exhibited ion dependency and pH stability. The saturation adsorption capacities of AOS1-4 on SM-7 resin were 1.144 mmol/g, 0.810 mmol/g, 0.730 mmol/g, and 0.582 mmol/g, respectively. The external diffusion was the primary rate-limiting phase in the adsorption kinetics of AOS1-4, which followed the pseudo-second-order kinetic model. As the increasing of DPs of AOS, the hydroxyl, carboxyl, and molecular volume rose, which decreased the adsorption capacity and rate. Simulation results showed that interaction energies between SM-7 resin and AOS enhanced while the diffusion coefficient declined with rising DPs of AOS. Hydrogen bond interaction and electrostatic attraction promoted the adsorption of AOS on the novel resin. The fundamental theoretical data in this study can provide guidance for the large-scale preparation of AOS with specific DPs.

Alginate Oligosaccharides Repair Liver Injury by Improving Anti-Inflammatory Capacity in a Busulfan-Induced Mouse Model.

Liver diseases are associated with many factors, including medicines and alcoholics, which have become a global problem. It is crucial to overcome this problem. Liver diseases always come with inflammatory complications, which might be a potential target to deal with this issue. Alginate oligosaccharides (AOS) have been demonstrated to have many beneficial effects, especially anti-inflammation. In this study, 40 mg/kg body weight (BW) of busulfan was intraperitoneally injected once, and then the mice were dosed with ddH2O or AOS 10 mg/kg BW every day by oral gavage for five weeks. We investigated AOS as a potential no-side-effect and low-cost therapy for liver diseases. For the first time, we discovered that AOS 10 mg/kg recovered liver injury by decreasing the inflammation-related factors. Moreover, AOS 10 mg/kg could improve the blood metabolites related to immune and anti-tumor effects, and thus, ameliorated impaired liver function. The results indicate that AOS may be a potential therapy to deal with liver damage, especially in inflammatory conditions.

Alginate oligosaccharides enhance the antifungal activity of nystatin against candidal biofilms.

The increasing prevalence of invasive fungal infections in immuno-compromised patients is a considerable cause of morbidity and mortality. With the rapid emergence of antifungal resistance and an inadequate pipeline of new therapies, novel treatment strategies are now urgently required. The antifungal activity of the alginate oligosaccharide OligoG in conjunction with nystatin was tested against a range of Candida spp. (C. albicans, C. glabrata, C. parapsilosis, C. auris, C. tropicalis and C. dubliniensis), in both planktonic and biofilm assays, to determine its potential clinical utility to enhance the treatment of candidal infections. The effect of OligoG (0-6%) ± nystatin on Candida spp. was examined in minimum inhibitory concentration (MIC) and growth curve assays. Antifungal effects of OligoG and nystatin treatment on biofilm formation and disruption were characterized using confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM) and ATP cellular viability assays. Effects on the cell membrane were determined using permeability assays and transmission electron microscopy (TEM). MIC and growth curve assays demonstrated the synergistic effects of OligoG (0-6%) with nystatin, resulting in an up to 32-fold reduction in MIC, and a significant reduction in the growth of C. parapsilosis and C. auris (minimum significant difference = 0.2 and 0.12 respectively). CLSM and SEM imaging demonstrated that the combination treatment of OligoG (4%) with nystatin (1 µg/ml) resulted in significant inhibition of candidal biofilm formation on glass and clinical grade silicone surfaces (p < 0.001), with increased cell death (p < 0.0001). The ATP biofilm disruption assay demonstrated a significant reduction in cell viability with OligoG (4%) alone and the combined OligoG/nystatin (MIC value) treatment (p < 0.04) for all Candida strains tested. TEM studies revealed the combined OligoG/nystatin treatment induced structural reorganization of the Candida cell membrane, with increased permeability when compared to the untreated control (p < 0.001). Antimicrobial synergy between OligoG and nystatin against Candida spp. highlights the potential utility of this combination therapy in the prevention and topical treatment of candidal biofilm infections, to overcome the inherent tolerance of biofilm structures to antifungal agents.

Spraying alginate oligosaccharide improves photosynthetic performance and sugar accumulation in citrus by regulating antioxidant system and related gene expression.

Alginate oligosaccharides (AOS) are functional substances in seaweed extracts that regulate crop quality and stress tolerance. In this paper, the effects of AOS spray application on the antioxidant system, photosynthesis and fruit sugar accumulation in citrus was investigated through a two-year field experiment. The results showed that 8-10 spray cycles of 300-500 mg L-1 AOS (once per 15 days) increased soluble sugar and soluble solid contents by 7.74-15.79% and 9.98-15.35%, respectively, from citrus fruit expansion to harvesting. Compared with the control, the antioxidant enzyme activity and the expression of some related genes in citrus leaves started to increase significantly after the 1st AOS spray application, while the net photosynthetic rate of leaves increased obviously only after the 3rd AOS spray cycle, and the soluble sugar content of AOS-treated leaves increased by 8.43-12.96% at harvest. This suggests that AOS may enhance photosynthesis and sugar accumulation in leaves by antioxidant system regulation. Moreover, analysis of fruit sugar metabolism showed that during the 3rd to 8th AOS spray cycles, AOS treatment increased the activity of enzymes related to sucrose synthesis (SPS, SSs), upregulated the expression of sucrose metabolism (CitSPS1, CitSPS2, SUS) and transport (SUC3, SUC4) genes, and promoted the accumulation of sucrose, glucose and fructose in fruits. Notably, the concentration of soluble sugars in citrus fruits was significantly reduced at all treatments with 40% reduction in leaves of the same branch, but the loss of soluble sugars in AOS-treated fruits (18.18%) was higher than that in the control treatment (14.10%). It showed that there was a positive effect of AOS application on leaf assimilation product transport and fruit sugar accumulation. In summary, AOS application may improve fruit sugar accumulation and quality by regulating the leaf antioxidant system, increasing the photosynthetic rate and assimilate product accumulation, and promoting sugar transfer from leaves to fruits. This study shows the potential application of AOS in the production of citrus fruits for sugar enhancement.

Effects of Alginate Oligosaccharide on Testosterone-Induced Benign Prostatic Hyperplasia in Orchiectomized Rats.

Benign prostatic hyperplasia (BPH) is an age-related disease of the urinary system that affects elderly men. Current treatments for BPH are associated with several adverse effects, thus highlighting the need for alternative agents. Alginate oligosaccharide (AOS), a water-soluble functional oligomer derived from brown algae, inhibits prostate cancer cell proliferation. However, the effects of AOS on BPH and the underlying molecular mechanisms remain unclear. Therefore, here, we aimed to investigate the therapeutic potential of AOS in BPH by using human benign prostatic epithelial cells (BPH-1) and a rat model of testosterone-induced BPH. Treatment with AOS inhibited in vitro and in vivo proliferation of prostatic epithelial cells and the testosterone-induced expression of androgen receptor (AR) and androgen-associated genes, such as those encoding 5α-reductase type 2 and prostate-specific antigen. Oral administration of AOS remarkably reduced the serum levels of dihydrotestosterone (DHT) and testosterone as well as the expression of proliferating cell nuclear antigen, inflammatory cytokines, and enzymes, which showed increased levels in prostatic tissues of rats with testosterone-induced BPH. Taken together, these data demonstrate that AOS suppresses testosterone-induced BPH in rats by downregulating AR and the expression of androgen-associated genes, supporting the hypothesis that AOS might be of potential use for the treatment of BPH.

An exploration of alginate oligosaccharides modulating intestinal inflammatory networks via gut microbiota.

Alginate oligosaccharides (AOS) can be obtained by acidolysis and enzymatic hydrolysis. The products obtained by different methods have different structures and physiological functions. AOS have received increasing interest because of their many health-promoting properties. AOS have been reported to exert protective roles for intestinal homeostasis by modulating gut microbiota, which is closely associated with intestinal inflammation, gut barrier strength, bacterial infection, tissue injury, and biological activities. However, the roles of AOS in intestinal inflammation network remain not well understood. A review of published reports may help us to establish the linkage that AOS may improve intestinal inflammation network by affecting T helper type 1 (Th1) Th2, Th9, Th17, Th22 and regulatory T (Treg) cells, and their secreted cytokines [the hub genes of protein-protein interaction networks include interleukin-1 beta (IL-1β), IL-2, IL-4, IL-6, IL-10 and tumor necrosis factor alpha (TNF-α)] via the regulation of probiotics. The potential functional roles of molecular mechanisms are explored in this study. However, the exact mechanism for the direct interaction between AOS and probiotics or pathogenic bacteria is not yet fully understood. AOS receptors may be located on the plasma membrane of gut microbiota and will be a key solution to address such an important issue. The present paper provides a better understanding of the protecting functions of AOS on intestinal inflammation and immunity.