Pleurotus sajor-caju (Fr.) Singer ß-1,3-Glucanoligosaccharide (Ps-GOS) Suppresses RANKL-Induced Osteoclast Differentiation and Function in Pre-Osteoclastic RAW 264.7 Cells by Inhibiting the RANK/NFκB/cFOS/NFATc1 Signalling Pathway.

Edible grey oyster mushroom, Pleurotus sajor-caju, ß (1,3), (1,6) glucan possesses a wide range of biological activities, including anti-inflammation, anti-microorganism and antioxidant. However, its biological activity is limited by low water solubility resulting from its high molecular weight. Our previous study demonstrated that enzymatic hydrolysis of grey oyster mushroom ß-glucan using Hevea ß-1,3-glucanase isozymes obtains a lower molecular weight and higher water solubility, Pleurotus sajor-caju glucanoligosaccharide (Ps-GOS). Additionally, Ps-GOS potentially reduces osteoporosis by enhancing osteoblast-bone formation, whereas its effect on osteoclast-bone resorption remains unknown. Therefore, our study investigated the modulatory activities and underlying mechanism of Ps-GOS on Receptor activator of nuclear factor kappa-Β ligand (RANKL) -induced osteoclastogenesis in pre-osteoclastic RAW 264.7 cells. Cell cytotoxicity of Ps-GOS on RAW 264.7 cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and its effect on osteoclast differentiation was determined by tartrate-resistant acid phosphatase (TRAP) staining. Additionally, its effect on osteoclast bone-resorptive ability was detected by pit formation assay. The osteoclastogenic-related factors were assessed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), Western blot and immunofluorescence. The results revealed that Ps-GOS was non-toxic and significantly suppressed the formation of mature osteoclast multinucleated cells and their resorption activity by reducing the number of TRAP-positive cells and pit formation areas in a dose-dependent manner. Additionally, Ps-GOS attenuated the nuclear factor kappa light chain-enhancer of activated B cells' P65 (NFκB-P65) expression and their subsequent master osteoclast modulators, including nuclear factor of activated T cell c1 (NFATc1) and Fos proto-oncogene (cFOS) via the NF-κB pathway. Furthermore, Ps-GOS markedly inhibited RANK expression, which serves as an initial transmitter of many osteoclastogenesis-related cascades and inhibited proteolytic enzymes, including TRAP, matrix metallopeptidase 9 (MMP-9) and cathepsin K (CTK). These findings indicate that Ps-GOS could potentially be beneficial as an effective natural agent for bone metabolic disease.

Nutraceutical blends predict enhanced health via microbiota reshaping improving cytokines and life quality: a Brazilian double-blind randomized trial.

Nutraceutical interventions supporting microbiota and eliciting clinical improvements in metabolic diseases have grown significantly. Chronic stress, gut dysbiosis, and metainflammation have emerged as key factors intertwined with sleep disorders, consequently exacerbating the decline in quality of life. This study aimed to assess the effects of two nutraceutical formulations containing prebiotics (fructooligosaccharides (FOS), galactooligosaccharides (GOS), yeast ß-glucans), minerals (Mg, Se, Zn), and the herbal medicine Silybum marianum L. Gaertn., Asteraceae (Milk thistle or Silymarin). These formulations, namely NSupple (without silymarin) and NSupple_Silybum (with silymarin) were tested over 180 days in overweight/obese volunteers from Brazil's southeastern region. We accessed fecal gut microbiota by partial 16S rRNA sequences; cytokines expression by CBA; anthropometrics, quality of life and sleep, as well as metabolic and hormonal parameters, at baseline (T0) and 180 days (T180) post-supplementation. Results demonstrated gut microbiota reshaping at phyla, genera, and species level post-supplementation. The Bacteroidetes phylum, Bacteroides, and Prevotella genera were positively modulated especially in the NSupple_Silybum group. Gut microbiota modulation was associated with improved sleep patterns, quality-of-life perception, cytokines expression, and anthropometric parameters post-supplementation. Our findings suggest that the nutraceutical blends positively enhance cardiometabolic and inflammatory markers. Particularly, NSupple_Silybum modulated microbiota composition, underscoring its potential significance in ameliorating metabolic dysregulation. Clinical trial registry number: NCT04810572. 23/03/2021.

Exploring Synergistic Effects of Levan and Levan-Metabolizing Bacillaceae in Promoting Growth and Enhancing Immunity of Tomato and Wheat.

Boosting plant immunity by priming agents can lower agrochemical dependency in plant production. Levan and levan-derived oligosaccharides (LOS) act as priming agents against biotic stress in several crops. Additionally, beneficial microbes can promote plant growth and protect against fungal diseases. This study assessed possible synergistic effects caused by levan, LOS and five levan- and LOS-metabolizing Bacillaceae (Bacillus and Priestia) strains in tomato and wheat. Leaf and seed defense priming assays were conducted in non-soil (semi-sterile substrate) and soil-based systems, focusing on tomato-Botrytis cinerea and wheat-Magnaporthe oryzae Triticum (MoT) pathosystems. In the non-soil system, seed defense priming with levan, the strains (especially Bacillus velezensis GA1), or their combination significantly promoted tomato growth and protection against B. cinerea. While no growth stimulatory effects were observed for wheat, disease protective effects were also observed in the wheat-MoT pathosystem. When grown in soil and subjected to leaf defense priming, tomato plants co-applied with levan and the bacterial strains showed increased resistance to B. cinerea compared with plants treated with levan or single strains, and these effects were synergistic in some cases. For seed defense priming in soil, more synergistic effects on disease tolerance were observed in a non-fertilized soil as compared to a fertilized soil, suggesting that potential prebiotic effects of levan are more prominent in poor soils. The potential of using combinations of Bacilliaceae and levan in sustainable agriculture is discussed.

Understanding Antidiabetic Potential of Oligosaccharides from Red Alga Dulse Devaleraea inkyuleei Xylan by Investigating α-Amylase and α-Glucosidase Inhibition.

In this study, the α-glucosidase (maltase-glucoamylase: MGAM) and α-amylase inhibitory properties elicited by xylooligosaccharides (XOSs) prepared from dulse xylan were analysed as a potential mechanism to control postprandial hyperglycaemia for type-2 diabetes prevention and treatment. Xylan was purified from red alga dulse powder and used for enzymatic hydrolysis using Sucrase X to produce XOSs. Fractionation of XOSs produced xylobiose (X2), ß-(1→3)-xylosyl xylobiose (DX3), xylotriose (X3), ß-(1→3)-xylosyl-xylotriose (DX4), and a dulse XOS mixture with n ≥ 4 xylose units (DXM). The different fractions exhibited moderate MGAM (IC50 = 11.41-23.44 mg/mL) and α-amylase (IC50 = 18.07-53.04 mg/mL) inhibitory activity, which was lower than that of acarbose. Kinetics studies revealed that XOSs bound to the active site of carbohydrate digestive enzymes, limiting access to the substrate by competitive inhibition. A molecular docking analysis of XOSs with MGAM and α-amylase clearly showed moderate strength of interactions, both hydrogen bonds and non-bonded contacts, at the active site of the enzymes. Overall, XOSs from dulse could prevent postprandial hyperglycaemia as functional food by a usual and continuous consumption.

Effects of xylo-oligosaccharide on gut microbiota, brain protein expression, and lipid profile induced by high-fat diet.

Midlife overweight and obesity are risk factors of cognitive decline and Alzheimer' s disease (AD) in late life. In addition to increasing risk of obesity and cognitive dysfunction, diets rich in fats also contributes to an imbalance of gut microbiota. Xylo-oligosaccharides (XOS) are a kind of prebiotic with several biological advantages, and can selectively promote the growth of beneficial microorganisms in the gut. To explore whether XOS can alleviate cognitive decline induced by high-fat diet (HFD) through improving gut microbiota composition, mice were fed with normal control or 60% HFD for 9 weeks to induce obesity. After that, mice were supplemented with XOS (30 g or 60 g/kg-diet) or without, respectively, for 12 weeks. The results showed that XOS inhibited weight gain, decreased epidydimal fat weight, and improved fasting blood sugar and blood lipids in mice. Additionally, XOS elevated spatial learning and memory function, decreased amyloid plaques accumulation, increased brain-derived neurotrophic factor levels, and improved neuroinflammation status in hippocampus. Changes in glycerolipids metabolism-associated lipid compounds caused by HFD in hippocampus were reversed after XOS intervention. On the other hand, after XOS intervention, increase in immune-mediated bacteria, Faecalibacterium was observed. In conclusion, XOS improved gut dysbiosis and ameliorated spatial learning and memory dysfunction caused by HFD by decreasing cognitive decline-associated biomarkers and changing lipid composition in hippocampus.

Effect of inulin, galacto-oligosaccharides, and polyphenols on the gut microbiota, with a focus on Akkermansia muciniphila.

Inulins, galacto-oligosaccharides (GOS) and polyphenols are considered to stimulate the growth of Akkermansia muciniphila (A. muciniphila) in the gut. We performed a meta-analysis of six microbiome studies (821 stool samples from 451 participants) to assess the effects of inulin, GOS, and polyphenols on the abundance of A. muciniphila in the gut. The intervention of GOS increased the relative abundance of A. muciniphila in healthy participants. Additionally, metabolic pathways associated with carbohydrate metabolism and short-chain fatty acid release were enriched following the GOS intervention. Furthermore, after the GOS intervention, the coexisting microbial communities of A. muciniphila, such as Eubacterium hallii and Bacteroides, exhibited an enhanced correlation with A. muciniphila. In conclusion, our findings suggest that GOS may promote the growth of A. muciniphila in the gut by modulating the gut microbiota composition.

Inhibition of insulin fibrillation by carboxyphenylboronic acid-modified chitosan oligosaccharide based on electrostatic interactions and hydrophobic interactions.

A novel inhibitor, carboxyphenylboronic acid-modified chitosan oligosaccharide (COS-CPBA), was developed by coupling carboxyphenylboronic acid (CPBA) with chitosan oligosaccharide (COS) to inhibit insulin fibrillation. Extensive biophysical assays indicated that COS-CPBA could decelerate insulin aggregation, hinder the conformational transition from α-helix to ß-sheet structure, change the morphology of insulin aggregates and alter fibrillation pathway. A mechanism for the inhibition of insulin fibrillation by COS-CPBA was proposed. It considers that insulin molecules bind to COS-CPBA via hydrophobic interactions, while the positively charged groups in COS-CPBA exert electrostatic repulsion on the bound insulin molecules. These two opposite forces cause the insulin molecules to display extended conformations and hinder the conformational transition of insulin from α-helix to ß-sheet structure necessary for fibrillation, thus decelerating aggregation and altering the fibrillation pathway of insulin. The studies provide novel ideas for the development of more effective inhibitors of amyloid fibrillation.

Fructooligosaccharides Intake during Pregnancy Improves Metabolic Phenotype of Offspring in High Fat Diet-Induced Obese Mice.

SCOPE: Obesity and metabolic diseases are closely associated, and individuals who become obese are also prone to type 2 diabetes and cardiovascular disorders. Gut microbiota is mediated by diet and can influence host metabolism and the incidence of metabolic disorders. Recent studies have suggested that improving gut microbiota through a fructooligosaccharide (FOS)-supplemented diet may ameliorate obesity and other metabolic disorders. Although accumulating evidence supports the notion of the developmental origins of health and disease, the underlying mechanisms remain obscure. METHODS AND RESULTS: ICR mice are fed AIN-93G formula-based cellulose -, FOS-, acetate-, or propionate-supplemented diets during pregnancy. Offspring are reared by conventional ICR foster mothers for 4 weeks; weaned mice are fed high fat diet for 12 weeks and housed individually. The FOS and propionate offspring contribute to suppressing obesity and improving glucose intolerance. Gut microbial compositions in FOS-fed mothers and their offspring are markedly changed. However, the beneficial effect of FOS diet on the offspring is abolished when antibiotics are administered to pregnant mice. CONCLUSION: The findings highlight the link between the maternal gut environment and the developmental origin of metabolic syndrome in offspring. These results open novel research avenues into preemptive therapies for metabolic disorders by targeting the maternal gut microbiota.

[Immunoadjuvant Effect of Chitosan Oligosaccharide and Its Feasibility of Being Used as an Adjuvant for Attenuated Live Bacteria Vector Vaccines]. / å£³å¯¡ç³–çš„å ç–«ä½å‰‚æ•ˆæžœåŠä½œä¸ºå‡æ¯’æ´»èŒè½½ä½“ç–«è‹—ä½å‰‚çš„å¯è¡Œæ€§æŽ¢ç´¢.

Objective: To study the immunoadjuvant effects of chitosan oligosaccharide (COS), including the immune activation and the triggering of lysosomal escape, and to explore whether COS can be used as an adjuvant for attenuated live bacteria vector vaccines. Methods: 1) Mouse macrophages RAW264.7 cells were cultured with COS at 0 mg/mL (the control group) and 0.1-4 mg/mL for 24 h and the effect on cell viability was measured by CCK8 assay. Mouse macrophages RAW264.7 were treated with COS at 0 (the control group), 1, 2, and 4 mg/mL for 24 h. Then, the mRNA expression levels of the cytokines, including IFN-γ, IL-10, TGF-ß, and TLR4, were determined by RT-qPCR assay. 2) RAW264.7 cells were treated with 1 mL of PBS containing different components, including calcein at 50 µg/mL, COS at 2 mg/mL, and bafilomycin A1, an inhibitor, at 1 µmol/mL, for culturing. The cells were divided into the Calcein group, Calcein+COS group, and Calcein+COS+Bafilomycin A1 group accordingly. Laser scanning confocal microscopy was used to observe the phagocytosis and the intracellular fluorescence distribution of calcein, a fluorescent dye, in RAW264.7 cells in the presence or absence of COS intervention to determine whether COS was able to trigger lysosomal escape. 3) LM∆E6E7 and LI∆E6E7, the attenuated Listeria vector candidate therapeutic vaccines for cervical cancer, were encapsulated with COS at the mass concentrations of 0.5 mg/mL, 1 mg/mL, 2 mg/mL , 4 mg/mL, and 8 mg/mL. Then, the changes in zeta potential were measured to select the concentration of COS that successfully encapsulated the bacteria. Phagocytosis of the vaccine strains by RAW264.7 cells was measured before and after LM∆E6E7 and LI∆E6E7 were coated with COS at 2 mg/mL. Results: 1) CCK8 assays showed that, compared with the findings for the control group, the intervention of RAW264.7 cells with COS at different concentrations for 24 h was not toxic to the cells and promoted cell proliferation, with the difference being statistically significant (P<0.05). According to the RT-qPCR results, compared with those of the control group, the COS intervention up-regulated the mRNA levels of TLR4 and IFN-γ in RAW264.7 cells, while it inhibited the mRNA expression levels of TGF-ß and IL-10, with the most prominent effect being observed in the 4 mg/mL COS group (P<0.05). 2) Laser scanning confocal microscopy revealed that the amount of fluorescent dye released from lysosomes into the cells was greater in the Calcein+COS group than that in the Calcein group. In other words, a greater amount of fluorescent dye was released from lysosomes into the cells under COS intervention. Furthermore, this process could be blocked by bafilomycin A1. 3) The zeta potential results showed that COS could successfully encapsulate the surface of bacteria when its mass concentration reached 2 mg/mL. Before and after the vaccine strain was encapsulated by COS, the phagocytosis of LM∆E6E7 by RAW264.7 cells was 5.70% and 22.00%, respectively, showing statistically significant differences (P<0.05); the phagocytosis of LI∆E6E7 by RAW264.7 cells was 1.55% and 6.12%, respectively, showing statistically significant differences (P<0.05). Conclusion: COS has the effect of activating the immune response of macrophages and triggering lysosomal escape. The candidates strains of coated live attenuated bacterial vector vaccines can promote the phagocytosis of bacteria by macrophages. Further research is warranted to develop COS into an adjuvant for bacterial vector vaccine.

Feruloylated Oligosaccharides Prevented Influenza-Induced Lung Inflammation via the RIG-I/MAVS/TRAF3 Pathway.

Uncontrolled inflammation contributes significantly to the mortality in acute respiratory infections. Our previous research has demonstrated that maize bran feruloylated oligosaccharides (FOs) possess notable anti-inflammatory properties linked to the NF-kB pathway regulation. In this study, we clarified that the oral administration of FOs moderately inhibited H1N1 virus infection and reduced lung inflammation in influenza-infected mice by decreasing a wide spectrum of cytokines (IFN-α, IFN-ß, IL-6, IL-10, and IL-23) in the lungs. The mechanism involves FOs suppressing the transduction of the RIG-I/MAVS/TRAF3 signaling pathway, subsequently lowering the expression of NF-κB. In silico analysis suggests that FOs have a greater binding affinity for the RIG-I/MAVS signaling complex. This indicates that FOs have potential as promising targets for immune modulation. Moreover, in MAVS knockout mice, we confirmed that the anti-inflammatory function of FOs against influenza depends on MAVS. Comprehensive analysis using 16S rRNA gene sequencing and metabolite profiling techniques showed that FOs have the potential to restore immunity by modulating the gut microbiota. In conclusion, our study demonstrates that FOs are effective anti-inflammatory phytochemicals in inhibiting lung inflammation caused by influenza. This suggests that FOs could serve as a potential nutritional strategy for preventing the H1N1 virus infection and associated lung inflammation.

Enzymatically stable unsaturated hyaluronan-derived oligosaccharides with selective cytostatic properties.

Hyaluronan, a linear glycosaminoglycan comprising D-N-acetylglucosamine and D-glucuronic acid, is the main component of the extracellular matrix. Its influence on cell proliferation, migration, inflammation, signalling, and other functions, depends heavily on its molecular weight and chemical modification. Unsaturated HA oligosaccharides are available in defined length and purity. Their potential therapeutic utility can be further improved by chemical modification, e. g., reduction. No synthesis of such modified oligosaccharides, either stepwise or by hyaluronan cleavage, has been reported yet. Here we show a three-step synthesis (esterification, depolymerization and reduction) of unsaturated even numbered hyaluronan oligosaccharides with carboxylates and the reducing terminus reduced to an alcohol. Particular oligosaccharides were synthesised. The modified oligosaccharides are not cleaved by mammalian or bacterial hyaluronidase and do not affect the growth of mouse and human fibroblasts. Further, MTT and NRU viability tests showed that they inhibit the growth of human colon carcinoma cells HT-29 by 20-50 % in concentrations 500-1000 µg/mL. Interestingly, this effect takes place regardless of CD44 receptor expression and was not observed with unmodified HA oligosaccharides. These compounds could serve as enzymatically stable building blocks for biologically active substances.

Curd, seed yield and disease resistance of cauliflower are enhanced by oligosaccharides.

Background: Oligosaccharides have been demonstrated as promoters for enhancing plant growth across several crops by elevating their secondary metabolites. However, the exploration of employing diverse oligosaccharides for qualitative trait improvements in cauliflower largely unknown. This study was intended to uncover the unexplored potential, evaluating the stimulatory effects of three oligosaccharides on cauliflower's curd and seed production. Methods: Two experiments were initiated in the early (15 September) and mid-season (15 October). Four treatments were implemented, encompassing a control (water) alongside chitosan oligosaccharide (COS 50 mg.L-1) with a degree of polymerization (DP) 2-10, oligo galacturonic acid (OGA 50 mg.L-1) with DP 2-10 and alginate oligosaccharide (AOS 50 mg.L-1) with DP 2-7. Results: Oligosaccharides accelerated plant height (4-17.6%), leaf number (17-43%), curd (5-14.55%), and seed yield (17.8-64.5%) in both early and mid-season compared to control. These enhancements were even more pronounced in the mid-season (7.6-17.6%, 21.37-43%, 7.27-14.55%, 25.89-64.5%) than in the early season. Additionally, three oligosaccharides demonstrated significant disease resistance against black rot in both seasons, outperforming the control. As a surprise, the early season experienced better growth parameters than the mid-season. However, performance patterns remained more or less consistent in both seasons under the same treatments. COS and OGA promoted plant biomass and curd yield by promoting Soil Plant Analysis Development (SPAD) value and phenol content. Meanwhile, AOS increased seed yield (56.8-64.5%) and elevated levels of chlorophyll, ascorbic acid, flavonoids, while decreasing levels of hydrogen per oxide (H2O2), malondialdehyde (MDA), half maximal inhibitory concentration (IC50), and disease index. The correlation matrix and principal component analysis (PCA) supported these relations and findings. Therefore, COS and OGA could be suggested for curd production and AOS for seed production in the early season, offering resistance to both biotic and abiotic stresses for cauliflower cultivation under field conditions.

Impacts of monosaccharide composition on immunomodulation by cello-pentaose, manno-pentaose, and xylo-pentaose: Unraveling the underlying molecular mechanisms.

Different types of functional oligosaccharides exhibit varying degrees of immune-enhancing effects, which might be attributable to differences in their glycosyl structures. The differences in the immunomodulatory action of three functional oligosaccharides with distinct glycosyl compositions: cello-oligosaccharides (COS), manno-oligosaccharides (MOS), and xylo-oligosaccharides (XOS), were investigated in mouse-derived macrophage RAW264.7. Moreover, the immune enhancement mechanism of oligosaccharides with diverse glycosyl compositions was investigated from a molecular interaction perspective. The TLR4-dependent immunoregulatory effect of functional oligosaccharides was shown by measuring the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in RAW264.7 cells treated with different functional oligosaccharides, both with and without Resatorvid [TAK-242] (a Toll-like receptor 4 [TLR4] inhibitor). Western blot analysis showed that binding of the three oligosaccharides to TLR4 activated the downstream signaling pathway and consequently enhanced the immune response. The fluorescence spectra and molecular docking results revealed that the main mechanisms by which these oligosaccharides attach to the TLR4 active pocket are hydrogen bonds and van der Waals forces. Functional oligosaccharides were ranked according to their affinity for TLR4, as follows: MOS > COS > XOS, indicating that oligosaccharides or polysaccharides containing mannose units may confer significant advantages for immune enhancement.

Preparation, characterization, antioxidant, and antifungal activity of phenyl/indolyl-acyl chitooligosaccharides.

In this study, carboxylic acids compounds were grafted onto chitooligosaccharides to prepare seven phenyl/indolyl-acyl chitooligosaccharides derivatives. The structures of the derivatives were characterized by IR spectroscopy, 13C NMR and elemental analysis. Meanwhile, antioxidant activities in vitro of the novel derivatives were analyzed. Compared to COS and carboxylic acid, the derivatives showed higher scavenging capacity for superoxide anion and DPPH radicals, with scavenging rates of 59.39% and 94.86%, respectively. The hydroxyl radical scavenging ability of the derivatives was only 18.89%. The antifungal activities of chitooligosaccharide derivatives against Diaporthe batatas and Phytophthora capsici were studied by the growth rate method. Compared with chitooligosaccharide itself, derivatives were inhibited by 97.77% and 100%. The above results showed that chitooligosaccharide derivatives have good biocompatibility and can be used in food, agriculture and medicine.

Human milk oligosaccharides differentially support gut barrier integrity and enhance Th1 and Th17 cell effector responses in vitro.

Human milk oligosaccharides (HMOs) can modulate the intestinal barrier and regulate immune cells to favor the maturation of the infant intestinal tract and immune system, but the precise functions of individual HMOs are unclear. To determine the structure-dependent effects of individual HMOs (representing different structural classes) on the intestinal epithelium as well as innate and adaptive immune cells, we assessed fucosylated (2'FL and 3FL), sialylated (3'SL and 6'SL) and neutral non-fucosylated (LNT and LNT2) HMOs for their ability to support intestinal barrier integrity, to stimulate the secretion of chemokines from intestinal epithelial cells, and to modulate cytokine release from LPS-activated dendritic cells (DCs), M1 macrophages (MØs), and co-cultures with naïve CD4+ T cells. The fucosylated and neutral non-fucosylated HMOs increased barrier integrity and protected the barrier following an inflammatory insult but exerted minimal immunomodulatory activity. The sialylated HMOs enhanced the secretion of CXCL10, CCL20 and CXCL8 from intestinal epithelial cells, promoted the secretion of several cytokines (including IL-10, IL-12p70 and IL-23) from LPS-activated DCs and M1 MØs, and increased the secretion of IFN-γ and IL-17A from CD4+ T cells primed by LPS-activated DCs and MØs while reducing the secretion of IL-13. Thus, 3'SL and 6'SL supported Th1 and Th17 responses while reducing Th2 responses. Collectively, our data show that HMOs exert structure-dependent effects on the intestinal epithelium and possess immunomodulatory properties that confer benefits to infants and possibly also later in life.

Unraveling the potential of Morinda officinalis oligosaccharides as an adjuvant of escitalopram in depression treatment and exploring the underlying mechanisms.

ETHNOPHAMACOLOGICAL RELEVANCE: Morinda officinalis oligosaccharides (MOs) is a mixture of oligosaccharides extracted from the roots of Morinda officinalis (MO). It is approved by Chinese Food and Drug Administration (CFDA) for depression treatment. MOs could improve the antidepressant efficacy of escitalopram in clinic. AIM OF THE STUDY: We aim to explore the antidepressant activity and potential mechanism of the combination usage of MOs and escitalopram on animal model of depression. MATERIALS AND METHODS: Depressive animal model was induced by chronic mild stress (CMS). Behavioral tests were conducted to evaluate the antidepressant efficacy of MOs and escitalopram. Serum neurotransmitter levels were detected by High-performance liquid chromatography (HPLC). Quantitative real-time PCR and Western blotting were applied to assay the hippocampus neurotrophic factors' mRNA and protein levels. Peripheral cytokines levels were measured through Enzyme-Linked Immunosorbent Assay (ELISA). Micorglia polization phenotype was assayed by immunofluorescence and flow cytometry. RESULTS: MOs and escitalopram obviously attenuated depression-like behaviors of CMS mice. Importantly, MOs plus escitalopram exhibited better antidepressant activity on CMS mice than monotherapy. At the same time, MOs combined escitalopram treatment significantly increased hippocampus neurotransmitters and neurotrophic factor levels, stimulated hippocampus neurogenesis and relieved central nervous system (CNS) microglia over-activation of CMS mice. The combination therapy had greater effect on neuroprotection and inflammation attenuation of CMS mice than monotherapy. CONCLUSION: Our results indicates MOs combined escitalopram might produce antidepressant activity through protecting neuron activity, relieving inflammation and modulating microglia polarization process.

Ameliorative Effect of Morinda Officinalis Oligosaccharides on LPS-Induced Acute Lung Injury.

Acute lung injury (ALI) is a disease characterized by extensive lung damage and rampant inflammation, with a high mortality rate and no effective treatments available. Morinda officinalis oligosaccharides (MOOs), derived from the root of the traditional Chinese medicinal herb Morinda officinalis, known for its immune-boosting properties, presents a novel therapeutic possibility. To date, the impact of MOOs on ALI has not been explored. Our study aimed to investigate the potential protective effects of MOOs against ALI and to uncover the underlying mechanisms through an integrated approach of network pharmacology, molecular docking, and experimental validation. We discovered that MOOs significantly mitigated the pathological damage and decreased the expression of pro-inflammatory cytokines in LPS-induced ALI in mice. Complementary in vitro studies further demonstrated that MOOs effectively attenuated the M1 polarization induced by LPS. Network pharmacology analysis identified HSP90AA1, HSP90AB1, and NF-κB as key overlapping targets within a protein-protein interaction (PPI) network. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses elucidated the biological processes and signaling pathways implicated in MOOs' therapeutic action on ALI. Subsequently, molecular docking affirmed the binding of MOOs to the active sites of these identified targets. Corroborating these findings, our in vivo and in vitro experiments consistently demonstrated that MOOs significantly inhibited the LPS-induced upregulation of HSP90 and NF-κB. Collectively, these findings suggest that MOOs confer protection against ALI through a multi-target, multi-pathway mechanism, offering a promising new therapeutic strategy to mitigate this severe pulmonary condition.

Biomedical potency and mechanisms of marine polysaccharides and oligosaccharides: A review.

Derived from bountiful marine organisms (predominantly algae, fauna, and microorganisms), marine polysaccharides and marine oligosaccharides are intricate macromolecules that play a significant role in the growth and development of marine life. Recently, considerable attention has been paid to marine polysaccharides and marine oligosaccharides as auspicious natural products due to their promising biological attributes. Herein, we provide an overview of recent advances in the miscellaneous biological activities of marine polysaccharides and marine oligosaccharides that encompasses their anti-cancer, anti-inflammatory, antibacterial, antiviral, antioxidant, anti-diabetes mellitus, and anticoagulant properties. Furthermore, we furnish a concise summary of the underlying mechanisms governing the behavior of these biological macromolecules. We hope that this review inspires research on marine polysaccharides and marine oligosaccharides in medicinal applications while offering fresh perspectives on their broader facets.

Chitosan oligosaccharide accelerates the dissemination of antibiotic resistance genes through promoting conjugative plasmid transfer.

The dissemination of antibiotic resistance genes (ARGs), especially via plasmid-mediated horizontal gene transfer, poses a pervasive threat to global health. Chitosan-oligosaccharide (COS) is extensively utilized in medicine, plant and animal husbandry. However, their impact on microflora implies the potential to exert selective pressure on plasmid transfer. To explore the role of COS in facilitating the dissemination of ARGs via plasmid conjugation, we established in vitro mating models. The addition of COS to conjugation mixtures significantly enhanced the transfer of RP4 plasmid and mcr-1 positive IncX4 plasmid in both intra- and inter-specific. Phenotypic and transcriptome analysis revealed that COS enhanced intercellular contact by neutralizing cell surface charge and increasing cell surface hydrophobicity. Additionally, COS increased membrane permeability by inhibiting the Tol-Pal system, thereby facilitating plasmid conjugative transfer. Furthermore, COS served as the carbon source and was metabolized by E. coli, providing energy for plasmid conjugation through regulating the expression of ATPase and global repressor factor-related genes in RP4 plasmid. Overall, these findings improve our awareness of the potential risks associated with the presence of COS and the spread of bacterial antibiotic resistance, emphasizing the need to establish guidelines for the prudent use of COS and its discharge into the environment.

Konjac Oligosaccharides Alleviated Ovariectomy-Induced Bone Loss through Gut Microbiota Modulation and Treg/Th17 Regulation.

Oligosaccharides from the plant Amorphophallus konjac were potentially effective in menopausal osteoporosis due to their prebiotic attributes. The present work mainly studied the regulation of konjac oligosaccharides (KOS) on menopausal bone loss. Experiments were carried out in ovariectomized (OVX) rats, and various contents of KOS were correlated with diet. After 3 months of treatment, the degree of osteoporosis was determined by bone mineral density and femoral microarchitecture. The research data showed that the 8% dietary KOS significantly alleviated bone loss in OVX rats, as it promoted the bone trabecular number by 134.2% and enhanced the bone bending stiffness by 103.1%. From the perspective of the gut-bone axis, KOS promoted gut barrier repair and decreased pro-inflammatory cytokines. Besides, KOS promoted the growth of Bifidobacterium longum and restored Treg/Th17 balance in bone marrow. The two aspects contributed to decreased osteoclastogenic activity and thus inhibited inflammation-related bone loss. This work extended current knowledge of prebiotic inhibition on bone loss and provide an alternative strategy for osteoporosis prevention.