PMID: 

Phytomedicine. 2019 Dec 23 ;67:153157. Epub 2019 Dec 23. PMID: 31896054

Abstract Title: 

Fructo-oligosaccharides from Morinda officinalis remodeled gut microbiota and alleviated depression features in a stress rat model.

Abstract: 

BACKGROUND: Inulin-type fructo-oligosaccharides (FOSs) purified from Morinda officinalis How., an effective oral antidepressant for mild to moderate depression, have a largely unknown efficacy and poor bioavailability.PURPOSE: Therefore, the microbiota-gut-brain axis was used to investigate the antidepressive properties of FOSs at the interface of the gut microbiota (GM).STUDY DESIGN AND METHODS: FOSs was introduced via intragastric gavage to rats exposed to chronic unpredictable mild stress (CUMS), and the antidepressive effects were investigated through behavioral tests, intestinal morphology and corticosterone levels. Bacterial genomic DNA was extracted from feces, and the GM was profiled for using enterobacterial repetitive intergenic consensus (ERIC)-PCR analysis, partial least squares-discriminant analysis (PLS-DA) and 16S rRNA gene pyrosequencing.RESULTS: It was observed that FOSs alleviated depression-like behaviors and repaired intestinal epithelia damages. FOSs treatment lowered corticosterone levels in the plasma and urine of the model rats. Moreover, the GM compositions of normal and model rats were distantly clustered and were mainly related to the disappearance of beneficial bacteria (e.g., Acinetobacter, Barnesiella, Coprococcus, Dialister, Lactobacillus, and Paenibacillus) and appearance of depression-associated bacteria (e.g., Anaerostipes, Oscillibacter, Proteobacteria, and Streptococcus) in depressive rats. Interestingly, the dysbiosis in depressive rats' gut was reinstated with FOSs treatments. Notably, FOSs promoted the abundance of the bacterial phylum Cyanobacteria, a group of bacteria known for the secretion of pharmacologically important metabolites, such as HS, that exhibit antidepressant-like properties. Apparently, FOSs-induced modulation of GM was more antidepressive compared to a component of FOSs, degrees of polymerization (DP) 5, and fluoxetine, the standard antidepressant drug.CONCLUSION: In conclusion, this study implied that antidepressant efficacy of FOSs was inseparable from and strongly associated with the modulation of the host' s GM.

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PMID: 

J Nutr. 2020 Jan 8. Epub 2020 Jan 8. PMID: 31915826

Abstract Title: 

Human Milk Oligosaccharides Activate Epidermal Growth Factor Receptor and Protect Against Hypoxia-Induced Injuries in the Mouse Intestinal Epithelium and Caco2 Cells.

Abstract: 

BACKGROUND: Hypoxia-induced intestinal barrier injuries lead to necrotizing enterocolitis (NEC). Although NEC in preterm neonates is preventable by human milk oligosaccharides (HMOs), the underlying mechanism remains unknown.OBJECTIVE: To reveal the role and mechanism of HMOs in protecting against hypoxia-induced injuries in intestinal epithelium of neonatal mice and cultured Caco2 cells.METHODS: NEC was induced by hypoxia and cold stress. Seventy C57BL/C pups (7-d-old) were divided into 5 groups and fed maternal breast milk (BM), formula alone (FF), or the formula added with HMOs at 5 (LHMO), 10 (MHMO), or 20 mg/mL (HHMO) for 3 d. Ileal hypoxia inducible factor 1α (HIF1α) and cleaved Caspase 3 were determined, along with staining for Ki-67 protein to labeled proliferative cells. In vitro, adherent Caco2 cells (undifferentiated, passage 14) were treated with HMOs, galacto-oligosaccharides, fructo-oligosaccharides, or mixed oligosaccharides at 10 mg/mL for 1 d exposed to 1% O2. Cell proliferation and apoptosis, along with phosphorylated epidermal growth factor receptor (P-EGFR) and 38KD MAPK (P-P38), were assayed in differentiated or undifferentiated Caco2 cells.RESULTS: Compared with the FF-fed mice, those fed MHMO and HHMO had 52% lower (P

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PMID: 

Annu Rev Food Sci Technol. 2020 Jan 17. Epub 2020 Jan 17. PMID: 31951486

Abstract Title: 

Effects of Nondigestible Oligosaccharides on Obesity.

Abstract: 

Obesity is a major public health concern that has almost reached the level of pandemic and is rapidly progressing. Gut microbiota has emerged as a crucial regulator involved in the etiology of obesity, and the manipulation of it by dietary intervention has been widely used for reducing the risk of obesity. Nondigestible oligosaccharides (NDOs) are attracting increasing interests as prebiotics, as the indigestible ingredients can induce compositional or metabolic improvement to the gut microbiota, thereby improving gut health and giving rise to the production of short-chain fatty acids (SCFAs) to elicit metabolic effects on obesity. In this review, the role NDOs play in obesity intervention via modification of the gut microecology, as well as the physicochemical and physiological properties and industrial manufacture of NDOs, is discussed. Our goal is to provide a critical assessment of and stimulate comprehensive research into NDO use in obesity. Expected final online publication date for the, Volume 11 is March 25, 2020. Please see https://ift.tt/2CYBVUj for revised estimates.

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PMID: 

Evid Based Complement Alternat Med. 2019 ;2019:9306834. Epub 2019 Dec 19. PMID: 31929824

Abstract Title: 

Oligosaccharides fromSlow the Progress of Aging Mice by Regulating the Key Microbiota-Metabolite Pairs.

Abstract: 

The gut microbiota is considered an important factor in the progression of Alzheimer's disease (AD). Active research on the association between the metabolome and the gut microbiome is ongoing and can provide a large amount of beneficial information about the interactions between the microbiome and the metabolome. Previous studies have shown that the oligosaccharides from(OMO) can delay the progress of AD in model animals by regulating the diversity of the gut microbiome and metabolic components, and the correlation between the gut microbiome and metabolic components still needs to be further verified. This study applied a new two-level strategy to investigate and ensure the accuracy and consistency of the results. This strategy can be used to determine the association between the gut microbiome and serum metabolome in APP/PS1 transgenic mice and C57BL/6J male mice. The"spp.-Cholesterol,""spp.-L-valine,""spp.-L-acetylcarnitine,""spp.-L-valine,""spp.-L-valine,"and"spp.-L-acetylcarnitine"associations among specific"microbiota-metabolite"pairs were further identified based on univariate and multivariate correlation analyses and functional analyses. The key relevant pairs were verified by an independent oligosaccharide intervention study, and the gut microbiome and serum metabolome of the OMO intervention group were similar to those of the normal group. The results indicate that OMO can significantly suppress Alzheimer's disease by regulating the key microbiota-metabolite pairs. Therefore, this two-level strategy is effective in identifying the principal correlations in large datasets obtained from combinations of multiomic studies and further enhancing our understanding of the correlation between the brain and gut in patients with AD.

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PMID: 

Inflammation. 2020 Jan 6. Epub 2020 Jan 6. PMID: 31903511

Abstract Title: 

Evidence on n-3 Fatty Acids and Oleic Acid Role in Retinal Inflammation and Microvascular Integrity: Insight from a Hyperlipidemic Rat Model.

Abstract: 

Loss of retinal function due to manifestation of chronic inflammation and oxidative stress in hyperglycemia is well addressed. However, the effect of hyperlipidemia on retinal inflammation and microvascular integrity, and the modulatory effects of oxidation-stable oleic acid and long-chain n-3 fatty acids have never been addressed. The objective of this investigation was to assess the retinoprotective effect of oxidation stable oleic acid and oxidation-susceptible EPA + DHA on retinal inflammation and microvascular integrity, under hyperlipidemic conditions. Male Wistar rats were fed with control (7.0% lard), high-fat (35.0% lard), high-fat with fish oil (17.5% fish oil + 17.5% lard), high-fat with olive oil (17.5% olive oil + 17.5% lard), and high-fat with fish oil and olive oil (11.66% fish oil + 11.66% of olive oil + 11.66% of lard) diet for 90 days. Systemic and retinal inflammation, as measured by eicosanoids and cytokines, retinal expression of NF-kB, capillary degeneration, and pericyte loss, were assessed. Hyperlipidemia significantly (p 

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PMID: 

J Med Food. 2020 Jan 15. Epub 2020 Jan 15. PMID: 31939715

Abstract Title: 

Antiproliferative Activity of the Olive Extract Rich in Polyphenols and Modified Pectin on Bladder Cancer Cells.

Abstract: 

Bladder cancer (BC) is one of the most common human cancers. There is an interest in controlling and treating BC and other types of cancer via the use of natural substances and/or combination chemotherapy. Modified forms of pectin have been reported to possess anticancer bioactivity related to the interaction of galactosyl, a main component of pectin, with galectin-3, a carbohydrate-binding protein that is overexpressed on many types of cancer cells. In this study, the antiproliferative effect on BC of novel modified pectins extracted from olives was evaluated. Pectoliv extracts, with high polyphenol content associated to polysaccharides rich in pectin, exhibited an important antiproliferative capacityagainst four human BC cells lines, RT112, T24, J82, and SCaBER. Pectoliv treatment reduced the expression of galectin-1 and galectin-3 and significantly inhibited the agglutination of erythrocytes. Thus, Pectoliv may have the potential for development as a novel galectin-3 inhibitor.

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PMID: 

Food Funct. 2020 Jan 14. Epub 2020 Jan 14. PMID: 31932824

Abstract Title: 

Citrus flavonoids suppress IL-5 and ROS through distinct pathways in PMA/ionomycin-induced EL-4 cells.

Abstract: 

Interleukin-5 (IL-5) strongly initiates the asthmatic inflammatory response, which affects 300 million patients with asthma annually worldwide, through oxidative stress generation. Citrus flavonoids have beneficial properties, such as anti-inflammatory and antioxidant properties, but the precise molecular mechanism of the inhibition of the asthmatic inflammatory response is still unclear. This study aimed to investigate the underlying mechanisms of ROS and IL-5 reduction with citrus flavonoid treatment in PMA/ionomycin-induced EL-4 cells. Our results showed that hesperetin and gardenin A dramatically suppressed ROS and IL-5 production through distinct pathways. Interestingly, hesperidin induced HO-1 expression through the transcription factor Nrf2 coupled with the PI3K/AKT or ERK/JNK signaling pathway, consequently downregulating NFAT activity and IL-5 secretion. Likewise, gardenin A induced HO-1 expression and subsequently suppressed IL-5 production by reducing NFAT activity and upregulating PPARγ in EL-4 cells, suggesting that inducing HO-1 expression may inhibit asthmatic inflammation. Altogether, hesperidin and gardenin A have great potential for regulating the asthma-associated immune responses through antioxidant properties.

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PMID: 

Carbohydr Polym. 2019 Sep 1 ;219:121-129. Epub 2019 May 8. PMID: 31151509

Abstract Title: 

Selective effects of ginseng pectins on galectin-3-mediated T cell activation and apoptosis.

Abstract: 

Galectin-3 (Gal-3) can induce T-cell activation and apoptosis and plays a role in tumor immune tolerance. Here, we demonstrate that ginseng pectins selectively inhibit Gal-3-induced T-cell apoptosis, while not affecting T-cell activation. This finding stands in contrast to that from the use of modified citrus pectin (MCP) and potato galactan (P-galactan) that inhibit both. Whereas PKC/ERK and ROS/ERK pathways are involved in both T-cell activation and apoptosis, the Ras/PI3K/Akt pathway is unique to T-cell activation. Ginseng pectins selectively inhibit the ROS/ERK pathway. Using the Sarcomar-180 mouse model in which Gal-3 expression is increased, we found that ginseng pectins (but not MCP or P-galactan) significantly promote T-cell proliferation and IL-2 expression, and inhibit tumor growth by 45%. These in vivo data correlate well with selective effects of pectins on Gal-3-mediated T-cell apoptosis and activation. Our study suggests a novel approach for the development of polysaccharide-based agents that target Gal-3 function.

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PMID: 

Cancer Med. 2019 Aug ;8(9):4315-4329. Epub 2019 Jun 13. PMID: 31197964

Abstract Title: 

Pectasol-C Modified Citrus Pectin targets Galectin-3-induced STAT3 activation and synergize paclitaxel cytotoxic effect on ovarian cancer spheroids.

Abstract: 

Here we sought to determine the relationship between STAT3 activity and Galectin-3 (Gal-3) and to investigate the cytotoxic effect of PectaSol-C Modified Citrus Pectin (Pect-MCP) as a specific competitive inhibitor of Galectin-3 (Gal-3) in combination with Paclitaxel (PTX) to kill the ovarian cancer cell SKOV-3 multicellular tumor spheroid (MCTS). To this order, SKOV-3 cells in 2D and 3D cultures were treated with exogenous Gal-3 for the assessment of STAT3 activity. Two-way ANOVA main effect and ICof each drug Paclitaxel (PTX) and Pect-MCP or in combination were obtained from MTT assay results. The phosphorylated STAT3 levels, migration, invasion, integrin mRNA and p-AKTserlevels were assessed in the absence or presence of each drug alone or in combination. Gal-3 expression levels were assessed in human serous ovarian cancer (SOC) specimens and its correlation with different integrin mRNA levels was further assessed. Our results showed that Gal-3 expression level was significantly increased in MCTS compared to monolayer SKOV-3 cells which triggered STAT3 phosphorylation. Moreover, Pect-MCP synergized with PTX to kill SKOV3 MCTS through abrogation of STAT3 activity and reduced expression of its downstream target HIF-1α, reduced integrin mRNA levels, and subsequently decreased AKT activity. There were higher expression levels of Gal-3 in human high-grade SOC specimens compared to the normal ovary and borderline SOC which positively and significantly correlated with α5, β2 and β6 integrin mRNA levels. Together, these results revealed for the first time that Pect-MCP could be considered as a potential drug to enhance the PTX effect on ovarian cancer cells MCTS through inhibition of STAT3 activity.

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PMID: 

Front Immunol. 2019 ;10:2979. Epub 2019 Dec 19. PMID: 31921214

Abstract Title: 

Dietary Fiber Pectin Ameliorates Experimental Colitis in a Neutral Sugar Side Chain-Dependent Manner.

Abstract: 

Dietary fiber, with intake of soluble fibers in particular, has been reported to lower the risk for developing inflammatory bowel diseases (IBD). This is at least partly attributable to the fermentation of dietary fiber by the colonic microbiota to produce short chain fatty acids. Pectin, a widely consumed soluble fiber, is known to exert a protective effect in murine models of IBD, but the underlying mechanism remains elusive. Apart from having a prebiotic effect, it has been suggested that pectin direct influences host cells by modulating the inflammatory response in a manner dependent on its neutral sugar side chains. Here we examined the effect of the side chain content of pectin on the pathogenesis of experimental colitis in mice. Male C57BL/6 mice were fed a pectin-free diet, or a diet supplemented with characteristically high (5% orange pectin) or low (5% citrus pectin) side chain content for 10-14 days, and then administered 2,4,6-trinitrobenzene sulfonic acid or dextran sulfate sodium to induce colitis. We found that the clinical symptoms and tissue damage in the colon were ameliorated in mice that were pre-fed with orange pectin, but not in those pre-fed with citrus pectin. Although the population of CD4Foxpregulatory T cells and CD4RORγtinflammatory T cells in the colon were comparable between citrus and orange pectin-fed mice, colonic interleukin (IL)-1β and IL-6 levels in orange pectin-fed mice were significantly decreased. The fecal concentration of propionic acid in orange pectin-fed mice was slightly but significantly higher than that in control and citrus pectin-fed mice but the cecal concentration of propionic acid after the induction of TNBS colitis was comparable between orange and citrus pectin-fed mice. Furthermore, the protective effect of orange pectin against colitis was observed even in mice treated with antibiotics. IL-6 production from RAW264.7 cells stimulated with the toll-like receptor agonist Pam3CSK4 or lipopolysaccharide was suppressed by pre-treatment with orange pectin. Taken together, these results suggest that the side chains of pectin not only augment prebiotic effects but also directly regulate IL-6 production from intestinal host cells in a microbiota-independent fashion to attenuate colitis.

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