The protective effect of dulcitol on lipopolysaccharide-induced intestinal injury in piglets: mechanistic insights.

This study investigated the protective effect of dulcitol on LPS-induced intestinal injury in piglets and explored the underlying molecular mechanisms. A total of 108 piglets were divided into three groups: CON, LPS, and DUL. The CON and LPS groups were fed a basal diet, the DUL group was fed a diet supplementation with 500 mg/kg dulcitol. On day 29, 6 piglets in the LPS and DUL groups were injected with 100 µg/kg BW of LPS. At 4 h post-challenge, all pigs were slaughtered, and colonic samples were collected. Results showed that dulcitol supplementation boosted intestinal barrier function in LPS-challenged piglets by enhancing intestinal morphology and integrity, and increasing the gene expression of zonula occludens-1, claudin-1, and occludin in the colonic mucosa (P <0.05). Metabolomics showed DUL supplementation mainly increased (P <0.05) the metabolites related to steroid and vitamin metabolism (Cholesterol and Vitamin C). Proteomics showed that dulcitol supplementation altered the protein expression involved in maintaining barrier integrity (FN1, CADM1, and PARD3), inhibiting inflammatory response (SLP1, SFN, and IRF3), and apoptosis (including FAS, ING1, BTK, MTHFR, NOX, and P53BP2) in LPS-challenged piglets (P <0.05). Additionally, dulcitol addition also suppressed the TLR4/NF-κB signaling pathway and apoptosis in mRNA and protein levels. Dulcitol increased the abundance of short-chain fatty acid-producing bacteria (Lactobacillus, Blautia, and Faecalibacterium) at the genus level, but decreased the relative abundance of Proteobacteria at the phylum level and Pseudomonas and Delftia at the genus level in piglets (P < 0.05). In conclusion, these results suggested that the addition of dulcitol alleviated LPS-induced intestinal barrier injury in piglets, probably by maintaining its integrity, inhibiting the TLR4/NF-κB signaling pathways and apoptosis, and modulating the gut microbiota. Therefore, dulcitol can be considered a potential dietary additive for improving intestinal health in pig models.

Low molecular weight carbohydrate patterns of mangrove macroalgae from different climatic niches under ocean acidification, warming and salinity variation.

Ocean acidification has increased due to the enhanced solubility of CO2 in seawater. Mangrove macroalgae in tropical and subtropical coastal regions can benefit from the higher availability of CO2 for photosynthesis and primary production. However, they can be negatively affected by the simultaneously occurring warming and increased salinity in estuaries. Thus, we analyzed the isolated effects of ocean acidification and the interactive effects of increased temperature and salinity on the low molecular weight carbohydrate (LMWC) contents of the mangrove red macroalgae Bostrychia montagnei and Bostrychia calliptera from Brazilian tropical and subtropical populations. Specimens from both climatic niches were tolerant to pH decreased by CO2 enrichment and enhanced their LMWC contents under increased availability of CO2. Specimens from both climatic niches also accumulated their dulcitol and sorbitol contents to cope with warming and salt stress. Nevertheless, temperature of 34 °C was lethal for tropical macroalgae, while 29 °C and 31 °C were lethal for subtropical B. calliptera under salinity of 35. Tropical and subtropical B. montagnei synthesized dulcitol (5-110 mmol kg-1 dry weight) and sorbitol (5-100 mmol kg-1 dry weight) as osmoregulatory, energy and thermal protection compounds, whereas tropical and subtropical B. calliptera synthesized mainly dulcitol (10-210 mmol kg-1 dry weight). Although digeneaside has an energy function in Bostrychia spp., it is not an osmolyte or thermal protection compound. Our data demonstrated that both tropical and subtropical Bostrychia spp. benefit from ocean acidification by CO2 enrichment, increasing their LMWC contents. However, warming and increased salinity in estuaries will be detrimental to them, even they producing protective metabolites. Multifactorial approaches are recommended to investigate whether negative effects of increased temperature and salinity nullify positive effects of ocean acidification on these Bostrychia species/populations.

Dulcitol suppresses proliferation and migration of hepatocellular carcinoma via regulating SIRT1/p53 pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) spreads further with continuance and increasing incidence due to its high-grade malignancy and metastasis. More effectual strategies on blocking proliferation and metastasis of cancer cells should be studied in HCC. Dulcitol, a natural product extracted from euonymus alatus, was reported that it could induce apoptosis of C6 glioma cells. However, the underlying mechanism of Dulcitol on HCC remains unclea. PURPOSE: In this study, we aimed to reveal the effect and potential mechanisms of Dulcitol on hepatocellular carcinoma in vitro and in vivo. Study design and methods The cell proliferation and apoptosis were evaluated by MTT, Ki-67 and Hoechst 33258/PI double staining. The migratory and invasive abilities of HepG2 cells were measured by wound-healing and transwell assays. Pathological changes of tumor tissue were observed by HE staining and IHC methods. The expression levels of protein were detected using Western Blot analysis. RESULTS: The results showed that Dulcitol inhibited HepG2 cells proliferation by down-regulating the protein expression of SIRT1, Bcl-2, along with up-regulating p53, acetylated-p53 (K382), cleaved-caspase9, cleaved-caspase3, Bax, and cytochrome c in a dose-dependent manner. Furthermore, Dulcitol surpressed the migration and invasion of HepG2 cells through decreasing the levels of MMP-2, uPA and MMP-9 and increasing E-cadherin associated with tumor invasion. In vivo, Dulcitol distinctly inhibited the growth of HepG2 cancer xenograft tumors via inhibiting SIRT1/p53 pathway. CONCLUSIONS: Our findings suggested that Dulcitol acted as a SIRT1 inhibitor, inducing apoptosis and inhibiting proliferation, migration and invasion of HepG2 cells and its modulatory mechanism seemed to be associated with regulation of MMPs, SIRT1/p53 pathways.

Inhibitory effects of Dulcitol on rat C6 glioma by regulating autophagy pathway.

In the study, we treated C6 rat glioma cells with 25 mg/ml Dulcitol for 24 h. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were used to detect cellular growth. The measurements of the superoxide dismutase (SOD), malondialdehyde (MDA) and catalase (CAT) were used to assess oxidative stress level. Western was performed to detect the autophagy and apoptosis expression. The data showed that Dulcitol significantly decreased the cell viability, upregulated the Bax level in mitochondria and the Cytochrome C level in cytoplasm, and downregulated anti-apoptotic protein Bcl-xl. Moreover, it enhanced MDA level, reduced CAT and SOD activities, decreased LC3-II/LC3-I ratio, and increased P62 expression. However, rapamycin increased autophagy level and cell viability, and decreased ROS in Dulcitol treated C6 cells. Moreover, Dulcitol inhibited the glioma growth and enhanced survival in vivo. These results suggest that Dulcitol evidently increase cellular ROS levels and apoptosis in glioma cells, which can be significantly regulated by autophagy.

Metabolites analysis for cold-resistant yeast (Wickerhamomyces anomalus) strains own antioxidant activity on cold stored fish mince.

The effect of eight cold-resistant yeast strains (J3, J7, J8, J9, J12, J15, J18, and J25) of Wickerhamomyces anomalus on the lipid oxidation of cold stored fish mince (4 °C) were investigated. And the metabolites of these yeast were determined with gas chromatography-mass spectrometry. These strains could effectively inhibit the increase of hydroperoxides value (p < 0.05), and the inhibiting rate was positively correlated with the content of isolongifolene, xylitol, turanose, thymol-glucoside, and uridine. Especially, the J3, J7, J8, J9, J12, and J18 could eliminate a large part of thiobarbituric acid reactive substances (TBARS) (p < 0.05), the eliminating rate was proportionate to the aldehyde dehydrogenase activity. Several bacteriostatic metabolites were detected: thymol-glucoside, 2-phenylethanol, cedro, and 2,4-bis (1,1-dimethylethyl) phenol. In addition, W. anomalus produced many metabolites with fruit and floral notes. In conclusion, cold-resistant W. anomalus strains own antioxidant activity were potential new bio-preservatives in the cold storage of muscle products.

The Structural Signs of Sweetness in Artificial Sweeteners: A Rotational Study of Sorbitol and Dulcitol.

A gas-phase study on the artificial sweeteners sorbitol and dulcitol has been carried out for the first time by using a combination of chirped-pulse Fourier-transform microwave (CP-FTMW) spectroscopy and laser ablation (LA). The isolation conditions provided by the supersonic expansion reveal the intrinsic conformational structures of these sweeteners. The three and five observed conformers for sorbitol and dulcitol, respectively, are stabilized by networks of cooperative intramolecular hydrogen bonds between vicinal hydroxyl groups in clockwise or counterclockwise arrangements. Suitable places in the structure of seven out of eight conformers identified for both polyalcohols meet the requirements of the glucophore proposed by Shallenberger and Acree's molecular theory of sweet taste. Present results provide the first linkage between sweetness and structure in sugar alcohols.

Escalation of liver malfunctioning: A step toward Herbal Awareness.

ETHNOPHARMACOLOGICAL RELEVANCE: About 2-5% of the world's population is suffering from liver toxicity including Pakistan with the second highest rate of hepatitis prevalence. Liver is a vital body organ which not only performs metabolic activities but also aids in detoxification, storage and digestion of food. Now a day's malnutrition, alcohol consumption and drug addiction are major causes of liver diseases throughout the world. In fact, there is no possible outcome to compensate liver malfunction for long term, and transplantation of liver is the only option left after the irretrievable injury of hepatic function. Subsequently, natural based therapeutic approaches are in the process of scrupulous testing as strong hepatoprotective mediator. In this regard plants are well thought hepatoprotective agents having multiple active components. In this review, based on species' pharmacology and safety we have compiled some plants which show strong hepatoprotective activity, main phytoconstituents with biological activities and few commercially used herbal formulations. MATERIALS AND METHODS: Ethnopharmacological information was gathered by an extensive literature survey like WHO monographs on selected herbal medicinal plants (Vol 1-Vol 4); Principles and Practice of Phytotherapy, Mills S and Bone K, Churchill Livingstone, London, UK; Herbal Drugs and Phytopharmaceuticals, Wichtl M Medpharm Press, Stuttgart 3rd edn; Pharmacology and Applications of Chinese Materia Medica Vols 1 and 2, Chang H-M and But P P-H World Scientific, Singapore; British Herbal Compendium Vol. 2, Bradley P British Herbal Medicine Association, Bournemouth, UK; ESCOP Monographs 2nd edn. Thieme, Stuttgart, Germany; as well as by using electronic databases such as Pubchem, Chemspider, http://www.herbal-ahp.org; http://www.ahpa.org; http://whqlibdoc.who.int/publications/2003/9241546271.pdf; http://www.escop.com, Pubmed, HubMed and Scopus. RESULTS: Data for more about 29 plants have been accomplished for their bioactive constituent(s), biological activities and medicinal uses. Some of the plants have been identified as strong hepato-modulator. Such knowledge about traditional medicinal plants can be globally applied for safe and evidence based use in pharmacological applications. CONCLUSION: With the rise in liver risks a meek struggle has been made to draw attention toward herbal therapy. Hepatoprotective constituents of said plants are expressed with chemical structures. However, for certain plants active constituents are not still isolated/purified but overall plant extract was found effective in providing protection against hepatic injury. As a future perspective, there is need to purify plant active constituents for ethnomedical rationale.

Application of Monoclonal Antibodies to Dulcitol 1-Phosphate Dehydrogenase for Rapid Detection of Salmonella.

Monoclonal antibodies raised against dulcitol 1-phosphate dehydrogenase of Salmonella typhimurium IFO 12529 were screened against 20 serotypes of Salmonella and 13 non- Salmonella bacteria. A sandwich-capture, enzyme-linked immunosorbent assay (sandwich ELISA) was developed for detection of Salmonella in food. The assay utilizes two monoclonal antibodies (DUI2 and DU28) which show no cross-reactions with non- Salmonella bacteria. The limit of detection of the sandwich ELISA was about 1 × 107 CPU/ml. After cultivation in a medium containing dulcitol at 37°C for 18 h followed by the sandwich ELISA. 1 CPU of Salmonella was detected. Although a high inoculum level of E. coli interfered with the detection of Salmonella , the interference was minimized by using a selective dulcitol-magnesium chloride-pyridinesulfonic acid medium for enrichment. The novel ELISA procedure detected Salmonella in chicken filtrates inoculated with 1.4 CPU/50 m1 and 1.3 × 107 CPU/50 ml of E. coli within 25 h.

Determination of dulcitol and astragaloside in Compound Fufangteng Capsules by HPLC-ELSD / 中成药

AIM:To establish an HPLC-ELSD method for determing dulcitol and astragaloside in Compound Fufangteng Capsules(Radix et Rhizoma Ginseng rubra,Radix Astragali,Herba Euonymi,etc).METHOD:Chro-matographic conditions included Lichrospher 5-NH_2 column(250 mm?4.6 mm,5 ?m)and the mobile phase consisting of a mixture of acetonitrile-water(91 ∶9).The flow rate of mobile phase was 1.0 mL/min.The column tempe-rature was at 28 ℃.Detector:PL-ELS2100 ELSD(Eva:65 ℃,Ned:50 ℃,gas flow:0.9 L/min).RESULTS:The linear ranges of dulcitol and astragaloside were 2.91-29.1 ?g(r= 0.999 8)and 1.03-10.3 ?g(r= 0.999 1),respectively.The average recoveries of dulcitol and astragaloside were 99.24% and 103.17% with corresponding RSD of 2.6 % and 1.8%(n=6),respectively.CONCLUSION:The method is steady and with good repeatability,and can be used to determine the content of dulcitol and astragaloside in Compound Fufangteng Capsules.