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Background and Purpose: Dietary fibre comprises a complex group of polysaccharides that are indigestible but are fermented by gut microbiota, promoting beneficial effects to the intestinal mucosa indirectly through the production of short chain fatty acids. We found that a polysaccharide, rhamnogalacturonan (RGal), from the plant Acmella oleracea, has direct effects on intestinal epithelial barrier function. Our objective was to determine the mechanism whereby RGal enhances epithelial barrier function. Experimental Approach Monolayers of colonic epithelial cell lines (Caco‐2, T84) and of human primary cells from organoids were mounted in Ussing chambers to assess barrier function. The cellular mechanism of RGal effects on barrier function was determined using inhibitors of TLR‐4 and PKC isoforms. Key Results: Apically applied RGal (1000 μg ml−1) significantly enhanced barrier function as shown by increased transepithelial electrical resistance (TER) and reduced fluorescein isothiocyanate (FITC)‐dextran flux in Caco‐2, T84 and human primary cell monolayers, and accelerated tight junction reassembly in Caco‐2 cells in a calcium switch assay. RGal also reversed the barrier‐damaging effects of inflammatory cytokines on FITC‐dextran flux and preserved the tight junction distribution of occludin. RGal activated TLR4 in TLR4‐expressing HEK reporter cells, an effect that was inhibited by the TLR4 inhibitor, C34. The effect of RGal was also dependent on PKC, specifically the isoforms PKCδ and PKCζ. Conclusion and Implications: RGal enhances intestinal epithelial barrier function through activation of TLR4 and PKC signalling pathways. Elucidation of RGal mechanisms of action could lead to new, dietary approaches to enhance mucosal healing in inflammatory bowel diseases. [ABSTRACT FROM AUTHOR]

The inflamed mucosa contains a complex assortment of proteases that may participate in wound healing or the development of inflammation-associated colon cancer. We sought to determine the role of protease-activated receptor 2 (PAR2) in epithelial wound healing in both untransformed and transformed colonic epithelial cells. Monolayers of primary epithelial cells derived from organoids cultivated from patient colonic biopsies and of the T84 colon cancer cell line were grown to confluence, wounded in the presence of a selective PAR2-activating peptide, and healing was visualized by live cell microscopy. Inhibitors of various signaling molecules were used to assess the relevant pathways responsible for wound healing. Activation of PAR2 induced an enhanced wound-healing response in T84 cells but not primary cells. The PAR2-enhanced wound-healing response was associated with the development of lamellipodia in cells at the wound edge, consistent with sheet migration. The response to PAR2 activation in T84 cells was completely dependent on Src kinase activity and partially dependent on Rac1 activity. The Src-associated signaling molecules, focal adhesion kinase, and epidermal growth factor receptor, which typically mediate wound-healing responses, were not involved in the PAR2 response. Experiments repeated in the presence of the inflammatory cytokines TNF and IFNγ revealed a synergistically enhanced PAR2 wound-healing response in T84s but not primary cells. The epithelial response to proteases may be different between primary and cancer cells and is accentuated in the presence of inflammatory cytokines. Our findings have implications for understanding epithelial restitution in the context of inflammatory bowel disease (IBD) and inflammation-associated colon cancer. NEW & NOTEWORTHY: Protease-activated receptor 2 enhances wound healing in the T84 colon cancer cell line, but not in primary cells derived from patient biopsies, an effect that is synergistically enhanced in the presence of the inflammatory cytokines TNF and IFNγ. [ABSTRACT FROM AUTHOR]

The Ascomycete Cordyceps militaris, an entomopathogenic fungus, is one of the most important traditional Chinese medicines. Studies related to its pharmacological properties suggest that this mushroom can exert interesting biological activities. Aqueous (CW and HW) and alkaline (K5) extracts containing polysaccharides were prepared from this mushroom, and a β-D-glucan was purified. This polymer was analysed by GC-MS and NMR spectrometry, showing a linear chain composed of β-D-Glcp (1→3)-linked. The six main signals in the 13C-NMR spectrum were assigned by comparison to reported data. The aqueous (CW, HW) extracts stimulated the expression of IL-1β, TNF-α, and COX-2 by THP-1 macrophages, while the alkaline (K5) extract did not show any effect. However, when the extracts were added to the cells in the presence of LPS, K5 showed the highest inhibition of the pro-inflammatory genes expression. This inhibitory effect was also observed for the purified β-(1→3)-D-glucan, that seems to be the most potent anti-inflammatory compound present in the polysaccharide extracts of C. militaris. In vivo, β-(1→3)-D-glucan also inhibited significantly the inflammatory phase of formalin-induced nociceptive response, and, in addition, it reduced the migration of total leukocytes but not the neutrophils induced by LPS. In conclusion, this study clearly demonstrates the anti-inflammatory effect of β-(1→3)-D-glucan. [ABSTRACT FROM AUTHOR]

Recognizing that enteric tuft cells can signal the presence of nematode parasites, we investigated whether tuft cells are required for the expulsion of the cestode, Hymenolepis diminuta, from the non-permissive mouse host, and in concomitant anti-helminthic responses. BALB/c and C57BL/6 mice infected with H. diminuta expelled the worms by 11 days post-infection (dpi) and displayed DCLK1+ (doublecortin-like kinase 1) tuft cell hyperplasia in the small intestine (not the colon) at 11 dpi. This tuft cell hyperplasia was dependent on IL-4Rα signalling and adaptive immunity, but not the microbiota. Expulsion of H. diminuta was slowed until at least 14 dpi, but not negated, in tuft cell-deficient Pou2f3-/- mice and was accompanied by delayed goblet cell hyperplasia and slowed small bowel transit. Worm antigen and mitogen evoked production of IL-4 and IL-10 by splenocytes from wild-type and Pou2f3-/- mice was not appreciably different, suggesting similar systemic immune reactivity to infection with H. diminuta. Wild-type and Pou2f3-/- mice infected with H. diminuta displayed partial protection against subsequent infection with the nematode Heligmosomoides bakeri. We speculate that, with respect to H. diminuta, enteric tuft cells are important for local immune events driving the rapidity of H. diminuta expulsion but are not critical in initiating or sustaining systemic Th2 responses that provide concomitant immunity against secondary infection with H. bakeri. Author summary: The small intestinal tuft cell is emerging as a versatile sentinel cell type in a variety of infections involving protozoans, nematodes, and certain bacteria. Whether the tuft cell responds to enteric cestode infections and the extent of its involvement in mediating the anti-helminth response is not yet characterized. Using mice infected with Hymenolepis diminuta, we show that tuft cells help accelerate expulsion of this lumen-dwelling cestode, by coordinating local events that form an integral part of the classical "weep and sweep" anti-helminthic response. We further show that although infection with H. diminuta induces both tuft cell hyperplasia as well as protection from subsequent infection with the nematode Heligmosmoides bakeri, the tuft cell is not solely responsible for mediating systemic and other local Th2 responses against H. diminuta. Our work reveals subtle roles for the tuft cell in initiating and coordinating host anti-parasitic activity in cestode infections. At the same time, we show that redundancies exist in the host's mucosal arsenal that ultimately mediate worm expulsion in tuft cell deficient mice. [ABSTRACT FROM AUTHOR]

Abstract: Aquaporin (AQP) 3 expression is altered in inflammatory bowel diseases, although the exact mechanisms regulating AQP abundance are unclear. Although interferon gamma (IFNγ) is centrally involved in intestinal inflammation, the effect of this cytokine on AQP3 expression remains unknown. HT-29 human colonic epithelial cells were treated with IFNγ to assess AQP3 mRNA expression by real-time RT-PCR and functional protein expression through the uptake of radiolabelled glycerol. Transient knockdown of signal transducer and activator of transcription 1 (STAT1), STAT3, Sp1, and Sp3 were performed to determine the involvement of these transcription factors in the IFNγ-induced signalling cascade. AQP3 promoter regions involved in the response to IFNγ were assessed using a luciferase reporter system. Likewise, enteroids derived from human colonic biopsies were also treated with IFNγ to assess for changes in AQP3 mRNA expression. IFNγ decreased AQP3 mRNA expression in HT-29 cells in a time- and concentration-dependent manner and reduced functional AQP3 protein expression (decreased 3H-labelled glycerol uptake). IFNγ also reduced AQP3 expression in enteroids derived from human colonic biopsies. Knockdown of STAT1 partially prevented the IFNγ-induced downregulation of AQP3 expression, whereas STAT3 and Sp3 knockdowns resulted in increased baseline expression of AQP3 but did not alter IFNγ-induced downregulation. Constitutive transcription of AQP3 is downregulated by IFNγ as demonstrated using the luciferase reporter system, with Sp3 bound to the AQP3 promoter as shown by chromatin immunoprecipitation. AQP3 constitutive transcription in intestinal epithelial cells is downregulated by IFNγ. This response requires STAT1 that is postulated to drive the downregulation of AQP3 expression through increased acetylation or decreased deacetylation the AQP3 promoter, ultimately resulting in decreased constitutive transcription of AQP3.Key messages: • IFNγ suppresses the expression of AQP3 in intestinal epithelial cells.• Proximal AQP3 promoter elements are sufficient to drive constitutive expression and mediate the IFNγ-induced downregulation of AQP3 mRNA expression.• IFNγ-induced suppression of AQP3 is dependent upon STAT1 expression, but not STAT3, Sp1, or Sp3. [ABSTRACT FROM AUTHOR]

The plant Arctium lappa L. is popularly used to relieve symptoms of inflammatory disorders. A crude polysaccharide fraction (SAA) resulting of aqueous extraction of A. lappa leaves showed a dose dependent anti-edematogenic activity on carrageenan-induced paw edema, which persisted for up to 48 h. Sequential fractionation by ultrafiltration at 50 kDa and 30 kDa cut-off membranes yielded three fractions, namely RF50, RF30, and EF30. All these maintained the anti-edematogenic effect, but RF30 showed a more potent action, inhibiting 57% of the paw edema at a dose of 4.9 mg/kg. The polysaccharide RF30 contained galacturonic acid, galactose, arabinose, rhamnose, glucose, and mannose in a 7:4:2:1:2:1 ratio and had a M w of 91,000 g/mol. Methylation analysis and NMR spectroscopy indicated that RF30 is mainly constituted by a type I rhamnogalacturonan branched by side chains of types I and II arabinogalactans, and arabinan. [ABSTRACT FROM AUTHOR]

Structurally different water-insoluble (1 → 3),(1 → 6) β- d -glucans were isolated from aqueous and alkaline extracts of the mushroom-forming ascomycete Cookeina tricholoma , a wild edible mushroom found in Brazilian Amazon forest. The structures showed different substitution patterns, which may influence their extractability and consequently their conformation in solution, and different M W (4.3 × 10 5 Da, 3.7 × 10 5 Da and 8.2 × 10 5 Da, for ICW- Ct , IHW- Ct and IK2- Ct , respectively). The main-chains are composed of (1 → 3)-linked β- d -Glc p units O-6 substituted by side chains with different lengths of (1 → 6)-linked β- d -Glc p units (ICW- Ct and IHW- Ct ) or by a combination of (1 → 6)-linked β- d -Glc p units and single units of β- d -Glc p (IK2- Ct ). β- d -glucans with similar M W and showing only (1 → 6)-linked β- d -Glc p units as side chains (ICW- Ct and IHW- Ct ) showed significant inhibition of neurogenic pain, 69 ± 11 and 57 ± 11% at the dose of 10 mg kg −1 , respectively, in the model of nociception induced by intraplantar injection of formalin. [ABSTRACT FROM AUTHOR]

Highlights: [•] A galactoarabinoglucuronoxylan was found in the pulp of tamarillo fruits. [•] The polysaccharide was composed of Xylp, Araf, Galp, GlcpA and 4-O-Me-GlcpA. [•] The galactoarabinoglucuronoxylan had a main chain branched only at O-2. [•] It showed an antinociceptive effect on inflammatory pain models. [ABSTRACT FROM AUTHOR]

Abstract: The plant Acmella oleracea (L.) R.K.Jansen (Asteraceae), locally known as jambu, is widely used in Legal Amazon in local dishes and in folk medicine. A polysaccharide (SC) was isolated from this plant, following aqueous extraction, which contained uronic acid, galactose, arabinose, rhamnose, and glucose in a 15:2:1:1:0.5 molar ratio and had a M w 226,000g/mol. Methylation analysis and NMR spectroscopy indicated that SC is a rhamnogalacturonan composed of a long chain of →4)-6-OMe-α-d-GalpA-(1→, interspersed with some α-l-Rhap residues, partly substituted by side-chains of type II arabinogalactans. SC significantly inhibited ethanol-induced gastric ulcers in rats with an ED50 of 1.5mg/kg, indicating that SC acts as gastroprotective agent. [Copyright &y& Elsevier]

Abstract: After removal of starch, cell wall polysaccharides of seeds of quinoa were studied. They were extracted successively with water and with aq. 10% KOH. The extracted polysaccharides were fractionated and purified by freeze–thaw treatment and by sequential ultrafiltration through membranes. The purified fractions (PQW, K2-30EM, K1-10RM and K1-30RM) were analyzed by sugar composition, HPSEC, methylation and 13C NMR spectroscopy analysis. The results showed that PQW consisted of a linear arabinan with (1→5)-linked α-l-arabinofuranosyl units. Fractions K2-30EM, K1-10RM and K1-30RM were related to rhamnogalacturonan type I with a branched arabinan and galactan side-chains. This arabinan has (1→5)-linked α-l-arabinofuranosyl units substituted exclusively in O-3. The main differences between these fractions were their molecular mass and content of Rha and GalA, which probably arise from an increase in their rhamnogalacturonan backbone. A pool of these polysaccharides (arabinan and arabinan-rich pectic polysaccharides) showed gastroprotective activity on ethanol-induced acute gastric lesions in rats. [Copyright &y& Elsevier]

The gut microbiome contributes to inflammatory bowel disease (IBD), in which bacteria can be present within the epithelium. Epithelial barrier function is decreased in IBD, and dysfunctional epithelial mitochondria and endoplasmic reticulum (ER) stress have been individually associated with IBD. We therefore hypothesized that the combination of ER and mitochondrial stresses significantly disrupt epithelial barrier function. Here, we treated human colonic biopsies, epithelial colonoids, and epithelial cells with an uncoupler of oxidative phosphorylation, dinitrophenol (DNP), with or without the ER stressor tunicamycin and assessed epithelial barrier function by monitoring internalization and translocation of commensal bacteria. We also examined barrier function and colitis in mice exposed to dextran sodium sulfate (DSS) or DNP and co-treated with DAPK6, an inhibitor of death-associated protein kinase 1 (DAPK1). Contrary to our hypothesis, induction ofERstress (i.e. the unfolded protein response) protected against decreased barrier function caused by the disruption of mitochondrial function. ER stress did not prevent DNP-driven uptake of bacteria; rather, specific mobilization of the ATF6 arm of ER stress and recruitment of DAPK1 resulted in enhanced autophagic killing (xenophagy) of bacteria. Of note, epithelia with a Crohn’s disease–susceptibility mutation in the autophagy gene ATG16L1 exhibited less xenophagy. Systemic delivery of the DAPK1 inhibitor DAPK6 increased bacterial translocation in DSS- or DNP-treated mice. We conclude that promoting ER stress–ATF6–DAPK1 signaling in transporting enterocytes counters the transcellular passage of bacteria evoked by dysfunctional mitochondria, thereby reducing the potential for metabolic stress to reactivate or perpetuate inflammation. [ABSTRACT FROM AUTHOR]

In order to obtain polysaccharides from green and black teas ( Camellia sinensis ), commercial leaves were submitted to infusion and then to alkaline extraction. The extracts were fractionated by freeze-thawing process, giving insoluble and soluble fractions. Complex arabinogalactan protein from the soluble fractions of both teas (GTPS and BTPS) were determined by methylation analysis and 1 H/ 13 C-HSQC spectroscopy, showing a main chain of (1 → 3)-β-Gal p , substituted at O -6 by (1 → 6)-linked β-Gal p with side chains of α-Ara f and terminal units of α-Ara f, α-Fuc p and α-Rha p . A highly branched heteroxylan from the insoluble fractions (GTPI and BTPI) showed in methylation analysis and 1 H/ 13 C-HSQC spectroscopy the main chain of (1 → 4)-β-Xyl p , substituted in O -3 by α-Ara f , β-Gal p and α-Glc p units. Evaluating their gastroprotective activity, the fractions containing the soluble heteropolysaccharides from green (GTPS) and black teas (BTPS) reduced the gastric lesions induced by ethanol. Furthermore, the fraction of insoluble heteropolysaccharides of green (GTPI) and black (BTPI) teas also protected the gastric mucosa. In addition, the maintenance of gastric mucus and reduced glutathione (GSH) levels was involved in the polysaccharides gastroprotection. [ABSTRACT FROM AUTHOR]

Hydro-alcoholic extracts from leaves of Camellia sinensis (green- and black-tea leaves) were submitted to a fractionation, promoting the compound separation according to their polarity, and analyzed by ultra-high performance liquid chromatography–mass spectrometry. A wide range of compounds could be identified, such as catechins and their gallate (esters) or oxidation derivatives (theaflavins), glycosylated flavonoids and other phenolics, as well as lipids, saponins and alkaloids. Also have been developed, via bio-guided examination, the gastroprotective property of the compounds identified. The samples were assayed using the model of acute gastric lesions induced in rats by ethanol. Hydro-alcoholic extracts of green-tea and black-tea protected the gastric mucosa with ED 50 = 3.6 and 10.2 mg/kg, respectively, with participation of gastric mucus and reduced glutathione (GSH). The ethyl acetate fraction from green-tea and aqueous fraction from black-tea were, respectively, 6 and 10 times more effectiveness than the initial extracts. Moreover, the epigallocatechin gallate (EGCG, 0.204 mg/kg), a main component of ethyl acetate fraction from green tea, reduced the gastric lesion by 56% and restored the mucus levels, however the rutin (0.0133 mg/kg), a flavonoid found in the most active fraction of black-tea, was less significant at the natural concentrations. These results have confirmed that the different compounds present in green- and black-tea hydro-alcoholic extracts and partitioned fractions produce relevant gastroprotection mainly via maintenance of the protective factors, mucus and GSH. [ABSTRACT FROM AUTHOR]

Highlights: [•] A complex glucuronoarabinoxylan (CNAL) was isolated from C. nucifera gum exudate. [•] The presence of Xylp di- and tri-substituted indicated a highly branched structure. [•] The presence of Fuc as non-reducing end units is typical of palm gum exudates. [•] The glucuronoarabinoxylan showed gastroprotective effect in rats. [•] Rats treated with CNAL presented a reduction in ethanol-induced gastric lesions. [ABSTRACT FROM AUTHOR]

Abstract: Glucomannan (GM) is a polysaccharide obtained from Heterodermia obscurata lichens. The present study was conducted to elucidate the antinociceptive effect of GM in behavioural models of acute and chronic pain in mice. GM reduced mechanical allodynia and the levels of interleukin 1-β (IL-1β) in spinal cord and nerve in the partial sciatic nerve ligation (PSNL) model. Systemic treatment with GM inhibited the nociception induced by intraplantar injection of glutamate and by intrathecal injection of N-methyl-d-aspartic acid (NMDA), (±)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD), tumour necrosis factor α (TNF-α) and IL-1β. Taken together, our data demonstrate that GM has significant antinociceptive effect in acute and chronic pain, suggesting a potential interest in the development of new clinically relevant drugs for the management of pain. [Copyright &y& Elsevier]

Abstract: The fucogalactan from Agaricus bisporus (EFP-Ab) obtained on aqueous extraction followed by purification had M w 37.1×104 gmol−1 relative to a (1→6)-linked α-d-Galp main-chain partially methylated at HO-3, and partially substituted at O-2 by nonreducing end-units of α-l-Fucp or β-d-Galp. EFP-Ab also inhibited significantly the neurogenic and inflammatory phases of formalin-induced licking, however, the antinociceptive effect was more pronounced against the inflammatory phase with ID50 of 36.0 (25.8–50.3)mgkg−1. In addition, EFP-Ab decreased the lethality induced by CLP. Its administration reduced the late mortality rate by 40%, prevented neutrophil accumulation in lungs and markedly decreased iNOS and COX-2 protein expression by ileum cells. These data show for the first time that EFP-Ab has significant anti-sepsis, antinociceptive and anti-inflammatory actions, which seems to be related to the decreased iNOS and COX-2 expression. Collectively, the present results demonstrate that EFP-Ab could constitute an attractive molecule of interest for the development of new drugs. [Copyright &y& Elsevier]

Abstract: After industrial processing, one-third of sugarcane culms is converted into residual bagasse. The xylan-rich hemicellulose components of the bagasse were extracted with hot aqueous alkali (AX-CRUDE). Approximately 82% of the extracted hemicelluloses was precipitated with ethanol (AX-PET). Both AX-CRUDE and AX-PET contained an arabinoxylan as confirmed by 13C NMR and methylation analysis. Fraction AX-PET was fed to female Wistar rats with ethanol-induced gastric lesions. Oral administrations of 30, 100, and 300mg/kg reduced the gastric lesion area by over 50%, and replenished ethanol-induced depletion of glutathione. The polysaccharide also increased mucus production by over 70%, indicating its cytoprotective action on experimentally induced gastric ulcers. These findings are significant, since a biologically active compound can be extracted in high yields from an abundant, readily available residue. [Copyright &y& Elsevier]

Abstract: Successive aqueous and alkaline extraction of the thallus of the lichenized fungus Heterodermia obscurata provided a highly branched glucomannan fraction (GM), whose chemical structure was determined. This was based on monosaccharide composition, methylation, partial acid hydrolysis, and NMR spectroscopic analysis. It consisted of a main chain of (1→6)-linked α-d-mannopyranosyl units, almost all being substituted at O-2 with α-d-glucopyranosyl, α-d-mannopyranosyl, and 4-O-substituted α-d-mannopyranosyl groups. Intra-peritoneal administration of this GM induced a marked and dose-dependent inhibition of acetic acid-induced visceral pain with an ID50 of 0.6 (0.2-2.0) mg/kg and inhibition of 88±4%. It also reduced leukocyte migration by 58±4%, but did not alter plasmatic extravasation to the peritoneal cavity. The results suggest that the glucomannan from the H. obscurata might have potential for antinociceptive and anti-inflammatory utilization. [ABSTRACT FROM AUTHOR]

Abstract: Fucogalactans from Agaricus brasiliensis (EPF-Ab) and A. bisporus var. hortensis (EPF-Ah) were prepared via by aqueous extraction and a purification procedure. EPF-Ab had M w 19.4×103 g/mol and EPF-Ah M w 31.1×103 g/mol. EPF-Ab had a (1→6)-linked α-D-Galp main-chain partially substituted in O-2 by non-reducing end-units of α-L-Fucp. EPF-Ah had a similar main-chain with O-2 substitution, but was partially methylated at HO-3, as well as having 2.5% non-reducing end-units of β-D-Gal. In mice, EPF-Ab gave 39% antinociceptive inhibition (ID50 >100mg/kg) and no anti-inflammatory activity. EPF-Ah also gave an inhibition of 39% at ID50 0.33mg/kg and also inhibited by 61% (ID50 5.0mg/kg) total cell migration and by 32% peritoneal capillary permeability, which is related to the anti-inflammatory effect. The small differences in chemical structure in these polysaccharides thus modified their biological activities. [Copyright &y& Elsevier]

Abstract: A highly purified type I arabinogalactan (AG) from soybean meal was prepared. It contained galactose, arabinose, galacturonic acid and rhamnose in a 52:41:4:3 molar ratio and had M w 124,000g/mol. Methylation analysis and 13C NMR spectroscopy indicated that AG is constituted by a (1→4)-linked β-Galp main chain with substituents of α-Araf at O-3, which are in turn substituted at O-5, O-3,5, and O-2,5. It is probably linked to O-4 of some rhamnosyl units of a type I rhamnogalacturonan, formed by repeating (1→4)-α-D-GalpA-(1→2)-α-L-Rhap groups. AG significantly inhibited ethanol-induced gastric lesions in rats at an ED50 of 35mg/kg, indicating that it has a gastroprotective effect. [Copyright &y& Elsevier]

Abstract: A glucan was extracted with hot water from the basidiomycete Pleurotus pulmonarius and shown to have a (1→3)-linked β-d-glucopyranosyl main-chain substituted at O-6 of every third unit by single β-d-glucopyranosyl non-reducing end units. This was shown by mono- and bidimensional nuclear magnetic resonance (NMR) spectroscopy, methylation analysis, and a controlled Smith degradation. The glucan was tested for its effects on the acetic acid-induced writhing reaction in mice, a typical model for quantifying inflammatory pain. It caused a marked and dose-dependent anti-inflammatory response, demonstrated by the inhibition of leukocyte migration to injured tissues (82±6%) with an ID50 of 1.19 (0.74–1.92) mg/kg. Furthermore, animals previously treated with the glucan (3 mg/kg i.p.), showed a reduction of 85±5% of writhes, after receiving the acetic acid injection. Furthermore, in the formalin test, the glucan (3–30 mg/kg, i.p.) also caused significant inhibition of both the early (neurogenic pain) and the late phases (inflammatory pain) of formalin-induced licking. However, it was more potent and effective in relation to the late phase of the formalin test, with mean ID50 values for the neurogenic and the inflammatory phases of >30 and 12.9 (6.7–24.6) mg/kg and the inhibitions observed were 43±5% and 96±4%, respectively. These data showed that the glucan had potent anti-inflammatory and analgesic (antinociceptive) activities, possibly by the inhibition of pro-inflammatory cytokines. [Copyright &y& Elsevier]

Abstract: Xylans are the main hemicelluloses found in higher plants, and are often present in phytotherapic medicines. An acidic heteroxylan was obtained from Maytenus ilicifolia leaves by hot 10% aqueous KOH extraction. This was subjected to freeze-thawing process, giving insoluble and soluble fractions and the latter treated with Fehling solution. Its insoluble fraction (MI-HX) was further examined. The acidic heteroxylan gave xylose, galactose, glucose, and 4-O-methylglucuronic acid in a 76:6:9:9 molar ratio and methylation analyses and 13C NMR spectroscopy showed its main chain consists of 4-O-linked β-d-Xylp units. This polysaccharide and another acidic heteroxylan from Phyllanthus niruri had anti-ulcer activity and were able to reduce gastric lesions induced by ethanol by 65% and 78%, with ED50 =40.0 and 20.4mg/kg, each respectively. These results suggest that this class of polysaccharide has a protective anti-ulcer effect, and that there is a relation between its chemical structure and biological function. [Copyright &y& Elsevier]

Abstract: Maytenus ilicifolia is one of frequently used medicinal plants in Brazil. Its leaves are used in homemade and industrial medicines for effective treatment of stomach ulcers. A polygalacturonic acid (PGA) was obtained from its leaves by aqueous extraction, followed by fractionation via a freezing–thawing process and Fehling precipitation. Methylation analysis and 13C NMR spectroscopy showed PGA to consist of (1→4)-linked α-d-GalpA repeating units. It significantly inhibited ethanol-induced gastric lesions in rats, with an ED50 of 103mg/kg, suggesting that it has a protective anti-ulcer effect. This polysaccharide may thus play an important role in the anti-ulcer effect of M. ilicifolia. [Copyright &y& Elsevier]