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Yellow passion fruit peel (PFP) is considered an important source of dietary fibre (DF) and its consumption has been associated with health benefits in metabolic and gut disturbs. This work aimed to characterize the chemical structure of soluble DF (SDF) from PFP and evaluate its gastroprotective activity in acute gastric-ulcer model induced by ethanol in rats. SDF was composed of 92% of GalA and presented high methyl esterified homogalacturonan (DE = 70%), with relative Mw of 53 kDa. Oral pre-treatment of animals with SDF (0.1, 1 and 10 mg/kg) significantly reduced gastric ulcer lesions by 72%, 79% and 87% respectively. The gastroprotective effect was maintained when SDF was administered by the intraperitoneal route. SDF also prevented the depletion of GSH levels and gastric wall mucus when administered by both routes. These results demonstrated that ingestion of SDF from PFP exerts significant gastroprotective effects in vivo on experimentally induced gastric ulcers.

A β-D-glucan was obtained from the edible mushroom Pholiota nameko by hot aqueous extraction and purification. NMR and methylation analyses of the purified fraction (GHW-PN, 1.46% yield) indicated the presence of a (1 → 3)-linked β-D-glucan, highly substituted (~27%) at O-6 by single units of β-D-Glcp or by (1 → 6)-β-D-Glcp fragments. The β-glucan (at 0.5, 1, and 2%) showed shear thinning behavior and when the concentration of the solution increased, there was an increase in apparent viscosity. The β-D-glucan presented gel-like behavior and thermal stability under a simulated pasteurization process, suggesting its potential as a thickening and gelling agent in products submitted to temperature variations. The β-D-glucan at 0.3, 1.0 and 3.0 mg kg−1 significantly inhibited the inflammatory pain in 24.8, 56.9 and 82.3%, respectively, in the formalin-induced nociception in mice. The results pointed out that the β-D-glucan (GHW-PN) isolated from P. nameko presents potential application for the food industry or for medical purposes.

Handroanthus albus, commonly known as yellow ipe, is a native and widely distributed tree in Brazil. An aqueous soluble polysaccharide fraction (HASP) was obtained from its leaves, and monosaccharide composition, glycosidic linkage analysis by methylation and NMR spectroscopy indicated that HASP is mainly composed of a type II arabinogalactan, and suggested that other polysaccharides could also be present in a smaller proportion. HASP was able to promote antinociception in formalin-induced (second phase) and on glutamate-induced nociception tests, besides reducing the number of abdominal contortions induced by acetic acid in mice. Moreover, HASP reduced acetic acid-induced leukocyte infiltration in the peritoneal cavity and showed anti-edematogenic activity, decreasing mechanical allodynia and myeloperoxidase activity in the carrageenan-induced paw edema model. These results showed that the polysaccharide fraction HASP from H. albus leaves has interesting antinociceptive and anti-inflammatory activities.

Acmella oleracea (jambu), is used as ingredient for food and in folk medicine to relief toothache. Jambu edible flowers are rich in alkylamides, mainly spilanthol, which are responsible to evoke chemesthetic sensations. This study aimed to investigate the local effects promoted by the intraplantar injection of the hexanic fraction (HF) rich in alkylamides from jambu flowers and compare to synthetic isobutylalkyl amide (IBA). Swiss male mice were intraplantarly administrated with HF and IBA (0.1–30 μg/20 μL), and the underlying mechanisms associated to the antinociceptive (0.1 μg) and pronociceptive (30 μg) effects were evaluated in chemical and sensorial tests. HF and IBA at 0.1 μg promoted analgesia in neurogenic and inflammatory phases of formalin test, against glutamate-induced nociception and independent of the activation of endogenous opioidergic system and dependent of TRPV1 modulation, whereas only HF reduced both nociception and mast cell degranulation in hindpaw induced by compound 48/80. However, both potentiated the TRPA1-mediated nociception. In contrast, HF and IBA (30 μg)-evoked nociceptive behaviors were reduced by the activation of opioidergic system, by TRPA1 antagonist and TRP nociceptive fibers desensitization. In addition, 30 μg IBA-evoked nociception by activation of TRPV1, and 30 μg HF by mast cell degranulation. Furthermore, on the contrary of IBA, HF elevated both mechanical and thermal paw threshold. Altogether, these results indicate that alkylamides could elicited dual effects, adding new evidences and mechanisms for these opposite actions in different doses. Although further research is needed, we confirmed that alkylamides displays local analgesic and/or anesthetic effects.

The gastrointestinal tract is extremely sensitive to ischemia and reperfusion (I/R). Studies have reported that resveratrol (RSV) is able to combat damage caused by intestinal I/R. Because of its effectiveness in increasing the permanence and bioavailability of resveratrol in the intestinal epithelium, we investigated whether the effect of resveratrol-loaded in poly(anhydride) nanoparticles reduce oxidative stress and promote myenteric neuroprotection in the ileum of rats subjected to I/R. Physicochemical evaluations were performed on nanoparticles. The animals were divided into nine groups (n = 6/group) and treated every 48 h. Treatments with resveratrol (7 mg/kg of body weight) were applied 5 days before surgery and continued for 7 days after surgery (reperfusion period). The superior mesenteric artery was occluded to cause I/R injury. Oxidative stress, myeloperoxidase, nitrite, aspartate aminotransferase, alanine aminotransferase, immunolabeling of myenteric neurons and glial cells, and gastrointestinal transit was evaluated. Both nanoparticle formulations presented negative charge with homogeneous distribution, and the payload, showed an encapsulation efficiency of 60%. Resveratrol administered in free form prevented alterations that were caused by I/R. The results of the groups treated with RSV-loaded nanoparticles presented similar results to the group treated with free resveratrol. Treatment with empty nanoparticles showed that poly(anhydride) is not an ideal nanocarrier for application in in vivo models of intestinal I/R injury, because of hepatotoxicity that may be caused by epithelial barrier dysfunction that triggers the translocation of nanoparticles.

Background Sedum dendroideum, popularly known in Brazil as balsam, is traditionally used as a wound healing agent, to treat gastritis, and several other health problems. Some studies have shown that plant polysaccharides may have gastroprotective properties. Purpose Considering the popular use of S. dendroideum and the gastroprotective activity of polysaccharides, the objective of this work was to obtain, to characterize, and to evaluate the gastroprotective activity of a polysaccharide fraction from this plant. Methods Polysaccharides of S. dendroideum were extracted with water by infusion, fractionated by freeze-thawing process and dialyzed at a 100 kDa cut-off membrane, and characterized by monosaccharide composition and NMR analysis. The gastroprotective activity of the pectic polysaccharide fraction RSBAL was evaluated in the ethanol-induced ulcer model in rats, followed by determination of the mucus and glutathione levels in the gastric tissue. Results RSBAL was constituted by a homogalacturonan and a homogalacturonan branched by side chains of arabinans and type II arabinogalactans. It reduced ethanol-induced gastric ulcers in rats, preserving mucus and glutathione levels in the stomach. Conclusion This study demonstrated that polysaccharides could be related to the pharmacological activity of S. dendroideum.

Ethnopharmacological relevance Peptic ulcer is an inflammatory disease that therapeutic options are mainly focused in antisecretory drugs. Sedum dendroideum Moc & Sesse ex DC (Crassulaceae) is employed in folk medicine for the treatment of gastric ulcers. Recently, our group demonstrated that Sedum dendroideum infusion (SDI) is rich in polyphenols (flavonol glycosides, myricetin, quercetin and kaempferol) and promoted gastroprotection against acute ulcer models, without changes gastric acid secretion. Aim of the study Here, we follow the investigation of the healing effects of SDI (ED50 = 191 mg/kg) in the chronic gastric ulcer model induced by 80% acetic acid in rats, elucidating underlying mechanisms. Material and methods Rats were orally treated with vehicle (water, 1 mL/kg), SDI (191 mg/kg), omeprazole (40 mg/kg) or sucralfate (100 mg/kg) twice daily for 5 days after ulcer induction. Following treatments, toxicological effects, macroscopic ulcer appearance, microscopic histological (HE, mucin PAS-staining) and immunohistochemical (PCNA and HSP70) analysis, inflammatory (MPO and NAG activity, cytokine levels measurements) and antioxidant (SOD and CAT) parameters were investigated in gastric ulcer tissues. Results Oral treatment with SDI accelerated gastric ulcer healing, maintained mucin content and promoted epithelial cell proliferation. SDI also reduced neutrophil and mononuclear leukocyte infiltration, TNF-α and IL-1β levels and the oxidative stress, restoring SOD and CAT activities in the ulcer tissue. Conclusions The gastric healing effect of SDI was mediated through endogenous protective events as well as due to the anti-inflammatory and antioxidant actions. Our observations support and reinforce the traditional utilize of Sedum dendroideum as a natural nontoxic therapeutic alternative for the treatment of gastric ulcers.

A polysaccharide fraction from Handroanthus heptaphyllus leaves was obtained with a simple and quick purification method. Methylation analysis and NMR spectroscopy indicated the presence of a complex polysaccharide fraction mainly constituted by a type II arabinogalactan. This is the first report in literature on structural elucidation of polysaccharides of species from genus Handroanthus. Oral and intraperitoneal administration of the polysaccharide fraction from Handroanthus heptaphyllus (HHSF) protected the gastric mucosa in an acute model of gastric lesion induced by ethanol, preserving gastric mucus. Furthermore, in the indomethacin model, HHSF reduced wounded area and inhibited mucus and GSH depletion. HHSF also accelerated gastric ulcer healing, accompanied by the maintenance of GSH levels. In addition, in an oxidative stress model with human epithelial cell line (Caco-2), HHSF was able to preserve GSH levels and was not toxic to cells. Collectively, these results showed that HHSF has an interesting antiulcerogenic activity and could constitute an interesting option for the treatment of gastric ulcer.

We investigated long-lasting changes in endothelial and vascular function in adult rat survivors of severe sepsis induced by cecal ligation and puncture (CLP) model. For this, male Wistar rats (200–350 g) had their cecum punctured once (non-transfixing hole) with a 14-gauge needle. Performed in this way, a mortality rate around 30% was achieved in the first 72 h. The survivors, together with age-matched control rats (not subjected to CLP), were maintained in our holding room for 60 days (S60 group) and had the descending thoracic aorta processed for functional, histological, biochemical or molecular analyses. Endothelium-intact aortic rings obtained from sepsis-surviving S60 group displayed increased angiotensin II-induced contraction, accompanied by decreased activity of the endogenous superoxide dismutase, augmented reactive oxygen species generation, and increased levels of tyrosine nitration compared with vessels from control group. The superoxide scavengers superoxide dismutase and tempol, and the antioxidant apocynin, were able to avoid this enhanced contractility to angiotensin II in aortic rings from the S60 group. In addition, aortic rings from the S60 group presented reduced sensitivity to Y-27632, a Rho-kinase (ROCK) inhibitor. Immunoblot analyses revealed augmented RhoA and ROCK II, and high levels of phosphorylation of myosin phosphatase target subunit 1 in vessels from S60 rats. In conclusion, aortic rings from sepsis-surviving rats display endothelial dysfunction mediated by the increased production of reactive oxygen species, which in turn reduces the bioavailability of nitric oxide and increases the formation of peroxynitrite, and enhances RhoA-ROCK-mediated calcium sensitization, leading to augmented contractile responses to angiotensin II. Notably, this is the first study demonstrating long-term dysfunction in the vasculature of sepsis-surviving rats, which take place or remain beyond the acute septic insult., Graphical abstract fx1, Highlights • Vessels from sepsis-surviving rats develop enhanced contractile responses to angiotensin II. • This hyperreactivity is avoided by the superoxide scavengers superoxide dismutase and tempol. • Generation of reactive oxygen species by angiotensin II is enhanced in these vessels. • Vessels from sepsis-surviving rats present an augmented degree of tyrosine nitration. • The activity of the RhoA-Rho-kinase pathway is enhanced in the aorta from sepsis-surviving rats.

Tomato is a known functional food due to its content of bioactive compounds. Herein, polysaccharides were extracted from mucilage of tomatoes, and a purified fraction (PTOK) was analyzed by sugar composition, methylation, and NMR spectroscopy analysis. The results showed the presence of an arabinoxylan, having (1→4)-linked β-d-Xylp units in the main chain, which carried a low proportion of branching (∼5.6%), at O-2 and O-3 position, with side chains constituted by single Araf or Xylp units. Intraperitoneal administration of the arabinoxylan in mice significantly reduced the number of abdominal constrictions induced by 0.6% acetic acid and the inflammatory phase of nociception induced by 2.5% formalin, indicating that it had an antinociceptive effect on inflammatory pain models, amplifying the biological role displayed by arabinoxylans in the diet. Furthermore, this study reports the presence of an arabinoxylan in a dicotyledon plant, and also it is the first study of polysaccharides from mucilage of tomatoes.

Ethnopharmacological relevance Sedum dendroideum Moc & Sesse ex DC (Crassulaceae) is a medicinal plant employed in Mexican and Brasilian folk medicine as juice or infusion, as remedy for the treatment of different diseases, including gastric disorders. Aim of the study Although some studies carried out with Sedum dendroideum have demonstrated its gastroprotective effect, the purpose of this study was to elucidate the chemical constituents, antioxidant, cytotoxic and mechanisms underlying the gastrointestinal properties of Sedum dendroideum accordingly its traditional use, as fresh leaves tea infusion (SDI). Materials and methods Chemical constituents were analyzed using high performance liquid chromatography and mass spectrometry (HPLC-MS). Antioxidant and cytotoxicity were evaluated in in vitro assays. The efficacy of the SDI on macroscopic ulcer appearance, mucus and GSH maintenance on ethanol- and indomethacin-induced ulcer models, gastric acid secretion and gastrointestinal motility were investigated. Results Phytochemical analysis by HPLC–MS revealed the presence of different flavonol glycosides, containing myricetin and quercetin, along with the kaempferol as aglycones. In vitro pharmacological investigation of SDI demonstrated potent antioxidant activity in DPPH assay (IC50: 13.25 ± 3.37 µg/mL) and absence of cytotoxicity in Caco-2 cells by MTT method. Oral administration of SDI (ED50 of 191.00 ± 0.08 mg/kg) in rats promoted gastroprotection against ethanol or indomethacin in rats through reinforcement of gastric wall mucus, GSH content and nitric oxide release, without present antisecretory properties. The gastroprotective effect was maintained when SDI (19 mg/kg) was administrated by intraperitoneal route. Furthermore, SDI (150 mg/kg) unchanged the gastric emptying but increase small bowel transit in mice through cholinergic pathways. Conclusions Collectively, this study confirmed that Sedum dendroideum promotes gastroprotection through preventing of endogenous defense mechanisms, represented by mucus and GSH without changes gastric acid secretion. Sedum dendroideum tea infusion features a chemical profile that contributes to the antioxidant and gastric health-promoting effects, supporting the use in folk medicine for the treatment of gastrointestinal disorders.

A water-soluble β-D-glucan was obtained from fruiting bodies of Piptoporus betulinus, by hot aqueous extraction followed by freeze-thawing procedure and dialysis. Its molar mass distribution and conformational behavior in solution was assessed by size-exclusion chromatography coupled with multiangle laser light scattering, showing a polysaccharide with an average molecular weight of 2.5 × 105 Da with a random coil conformation for molecular weights below 1 × 106 Da. Typical signals of β-(1 → 3)-linkages were observed in NMR spectrum (δ 102.7/4.76; 102.8/4.74; 102.9/4.52; and δ 85.1/3.78; 85.0/3.77) and also signals of O-6 substitution at δ 69.2/4.22 and 69.2/3.87. The analysis of partially O-methylated alditol acetates corroborates the NMR results, indicating the presence of a β-D-glucan with a main chain (1 → 3)-linked, substituted at O-6 by single-units of glucose. The β-D-glucan showed no toxicity on human colon carcinoma cell line (Caco-2) up to 1000 μg mL-1 and promoted cell migration on in vitro scratch assay, demonstrating a potential wound healing capacity.

The aim of this study was to investigate the chemical structure and biological activity of a pectic fraction isolated from the aerial parts of A. campestris L. subsp. maritima Arcangeli. The chemical and spectroscopic analyses of the pectic fraction (ACP-E10) demonstrated that ACP-E10 was composed of homogalacturonan (HG) (60%) and rhamnogalacturonan-I (RG-I) (29%) regions. Side chains of the RG-I included mainly branched arabinans and type II arabinogalactans (AG-II). The molar mass of ACP-E10 determined by HPSEC-MALLS was 16,600g/mol. ACP-E10 was evaluated for its gastroprotective effect against ethanol-induced gastric lesions in rats. Oral pretreatment of animals with ACP-E10 (0.3, 3 and 30mg/kg) significantly reduced gastric lesions by 77±7.9%, 55±11.1% and 65±11.8%. ACP-E10 also maintained mucus and glutathione (GSH) contents in the gastric mucosa. In addition, ACP-E10 demonstrated antioxidant activity in vitro by the DPPH assay. These results demonstrated that the pectin from A. campestris had significant gastroprotective effects in vivo, which were likely attributable to their capacity to increase the protective defenses of gastric mucosa.

Ethnopharmacological relevance In Brazil, Acmella oleracea (L.) R.K. Jansen, popularly known as “jambu”, has been used by some communities from Amazon region to treat toothache. In this study we examined the antinociceptive effect of the ethanolic extract obtained from the flowers of Acmella oleracea (EEAO) in animal models of nociceptive (chemical and thermal) and neuropathic (partial sciatic nerve ligation) pain. Materials and methods Adult male mice were treated by intraperitoneal route (i.p.) with EEAO before the induction of nociceptive response by formalin, capsaicin and cinnamaldehyde, thermal heat hyperalgesia (hot plate test) and mechanical allodynia (traumatic sciatic nerve injury). Acute toxicity and non-specific sedative effects were evaluated. Results EEAO (10, 30 and 100 mg/kg) reduced both neurogenic and inflammatory phases of the formalin- and also capsaicin- and cinnamaldehyde-induced orofacial nociception. Interestingly, EEAO at 100 mg/kg (i.p.) also reversed capsaicin-induced heat hyperalgesia assessed as the latency to paw withdrawal in the hot plate test. Also in the hot plate test, paw withdrawal latency was increased by EEAO (100 mg/kg) and this response was only partially reversed by naloxone. Furthermore, EEAO (100 mg/kg) also reduced mechanical allodynia caused by partial sciatic nerve ligation for 3 h. The estimated LD50 value was 889.14 mg/kg and EEAO did not alter the locomotion of animals in the open-field test. Conclusion Taken together, our data show that EEAO produces prevalent antinociceptive effects and does not cause adverse effects. The presence of N-alkylamides, including spilanthol, suggests that the therapeutic effect of EEAO is related to its highest anesthetic activity.

Ethnopharmacological relevance Piper tuberculatum Jacq. (Piperaceae) is medicinally used as an analgesic and as a treatment for gastric complaints. Thus, the current study aimed to investigate the gastroprotective and antisecretory properties of the dichloromethane fraction of the fruit of Piper tuberculatum (DFPT) and piplartine, a compound isolated from the DFPT, in rats. Materials and methods Gastric ulcers were induced in fasted rats by oral administration of absolute ethanol and then mucus content and glutathione (GSH) levels were measured. Mechanisms underlying the antisecretory action were studied through gastric H + ,K + -ATPase activity of highly purified rabbit gastric microsomes and pylorus ligature method in rats. Results In the acute toxicity test the values of estimated LD 50 for oral and intraperitoneal administration of DFPT were 1.6266 and 0.2684 g/kg, respectively. The DFPT (ED 50 =29 mg/kg, p.o.) and piplartine (4.5 mg/kg, p.o.) promoted gastroprotection against acute lesions induced by ethanol, effect that could be related with the maintenance of GSH levels in the gastric mucosa. However, only DFPT stimulated gastric mucus secretion. In vitro , the DFPT and piplartine inhibited the H + ,K + -ATPase activity and, in vivo DFPT and piplartine also reduced basal gastric acid secretion, as well as that stimulated by pentagastrin. Conclusions These results demonstrate that DFPT and piplatine cause marked gastroprotective effects accompanied by the increase and maintenance of gastric mucus and GSH levels, as well as a reduction in gastric acid secretion through the gastrinergic pathway.

β-d-Glucan, a polysaccharide isolated from an edible mushroom Pleurotus pulmonarius (Fr.) Quel., presented antinociceptive activity in mice. This study evaluated the involvement of transient receptor potential (TRP) channels and protein kinase C (PKC) on antinociceptive effect of a (1→3),(1→6)-linked β-d-glucan (GL) in mice. Intraperitoneal administration of GL potently inhibited nociceptive responses induced by intraplantar injections of capsaicin, cinnamaldehyde, menthol, acidified saline and phorbol myristate acetate (PMA). Moreover, Western blot analysis revealed that GL treatment also prevented PMA-induced PKCɛ activation. Collectively, present results demonstrate that GL could constitute an attractive molecule of interest for the development of new analgesic drugs.

In this study, we determined the anti-inflammatory effect of manual acupuncture at the Sanyinjiao or Spleen 6 (SP6) point on carrageenan-induced peritonitis in mice and investigated mechanisms that may underlie this effect. In the first set of experiments, male Swiss mice were allocated into five groups: the control (sterile saline), dexamethasone (DEXA), invasive sham-acupuncture (non-acupoint), SP6 acupuncture and carrageenan-treated groups. Ten minutes after needle retention or 30 min after DEXA treatment, mice received an intraperitoneal injection of carrageenan (750 μg/mouse). After 4 h, total leukocyte and differential cell counts (neutrophils and mononuclear), myeloperoxidase (MPO) activity, vascular permeability and cytokine levels were evaluated. In another set of experiments, adrenalectomized (ADX) mice were used to study the involvement of the adrenal gland on the therapeutic effects of acupuncture. Mice were allocated into two groups: the ADX and sham-operated animals (Sham ADX) that were subdivided into four subgroups each: the control (sterile saline), DEXA, SP6 acupuncture and carrageenan-treated groups. The SP6 and DEXA treatments inhibited the inflammatory cell infiltration, vascular permeability and MPO activity in carrageenan-injected mice. In addition, the SP6 treatment also increased interleukin (IL)-10 levels. In contrast, when the animals were adrenalectomized, the SP6 treatment failed to reduce total leukocyte and the plasma extravasation. In conclusion, this study clearly demonstrates the anti-inflammatory effect of SP6 acupuncture in a model of carrageenan-induced peritonitis. Our results demonstrated that SP6 acupuncture depends of the adrenal glands and increased IL-10 levels to produce its anti-inflammatory action.

A type I arabinogalactan (CPP) was isolated from the viscous gum exuded by Cereus peruvinus (Cactaceae). It contained arabinose, galactose, galacturonic acid, and rhamnose in a 15:66:6:13 molar ratio and had Mw 9 × 105 g mol−1. Methylation analysis and 13C NMR spectroscopy indicated that CPP is composed of a (1 → 4)-linked β- d -Galp main-chain with substituents of α- l -Araf at O-2, O-3 and O-6, which are in turn substituted at O-2, O-3, and O-2,3. These are probably linked to O-4 of some rhamnosyl units of a type I rhamnogalacturonan (RG1). The main chain is formed by repeating (1 → 4)-α- d -GalpA-(1 → 2)-α- l -Rhap groups. The methylation analysis suggested the presence of (1 → 3)-linked β-Galp structures, perhaps linked to the (1 → 4)-linked β- d -Galp backbone. CPP significantly inhibited ethanol-induced gastric lesions in rats at an ED50 of 49 mg kg−1, indicating that it has a gastroprotective effect. The gastric lesion inhibition by CPP suggests a potential use of this polysaccharide, or the crude plant extract, in phytotherapy.

A rhamnogalacturonan (RGal) isolated from Acmella oleracea (L.) R.K. Jansen administered by oral route showed gastroprotective activity against acute lesions induced by ethanol. In this study, we investigated the gastric ulcer healing effect of RGal and its mechanisms of action. Intraperitoneal treatment of animals with RGal protected the gastric mucosa against acute lesions induced by ethanol, with participation of gastric mucus. Furthermore, in the chronic ulcer model, oral administration of RGal accelerates the gastric ulcer healing, accompanied by increasing of cellular proliferation and gastric mucus content, reducing inflammatory parameters and oxidative stress. In addition, the repeated 7 days-treatment of animals with RGal did not show alterations of clinical and behavioral symptoms, body and organs weights or plasmatic biochemical parameters. Collectively, these results showed that RGal has an interesting antiulcerogenic activity and could constitute an attractive molecule of interest for the development of new antiulcer agents.

A structural characterization of polysaccharides obtained by aqueous extraction of ripe pulp of the edible exotic tropical fruit named tamarillo (Solanum betaceum) was carried out. After fractionation by freeze–thaw and α-amylase treatments, a fraction containing a mixture of highly-methoxylated homogalacturonan and of arabinogalactan was obtained. A degree of methylesterification (DE) of 71% and a degree of acetylation (DA) of 1.3% was determined by 1H NMR spectroscopy and spectrophotometric quantification, respectively. A type I arabinogalactan was purified via Fehling precipitation and ultrafiltration through 50 kDa (cut-off) membrane. Its chemical structure was performed by sugar composition, HPSEC, methylation, carboxy-reduction and 13C NMR spectroscopy analysis. Intraperitoneal administration of the arabinogalactan did not reduce the nociception induced by intraplantar injection of 2.5% formalin in mice, but significantly reduced the number of abdominal constrictions induced by 0.6% acetic acid, indicating that fraction has an antinociceptive effect on the visceral inflammatory pain model.

Depression is a common comorbid in diabetic patients. The pathophysiologic mechanisms that relate this comorbidity is not completely elucidated yet, although several lines of evidence point out that increased oxidative stress resulting from hyperglycemia may have a crucial role. Thus, the effect of prolonged treatment with insulin (INS), the antioxidant vitamin E (VIT E) or the antidepressant imipramine (IMI) was evaluated in animals submitted to forced swimming test. Oxidative stress parameters (lipid peroxidation product levels, reduced gluthatione levels and catalase and superoxide dismutase activities) were also evaluated in brain areas related to depression, prefrontal cortex (PFC) and hippocampus (HIP). Our data show that treatment of streptozotocin-induced diabetic (DBT) rats with INS (6 UI/day, s.c.) prevented the blood glucose increase, reduced the immobility time, an antidepressant-like behavior, and normalized the reduced weight gain. Although the VIT E treatment (300 mg/kg, p.o.) had not altered the blood glucose levels, this treatment was able to reduce the immobility time and to reestablish the reduced weight gain in DBT rats. Differently, treatment with IMI (15 mg/kg, i.p.) induced antidepressant-like behavior in normoglycemic besides DBT animals. While VIT E and IMI treatments restored only specific oxidative stress parameters, INS was able to prevent all changed parameters evaluated in both PFC and HIP from DBT animals. Therefore, our data provide further evidence of the importance of oxidative stress in PFC and HIP in the pathophysiology of depression related to diabetes.

Beyond the current hypothesis of depression, several new biological substrates have been proposed for this disorder. The present study investigated whether the anti-inflammatory drugs celecoxib and piroxicam have antidepressant activity in animal models of depression. After acute administration, we observed antidepressant-like effects of celecoxib (10 mg/kg) and piroxicam (10 mg/kg) in the modified forced swim test in rats. Piroxicam increased serotonin and norepinephrine levels in the hippocampus. Prolonged (21-day) treatment with celecoxib (10 mg/kg) and piroxicam (10 mg/kg) rescued sucrose preference in a chronic mild stress model of depression. Additionally, the chronic mild stress-induced reduction of hippocampal glutathione was prevented by treatment with celecoxib and piroxicam. Superoxide dismutase in the hippocampus was increased after chronic mild stress compared with the non-stressed saline group. The non-stressed celecoxib and piroxicam groups and stressed piroxicam group exhibited an increase in hippocampal superoxide dismutase activity compared with the stressed saline group. Lipid hydroperoxide was increased in the stressed group treated with vehicle and non-stressed group treated with imipramine but not in the stressed groups treated with celecoxib and piroxicam. These results suggest that the antidepressant-like effects of anti-inflammatory drugs might be attributable to enhanced antioxidant defenses and attenuated oxidative stress in the hippocampus.

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) 226,000 g/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 1.5 mg/kg, indicating that SC acts as gastroprotective agent.

Tabebuia avellanedae (syn. Handroanthus impetiginosus) is popularly known as 'ipe-roxo' and has been used in folk medicine as anti-inflammatory and in the treatment of ulcers, bacterial and fungal infections. This study evaluated the gastric ulcer healing property of the ethanolic extract (EET) of barks from Tabebuia avellanedae and investigated the mechanisms that may underlie this effect. Rats were treated with EET (twice a day for 7 days) after induction of chronic gastric ulcers by 80% acetic acid. Following treatment, histological and immunohistochemical analysis were performed in gastric ulcer tissues. Oral administration of EET (100 and 300 mg/kg) significantly reduced the gastric lesion induced by acetic acid in 44 and 36%, respectively. Histopathological evaluation demonstrated a contraction of gastric ulcer size, increase of mucus layer (periodic acid-Schiff stained mucin-like glycoproteins) and cell proliferation (proliferating cell nuclear antigen immunohistochemistry) in animals treated with EET (100 and 300 mg/kg). The results demonstrate that EET significantly accelerates healing of acetic acid induced gastric ulcer in rats through increase of mucus content and cell proliferation, indicating a potential usefulness for treatment of peptic ulcer diseases.

Achillea millefolium L. is a member of the Asteraceae family that is commonly referred to as “yarrow” and has been used in folk medicine against several disturbances including skin inflammations, spasmodic and gastrointestinal disorders, as well as hepato-biliary complaints. Aim of the study In the present study, we evaluated the efficacy of a hydroalcoholic extract from the Achillea millefolium (HE) for gastroprotective properties and additional mechanism(s) involved in this activity. Material and methods Rats were treated with HE and subsequently exposed to both acute gastric lesions induced by ethanol P.A. and chronic gastric ulcers induced by 80% acetic acid. Following treatment, glutathione (GSH) levels and superoxide dismutase (SOD) activity were measured. The activity of myeloperoxidase (MPO) and histological and immunohistochemical analysis were performed in animals with acetic acid-induced gastric ulcers. Results Oral administration of HE (30, 100 and 300 mg/kg) inhibited ethanol-induced gastric lesions by 35, 56 and 81%, respectively. Oral treatment with HE (1 and 10 mg/kg) reduced the chronic gastric ulcers induced by acetic acid by 43 and 65%, respectively, and promoted significant regeneration of the gastric mucosa after ulcer induction denoting increased cell proliferation, which was confirmed by PCNA immunohistochemistry. HE treatment prevented the reduction of GSH levels and SOD activity after acetic acid-induced gastric lesions. In addition, HE (10 mg/kg) inhibited the MPO activity in acetic acid-induced gastric ulcers. Conclusions The results of the present study indicate that the antioxidant properties of HE may contribute to the gastroprotective activity of this extract.

This study evaluates the antipyretic activity of nimesulide, a cyclooxygenase (COX-2) selective inhibitor in rats. The effects of nimesulide on lipopolysaccharide (LPS)-induced cerebrospinal prostaglandin E(2) (PGE(2)) and prostaglandin F(2alpha) (PGF(2alpha)) and on plasma tumor necrosis factor-alpha (TNF-alpha) levels were also evaluated. Male Wistar rats received an i.p. injection of LPS, or i.c.v. injections of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), TNF-alpha, macrophage inflammatory protein-1alpha (MIP-1alpha), arachidonic acid, PGE(2), PGF(2alpha), corticotrophin-releasing factor (CRF) or endothelin-1 (ET-1). Nimesulide or indomethacin administered i.p 30 min prior LPS, IL-1beta, IL-6, TNF-alpha or arachidonic acid reduced the febrile response and PGE(2) or PGF(2alpha) levels in LPS-febrile rats but did not modify PGE(2)-induced fever. Nimesulide, but not indomethacin, reduced the fever induced by MIP-1alpha, PGF(2alpha), CRF or ET-1. Plasma TNF-alpha levels in LPS-treated rats were also reduced by nimesulide. These findings confirm that the antipyretic effect of nimesulide differs from the antipyretic scenario with the non-selective cyclooxygenase blocker indomethacin. Additional mechanisms, including inhibition of increased plasma TNF-alpha, may contribute to its antipyretic activity in rats.

Tamarillo ( Solanum betaceum ) is a tropical exotic fruit whose polysaccharides were extracted from the ripe pulp. After various purification steps, homogeneous fractions (designated PTW, STK-1000R and PF) were analyzed by sugar composition, HPSEC, methylation and NMR spectroscopy analysis. The results showed that the fraction PTW consisted of a linear arabinan with (1 → 5)-linked α- l -arabinofuranosyl units. Fractions designated as STK-1000R and PF contained galactoarabinoglucuronoxylans, with (1 → 4)-linked β- d -Xyl p residues in the backbone, carrying branches exclusively at O -2. The polysaccharide in STK-1000R is less branched than that in the PF fraction (∼20.0% and 36.5%, respectively), with side-chains formed by (1 → 5)-linked α- l -Ara f residues and (1 → 4)-linked α- d -Glc p A residues and with non-reducing end units formed by α- l -Ara f , β-Ara p , β- d -Gal p , α- d -GlcpA and 4- O -Me-α- d -Glc p A. Intraperitoneal administration of the STK-1000R fraction in mice significantly reduced the number of abdominal constrictions induced by 0.6% acetic acid and the inflammatory phase of nociception induced by 2.5% formalin, indicating that that fraction has an antinociceptive effect on inflammatory pain models.