Ana Cristina dos Santos

Ethanolic extract of roots from Arctium lappa L. accelerates the healing of acetic acid-induced gastric ulcer in rats: Involvement of the antioxidant system

We evaluate the curative efficacy of the ethanolic extract (EET) of roots from Arctium lappa (bardana) in healing of chronic gastric ulcers induced by 80% acetic acid in rats and additionally studies the possible mechanisms underlying this action. Oral administration of EET (1, 3, 10 and 30mg/kg) reduced the gastric lesion area in 29.2%, 41.4%, 59.3% and 38.5%, respectively, and at 10mg/kg promoted significant regeneration of the gastric mucosa, which was confirmed by proliferating cell nuclear antigen immunohistochemistry. EET (10mg/kg) treatment did not increase the gastric mucus content but restored the superoxide dismutase activity, prevented the reduction of glutathione levels, reduced lipid hydroperoxides levels, inhibited the myeloperoxidase activity and reduced the microvascular permeability. In addition, EET reduced the free radical generation and increased scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals in vitro. Furthermore, intraduodenal EET (10 and 30mg/kg) decreased volume and acidity of gastric secretion. Total phenolic compounds were high in EET (Folin-Ciocalteau assay) and the analysis by liquid chromatography-mass spectrometry revealed that the main compounds present in EET were a serie of hydroxycinnamoylquinic acid isomers. In conclusion, these data reveal that EET promotes regeneration of damaged gastric mucosa, probably through its antisecretory and antioxidative mechanisms.

Gastroprotective constituents of Salvia officinalis L.

The gastrointestinal activity of hydroalcoholic extract (HE) of Salvia officinalis was evaluated in a model of ethanol-induced gastric lesion. HE showed excellent activity, with ID(50) 84.0 (54.8-128.9) mg/kg. The acetic acid-induced ulcer and the total acidity of the gastric secretion were also reduced by HE, and, in vitro experiments, the H(+),K(+)-ATPase activity was inhibited. Carnosol was identified as a possible active constituent for the gastroprotective effect of HE.

Gastroprotective activity of the chloroform extract of the roots from Arctium lappa L.

Arctium lappa L. is used in folk medicine as a diuretic, depurative and digestive stimulant and in dermatological conditions. The objective of this study was to evaluate the effect and the possible mechanisms involved in the gastroprotective effects of a chloroform extract (CE) of the roots from A. lappa and its fractions. Oral pretreatment with CE (10, 30 and 100 mgkg−1) significantly reduced gastric lesions induced by ethanol by 61%, 70% and 76%, respectively. Oral administration of CE (100 mgkg−1 per day for 7 days) reduced the chronic gastric ulceration induced by acetic acid by 52%. Intraduodenal CE (100, 300 and 600 mgkg−1) reduced the total acidity of gastric secretion by 22%, 22% and 33%, respectively, while i.p. administration (10, 30 and 100 mgkg−1) inhibited total acidity by 50%, 60% and 67%, respectively. In‐vitro, CE inhibited H+, K+‐ATPase activity with an EC50 of 53 μgmL−1 and fraction A (30 and 100 μgmL−1) reduced this by 48% and 89%, respectively. CE had no effect on gastrointestinal motility. CE (250 μgmL−1) and fraction B (100 and 250 μgmL−1) had free‐radical scavenging ability, inhibiting 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical activity by 50%, 20% and 55%, respectively. Collectively, the results show that the CE protects animals from gastric lesions by reducing gastric acid secretion via inhibition of gastric H+, K+‐ATPase.

Antiulcerogenic activity of bark extract of Tabebuia avellanedae, Lorentz ex Griseb

Tabebuia avellanedae is commonly used for the treatment of peptic ulcers. We carried out this study with the ethanolic extract of bark from Tabebuia avellanedae (EET) (30-1000 mg/kg) to determine its gastroprotective activity and to clarify the pathways involved in this effect. Acute gastric ulceration in rats was produced by oral administration of ethanol and ibuprofen. After ethanol administration, the gastric wall mucus was examined. Chronic gastric ulceration was produced by injection of acetic acid in rat gastric subserosa. Anti-secretory studies were undertaken using Shay rat pylorus ligature technique and measurement of enzymatic activity of H+, K+-ATPase in vitro. Administration of EET p.o. or i.p. significantly inhibited gastric mucosa damage induced by ethanol and ibuprofen. The anti-ulcer effect was further confirmed by enhanced gastric mucus production. In pylorus ligature rats, EET significantly reduced the basal gastric acid secretion and total acidity; moreover, it inhibited the increase in total acidity induced by histamine. In addition, EET reduced the activity of H+, K+, ATPase. The results obtained in the present pharmacological assay indicate that this plant has a protective action against gastric lesions, involving the maintenance of protective factors, such as mucus and prostaglandin, besides the reduction of gastric total acidity.

Muscarinic-dependent inhibition of gastric emptying and intestinal motility by fractions of Maytenus ilicifolia Mart ex. Reissek

ETHNOPHARMACOLOGICAL RELEVANCE Maytenus ilicifolia Mart. ex. Reissek (Celastraceae) is widely used in Brazilian folk medicine to treat gastric disturbances. AIM OF THE STUDY This work intended to characterize the effects of Maytenus ilicifolia on gastrointestinal motility. MATERIALS AND METHODS Gastric emptying and intestinal transit were measured in the same animal. Mice received a semisolid marked with phenol red, half an hour after treatment with extracts. The amount of marker in the stomach and the distance reached in the intestine after 15 min were measured as index of gastrointestinal emptying and intestinal transit, respectively. RESULTS Intraperitoneal administration of a flavonoid-rich extract potently reduced the gastric emptying (ED(50)=89 mg/kg) and the intestinal transit (ED(50)=31 mg/kg) of mice. Bio-guided purification of the flavonoid-rich extract by chemical partition with solvents of decreasing polarity yielded fraction insF with about 12-14 times higher activity than the initial flavonoid extract in both the gastric emptying and the intestinal transit. The inhibitory effects of the insF (9.7 mg/kg, i.p.) on gastric emptying and intestinal transit were reversed by co-administration of bethanechol (10 mg/kg, s.c.) but not by co-administration of metoclopramide (30 mg/kg, p.o.) indicating muscarinic but not dopaminergic interaction of the compounds of Maytenus. Chemical investigation of the insF fraction by HPLC-MS allowed the identification of 4 free flavonoids (catechin, epicatechin, quercetin and kaempferol), 29 flavonol glycosides and 8 tannins. The flavonol glycosides ranged from 1 to 4 monosaccharide units, having mainly quercetin and kaempferol as aglycone moieties, and the tannins were composed by catechin/epicatechin and/or afzelechin/epiafzelechin. CONCLUSIONS Overall, the results indicate that the components of Maytenus ilicifolia have a potential use in the treatment of gastrointestinal motility disturbances such as diarrhea.

Antinociceptive properties of the hydroalcoholic extract, fractions and compounds obtained from the aerial parts of Baccharis illinita DC in mice.

The present study assessed the possible antinociceptive action of the hydroalcoholic extract, fractions and pure compounds obtained from the aerial parts of Baccharis illinita DC (Asteraceae) in behavioural models of chemical nociception in mice. The hydroalcoholic extract and fractions (hexane and aqueous but not EtOAc fraction) obtained from B. illinita (30-1000 mg/kg orally) produced a dose-related inhibition of the acetic acid-induced nociceptive response. However, the hexane fraction was more potent than the hydroalcoholic extract and the aqueous fraction. The hexane fraction derivatives baurenol, alpha-spinasterol and oleanolic acid (0.00001-10 mg/kg intraperitoneally) also caused potent inhibition of acetic acid-induced pain. The hexane fraction (300-1000 mg/kg orally) produced inhibition of both phases of formalin-induced pain. Moreover, the hexane fraction (30-600 mg/kg orally) also caused a dose-dependent inhibition of glutamate-induced pain. Nevertheless, the hexane fraction only at the dose of 300 mg/kg orally, produced partial inhibition of the paw oedema caused by carrageenan. Furthermore, the hexane fraction (300 mg/kg orally) caused inhibition of the nociceptive response induced by intrathecal injection of N-methyl-d-aspartic acid, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, tumour necrosis factor-alpha and interleukin-1beta. In contrast, the hexane fraction did not affect the biting response induced by the metabotropic or ionotropic glutamatergic receptor agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid and kainate, respectively. In addition, the antinociception caused by the hexane fraction (300 mg/kg orally) in the acetic acid test was not affected by intraperitoneal treatment of mice with naloxone (a non-selective opioid receptor antagonist). The precise mechanism responsible for the antinociceptive effect of the hexane fraction remains unclear, but appears to be partly associated with an inhibition of glutamatergic transmission and an inhibition of pathways dependent on pro-inflammatory cytokines. Finally, baurenol, alpha-spinasterol and oleanolic acid have an important role in the antinociceptive effects of the hexane fraction. Moreover, the antinociceptive action demonstrated in the present study supports the ethnomedical uses of this plant.

Subcapsular liver hematoma as a complication of an atypical hemolytic uremic syndrome.

Atypical hemolytic uremic syndrome (aHUS) is a rare, lifethreatening systemic inflammatory disease that presents classically with microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury.1 Extra renal manifestations are observed in 20% of patients.2 A 42-year-old woman with unremarkable past medical history presented in our hospital reporting a 6-day history of headache, nausea and vomiting. Physical examination showed hypertension (220/120 mmHg), cutaneous pallor and moderate lower limbs edema. Laboratory results revealed anemia (hemoglobin 8.4 g/dl), thrombocytopenia (76,000/ l), severe azotemia (urea 16.9 mmol/l, creatinine 448.8 mol/l), schistocytosis, a negative Coombs test, low blood haptoglobin (<0.07 g/L) and high lactate dehydrogenase levels (1234 U/l). Renal ultrasonography was normal. Blood pressure was hardly controlled with oral medication. A diagnosis of acute thrombotic microangiopathy (ATM) was made and daily plasma exchange (PEX) was started. Investigations for secondary causes of ATM (pregnancy, auto-immune disease, malignancy, drug-induced), infectioninduced HUS and thrombotic thrombocytopenic purpura were normal. A presumptive diagnosis of aHUS was made and the administrative process of Eculizumab acquisition was initiated. On the 15th day of admission (D15), hemodialysis was started due to progressive renal failure. All attempts to stop PEX resulted in increased hemolytic activity, forcing to maintain 3 sessions a week. On the D72, after performing 44 PEX sessions, we were still waiting for Eculizumab acquisition. Attending to clinical and analytical stability (Fig. 1), the patient was discharged home to continue hemodialysis and PEX three times a week as an outpatient. Four days after discharge, she was admitted in the emergency room with a 12-hour history of severe right upper quadrant pain and vomiting without history of trauma. Laboratory results revealed stabilized hemoglobin (11.1 g/dl) and both normal platelet count (157,000/mm3) and coagulation tests. Abdominal ultrasonography and Computed Tomography scan showed a large subcapsular liver hematoma (SLH) (Fig. 2). She was transferred to the Intensive Care Unit (ICU). Attending to hemodynamic stability, a conservative approach was attempted. PEX was suspended to prevent increased