Croton antisyphiliticus Mart. attenuates the inflammatory response to carrageenan-induced pleurisy in mice.

The aim of this study was to investigate the anti-inflammatory effect of the crude hydroalcoholic extract (CHE) from the aerial parts of Croton antisyphiliticus, its fractions and isolated compounds derived from it on the mouse model of pleurisy induced by carrageenan. The aerial parts of C. antisyphiliticus were dried, macerated and extracted with ethanol to obtain the CHE, which was fractionated by liquid-liquid extraction using solvents with increasing polarity to obtain hexane (Hex), ethyl acetate (EA) and aqueous (Aq) fractions. Vitexin and quinic acid were isolated from Aq fraction. Capillary electrophoresis analysis, physical characteristics and spectral data produced by infrared (IR), nuclear magnetic resonance ((1)H and (13)C NMR) and mass spectrometry analyses were used to identify and elucidate the structure of the isolated compounds. The experimental model of pleurisy was induced in mice by a single intrapleural injection of carrageenan (1 %). Leukocytes, exudate concentrations, myeloperoxidase (MPO) and adenosine-deaminase (ADA) activities and nitrate/nitrite (NOx), tumor necrosis factor-α (TNF-α) and interleukin-17 (IL-17) levels were determined in the pleural fluid leakage at 4 h after pleurisy induction. Animals pre-treated with CHE, Hex, EA, Aq, vitexin and quinic acid exhibited decreases in leukocytes, exudate concentrations, MPO and ADA activities and NOx levels (p < 0.05). Also CHE, Hex, EA and vitexin but not quinic acid inhibited TNF-α and IL-17 levels (p < 0.05). C. antisyphiliticus caused anti-inflammatory effect by inhibiting the activated leukocytes, exudate concentrations, NOx, TNF-α, and IL-17 levels. The compounds vitexin and quinic acid may be responsible for this anti-inflammatory action.

NMDA receptors and the L-arginine-nitric oxide-cyclic guanosine monophosphate pathway are implicated in the antidepressant-like action of the ethanolic extract from Tabebuia avellanedae in mice.

Bark infusion of Tabebuia avellanedae Lorentz ex Griseb is consumed in tropical America folk medicine for the treatment of several diseases, including depressive disorders. It was recently demonstrated that the extract from this plant has antidepressant properties. The present study was aimed at investigating the contribution of N-methyl-D-aspartate (NMDA) receptors and the L-arginine-nitric oxide (NO)-cyclic guanosine 3'5'-monophosphate (cGMP) pathway to the antidepressant-like action of the ethanolic extract from T. avellanedae (EET) in the tail suspension test (TST). The anti-immobility effect of the extract (30 mg/kg, orally [p.o.]) was prevented by pretreatment of mice with NMDA (0.1 pmol/site, intracerebroventicular [i.c.v.]), L-arginine (750 mg/kg, intraperitoneally [i.p.]), and sildenafil (5 mg/kg, i.p.). Additionally, the combination of MK-801 (0.01 mg/kg, p.o.), 7-nitroindazole (25 mg/kg, i.p.), and 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ) (30 pmol/site, i.c.v.) with a subeffective dose of EET (1 mg/kg, p.o.) produced a synergistic antidepressant-like effect in the TST, without causing significant alterations in the locomotor activity. Moreover, the administration of an effective dose of EET (30 mg/kg, p.o.) produced a reduction in NOx levels in the cerebral cortex. Conversely, a subeffective dose of EET (1 mg/kg, p.o.) caused no changes in the cortical NOx levels. Results suggest that the antidepressant-like effect of EET in the TST is dependent on a blockade of NMDA receptor activation and inhibition of NO-cGMP synthesis, significantly extending literature data about the antidepressant-like action of this plant and reinforcing the notion that this plant may be useful in the management of depressive disorders.

Relationship of chemical structure and anti-inflammatory activity of dihydrocorynantheol and its analogues.

BACKGROUND: Dihydrocorynantheol (DHC) is an alkaloid compound isolated from Esenbeckia leiocarpa Engl. that has demonstrated anti-inflammatory properties in experimental models. The aim of this study was to investigate whether the modification of the chemical structure of DHC could alter its anti-inflammatory effect in a mouse model of pleurisy induced by carrageenan. METHODS: DHC was isolated from Esenbeckia leiocarpa Engl. Capillary electrophoresis, physical characteristics, spectral data produced by infrared analysis and nuclearmagnetic resonance ((1)H and (13)C), and mass spectrometry analysis were used to identify and elucidate DHC structure. The DHC compound was subjected to chemical structural modifications by nucleophilic substitution reactions, yielding five analogous compounds: acetyl (1), p-methylbenzoyl (2), benzoyl (3), p-methoxybenzoyl (4) and p-chlorobenzoyl (5). Swiss mice were used throughout the experiments. Pro-inflammatory parameters leukocyte migration, exudate concentrations and myeloperoxidase (MPO) activity were quantified in the fluid leakage from the mouse pleural cavities at 4 h after pleurisy induction. RESULTS: DHC and its analogues acetyl, p-methylbenzoyl, benzoyl, p-methoxybenzoyl and p-chlorobenzoyl inhibited total and differential leukocyte migration and MPO activity (p < 0.05). Only DHC significantly decreased the exudate concentrations (p < 0.01). CONCLUSIONS: DHC was more effective than its analogues as an anti-inflammatory agent in the mouse model of pleurisy induced by carrageenan. We did not determine what physicochemical modifications altered the anti-inflammatory effect of DHC, but this effect may be due to the modifications on the hydroxyl group at carbon 17 of the DHC.

Antiulcer effect of bark extract of Tabebuia avellanedae: activation of cell proliferation in gastric mucosa during the healing process.

Tabebuia avellanedae (syn. Handroanthus impetiginosus) is popularly known as 'ipê-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.

Antidepressant-like action of the bark ethanolic extract from Tabebuia avellanedae in the olfactory bulbectomized mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Tabebuia avellanedae Lorentz ex Griseb is a plant employed in tropical America folk medicine for the treatment of several diseases, including depressive disorders. AIM OF THE STUDY: To investigate the ability of Tabebuia avellanedae ethanolic extract (EET) administered chronically to cause an antidepressant-like effect in the tail suspension test (TST), a predictive test of antidepressant activity, and to reverse behavioral (hyperactivity, anhedonic-like behavior and increased immobility time in the TST) and biochemical changes induced by olfactory bulbectomy (OB), a model of depression, in mice. MATERIALS AND METHODS: Mice were submitted to OB to induce depressive-related behaviors, which were evaluated in the open-field test (hyperactivity), splash test (loss of motivational and self-care behavior indicative of an anhedonic-like behavior) and TST (increased immobility time). Phosphorylation levels of Akt, GSK-3ß, ERK1/2 and CREB, as well as BDNF immunocontent, were evaluated in the hippocampus of bulbectomized mice or sham-operated mice treated for 14 days by p.o. route with EET or vehicle. RESULTS: EET (10 and 30mg/kg) given 14 days by p.o route to mice reduced the immobility time in the TST without altering locomotor activity, an indicative of an antidepressant-like effect. EET per se increased both CREB (Ser(133)) and GSK-3ß (Ser(9)) phosphorylation (at doses of 10-30 and 30mg/kg, respectively) in sham-operated mice. OB caused hyperactivity, loss of motivational and self-care behavior, increased immobility time in the TST and an increase in CREB and ERK1 phosphorylation, as well as BDNF immunocontent. EET abolished all these OB-induced alterations except the increment of CREB phosphorylation. Akt (Ser(473)) and ERK2 phosphorylation levels were not altered in any group. CONCLUSIONS: EET ability to abolish the behavioral changes induced by OB was accompanied by modulation of ERK1 and BDNF signaling pathways, being a promising target of EET. Results indicate that this plant could constitute an attractive strategy for the management of depressive disorders, once more validating the traditional use of this plant.

Optimisation of a capillary zone electrophoresis methodology for simultaneous analysis of organic aliphatic acids in extracts of Brachiaria brizantha.

INTRODUCTION: Aluminum toxicity is commonly verified in acidic soils, and poses a severe limitation to plant growth and development. Therefore, Al complexation by the root system mucilage, Al complexation by organic compounds that are exuded by the roots and internal metabolic processes must be monitored by organic acids (OA), since they play a central role in these aluminum tolerance mechanisms. OBJECTIVE: To optimise a capillary zone electrophoresis method able to perform simultaneous separation of acetic, citric, formic, lactic, malic, oxalic, pyruvic, succinic, tartaric and aspartic acid in plant extract solutions. METHODOLOGY: Method optimisation was achieved by a chemometric approach through experimental designs. The optimal condition found was: 20 mmol/L phthalic acid buffer; 0.8 mmol/L cetyltrimethyl-ammonium bromide; pH 3.4 adjusted with tris(hydroxymethyl)aminomethane (around 16 mmol/L); -15 kV of voltage; 25 °C of cartridge temperature; indirect ultraviolet detection at 240 nm; and 25 mbar injection for 2 s, within an analysis time of 4 min. RESULTS: As a repeatability test of the optimal condition, 30 replicates were carried out with the same working electrolyte, where the relative standard deviation of each peak ranged from 0.081 to 0.36% (for migration time) and from 2.4 to 4.6% (for peak area). CONCLUSION: The methodology was successfully applied to simultaneously determine citric, malic and aspartic acid in roots and leaves extract solutions of Brachiaria brizantha, demonstrating its usefulness to study aluminum tolerance.

Esenbeckia leiocarpa Engl. inhibits inflammation in a carrageenan-induced murine model of pleurisy.

OBJECTIVES: The aim of this study was to investigate the anti-inflammatory effects of the crude hydroalcoholic extract (CHE) isolated from Esenbeckia leiocarpa Engl., and fractions and subfractions derived from it. METHODS: Dried E. leiocarpa Engl. bark was macerated and extracted with ethanol to obtain the CHE. The n-hexane, ethyl acetate, aqueous and alkaloid fractions, as well as two alkaloid subfractions (polar and nonpolar) were obtained from the CHE. A preliminary analysis using thin-layer chromatography was performed. Capillary electrophoresis, physical characteristics and spectral data produced by IR analysis and nuclear magnetic resonance (¹H and ¹³C NMR), and mass spectrometry analysis were used to identify and elucidate the structure of the major compounds. Swiss mice were used in a carrageenan-induced pleurisy model. Pro-inflammatory parameters (leukocyte and exudate concentrations, myeloperoxidase and adenosine-deaminase activity, and nitrate/nitrite, interleukin 1ß and tumour necrosis factor α levels) were quantified in exudates at 4 h after carrageenan-induced pleurisy in mice. KEY FINDINGS: The dihydrocorynantheol alkaloid was isolated as the majority compound in the CHE, ethyl acetate and alkaloid fractions, and in the polar and nonpolar alkaloid subfractions. The CHE, fractions and subfractions inhibited the increases in leukocyte and exudate concentrations, myeloperoxidase and adenosine-deaminase activity, and nitrite/nitrate, interleukin 1ß, and tumour necrosis factor α levels (P<0.05) in the fluid secreted from the pleural cavity of the carrageenan-treated mice. CONCLUSIONS: E. leiocarpa Engl. showed significant in vivo anti-inflammatory action by inhibiting the inflammation caused by carrageenan. This effect may be, in part, due to the dihydrocorynantheol alkaloid, which was identified as the majority compound isolated from E. leiocarpa bark.

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.

Biosensor for chlorogenic acid based on an ionic liquid containing iridium nanoparticles and polyphenol oxidase.

A biosensor based on the ionic liquid, 1-n-butyl-3-methylimidazolium hexafluorophosphate containing dispersed iridium nanoparticles (Ir-BMI.PF(6)) and polyphenol oxidase was constructed. This enzyme was obtained from the sugar apple (Annona squamosa), immobilized in chitosan ionically crosslinked with oxalate. The biosensor was used for determination of chlorogenic acid by square wave voltammetry. The polyphenol oxidase catalyzes the oxidation of chlorogenic acid to the corresponding o-quinone, which is electrochemically reduced back to this substance at +0.25V vs. Ag/AgCl. Under optimized operational conditions the chlorogenic acid concentration was linear in the range of 3.48x10(-6) to 4.95x10(-5)mol L(-1) with a detection limit of 9.15x10(-7)mol L(-1). The biosensor was applied in the determination of chlorogenic acid in organic and decaffeinated coffee and the results compared with those obtained using the capillary electrophoresis method. The recovery study for chlorogenic acid in these samples gave values of 93.2-105.7%.