Crude extract and fractions from Eugenia uniflora Linn leaves showed anti-inflammatory, antioxidant, and antibacterial activities.

BACKGROUND: This study showed phytochemical composition and evaluates the anti-inflammatory, and analgesic activities of crude extract (CE) and fractions from E. uniflora Linn leaves. METHODS: Polyphenols present in crude extract (CE), in aqueous fraction (AqF), and ethyl acetate (EAF) treated fractions from E. uniflora Linn leaves were shown by chromatographic analysis in order to conduct a phytochemical characterization. Antibacterial activity was evaluated based on minimum inhibitory concentrations (MICs) determined using the agar dilution method. Doses of 50, 100, and 200 mg/kg of the CE and fractions were applied for conducting in vivo models (male Swiss mice, 8-10 weeks old). The peritonitis experimental model was induced by carrageenan following of Myeloperoxidase activity (MPO), Total glutathione and malondialdehyde (MDA), IL-1ß and TNF-α levels by spectroscopic UV/VIS analysis. Antinociceptive activity was evaluated based on an abdominal writhing model and hot plate test. The results were statistically evaluated using one-way analysis of variance (ANOVA), followed by Bonferroni's post-hoc test. The level of statistical significance was p < 0.05. RESULTS: High-performance liquid chromatography with photodiode array detection (HPLC-DAD) detected varying concentrations of gallic acid, ellagic acid, and myricitrin in the CE and fractions obtained from E. uniflora Linn leaves (0.05-0.87%w/w, 0.20-0.32%w/w, and 1.71-6.56%w/w, respectively). In general, the CE had lower MIC values than the fractions, including the lowest MIC against the MRSA strain. The CE and AqF also significantly reduced leukocyte migration and MPO activity (p < 0.05). In addition, AqF significantly reduced IL-1ß and TNF-α levels (p < 0.05). Furthermore, the CE and fractions exhibited an antioxidant effect (p < 0.05) and peripheral analgesic activity (p < 0.05). CONCLUSIONS: The CE and fractions from the studied E. uniflora Linn leaves exhibited antibacterial, anti-inflammatory, antioxidant, and analgesic activity in the performed assays.

Quality of Life, Family Support, and Comorbidities in Institutionalized Elders With and Without Symptoms of Depression.

The institutionalization of elders can decrease the health status and quality of life in this population. The aim of this study was to analyze the socio-demographic, quality of life, family support, and comorbidities variables in institutionalized elders with and without symptoms of depression. This was a cross-sectional study in institutions for long permanence for the elderly in the State of Rio Grande do Norte, Brazil. Two institutionalized elderly groups were compared (138 elders: 69 with and 69 without depressive symptoms). The instruments used were: mini-mental state examination, geriatric depression scale in the reduced version, socio-demographic questionnaire, quality of life (World Health Organization Quality of Life abbreviated-WHOQOL-bref), and inventory of perception of family support. Elders with depressive symptoms had inferior quality of life than those without depressive symptoms. Other factors that negatively influenced the quality of life in this population include: low economic conditions, occurrence of comorbidities, and deficient family assistance. These results have important implications in the decision making process with regard to strategies for improving the health status of institutionalized elders.

Quality of life in patients with schizophrenia: the impact of socio-economic factors and adverse effects of atypical antipsychotics drugs.

This cross-sectional study compared the effects of treatment with atypical antipsychotic drugs on quality of life (QoL) and side effects in 218 patients with schizophrenia attending the ambulatory services of psychiatric in Rio Grande do Norte, Brazil. Socio-economic variables were compared. The five-dimension EuroQoL (EQ-5D) was used to evaluate QoL, and side effects were assessed using the Udvalg for Kliniske Undersøgelser (UKU) Side Effect Rating Scale and the Simpson-Angus Scale. Data were analysed using the χ (2) test and Student's t test, with a significance level of 5 %. Average monthly household incomes in the medication groups were 1.1-2.1 minimum wages ($339-$678). UKU Scale scores showed significant differences in side effects, mainly, clozapine, quetiapine and ziprasidone (p < 0.05). EQ-5D scores showed that all drugs except olanzapine significantly impacted mobility (p < 0.05), and proportions of individuals reporting problems in other dimensions were high: 63.6 % of clozapine users reported mobility problems, 63.7 and 56.3 % of clozapine and ziprasidone users, respectively, had difficulties with usual activities, 68.8 and 54.5 % of ziprasidone and clozapine users, respectively, experienced pain and/or discomfort, and 72.8 % of clozapine users reported anxiety and/or depression. Psychiatric, neurological, and autonomous adverse effects, as well as other side effects, were prevalent in users of atypical antipsychotic drugs, especially clozapine and ziprasidone. Olanzapine had the least side effects. QoL was impacted by side effects and economic conditions in all groups. Thus, the effects of these antipsychotic agents appear to have been masked by aggravating social and economic situations.

Libidibia ferrea Fruit Crude Extract and Fractions Show Anti-Inflammatory, Antioxidant, and Antinociceptive Effect In Vivo and Increase Cell Viability In Vitro.

BACKGROUND: Libidibia ferrea (L. ferrea) is found throughout the northeastern region of Brazil, where it has been used in folk medicine with beneficial effects on many inflammatory disorders. PURPOSE: This study investigated the phytochemical composition of the crude extract and fractions of L. ferrea fruit and evaluated its anti-inflammatory and antinociceptive activities in vivo and effect on cell viability in vitro. METHODS: Characterization of polyphenols present in crude extract (CE), hydroalcoholic fractions of 20-80% ethanol (CE20, CE40, CE60, and CE80), aqueous fraction (AqF), and ethyl acetate (EAF) fractions of L. ferrea fruit was performed by chromatographic analysis. Anti-inflammatory activity was evaluated by using a carrageenan-induced peritonitis model submitted to a leukocyte migration assay and myeloperoxidase activity (MPO) analysis. Total glutathione and malondialdehyde (MDA) levels were assessed to evaluate the oxidative stress level. Antinociceptive activity was evaluated by acetic acid-induced abdominal writhing and hot plate test. In vitro cell viability was determined by using MTT assay in a mouse embryonic fibroblast cell line (3T3 cells). RESULTS: Chromatography revealed the presence of ellagic acid content in EAF (3.06), CE (2.96), and CE40 (2.89). Gallic acid was found in EAF (12.03), CE 20 (4.43), and CE (3.99). L. ferrea crude extract and all fractions significantly reduced leukocyte migration and MPO activity (p<0.001). L. ferrea antioxidant effect was observed through high levels of total glutathione and reduction of MDA levels (p<0.001). Acetic acid-induced nociception was significantly inhibited after administration of L. ferrea crude extract and all fractions (p<0.001). Crude extract and all fractions significantly increased the viability of the 3T3 cell line (p<0.05). CONCLUSIONS: The appropriate extraction procedure preserves the chemical components of L. ferrea fruit, such as gallic acid and ellargic acid. Crude extract and fractions of L. ferrea fruit exhibited anti-inflammatory, antioxidant, antinociceptive activities in vivo and enhanced cell viability in vitro.

Gliclazide Prevents 5-FU-Induced Oral Mucositis by Reducing Oxidative Stress, Inflammation, and P-Selectin Adhesion Molecules.

Oral mucositis (OM) is one of the main side effects of the head and neck cancer treatment, particularly radiotherapy and/or chemotherapy. OM is characterized by ulcers, erythema, dysphagia, xerostomia, and increased susceptibility to opportunistic infections. In the perspective of finding pharmacological therapies to prevent inflammation and ulceration of OM, the investigation of the pleiotropic effect of commercial drugs is needed, among them gliclazide, an antidiabetic drug. This study aimed to evaluate the effect of gliclazide in an experimental OM model induced by 5-fluorouracil. Male hamsters were pre-treated with oral gliclazide (1, 5, or 10 mg/kg) for 10 days. Cheek pouch samples were subjected to histopathological and immunohistochemical analysis (COX2, iNOS, MMP-2, NFκB P65, GPx) and imunofluorescence (P-selectin). IL-1ß and TNF-α levels, Myeloperoxidase activity (MPO) and malondialdehyde (MDA) levels were investigated by ultraviolet-visible spectroscopy analysis. NFκB NLS P50 protein levels were analyzed by western blotting. The group treated with gliclazide at a dose of 10 mg/kg showed presence of erythema, no evidence of erosion, and absence of mucosal ulceration with a score of 1 (1-2) (p < 0.01). Histopathological data for the group treated with gliclazide 10 mg/kg showed re-epithelialization, discrete mononuclear inflammatory infiltrate and absence of hemorrhage, edema, ulcers and abscesses with a score of 1 (1-1) (p < 0.01). Treatment with gliclazide 10 mg/kg reduced MPO activity (p < 0.001), MDA levels (p < 0.001) and NFκB NLS P50 (p < 0.05) protein levels, resulting in low immunostaining to Cox-2, iNOS (p < 0.05), NFκB P65 (p < 0.05), and negative immunoreaction to MMP-2 (p < 0.001). However, it appeared that for Gpx1, the staining was restored in the GLI 10-FUT group compared with 5FUT/saline (p < 0.05). Immunofluorescence revealed decreased levels of P-selectin (p < 0.001) after treatment with gliclazide 10 mg/kg (p < 0.05). In summary, gliclazide accelerated mucosal recovery and reduced oxidative stress and inflammation in the 5-FU-induced OM in hamsters.

Intestinal anti-inflammatory activity of xique-xique (Pilosocereus gounellei A. Weber ex K. Schum. Bly. Ex Rowl) juice on acetic acid-induced colitis in rats.

Inflammatory bowel disease (IBD) is characterized by severe mucosal damage in the intestine and a deregulated immune response. Natural products derived from plants that are rich in bioactive compounds are used by many patients with IBD. Xique-xique (Pilosocereus gounellei) is a cactus of the Caatinga family that has been used by the local population for food and medicinal purposes. The intestinal anti-inflammatory effect of xique-xique cladode juice was evaluated in the present study. A dose of 5 mL kg-1 had a protective effect on intestinal inflammation, with an improvement in macroscopic damage, and a decrease in pro-inflammatory markers and oxidative stress, in addition to preserving the colonic tissue. Immunohistochemical analysis revealed the downregulation of IL-17, NF-κB, and iNOS, and upregulation of SOCs-1, ZO-1, and MUC-2. These protective effects could be attributed to the phenolic compounds as well as the fibers present in xique-xique juice. Further studies are needed before suggesting the use of xique-xique juice as a new alternative for treating IBD.

Prognostic significance of the anatomical location and TNM clinical classification in oral squamous cell carcinoma.

OBJECTIVES: The aim of this study was to investigate the existence of correlation between the TNM clinical classification, anatomical location and prognosis of oral squamous cell carcinoma. STUDY DESIGN: A total of 130 oral squamous cell carcinomas were selected from the files of the Dr. Luiz Antonio Hospital (Natal, Rio Grande do Norte, Brazil). Data concerning TNM clinical classification, anatomical location and prognosis were obtained. Pearsons correlation test was applied for the statistical analysis of data. RESULTS: It revealed a statistically significant correlation (p = 0.01) between TNM clinical classification and prognosis. It also revealed correlation between TNM classification and the anatomical location of oral squamous cell carcinomas (p = 0.01). CONCLUSIONS: We concluded that TNM classification presented correlation with prognosis and with the different anatomical locations of oral squamous cell carcinomas.

Chitosan Membrane Modified With a New Zinc(II)-Vanillin Complex Improves Skin Wound Healing in Diabetic Rats.

The treatment of chronic wounds is considered a public health problem. When the condition affects at-risk groups such as those with diabetics, it becomes a great clinical challenge. In this work, we evaluated the healing effects of a new zinc complex, [Zn(phen)(van)2], identified as ZPV, which was synthesized, characterized and associated with chitosan (CS) membranes and tested on cutaneous wounds of diabetic rats. Chitosan membranes were modified by Schiff base reaction with the complex under two experimental conditions (14 and 21 days), resulting in membranes with concentrations of complex equal to 0.736 µmol cm-2 (CS-ZPV1) and 1.22 µmol cm-2 (CS-ZPV2). Release assays in aqueous medium indicated that the membranes release the complex gradually when exposed to an aqueous medium. Diabetes was inducted in Wistar rats using 40 mg/kg (i.v.) streptozotocin. On the 7th day after diabetic induction, a circular excision on the skin (1.0 cm) was performed with a punch. The lesions were treated with the pure chitosan membrane and the membrane associated with the zinc-vanillin complex in two different doses. Skin samples were subjected to macroscopic and histopathological analyses, cytokine (TNF-α, IL-1ß, and IL-10) quantification and reverse transcriptase polymerase chain reaction (TGF-ß and VEGF) assays. The analyses showed a decrease in wound size, reepithelialization, angiogenic stimulus, collagen deposition, and reduced levels of TNF-α and IL-1ß as well as increased IL-10 and gene expression of TGF-ß and VEGF. The evaluated parameters suggest that CS-ZPV in the two concentrations tested may be effective in the treatment of chronic wounds.

Anti-inflammatory, analgesic and anti-tumor properties of gold nanoparticles.

BACKGROUND: Gold nanoparticles (GNPs) are regarded as potential platforms for drug delivery. However, their interaction with live organisms must be understood prior to their utilization as drug carriers. The present study reports the anti-inflammatory, analgesic and anti-tumor effects of GNPs. The biodistribution of GNPs and their effect on various tissues have also been studied. METHODS: GNPs were synthesized through an environmentally friendly route and characterized with TEM and UV-vis. After HT-29 cells had been exposed to GNPs, apoptosis was assessed with Annexin V and propidium iodide staining and caspase-3 activity determined with a confocal laser scanning microscope. GNPs were administrated to male and female Swiss mice for posterior assessment of their anti-inflammatory and analgesic properties. The biodistribution of GNPs and their impact on tissues were studied with UV-vis and histopathological analysis, respectively. RESULTS: Cell apoptosis was observed in a dose-dependent manner for GNPs concentrations ranging from 40µg/mL to 80µg/mL (p<0.05). The best anti-inflammatory activity was observed at the dose of 1500µg/kg, which caused a reduction of 49.3% in leukocyte migration. GNPs showed peripheral analgesia at the dose of 1500µg/kg and have been found in liver, spleen, kidney and lungs. Histopathological examination revealed extravasation of red blood cells in lungs. CONCLUSION: The study draws attention to gold nanoparticles as a resource for technological innovation in the anti-inflammatory, analgesic and anti-tumor fields. GNPs have biological effects that deserve investigation to assess their full interaction with organic systems.

Spray-dried extract of Phyllanthus niruri†L. reduces mucosal damage in rats with intestinal inflammation.

Phyllanthus niruri L. belongs to the Euphorbiaceae, and is known by the common name of 'stonebreaker' in Brazil. Some species within the Phyllanthus genus are widely used in traditional medicine to counteract different types of anti-inflammatory diseases. OBJECTIVES: In this study, the preventive intestinal anti-inflammatory activity of spray-dried extract of P. niruri (SDEPn) was tested in the model of acetic acid (10%)-induced ulcerative colitis in the rat. METHODS: Colitis animals were given orally at doses 25, 100 and 200 mg/kg. Colons tissue was analysed by macroscopic score, by histopathology score, by the immunohistochemical examination of tumour necrosis factor alpha, p53 and interferon gamma; by spectroscopic ultraviolet-visible spectrophotometry (UV/VIS) analysis of the levels of myeloperoxidase, malonaldehyde and total glutathione. KEY FINDINGS/RESULT: Pretreatment of the extract to colitic rats significantly attenuated colonic macroscopic damage induced by acetic acid (P < 0.01). Spray-dried extract of P. niruri prevented glutathione depletion (P < 0.001) and malondialdehyde levels (P < 0.05) declined. Spray-dried extract of P. niruri significantly reduced microscopic damage to tissues, such as leukocyte infiltration accompanied by a significant reduction in myeloperoxidase activity (P < 0.5). Immunohistochemistry revealed a decline in the TNF-α, IFN-γ and p53 protein (P < 0.05). CONCLUSION: Spray-dried extract of P. niruri has a beneficial effect in the acute phase of acetic acid-induced colitis in the rat, which is probably related to its antioxidant properties.

Olmesartan decreased levels of IL-1ß and TNF-α, down-regulated MMP-2, MMP-9, COX-2, RANK/RANKL and up-regulated SOCs-1 in an intestinal mucositis model.

Methotrexate (MTX) is a pro-oxidant compound that depletes dihydrofolate pools and is widely used in the treatment of leukaemia and other malignancies. The efficacy of methotrexate is often limited by mucositis and intestinal injury, which are major causes of morbidity in children and adults. The aim of this study was to evaluate the effect of olmesartan (OLM), an angiotensin II receptor antagonist, on an Intestinal Mucositis Model (IMM) induced by MTX in Wistar rats. IMM was induced via intraperitoneal (i.p.) administration of MTX (7 mg/kg) for three consecutive days. The animals were pre-treated with oral OLM at 0.5, 1 or 5 mg/kg or with vehicle 30 min prior to exposure to MTX. Small intestinal homogenates were assayed for levels of the IL-1ß, IL-10 and TNF-α cytokines, malondialdehyde and myeloperoxidase activity. Additionally, immunohistochemical analyses of MMP-2, MMP-9, COX-2, RANK/RANKL and SOCS-1 and confocal microscopy analysis of SOCS-1 expression were performed. Treatment with MTX + OLM (5 mg/kg) resulted in a reduction of mucosal inflammatory infiltration, ulcerations, vasodilatation and haemorrhagic areas (p<0.05) as well as reduced concentrations of MPO (p<0.001) and the pro-inflammatory cytokines IL-1ß (p<0.001) and TNF-a (p<0.01), and increase anti-inflammatory cytocine IL-10 (p<0.05). Additionally, the combined treatment reduced expression of MMP-2, MMP-9, COX-2, RANK and RANKL(p<0.05) and increased cytoplasmic expression of SOCS-1 (p<0.05). Our findings confirm the involvement of OLM in reducing the inflammatory response through increased immunosuppressive signalling in an IMM. We also suggest that the beneficial effect of olmesartan treatment is specifically exerted during the damage through blocking inflammatory cytocines.

Quantification of polyphenols and evaluation of antimicrobial, analgesic and anti-inflammatory activities of aqueous and acetone-water extracts of Libidibia ferrea, Parapiptadenia rigida and Psidium guajava.

ETHNOPHARMACOLOGICAL RELEVANCE: Vast numbers of plant species from northeastern Brazil have not yet been phytochemically or biologically evaluated. AIM OF THE STUDY: The goal of this work was to obtain, characterize and show the antimicrobial, analgesic and anti-inflammatory activities of aqueous and acetone-water extracts of Libidibia ferrea, Parapiptadenia rigida and Psidium guajava. MATERIALS AND METHODS: The plant material (100g) was dried, and the crude extracts were obtained by using turbo-extraction (10%; w/v) with water or acetone:water (7:3, v/v) as the extraction solvent. High-performance liquid chromatography (HPLC) methods were used to screen the crude extracts for hydrolysable tannins (gallic acid) and condensed tannins (catechins). The antibacterial activity was evaluated by agar-diffusion and microdilution methods against Gram-positive strains (Staphylococcus aureus ATCC 25923, Staphylococcus epidermidis INCQS 00016, Enterococcus faecalis ATCC 29212 and a clinical isolate of methicillin-resistant Staphylococcus aureus) as well as Gram-negative strains (Escherichia coli ATCC 25922, Salmonella enteritidis INCQS 00258, Shigella flexneri and Klebsiella pneumoniae). To evaluate the anti-inflammatory activity, a leukocyte migration model was used. Analgesic activity was determined by the hot plate test and the acetic acid-induced abdominal writhing test. Data were analyzed by analysis of variance (ANOVA) at a significance level of 5%. RESULTS: Parapiptadenia rigida presented the highest amount of total polyphenols (35.82 ± 0.20%), while the greatest catechin content was found in the acetone-water extract of Psidium guajava (EAWPg; 1.04 µg/g). The largest amounts of catechins were found in the aqueous extract of Libidibia ferrea (EALf; 1.07 µg/g) and the acetone-water extract of Parapiptadenia rigida (EAWPr; 1.0 µg/g). All extracts showed activity against Gram-positive bacteria. The aqueous and acetone-water extracts of Psidium guajava showed the greatest inhibition zones in the agar diffusion tests. In the evaluation of the minimum inhibitory concentration (MIC), the most susceptible Gram-positive bacterium was Staphylococcus epidermidis and the most susceptible Gram-negative bacterium was Shigella flexneri. EAPg and EAWPg showed the greatest MIC values. All extracts were significant inhibitors of leukocyte migration (p<0.05). Using the writhing test, significant analgesic activity was found for EAPr (50 mg/kg), EAWPr (100 mg/kg and 200 mg/kg) and EAWPg (50 mg/kg) (p<0.05). CONCLUSIONS: Thus, the appropriate extraction procedure preserves the chemical components such as gallic acid and catechin, and showed antimicrobial, anti-inflammatory and analgesic properties.