Identification of the Active Principle Conferring Anti-Inflammatory and Antinociceptive Properties in Bamboo Plant.

Early plants began colonizing earth about 450 million years ago. During the process of coevolution, their metabolic cellular pathways produced a myriad of natural chemicals, many of which remain uncharacterized biologically. Popular preparations containing some of these molecules have been used medicinally for thousands of years. In Brazilian folk medicine, plant extracts from the bamboo plant Guadua paniculata Munro have been used for the treatment of infections and pain. However, the chemical basis of these therapeutic effects has not yet been identified. Here, we performed protein biochemistry and downstream pharmacological assays to determine the mechanisms underlying the anti-inflammatory and antinociceptive effects of an aqueous extract of the G. paniculata rhizome, which we termed AqGP. The anti-inflammatory and antinociceptive effects of AqGP were assessed in mice. We identified and purified a protein (AgGP), with an amino acid sequence similar to that of thaumatins (~20 kDa), capable of repressing inflammation through downregulation of neutrophil recruitment and of decreasing hyperalgesia in mice. In conclusion, we have identified the molecule and the molecular mechanism responsible for the anti-inflammatory and antinociceptive properties of a plant commonly used in Brazilian folk medicine.

In vitro and in vivo genotoxic evaluation of Bothrops moojeni snake venom.

CONTEXT: Bothrops moojeni Hoge (Viperidae) venom is a complex mixture of compounds with therapeutic potential that has been included in the research and development of new drugs. Along with the biological activity, the pharmaceutical applicability of this venom depends on its toxicological profile. OBJECTIVE: This study evaluates the cytotoxicity and genotoxicity of the Bothrops moojeni venom (BMV). MATERIAL AND METHODS: The in vitro cytotoxicity and genotoxicity of a pooled sample of BMV was assessed by the MTT and Comet assay, respectively. Genotoxicity was also evaluated in vivo through the micronucleus assay. RESULTS: BMV displayed a 50% cytotoxic concentration (CC50) on Vero cells of 4.09 µg/mL. Vero cells treated with 4 µg/mL for 90 min and 6 h presented significant (p < 0.05, ANOVA/Newman-Keuls test) higher DNA damage than the negative control in the Comet assay. The lower DNA damage found after 6 h compared with the 90 min treatment suggests a DNA repair effect. Mice intraperitoneally treated with BMV at 10, 30, or 80 µg/animal presented significant genotoxicity (p < 0.05, ANOVA/Newman-Keuls test) in relation to the negative control after 24 h of treatment. Contrary to the in vitro results, no DNA repair seemed to occur in vivo up to 96 h post-venom inoculation at a dose of 30 µg/animal. DISCUSSION AND CONCLUSION: The results show that BMV presents cyto- and genotoxicity depending on the concentration/dose used. These findings emphasize the importance of toxicological studies, including assessment of genotoxicity, in the biological activity research of BMV and/or in the development of BMV-derived products.

Neuroinflammation: An overview of neurodegenerative and metabolic diseases and of biotechnological studies.

Neuroinflammation is an important factor contributing to cognitive impairment and neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), ischemic injury, and multiple sclerosis (MS). These diseases are characterized by inexorable progressive injury of neuron cells, and loss of motor or cognitive functions. Microglia, which are the resident macrophages in the brain, play an important role in both physiological and pathological conditions. In this review, we provide an updated discussion on the role of ROS and metabolic disease in the pathological mechanisms of activation of the microglial cells and release of cytotoxins, leading to the neurodegenerative process. In addition, we also discuss in vivo models, such as zebrafish and Caenorhabditis elegans, and provide new insights into therapeutics bioinspired by neuropeptides from venomous animals, supporting high throughput drug screening in the near future, searching for a complementary approach to elucidating crucial mechanisms associated with neurodegenerative disorders.

Synthesis and biological activities of a nitro-shiff base compound as a potential anti-inflammatory agent.

In order to discover a new compound having anti-inflammatory activity, a nitro-Schiff base was evaluated. The compound was synthesized and characterized by 1H NMR and 13C NMR. The cytotoxic activity was evaluated in vitro by hemolysis and MTT cell viability assay. To evaluate genotoxicity, the micronucleus assay was performed in vivo. The anti-inflammatory effects of the compound were examined using in vivo models of inflammation such as neutrophil migration assay, paw edema, and exudation assay. The production of NO was also estimated in vivo and in vitro. The data showed that the compound did not induce hemolysis at all the tested concentrations. Similarly, the compound did not induce cytotoxicity and genotoxicity to the cells. The neutrophil migration assay showed that the compound reduced the number of neutrophils recruited to the peritoneal cavity by approximately 60% at all the tested concentrations. In the exudation assay, the compound showed a reduction in extravasation by 24%. The paw edema model demonstrated a significant reduction in the paw volume at all the evaluated time points. The production of NO was decreased both in vitro and in vivo. These results suggest that the nitro-Schiff base compound efficiently inhibited inflammation and might be a good candidate for the treatment of inflammatory-associated conditions.

Systemic Administration of Antipsychotic Asenapine Pre or Postnatal does not Induce Anxiety-like Behaviors in Mice.

BACKGROUND AND OBJECTIVE: Asenapine is an atypical antipsychotic approved by US Food and Drug Administration in 2009 and by European Medicines Agency in 2010 for Schizophrenia and Bipolar Disorder treatment. Currently, many studies have been developed in an attempt to clarify and minimize the risks related to the use of psychotropic during pre/postnatal period on patients with a history of mental disorders. CONCLUSION: The aim of this study was to test the impact of pre and/or postnatal exposition to asenapine on mice offspring behavior. Four groups of animals, previously treated with a dosage equivalent to 50% of the bioavailability obtained with a 20 mg daily use for human treatment, were exposed to the Open Field and Elevated plus Maze test. Only the group exposed to asenapine during both pre and postnatal periods showed response difference in the Elevated Plus Maze test, which was restricted to urination. However, our data suggest that the administration of asenapine does not induce significant anxiety-like behaviors in mice.

Adhesion molecules and Differentiation Syndrome: phenotypic and functional analysis of the effect of ATRA, As2O3, phenylbutyrate, and G-CSF in acute promyelocytic leukemia.

BACKGROUND AND OBJECTIVES: Differentiation Syndrome (DS) is a treatment complication which can occur in patients treated with acute promyelocytic leukemia (APL) with all transretinoic acid (ATRA) or As(2)O(3), and is characterized by enhanced leukocyte transmigration. As(2)O(3), Phenylbutyrate (PB) and G-CSF are known to potentiate ATRA effects. Our aim was to analyze the changes in expression and function of adhesion molecules induced by ATRA, As(2)O(3), G-CSF and PB, and their association. DESIGN AND METHODS: APL blasts and NB4 cells were treated with ATRA, As(2)O(3), PB, G-CSF or their association and the expression of adhesion molecules was determined by flow cytometry. Cell adhesion was evaluated in vitro using Matrigel and for the in vivo analysis, Balb-c mice were injected with NB4 cells pre-treated with ATRA, As(2)O(3), ATRA+G-CSF or ATRA+As(2)O(3). In addition, CD54 and CD18 knock-out mice were injected with NB4 cells and concomitantly treated with ATRA. In both models, the MPO activity in the lungs was determined 6 hours after the injection of the cells. RESULTS: In NB4 and APL blasts, ATRA and As(2)O(3) increased CD54 expression, but no synergism was detected. CD11b and CD18 were also up-regulated by ATRA in primary cells. PB and G-CSF had no effect, but the latter potentiated ATRA-induced CD18 up-regulation. These changes were accompanied by increased adhesion to Matrigel and to lung microvasculature, and reversed by anti-CD54, anti-CD18 antibodies. In CD54 and CD18 knock-out mice the ATRA effect was canceled. INTERPRETATION AND CONCLUSIONS: The use of As(2)O(3), PB and G-CSF in association with ATRA should not aggravate DS in APL.