Cordia oncocalyx and oncocalyxones: From the phytochemistry to the anticancer action and therapeutic benefits against chronic diseases.

Cordia oncocalyx Allemão is an endemic economically underexploited plant from Brazilian semi-arid region. Herein, we carried out a well-defined bibliographic review about the pharmacological activities of oncocalyxones from C. oncocalyx and mechanisms responsible for the biomedical properties. MeSH terms were used in the scientific databases for a narrative exploration. Technological development and bioproducts were also examined. Cordia oncocalyx is a deciduous tree of sexual reproduction rich in terpenoid quinones. Among them, oncocalyxone A, a 1,4-benzoquinone, the main compound from heartwood ethanol extracts, revealed anti-inflammatory and anti-edematogenic actions induced by carrageenan and dextran and antinociceptive potential in mice provoked by acetic acid and formalin. Oncocalyxone A inhibits platelet aggregation via activation of the soluble guanylate cyclase enzyme and blocks glycation processes. In addition to the antimicrobial effects against protozoa, fungi and bacteria and relaxation of smooth muscles, oncocalyxone A reduces mean blood pressure and glycemia in diabetic rats, decreases glomerular filtration parameters and tubular transport of electrolytes, and presents in vitro antimitotic and cytotoxic action upon different types of cancers, including resistant lung carcinoma lines. It has low oral acute toxicity (LD50 > 2000 mg/kg) and activates cellular apoptosis through the production of free radicals and interactions with DNA. However, no patents were found, which also emphasizes that Brazil, as the cradle of the main articles on C. oncocalyx, is wasting time and money. Moreover, slight systemic deleterious effects in mammals stimulate the use of oncocalyxone A and related compounds as lead constituents of safer drugs against chronic diseases.

Anti-inflammatory mechanisms of fruits and by-products from Mauritia flexuosa, an exotic plant with functional benefits.

Mauritia flexuosa L., traditionally known as "buriti", exhibits chemoprotective properties including antioxidant, antithrombotic, and nutritional actions. The aim of this study was to examine the oral anti-inflammatory activity of epicarp, mesocarp and endocarp obtained from M. flexuosa fruits using in vivo models to verify physiological benefits. The anti-edematogenic action was determined using phlogistic agents to induce paw edema and peritonitis. Pro-inflammatory cytokines, cell migration of peritoneal cells, histological changes, and abdominal swelling induced by acetic acid were also investigated. Carrageenan-induced edema was found to be decreased in mice pre-treated with epicarp by 50.8%, 53.7% and 39.2% and mesocarp by 41.8%, 65.3% and 71.9% after 2, 3, and 4 hr stimuli, respectively. Edema initiated by specific agents such as compound 48/80, histamine, serotonin, and prostaglandin E2 were also reduced, and better outcomes were found against histamine-induced edema, as evidenced by the decline at all times analyzed (30-120 min) with both doses of water extract of mesocarp (500 or 1000 mg/kg). Mesocarp-pre-treatment reduced inflammatory tissue parameters such as number of peritoneal leukocytes and TNF-α levels, but only epicarp diminished abdominal pain. In summary, M. flexuosa fruits, especially mesocarp, exhibited oral physiological benefits and capacity to modify biochemical and cellular steps in the inflammatory cascade, indicating that dietary supplements containing these fruits may be combined with pharmacological tools to ameliorate or prevent diseases of inflammatory origin.

Non-clinical toxicity of (+)-limonene epoxide and its physio-pharmacological properties on neurological disorders.

The compound (+)-limonene epoxide has antioxidant, anxiolytic, and antihelminthic properties. However, investigations to determine its long-term exposure were not performed. We investigated the systemic toxicological profile after chronic exposure as well as the antidepressant and antiepileptic potentialities of (+)-limonene epoxide on mice. Initially, we evaluated acute toxicity on Artemia salina nauplii and cytotoxicity on mice erythrocytes and peripheral blood mononuclear cells (PBMC). Aftterwards, mice were chronically treated for 120 days by gavage with (+)-limonene epoxide (25, 50, and 75 mg/kg/day) and this exposure was assessed by pathophysiological measurements. For antidepressant and anticonvulsivant analysis, we performed the forced swimming and tail suspension protocols and pentylenetetrazol- and picrotoxin-induced seizures, respectively. (+)-Limonene epoxide showed a LC50 value of 318.7 µg/mL on A. salina shrimps, caused lysis of red blood cells at higher concentrations only but did not show cytotoxicity on PMBC, which suggests pharmacological safety if plasma concentrations do not exceed 100 µg/mL. Macroscopic, hematological, clinical chemistry, and nutritional changes were not detected, though focal areas of hepatic necrosis, inflammatory infiltrate, and karyolysis have been detected at 75 mg/kg/day. The compound inhibited the developing of pentylenetetrazol- and picrotoxin-induced seizures, decreased deaths, and reduced immobility times, mainly at 75 mg/kg. So, it reversed reserpine effects, suggesting antidepressant effects should be linked to serotonergic and/or adrenergic transmission. It is feasible that (+)-limonene epoxide plays a benzodiazepine-like anticonvulsive action and may be also recommended as an antidote for poisonings caused by central depressants.

Pharmacological and physicochemical profile of arylacetamides as tools against human cancers.

Arylacetamides are widely used as synthetic intermediates to obtain medicinal substances. This work evaluated in vitro antiproliferative activity of ten 2-Chloro-N-arylacetamides on human normal and cancer cells and detailed in vivo toxicological and anticancer investigations. Initially, cytotoxic colorimetric assays were performed using tumor lines, peripheral blood mononuclear cells (PBMC) and erythrocytes. Compounds 2, 3 and 4 were tested for acute toxicity (50, 150 and 300 mg/kg) and for subacute antitumoral capacity in HCT-116 colon carcinoma-bearing xenograft mice for 15 days at 25 mg/kg/day. Most compounds revealed cytotoxic action on tumor lines and PBMC, but activity on human erythrocytes were not detected. Molecular dipole moment, lipophilicity and electronic constant of aryl substituents had effects upon in vitro antiproliferative capacity. More common in vivo acute behavioral signals with compounds 2, 3 and 4 were muscle relaxation, reduction of spontaneous locomotor activity and number of entries in closed arms and increased number of falls andtime spent in open arms, suggesting diazepam-like anxiolytic properties. Decrease of grabbing strength and overall activity were common, but palpebral ptosis and deaths occurred at 300 mg/kg only. Compounds 2 and 3 reduced colon carcinoma growth (21.2 and 27.5%, respectively, p < 0.05) without causing apparent signals of organ-specific toxicity after subacute exposure. The structural chemical simplicity of arylacetamides make them cost-effective alternatives and justifies further improvements to enhance activity, selectivity and the development of pharmaceutical formulations.

Pathophysiological investigations, anxiolytic effects and interaction of a semisynthetic riparin with benzodiazepine receptors.

We have reported Riparin A as a promising antiparasitic molecule ​​against Leishmania amazonensis promastigotes. This work evaluated the acute oral toxicity of Riparin A and its anxiolytic effects using in vivo models and computational tools. Mice were submitted to acute oral toxicity tests (Guideline OECD 423). Later, anxiety assays with Riparin A (50, 100 and 200 mg/kg: elevated plus maze, light/dark box and marble burying) were performed. Theoretical calculations analyzed interaction of Riparin A with gamma-amino butyric acid (GABA) receptors. Only Riparin A at 2000 mg/kg alter body weight, food and water consumption and urine production after 7 and/or 14 days treatment and increased serum triglycerides. There was increase in the time spent in the open arms (TSOA) and number of transitions between compartments (NTC) and decrease in number of hidden balls (NHB) in Riparin A-treated animals at 200 mg/kg (P < 0.05), whose approximate ED50 was 283.1 (156.5-397.1) mg/kg. The functional amide of Riparin A interacted with the GABAA receptor mainly at subunits α2 and ß1 and presented strong interaction with the Asp68 residue, which is part of the pharmacophore group. Riparin A was toxically safe and pharmacologically active for anxiolytic purposes, revealed NOAEL of 200 mg/kg and probably interacts with Asp68 residues of benzodiazepine receptors by hydrogen bonds.

Effects of isopentyl ferulate on oxidative stress biomarkers and a possible GABAergic anxiolytic-like trait in Swiss mice.

This study aimed to evaluate the anxiolytic-like effect and the possible neuronal mechanism of action of isopentyl ferulate (IF). For this purpose, we used the marble burying test in Swiss albino mice. The biomarkers involved in oxidative stress were measured in the hippocampus homogenate of the test animals. In addition, the toxicity and antioxidant capacities were tested in Artemia salina and rat erythrocytes, respectively. The results suggest that, an acute administration of the IF at doses of 25, 50, 75 and 150 mg/kg (intraperitoneal, i.p.) significantly (p < 0.05) reduced the marble burying behavior of the animals as compared to the vehicle group, which demonstrates a calming effect of this chemical. It was observed that, the pre-treatment with flumazenil (2.5 mg/kg, i.p.), an antagonist of the gamma-amino butyrinc acid (GABAA) receptor, significantly reversed the marble burying behavioral activity in the animals treated with the IF 150 mg/kg dose. Moreover, the reduction in nitrite content and lipid peroxidation levels, while an increased in the reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities were also observed their hippocampus. Although, IF (2.36-14.16 mM) did not show toxicity in A. salina but exhibited a prominent antioxidant capacity in hydrogen peroxide-induced oxidative damage in rat erythrocytes. In conclusion, IF exhibited an anxiety-like effect in mice along with a potent antioxidant capacity, and we suppose it may have neuroprotective effects possibly via GABAergic transmission pathway.

Nerolidol and its Pharmacological Application in Treating Neurodegenerative Diseases: A Review.

BACKGROUND: Research on natural bioactive compounds has increased exponentially over the last decades. The discovery of new phytochemicals that possess pharmaceutical properties is useful in the development of therapeutic alternatives. The nerolidol (3,7,11-trimetil-1,6,10-dodecatrien-3-ol or 3,7,11-trimetildodeca-1,6,10-trien-3-ol) has been extensively studied for its therapeutic potential because of its pharmacological activities in the treatment of neurodegenerative diseases. METHOD: All articles and patents regarding nerolidol and its pharmacological properties were revised, focusing mainly on the important properties in the treatment of neurodegenerative diseases. A thorough search in article databases (Science Direct, MEDLINE/PubMed, Scopus and Scielo) and patent database (WIPO, EPO, ESPTO, LATIPAT and INPI) was performed over the course of this study. RESULTS: Several studies stood out for their relevance regarding the treatment of neurodegenerative diseases. Nerolidol demonstrated anticholinesterasic, antioxidant, antinociceptive, anti-inflammatory and anxiolytic activities, thus classifying it as a promising phytochemical for the development of therapeutic drugs. CONCLUSION: Analysis suggested that nerolidol is a promising target for new drugs and treatment of neurodegenerative diseases.

Behavioral effects induced by antitumor cleronade diterpenes from Casearia sylvestris and in silico interactions with neuron receptors.

ETHNOPHARMACOLOGICAL RELEVANCE: Casearia sylvestris is a medicinal plant traditionally used to treat snakebites, wounds, inflammation and gastric ulcers and scientific supports for have demonstrated its antitumor, antihyperlipidemic and antiparasitic properties. AIM OF THE STUDY: To assess the effects of a fraction with casearins (FC) on adult mice using classical experimental models of animal behavior and theoretical calculations to verify the interaction of Casearin X (Cas X) with neuron receptors. MATERIALS AND METHODS: Animals divided in 6 groups (n=9/group) were intraperitoneally treated with vehicle (DMSO 4%), FC (2.5, 5, 10 and 25mg/kg/day) and diazepam (2mg/kg) for 7 days. Thirty minutes after the last dose of treatment, acute toxicity and behavioral experiments were performed. RESULTS: The highest dose of FC (25mg/kg/day) caused diarrhea, weight loss and death of one animal. Elevated plus maze test showed that lower doses [2.5mg/kg/day (36.4±5.1s) and 5mg/kg/day (43.9±6.2s)] increased the time spent in open arms (TSOA). Open field test revealed reduction in the number of crossings (54.9%, 51.1%, 48% and 67.7% for 2.5, 5, 10 and 25mg/kg/day, respectively) in all doses of FC studied and decrease of rearings at 25mg/kg/day (p<0.05). Computational calculations showed that the inhibition constant (Ki) for the Cas X-D1 complex is up to 1000-fold more favourable than the Cas X-GABAA complex. All ∆G° values obtained for Cas X-D1 complexes were more negative than those seen with Cas X-GABAA complexes. CONCLUSIONS: Findings indicate a probable anxiolytic action of the FC since it reduces the number of crossings and rearings and prolonged the time spent in open arms, without sedative and myorelaxant effects, probably due to the interaction of Cas X with dopaminergic system.

Physio-pharmacological Investigations About the Anti-inflammatory and Antinociceptive Efficacy of (+)-Limonene Epoxide.

D-limonene epoxidation generates (+)-limonene epoxide, an understudied compound in the pharmacologically point of view. Herein, we investigated the anti-inflammatory and antinociceptive potentialities of (+)-limonene epoxide and suggested a mechanism of action. The anti-inflammatory potential was analyzed using agents to induce paw edema, permeability, and myeloperoxidase (MPO) activity. Pro-inflammatory cytokines and cell migration of peritoneal cells were also assessed. Antinociceptive effects were evaluated by writhing test induced by acetic acid, formalin, and hot plate assays and contribution of opioid pathways. Pretreated animals with (+)-limonene epoxide showed reduced carrageenan-induced paw edema in all doses (25, 50, and 75 mg/kg) (P < 0.05). At 75 mg/kg, it suppressed edema provoked by compound 48/80, histamine, prostaglandin E2, and serotonin and reduced permeability determined by Evans blue and MPO activity. It also reduced leukocytes, neutrophils, and IL-1ß levels in the peritoneal cavity in comparison with carrageenan group (P < 0.05). (+)-Limonene epoxide diminished abdominal contortions induced by acetic acid (78.9%) and paw licking times in both 1 (41.8%) and 2 (51.5%) phases and a pretreatment with naloxone (3 mg/kg) reverted the antinociceptive action in morphine- and (+)-limonene epoxide-treated groups (P < 0.05). Additionally, it enlarged response times to the thermal stimulus after 60 and 90 min. In conclusion, (+)-limonene epoxide inhibited release/activity of inflammatory mediators, vascular permeability, migration of neutrophils and displayed systemic and peripheral analgesic-dependent effects of the opioid system.

Neuropharmacological effects of carvacryl acetate on δ-aminolevulinic dehydratase, Na+, K+-ATPase activities and amino acids levels in mice hippocampus after seizures.

Epileptic syndromes are highly prevalent neurological conditions and can often be disabling. In order to find an alternative for treatment, this study evaluated anticonvulsant effects of carvacryl acetate (CA), a derivative of monoterpene carvacrol, after seizures induced by pilocarpine (P400), picrotoxin (PIC) or pentylenetetrazol (PTZ). We also analyzed the CA effects on Na+, K+-ATPase and δ-aminolevulinic acid dehydratase (δ-ALA-D) activities in hippocampus mice after seizures induced by P400, PIC or PTZ. In addition, glutamate, δ-aminobutyric acid (GABA), glutamine and aspartate levels in mice hippocampus treated with CA after seizures induced by P400, PIC or PTZ were also measured. CA produced anticonvulsant effects against seizures induced by P400, PIC or PTZ, and its effects were reversed by flumazenil, suggesting that action mechanism can be mediated by GABAergic system. CA increased GABA levels, but did not alter glutamate and aspartate concentrations in mice hippocampus after seizures induced by P400, PIC or PTZ when compared with seizures induced by P400, PIC or PTZ (p<0.05), respectively, as well as decreased glutamine content in mice hippocampus after seizures induced by PIC when compared with seizures induced by PIC (p<0.05). In addition, CA also increased Na+, K+-ATPase and δ-aminolevulinic acid dehydratase activities after seizures induced by P400, PIC or PTZ when compared with seizures induced by P400, PIC or PTZ (p<0.05), respectively. This study demonstrated that CA could be a future therapeutic option for treatment of epilepsy, with a multifactorial brain action mechanism.

Anxiolytic-like effects and mechanism of (-)-myrtenol: a monoterpene alcohol.

The essential oil of Myrtus communis L. (Myrtaceae) and its compounds have been popularly used in numerous health disorders, including insomnia and nervous conditions, but their effects on central nervous system (CNS) have not been explored yet. We evaluated the anxiolytic-like effects and possible action mechanism of (-)-myrtenol (MYR), a monoterpenoid alcohol present in essential oil of M. communis L. Animal models of elevated plus maze (EPM), light-dark transition (LDT), open field and rotarod tests were used in the present study. MYR was administered in male rats. Diazepam was used as the standard drug (positive control) and flumazenil was used to elucidate the possible action mechanism. The results showed that none of the doses of MYR had effect on the resistance time in rotating bar, but caused reduction in the number of falls in rotarod tests when compared with a negative control. Similarly, MYR had no effect on the number of crossings, groomings or rearings in open field tests when compared with a negative control. However, in EPM and LDT tests, MYR significantly increased (p<0.001) the number of entries in open arms (F7,49=9.867), the time spent in open arms (F7,49=53.97) and the time spent in light compartment (F7,56=27.38), when compared with negative and positive controls, respectively. Flumazenil was able to reverse the effects of diazepam and MYR. These results suggest that MYR presents anxiolytic-like activity and that effect can be mediated by GABAergic transmission.

Is there a correlation between in vitro antioxidant potential and in vivo effect of carvacryl acetate against oxidative stress in mice hippocampus?

This study investigated in vitro and in vivo antioxidant potential of carvacryl acetate (CA), a derivative of carvacrol, monoterpenic component of oregano. The correlation between in vitro and in vivo CA effects was also determined. In vitro tests measured thiobarbituric acid reactive species content, nitrite formation and hydroxyl radical levels. In vivo tests measured thiobarbituric acid reactive species content, nitrite concentration and reduced glutathione (GSH) levels, as well as glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase activities were measured, using mice hippocampus. The CA administrations for in vivo tests were intraperitoneally and acutely improved. CA reduced lipid peroxidation, nitrite and hydroxyl radical contents in vitro as well as lipid peroxidation and nitrite content in vivo. It also increased reduced GSH levels and GPx as well as catalase activities. Moreover, CA required a lower concentration to inhibit 50 % of free radicals measured in vitro than trolox. There was significant negative correlation between in vitro nitrite levels and in vivo reduced GSH levels; in vitro nitrite content and in vivo GPx activity as well as in vitro hydroxyl radical levels and in vivo SOD activity. To date, this is the first study which suggests vitro and in vivo antioxidant potential to this monoterpene and the correlation between these parameters.

Potential antioxidant and anxiolytic effects of (+)-limonene epoxide in mice after marble-burying test.

The present study evaluated anxiolytic activity of (+)-limonene epoxide (EL), through the marble burying test (MBT) assay, and the antioxidant potential in vitro and in vivo in mice hippocampus of adult mice subjected to experimental anxiety protocol. For behavioral studies, and in vivo antioxidant analyses, mice were treated orally with 0.05% Tween 80 dissolved in 0.9% saline solution (vehicle), ascorbic acid 250 mg/kg, diazepam (2 mg/kg) and EL (25, 50 and 75 mg/kg). Results suggest an anxiolytic effect of (+)-limonene epoxide. A reduction in number of buried marbles in groups treated with EL doses of 25, 50 and 75 mg/kg was observed when compared with diazepam and vehicle groups. This reduction was observed after treatments with single and repeated doses, reinforcing the hypothesis of anxiolytic effect. The anxiolytic effect was reversed by pretreatment with flumazenil (25 mg/kg, o.r) in the same way as it was observed with diazepam (2 mg/kg, o.r, positive control), suggesting that these drugs possess a similar mechanism of action. In antioxidant tests in vitro, the concentrations from 0.9 to 7.2 µg/ml were tested. The results of in vitro antioxidant tests demonstrated a 50% inhibitory effective concentration of 0.7342, 1.296 and 1.169 µg/ml against the formation of nitrite ion, hydroxyl radical and reactive substances to thiobarbituric acid, respectively. The treatment with EL reduced the lipid peroxidation level and nitrite content, suggesting an antioxidant role in vivo since it was able to reduce the formation of reactive species derived from oxygen and nitrogen. Furthermore, the EL increased activity of enzymes catalase and superoxide dismutase in mice hippocampus, suggesting that their role may be due to antioxidant upregulation of these enzymes.

Anxiolytic-like effects of carvacryl acetate, a derivative of carvacrol, in mice.

Studies showing anxiolytic-like properties of natural products have grown. This paper evaluated if carvacryl acetate (CA) could be studied as an alternative drug to treat anxiety disorders. Elevated plus maze (EPM) tests , light-dark box (LDB) tests, and marble-burying tests (MBTs) were performed on mice. In the first protocol, the anxiolytic-like activities of CA 25, 50, 75 and 100mg/kg at single doses were compared to those of the vehicle, buspirone 5mg/kg (BUSP) and diazepam 1mg/kg (DZP). In the second protocol, the anxiolytic-like actions of CA were tested for GABAergic and serotonergic systems. The time spent in the open arms (TSOA) and the number of open arms entries (NOAE) were measured in EPM; the time spent in the light box (TSLB) and the number of entries to light box (NELB) were measured in LDB; and the number of marbles buried (NMB) were measured in MBT. CA increased TSOA and NOAE in the EPM, as well as TSLB and NELB in the LDB and the NMB in the MBT. The anxiolytic-like activity of CA 25; 50; 75 and 100mg/kg was not associated with psychomotor retardation in the open field test and in the Rota rod test, contrarily with what happened with DZP. In the second protocol, to suggest the mechanism of action of CA, flumazenil 25mg/kg ip (FLU) and WAY 100,635 10mg/kg ip (WAY-5-HT1A antagonist) were also used. FLU+CA100 reduced TSOA in the EPM when compared to CA100 but WAY+CA100 did not. In LDB, FLU+CA100 reduced the TSLB when compared to CA100 but WAY+CA100 did not. In the MBT, FLU+CA100 inhibited the effect of CA100 on the NMB but WAY+CA100 did not. In conclusion, CA seems to have an anxiolytic-like effect, probably due to GABAergic agonist action, without psychomotor side effects.

Antioxidant effects of nerolidol in mice hippocampus after open field test.

The aim of this study was to evaluate the neuroprotective effects of nerolidol in mice hippocampus against oxidative stress in neuronal cells compared to ascorbic acid (positive control) as well as evaluated the nerolidol sedative effects by open field test compared to diazepam (positive control). Thirty minutes prior to behavioral observation on open field test, mice were intraperitoneally treated with vehicle, nerolidol (25, 50 and 75 mg/kg), diazepam (1 mg/kg) or ascorbic acid (250 mg/kg). To clarify the action mechanism of of nerolidol on oxidative stress in animals subjected to the open field test, Western blot analysis of Mn-superoxide dismutase and catalase in mice hippocampus were performed. In nerolidol group, there was a significant decrease in lipid peroxidation and nitrite levels when compared to negative control (vehicle). However, a significant increase was observed in superoxide dismutase and catalase activities in this group when compared to the other groups. Vehicle, diazepam, ascorbic acid and nerolidol groups did not affected Mn-superoxide dismutase, catalase mRNA or protein levels. Our findings strongly support the hypothesis that oxidative stress occurs in hippocampus. Nerolidol showed sedative effects in animals subjected to the open field test. Oxidative process plays a crucial role on neuronal pathological consequence, and implies that antioxidant effects could be achieved using this sesquiterpene.

Cytotoxic and leishmanicidal properties of garcinielliptone FC, a prenylated benzophenone from Platonia insignis.

Garcinielliptone FC (GFC), a natural prenylated benzophenone, was extracted from Platonia insignis Mart. (Clusiaceae), a native plant commonly known as bacuri and used in traditional Brazilian medicine for the treatment of skin diseases. The aim of this study was to evaluate the cytotoxic and leishmanicidal effects of GFC using in vitro models. The experimental data demonstrated that the polyisoprenylated benzophenone GFC possesses cytotoxic and leishmanicidal activities.

Anthelmintic activity of carvacryl acetate against Schistosoma mansoni.

Blood flukes of the genus Schistosoma are the causative agents of human schistosomiasis, a debilitating disease that afflicts over 200 million people worldwide. Praziquantel is the drug of choice but concerns over praziquantel resistance have renewed interest in the search for alternative drug therapies. Carvacrol, a naturally occurring monoterpene phenol and food additive, has been shown high medicinal importance, including antimicrobials activities. The aim of this study was to evaluate in vitro effect of carvacryl acetate, a derivative of carvacrol, on Schistosoma mansoni adult worms. We demonstrated that carvacryl acetate at 6.25 µg/mL has antischistosomal activity, affecting parasite motility and viability. Additionally, confocal laser scanning microscopy pictures revealed morphological alterations on the tegumental surface of worms, where some tubercles appeared to be swollen with numerous small blebs emerging from the tegument around the tubercles. Furthermore, experiments performed using carvacryl acetate at sub-lethal concentrations (ranging from 1.562 to 6.25 µg/mL) showed an inhibitory effect on the daily egg output of paired adult worms. Thus, carvacryl acetate is toxic at high doses, while at sub-lethal doses, it significantly interferes with the reproductive fitness of S. mansoni adult worms. Due to its safety and wide use in the industry, carvacryl acetate is a promising natural product-derived compound and it may represent a step forward in the search for novel anthelmintic agents, at a time when there is an urgent need for novel drugs.

Antinociceptive and Antioxidant Activities of Phytol In Vivo and In Vitro Models.

The objective of the present study was to evaluate the antinociceptive effects of phytol using chemical and thermal models of nociception in mice and to assess its antioxidant effects in vitro. Phytol was administered intraperitoneally (i.p.) to mice at doses of 25, 50, 100, and 200 mg/kg. In the acetic acid-induced writhing test, phytol significantly reduced the number of contortions compared to the control group (P < 0.001). In the formalin test, phytol reduced significantly the amount of time spent in paw licking in both phases (the neurogenic and inflammatory phases), this effect being more pronounced in the second phase (P < 0.001). Phytol also provoked a significant increase in latency in the hot plate test. These antinociceptive effects did not impaire the motor performance, as shown in the rotarod test. Phytol demonstrated a strong antioxidant effect in vitro in its capacity to remove hydroxyl radicals and nitric oxide as well as to prevent the formation of thiobarbituric acid reactive substances (TBARS). Taken as a whole, these results show the pronounced antinociceptive effects of phytol in the nociception models used, both through its central and peripheral actions, but also its antioxidant properties demonstrated in the in vitro methods used.

Efeito antioxidante da buspirona no modelo de epilepsia induzida por pilocarpina / Antioxidant effect of buspirone in epilepsy model induced by pilocarpine

CONTEXTO: Crises epilépticas induzidas por pilocarpina podem produzir alterações histopatológicas em muitas regiões cerebrais como consequência da produção excessiva de radicais livres.OBJETIVO: O objetivo do presente estudo foi avaliar o efeito antioxidante da buspirona no modelo de epilepsia induzida por pilocarpina.MATERIAL E MÉTODOS: Quarenta e oito animais foram divididos em quatro grupos. O primeiro grupo foi tratado com solução salina 0,9% (Controle). O segundo grupo foi tratado com pilocarpina 400 mg/kg (P400). Por sua vez, o terceiro grupo foi tratado com buspirona 5 mg/kg (BUSP) durante 14 dias consecutivos. Já os animais do quarto grupo foram tratados com buspirona durante 14 dias consecutivos, e, 30 minutos após a última administração dela, os camundongos receberam P400 (BUSP + P400).RESULTADOS: Durante o período do tratamento não se observaram sinais de toxicidade e nenhuma morte entre os animais tratados com buspirona. Em nosso estudo o grupo tratado com P400 demonstrou um aumento significativo da produção de nitrito e nos níveis de peroxidação lipídica após as crises epilépticas. Por outro lado, no hipocampo dos animais que receberam o pré-tratamento com buspirona e após 30 minutos receberam P400, foi observada redução significativa nos níveis de peroxidação lipídica (65%) e nitrito (85%), bem como aumento na atividade da enzima superóxido dismutase.CONCLUSÃO: O pré-tratamento com BUSP aumentou a latência para primeira crise epiléptica e diminuiu a taxa de mortalidade e o número de animais que apresentaram crise epiléptica e que progridem para o estado de mal epiléptico. Além disso, apresentou efeitos anticonvulsivantes associados com a redução do estresse oxidativo hipocampal no modelo de epilepsia induzida por pilocarpina.

BACKGROUND: Pilocarpine-induced seizures can cause pathological changes in many brain regions as a result of excessive production of free radicals.OBJECTIVE: The objective of this study was to evaluate the antioxidant effect of buspirone in the epilepsy model induced by pilocarpine.MATERIAL AND METHODS: Forty-eight animals were divided into four groups. The first group was treated with saline 0.9% (control); the second group received pilocarpine 400 mg/kg (P400); the third group was treated with buspirone 5 mg/kg (BUSP) for 14 consecutive days and animals in the fourth group were treated with buspirone for 14 consecutive days, and 30 minutes after the last buspirone administration were administered with P400 (BUSP + P400).RESULTS: No toxicity signs or death were observed in buspirone-treated animals. P400 group showed a significant increase in nitrite production and lipid peroxidation after seizures. Moreover, reduction in both the lipid peroxidation level (65%) and nitrite content (85%) as well as an increase in superoxide dismutase activity was detected following P400 injection in the hippocampus of buspirone-pretreated mice.DISCUSSION: Pretreatment with BUSP increased latency to first seizure, decreased the mortality rate and number of animals that presented seizures and progression to status epilepticus, showing potent anticonvulsant effects associated with reduction of hippocampal oxidative stress.