Increasing evidence suggests that plant-derived extracts and their isolated components are useful for treatment of seizures and, hence, constitute a valuable source of new antiepileptic drugs with improved efficacy and better adverse effect profile. β-Caryophyllene is a natural bicyclic sesquiterpene that occurs in a wide range of plant species and displays a number of biological actions, including neuroprotective activity. In the present study, we tested the hypothesis that β-caryophyllene displays anticonvulsant effects. In addition, we investigated the effect of β-caryophyllene on behavioral parameters and on seizure-induced oxidative stress. Adult C57BL/6 mice received increasing doses of β-caryophyllene (0, 10, 30, or 100mg/kg). After 60 min, we measured the latencies to myoclonic and generalized seizures induced by pentylenetetrazole (PTZ, 60 mg/kg). We found that β-caryophyllene increased the latency to myoclonic jerks induced by PTZ. This result was confirmed by electroencephalographic analysis. In a separate set of experiments, we found that mice treated with an anticonvulsant dose of β-caryophyllene (100mg/kg) displayed an improved recognition index in the object recognition test. This effect was not accompanied by behavioral changes in the open-field, rotarod, or forced swim tests. Administration of an anticonvulsant dose of β-caryophyllene (100mg/kg) did not prevent PTZ-induced oxidative stress (i.e., increase in the levels of thiobarbituric acid-reactive substances or the decrease in nonprotein thiols content). Altogether, the present data suggest that β-caryophyllene displays anticonvulsant activity against seizures induced by PTZ in mice. Since no adverse effects were observed in the same dose range of the anticonvulsant effect, β-caryophyllene should be further evaluated in future development of new anticonvulsant drugs.

In this acute protocol, a single oral administration of AFB1 was able to cause changes in important neurochemical parameters, without concomitant, detectable behavioral alterations. These results reinforce that monitoring mycotoxin levels in food is essential to guarantee food security.

Food products are susceptible to contamination by mycotoxins, and aflatoxin B1 (AFB1) stands as the most toxic among them. AFB1 intoxication results in distinct signs, including widespread systemic toxicity. Aspartame (ASP) is an artificial sweetener used as a sugar substitute in many products, and compelling evidence indicates ASP can be toxic. Interestingly, mechanisms underlying ASP and AFB1 toxicity involve oxidative stress. In this context, concomitant use of ASP and AFB1 in a meal may predispose to currently unidentified behavioural and biochemical changes. Therefore, we evaluated the effect of AFB1 (250 μg/kg, intragastrically (i.g.)) and/or ASP (75 mg/kg, i.g.) exposure for 7 days on behavioural and biochemical markers of oxidative stress in male Wistar rats. AFB1 and/or ASP increased hepatic glutathione S-transferase (GST) activity when compared to controls. In the kidneys, increased GST activity was detected in AFB1 and AFB1+ASP groups. In addition, AFB1 and or ASP elicited behavioural changes in the open field, marble burying and splash tests, however no additive effects were detected. Altogether, present data suggest AFB1 and ASP predispose to anxiety- and obsessive-compulsive-like symptoms, as well as to enzymatic defence system imbalance in liver and kidney of Wistar rats.

Epilepsy is a chronic neurological disease characterized by spontaneous recurrent seizures (SRS). Current anticonvulsant drugs are ineffective in nearly one-third of patients and may cause significant adverse effects. Rosmarinic acid is a naturally occurring substance which displays several biological effects including antioxidant and neuroprotective activity. Since oxidative stress and excitotoxicity play a role in the pathophysiology of seizures, we aimed the present study to test the hypothesis that rosmarinic acid displays anticonvulsant and disease-modifying effects. Female C57BL/6 mice received rosmarinic acid (0, 3, 10, or 30mg/kg; p.o.) 60min before the injection of pentylenetetrazol (PTZ, 60mg/kg; i.p.) or pilocarpine (300mg/kg, i.p.). Myoclonic and generalized tonic-clonic seizure latencies and generalized seizure duration were analyzed by behavioral and electroencephalographic (EEG) methods. The effect of acute administration of rosmarinic acid on mice behavior in the open-field, object recognition, rotarod, and forced swim tests was also evaluated. In an independent set of experiments, we evaluated the effect of rosmarinic acid (3 or 30mg/kg, p.o. for 14days) on the development of SRS and behavioral comorbidities in the pilocarpine post-status epilepticus (SE) model of epilepsy. Rosmarinic acid dose-dependently (peak effect at 30mg/kg) increased the latency to myoclonic jerks and generalized seizures in the PTZ model and increased the latency to myoclonic jerks induced by pilocarpine. Rosmarinic acid (30mg/kg) increased the number of crossings, the time at the center of the open field, and the immobility time in the forced swim test. In the chronic epilepsy model, treatment with rosmarinic acid did not prevent the appearance of SRS or behavioral comorbidities. In summary, rosmarinic acid displayed acute anticonvulsant-like activity against seizures induced by PTZ or pilocarpine in mice, but further studies are needed to determine its epilepsy-modifying potential.

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