(-)-α-Bisabolol is an unsaturated, optically active sesquiterpene alcohol obtained by the direct distillation of essential oil from plants such as Vanillosmopsis erythropappa and Matricaria chamomilla. (-)-α-Bisabolol has generated considerable economic interest, as it possesses a delicate floral odour and has been shown to have antiseptic and gastroprotective activities. In this study, (-)-α-bisabolol was tested in standardised rodent models by gavage administration at doses of 100 and 200 mg/kg in the models of inflammation and 25 and 50 mg/kg in the models of nociception. In the inflammatory models of paw oedema induced by carrageenan and dextran, the mice treated with (-)-α-bisabolol showed smaller oedemas compared to animals treated only with the vehicle. (-)-α-Bisabolol was capable of reducing paw oedemas induced by 5-HT but not oedemas induced by histamine. (-)-α-Bisabolol demonstrated anti-nociceptive activity in the models of visceral nociception induced by acetic acid and in the second phase of the nociception test induced by the intraplantar administration of formalin. (-)-α-Bisabolol did not have any effect in a thermal nociception model using a hot plate but was able to diminish mechanical inflammatory hypernociception evoked by carrageenan. These findings suggest that the anti-nociceptive action of (-)-α-bisabolol is not linked to a central mechanism but instead is related to the inflammatory process. (-)-α-Bisabolol was able to decrease leukocyte migration, protein extravasations and the amount of TNF-α to the peritoneal cavity in response to carrageenan. Additionally, (-)-α-bisabolol reduced neutrophil degranulation in response to phorbol-myristate-acetate. We demonstrate, for the first time, the peripheral anti-inflammatory and anti-nociceptive activities of (-)-α-bisabolol.

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Recent studies have shown that some monoterpenes exert anxiolytic- and depressant-like actions, however, these effects from monoterpene 1,4-cineole are still unknown. This work aimed to study the effects of 1,4-cineole in classic animal models for depression- and anxiety-like behavior, specifically the elevated plus maze (EPM), hole board, open field, pentobarbital sleeping time, forced swimming, tail suspension and rota rod tests. 1,4-Cineole was administered orally to mice (100, 200 and 400 mg/kg), while diazepam (1 or 2 mg/kg) and imipramine (10 or 30 mg/kg) were used as standard drugs. 1,4-Cineole (400 mg/kg) modified all parameters observed in the EPM, while no significant variation was observed on general motor activity in the open-field test. In the hole-board assay, 1,4-cineole induced increase on the number of head dips. Forced swimming and tail suspension tests showed that cineole (200 and/or 400 mg/kg) was able to promote significant increase on the immobility time, while a decreased sleep latency was observed (200 and 400 mg/kg ) on the pentobarbital sleeping time. Cineole had no effect on the motor coordination of animals in the rota rod test. The results suggest that 1,4-cineole presents potential anxiolytic-like action consistent with possible general depression of the CNS.

Sleep has important functions for every organ in the body and sleep deprivation (SD) leads to disorders that cause irreparable damage. The aim of this study was to investigate behavioral and brain structural alterations in mice deprived of paradoxical sleep for 48 and 72 h. Working memory, aversive memory as well as levels of nitric oxide (NO) and thiobarbituric acid reactive substances (TBARS) in the hippocampus, body striatum, and prefrontal cortex were evaluated. Working memory was affected in the 48- and 72-h SD groups while aversive memory was altered only in the 48-h SD group (p ≤ 0.05). Our findings showed that SD reduces NO levels in most brain areas (p < 0.05): NO levels were unaltered in the striatum of animals sleep-deprived for 48 h. Higher levels of TBARS were observed in all areas of the SD groups (p ≤ 0.05). Thus, we confirmed that SD has duration-dependent effects on behavior as well as on NO and TBARS levels in the brain. Preserved striatum NO levels suggest that this structure is less vulnerable to oxidative stress and is only affected by SD of longer duration. Increased TBARS and reduced NO levels in the hippocampus and prefrontal cortex confirm a central role for both these structures in working memory and aversive memory. Contextual fear conditioning was not affected by longer periods of SD. Thus, our findings suggest that shorter SD time may be more beneficial to avoid aversive memory where this may have implications for the management of posttraumatic stress.

Based on these results, it has been suggested that carvacrol presents antinociceptive activity that may not act through the opioid system nor through inhibition of the nitric oxide pathway.

Melatonin, N-acetyl-5-methoxytryptamine, the major hormone produced by the pineal gland under the influence of the dark/light cycle, has been shown to have a large number of therapeutic possibilities. It has been utilized in several countries for circadian rhythm disorders, sleep disturbances, jet lag, and sleep-wake cycle disturbances in blind people, and shift workers. In our mechanism of act, the G(i) protein-coupled metabotropic melatonin receptors MT1 and MT2 are the primary mediators of the physiological actions of melatonin. This hormone plays an important role in the regulation of physiological and neuroendocrine functions, such as synchronization of seasonal reproductive rhythms and entrainment of circadian cycles. In addition to its chronobiological role, several pharmacological effects of melatonin have been reported in mammals including sedative, antioxidant, anxiolytic, antidepressant, anticonvulsant, and analgesic activities. There is some evidence from clinical trials that melatonin can be helpful in that event. Current trends of pharmacological functions of melatonin pointed out its use in the treatment of neurodegenerative and neoplastic diseases. These effects and uses of melatonin are mentioned but further confirmatory studies are needed in most of them.

This work describes the gastroprotective actions of esculin (6,7-dihydroxycoumarin-6-o-glucoside) against indomethacin- or ethanol-induced lesions and verifies the role of nitric oxide, ATP-dependent K(+) channels, prostaglandins, transient receptor potential vanilloid 1 and antioxidant effects in the gastroprotective mechanism of esculin in the ethanol-induced gastric lesion model. The intragastric administration of esculin at doses of 12.5, 25 and 50 mg/kg was able to protect the gastric mucosa against ethanol (0.2 mL/animal p.o.), and esculin at doses of 25 and 50 mg/kg protected against indomethacin-induced lesions (20mg/kg p.o.). Administration of l-NAME (10mg/kg i.p.), glibenclamide (10mg/kg i.p.) or indomethacin (10mg/kg p.o.), but not capsazepine (5mg/kg p.o.), was able to reduce the gastroprotection promoted by esculin (25mg/kg) on the ethanol-induced lesions. Measurements of nitrite, a NO metabolite, were increased in the group that was pretreated with esculin. In terms of antioxidant activity as a gastroprotective mechanism of esculin, the results show that pre-treatment with esculin decreased the amount of GSH, increased SOD activity, did not interfere with the CAT activity and decreased both the MPO activity and the MDA amount. In conclusion, pre-treatment with esculin confers significant gastroprotective and antioxidant activity and leads to a reduction in gastric injury; the mechanisms underlying these effects include stimulation of endogenous prostaglandins, nitric oxide synthesis, opening of K(ATP) channels and reduction of free radicals or modulation of antioxidant enzyme systems.

Exercise is a promising adjunctive therapy for depressive behavior, sleep/wake abnormalities, cognition and motor dysfunction. Conversely, sleep deprivation impairs mood, cognition and functional performance. The objective of this study is to evaluate the effects of exercise on anxiety and depressive behavior and striatal levels of norepinephrine (NE), serotonin and its metabolites in mice submitted to 6h of total sleep deprivation (6h-TSD) and 72h of Rapid Eye Movement (REM) sleep deprivation (72h-REMSD). Experimental groups were: (1) mice submitted to 6h-TSD by gentle handling; (2) mice submitted to 72h-REMSD by the flower pot method; (3) exercise (treadmill for 8 weeks); (4) exercise followed by 6h-TSD; (5) exercise followed by 72h-REMSD; (6) control (home cage). Behavioral tests included the Elevated Plus Maze and tail-suspension. NE, serotonin and its metabolites were determined in the striatum using high-performance liquid chromatography (HPLC). Sleep deprivation increased depressive behavior (time of immobilization in the tail-suspension test) and previous exercise hindered it. Sleep deprivation increased striatal NE and previous exercise reduced it. Exercise only was associated with higher levels of serotonin. Furthermore, exercise reduced serotonin turnover associated with sleep deprivation. In brief, previous exercise prevented depressive behavior and reduced striatal high NE levels and serotonin turnover. The present findings confirm the effects of exercise on behavior and neurochemical alterations associated with sleep deprivation. These findings provide new avenues for understanding the mechanisms of exercise.