Efecto antinociceptivo y antiinflamatorio del aceite esencial de Lippia pedunculosa Hayek y su complejo de inclusión de ß-ciclodextrina / Antinociceptive and anti-inflammatory effect of Lippia pedunculosa Hayek essential oil and its ß-cyclodextrin inclusion complex

Lippia pedunculosa Hayek (EOLp) presenta efectos tripanocidas y amebicidas. En este trabajo se estudia su aceite esencial en modelos experimentales de analgesia e inflamación una vez que la prevalencia del dolor en la población genera un gran sufrimiento y discapacidad, y los medicamentos que se usan con mayor frecuencia tienen efectos secundarios indeseables. También se evalúa si la formulación del complejo de inclusión EOLp/ß-ciclodextrina (ß-CD) fue capaz de mejorar la actividad antinociceptiva de la EOLp sola. Los datos se evaluaron mediante análisis de varianza (ANOVA), seguido de la prueba de Tukey. Las diferencias se consideraron significativas si p<0,05. EOLp presentó un mejor efecto antinociceptivo en comparación con el complejo de inclusión EOLp/ß-CD. De esta manera, las ciclodextrinas parecen no ser eficientes para aceites esenciales con sustancias de peróxido. Sin embargo, en peritonitis, EOLp redujo la migración total de leucocitos y los niveles de IL-1ß en el líquido peritoneal, lo que confirma su efecto antiinflamatorio. Los efectos observados sugieren que EOLp es una buena y prometedora opción para el tratamiento de la inflamación y los trastornos relacionados con el dolor.

Lippia pedunculosa Hayek (EOLp) presents tripanocid and amebicid effects. However essential oil needs to be further studied in experimental models of analgesia and inflammation once the prevalence of pain in the population generates great suffering and disability and the drugs most often used have undesirable side effects. We also evaluated whether the inclusion complex formulation EOLp/ß-cyclodextrin (ß-CD) was able to improve the antinociceptive activity of the EOLp alone. Data were evaluated by analysis of variance (ANOVA), followed by Tukey's test. Differences were considered significant if p<0.05. EOLp presented better antinociceptive effect when compared to the EOLp/ß-CD inclusion complex. Thus, cyclodextrins appear not to be efficient for essential oils with peroxide substances. However, in peritonitis, EOLp reduced total leucocyte migration and IL-1ß levels in the peritoneal fluid, which confirmed its anti-inflammatory effect. The observed effects suggest that EOLp is the best promising option for the treatment of inflammation and pain-related disorders.

Anticonvulsant Essential Oils and Their Relationship with Oxidative Stress in Epilepsy.

Epilepsy is a most disabling neurological disorder affecting all age groups. Among the various mechanisms that may result in epilepsy, neuronal hyperexcitability and oxidative injury produced by an excessive formation of free radicals may play a role in the development of this pathology. Therefore, new treatment approaches are needed to address resistant conditions that do not respond fully to current antiepileptic drugs. This paper reviews studies on the anticonvulsant activities of essential oils and their chemical constituents. Data from studies published from January 2011 to December 2018 was selected from the PubMed database for examination. The bioactivity of 19 essential oils and 16 constituents is described. Apiaceae and Lamiaceae were the most promising botanical families due to the largest number of reports about plant species from these families that produce anticonvulsant essential oils. Among the evaluated compounds, ß-caryophyllene, borneol, eugenol and nerolidol were the constituents that presented antioxidant properties related to anticonvulsant action. These data show the potential of these natural products as health promoting agents and use against various types of seizure disorders. Their properties on oxidative stress may contribute to the control of this neurological condition. However, further studies on the toxicological profile and mechanism of action of essential oils are needed.

Geraniol Induces Antinociceptive Effect in Mice Evaluated in Behavioural and Electrophysiological Models.

Geraniol (GER) is a monoterpene alcohol with various biochemical and pharmacological properties present in the essential oil of more than 160 species of herbs (especially the Cymbopogon genus). In this study, we evaluated the antinociceptive activity of GER in behavioural and electrophysiological in vitro experimental models of nociception using male Swiss mice. GER (12.5, 25 or 50 mg/kg i.p. and 50 or 200 mg/kg p.o.) reduced the number of writhes induced by acetic acid. The opioid antagonist naloxone (5 mg/kg s.c.) administered in mice subsequently treated with GER (25 mg/kg i.p.) did not reverse such antinociceptive activity, suggesting a non-opioid pathway for the mechanism of action. GER (12.5, 25 and 50 mg/kg i.p.) reduced paw licking time in the second phase of the formalin test. Also, in the glutamate test, GER when administered 50 mg/kg i.p. reduced paw licking time, probably modulating glutamatergic neurotransmission. GER blocked reversibly components of the compound action potential (CAP) recorded in isolated sciatic nerve in a concentration- and drug exposure time-dependent manner: 1 mM to 120 min. for the first component and 0.6 mM to 90 min. for the second component. The IC50 was calculated for the peak-to-peak amplitude (PPA) at 0.48 ± 0.04 mM. The conduction velocity was also reduced by exposure to GER starting from the concentration of 0.3 mM for both components of the CAP. In conclusion, it is suggested that GER has antinociceptive activity, especially in pain related to inflammation, and in part related to reduced peripheral nerve excitability.

Anti-asthmatic and anxiolytic effects of Herissantia tiubae, a Brazilian medicinal plant.

Herissantia tiubae (HtE) is a Brazilian plant used in folk medicine to treat inflammatory diseases. Our aim was to determine whether the HtE has anti-inflammatory and anxiolytic effects in a murine model of asthma. Ovalbumin (OVA)-sensitized BALB/c mice were treated with HtE (50, 100, or 200 mg/kg) or dexamethasone before each OVA challenge. After the last challenge, animals were subjected to anxiety tests and respiratory measurements. Following euthanasia, we quantified immune cells in the bronchoalveolar lavage (BAL), serum IgE titer and cytokine levels, cellular infiltration and mucus content in the lung tissues, and cellular composition of the mediastinal lymph nodes. OVA challenge in sensitized animals caused: (1) reduction of mean respiratory and dominant respiratory rate (from 398 ± 12 to 286 ± 20 cicles per minute (cpm) and from 320 ± 14 to 162 ± 15 cpm, respectively); (2) increase in behavioral markers of anxiety tests; (3) substantial pro-inflammatory effects, including rise in OVA-specific IgE titer (from 0 to 1:2048) and these inflammatory effect diminished the titer to 1:512 after HtE treatment; rise in plasma IL-13 (from 13 ng/mL in saline to 227 ng/mL in OVA and HtE treatment restored to 1.29 ng/mL; rise in total BAL cell count (from 0.742 cells/mL in saline to 11.77 cells/mL in OVA), with prominent eosinophilia. H. tiubae extract affected respiratory parameters similarly to aminophylline, behavioral changes comparable to diazepam, and inflammation being as efficient as dexamethasone. H. tiubae extract (HtE) possesses both anti-inflammatory and anxiolytic properties in the murine model of asthma.

Anxiolytic Effect of Citrus aurantium L. on Patients with Chronic Myeloid Leukemia.

The bone marrow aspiration procedure is used in hematological diseases and consists of a painful, invasive procedure causing anxiety-associated symptoms. The present study assessed the effect of Citrus aurantium L. essential oil on the treatment of anxiety, in the moment that precedes the collection of medullary material in patients with chronic myeloid leukemia (CML). Volunteers from both sexes were divided into groups receiving either the C. aurantium essential oil through inhalation, diazepam (10 mg), or the placebo. The evaluation was performed through psychometric scales [State-Trait Anxiety Inventory (STAI)] and physiological measurements (blood pressure and cardiac and respiratory frequency). Inhalation of C. aurantium was associated with a decrease in the STAI-S scores, suggesting an anxiolytic effect. In support of these results, a change in all the physiological measurements was observed in the group exposed to C. aurantium. In the diazepam group, only the diastolic pressure decreased, and no effect was observed in the placebo group. Therefore, the results showed that C. aurantium exhibits an anxiolytic effect and reduces the signs and symptoms associated with anxiety in patients with CML.

Curine, an alkaloid isolated from Chondrodendron platyphyllum inhibits prostaglandin E2 in experimental models of inflammation and pain.

Curine is a bisbenzylisoquinoline alkaloid that is isolated from Chondrodendron platyphyllum, a plant that is used to treat malaria, inflammation, and pain. Recent reports have demonstrated the antiallergic effects of curine at nontoxic doses. However, its anti-inflammatory and analgesic properties remain to be elucidated. This study investigated the anti-inflammatory and analgesic effects of curine in mice. We analyzed the effects of an oral treatment with curine in the formation of paw edema, vascular permeability, abdominal contortion, licking behavior, and hyperalgesia using different inflammatory stimuli. Curine significantly inhibited the formation of paw edema by decreasing vascular permeability, inhibited the acetic acid-induced writhing response, inhibited the licking behavior during inflammation but not during the neurogenic phase of the formalin test, and inhibited carrageenan-induced hyperalgesia. Finally, curine inhibited prostaglandin E2 production in vitro without affecting cyclooxygenase-2 expression. The effects of curine treatment were similar to the effects of indomethacin, but were different from the effects of morphine treatment, suggesting that the analgesic effects of curine do not result from the direct inhibition of neuronal activation but instead depend on anti-inflammatory mechanisms that, at least in part, result from the inhibition of prostaglandin E2 production. In conclusion, curine presents anti-inflammatory and analgesic effects at nontoxic doses and has the potential for use in anti-inflammatory drug development.

In vitro evaluation of schistosomicidal activity of essential oil of Mentha x villosa and some of its chemical constituents in adult worms of Schistosoma mansoni.

This study aimed to determine the composition of the essential oil of Mentha x villosa and to evaluate its biological effects in vitro on adult worms of S. mansoni. Rotundifolone (70.96 %), limonene (8.75 %), trans-caryophyllene (1.46 %), and ß-pinene (0.81 %) were shown to be the major constituents of this oil. Adult worms of S. mansoni were incubated with different concentrations of the essential oil (1, 10, 100, 250, 500, and 1000 µg/mL) and of its constituents rotundifolone (0.7, 3.54, 7.09, 70.96, 177.4, 354.8, and 700.96 µg/mL), limonene (43.75 µg/mL), trans-caryophyllene (7.3 µg/mL), and ß-pinene (4.03 µg/mL). No schistosomicidal activity was identified at the trans-caryophyllene and ß-pinene concentrations studied. However, use of the essential oil (10 µg/mL), rotundifolone (7.09 µg/mL), and limonene (43.75 µg/mL) resulted in decreased worm motility continuing until 96 hours of observation. At higher concentrations (100 and 70.96 µg/mL, respectively), both the essential oil and rotundifolone caused mortality among adult worms of S. mansoni. The positive control praziquantel caused the death of all parasites after 24 h of evaluation. The results from this study suggest that the essential oil of Mentha x villosa presents schistosomicidal efficacy.

Antinociceptive activity of the chloroform fraction of Dioclea virgata (Rich.) Amshoff (Fabaceae) in mice.

Acute treatment with the chloroform fraction of Dioclea virgata (Rich.) Amshoff (CFDv) in mice produced decreased ambulation and sedation in the behavioral pharmacological screening. Doses of 125 and 250 mg/kg CFDv decreased latency of sleep onset in the test of sleeping time potentiation. In the open field, animals treated with CFDv reduced ambulation and rearing (250 mg/kg), as well as defecation (125; 250 mg/kg). Regarding the antinociceptive activity, CFDv (125, 250, 500 mg/kg) increased latency to first writhing and decreased the number of writhings induced by acetic acid. In the formalin test, CFDv (250 mg/kg) decreased paw licking time in the first and second phases indicating antinociceptive activity that can be mediated both peripherally and at the central level. CFDv did not affect motor coordination until 120 minutes after treatment. CFDv shows psychopharmacological effects suggestive of CNS-depressant drugs with promising antinociceptive activity.

Non-pharmacological therapy and complementary and alternative medicine in fibromyalgia.

Fibromyalgia is a chronic painful syndrome that affects up to 5% of the world population. It is associated with sleep and mood disorders, fatigue, and functional disability. Its pathogenesis involves a disorder of the central modulation of pain, impairment of the descending inhibitory system, and hyperactivity of substance P. Because of the extensive symptomatology of patients with fibromyalgia and its multifactorial pathogenesis, its ideal treatment requires a multidisciplinary approach including the association of pharmacological and non-pharmacological therapies. The pharmacological therapy currently recommended for the syndrome includes antidepressants, calcium-channel modulators, muscle relaxants, and analgesics. In most cases, the non-pharmacological treatment consists of patient education, supervised aerobic physical activity, and cognitive-behavioral therapy. However, many patients do not respond satisfactorily, or have side effects associated with the long-term use of drugs, in addition to reporting difficulties in adhering to a therapy based on exercises and physical medicine. Thus, physicians and patients are increasingly interested in an alternative and complementary therapy for fibromyalgia. This review approaches the different therapeutic modalities used in fibromyalgia, emphasizing the evidence of non-pharmacological therapy and use of alternative and complementary medicine for these patients.

Antinociceptive and toxicological effects of Dioclea grandiflora seed pod in mice.

The acute treatment of mice with an ethanolic extract from the seed pod of Dioclea grandiflora (EDgP) at doses of 75, 150 and 300 mg/kg by intraperitoneal administration produced a significant antinociceptive effect as displayed by the acetic acid-induced writhing test and the formalin test. The antinociception was observed through the first (neurogenic pain) and second (inflammatory pain) phases in the formalin test. The hot plate test did not show an increase in the antinociceptive latency whereas the motor performance was affected by the administration at 300 mg/kg at the beginning (30 minutes) of the observation period but not at later periods (60 and 120 minutes). These results suggest that EDgP has a central antinociceptive action and a possible anti-inflammatory activity in mice.

Rosewood oil induces sedation and inhibits compound action potential in rodents.

AIM OF THE STUDY: Aniba rosaeodora is an aromatic plant which has been used in Brazil folk medicine due to its sedative effect. Therefore, the purpose of the present study was to evaluate the sedative effect of linalool-rich rosewood oil in mice. In addition we sought to investigate the linalool-rich oil effects on the isolated nerve using the single sucrose-gap technique. MATERIALS AND METHODS: Sedative effect was determined by measuring the potentiation of the pentobarbital-induced sleeping time. The compound action potential amplitude was evaluated as a way to detect changes in excitability of the isolated nerve. RESULTS: The results showed that administration of rosewood oil at the doses of 200 and 300 mg/kg significantly decreased latency and increased the duration of sleeping time. On the other hand, the dose of 100 mg/kg potentiated significantly the pentobarbital action decreasing pentobarbital latency time and increasing pentobarbital sleeping time. In addition, the effect of linalool-rich rosewood oil on the isolated nerve of the rat was also investigated through the single sucrose-gap technique. The amplitude of the action potential decreased almost 100% when it was incubated for 30 min at 100 microg/ml. CONCLUSIONS: From this study, it is suggested a sedative effect of linalool-rich rosewood oil that could, at least in part, be explained by the reduction in action potential amplitude that provokes a decrease in neuronal excitability.

Study of anticonvulsant effect of citronellol, a monoterpene alcohol, in rodents.

Citronellol is one monoterpene alcohol, which is present in the essential oils of various aromatic plant species. This study evaluated the neuroprotective activity of citronellol on pentylenetetrazol- and picrotoxin-induced convulsions and maximal electroshock-induced seizures in mice. Administration of citronellol significantly reduced the number of animals of convulsion induced by pentylenetetrazol and eliminated the extensor reflex of maximal electroshock-induced seizures test in about 80% of the experimental animals. In addition, administration of citronellol showed protection in the pentylenetetrazol and picrotoxin tests by increasing the latency of clonic seizures. We also investigated the effect of citronellol in the rat isolated nerve using the single sucrose-gap technique. We showed that the amplitude of the compound action potential decreased more than 90% when the monoterpene was incubated for 30 min at 6.4 mM and we did not verify any effect on the repolarization of the compound action potential. Taken together, our results demonstrated an anticonvulsant activity of the citronellol that could be, at least in part, explained by the diminution of the action potential amplitude.

Neuroleptic-like properties of the chloroform extract of Maytenus obtusifolia MART. roots.

The effects of the chloroform extract of Maytenus obtufisolia MART. roots on locomotor activity, catalepsy test, amphetamine-induced toxicity and active-avoidance test were studied. The results revealed that the extract caused a decrease in spontaneous activity and induced catalepsy in mice up to 240 min. The extract significantly protected the mice against amphetamine-induced toxicity and decreased the conditioned response in rats, in a dose-related manner. The results suggest that the chloroform extract of Maytenus obtusifolia MART. possesses neuroleptic-like properties.

Anxiolytic-like effects of rose oil inhalation on the elevated plus-maze test in rats.

The effect of rose oil inhalation (1.0%, 2.5%, and 5.0% w/w) on the elevated plus-maze (EPM) test was investigated in adult male rats and compared with the effect of diazepam (DZP) (1.0 and 2.0 mg/kg) administered intraperitoneally 30 min before testing. Exposure to rose oil produced an anxiolytic-like effect similar to DZP (anxiolytic reference drug). Thus, at some concentrations, rose oil significantly increased the number of visits to and time spent in the open arms of the EPM. Anxiolytic-like properties of rose oil were observed using the EPM, being consistent with other behavioral and clinical studies.

Evaluation of long-term exposure to Mikania glomerata (Sprengel) extract on male Wistar rats' reproductive organs, sperm production and testosterone level.

Many plant substances are known for their interference with the reproductive system. Mikania glomerata is a plant popularly used to treat respiratory diseases and is reported to have flavonoids and coumarin, which have been shown to have antifertility activity in male dogs and female rats, respectively. This work analyzes the effect of a high dose of M. glomerata extract administered during the spermatogenic cycle of rats. Adult Wistar rats were treated with 1 mL of a M. glomerata extract at a dose level of 3.3 g/kg of body weight for 52 days. Body and organ weights, sperm production, circulating testosterone level and food consumption were evaluated. The results showed that the administration of the M. glomerata extract during the rat spermatogenic cycle did not significantly alter the body and organ weights nor did it interfere with gamete production, serum testosterone level or food intake.