Anti-inflammatory and redox-protective activities of citronellal.

The anti-inflammatory and redox protective effects of the citronellal (CT) were evaluated using in vivo and in vitro tests. Intraperitoneal (i.p.) administration of CT (50, 100, and 200 mg/kg) inhibited (p < 0.05) the carrageenan-induced leukocyte migration to the peritoneal cavity. Additionally, the carrageenan- and arachidonic acid-induced rat hind paw edema was significantly inhibited (p < 0.05) by i.p. administration of 100 and 200 mg/kg of the compound. When the redox activity was evaluated, CT (200 mg/kg) significantly reduced hepatic lipoperoxidation (p < 0.001), as well as oxidation of plasmatic (p < 0.05) and hepatic (p < 0.01) proteins. The results of the present study support the hypothesis that CT possesses anti-inflammatory and redox protective activities. It is suggested that its effects are associated with the inhibition of the enzymes in the arachidonic acid pathway, which prevent cell migration by inhibiting leukotriene production, edema formation and the increase of reactive oxygen species in tissues. Therefore, CT is of potential benefit to manage inflammatory disorders and correlated damages caused by oxidant agents.

Nociception alterations precede motor symptoms in a progressive model of parkinsonism induced by reserpine in middle-aged rats.

Nociception alterations are frequent non-motor symptoms of the prodromal phase of Parkinson's disease (PD). The period for the onset of symptoms and the pathophysiological mechanisms underlying these alterations remain unclear. We investigated the course of nociception alterations in a progressive model of parkinsonism induced by reserpine (RES) in rats. Male Wistar rats (6-7 months) received 5 or 10 subcutaneous injections of RES (0.1 mg/kg) or vehicle daily for 20 days. Motor evaluation and nociceptive assessment were performed throughout the treatment. At the end of the treatment rats were euthanized, the brains removed and processed for immunohistochemical analysis (TH and c-Fos). The RES-treated rats exhibited an increased nociceptive response to mechanical and chemical stimulation in the electronic von Frey and formalin tests, respectively. Moreover, these alterations preceded the motor impairment observed in the catalepsy test. In addition, the RES treatment reduced the TH-immunoreactivity in the ventral tegmental area (VTA) and increased the c-Fos expression in the ventral-lateral periaqueductal gray (vlPAG), rostral ventral medulla (RVM) and dorsal raphe nucleus (DRN) after noxious stimuli induced by formalin. Taken together, our results reinforce that nociceptive changes are one of the early signs of PD and monoamine depletion in basal ganglia can be involved in the abnormal processing of nociceptive information in PD.

Antinociceptive effects of citronellal in formalin-, capsaicin-, and glutamate-induced orofacial nociception in rodents and its action on nerve excitability.

AIMS: To evaluate the antinociceptive effects of citronellal (CTL) on formalin-, capsaicin-, and glutamate-induced orofacial nociception in mice and to investigate whether such effects might involve a change in neural excitability. METHODS: Male mice were pretreated with CTL (50, 100, and 200 mg/kg, ip), morphine (5 mg/kg, ip), or vehicle (distilled water plus one drop of Tween 80 0.2%) before formalin (20 microL, 2%), capsaicin (20 microL, 2.5 microg) or glutamate (40 microL, 25 microM) injection into the right vibrissa. Sciatic nerve recordings were made using the single sucrose gap technique in rats. The data obtained were analyzed by ANOVA followed by Dunnett's test for the behavioral analyses and by the Student t test for CAP evaluation. RESULTS: Pretreatment with CTL was effective in reducing nociceptive face-rubbing behavior in both phases of the formalin test, which was also naloxone-sensitive. CTL produced significantly antinociceptive effect at all doses in the capsaicin- and glutamate- tests. Rota-rod testing indicated that such results were unlikely to be provoked by motor abnormality. Recordings using the single sucrose gap technique revealed that CTL (10 mM) could reduce the excitability of the isolated sciatic nerve through a diminution of the compound action potential amplitude by about 42.4% from control recordings. CONCLUSION: These results suggest that CTL might represent an important tool for management and/or treatment of orofacial pain.

Antinociceptive and anti-inflammatory effects of Costus spicatus in experimental animals.

CONTEXT: Costus spicatus Swartz (Costaceae), commonly called "cana-do-brejo'" in Brazil's northeast, is a medicinal plant found in wet coastal forests. In folk medicine an infusion of the aerial parts is taken to treat inflammation and pain. OBJECTIVE: The methanol extract obtained from the leaves of Costus spicatus (MECs) was evaluated for antinociceptive and anti-inflammatory activities. METHODS: Analgesic and anti-inflammatory activities were studied by measuring nociception through acetic acid, formalin, and hot-plate tests, while inflammation was induced by carrageenan. All experiments were conducted with experimental animals. RESULTS AND DISCUSSION: Following oral administration, MECs (100, 200, and 400 mg/kg) significantly reduced the number of writhes (52.8, 43.1, and 55.3%, respectively) in the writhing test and the number of paw licks during phase 1 (61.9, 54.1, and 92.1%) and phase 2 (62.5, 82.9, and 98.1%, all doses) during the formalin test when compared to the control group animals. The reaction time during the hot-plate test was increased significantly and was dose-dependent, whereas pretreatment with naloxone rigorously reduced the analgesic potential of MECs, which suggested participation of the opioid system in the modulation of pain induced by MECs. Such results were unlikely to be provoked by motor abnormality, as MECs-treated mice did not exhibit any performance alteration during the Rota-rod test. The administration of 200 and 400 mg/ kg (i.p.) of MECs exhibited an anti-inflammatory effect during the carrageenan test, which was based on interference with inflammatory mediator synthesis. CONCLUSION: We conclude that MECs has antinociceptive and anti-inflammatory activities in rodents.

Bioassay-guided evaluation of antioxidant and antinociceptive activities of carvacrol.

We examined the antioxidant properties in vitro and the antinociceptive effect of carvacrol (CARV) in several models of pain in mice. CARV presented a strong antioxidant potential according to the TRAP/TAR evaluation; it also presented scavenger activity against nitric oxide and prevented lipid peroxidation in vitro. In mice, when evaluated against acetic acid-induced abdominal writhing, CARV (25, 50 and 100 mg/kg, i.p.) reduced (p < 0.001) the number of writhing compared to the control group, without opioid participation. In the formalin test, CARV also significantly inhibited both the early (neurogenic pain) and the late (inflammatory pain) phases of formalin-induced licking, with inhibition percentage values of 56.8% (100 mg/kg) for the neurogenic phase and 41.2% (25 mg/kg), 73.8% (50 mg/kg) and 99.7% (100 mg/kg) for the inflammatory phase. CARV also produced a significant inhibition of the pain caused by capsaicin (63.1, 67.1 and 95.8%, p < 0.001) and glutamate (46.4, 61.4 and 97.9%, p < 0.01). When assessed in a thermal model of pain, CARV (100 mg/kg, i.p.) caused a significant increase (p < 0.05) in the latency response on the hot-plate test. Such results were unlikely to be provoked by motor abnormality. Together, these results indicate that the properties of CARV should be more thoroughly examined in order to achieve newer tools for management and/or treatment of painful conditions, including those related to pro-oxidant states.

Hyptis pectinata gel prevents alveolar bone resorption in experimental periodontitis in rats

Hyptis pectinata (L.) Poit., Lamiaceae, is an aromatic, abundant and broadly used plant species in Sergipe to treat oral and gastrointestinal pain and inflammation. The aim of the present study was to analyze the relation between periodontitis and changes in the corporal mass and alveolar bone structure after induction of experimental periodontal disease in rat treated or not treated with H. pectinata gel at 5% (GS5%) and 10% (GS10%), comparing their effects with doxycycline gel at 10% (D10%, positive control), vehicle gel (negative control) and a group with experimental periodontal disease, but non-treated. The gels were locally applied in the gingival region immediately after the experimental periodontal disease induction by ligature (3×/day, 11 days). Bone destruction was determined through clinical exam, histopathological analysis and cone beam computed tomography of the experimental animals (n = 36). After 11 days of periodontitis induction, all groups that received ligature presented a decrease in the corporal mass, except to the naïve group (without experimental periodontal disease) (p < 0.05). Computed tomography results have shown healthy bone structure in the group I and bone resorption for the test groups. Histopathological analysis confirmed the healthy bone structure for naïve group animals, while the test groups exhibited bone loss in several degrees. In particular, the non-treated group animals had an intense inflammatory process. When the periodontium of the animals treated with GS10% was histopathologically analyzed, insertion periodontium was preserved. The results for these groups were significantly different of the vehicle group (p < 0.05). According to the results, the gel based in the aqueous extract of H. pectinata at 10% can prevent bone loss in experimental periodontal disease similarly to doxycycline 10%.

Phytochemical screening, antinociceptive and anti-inflammatory activities of Chrysopogon zizanioides essential oil

Chrysopogon zizanioides (L.) Roberty, Poaceae, is a plant widely used in northeast Brazil in folk medicine for the treatment of various pathological conditions, including inflammatory pain. The present study evaluated the antinociceptive and anti-inflammatory effects of C. zizanioides essential oil (EO) in rodents. EO was further characterized by GC/MS. The major components of EO were identified as khusimol (19.57%), E-isovalencenol (13.24%), α-vetivone (5.25%), β-vetivone (4.87%) and hydroxy-valencene (4.64%). Following intraperitoneal injection (i.p.), EO at 50 and 100 mg/kg significantly reduced the number of writhes (51.9 and 64.9%, respectively) and the number of paw licks during phase 2 (56.7 and 86.2%, respectively) of a formalin model when compared to control group animals. However, EO-treated mice were ineffective at all doses in hot-plate and rota-rod tests. The EO inhibited the carrageenan-induced leukocyte migration to the peritoneal cavity in a dose-dependent manner (34.7, 35.4, and 62.5% at doses of 25, 50 and 100 mg/kg, respectively). In the paw edema test, the EO (100 mg/kg) inhibited all three phases of the edema equally well, suggesting that the EO has a non-selective inhibitory effect on the release or actions of these mediators. Our results suggest possible antinociceptive and anti-inflammatory effects of the EO.

Ocimum basilicum leaf essential oil and (-)-linalool reduce orofacial nociception in rodents: a behavioral and electrophysiological approach

The present study investigated the antinociceptive effects of Ocimum basilicum L. (Lamiaceae) leaf essential oil (LEO) and (-)-linalool (LIN) in formalin (2 percent)-, glutamate (25 µM)- and capsaicin (2.5 µg)- induced orofacial nociception models in mice. The involvement of these substances was further evaluated on the neuronal excitability of the hippocampal dentate gyrus. Male mice (n=8/group) were pretreated separately with LEO and by LIN (50, 100, and 200 mg/kg, i.p.), morphine (5 mg/kg, i.p.) and vehicle (saline + Tween 80 0.2 percent), before injection of nociceptive agent into the right upper lip (perinasal area). The LEO and LIN reduced the nociceptive face-rubbing behaviour in both phases on formalin test. LEO and LIN, at high doses, produced significantly antinociceptive effect in the capsaicin and glutamate tests. In hippocampal slices, LEO inhibited the population spike generated by stimulation of the hylus (antidromic stimulation), with an IC50 of 0.1±0.05 mg/mL. This response was reversibly blocked by lidocaine (0.5 mg/mL), a known voltage-dependent sodium channel antagonist and by LIN (0.5 mg/mL). Our results suggest that LEO and LIN modulate neurogenic and inflammatory pain in the tests of orofacial nociception induced by formalin, capsaicin and glutamate. Part of these effects may be associated with decreased peripheral and central neuronal excitability.

p-Cymene reduces orofacial nociceptive response in mice

This study investigated the possible antinociceptive effect of p-cymene in different tests of orofacial nociception. The animals (mice) were pretreated (i.p.) with p-cymene (25, 50, 100 mg/kg), morphine (5 mg/kg), or vehicle (0.2 percent Tween 80+saline), and were then subsequently administered, subcutaneously into their upper lip: formalin, capsaicin, and glutamate. The nociceptive behavior response was characterized by the time in s that the mice remained rubbing the orofacial region, for a period of 40 min in the formalin test (first phase, 0-6 min; and second phase, 21-40 min), and for 42 and 15 min in the capsaicin and glutamate tests, respectively. To verify the possible opioid involvement in the antinociceptive effects, naloxone (i.p.) was administered into the mice 15 min prior to the pretreatment with p-cymene (100 mg/kg). Finally, whether or not the p-cymene evoked any change in motor performance in the Rota-rod test was evaluated. The results showed that the treatment with p-cymene, at all doses, reduced (p<0.001) the nociceptive behavior in all nociception tests. The antinociceptive effect of p-cymene was antagonized by naloxone (1.5 mg/kg). Additionally, mice treated with p-cymene did not show any change in motor performance. In conclusion, p-cymene attenuated orofacial nociception, suggesting an involvement of the opioid system in this effect. Thus, p-cymene might represent an important biomolecule for management and/or treatment of orofacial pain.

Bioassay-guided evaluation of central nervous system effects of citronellal in rodents

The central nervous system (CNS) depressant and anticonvulsant activities of citronellal (CT) were investigated in animal models. The CT in doses of 100, 200 and 400 mg/kg injected by i.p. route in mice caused a significant decrease in the motor activity of animals when compared with the control group. The highest dose of CT significantly reduced the remaining time of the animals on the Rota-rod apparatus up to 2 h. Additionally, CT at doses 100, 200 and 400 mg/ kg (i.p.) was also capable to promote an increase of latency for development of convulsions induced by pentylenetetrazole (PTZ). It was efficient in prevents the tonic convulsions induced by maximal electroshock (MES) in doses of 200 and 400 mg/kg, resulting in 30 and 40 percent of protection, respectively. This compound was also capable to promote an increase of latency for development of convulsions induced by picrotoxin (PIC) at 400 mg/kg. In the same way, the anticonvulsant effect of CT was affected by pretreatment with flumazenil, a selective antagonist of benzodiazepine site of GABA A receptor. These results suggest a possible CNS depressant and anticonvulsant activities.

Anti-inflammatory and redox-protective activities of citronellal

The anti-inflammatory and redox protective effects of the citronellal (CT) were evaluated using in vivo and in vitro tests. Intraperitoneal (i.p.) administration of CT (50, 100, and 200 mg/kg) inhibited (p < 0.05) the carrageenan-induced leukocyte migration to the peritoneal cavity. Additionally, the carrageenan- and arachidonic acid-induced rat hind paw edema was significantly inhibited (p < 0.05) by i.p. administration of 100 and 200 mg/kg of the compound. When the redox activity was evaluated, CT (200 mg/kg) significantly reduced hepatic lipoperoxidation (p < 0.001), as well as oxidation of plasmatic (p < 0.05) and hepatic (p < 0.01) proteins. The results of the present study support the hypothesis that CT possesses anti-inflammatory and redox protective activities. It is suggested that its effects are associated with the inhibition of the enzymes in the arachidonic acid pathway, which prevent cell migration by inhibiting leukotriene production, edema formation and the increase of reactive oxygen species in tissues. Therefore, CT is of potential benefit to manage inflammatory disorders and correlated damages caused by oxidant agents.

Anticonvulsant evaluation of Rauvolfia ligustrina Willd. ex Roem. & Schult., Apocynaceae, in rodents / Avaliação anticonvulsivante de Rauvolfia ligustrina Willd. ex Roem. & Schult., Apocynaceae, em roedores

The Aim of this study was to evaluated the effects of the ethanol extract of Rauvolfia ligustrina Willd. ex Roem. & Schult., Apocynaceae, roots (EER) in animal models of epilepsy. The EER increased the latency for convulsions significantly different from control (p<0,05) and in the PTZ induced convulsions test on 62,5 mg/kg (i.p.) decreased mortality. This effect was blocked by flumazenil administration, suggesting an involvement of GABAergic system in the anticonvulsant activity of EER. The EER had a moderate effect only against PIC- or STR-induced convulsions at doses 125 and 250 mg/kg. But in the MES test it did not demonstrate effect on this animal model. Therefore, the EER reduced the development of PTZ-induced kindling in both experimental groups. It also significantly (p<0.05) decreased the latency for convulsions and reduced its percentage. Our results suggest that EER owns anticonvulsant property.

O presente estudo buscou avaliar os efeitos do extrato etanólico das raízes de Rauvolfia ligustrina Willd. ex Roem. & Schult., Apocynaceae, (EER) e sua possível atividade anticonvulsivante em roedores. No teste das convulsões induzidas pelo pentilenotetrazol (PTZ) os animais tratados com EER, 250 mg/kg (i.p.), apresentaram aumento significativo (p<0,05) da latência para o aparecimento das convulsões (328,9±47,5) quando comparado aos do grupo controle (103,5±21,8) e reduziu o número de óbitos. Esse efeito foi bloqueado pela administração do flumazenil. O EER produziu aumento significativo (p<0,05) na latência nos testes da picrotoxina (PIC) e da estricnina (EST), nas maiores doses. No modelo do eletrochoque auricular o EER não produziu alterações significativas em nenhum dos parâmetros avaliados. Entretanto, no modelo do abrasamento induzido pelo PTZ, a administração com o EER produziu um efeito protetor, atenuando de forma significativa (p<0,05) o desenvolvimento e a severidade das crises convulsivas. Os resultados, sugerem que o EER induziu efeito anticonvulsivante em roedores e que o sistema GABAérgico pode estar envolvido nessa resposta.

Antinociceptive and anti-inflammatory effects of the essential oil of Eugenia candolleana DC., Myrtaceae, on mice / Efeito antinociceptivo e antiinflamatório do óleo essencial de Eugenia candolleana DC. (Myrtaceae) em roedores

Eugenia candolleana DC. (Myrtaceae), commonly known as "murta" or "murtinha", is a plant species without any chemical or pharmacological study described in the literature. It has been popularly used for the treatment of pain and fever. This report aimed to investigate the possible antinociceptive and anti-inflammatory effects of the essential oil extracted from fresh leaves of Eugenia candolleana DC. (EOEc) in rodents. Following intraperitoneal injection, EOEc (25, 50 and 100 mg/kg) reduced the number of writhes significantly in a writhing test and the number of paw licks during phase two of formalin test (p < 0.001). However, administration of EOEc did not alter the time of reaction in hot plate test. Furthermore, EOEc inhibited (p < 0.01) the carrageenan-induced leukocyte migration to the peritoneal cavity. These results indicate antinociceptive and anti-inflammatory properties of EOEc probably mediated via inhibition of prostaglandin synthesis or other peripherally pathway.

Eugenia candolleana DC. (Myrtaceae), conhecida popularmente como "murta" ou "murtinha", é uma espécie vegetal sem estudos químicos e farmacológicos descritos na literatura, distribuída no Nordeste brasileiro, principalmente, na Zona da Mata. Na medicina popular do Estado de Sergipe é utilizada no tratamento de distúrbios febris e da dor. O presente estudo buscou avaliar as possíveis atividades antinociceptiva e antiinflamatória do óleo essencial extraído das folhas de E. candolleana DC (OEEc) em roedores. A administração intraperitoneal (i.p.) do OEEc (25, 50 e 100 mg/kg) reduziu significativamente o número de contorções no teste das contorções abdominais e a duração da lambida da pata na segunda fase do teste da formalina (p < 0,001). Entretanto, a administração do OEEc não alterou o tempo de reação no teste da placa quente. No experimento de peritonite induzido por carragenina, o OEEc reduziu de forma significativa (p < 0,01) a migração de leucócitos para a cavidade peritoneal. Os resultados obtidos sugerem que o OEEc possui ação antinociceptiva, provavelmente mediado por mecanismos periféricos, e ação antiinflamatória.