Evaluation of the antinociceptive activity of extracts of Sonchus oleraceus L. in mice

Ethnopharmacological relevance

Sonchus oleraceus L. has been used to relieve pain in Brazilian folk medicine.

Aim of the study

Sonchus oleraceus L. has been used to relieve pain in Brazilian folk medicine. This study was conducted to establish the antinociceptive properties of hydroethanolic and dichloromethane extracts from aerial parts of Sonchus oleraceus in mice using chemical and thermal models of nociception.

Materials and methods

The formalin, hot plate, and tail immersion tests as well as acetic acid-induced writhing were used to investigate the antinociceptive activity in mice.

Results

Given orally, the extracts at test doses of 30–300 mg/kg, produced significant inhibitions on chemical nociception induced by intraperitoneal acetic acid and subplantar formalin since decreased the number of writhing episodes and the time licking. Treatment with the extracts in the same doses produced a significant increase of the reaction time in tail immersion and in the hot plate test. The extracts administered at 300 mg/kg, p.o. had a stronger antinociceptive effect than indomethacin (5 mg/kg, p.o.) and morphine (10 mg/kg, p.o.).

Conclusion

The extracts of Sonchus oleraceus markedly demonstrated antinociceptive action in mice, which supports previous claims of its traditional use.     

Antinociceptive activity of Amaranthus spinosus in experimental animals

Aim of the study

50% ethanol extract (ASE) of Amaranthus spinosus (whole plant) has been evaluated for antinociceptive and antiinflammatory activities.

Materials and methods

Analgesic and antiinflammatory activities were studied by measuring nociception by formalin, acetic acid, hot plate, tail immersion method while inflammation was induced by carrageenan.

Results

ASE had significant dose dependent percentage protection against acetic acid (0.6% of 10 ml) induced pain and the effects were also compared to aspirin, morphine and naloxone while formalin induced pain (0.05 ml of 2.5%) was significantly blocked only at higher dose (400 mg/kg) in first phase. ASE significantly blocked pain emanating from inflammation at all the doses in second phase. The reaction time in hot plate was increased significantly and dose dependently where as pretreatment with naloxone rigorously reduced the analgesic potentials of ASE. Further in tail immersion test the same dose dependent and significant activity was observed. Aspirin had no effect on thermal induced pain i.e. hot plate and tail immersion tests but showed an effect on writhing test.

Conclusions

Our investigation show that Amaranthus spinosus possess significant and dose dependant antiinflammatory activity, it has also central and peripheral analgesic activity.     

Antinociceptive effects of ethanolic extract from the flowers of Acmella oleracea (L.) R.K. Jansen in mice

Ethnopharmacological relevance

In Brazil, Acmella oleracea (L.) R.K. Jansen, popularly known as “jambu”, has been used by some communities from Amazon region to treat toothache. In this study we examined the antinociceptive effect of the ethanolic extract obtained from the flowers of Acmella oleracea (EEAO) in animal models of nociceptive (chemical and thermal) and neuropathic (partial sciatic nerve ligation) pain.

Materials and methods

Adult male mice were treated by intraperitoneal route (i.p.) with EEAO before the induction of nociceptive response by formalin, capsaicin and cinnamaldehyde, thermal heat hyperalgesia (hot plate test) and mechanical allodynia (traumatic sciatic nerve injury). Acute toxicity and non-specific sedative effects were evaluated.

Results

EEAO (10, 30 and 100 mg/kg) reduced both neurogenic and inflammatory phases of the formalin- and also capsaicin- and cinnamaldehyde-induced orofacial nociception. Interestingly, EEAO at 100 mg/kg (i.p.) also reversed capsaicin-induced heat hyperalgesia assessed as the latency to paw withdrawal in the hot plate test. Also in the hot plate test, paw withdrawal latency was increased by EEAO (100 mg/kg) and this response was only partially reversed by naloxone. Furthermore, EEAO (100 mg/kg) also reduced mechanical allodynia caused by partial sciatic nerve ligation for 3 h. The estimated LD50 value was 889.14 mg/kg and EEAO did not alter the locomotion of animals in the open-field test.

Conclusion

Taken together, our data show that EEAO produces prevalent antinociceptive effects and does not cause adverse effects. The presence of N-alkylamides, including spilanthol, suggests that the therapeutic effect of EEAO is related to its highest anesthetic activity.     

Venom's antinociceptive property in the primitive ant Dinoponera quadriceps

Ethnopharmacological relevance

In northeastern Brazil, Dinoponera (Ponerinae) ants macerate are used to treat ear ache and its sting, rheumatism, and back pain. Such a popular use is a relevant fact that called for experimental evaluation of the antinociceptive activity of Dinoponera venom.

Materials and methods

Dinoponera quadriceps venom (DqV; 5–500 μg/kg; i.v.) or morphine (3.4 mg/kg; s.c.) were evaluated in mice models of nociception (n=8 animals/group). Negative controls received sterile saline (0.9% NaCl; i.v.).

Results

DqV showed 64% protein content and exhibited antinociceptive activity, without affecting motor function, in the tests: formalin (72%), writhing (52%), von Frey (71%) and hot plate (45%). The antinociceptive activity was abolished under protein denaturant conditions.

Conclusions

This study provided the first demonstration of the antinociceptive property of Dinoponera quadriceps venom in mice models of chemical, mechanical and thermal nociception, corroborating the popular use and suggesting its potential therapeutic utilization in painful conditions.     

Anti-inflammatory and anti-nociceptive properties of Prunus padus

Ethnopharmacological relevance

Prunus padus Linne has been widely used as a traditional medicine, with beneficial effects in numerous diseases, including stroke, neuralgia and hepatitis. In this study, we demonstrated anti-inflammatory and anti-nociceptive activities of the methylene chloride fraction of P. padus (MPP).

Materials and methods

In vitro studies, the anti-inflammatory effects of MPP were examined using IFN-γ/LPS-activated murine peritoneal macrophage model. To confirm the anti-inflammatory effects of MPP in vivo, trypsin-induced paw edema test was also conducted. The anti-nociceptive activities of MPP were measured using various experimental pain models including thermal nociception methods such as the tail immersion test and the hot plate test as well as chemical nociception methods like acetic acid-induced writhing test and formalin test. To determine whether analgesic activity of MPP is connected with the opioid receptor, we carried out combination test with naloxone, a nonselective opioid receptor antagonist.

Results

In the current study, MPP showed potent inhibitory effect on IFN-γ/LPS-induced NO production. MPP also suppressed not only iNOS enzyme activity but also iNOS expression. Moreover, MPP inhibited COX-2 expression dose dependently. IFN-γ/LPS stimulation induced the translocation of NF-κB to nucleus but it was attenuated in the presence of MPP. In vivo study revealed that MPP could reduce paw volume after subplantar injection of trypsin. In addition, MPP showed potent analgesic activities both thermal and chemical nociception compared to tramadol and indomethacin. Furthermore, pre-treatment of naloxone slightly suppress the analgesic activity of MPP indicating that MPP acts as a partial opioid receptor agonist.

Conclusions

In the present study, MPP showed potent anti-inflammatory properties through not only by suppressing various inflammatory mediators in vitro, but reducing the inflammatory edema in vivo. MPP also exhibited strong anti-nociceptive activities via both central and peripheral mechanism by acting as a partial opioid agonist. Based on these results we suggest that P. padus has the potential to provide a therapeutic approach to inflammation-mediated chronic diseases as an effective anti-inflammatory agent and painkiller.     

The antinociceptive and anti-inflammatory activities of Piptadenia stipulacea Benth. (Fabaceae)

Aim

In this study, we attempted to identify the possible antinociceptive and anti-inflammatory actions of the aqueous phase, the ethyl acetate phase and one unknown flavonoid obtained from aerial parts of Piptadenia stipulacea, known in Brazil as “jurema-branca”, “carcará” and “rasga-beiço”.

Materials and methods

Aerial parts of Piptadenia stipulacea were used and after fractionation, the flavonoid FGAL was obtained. Experiments were conducted on Swiss mice using the acetic acid-induced writhing test, the hot plate test, the formalin-induced pain test and zymosan A-induced peritonitis test.

Results

The aqueous and ethyl acetate phases (p.o., 100 mg/kg); and the flavonoid FGAL (p.o. and i.p. at 100 μmol/kg), reduced the nociception produced by acetic acid, by 49.92%, 54.62%, 38.97% and 64.79%, respectively. In vivo inhibition of nociception by the ethyl acetate phase (100 mg/kg, p.o.) in the hot plate test was favorable, indicating that this fraction exhibited central activity. The ethyl acetate phase (100 mg/kg, p.o.) reduced the formalin effects in both phases by 28.51% and 55.72%, respectively. Treatment with the aqueous phase (100 mg/kg, p.o.) and FGAL (100 μmol/kg, i.p.) only protected the second phase by 69.76% and 68.78%, respectively. In addition, it was observed in the zymosan A-induced peritonitis test that the aqueous phase, the ethyl acetate phase and the FGAL exhibited anti-inflammatory activity, reducing significantly the number of recruit cells by 35.84%, 37.70% and FGAL (1), respectively.

Conclusions

These data demonstrate that the FGAL elicits pronounced antinociceptive activity against several pain models. The actions of this flavonoid probably are due to antioxidative properties. However, pharmacological and chemical studies are continuing in order to characterize the mechanism(s) responsible for this antinociceptive action and also to identify other active substances present in Piptadenia stipulacea.     

Anti-hyperalgesic activity of corilagin,a tannin isolated from Phyllanthus niruri L. (Euphorbiaceae)

Ethnopharmacological relevance

Corilagin (β-1-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-d-glucose) is a tannin isolated from Phyllanthus niruri (Euphorbiaceae). This plant is well known for their therapeutic purposes to treat several diseases associated with dolorous process and are used in several ethno-medicines in tropical and subtropical countries.

Aim of the study

This study was designed to evaluate the anti-hyperalgesic activity of corilagin using chemically and thermally based nociception models in mice.

Materials and methods

Corilagin was isolated from Phyllanthus niruri (Euphorbiaceae) by extraction and chromatographic procedures and the anti-hyperalgesic activity was evaluated by using writhing, formalin, capsaicin, glutamate and hot plate tests in mice.

Results

Corilagin presented activity in acetic acid model with the ID₅₀ calculated value of 6.46 (3.09–13.51) being about 20.6 fold more potent than acetylsalicylic acid. It also exhibited activity against the first phase of formalin test with ID₅₀ value of 18.38 (15.15–22.59) μmol/kg. In the capsaicin and glutamate models, corilagin demonstrated significant activity at the 3 mg/kg.

Conclusion

The experimental data demonstrated that corilagin exhibits anti-hyperalgesic activity that may be due to interaction with the glutamatergic system.     

Antinociceptive activity of aqueous extract and isolated compounds of Lithrea molleoides

Ethnopharmacological relevance

Lithrea molleoides (Vell.) Engl. (Anacardiaceae) is a medicinal plant commonly used in traditional medicine in South America.

Aim of the study

In the present study, the in vivo antinociceptive effect of L. molleoides' aqueous extract and its isolated compounds has been investigated.

Materials and Methods

Antinociceptive activity was evaluated through writhing, formalin and hot plate tests in mice. The phytochemical analysis was performed.

Results

The extract produced significant inhibition on nociception induced by acetic acid (ED50: 8.7 mg/kg, i.p.) and formalin (ED50: 7.7 mg/kg, i.p.) administered intraperitoneally and also orally. Yohimbine diminished the activity of the extract in the acetic acid test meanwhile haloperidol enhanced its effect. Two majority compounds, shikimic and vanillic acid were active in chemical nociceptive models used in this work, producing the highest inhibition of the writhing response at a dose of 30 mg/kg i.p. (55.4% and 57.1%, respectively) meanwhile at 100 mg/kg p.o. produced a slight response (23.3% and 23.9%, respectively).

Conclusions

These results suggest that L. molleoides' aqueous extract produced antinociception possibly related to the presence of shikimic and vanillic acid. The adrenergic and dopaminergic systems seem to be involved in the mechanism of antinociception of the extract.     

Antinociceptive activity of methanolic extract of Acmella uliginosa (Sw.) Cass

Ethnopharmacological relevance

Acmella uliginosa (Sw.) Cass. is a medicinal herbaceous plant that is commonly used by the Malay community in Malaysia to relieve pain often associated with mouth ulcers, toothache, sore throat, and stomach ache.

Aim

The study was carried out to investigate the antinociceptive effect of the methanolic extract of A. uliginosa (Sw.) Cass. flowers (MEAU) using murine models of chemicals and thermal nociception.

Materials and methods

Chemicals (acetic acid-induced abdominal constriction and formalin-, capsaicin-, glutamate-induced paw licking test) and thermal models (hot plate test) of nociception in mice were employed to evaluate the MEAU analgesic effect. The extract was given via oral administration at doses of 3, 10, 30 and 100 mg/kg.

Results

It was demonstrated that MEAU produced significant antinociceptive response in all the chemical- and thermal-induced nociception models, which indicates the presence of both centrally and peripherally mediated activities. Furthermore, the reversal of antinociception of MEAU by naloxone suggests the involvement of opioid system in its centrally mediated analgesic activity. Moreover, MEAU-treated mice did not show any significant motor performance alterations. No mortality and signs of toxicity were recorded following treatment of the MEAU.

Conclusion

The results from the present study appear to support the folkloric belief in the medicinal properties of A. uliginosa (Sw.) Cass. which against pain at both central and peripheral levels, in which the central antinociception is probably due to the participation of the opioid receptors.     

Antinociceptive activity of fruits extracts and “arrope” of Geoffroea decorticans (chañar)

Ethnopharmacological relevance

Geoffroea decorticans (chañar) fruits and their derivate product (arrope) have been traditionally used as food and a folk medicine for the treatment of a wide variety of diseases including bronchopulmonary disorders and to relieve dolorous process.

Aim of the study

In order to evaluate the pharmacology action of this plant, studies were performed of antinociceptive and antioxidant activities.

Materials and methods

The aqueous and ethanolic extracts and arrope of chañar were evaluated in various established pain models, including chemical nociception induced by subplantar formalin and intraperitoneal acetic acid and thermal nociception method, such as tail immersion test in rats. To examine the possible connection of the opioid receptor to the antinociceptive activity of extracts and arrope it was performed a combination test with naloxone, a non-selective opioid receptor antagonist.

Results

The aqueous extract and arrope (1000 mg/kg) caused an inhibition of the pain in formalin test in the first phase, similar to morphine and decrease in the second phase. In a combination test using naloxone, diminished analgesic activity of aqueous extract and arrope were observed, indicating that antinociceptive activity is connected with the opioid receptor. The aqueous extract and arrope, caused an inhibition of the writhing response induced by acetic acid. Central involvement in analgesic profile was confirmed by the tail immersion test, in which the aqueous extract and arrope showed a significant analgesic activity by increasing latency time. The aqueous extract showed higher antioxidant activity than the arrope, it may be due to the cooking process.

Conclusions

This study has shown that the aqueous extract and arrope of Geoffroea decorticans (chañar) fruits, does possess significant antinociceptive effects. It is further concluded that aqueous extract with maximum inhibition of free radical is the most potent extract amount tested extracts. At the oral doses tested the aqueous extract and arrope were non-toxic. The present results justifies their popular use and constitutes the first validation study of the antinociceptive action.     

Antinociceptive effect of ethanol extract of leaves of Lannea coromandelica

Ethnopharmacological relevance

Lannea coromandelica (Houtt.) Merr. is a plant locally called “Jiga”, found all over Bangladesh. Leaf of the plant is traditionally used in the treatment of local swellings, pains of body, toothache etc. This study evaluated the antinociceptive effect of the ethanol extract of L. coromandelica leaves (EELC).

Materials and methods

The antinociceptive activity of the extract (at the doses of 50, 100, and 200 mg/kg) was evaluated by using chemical- and heat-induced pain models such as acetic acid-induced writhing, hot plate, tail immersion, formalin, and glutamate test. To verify the possible involvement of opioid receptor in the central antinociceptive effect of EELC, naloxone was used to antagonize the effect. Besides, the involvements of ATP-sensitive K⁺ channel and cGMP pathway were also justified by using glibenclemide and methylene blue.

Results

EELC demonstrated significant dose-dependent antinociceptive activity in the chemical- and heat-induced nociception in mice models (p<0.05). These findings imply the involvement of both peripheral and central antinociceptive mechanisms. The use of naloxone confirmed the association of opioid receptors in the central antinociceptive effect. EELC also showed the involvements of ATP-sensitive K⁺ channel and cGMP pathway for antinociceptive activity.

Conclusions

This study reported the antinociceptive activity of the leaf of L. coromandelica and rationalized the traditional use of the leaf in the treatment of different painful conditions.     

Evaluation of antinociceptive effects of Crassocephalum bauchiense Hutch (Asteraceae) leaf extract in rodents

Ethnopharmacological relevance

The leaves of Crassocephalum bauchiense have long been used in traditional Cameroonian medicine for the treatment of epilepsy, pain, inflammatory disorders, arthritis and intestinal pain.

Aim of the study

In this study, we attempted to identify the possible antinociceptive action of the aqueous extract and the alkaloid fraction prepared from the leaves of Crassocephalum baucheiense.

Materials and methods

Using acetic acid induced abdominal constrictions, formalin-, capsaisin- and glutamate-induced nociception, and hot plate assay procedures, the antinociceptive effects of the aqueous extract and the alkaloid fraction was assessed after oral administration in mice. Morphine sulfate was used as reference analgesic agent. Mice were submitted to the rota-rod task and open-field test in order to assess any non-specific muscle-relaxant or sedative effects of the extracts of Crassocephalum bauchiense. Male and female Swiss mice were used to assess acute toxicity of these extracts.

Results

The aqueous extract and the alkaloid fraction of Crassocephalum bauchiense produced a significant antinociceptive effects in the acetic acid, formalin, glutamate, capsaicin and hot plate tests. These antinociceptive effects of Crassocephalum bauchiense were significantly attenuated by pretreatment with naloxone. The extracts of Crassocephalum bauchiense did not alter the locomotion of animals in the open-field or rotarod tests, which suggest a lack of a central depressant effect. The animals did not exhibit any acute toxicity to the aqueous extract and the alkaloid fraction, so it was not possible to calculate the LD₅₀.

Conclusion

The results confirm the popular use of Crassocephalum bauchiense as an antinociceptive, and contribute to the pharmacological knowledge of this species because it was shown that the aqueous extract and the alkaloid fraction of Crassocephalum bauchiense produced dose related antinociception in models of chemical and thermal nociception through mechanisms that involve an interaction with opioidergic pathway.     

Effects of Sceletium tortuosum in rats

Ethnopharmacological relevance

Broad historical and current uses in addition to diverse activity on CNS targets may make Sceletium tortuosum a useful therapeutic in a variety of clinical settings. This study sought to more broadly characterize activity of Sceletium tortuosum and mesembrine in a number of common, rodent-based assays that model nociception, depression, anxiety, ataxia, and abuse liability.

Materials and methods

Male Sprague-Dawley were administered Sceletium tortuosum extract products and behavioral responses were evaluated in the conditioned place preference (CPP), hot plate, forced swim, elevated plus, and rotarod tests.

Results and conclusions

Sceletium tortuosum does not cause preference or aversion in CPP. Mesembrine appears to have analgesic properties without abuse liabilities or ataxia. The Sceletium tortuosum fraction has antidepressant properties but does produce ataxia. The ataxia may limit its usefulness as an antidepressant unless the antidepressant activity is associated with one constituent and the ataxia is associated with a separate constituent.     

Neuropharmacological study of Dracocephalum moldavica L. (Lamiaceae) in mice: sedative effect and chemical analysis of an aqueous extract

Ethnopharmacological relevance

Dracocephalum moldavica is used as a tranquilizer and as remedy for nervous conditions relief in the Mexican traditional medicine. Despite its intensive use no literature reported neuropharmacological studies on Dracocephalum moldavica as yet.

Aim of the study

The sedative, anxiolytic-like and antidepressant-like effects of the aqueous extract of aerial parts of Dracocephalum moldavica (Lamiaceae) (DM) were evaluated in behavioral models in mice. The general toxic effects of DM were evaluated as well as their chemical analysis was performed.

Materials and methods

DM effects were evaluated on pentobarbital-induced sleeping time (SPT), the hole-board (HBT), and the avoidance exploratory behavior (AEBT) tests and on the forced swimming test (FST). General activity and motor coordination were evaluated in the open field (OFT) and Rota-rod tests, respectively. The acute toxicity of DM was determinate by its LD₅₀ dose. The chemical analyses DM were performed by chromatographic and HPLC–ESI-MS techniques.

Results

DM prolonged the pentobarbital-induced sleeping time, induced sedation in the HBT, decreased spontaneous activity and produced motor coordination impairment in mice. However, DM did not show anxiolytic effects in the AEBT or HBT and it was not effective in FST. The DM-treatment produced mortalities with LD₅₀ = 470 mg/kg body weight.The HPLC–ESI-MS analysis of DM revealed that (acacetin, apigenin and luteolin)-7-O-β-d-(6″-O-malonyl)-glucoside derivates are the main compounds of DM.

Conclusions

DM induced sedative actions and a general inhibition of CNS activity observed by the decrease of animals’ general activity, motor coordination and exploration.     

Aqueous root extracts from Mimosa albida Humb. & Bonpl. ex Willd display antinociceptive activity in mice

Ethnopharmacological relevance

In this work, we study whether aqueous extracts from the roots of Mimosa albida Humb. & Bonpl. ex Willd, a plant known in the Highlands of Chiapas, Mexico as “Lotóm chíx” are endowed with both antinociceptive and anxiolytic effects.

Materials and methods

ICR mice were systemically treated with aqueous extracts from Mimosa albida and the reference compounds (diazepam, dipyrone and/or fentanyl) and their behavior was evaluated in several behavioral tests.

Results

Administration of aqueous extracts from the roots of Mimosa albida resulted in a reduction of the nociception elicited in mice by both the hot plate (12.5, 25 and 50 mg/kg; i.p.) and the acetic acid-induced writhing (25 and 50 mg/kg; i.p.) tests. No effects were however observed both in the elevated plus-maze and hole board test (3.2, 12.5 and 25 mg/kg; i.p.). In contrast, both locomotion (open field test) and motor coordination (rotarod test) were affected at doses (50, 100 y 200 mg/kg; i.p.) higher than those having antinociceptive effects.

Conclusion

These data suggest that in mice the systemic administration of low doses of aqueous extracts from the roots of Mimosa albida results in antinociceptive effects in several models of pain through mechanisms that do not involve the opioid system pathway. These results support the ethnopharmacological use of Mimosa albida in popular medicine.     

Towards a better understanding of the psychopharmacology of nutmeg: Activities in the mouse tetrad assay

Ethnopharmacological relevance

Nutmeg, the seeds of Myritica fragrans (family Myristicaceae), is a well known kitchen spice with a long-standing reputation as a psychoactive herb. Nutmeg at high doses is considered a cheap substitute to several drugs of abuse. Earlier reports have attributed amphetamine-like activities to nutmeg.

Aim of the study

To characterize the neuropharmacological effects of different nutmeg extracts, administered orally and intraperitoneally, in comparison to Δ⁹-terahydrocannabinol, amphetamine, and morphine.

Materials and methods

Methanolic (ME), dichloromethane (DE), and hexane (HE) extracts were obtained from a chromatographically fingerprinted batch of nutmeg. Biological evaluation was conducted in sets of 6–8 mice in the tetrad assay at doses ranging from 100 to 500 and 500 to 1000 mg/kg for i.p. and oral administration, respectively.

Results

While oral administration of all the nutmeg extracts at 500 mg/kg caused a significant increase in locomotor activity, the i.p. administration of DE showed significant reduction in rectal temperature along with a significant increase in tail flick latency at 300 mg/kg. A significant decrease in core body temperature was observed with HE at 100 mg/kg, while higher doses caused significant increases in hot plate latency.

Conclusion

Different behavioral effects were observed that varied by the type of extract as well as by the route of administration.     

Antinociceptive activities of the methanol extract of the bulbs of Dioscorea bulbifera L. var sativa in mice is dependent of NO–cGMP–ATP-sensitive-K channel activation

Ethnopharmacological relevance

Dioscorea bulbifera var sativa is a medicinal plant commonly used in Cameroonian traditional medicine to treat pain and inflammation.

Aim

The present work evaluated the effects of the methanol extract of the bulbs of Dioscorea bulbifera in inflammatory and neuropathic models of pain and further investigated its possible mechanism of action.

Materials and methods

The effects of Dioscorea bulbifera administered orally at the doses of 250 and 500 mg/kg were tested in mechanical hypernociception induced by intraplantar (i.pl.) injection of complete Freund's adjuvant (CFA), lipopolysaccharides (LPS) or prostaglandin-E₂ (PGE₂), as well as in partial ligation sciatic nerve (PLSN), nociception induced by capsaicin and thermal hyperalgesia induced by i.pl. injection of CFA. The therapeutic effects of Dioscorea bulbifera on PGE₂-induced hyperalgesia were evaluated in the absence and in the presence of l-NAME, an inhibitor of nitric oxide synthase (NOS) and glibenclamide, an inhibitor of ATP-sensitive potassium channels.

Results

The extract showed significant antinociceptive effects in persistent pain induced by CFA and on neuropathic pain induced by PLSN. The effects of Dioscorea bulbifera persisted for 5 days after two administrations in CFA-induced hypernociception. Dioscorea bulbifera significantly inhibited acute LPS-induced pain but failed to reduce thermal hypernociception and capsaicin-induced spontaneous nociception. The antinociceptive effects of this plant extract in PGE₂ model was antagonized by either l-NAME or glibenclamide.

Conclusion

Present demonstrate the antinociceptive activities of Dioscorea bulbifera both in inflammatory and neuropathic models of pain and these effects may result, at least partially, from its ability to activate the NO–cGMP–ATP-sensitive potassium channels pathway.     

Antiinflammatory and antinociceptive activities of Blechnum occidentale L. extract

Aim of study

Blechnum occidentale L. is a terrestrial fern that ranges from the United States to South America, and is employed in Brazilian folk medicine. In the present study we investigated the antinociceptive and antiinflammatory activities of the methanolic extract of Blechnum occidentale L. (MEB) in animal models of pain and inflammation to support its medicinal use in treatment of inflammatory and pulmonary diseases, urinary infections and liver diseases.

Materials and methods

The antinociceptive activity of MEB was evaluated using the writhing, formalin, and tail flick tests. The antiinflammatory activity of MEB was evaluated in carrageenan-induced paw oedema and neutrophil migration. In order to discard possible non-specific muscle relaxant or sedative effects of MEB, mice motor performance was evaluated in the rota rod test and its toxicity evaluated over 14 days.

Results

Intraperitoneal (IP) administration of MEB (0.01–100 mg/kg) produced a dose-related antinociception on acetic acid-induced writhing in mice. Oral administration of MEB, at a different range of doses (100–400 mg/kg), also produced significant antinociceptive effect on the writhing test. Furthermore, treatment with MEB (100 and 200 mg/kg IP) inhibited significantly both the early and late phases of formalin-induced hypernociception in rats. In contrast, treatment with MEB (100 and 200 mg/kg IP) did not prevent the thermal nociception in the tail flick test. The IP administration of MEB (100 and 300 mg/kg) significantly reduced the paw oedema induced by carrageenan. Moreover, systemic treatment with MEB (11–300 mg/kg) reduced the neutrophil migration in the carrageenan-induced migration to the peritoneal cavity. In the rota rod test, MEB-treated mice did not show any significant motor performance alterations with the dose of 300 mg/kg. In addition, over the study duration of 14 days, there were no deaths or toxic signs recorded in the mice given 100 or 1000 mg/kg of MEB.

Conclusion

The results described here are the first report of pharmacological studies of Blechnum occidentale L. and indicate that this plant has antinociceptive and antiinflammatory activities which support its folk medicine use.     

Anti-hypoxic activity of the ethanol extract from Portulaca oleracea in mice

Aim of the study

To investigate the effects of the ethanol extract from Portulaca oleracea (EEPO) on hypoxia models mice and to find the possible mechanism of its anti-hypoxic actions so as to elucidate the anti-hypoxia activity and provide scientific basis for the clinical use of Portulaca oleracea.

Materials and methods

EEPO was evaluated on anti-hypoxic activity in several hypoxia mice models, including closed normobaric hypoxia and sodium nitrite or potassium cyanide toxicosis. To verify the possible mechanism(s), we detected the activities of pyruvate kinase (PK), phosphofructokinase (PFK), lactate dehydrogenase (LDH) and the level of adenosine triphosphate (ATP) in mice cortices.

Results

Given orally, the EEPO at doses of 100, 200, 400 mg/kg could dose-dependently enhance the survival time of mice in both of the normobaric and chemical hypoxia models. The activity of the glycolysis enzymes and the level of ATP were higher than those of the control. In the pentobarbital sodium-induced sleeping time test and the open-field test, EEPO neither significantly enhanced the pentobarbital sodium-induced sleeping time nor impaired the motor performance, indicating that the observed anti-hypoxic activity was unlikely due to sedation or motor abnormality.

Conclusions

These results demonstrated that the EEPO possessed notable anti-hypoxic activity, which might be related to promoting the activity of the key enzymes in glycolysis and improving the level of ATP in hypoxic mice.     

Antinociceptive,neurobehavioral and antioxidant effects of Eupatorium triplinerve Vahl on rats

Ethnopharmacological relevance

Eupatorium triplinerve Vahl belongs to the Asteraceae family, popularly known as Japana. It is a perennial shrub native to Amazon rainforests of South America. Its leaves are used through infusions, decoctions, baths, and tea. It is largely used in Brazilian folk medicine as sedative, febrifuge, stimulant, tonic and anti-inflammatory.

Aim of the study

The present study evaluated the putative effects of Eupatorium triplinerve on the central nervous system (CNS), including locomotor and anxiety activity, depression-like behavior, and antinociception and oxidative stress.

Materials and methods

Two-month-old male Wistar rats (n=7–10 rats/group) and Swiss male and female mice of the species Mus musculus (n=7–10 per group) were administered with 100 mg/kg, 200 mg/kg, 400 mg/kg, 600 mg/kg, and 800 mg/kg of hydroalcoholic extracts of Eupatorium triplinerve (HEET). The behavioral assays included open-field (OF), elevated Plus-maze (EPM), and forced swimming tests (FS). The antinociceptive activity was verified using chemical (acetic acid and formalin) and thermal (hot plate) models of nociception. The oxidative stress levels were measured in rat blood samples after behavioral assays and Trolox equivalent antioxidant capacity (TEAC), nitric oxide and malondialdehyde (MDA) levels were measured in vivo.

Results

Oral pretreatment with HEET reduced the locomotion in OF test (200–800 mg/kg), increased central locomotion and open arms entries in the OF and EPM tests, respectively (600–800 mg/kg), and decreased the immobility time in the FS (200–800 mg/kg). It also reduced the writhing number evoked by acetic acid injection (200–800 mg/kg) and licking time in the first phase of the formalin test (400–800 mg/kg). In the oxidative stress assays, the extract decreased TEAC, Nitric Oxide and MDA levels in response to swimming stress induced in rats.

Conclusions

These results were indicative for the first time that Eupatorium triplinerve exerted mild sedative, anxiolytic and antidepressive effects on the CNS. Antinociceptive effects not related to opioid system and antioxidant activity were also observed. These results support the ethnopharmacological use of Eupatorium triplinerve in popular medicine.