Antinociceptive and antiinflammatory activities of Adiantum latifolium Lam.: Evidence for a role of IL-1β inhibition

Aim of study

Adiantum, one of the most widely distributed genera of the family Pteridaceae, is employed in folk medicine worldwide. Adiantum latifolium Lam. has been used in Latin American traditional medicine as anxiolytic, analgesic and antiinflammatory. The present study investigates the antinociceptive and antiinflammatory properties of the methanolic extract of Adiantum latifolium (MEA) in animal models of pain and inflammation to confirm its medicinal use.

Material and methods

The antinociceptive and antiinflammatory activities of MEA were evaluated using the writhing, formalin, and tail-flick tests, carrageenan-induced paw edema and arachidonic acid-induced ear edema. Mice motor performance was evaluated in the rota rod test and the acute toxicity evaluated over 14 days.

Results

Intraperitoneal (1-100 mg/kg) or oral (100-400 mg/kg) administration of MEA produced a dose-related inhibition of acetic acid-induced writhing in mouse. Furthermore, treatment with MEA (100 mg/kg) inhibited both the early and late phases of formalin-induced hypernociception. In contrast, MEA (100 mg/kg/IP) did not prevent the thermal nociception in the tail-flick test. In addition, MEA (100 and 200 mg/kg/IP) inhibited important events related to the inflammatory response induced by carrageenan or arachidonic acid, namely local edema and increase in tissue interleukin-1β levels. MEA (300 mg/kg/IP)-treated mice did not show any motor performance alterations. Over the study period of 14 days, there were no deaths or toxic signs recorded in the group of mice given 1000 mg/kg of MEA.

Conclusion

The results demonstrate that Adiantum latifolium has antinociceptive and antiinflammatory activities, acting through the inhibition of IL-1β production.     

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 and anti-inflammatory activities of Bowdichia virgilioides (sucupira)

Ethnopharmacological relevance

Bowdichia virgilioides Kunth (Leguminosae Papilonoideae) is a plant with anti-inflammatory activity used in folk medicine. The importance of this plant promoted its inclusion in Brazilian Pharmacopoeia.

Aim of the study

In order to evaluate the actions of this plant, studies were performed on antinociceptive and anti-inflammatory activities.

Materials and methods

The aqueous extracts (AE) of Bowdichia virgilioides inner bark and leaves were used at 100, 200, and 400 mg/kg. Antinociceptive activity of plant extract was evaluated by writhing, hot-plate and formalin tests. Anti-inflammatory activity was evaluated using paw oedema and peritonitis methods.

Results

Oral treatment with the AE of inner bark or leaves elicited inhibitory activity (P < 0.01) on acetic acid effect at 200 and 400 mg/kg, and reduced the formalin effect at the second-phase (200 and 400 mg/kg, P < 0.01), however it did not elicit any inhibitory effect on hot-plate test. The indomethacin inhibited the acetic acid-induced writhing and the formalin effect at the second-phase (P < 0.001), and the morphine reduced the both phases of formalin test (P < 0.001). Carrageenan-induced oedema formation and neutrophil migration into the peritoneal cavity were reduced with the AE of inner bark or leaves at 100, 200, and 400 mg/kg (P < 0.05), and by the reference compounds aspirin (P < 0.001) and dexamethasone (P < 0.001), respectively.

Conclusions

The AE of Bowdichia virgilioides shows antinociceptive and anti-inflammatory activities, supporting the folkloric usage of the plant to treat various inflammatory diseases.     

Anti-inflammatory and antinociceptive activities of Campomanesia adamantium

Ethnopharmacological relevance

Campomanesia species are used in folk medicine as anti-inflammatory, anti-rheumatic, anti-diarrheal and hypocholesterolemic.

Aim of the study

The present study investigated the in vivo anti-inflammatory and antinociceptive properties of ethyl acetate (AE) and aqueous (Aq) extracts from leaves of Campomanesia adamantium and in vitro anti-inflammatory activity of AE and its isolated flavonols, myricitrin and myricetin.

Materials and methods

The antinociceptive activity of AE and Aq was evaluated using acetic acid-induced writhing and formalin methods. The in vivo anti-inflammatory effect of AE and Aq was evaluated using carrageenan-induced paw oedema in mice. AE, myricitrin and myricetin were evaluated for their abilities to modulate the production of NO, TNF-α and IL-10 in LPS/IFN-γ stimulated J774.A1 macrophages.

Results

It was found that orally administrated AE and Aq (125 and 250 mg/kg) inhibited carrageenan-induced paw oedema in mice. AE (125 and 250 mg/kg) and Aq (125 mg/kg) reduced the time to licking at the second phase of the formalin method in vivo in mice. AE (250 mg/kg) and Aq (125 mg/kg) also reduced the number of writhes. AE, myricitrin and myricetin inhibited NO (320 μg/mL and 6.25–100 μM, respectively) and TNF-α production by macrophages (320 μg/mL for AE, 100 μM for myricitrin and 25–100 μM for myricetin). AE (160 and 320 μg/mL), myricitrin (50 and 100 μM) and myricetin (25–100 μM) increased IL-10 production by macrophages.

Conclusions

The ethyl acetate and aqueous extracts from Campomanesia adamantium showed antinociceptive and anti-inflammatory effects supporting the use of the plant in folk medicine. The results suggest that anti-oedematogenic effect promoted by aqueous extract involves several anti-inflammatory mechanisms of action. The antinociceptive effect shown by aqueous extract can be due to the modulation of release of inflammatory mediators involved in nociception. The anti-inflammatory effects of AE and of its isolated flavonols may be attributed to inhibition of pro-inflammatory cytokines production, TNF-α and NO and to the increased of IL-10 production.     

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.     

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.     

Characterization of the antinociceptive and anti-inflammatory activities from Cocos nucifera L. (Palmae)

Aim of the study

Cocos nucifera cultivated in Brazil is known as “coco-da-Bahia” or “coqueiro-da-Índia”. The tea from the husk fiber is widely used to several inflammatory disorders. Crude extract and fractions obtained from Cocos nucifera “common variety” were evaluated to test the anti-inflammatory and antinociceptive activities.

Materials and methods

Crude extract (CE, 50, 100, and 150 mg/kg), fraction 1 (F1, molecular weight lesser than 1 kDa, 1, 10, and 50 mg/kg), fraction 2 (F2, molecular weight higher than 1 kDa, 1, 10, and 50 mg/kg), and the references drugs morphine (5 mg/kg), acetilsalicilic acid (200 mg/kg), prometazine (30 mg/kg), and metisergide (5 mg/kg) were evaluated on models of analgesia and inflammation.

Results

CE, F1, and F2 significantly develop peripheral and central antinociceptive activity but with less effect on supra-spinal regions of the brain. Administration of the opioid antagonist, naloxone (5 mg/kg) inhibited the antinociceptive effect indicating that Cocos nucifera crude extract and fractions may be acting in opioid receptors. CE and F1 also inhibited rat paw edema induced by histamine, and serotonin.

Conclusions

results demonstrated that Cocos nucifera and its fractions have antinociceptive and anti-inflammatory activities which confirm the popular use of this plant in several inflammatory disorders.     

Evaluation of the antinociceptive and anti-inflammatory effect of Caralluma dalzielii

Ethnopharmacological relevance

Caralluma dalzielii has been used for treating several ailments including convulsion, leprosy, snake bites, otitis (ear pain), fungal diseases and rheumatoid arthritis in Northern Nigeria. However there is no scientific evidence to support its use in literature. To evaluate the antinociceptive and anti-inflammatory properties of the aqueous extract of Caralluma dalzielii in animal models.

Materials and methods

The antinociceptive and anti-inflammatory properties were assessed using acetic acid induced writhing test in mice, sub plantar formalin induced nociception, the tail-flick test and formalin induced oedema in rats. Three doses of the extract (25, 50, 100 mg/kg) were used for the assessment.

Results

Caralluma dalzielii extract demonstrated strong dose-dependent antinociceptive and anti-inflammatory activities in all the models employed. All doses (25, 50, 100 mg/kg) produced a significant percentage inhibition (41.77, 77.11, and 90.76% in the early phase and 52.02, 85.35, 93.93% in the late phase) in the acetic acid writhing test and (42.85, 55.71, 86.43% in the early phase and 23.26, 37.98, 72.87 in the late phase) in the formalin induced nociception test, respectively. The tail-flick test showed a significant increase in the antinociceptive effect of the extract in both early and late phases when compared with the control. The inhibition of oedema in the formalin test was significant when compared to the control.

Conclusion

The results indicated that Caralluma dalzielii showed excellent antinociceptive and anti-inflammatory properties suggesting that its traditional use in the treatment of pains and inflammatory diseases may be valid.     

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.     

Beneficial effects of Anadenanthera colubrina (Vell.) Brenan extract on the inflammatory and nociceptive responses in rodent models

Ethnopharmacological relevance

Anadenanthera colubrina (Vell.) Brenan, popularly known as “angico”, is a plant that has been widely used in folk medicine due to its anti-inflammatory property. To evaluate the pharmacological activities of this plant, studies were performed on its antinociceptive and anti-inflammatory properties.

Materials and methods

The AE of Anadenanthera colubrina, made from the bark, was used in rodents via oral route (p.o.), at 100, 200, and 400 mg/kg in classical models of nociception (acetic acid-induced writhing and hot-plate test) and inflammation evoked by carrageenan (e.g., paw edema, peritonitis, and synovitis).

Results

The acetic acid-induced abdominal writhes in mice were significantly reduced (P<0.001) by oral treatment with the extract (100, 200, and 400 mg/kg), but the extract did not significantly increase the latency in the nociceptive hot-plate test. Anadenanthera colubrina aqueous extract reduced significantly the edema and, besides, diminished the mieloperoxidase activity (200 and 400 mg/kg, P<0.01). The carrageenan-induced peritonitis was significantly reduced (P<0.05) by the aqueous extract at 100, 200, and 400 mg/kg. The aqueous extract (200 mg/kg) reduces the synovial leukocyte infiltration on carrageenan-induced synovitis in rats (P<0.01), but failed to significantly affect joint swelling and impaired mobility.

Conclusions

We show for the first time that the anti-inflammatory and peripheral antinociceptive activities of Anadenanthera colubrina are consistent, at least in part, with the use of this plant in popular medicine practices.     

Evaluation of the diuretic and analgesic activities of the rhizomes of Rumex abyssinicus Jacq in mice

Aim of the study

Rumex abyssinicus Jacq (Polygonaceae) has been used traditionally for treatment of hypertension, inflammatory and painful conditions in Ethiopia. The present study aimed to evaluate the diuretic and analgesic activities of extracts of Rumex abyssinicus at different doses in mice.

Materials and methods

The effect on urine volume and urinary electrolyte (Na⁺, K⁺ and Cl⁻) was assessed for a period of 5 h following oral administration of aqueous (500 mg/kg, 750 mg/kg or 1000 mg/kg) or 80% methanolic (250 mg/kg, 500 mg/kg or 750 mg/kg) extract or furosemide (10 mg/kg). Acetic acid-induced writhing and hot-plate tests were employed to study the analgesic effect of 80% methanolic extracts (250 mg/kg, 500 mg/kg or 1000 mg/kg, P.O.) and compared with that of aspirin (100 mg/kg, P.O.) or morphine (10 mg/kg, sc).

Results

The extracts displayed dose-dependent diuretic and analgesic effects. The highest doses of both extracts markedly and significantly increased (P < 0.001) urine volume and urinary electrolytes, qualitatively similar to that of furosemide. 1000 mg/kg of the extract reduced the number of writhing by 67.6% (P < 0.001) and conferred more than 70% protection against thermally induced pain stimuli after 45 min of treatment comparable to that of aspirin and morphine, respectively.

Conclusion

These findings collectively indicate that the extracts exhibited significant diuretic and analgesic activities, providing evidence, at least in part, for its folkloric use.     

Evidence for a role of 5-HT1A receptor on antinociceptive action from Geissospermum vellosii

Ethnopharmacological relevance

Geissospermum vellosii is a tree widely found throughout the Amazonic forest and frequently used by the native population for painful disorders.

Aim of the study

The present study examined the antinociceptive effects of Geissospermum vellosii in behavioral models of nociception.

Materials, methods and results

Oral administration of crude extract of Geissospermum vellosii or its dichloromethane fraction (1–100 mg/kg) inhibited formalin-induced inflammatory nociception and acetic acid-induced visceral nociception. The antinociceptive effect of Geissospermum vellosii was unrelated with motor dysfunctions. Furthermore, the alkaloid 12-metoxy-1-methyl-aspidospermidine (0.001–1 mg/kg), isolated from the dichloromethane fraction, also produced antinociception. The antinociception caused by the dichloromethane fraction was significantly attenuated by pre-treatment of mice with p-chlorophenylalanine methyl ester (PCPA, an inhibitor of serotonin synthesis, 100 mg/kg once a day for 4 consecutive days) and WAY-100635 (a 5-HT_1A receptor antagonist, 0.3 mg/kg). In contrast, dichloromethane fraction antinociception was not affected by pre-treatment of animals with ketanserin (a 5-HT₂ receptor antagonist, 0.3 mg/kg) or ondansetron (a 5-HT₃ receptor antagonist, 0.5 mg/kg).

Conclusions

Together, these results indicate that Geissospermum vellosii produces antinociception through an interaction with 5-HT_1A receptors. Furthermore, the alkaloid 12-metoxy-1-methyl-aspidospermidine contributes to the antinociceptive properties reported for Geissospermum vellosii.     

Antinociceptive activity of fractions from Couroupita guianensis Aubl. leaves

Ethnopharmacological relevance

Couroupitaguianensis Aubl. (Lecythidaceae) is popularly known in Brazil as “abricó-de-macaco”. Infusions or teas obtained from its leaves, flowers, and barks are used in South America for the treatment of several disorders such as pain and inflammatory processes.

Aim of the study

Evaluate antinociceptive effects of crude ethanol extract (CEE) and its fractions in three analgesic models (acetic acid-induced contortions, tail flick, and hot plate) and study the possible mechanism of their action.

Materials and methods

CEE, hexane, dichloromethane, ethyl acetate, and butanol fractions (10, 30, and 100 mg/kg, p.o.) and the reference drug morphine (5 mg/kg, s.c.) were evaluated. To elucidate the mechanism of action from the fractions, animals were pre-treated (30 min) with atropine (muscarinic receptor antagonist, 1 mg/kg, s.c.), mecamylamine (nicotinic receptor antagonist, 2 mg/kg, s.c.), naloxone (opioid receptor antagonist, 1 mg/kg, s.c.) or l-nitro arginine methyl ester (l-NAME, nitric oxide synthase inhibitor, 3 mg/kg, s.c.).

Results

CEE and fractions significantly inhibited the number of contortions induced by acetic acid. All fractions showed antinociceptive activity in the tail flick model, being the hexane and ethyl acetate the most potent and long acting fractions. In the hot plate method the highest effect observed was at the dose of 100 mg/kg from all fractions. Administration of naloxone inhibited the antinociceptive effect of fractions. Pre-treatment of mice with atropine reduced the antinociceptive activity of CEE and its fractions, the exception being the dichloromethane fraction. Mecamylamine did not inhibited the effect of dichloromethane fraction. l-NAME reduced the anti-hyperalgesic effect of all fractions, but the most prominent effect was observed in the antinociceptive activity caused by CEE and butanol fraction.

Conclusions

Results obtained demonstrated that Couroupita guianensis CEE and its fractions have antinociceptive activity that is mediated, at least in part, by opioid and cholinergic systems and nitric oxide pathway.     

Characterization of the antinociceptive and anti-inflammatory activities of fractions obtained from Copaifera multijuga Hayne

Ethnopharmacological relevance

Copaifera multijuga Hayne (Leguminosae) is a tree that produces an oleoresin, which is extensively commercialized in Brazil as capsules or crude oil for the treatment of several disorders. Ethnopharmacological studies show a diversity of indications such as anti-inflammatory and epidermal wound cicatrization.

Aim of the study

In the present work three fractions obtained from Copaifera multijuga oleoresin (hexane (HF), chloroform (CF), and methanol (MF) from a KOH impregnated silica gel column chromatography, representing the three main classes of compounds in the Copaifera genus (hydrocarbon sesquiterpenes, oxygenated sesquiterpenes and acidic diterpenes), were evaluated using antinociceptive and anti-inflammatory models.

Materials and methods

HF, CF, and MF (doses ranging between 1 and 150 mg/kg, depending on the model used), Copaifera multijuga oleoresin (CMO, 100 mg/kg, p.o.) and the reference drug morphine (5 mg/kg, p.o.) were evaluated using models for analgesia (acetic acid-induced contortions and tail flick) or inflammation (rat paw oedema and increase in vascular permeability). To elucidate the mechanism of action from the fractions, animals were pre-treated with naloxone (opioid receptor antagonist, 5 mg/kg, i.p.).

Results

Fractions significantly inhibited (in a concentration-dependant way) the number of contortions induced by acetic acid and the second phase of formalin-induced licking response. Similar results were observed in the tail flick model. The central antinociceptive effect for HF and CF at the doses of 50 and 100 mg/kg was higher than the one observed for morphine (1 mg/kg). Administration of naloxone inhibited the antinociceptive effect of fractions indicating that HF, CF, and MF may be acting on opioid receptors. All three fractions also inhibited rat paw oedema and the increase in vascular permeability induced by several phlogistic agents (carrageenan, histamine, and serotonin).

Conclusions

Our results indicate that fractions obtained from Copaifera multijuga Hayne demonstrate an antinociceptive effect probably mediated by opioid receptors, and anti-inflammatory activity through inhibition of histaminergic and serotoninergic pathways.     

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.     

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.     

Antinociceptive activity of methanol extract of fruits of Capparis ovata in mice

Ethnopharmacological relevance

Capparis ovata Desf. and Capparis spinosa L. have wide natural distribution in Turkey and they are consumed in pickled form. Flower buds, root bark, and fruits of the plant are used in folk medicine due to their analgesic, wound healing, cell regeneration, tonic, and diuretic effects.

Aim of the study

In this study, we attempted to identify the possible antinociceptive action of methanol extract prepared from fruits of Capparis ovata.

Materials and methods

Using tail immersion, hot plate and writhing tests, the antinociceptive effect of the methanol extract of Capparis ovata (MEC) fruits was assessed after intraperitoneal administration into mice. Morphine sulfate (5 mg/kg; i.p.) and diclofenac (10 mg/kg; i.p.) were used as reference analgesic agents. Naloxone (5 mg/kg; i.p.) was also tested.

Results

MEC was studied at the doses of 50, 100, and 200 mg/kg (i.p.) and exhibited significant antinociceptive activities in all tests used. The above-mentioned doses of the extract reduced the writhing responses by 32.21, 55.70, and 68.36%, respectively. MPE% were increased by 7.27, 12.07, 14.60% in the tail immersion, and 7.88, 11.71, 16.73% in the hot plate test at the tested doses, respectively. Naloxone antagonized antinociceptive effect at the doses of 100 and 200 mg/kg whereas partially antagonized the effect of MEC at the dose of 50 mg/kg.

Conclusions

Based on the results obtained, it can be concluded that MEC has antinociceptive effects both at the peripheral and central levels.     

Orofacial antinociceptive effect and antioxidant properties of the hydroethanol extract of Hyptis fruticosa salmz ex Benth

Ethnopharmacological relevance

Hyptis fruticosa is a plant native to Brazil with antinociceptive and antiinflamatory properties. This study evaluated the antinociceptive activity of the hydroethanol extract of the plant leaves (CHEE) against orofacial pain as well as its in vitro effect against lipid peroxidation.

Materials and methods

The antinociceptive activity was investigated in mice orally treated with different doses of the CHEE (50, 100, and 200 mg/kg) and morphine (5 mg/kg) using formalin, glutamate, and capsaicin orofacial pain models using. Lipoperoxidation was induced in egg yolk by AAPH and FeSO₄ in the absence and presence of the CHEE (5, 50, 100, and 150 μg/mL).

Results

CHEE (200 mg/kg) significantly reduced (ρ<0.001) the pain response in the first (69.6%) and second (81.8%) phases of the formalin test, while the nociception caused by capsaicin was significantly (ρ<0.001) reduced by up to 62% at 200 mg/kg of extract. When glutamate was used as algogen, a significant (ρ<0.001) nociception reduction of up to 85% at 200 mg/kg extract was observed. CHEE showed a higher protection against lipoperoxidation caused by FeSO₄ (82.3% TBARS inhibition) than AAPH (35.7% TBARS inhibition) at 150 μg/mL.

Conclusion

Hyptis fruticosa leaf CHEE is of pharmacological interest because it was able to inhibit the peripheral and central transmission of orofacial pain, while reducing the spreading of the inflammatory processes by neutralizing reactive oxygen species, which are by-products in the biosynthesis of pain mediators.     

Antinociceptive effect of Lecythis pisonis Camb. (Lecythidaceae) in models of acute pain in mice

Ethnopharmacological relevance

Lecythis pisonis Camb., also known in Brazil as sapucaia, is used in folk medicine against pruritus, muscle pain and gastric ulcer.

Aim of the study

To investigate the antinociceptive effect of ethanol extract from Lecythis pisonis leaves (LPEE), fractions (hexane-LPHF, ether-LPEF and ethyl acetate-LPEAF) and mixture of triterpenes [ursolic and oleanolic acids (MT)] in mice.

Materials and methods

LPEE and LPEF were evaluated on the acetic acid induced writhings and formalin, capsaicin and glutamate tests. In addition, MT was investigated on the writhings induced by acetic acid, capsaicin and glutamate tests. In the study of some possible mechanisms involved on the antinociceptive effect of LPEF, it was investigated the participation of opioid system, K⁺_ATP channels and l-arginine-nitric oxide pathway.

Results

LPEE (12.5 and 25 mg/kg, p.o.), LPEF and MT (6.25, 12.5 and 25 mg/kg, p.o.) reduced the writhings in comparison to saline. LPEE (100 mg/kg, p.o.) and LPEF (50 mg/kg, p.o.) were effective in inhibiting both phases of formalin test. In capsaicin test, LPEE (100 and 200 mg/kg, p.o.), LPEF (12.5–50 mg/kg, p.o) and MT (6.25–25 mg/kg, p.o.) showed a significant antinociceptive effect compared to the control. LPEE (25 and 50 mg/kg, p.o.), LPEF (50 and 100 mg/kg, p.o.) and MT (12.5 and 25 mg/kg, p.o.) reduced the glutamate-evoked nociceptive response. Treatment with naloxone, l-arginine and glibenclamide reversed the effect of LPEF in glutamate test.

Conclusions

These results indicate the antinociceptive effect of Lecythis pisonis leaves and suggest that this effect may be related to opioid pathway, K⁺_ATP channels, and l-arginine-nitric oxide modulation. Furthermore, these data support the ethnomedical use of this plant.     

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.