Antinociceptive and anti-inflammatory effects of Satureja hortensis L. extracts and essential oil

Satureja hortensis L. (Lamiaceae) is a medicinal plant used in Iranian folk medicine as muscle and bone pain reliever. In the present study, hydroalcoholic extract, polyphenolic fraction and essential oil of the aerial parts of the herb were prepared and evaluated for the analgesic activity using light tail flick, formalin and acetic acid-induced writhing in mice. Also, the anti-inflammatory effects of the above-mentioned preparations were assessed using carrageenan-induced paw edema in rats. Results showed that in the light tail flick test neither the essential oil nor the extracts could exert any significant effect. The hydroalcoholic extract (2000 mg/kg, p.o.) and the essential oil (200 mg/kg, p.o.) inhibited the mice writhing responses caused by acetic acid. In formalin test, hydroalcoholic extract (500-2000 mg/kg, p.o.), polyphenolic fraction (250-1000 mg/kg, p.o.) and the essential oil (50-200 mg/kg, p.o.) showed analgesic activity and pretreatment with naloxone (1 mg/kg, i.p.) or caffeine (20 mg/kg, i.p.) failed to reverse this antinociceptive activity. Polyphenolic fraction (1000 mg/kg, p.o.) and the essential oil (200 mg/kg) reduced edema caused by carrageenan. These results suggest that S. hortensis L. has antinociceptive and anti-inflammatory effects and probably mechanism(s) other than involvement of opioid and adenosine receptors mediate(s) the antinociception.     

Central Nervous System Activities of Hypericum origanifolium Extract via GABAergic and Opioidergic Mechanisms

Pharmacological effects of hydroalcoholic extract prepared from Hypericum origanifolium Willd. (Guttiferae) on behavioral parameters and pain perceptions of mice were investigated in this study. Depression, anxiety, spontaneous locomotor activity, and motor coordination parameters of mice were assessed by modified forced swimming, hole board, activity cage, and rota‐rod tests, respectively. In addition, antinociceptive effect was evaluated by performing hot‐plate, tail‐clip, and formalin tests. Reboxetine (20 mg/kg), diazepam (1 mg/kg), and morphine (10 mg/kg) were used as reference antidepressant, anxiolytic, and analgesic drugs, respectively. Phytochemical analyses exhibited that chlorogenic acid (2317.12 ppm) and rutin (2108.79 ppm) were the main phenolic compounds in the H. origanifolium extract. The extract (50, 100, and 250 mg/kg) induced significant antidepressant, anxiolytic, and antinociceptive activities following the acute administrations. Anxiolytic effect was antagonized by flumazenil (a benzodiazepine receptor antagonist, 2.5 mg/kg, i.p.) pre‐treatment, which indicated the participation of GABA(A)‐benzodiazepine receptor complex in the activity. Moreover, centrally and peripherally mediated antinociception reversed by naloxone (a non‐selective opioid receptor antagonist, 5 mg/kg, i.p.) pre‐treatment, indicating the involvement of opioid system in the pharmacological action. These findings are the first to indicate the pharmacological effects of the H. origanifolium extract on the emotional state and pain perceptions of mice. Copyright © 2012 John Wiley & Sons, Ltd.     

Analgesic Effect of the Herbal Medicine Catuama in Thermal and Chemical Models of Nociception in Mice

The antinociceptive effect of the herbal medicine Catuama and the hydroalcoholic extract (HE) of each plant present in this extract were investigated in chemical and thermal models of nociception in mice. The extract of Catuama (200 mg/kg, p.o.) caused time-dependent and long-lasting antinociception against acetic acid-induced writhing, formalin and capsaicin-induced licking and also in the tail-flick and hot-plate assays. Its maximal analgesic effect was reached 6 h after its oral administration and this effect lasted for at least 12 h. When given 6 h prior to testing (100 and 200 mg/kg, p.o.), the extract elicited dose-related antinociception, but at 400 mg/kg, its analgesic effect was greatly reduced. The antinociception caused by the extract of Catauma, like those produced by morphine, was largely antagonized by naloxone. The daily administration of the extract (200 mg/kg, p.o. for 4 days) or morphine (5 mg/kg, s.c. for 4 days) produced progressive tolerance, an effect which was reverted by naloxone (5 mg/kg, i.p.). In addition, the Catuama extract showed cross-tolerance with morphine. The Catuama antinociception was not due to its non-specific effects such as muscle relaxation or sedation of animals, nor was it secondary to its antiinflammatory property. When analysed separately the hydroalcoholic extract (HE) obtained from Trichilia catigua, Paullinia cupana, Ptychopelatum olacoids, Zinziber officinalis (200 mg/kg, p.o., 6 h prior) all inhibited acetic acid-induced pain (82%±2%; 66%±2%; 42%±2% and 30%±4% of inhibition, respectively ( p <0.01). In the formalin test the HE of P. olacoids; P. cupana; T. catigua and to a lesser extent, Z. officinalis (200 mg/kg, p.o., 6 h prior) also inhibited both phases of formalin-induced pain ( p <0.01). Thus, antinociception caused by the Catuama extract seems to be dependent on the interaction of the several active principles present in these plants. The mechanisms underlying the antinociception caused by extract of herbal medicine Catuama is still not completely understood, but a significant number of these effects are related to its interaction with the naloxone sensitive opioid system. Together, the results indicate that the herbal medicine Catuama may constitute a useful therapeutic agent for the treatment of clinical pain. © 1997 by John Wiley & Sons, Ltd.     

The juice of fresh leaves of Boerhaavia diffusa L. (Nyctaginaceae) markedly reduces pain in mice

The decoction or juice of leaves of Boerhaavia diffusa L. (Nyctaginaceae) is used in Martinican folk medicine for its analgesic and anti-inflammatory properties. In the present investigation we studied the acute oral (p.o.) toxicity of a crude extract obtained from a lyophilized decoction (DE) and from the juice (JE) of fresh leaves. We observed no signs of toxicity up to the dose of 5000 mg/kg (p.o.) in mice. At the dose of 1000 mg/kg, neither extract altered sleeping time evoked by the administration of pentobarbital sodium (i.p.). The DE and JE of B. diffusa were assessed in standard rodent models of algesia and inflammation. We investigated the antinociceptive effect of DE and JE in chemical (acetic acid) and thermal (hot plate) models of hyperalgesia in mice. Dipyrone sodium (200 mg/kg), JE (1000 mg/kg) and DE at the same dose (p.o.), produced a significant inhibition of acetic acid-induced abdominal writhing in mice (100, 50 and 47% inhibition, respectively) when compared with the negative control (P<0.001). In the hot-plate test in mice, morphine and JE produced a significant increase in latency during the observation time. The DE, however, only raised the pain thresholds during the first period (30 min) of observation (P<0.05). The extracts of B. diffusa were also investigated for their anti-edematogenic effect on carrageenan-induced edema in mice. However, neither extract inhibited the paw edema induced in mice (P>0.05). In the acetic acid-induced abdominal writhing in mice, pre-treatment of the animals with naloxone (5 mg/kg, i.p.) significantly reversed the analgesic effect of morphine and JE but not that of DE. These data show that the active antinociceptive principle of B. diffusa is present mainly in the juice of fresh leaves and has a significant antinociceptive effect when assessed in these pain models. The mechanism underlying this analgesic effect of fresh leaves of B. diffusa remains unknown, but seems to be related to interaction with the opioid system.     

Effect of crocin on the morphine‐induced antinociception in the formalin test in rats

In this study, the effects of intraperitoneal (i.p.) injection of crocin in the absence and presence of subcutaneous (s.c.) injections of morphine and naloxone were investigated on the formalin test in rats. The formalin test was induced by intra‐plantar (i.pl.) injection of formalin (50 μL, 1%), and the time spent licking and biting of the injected paw was measured for 1 h. Formalin induced a marked biphasic (first phase: 0–5 min and second phase: 15–45 min) pain response. Morphine (1 mg/kg, s.c.) significantly (p < 0.05) suppressed both phases of pain. Naloxone (2 mg/kg, s.c.) alone did not change the intensity of pain, but pretreatment with naloxone (2 mg/kg) significantly (p < 0.05) prevented morphine (1 mg/kg)‐induced antinociception. Crocin at doses of 50, 100 and 200 mg/kg significantly (p < 0.05) attenuated pain. Crocin (100 mg/kg, i.p.) significantly (p < 0.05) increased the morphine (1 mg/kg, s.c.)‐induced antinociception. Naloxone (2 mg/kg) did not reverse the suppressive effect of crocin (100 mg/kg) on pain. Crocin at a dose of 400 mg/kg significantly (p < 0.05) suppressed locomotor activities. These findings indicate that morphine through a naloxone‐sensitive mechanism produced analgesia. Crocin produced a dose‐dependent antinociceptive effect. In addition, crocin increased morphine‐induced antinociception, but naloxone did not change the antinociceptive effect of crocin. Copyright © 2009 John Wiley & Sons, Ltd.     

Dragon's blood from Croton urucurana (Baill.) attenuates visceral nociception in mice

Dragon's blood, the red sap from Croton urucurana Baill. (Euphorbiaceae) has a profound history of traditional use in conditions such as inflammation, diarrhoea and gastrointestinal distress. Previous studies established its anti-inflammatory, antidiarrhoeal and analgesic properties and in this study we verified its potential to suppress visceral pain, using capsaicin- and cyclophosphamide-induced models of visceral nociception. Mice that received intra-colonic capsaicin (0.3%, 50 microl/animal) or intraperitoneal injection of cyclophosphamide (400 mg/kg) manifested spontaneous nociceptive behaviors or crises, which were significantly suppressed in animal groups treated with red sap (200 and 400 mg/kg, p.o.) or that received N-acetylcysteine (750 mg/kg, i.p.) or morphine (7.5 mg/kg, s.c.), as positive controls. In capsaicin model, the antinociception produced by 200 mg/kg red sap was found to be naloxone-sensitive (2 mg/kg, i.p.), suggesting an opioid mechanism. In tests of open-field and pentobarbital-sleeping time, mice received 200mg/kg red sap showed no significant alterations in either locomotion frequency or on sleeping time, indicating that the observed antinociception is not a consequence of sedation or motor abnormality. These findings highlight the visceral antinociceptive property of Croton urucurana sap and further support its ethno-medical use to alleviate pain associated with gastrointestinal and other related disorders.     

Olive (Olea europaea L.) leaf extract elicits antinociceptive activity, potentiates morphine analgesia and suppresses morphine hyperalgesia in rats

Aim of the study

Olive (Olea europaea) leaves are used as anti-rheumatic, anti-inflammatory, antinociceptive, antipyretic, vasodilatory, hypotensive, antidiuretic and hypoglycemic agents in traditional medicine. Recently, it has been shown that olive leaf extract (OLE) has calcium channel blocker property; however, its influences on nociceptive threshold and morphine effects have not yet been clarified.

Materials and methods

All experiments were carried out on male Wistar rats. The tail-flick, hot-plate and formalin tests were used to assess the effect of OLE on nociceptive threshold. To determine the effect of OLE on analgesic and hyperalgesic effects of morphine, OLE (6, 12 and 25 mg/kg i.p.) that had no significant nociceptive effect, was injected concomitant with morphine (5 mg/kg and 1 μg/kg i.p., respectively). The tail-flick test was used to assess the effect of OLE on anti- and pro-nociceptive effects of morphine.

Results

The data showed that OLE (50-200 mg/kg i.p.) could produce dose-dependent analgesic effect on tail-flick and hot-plate tests. Administration of 200 mg/kg OLE (i.p.) caused significant decrease in pain responses in the first and the second phases of formalin test. In addition, OLE could potentiate the antinociceptive effect of 5 mg/kg morphine and block low-dose morphine-induced hyperalgesia.

Conclusion

Our results indicate that olive leaf extract has analgesic property in several models of pain and useful influence on morphine analgesia in rats. Therefore, it can be used for the treatment and/or management of painful conditions.     

Antinociceptive effect of the aqueous extract obtained from roots of Physalis angulata L. on mice

In this study, we attempted to identify the possible antinociceptive action of aqueous extract (AE) obtained from roots of Physalis angulata, known in Brazil as "Camapu", used to treat various pain-related physiological conditions. The AE of Physalis angulata (10-30 mg/kg) given by i.p. or p.o. route, 0.5 and 1h prior, produced significant inhibition of abdominal constrictions caused by acetic acid, with ID(50) values of 18.5 (17.4-19.8) and 21.5 (18.9-24.4)mg/kg and inhibitions of 83+/-8 and 66+/-5%, respectively. The AE (10-60 mg/kg, i.p.) also caused significant inhibition of the late-phase of formalin-induced pain, with an ID(50) value of 20.8 (18.4-23.4)mg/kg and inhibition of 100%. Treatment of mice with AE (60 mg/kg, i.p.) or with morphine (10mg/kg, i.p.) produced a significant increase of the reaction time in the hot-plate test. These results demonstrate, for the first time, that the AE of Physalis angulata produce marked antinociception against the acetic acid-induced visceral pain and inflammatory pain responses induced by formalin in mice. The mechanism by which the AE produces antinociception still remains unclear. However, pharmacological and chemical studies are continuing in order to characterize the mechanism(s) responsible for the antinociceptive action and also to identify the active principles present in Physalis angulata. Moreover, the antinociceptive action demonstrated in the present study supports, at least partly, the ethnomedical uses of this plant.     

Oleuropein,Chief Constituent of Olive Leaf Extract,Prevents the Development of Morphine Antinociceptive Tolerance through Inhibition of Morphine‐induced L‐type Calcium Channel Overexpression

It has been shown that blockade of L‐type calcium channels could abolish the development of opioid‐induced antinociceptive tolerance. Here, the antitolerant effects of olive leaf extract (OLE) and its main component, oleuropein, which have a calcium channel blocker property were determined. Adult male Wistar rats were injected with morphine (20 mg/kg, i.p.) for 8 days to induce antinociceptive tolerance. Then OLE (50–200 mg/kg i.g.) and oleuropein (1–10 mg/kg i.p.) were injected concomitantly with morphine. The tail‐flick test was used to assess the nociceptive threshold. The dorsal half of the lumbar spinal cord was assayed for the expression of L‐type calcium channel using semiquantitative RT‐PCR. The results showed that OLE (200 mg/kg) completely prevented morphine tolerance development. In addition, oleuropein in dose of 10 mg/kg, but not in 5 mg/kg, prevented the development of morphine antinociceptive tolerance. In addition, a significant increase in the mRNA levels of calcium channel (43.9%) was observed in the lumbar spinal cord of tolerant animals, which was reversed by effective of dose OLE. In conclusion, the results indicate that olive leaf extract has a potential antitolerant property against the chronic usage of morphine and that its main component, oleuropein, is responsible for such effect. Copyright © 2012 John Wiley & Sons, Ltd.     

Evaluation of the analgesic effect of alkaloid extract of Peganum harmala L.: possible mechanisms involved

The seeds of Peganum harmala L. (Pgh) (Zygophyllaceae) have been used in Moroccan traditional medicine for treatment of a various diseases and to relieve dolorous process. The major objective of this paper was to investigate the mechanism of the analgesia induced by alkaloid extract of Peganum harmala. In the present work, the antinociceptive action was assayed in several experimental models in mice: writhing, formalin, and hot plate tests. The alkaloid extract (12.5 and 25mg/kg) and in a dose-dependent manner significantly reduced the nociception by acetic acid intraperitoneal injection (p<0.001). In the formalin test, the extract also significantly reduced the painful stimulus in both phases of the test (p<0.001). Treatment with the extract when given by (i.p. or i.c.v.) or with morphine (10mg/kg, i.p.) produced a significant increase of the reaction time in hot plate test. These result showed that the alkaloid extract of Pgh contains active analgesic principles acting both centrally and peripherally. Furthermore, this antinociceptive effect has been avoided by naloxone at a dose of 1mg/kg in the first phase of formalin and hot plate tests indicating that this extract act partly through an opioid-mediated mechanism. In conclusion, the alkaloid extract of Peganum harmala seems to have both central and peripheral antinociceptive activities which may be mediated by opioid receptors.     

Antinociceptive and anti-inflammatory properties from the bulbs of Cipura paludosa Aubl

This study examined the antinociceptive and anti-inflammatory actions of Cipura paludosa Aubl. in several models of inflammatory pain in mice and rats. The ethanolic extract (EE) from Cipura paludosa (1-300mg/kg) given by i.p. and p.o. routes, 30 or 60min earlier, produced a dose-dependent inhibition of the acetic acid-induced pain and Evans blue leakage in mice with ID(50) values of 2.8 and 17.6mg/kg and 17.2 and 176.1mg/kg, respectively. The EE (10mg/kg, i.p.) also inhibited the allodynia (39+/-6%)- and oedema (97+/-6%)-induced by the intraplantar injection of CFA. In addition, the EE (1-30mg/kg, i.p.) inhibited both mechanical and thermal hyperalgesia induced by prostaglandin E(2), PMA and bradykinin in the rat paw, with ID(50) values of 7.3, 12.1 and 4.7 and 13.9, 18.9 and 1.5mg/kg, respectively. These data demonstrate that EE of Cipura paludosa elicited pronounced antinociceptive and anti-inflammatory actions against some models of inflammatory pain in mice and rats. The mechanism by which the extract produced antinociception still remains unclear, but a great part of this effect seems to be related to modulation of the release or action of pro-inflammatory mediators. Moreover, the antinociceptive action demonstrated in the present study supports, at least partly, the ethnomedical uses of this plant.     

Anti-inflammatory,analgesic activity and acute toxicity of Glaucium grandiflorum extract

The species of Glaucium have been used in Iranian herbal medicine as laxative, hypnotic, antidiabetic agents and also in the treatment of dermatitis. The anti-inflammatory and analgesic effects of the aerial parts of Glaucium grandiflorum Boiss & Huet (Papaveraceae), a native plant of Iran, were studied using carrageenan induced edema, formalin and hot plate tests. The G. grandiflorum extract at the dose of 200 mg/kg had more edema inhibition than indomethacin at the doses of 10 (P<0.01) and 8 mg/kg (P<0.001) in the carrageenan test. The ED₅₀ (i.p.) in the edema induced by carrageenan was 13.59 mg/kg. In formalin test, the extract (60–90 mg/kg, i.p.) caused graded inhibition of both phases of formalin-induced pain. In hot plate test, the i.p. administration of the extract at the doses of 60, 70, 80 and 90 mg/kg significantly raised the pain threshold at a observation time of 45 min in comparison with control (P<0.001). The extract, at the antinociceptive doses, did not affect motor coordination of animals when assessed in the rotarod model. The 72 h acute LD₅₀ value of this extract after i.p. administration in mice was 797.94 mg/kg.     

Anti-inflammatory and analgesic activity of Biebersteinia multifida DC. root extract

The root of Biebersteinia multifida DC (Geraniaceae), a native plant of Iran, has been used topically for the treatment of musculoskeletal disorders as a folk medicine. The anti-inflammatory and analgesic effects of the root extract were studied using carrageenan induced edema and formalin tests. A similar activity was seen between Biebersteinia multifida root extract (10 mg/kg; i.p.) and indomethacin (4 mg/kg; i.p.) in carrageenan test. The results of formalin test showed the analgesic activity of the root extract (50 mg/kg; i.p.) was comparable with morphine (10 mg/kg; i.p.) at the first phase of formalin test. Furthermore, the probable ulcerogenic activity of the root extract was also studied. The extract did not show any ulcerogenic effect at anti-inflammatory doses (10 mg/kg; p.o.).     

Antinociceptive and anti-inflammatory effects of Elaeagnus angustifolia fruit extract

In this study, probable antinociceptive and anti-inflammatory effects of Elaeagnus angustifolia fruit components, were evaluated. For evaluation of antinociceptive effects, the chronic (formalin test) and acute (tail-flick) pain models of rats were used. For the anti-inflammatory effects, the paw inflammation model was used through subcutaneous injection of 5% formalin to the paw of male rats. Water extracts of the fruit and its components in the single dose were assessed through comparison with the antinociceptive and anti-inflammatory effects of sodium salicylate (SS) as a positive control. Administration of 300 mg/kg of SS (i.p.) had no effect on tail flick latency, while 1000 mg/kg of total (i.p. and p.o.) and endocarp (i.p.) extract, increased this latency (P<0.01, P<0.001, respectively), which was not reversed by naloxone (2 mg/kg). In the formalin test, SS (300 mg/kg, i.p.) and the extract (1000 mg/kg, p.o. ) alleviated the animals nociception in the second phase, while in the first phase they were not effective. The total and endocarp extracts (1000 mg/kg, i.p.) showed a significant effect on both phases (P<0.01, P<0.001, respectively) which was also not reversed by naloxone (2 mg/kg, i.p.). In the acute anti-inflammatory test, the total extract and the aqueous extract of individual fruit components showed a significant effect (P<0.001). This anti-inflammatory effect was not significant compared with the anti-inflammatory effect of SS. Because of the extract effect on the tail-flick latency and both phases of the formalin test, the site of its analgesic action is probably central, and the mechanism of antinociceptive action of the extract are not related to the opioid system. Our phytochemical studies indicated that aqueous extract of E. angustifolia fruit contains flavonoids, terpenoids and cardiac glycosides.     

Antinociceptive and antiinflammatory activities of pine (Pinus densiflora) pollen extract

The study aimed to evaluate the antinociceptive and antiinflammatory activity of pine (Pinus densiflora) pollen in mice. The antinociceptive activity was determined using acetic acid-induced abdominal constriction and formalin-induced licking, and the hot plate test. Antiinflammatory effects were evaluated using carrageenan- and formalin-induced paw edema, and arachidonic acid-induced ear edema in mice. The ethanol extract of pine pollen (100 and 200 mg/kg, p.o.) produced a significant inhibition of both phases of the formalin pain test in mice, a reduction in mouse writhing induced by acetic acid and an elevation of the pain threshold in the hot plate test in mice. The pine pollen extract also produced a significant inhibition of carrageenan- and formalin-induced paw edema as well as arachidonic acid-induced ear edema in mice. The inhibitions were similar to those produced by aminopyrine and indomethacin, p.o. The different polyphenols found in pine pollen could account for the antinociceptive and antiinflammatory actions. The results obtained indicate that the extract possesses analgesic and antiinflammatory effects.     

Evaluation of the antidiarrhoeal activity of Byrsocarpus coccineus

Based on its use in traditional African medicine, the antidiarrhoeal activity of the aqueous leaf extract of Byrsocarpus coccineus, Connaraceae, was evaluated on normal and castor oil-induced intestinal transit, castor oil-induced diarrhoea, enteropooling and gastric emptying. The extract (50, 100, 200 and 400 mg/kg, p.o.) produced a significant (P<0.05) dose dependent decrease in propulsion in the castor oil-induced intestinal transit in mice. The mean peristaltic index (%) for these doses of extract, control (distilled water; 10 ml/kg, p.o.) and morphine (10 mg/kg, s.c.) were 55.27+/-1.86, 53.12+/-3.73, 38.60+/-3.79, 30.25+/-1.27, 89.33+/-5.62 and 20.29+/-3.38, respectively. The effect of the extract at the highest dose was significantly (P<0.05) lower than that of the standard drug. This effect was antagonised by yohimbine (1 mg/kg, s.c.) but not by isosorbide dinitrate (IDN, 150 mg/kg, p.o.). At 200 mg/kg, the extract produced a significant decrease in propulsion in normal intestinal transit. In a dose dependent manner, it delayed the onset of diarrhoea, produced a significant decrease in the frequency of defaecation, severity of diarrhoea and protected the mice treated with castor oil. Mean diarrhoea scores were 30.83+/-1.72, 22.40+/-1.71, 21.43+/-1.32, 13.80+/-0.33, 18.00+/-3.94 and 7.67+/-2.41 for control, extract (50, 100, 200 and 400 mg/kg) and morphine, respectively. This effect was not antagonized by IDN. The extract (400 mg/kg) significantly decreased the volume (ml) of intestinal fluid secretion induced by castor oil (0.60+/-0.23) compared with 1.27+/-0.12 for control. However, there was no significant effect on gastric emptying. The results obtained suggest that Byrsocarpus coccineus possesses antidiarrhoeal activity due to its inhibitory effect on gastrointestinal propulsion, mediated through alpha(2) adrenoceptors, and also inhibition of fluid secretion. Preliminary phytochemical analysis revealed the presence of alkaloids, tannins, saponins, reducing sugars, glycosides and anthraquinones.     

Antinociceptive and antipyretic activities of Pongamia pinnata leaves

In the present study, the antinociceptive activity of a 70% ethanol extract of Pongamia pinnata leaves (PLE) was investigated in different models of pain in mice and rats. Further, PLE was also evaluated for its antipyretic activity in Brewer's yeast-induced pyrexia in rats. Per os (p.o.) administration of the PLE (100-1000 mg/kg) produced significant antinociceptive activity in the hotplate and tail flick (central) as well as in acetic acid writhing and Randall-Selitto (peripheral) nociceptive tests suggesting the involvement of both central and peripheral mechanisms in alleviating the pain response. In addition, PLE also exhibited a significant antipyretic response in Brewer's yeast-induced pyrexia in rats. These results demonstrated that PLE possesses marked antinociceptive as well as antipyretic activities and thus scientifically validated its use in the treatment of pain and pyretic disorders.     

Characterisation of the anti-inflammatory and antinociceptive activities of the Hyptis pectinata (L.) Poit essential oil

Aim of the study

Hyptis pectinata Poit (Lamiaceae) is grown in the northeastern regions of Brazil and is popularly known as “sambacaitá” or “canudinho”. It is extensively used in folk medicine to treat inflammatory conditions, bacterial infections, pain, and cancer.

Materials and methods

Hyptis pectinata essential oil (EO, 10, 30, and 100 mg/kg, p.o.) and the reference drugs morphine (5 mg/kg, p.o.) and acetylsalicylic acid (ASA, 200 mg/kg, p.o.) were evaluated using models for analgesia (acetic acid-induced contortions and hot plate) or inflammation (formalin-induced licking response and the subcutaneous air-pouch model). To elucidate the EO's mechanism of action, animals were pre-treated with the opioid receptor antagonist naloxone (1 mg/kg, i.p.), the cholinergic antagonist atropine (1 mg/kg, i.p.), or l-nitro arginine methyl ester (l-NAME, 3 mg/kg, i.p.) 30 min prior to the oral administration of the EO.

Results

The EO significantly inhibited the number of writhings and the time the animals spent licking their formalin-injected paws (second phase). The EO, at doses of 30 and 100 mg/kg, increased baseline measurements and area under the curve measurements in the hot plate model, respectively. The administration of naloxone reversed the antinociceptive effect of the EO in the hot plate model. l-NAME significantly reversed the effects of the EO in the contortions and hot plate models. Atropine completely reversed the antinociceptive activity of the EO in all models. Additionally, the EO inhibited the inflammatory process induced by subcutaneous carrageenan injection by reducing cell migration, exudate volume, protein concentration, and inflammatory mediators (nitric oxide, prostaglandin E2, IL-6, and TNF-α) produced in the pouch.

Conclusions

Our results indicate that the Hyptis pectinata essential oil exhibits antinociceptive effects, likely mediated by opioid and cholinergic receptors, and anti-inflammatory activity through the inhibition of nitric oxide and PGE2 production.     

Antinociceptive and anti-inflammatory effects of Tanacetum parthenium L. extract in mice and rats

Oral administration of the feverfew (Tanacetum parthenium) extract led to significant antinociceptive and anti-inflammatory effects against acetic acid-induced writhing in mice and carrageenan-induced paw edema in rats, respectively. These responses were dose-dependent (10, 20, 40 mg/kg, p.o.). Parthenolide (1, 2 mg/kg i.p.), the active constituent of the extract also produced antinociceptive and anti-inflammatory effects. Naloxone (1 mg/kg i.p.), an opiate antagonist, failed to reverse feverfew extract and parthenolide-induced antinociception. Feverfew extract in higher doses (40, 60 mg/kg p.o.) neither altered the locomotor activity nor potentiated the pentobarbitone-induced sleep time in mice. It also did not change the rectal temperature in rats. Feverfew extract exerted antinociceptive and anti-inflammatory effects without altering the normal behaviour of the animals.     

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.