Analgesic and anti-inflammatory effects of Ligularia fischeri leaves in experimental animals

Aim of the study

The ethanol extract (LF) of Ligularia fischeri var. spiciformis (leaf) has been evaluated for antinociceptive and anti-inflammatory activities in mice.

Materials and Methods

Analgesic and anti-inflammatory activities were studied by measuring nociception induced by formalin, acetic acid and hot-plate, and inflammation induced by carrageenan, formalin, and arachidonic acid.

Results

The acute treatment of mice with LF at doses of 100 and 200 mg/kg, by oral administration, produced a significant antinociceptive effect in the acetic acid-induced writhing, formalin-induced pain licking and hot-plate-induced pain. Also, the LF significantly inhibited both carrageenan- and formalin-induced inflammation as well as arachidonic acid-induced ear edema in mice.

Conclusions

These inhibitions were statistically significant (P < 0.05). Thus, our investigation suggests a potential benefit of Ligularia fischeri in treating conditions associated with inflammatory pain.     

Inhibition of the human neutrophil oxidative metabolism by Baccharis dracunculifolia DC (Asteraceae) is influenced by seasonality and the ratio of caffeic acid to other phenolic compounds

Ethnopharmacological relevance

The great potential of phytotherapic drugs for treating and preventing inflammatory diseases mediated by increased neutrophil reactive oxygen species (ROS) generation has guided the search for new natural products with antioxidant and immunomodulatory properties. Baccharis dracunculifolia D.C. (Asteraceae), the main botanical source of Brazilian green propolis, is a native plant from Brazil widely used in folk medicine as anti-inflammatory. This study aims: (a) to determine the influence of seasonality on the chemical profile and biological activity of Baccharis dracunculifolia (Asteraceae) leaf extracts (BdE); (b) to analyze the correlation between the major compounds and the ability of BdE to modulate the superoxide anion and total ROS generation by human neutrophils.

Materials and methods

The extracts were obtained from leaf samples collected monthly during one year. The superoxide anion and total ROS generation were assessed by the lucigenin (CL-luc)- and luminol (CL-lum)-enhanced chemiluminescence assays.

Results

Seasonality influenced more the quantitative than the qualitative chemical profile of B. dracunculifolia, and affected its biological activity. The major compounds identified were caffeic acid, p-coumaric acid, aromadendrin-4′-methyl ether (AME), isosakuranetin and artepillin C. The IC₅₀ values obtained for CL-lum and CL-luc inhibition by BdE ranged from 8.1–15.8 and 5.8–13.3 µg mL⁻¹, respectively, and correlated positively with caffeic acid concentration. CL-luc inhibition correlated negatively with the concentration of artepillin C, AME, isosakuranetin and total flavonoids. The BdE sample from May/07 inhibited CL-lum and CL-luc the most strongly (IC₅₀=8.1±1.6 and 5.8±1.0 µg mL⁻¹, respectively), and contained the highest ratio of caffeic acid to the other isolated compounds; so, this ratio could be employed as chemical marker for this biological activity of B. dracunculifolia.

Conclusion

The ability of B. dracunculifolia to inhibit the neutrophil ROS generation depends more on the type and ratio of phenolic compounds and flavonoids than on their high absolute concentrations. Together, our results help select the most appropriate plant material for the production of phytotherapic drugs to be used in the treatment of inflammatory diseases mediated by increased neutrophil activation.     

Comparison of active constituents,acute toxicity,anti-nociceptive and anti-inflammatory activities of Porana sinensis Hemsl., Erycibe obtusifolia Benth. and Erycibe schmidtii Craib

Ethnopharmacological relevance

Erycibe obtusifolia and Erycibe schmidtii, which belong to the same genus as Erycibe, are widely used in traditional medicine for the treatment of joint pain and rheumatoid arthritis (RA). Porana sinensis has become a widely used substitute for Erycibe obtusifolia and Erycibe schmidtii as they have declined in the wild. In the present work, the content of the main active components, the acute toxicity, the anti-nociceptive and anti-inflammatory activities of Porana sinensis, Erycibe obtusifolia and Erycibe schmidtii were compared, and the mechanisms of anti-nociceptive and anti-inflammatory activities were discussed.

Materials and methods

A quantitative HPLC (high performance liquid chromatography) method was first developed to compare the content of the main active components (scopoletin, scopolin and chlorogenic acid). The anti-inflammatory and anti-nociceptive activities of 40% ethanolic extracts of the three plants were compared using the models of xylene-induced ear edema, formalin-induced inflammation, carrageenan-induced air pouch inflammation, acetic acid-induced writhing and formalin-induced nociception. The acute toxicity of the 40% ethanolic extracts of the three plants was studied.

Results

The assay suggested a large content of scopoletin, scopolin and chlorogenic acid in the three plants. The 40% ethanolic extracts of the three plants were almost non-toxic at the dose of 5 g/kg and all of them showed significant anti-inflammatory effects in the tests of xylene-induced ear edema and formalin-induced inflammation. In the carrageenan-induced air pouch inflammation test, the synthesis of PGE2 was significantly inhibited by all the extracts. They significantly inhibited the number of contortions induced by acetic acid and the second phase of the formalin-induced licking response. Naloxone was not able to reverse the analgesic effect of these extracts.

Conclusion

The study identifies the similarity of the three plants in their main active components as well as acute toxicity, anti-nociceptive and anti-inflammatory activities. It supports the use of Porana sinensis as a suitable substitute, but further studies are needed to confirm this.     

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.     

Geopropolis from Melipona scutellaris decreases the mechanical inflammatory hypernociception by inhibiting the production of IL-1β and TNF-α

Ethnopharmacological relevance

The pharmacological activity of geopropolis collected by stingless bees (important and threatened pollinators), a product widely used in folk medicine by several communities in Brazil, especially in the Northeast Region, needs to be studied.

Objective

The aim of this study was to evaluate the antinociceptive activity of Melipona scutellaris geopropolis (stingless bee) using different models of nociception.

Material and methods

The antinociceptive activity of the ethanolic extract of geopropolis (EEGP) and fractions was evaluated using writhing induced by acetic acid, formalin test, carrageenan-induced hypernociception, and quantification of IL-1β and TNF-α. The chemical composition was assessed by quantification of total flavonoids and phenolic compounds.

Results

EEGP and its hexane and aqueous fractions showed antinociceptive activity. Both EEGP and its aqueous fraction presented activity in the mechanical inflammatory hypernociception induced by the carrageenan model, an effect mediated by the inhibition of IL-1β and TNF-α. The chemical composition of EEGP and its hexane and aqueous fractions showed a significant presence of phenolic compounds and absence of flavonoids.

Conclusion

Our data indicate that geopropolis is a natural source of bioactive substances with promising antinociceptive activity.     

Pharmacological evidence favouring the use of Nauclea latifolia in malaria ethnopharmacy: Effects against nociception,inflammation, and pyrexia in rats and mice

Aim of the study

Nauclea latifolia Smith is used traditionally in the treatment of uncomplicated malaria and painful conditions among its several other applications. The objective of this study is to investigate the pharmacological activities of the plant relevant to the symptomatic treatment of malaria fever and other painful conditions as an initial step towards developing an effective therapy for the symptomatic management of malaria fever and relief of other painful conditions.

Materials and methods

Various concentrations of the aqueous extract of the root bark of this plant were evaluated for its anti-nociceptive, anti-inflammatory and anti-pyretic activities in mice and rats. Investigation of the anti-nociceptive activities was performed using the acetic acid-induced abdominal constriction and hot-plate tests in mice and formalin-induced pain test in rats, as models of nociception. The extract was also investigated for its effect against inflammation induced by egg-albumin and pyrexia induced by yeast in rats.

Results

Our data showed that the aqueous extract of Nauclea latifolia root bark (50–200 mg/kg p.o.) significantly (P < 0.05) attenuated writhing episodes induced by acetic acid and increased the threshold for pain perception in the hot-plate test in mice, dose-dependently. The product also remarkably decreased both the acute and delayed phases of formalin-induced pain in rats and also caused a significant reduction in both yeast-induced pyrexia and egg-albumin-induced oedema in rats. These effects were produced in a dose-dependent manner.

Conclusion

The results suggest the presence of biologically active principles in the extract with anti-nociceptive, anti-inflammatory and anti-pyretic activities that justifies its use in malaria ethnopharmacy and subsequent development for clinical application.     

Anti-inflammatory and analgesic properties of Heracleum persicum essential oil and hydroalcoholic extract in animal models

Ethnopharmacological relevance

Fruits of Heracleum persicum (Apiaceae) are used as pain killer in Iranian folkloric medicine.

Aims of study

To evaluate the anti-inflammatory and analgesic effects of the hydroalcoholic extract and essential oil of the plant fruits and analyzing the essential oil.

Materials and methods

Essential oil and hydroalcoholic extracts of the fruits were prepared according to standard methods and the components of essential oil were identified using GC–MS method. The acetic acid-induced writhing response and formalin test were used in male mice to assess analgesic activity. For evaluation of anti-inflammatory effect, carrageenan-induced rat paw edema was used.

Results

Hexyl butyrate (56.5%), octyl acetate (16.5%), hexyl 2-methylbutanoate (5.2%) and hexyl isobutyrate (3.4%) were identified as the major constituents of the oil. Oral or intraperitoneal administration of Heracleum persicum essential oil (HPEO) at doses of 50–200 mg/kg and Heracleum persicum hydroalcoholic extract (HPHE) at doses of 250 and 500 mg/kg significantly reduced acetic acid-induced abdominal constrictions. HPEO and HPHE also significantly attenuated the pain response of the second phase of formalin test.In carrageenan test HPEO at doses of 100 and 200 mg/kg and HPHE at a dose of 400 mg/kg induced a significant reduction of paw edema.

Conclusions

These results clearly show the analgesic and anti-inflammatory effects of the plant essential oil and hydroalcoholic extract. Further studies are needed to clarify the mechanism of action and the components responsible for these pharmacological effects.     

Anti-inflammatory and analgesic activities of methanolic extract of Kigelia pinnata DC flower

Ethnopharmacological relevance

Kigelia pinnata DC is extensively used in Indian traditional medicine for several diseases including inflammatory and painful disorders.

Aim of the study

The aim of the present study is to investigate the possible anti-inflammatory and analgesic activities of methanolic extract of Kigelia pinnata flower (MKFL) to support the medicinal uses claimed by folklore practitioners.

Materials and methods

MKFL is evaluated for its anti-inflammatory activity in carrageenan-induced paw edema model in rats and analgesic activity in acetic acid-induced writhing, hot plate and formalin-induced paw licking models in mice.

Results

MKFL exhibited a significant (P < 0.01) anti-inflammatory and analgesic activities with the doses of 100, 200 and 400 mg/kg b.w. in rats and mice respectively.

Conclusions

The results of the experimental study thus strongly support the traditional use of this plant for inflammatory and pain disorders.     

Evaluation of anti-nociceptive,anti-inflammatory and antipyretic activities of Artemisia scoparia hydromethanolic extract

Ethnopharmacological relevance

Artemisia scoparia (redstem wormwood) locally known as jhahoo or jaukay, is traditionally used in pain, inflammation and febrile conditions. So far, little or no scientific work has been reported to validate its folk uses in the alleviation of pain, fever and inflammation. The present study was designed to explore the analgesic, anti-inflammatory and antipyretic effects of the Artemisia scoparia hydromethanolic extract (ASHME), and to validate its traditional use in Asia.

Materials and methods

This study made use of thermal (hot plate induced) and chemical (acetic acid induced) nociception models in mice. In addition, the mechanism of antinociception in hot plate test was further evaluated in the presence of caffeine (10 mg/kg), naloxone (2 mg/kg) and monosodium glutamate (1 g/kg). While carrageenan induced rat paw edema and yeast induced mouse pyrexia models were used to test the anti-inflammatory and antipyretic activities.

Results

Administration of single intraperitoneal doses (400 mg/kg and 800 mg/kg) of ASHME significantly reduced the carrageenan induced paw edema in rats (P<0.05, P<0.001) by 54% and 74%, increased the thermal nociception time in the hot plate test up to 2- and 2.5-fold (P<0.01, P<0.001), inhibited the acetic acid induced writhings in mice by 41.12% and 61.53% (P<0.001), and attenuated the yeast induced pyrexia in mice by nearly 74% and 90% respectively (P<0.01, P<0.001). Caffeine (10 mg/kg), naloxone (2 mg/kg) and monosodium glutamate (1 g/kg) significantly (P<0.001) abolished the anti-nociceptive response of ASHME (400 mg/kg).

Conclusion

These findings suggest that the Artemisia scoparia hydromethanolic extract of ASHME possesses anti-nociceptive, anti-inflammatory and antipyretic potentials, which support its use, for the said conditions, in traditional medicine and should be further exploited for its use in clinical medicine.     

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.     

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.     

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.     

Anti-inflammatory effect of triterpene 3β, 6β, 16β-trihydroxylup-20(29)-ene obtained from Combretum leprosum Mart & Eich in mice

Ethnopharmacological relevance

The 3β, 6β, 16β-trihydroxylup-20(29)-ene (TTHL) is a pentacyclic triterpene obtained from a medicinal plant named Combretum leprosum. In folk medicine, this plant is used to treat several diseases associated with inflammation and pain. We previously demonstrated that TTHL presents a significant antinociceptive effect, suggesting the involvement of the glutamatergic system.

Aim of the study

This study was designed to investigate the effect of TTHL on nociception and vascular permeability induced by acetic acid. We also evaluated the effect of TTHL on carrageenan-induced peritonitis and the levels of cytokines (interleukin 1-β [IL-1β], tumor necrosis factor α [TNF-α] and interleukin 10 [IL-10]) on peritoneal fluid.

Materials and methods

TTHL was administered orally by intra-gastric gavage (i.g.) 60 min prior to experimentation. Abdominal contractions and vascular permeability were induced by an intraperitoneal (i.p.) injection of acetic acid (0.6%). We also investigated whether TTHL decreases carrageenan-induced peritonitis (750 μg/cavity) by measuring leukocyte migration and vascular permeability. In addition, we evaluated the effects of TTHL on TNF-α, IL-1β and IL-10 release induced by carrageenan on peritoneal fluid. The levels of these cytokines were measured by ELISA.

Results

TTHL (0.01–10 mg/kg) administered by intra-gastric (i.g.) gavage inhibited (69±3%) acetic acid-induced abdominal constrictions, with an ID₅₀ of 0.15 (0.03–0.8) mg/kg. TTHL (10 mg/kg) also reduced the leukocyte infiltration induced by acetic acid, with an inhibition of 59±9 but had no effect on abdominal vascular permeability. In addition, indomethacin (10 mg/kg, i.p.) reduced the nociceptive behavior (92±1%), total leukocyte migration (29±3%) and capillary permeability (71±3%) induced by acetic acid. While the glucocorticoid dexamethasone (2 mg/kg, s.c.) reduced partially but significantly the nociception (31±1%), besides to promote a marked reduction on total leukocyte migration (60±2%) to the peritoneal cavity caused by acetic acid. In a model of peritonitis induced by carrageenan, TTHL also reduced total leukocyte migration, mainly neutrophils (inhibition of 84±3% and 85±2% at 30 mg/kg and 100 mg/kg, respectively). Likewise, dexamethasone (0.5 mg/kg, i.p.) resulted in an inhibition of 93±3%. Nevertheless, carrageenan-induced abdominal vascular permeability was reduced by dexamethasone but was not altered by TTHL. Furthermore, dexamethasone and TTHL significantly reduced the TNF-α and IL-1β levels in peritoneal fluid, whereas the IL-10 levels were unchanged.

Conclusions

Altogether, our data confirm the antinociceptive effect of TTHL and demonstrate its effect in inflammatory animal models, providing novel data about this compound, which could be useful as an anti-inflammatory drug.     

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.     

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.     

Anti-nociceptive and anti-inflammatory effects of Croton crassifolius ethanol extract

Ethnopharmacological relevance

Croton crassifolius has been used to treat snake bites, stomach ache, sternalgia, joint pain, as well as pharyngitis, jaundice, and rheumatoid arthritis in traditional Chinese medicine. However, there is no scientific evidence which supports the use in the literature.

Aim of the study

To investigate the anti-nociceptive and anti-inflammatory effects of ethanol extract of C. crassifolius.

Materials and methods

Anti-nociceptive actions of C. crassifolius were assessed in mice using the hot-plate test, acetic acid-induced writhing test, and formalin test. Anti-inflammatory effects of C. crassifolius were determined in three animal models: acetic acid-induced capillary permeability accentuation in mice, carrageenan-induced edema of the hind paw in rats, and cotton pellet-induced granuloma formation in rats.

Results

Ethanol extract of C. crassifolius showed no significant anti-nociceptive activity in the hot-plate test. However, extract at dosages of 45, 90 and 180 mg/kg significantly reduced acetic acid-induced writhing by 28.89% (P<0.05), 38.37% (P<0.05), and 56.53% (P<0.001), respectively. The extract also caused marked dose-related inhibition of formalin-induced pain in the second phase (P<0.05 for 45 mg/kg, P<0.001 for 90 and 180 mg/kg extract). C. crassifolius extract at dosages of 45, 90 and 180 mg/kg significantly reduced acetic acid-induced capillary permeability accentuation in mice by 26.18% (P<0.05), 65.70% (P<0.001), and 79.19% (P<0.001), and suppressed carrageenan-induced paw edema by 21.28% (P<0.05), 30.69% (P<0.01), and 49.17% (P<0.001) at 6 h after carrageenan injection, respectively. 180 mg/kg of the extract also showed significant activity against carrageenan-induced paw edema at 4 h. At 90 and 180 mg/kg, the extract inhibited cotton pellet-induced granuloma formation in rats.

Conclusions

These results collectively demonstrate that the ethanol extract of C. crassifolius possesses peripheral anti-nociceptive and anti-inflammatory effects, providing evidence to rationalize the traditional use of C. crassifolius for the treatment of pain and inflammation.     

Anti-inflammatory and antinociceptive activities of the ethanolic extract of Bougainvillea xbuttiana

Ethnopharmacological relevance

Bougainvillea xbuttiana is widely distributed in Mexico and it is used as an analgesic in folk medicine.

Aim of the study

In the present study the in vivo antinociceptive and anti-inflammatory effects of the Bougainvillea xbuttiana ethanolic extract have been studied in mice.

Materials and methods

The phytochemical analysis was performed. Antinociceptive activity was evaluated through writhing and formalin test in mice. The anti-inflammatory activity was determined with the carrageenan-induced mice paw oedema model. IL-6, IL-10 and IFN-γ levels were determined by enzyme-like immunosorbent assay, whereas TNF and nitrite levels were detected by standard assay with L929 cells and colorimetric Griess reactive, respectively.

Results

The results showed that the ethanolic extract of the Bougainvillea xbuttiana has significant anti-inflammatory and antinociceptive activities, by inhibition of nociception induced by acetic acid and paw oedema. This extract also induced a decrease in TNF levels and an increase of IL-6, IFN-γ and NO levels that we observed up to 2 h. The highest levels of IL-10 were observed up to 4 h. The ratios of pro-/anti-inflammatory cytokines in sera from mice injected with the ethanolic extract, may be manifesting an anti-inflammatory status.

Conclusions

The present study provides convincing evidences that Bougainvillea xbuttiana extract possesses significant anti-nociceptive and anti-inflammatory effects.     

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.     

Analgesic and anti-inflammatory activities of a water extract of Trachelospermum jasminoides (Apocynaceae)

Aims of the study

This study investigated the analgesic and anti-inflammatory effects of a water extract of Trachelospermum jasminoides (WET) in ICR mice.

Materials and methods

In HPLC analysis, the fingerprint chromatogram of WET was established. Acetic acid-induced writhing response and formalin-induced pain were examined the analgesics effects of WET. WET on λ-Carrageenan(carr)-induced paw edema was performed. We investigate the anti-inflammatory mechanism of WET via studies of the activities of glutathione peroxidase (GPx), glutathione reductase (GRx) in the liver and the levels of malondialdehyde (MDA) and nitrite oxide (NO) in the edema paw. Serum NO and TNF-α were also measured.

Results

The fingerprint chromatogram of WET was established through HPLC analysis, and implies that WET contains the active ingredient gallic acid, chlorgenic acid, caffeic acid, taxifolin, isoquercitrin and quercetin. WET significantly inhibited the numbers of acetic acid-induced writhing responses and the formalin-induced pain in the late phase. In the anti-inflammatory test, WET inhibited the development of paw edema induced by carr. WET decreased the paw edema at the third, fourth and fifth hour after carr administration, and increased the activities of SOD, GPx and GRx in the liver tissue and decreased the MDA level in the edema paw at the third hour after carr injection. WET decreased the level of NO in edematous paw tissue and in serum level, and diminished the level of serum TNF-α at the fifth hour after carr injection.

Conclusions

These results demonstrated that WET is an effective anti-inflammatory agent in carr-induced inflammation. WET probably exerts anti-inflammatory effects by suppressing TNF-α and NO. The anti-inflammatory mechanism of WET might be related to the decrease in the level of MDA in the edema paw via increasing the activities of SOD, GPx and GRx in the liver.     

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.