Evaluation of the analgesic and anti-inflammatory effects of a Brazilian green propolis

Phamacological activities of a standard ethanol extract G1 from Brazilian green propolis, typified as BRP1, was evaluated in mouse models of pain and inflammation. Intraperitoneal injection ( I. P.) of G1 inhibited acetic acid-induced abdominal constrictions with an ID (50) = 0.75 +/- 0.05 mg/kg, and in the formalin test the ID (50) values were 0.85 +/- 0.07 mg/kg and 13.88 +/- 1.12 mg/kg, respectively, for the neurogenic and inflammatory phases. The extract was ineffective when assessed in the hot-plate assay. In serotonin-induced paw edema, G1 led to a maximal inhibition (MI) of 51.6 % after 120 min when administered I. P. and of 36 % after 15 min by the oral route ( O. R.). When the inflammatory agent was complete Freund's adjuvant, inhibition of paw edema was also observed after administration of the extract by both routes. In the capsaicin-induced ear edema the ID (50) values were 1.09 +/- 0.08 mg/kg ( I. P.) and 10.00 +/- 0.90 mg/kg ( O. R.). In the acute carrageenan-induced inflammatory reaction induced by carrageenan, G1 reduced the number of neutrophils in the peritoneal cavity with IC (50) values of 0.72 +/- 0.08 mg/kg and 4.17 +/- 0.50 mg/kg, by I. P. or O. R. administration, with a preferential migration of polymorphonuclear neutrophils. IN VITRO, G1 decreased nitric oxide production in LPS-stimulated RAW 264.7 cells (IC (50) = 41.60 microg/mL), and also the luciferase activity in TNF-alpha-stimulated HEK 293 cells transfected with NF-kappaB-luciferase reporter gene driven by the nuclear factor kappaB (NF-kappaB) (IC (50) = 200 microg/mL). This extract, which at low concentrations induces anti-inflammatory and analgesic effects in mouse models, presents a high content of flavonoids, known to inhibit inducible NOS (iNOS) activity. These data taken together led us to reinforce the hypothesis in the literature that the anti-inflammatory effect of propolis may be a due to inhibition of iNOS gene expression, through interference with NF-kappaB sites in the iNOS promoter.     

Enzymologic and pharmacologic profile of loxoprofen sodium and its metabolites

We investigated the mechanism of inhibition of loxoprofen sodium, a non-steroidal anti-inflammatory drug (NSAID), and its active metabolite (loxoprofen-SRS) on cyclooxygenase (COX). In in vitro assays, loxoprofen sodium appeared inactive against recombinant human COX-1 and COX-2, whereas loxoprofen-SRS inhibited both. In the investigation of kinetic behavior, loxoprofen-SRS showed time-dependent inhibition for both isozymes. Human whole blood assay also showed that loxoprofen-SRS possesses the profile of a non-selective inhibitor for COX. In a rat air pouch model, oral administration of loxoprofen sodium lowered prostaglandin (PG) E2 in both fluid exudates of the inflammatory pouch and stomach tissue with ED50 values of 2.0 and 2.1 mg/kg, respectively. Additionally, platelet thromboxane B2 production was also inhibited by loxoprofen sodium (ED50 of 0.34 mg/kg). In a rat carrageenan-induced paw edema model, loxoprofen sodium dose-dependently reduced the paw edema, accompanied by a decrease in PGE2 content in inflamed paw exudates. These findings suggest that the COX inhibitory activity of loxoprofen sodium is attributable to its active metabolite, loxoprofen-SRS, and that loxoprofen-SRS shows non-selective inhibition for COX.     

Enhancement of anti-inflammatory and antinociceptive actions of red ginseng extract by fermentation

Objectives This work aimed to compare some pharmacological properties of red ginseng extract (RG) and fermented red ginseng extract (FRG). Methods Antinociceptive activity was analysed using the acetic acid‐induced abdominal constriction response. Anti‐inflammatory activity was evaluated using acetic acid‐induced vascular permeability and carrageenan‐induced inflammation in the air pouch, and analysed through the measurement of nitrite content in the lipopolysaccharide (LPS)‐stimulated macrophage cells. Anti‐angiogenic activity was determined using the chick chorioallantoic membrane assay. Key findings In‐vivo anti‐inflammatory activity of FRG was stronger than that of RG in two animal models, vascular permeability and air‐pouch models. In the vascular permeability model, the doses of RG and FRG required for half‐maximal inhibition (IC50) were 181 and 59 mg/kg, respectively. FRG exhibited significantly stronger antinociceptive activity than RG. In the acetic acid‐induced abdominal constriction response, the IC50 values of RG and FRG were 153 and 27 mg/kg, respectively. Although both RG and FRG were able to suppress production of nitric oxide in the LPS‐stimulated RAW264.7 macrophage cells, the suppressive activity of FRG appeared to be stronger than that of RG. However, RG and FRG showed similar anti‐angiogenic activity. Conclusions FRG possesses enhanced anti‐inflammatory and antinociceptive activity but similar anti‐angiogenic activity than RG.     

Suppressive effects of propolis in rat adjuvant arthritis

The effects of ethanolic extract (EEP) of propolis on chronic inflammation were evaluated using rat adjuvant arthritis. In the chronic inflammatory animal model, the arthritis index was suppressed by EEP treatments (50 mg/kg/day and 100 mg/kg/day, p.o.). Moreover, physical weakness, induced by the chronic disease state, was dose-dependently improved in the EEP-treated groups. Its analgesic effect, assessed using the tail-flick test, was comparable to prednisolone (2.5 mg/kg/day, p.o.) and acetyl salicylic acid (100 mg/kg/day, p.o.). In carrageenan rat hind paw edema, which was conducted to test the effects of subfractions of EEP, the petroleum ether sub-fraction (100 mg/kg, p.o.) showed an inhibitory effect on the paw edema whereas EEP (200 mg/kg, p.o.) showed a significant anti-inflammatory effect at 3 and 4 hrs after carrageenan injection. From these results, we conclude that the ethanolic extract of propolis had a profound anti-inflammatory effects on both chronic and acute inflammations.     

Evaluation of COX-1/COX-2 selectivity and potency of a new class of COX-2 inhibitors

A new class of selective cyclooxygenase-2 (COX-2) inhibitors has been identified by high throughput screening. Structurally distinct from previously described selective COX-2 inhibitors, these benzopyrans contain a carboxylic acid function and CF3 functionality. The compound SC-75,416 is a representative of this class. A range if in vitro and in vivo tests were employed to characterize its potency and selectivity. Using human recombinant enzymes, this compound displays a concentration that provides 50% inhibition (IC50) of 0.25 microM for COX-2 and 49.6 microM for COX-1. A mutation of the side pocket residues in COX-2 to COX-1 had little effect on potency suggesting that these inhibitors bind in a unique manner in COX-2 distinct from COX-2 inhibiting diaryl heterocycles. Using rheumatoid arthritic synovial cells stimulated with interleukin-1beta (IL-1beta) and washed platelets the compound displayed IC50 of 3 nM and 400 nM respectively. Potency and selectivity was maintained but predictably right shifted in whole blood with IC50 of 1.4 microM for lipopolysaccharide (LPS) stimulated induction of COX-2 and >200 microM for inhibition of platelet thromboxane production. SC-75,416 is 89% bioavailable and its in vivo half life is sufficient for once a day dosing. In the rat air pouch model of inflammation, the compound inhibited PGE2 production with an effective dose that provides 50% inhibition (ED50) of 0.4 mg/kg, while sparing gastric prostaglandin E2 (PGE2) production with an ED50 of 26.5 mg/kg. In a model of acute inflammation and pain caused by carrageenan injection into the rat paw, the compound reduced edema and hyperalgesia with ED50s of 2.7 and 4 mg/kg respectively. In a chronic model of arthritis the compound demonstrated an ED50 of 0.081 mg/kg and an ED(80) of 0.38 mg/kg. In a model of neuropathic pain, SC-75,416 had good efficacy. This compound's unique chemical structure and effect on COX enzyme binding and activity as well as its potency and selectivity may prove useful in treating pain and inflammation.     

New anti-inflammatory formulation containingSynurus deltoides extract

Synurus deltoides was previously found to possess significant anti-inflammatory activity especially against chronic inflammation, and strong analgesic activity in vivo. In this study, new anti-inflammatory formulation containing S. deltoides extract as a major ingredient was prepared and in vivo activity was evaluated. The plausible action mechanism was also investigated. The new formulation (SAG) contains 1 part of S. deltoides extract, 0.9 part of Angelica gigas extract and 0.9 part of glucosamine sulfate (w/w). SAG inhibited dose-dependently edematic response of arachidonic acid (AA)- and 12-O-tetradecanoyl 13-acetate (TPA)-induced ear edema in mice, which is an animal model of acute inflammation. SAG showed 44.1% inhibition of AA-induced ear edema at an oral dose of 50 mg/kg. In an animal model of chronic inflammation, SAG clearly reduced the edematic response of 7-day model of multiple treatment of TPA (38.1% inhibition at 200 mg/kg/day). Furthermore, SAG (50-800 mg/kg/day) as well as S. deltoides extract (285 mg/kg/day) significantly inhibited prostaglandin E2 production from the skin lesion of the animals of 7-day model. These results were well correlated with in vitro finding that SAG as well as S. deltoides extract reduced cyclooxygenase (COX)-1- and COX-2-induced prostanoid production, measured in mouse bone marrow-derived mast cells. Therefore, these results suggest that SAG possesses anti-inflammatory activity in vivo against acute as well as chronic inflammatory animal models at least in part by inhibition of prostaglandin production through COX-1/COX-2 inhibition. And COX inhibition of SAG is possibly contributed by S. deltoides extract among the ingredients. Although the anti-inflammatory potencies of SAG were less than those of currently used anti-inflammatory drugs, this formulation may have beneficial effect on inflammatory disorders as a neutraceutical.     

Coordination of copper with aspirin improves its anti-inflammatory activity

Anti-inflammatory activity of copper aspirinate administered orally was investigated in several models of inflammation. The results showed that copper aspirinate 50 mg/kg markedly inhibited inflammatory processes of either ear swelling induced by xylene in mice or turpentine-elicited air pouch granuloma in rats, with an activity equal to that of aspirin 200 mg/kg. Copper aspirinate 25 mg/kg significantly suppressed acute paw oedema produced by injecting 1% carrageenan, with an action time lasting over 6 h; and that copper aspirinate 100 mg/kg decreased the content of protein in the inflammatory exudate from rats with air pouch synovitis caused by acetic acid. It is suggested that, compared with aspirin, copper aspirinate showed a similar anti-inflammatory spectrum but greater anti-inflammatory activity. Zhiqiang S, Lei WY, Li L, Chen ZH, Liu WP. Coordination of copper with aspirin improves its antiinflammatory activity. Inflammopharmacology 1998;6:357-362     

Antiinflammatory activity of a polyherbal formulation

The antiinflammatory activity of the polyherbal formulation Entox^® was investigated in rats for acute and sub acute models of inflammation using carrageenan-induced rat paw edema and cotton pellet granuloma methods respectively at a dose of 300 mg/kg and 600 mg/kg administered orally. The formulation in doses of 300 mg/kg and 600 mg/kg showed 51.61% and 54.84% inhibition of paw edema, respectively at the end of 3 h. The percent inhibition of granuloma by cotton pellet method was 27.92% and 53.17%, respectively. The formulation showed a significant antiinflammatory activity in both the experimental models and the activity was comparable to that of the standard drug, indomethacin.     

Evaluation of the Anti-inflammatory Properties of Chlorophora excelsa. Stem Bark Extract

ABSTRACT

A methanol extract of the stem bark of Chlorophora excelsa. (Welw.) Benth and Hook was evaluated for anti-inflammatory activity in different models. Acute inflammatory effects were studied in the carrageenan-induced rat paw edema, and the effect of the extract in chronic inflammation was evaluated using the cotton pellet granuloma test. The effect of the extract on topical inflammation induced with croton oil was also tested in mice. The extract produced a significant (p < 0.05) and dose-dependent inhibition of the carrageenan-induced pedal edema, as well as granuloma tissue formation in rats. Topical anti-inflammatory effect was only evident with 400 mg/kg of the extract. This study demonstrated acute, chronic, and topical anti-inflammatory properties of the methanol extract of C. excelsa..     

A new pyrazolo pyrimidine derivative inhibitor of cyclooxygenase-2 with anti-angiogenic activity

In a previous study, we reported a new pyrazolo pyrimidine derivative, N(4)-benzyl-N(6),N(6)-dimethyl-1-1(tert-butyl)-1H-pyrazolo[3,4-d]pyrimidine-6,4-diamine (DPP), which inhibited potently cyclooxygenase-2 activity in intact cell assays with minor activity against cyclooxygenase-1 (IC(50)=0.9 nM for cyclooxygenase-2 versus IC(50)=59.6 nM for cyclooxygenase-1). In the present work, this behaviour was confirmed in vivo by using the 24-h zymosan-injected mouse air pouch model (ID(50)=1.36 nM/pouch for prostaglandin E(2) level). We also studied the possible beneficial effect of DPP in the angiogenesis-dependent murine air pouch granuloma and rat paw carrageenan-induced hyperalgesia models. DPP exerted analgesic and anti-angiogenic (52% reduction in angiogenesis at 10 mg/kg, i.p.) effects that may be associated with inhibition of cyclooxygenase-2 activity.     

Anti-inflammatory activity of roots of Achyranthes aspera

This study investigated the anti-inflammatory potential of the alcohol extract of Achyranthes aspera Linn. (Amaranthaceae) in Wistar rats after oral administration (50, 100, and 200?mg/kg). This was done using the carrageenan-induced paw edema method (acute inflammatory model) and cotton pellet granuloma test (chronic inflammatory model). The alcohol extract showed significant suppressed granuloma formation. Collectively, these data demonstrate promising anti-inflammatory activity against both acute and chronic inflammation. In addition, inhibition of prostaglandins and bradykinins may play a role. This study revealing the promising anti-inflammatory activity of Achyranthes aspera roots has been carried out scientifically for the first time.     

Possible attenuation of nitric oxide expression in anti-inflammatory effect of Ziziphus jujuba in rat

The hydroalcoholic extract of fruits of Ziziphus jujuba (ZJ) was investigated for its anti-inflammatory effect using acute and chronic models of inflammation in rat. Wistar albino rats of either sex were employed in the present study (n = 6). Acute inflammation was induced by subplantar administration of carrageenan (1%) in rat hind paw. Chronic inflammation was induced by interscapular implantation of a sterile cotton pellet (50 mg). ZJ extract as test drug and indomethacin (10 mg/kg) as standard were used. Serum nitrite/nitrate was also estimated to determine the expression of nitric oxide. In the acute study, carrageenan (1%) administration caused marked paw edema. Pretreatment with ZJ extract exhibited marked dose-dependent attenuation in edema compared to control. In the chronic study, interscapular implantation of sterile cotton pellets caused significant granuloma formation after 7 days, serving as control. ZJ extract significantly decreased granuloma tissue formation compared to control. The serum nitrite/nitrate level was significantly increased after 7 days in the control group due to chronic inflammation, but was decreased by ZJ extract. Moreover, phytochemical studies indicated the presence of jujubosides, flavonoids and terpenes, which may produce the marked anti-inflammatory effect of ZJ fruit in acute and chronic inflammation, possibly by inhibiting nitric oxide expression. The study provides a scientific and ethnopharmacological rationale for the therapeutic use of ZJ fruit as an anti-inflammatory agent.     

Anti‐inflammatory Effect of Rosmarinic Acid and an Extract of Rosmarinus officinalis in Rat Models of Local and Systemic Inflammation

Rosmarinic acid is a polyphenolic compound and main constituent of Rosmarinus officinalis and has been shown to possess antioxidant and anti‐inflammatory properties. We aimed to evaluate the anti‐inflammatory properties of rosmarinic acid and of an extract of R. officinalis in local inflammation (carrageenin‐induced paw oedema model in the rat), and further evaluate the protective effect of rosmarinic acid in rat models of systemic inflammation: liver ischaemia–reperfusion (I/R) and thermal injury models. In the local inflammation model, rosmarinic acid was administered at 10, 25 and 50 mg/kg (p.o.), and the extract was administered at 10 and 25 mg/kg (equivalent doses to rosmarinic acid groups) to male Wistar rats. Administration of rosmarinic acid and extract at the dose of 25 mg/kg reduced paw oedema at 6 hr by over 60%, exhibiting a dose–response effect, suggesting that rosmarinic was the main contributor to the anti‐inflammatory effect. In the liver I/R model, rosmarinic acid was administered at 25 mg/kg (i.v.) 30 min. prior to the induction of ischaemia and led to the significant reduction in the serum concentration of transaminases (AST and ALT) and LDH. In the thermal injury model, rosmarinic acid was administered at 25 mg/kg (i.v.) 5 min. prior to the induction of injury and significantly reduced multi‐organ dysfunction markers (liver, kidney, lung) by modulating NF‐κB and metalloproteinase‐9. For the first time, the anti‐inflammatory potential of rosmarinic acid has been identified, as it causes a substantial reduction in inflammation, and we speculate that it might be useful in the pharmacological modulation of injuries associated to inflammation.     

The effects of newly synthesized pyrazole derivatives on formaldehyde-, carrageenan-, and dextran-induced acute paw edema in rats

The antiinflammatory effects of 10 newly synthesized pyrazole derivatives on formaldehyde-induced rat paw edema were investigated. The most effective of them (K-3) was investigated again in dextran- and carrageenan-induced paw edema. In formaldehyde-induced paw edema, K-3 50, 100, and 200 mg/kg p.o. inhibited the edema by 48.9% (p<0.002), 68.7% (p<0.001), and 79.1% (p<0.001), respectively, 3 h after administration. In dextran-induced paw edema, the same dose of K-3 produced 27.1% (p<0.05), 46.8% (p<0.01), and 63.8% (p<0.002) inhibition, respectively. In the carrageenan-induced paw edema test, K-3 100 mg/kg decreased the inflammatory response by 52.0% after 4 h. Acute toxicity studies revealed that K-3 was nontoxic up to an oral dose of 2500 mg/kg.     

Simvastatin and Indomethacin Have Similar Anti‐Inflammatory Activity in a Rat Model of Acute Local Inflammation

Abstract: Statins, such as simvastatin, lower circulating cholesterol levels and are widely prescribed for the treatment of hypercholesterolaemia. Several studies have shown unexpected effects of statins on inflammation. We studied the anti‐inflammatory effect of simvastatin using a standard model of an acute local inflammation, the carrageenan‐induced footpad oedema. Experimental groups (n = 6–8) were given simvastatin in a dose range 5–30 mg/kg, indomethacin 1–8 mg/kg and methylcellulose (control) per os. Footpad volume was measured with a plethysmograph and compared with the pre‐injection volume of the same paw. Swelling (in microlitres) was then calculated, and in drug‐treated animals, per cent inhibition was derived through comparison with the control group. Histopathological examination of the skin biopsies was performed to examine severity of paw skin lesions and to confirm the simvastatin‐induced inhibition of acute inflammation. Both simvastatin and indomethacin administered orally, 1 hr before carrageenan injection, significantly reduced the extent of footpad oedema. Indomethacin dose‐dependently blocked the swelling; the maximal effect was obtained with 8 mg/kg by 48.3% (P < 0.05). Simvastatin produced a comparable anti‐inflammatory activity at a dose of 5 mg/kg (32%), while 10 and 30 mg/kg caused a 47.6% and 51.7% reduction, respectively, with the maximal effect observed at 20 mg/kg by 57.2% (P < 0.05). The comparison of the ED₅₀ of these agents on molar basis showed equipotent anti‐inflammatory activity. Histopathological examination of the footpad skin biopsies revealed that simvastatin, dose‐dependently and comparablly to indomethacin, reduced polymorphonuclear leucocyte infiltration. These data support the hypothesis that simvastatin has an acute anti‐inflammatory activity.     

Potentiation of the antiinflammatory effect of Anacardium occidentale (Linn.) stem-bark aqueous extract by grapefruit juice

In an attempt to scientifically appraise some of the ethnomedical uses of Anacardium occidentale Linn. (family: Anacardiaceae), the present study was undertaken to examine the antiinflammatory effect of the plant's stem-bark aqueous extract in rats. Young adult male Wistar rats weighing 250-300 g were used. The antiinflammatory effect of A. occidentale stem-bark aqueous extract alone and in combination with grapefruit (Citrus paradisi Macf.) juice was investigated on fresh egg albumin-induced rat paw edema. Like diclofenac (100 mg/kg p.o.), aqueous extract of A. occidentale stem-bark (800 mg/kg p.o.) produced time-related, sustained and significant reduction (p < 0.05-0.001) of the fresh egg albumin-induced acute inflammation of the rat hind paw. However, the antiinflammatory effect of the plant extract was found to be approximately 8-15 times less than that of diclofenac. Coadministration of grapefruit juice (5 ml/kg p.o.) with A. occidentale stem-bark aqueous extract (800 mg/kg p.o.) or diclofenac (100 mg/kg p.o.) significantly potentiated (p < 0.05-0.001) the antiinflammatory effects of the crude plant extract and diclofenac on fresh egg albumin-induced rat paw edema. Although A. occidentale stem-bark aqueous extract is less potent than diclofenac as an antiinflammatory agent, the results of this experimental animal study indicate that the plant extract possesses antiinflammatory activity, and thus lend pharmacological support to the folkloric use of the plant in the management and/or control of arthritis and other inflammatory conditions among the Yoruba-speaking people of western Nigeria.     

Evaluation of anti-inflammatory potential of Bergenia ciliata Sternb. rhizome extract in rats

The methanol extract of the rhizome of Bergenia ciliata Sternb. (Saxifragaceae) has been evaluated for anti-inflammatory potential using two acute rat models (carrageenan- and serotonin (5-HT)-induced rat paw oedema) and a chronic rat model (cotton pouch-induced granuloma). Phenylbutazone (100 mg kg(-1)), a non-steroidal anti-inflammatory agent, was used as a standard. The methanol extract (100, 200 or 300 mg kg(-1)) exhibited significant (P < 0.05) anti-inflammatory activity in all the animal models. At 300 mg kg(-1) the methanol extract exhibited maximum inhibition of 32.4+/-2.89% in carrageenan-induced rat paw oedema while the standard showed an inhibition of 44.1+/-2.7% after 3 h of drug treatment. In the serotonin-induced rat paw oedema model, 300 mg kg(-1) methanol extract suppressed oedema by 45.33+/-2.09%, whereas the standard produced an inhibition of 53.5+/-4.3%. In the cotton pouch granuloma model the methanol extract inhibited significantly (P < 0.001) the granuloma weight in a dose-dependent manner. In this model, 300 mg kg(-1) extract produced a maximum inhibition of 31.4+/-1.09% in granuloma weight compared with 41.1+/-1.32% reduction in granuloma weight for the standard. The methanol extract of B. ciliata exhibited significant anti-inflammatory potential at the dose levels examined.     

Experimental myocardial infarction in adjuvant arthritis rats

We studied the influence of various inflammatory reactions on the survival rate and occurrence of arrhythmias in the acute phase of experimental myocardial infarction in conscious male Sprague--Dawley CFY rats. Chronic disseminated inflammatory disease was induced by subplantar injection of Freund complete adjuvant, while chronic local inflammatory lesion was produced by carrageenan granuloma pouch method. An acute inflammatory response in the rat paw was evoked by carrageenan. Myocardial infarction was provoked by tightening a previously implanted silk loop around the left anterior descending coronary artery 14 days after the induction of adjuvant disease, and 7 days or 4 h after the production of granuloma pouch or foot edema. Carrageenan paw swelling was induced in rats showing expressed primary and slight secondary lesions due to Freund adjuvant. Adjuvant arthritis, but not granuloma pouch or acute paw edema, protected the rat against the fatal complications of coronary ligation. This effect was characterized by a significant increase in the survival rate from 30% to 63%, and a reduction in the occurrence of various types of dysrhythmias. Carrageenan paw edema was also less expressed and of shorter duration in rats with adjuvant disease. The level of cardiolopin was considerably increased in the arthritic group, while the other phospholipids showed no change. We conclude that chronic disseminated inflammation markedly alters the reactivity of conscious rats to experimental myocardial infarction. The alterations observed may be related to an increased energy supply and/or to accumulation of some endogenous antiinflammatory substances during adjuvant arthritis.     

Analgesic and Anti-inflammatory Activities of the Aqueous Extract of Plantago major L.

This study aimed to validate the pharmacological effects of Plantago major L., a medicinal plant used to decrease pain and inflammation. The aqueous extract (AE) was prepared from the dried ground leaves. Pretreatment with AE (1 g/kg, p.o.) decreased writhing induced by acetic acid in mice, but it did not change the tail flick responses to heat nociceptive stimuli. In rats, AE (1 g/kg, p.o.) reduced the paw edema and pleurisy induced by carrageenin, but it did not alter the paw edema induced by dextran. The effect of AE on the carrageenin inflammatory responses was more intense than that obtained on the ear edema induced by croton oil in mice. In addition, daily treatment with AE (1 g/kg/day during 8 days, p.o.) inhibited the exudative process induced by croton oil injected into the air pouch of rats. The results indicate that the aqueous extract of Plantago major is endowed with effective antiinflammatory and analgesic activities.