Carrageenin-induced Edema In Rats Research Articles

Anti-inflammatory and anti-nociceptive activities of the stem bark extracts from Allanblackia monticola STANER L.C. (Guttiferae)

The aim of this study was to assess the anti-inflammatory and mechanism of action of Allanblackia monticola (Guttiferae). The anti-inflammatory activity “ in vivo” of the methylene chloride/methanol extract, methanol and methylene chloride fractions of stem barks of Allanblackia monticola, administered orally at doses of 37.5; 75; 150 and 300 mg/kg, was evaluated on carrageenan-induced oedema in rats to determine the most active fraction. Indomethacin, inhibitor of cyclo-oxygenase was used as reference drug. The effects of the most active fraction were then examined on the rat paw oedema caused by histamine, serotonin, arachidonic acid and dextran followed by its ulcerogenic effect. The results showed that the methylene chloride fraction of Allanblackia monticola was more effective on the oedema caused by the carrageenan. The anti-nociceptive activity of the methylene chloride fraction was assessed using the acetic acid-induced abdominal constriction model, formalin test and hot plate test. At 150 mg/kg, Allanblackia monticola caused maximum inhibitions of inflammation induced by carrageenan (83.33%), by histamine (42.10%), by dextran (40.29%) and by arachidonic acid (64.28%). Allanblackia monticola (75–300 mg/kg) did not cause significant modification of the oedema induced by serotonin. Concerning the anti-nociceptive properties of the plant, the methylene chloride fraction (75–300 mg/kg) caused a dose-dependent inhibition on abdominal contractions induced by acetic acid (32.34–77.37%) and significantly inhibited the inflammatory pain caused by formalin (40.71–64.78%) . Allanblackia monticola did not increase the latency time in the hot plate test. Like indomethacin (10 mg/kg), the fraction at the dose of 150 mg/kg caused ulceration of the gastric mucous membrane in treated rats. These results show that Allanblackia monticola has an anti-inflammatory and analgesic activities with gastric ulcerative side effects.

Effect of seasonal variation on the anti-inflammatory activity of Sargassum wightii growing on the N. Arabian Sea coast of Pakistan

The polar and nonpolar extracts of the brown alga Sargassum wightii (Greville) J. Agardh, collected during winter (November–January), spring (February–April), summer (May–July) and autumn (August–October) were evaluated for anti-inflammatory activity using carrageenan-induced paw edema in rats. Effect of hexane, methanol and butanol extracts was measured at a dose of 100 mg/kg from 1st–4th hour of inflammation. All the extracts of winter collection exhibited significant ( P < 0.001) anti-inflammatory property (∼ 80%) as compared to those of summer collection (34–59%). This difference could probably be related to seasonal variation due to nutrient availability thereby affecting synthesis of chemical constituents required for growth of the alga. Other studies also invoke seasonal changes in their epiphytic/edophytic microorganisms. It is noteworthy, that polar butanolic extract collected during winter season was most effective (86.7%) in reducing carrageenan-induced edema in rats as compared to reference drugs aspirin (79.4%) and ibuprofen (57.3%). All extracts were non-toxic up to 1 mg/ml in brine shrimp and 500 mg/kg in mice.

Development of photocrosslinked polyacrylic acid hydrogel as an adhesive for dermatological patches: Involvement of formulation factors in physical properties and pharmacological effects

Photocrosslinked polyacrylic acid hydrogel is a promising candidate adhesive for dermatological patches. In this study, we investigated the effects of the composition and molecular weight of the polymer on the characteristics of the hydrogel. Several photocrosslinkable polymers with different photocrosslinkable moieties or molecular weights were prepared, and various physical properties were measured. Differences in photocrosslinkable modifications markedly affected the swelling behavior of the hydrogel. The molecular weight of the polymer had a significant effect on various physical properties, such as the viscosity of the polymer solution, gel formation, and the swelling behavior of the prepared hydrogels. The pharmacological effects of the hydrogel were also evaluated using carrageenan-induced edema in rats. Application of the hydrogels maintained the skin surface at a reduced temperature throughout the experimental period, and the cooling effect was accompanied by an anti-inflammatory response. Because we can freely control the physical properties of the hydrogel and anticipate the significant pharmacological effects, photocrosslinked polyacrylic acid hydrogel is an attractive candidate adhesive for dermatological patches.

Analgesic mechanisms of Angelicae Tenuissimae Radix

Angelicae Tenuissimae Radix (ATR) has traditionally been used for flu-like symptoms, limb-ache and disability, and even for toothache. In the present study, anti-inflammatory and analgesic effect of ATR was investigated on lipopolysaccharide-induced inflammation was investigated by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, reverse transcription-polymerase chain reaction (RT-PCR), Western blot, prostaglandin E2 (PGE2) immunoassay, and nitric oxide (NO) detection in mouse BV2 microglial cells. In addition, the effect of ATR on carrageenan-induced edema, acetic acid-induced abdominal pain, and heat-induced hyperalgesia were investigated using rats and mice. The present results showed that ATR suppressed PGE2 synthesis and NO production by inhibiting LPS-induced expressions of cyclooxygenase-2 and inducible nitric oxide synthase mRNA and protein in mouse BV2 microglial cells. ATR reduced carrageenan-induced edema in rats and inhibited acetic acid-induced abdominal pain in mice. Here in this study, we have shown that ATR possesses anti-inflammatory and analgesic effects. This study was supported by a grant of the Oriental Medicine R&D Project, Ministry of Health & Welfare, Republic of Korea (0405-OD00-0815-B050049).

Anti-Inflammatory Effects of 4-Phenyl-3-butenoic Acid and 5-(Acetylamino)-4-oxo-6-phenyl-2-hexenoic Acid Methyl Ester, Potential Inhibitors of Neuropeptide Bioactivation

Substance P (SP) and calcitonin gene-related peptide (CGRP) are well established mediators of inflammation. Therefore, inhibition of the biosynthesis of these neuropeptides is an attractive potential strategy for pharmacological intervention against a number of inflammatory diseases. The final step in the biosynthesis of SP and CGRP is the conversion of their glycine-extended precursors to the active amidated peptide, and this process is catalyzed by sequential action of the enzymes peptidylglycine alpha-monooxygenase (PAM) and peptidylamidoglycolate lyase. We have demonstrated previously that 4-phenyl-3-butenoic acid (PBA) is a PAM inhibitor, and we have also shown that in vivo inhibition of serum PAM by PBA correlates with this compound's ability to inhibit carrageenan-induced edema in the rat. Here we demonstrate the ability of PBA to inhibit all three phases of adjuvant-induced polyarthritis (AIP) in rats; this represents the first time that an amidation inhibitor has been shown to be active in a model of chronic inflammation. We recently introduced 5-(acetylamino)-4-oxo-6-phenyl-2-hexenoic acid (AOPHA) as one of a new series of mechanism-based amidation inhibitors. We now report for the first time that AOPHA and its methyl ester (AOPHA-Me) are active inhibitors of serum PAM in vivo, and we show that AOPHA-Me correspondingly inhibits carrageenan-induced edema in rats in a dose-dependent manner. Neither PBA nor AOPHA-Me exhibits significant cyclooxygenase (COX) inhibition in vitro; thus, the anti-inflammatory activities of PBA and AOPHA-Me are apparently not a consequence of COX inhibition. We discuss possible pharmacological mechanisms that may account for the activities of these new anti-inflammatory compounds.

Antinociceptive and Anti-Inflammatory Effects of the Saponin and Sapogenins Obtained from the Stem of Akebia quinata

The stem of Akebia quinata Decasisne (Lardizabalaceae) has been used to treat urinary tract inflammatory disease. It has been reported that saponins in medicinal plants may act as bioactive components after biodegradation to sapogenins in the gastrointestinal tract. To find the active components, we obtained the methanol (MeOH) extract from A. quinata stems and fractionated this extract into CHCl(3), butanol (BuOH), and H(2)O fractions. A saponin-containing BuOH fraction was refluxed in an acidic solution to yield the hydrolyzed fraction. Silica gel column chromatography separated kalopanaxsaponin A (1) from the BuOH fraction, and oleanolic acid (2) and hederagenin (3) were obtained from the hydrolyzed fraction. The antinociceptive effect was tested by hot plate-writhing and tail-flicks methods using mice, and the anti-inflammatory effect was assayed using carrageenan-induced rat edema against the following samples: the MeOH extract of A. quinata stems, its fractions, the isolated saponin, kalopanaxsaponin A, and the sapogenins hederagenin and oleanolic acid. The MeOH extract exhibited antinociceptive/anti-inflammatory effects by oral administration of 100 and 250 mg/kg doses, indicating that the MeOH extract has an antinociceptive/anti-inflammatory activity. The BuOH fraction (crude saponin) also significantly exhibited those bioactivities. Treatments with 10 and 30 mg/kg perorally of these two sapogenins produced significant antinociceptive/ anti-inflammatory effects in the rat, suggesting that the sapogenins may act as resultant active compounds. Compounds 2 and 3 inhibited dye leakage into the peritoneal cavity induced by acetic acid, and the latter was more active than the former. The anti-inflammtory effects were further supported by the reduction of carrageenan-induced lipid peroxidation and hydroxy radical content in serum. These results suggest that the antinociceptive/anti-inflammatory properties of the stem of A. quinata can be attributed to the sapogenins oleanolic acid and hederagenin.

3D-QSAR and preliminary evaluation of anti-inflammatory activity of series of N-pyrrolylcarboxylic acids

The present study focuses on development of new potential inhibitors of cyclooxygenase-2 (COX-2): series of N-pyrrolylcarboxylic acids. 3D-QSAR (Quantitative Structure–Activity Relationship) CoMFA (Comparative Molecular Field Analysis) and CoMSIA (Comparative Molecular Similarity Index Analysis) models for predicting inhibitory activities against COX-1 and COX-2 as well as for evaluating in vivo anti-inflammatory activity were obtained and used for preliminary screening of new anti-inflammatory N-pyrrolylcarboxylic acids. Nine compounds were selected for in vivo testing and evaluated for their potency to decrease carrageenin-induced edema in rats. The compounds were applied i.p. at doses 20 mg/kg and 40 mg/kg and p.o. at doses 10 mg/kg and 40 mg/kg. Six compounds showed more than 70% protection of the edema. Indomethacin (2 mg/kg i.p.), used as a reference drug, possessed 54% anti-inflammatory activity under similar experimental conditions.

Evaluation of the anti-inflammatory and analgesic properties of the extract of Russelia equisetiformis (Schlecht &amp; Cham) Scrophulariacae

A methanolic extract of Russelia equisetiformis whole plant was studied for anti-inflammatory and analgesic activities in rats and mice using carrageenan-induced rat paw oedema, acetic-acid-induced writhing and tail-flick test. The extract, at 10, 20 and 40 mg/kg, significantly (P <0.05) inhibited carrageenan-induced oedema in rats. Abdominal constriction induced by acetic acid was also inhibited by the extract, within the same dose range. The extract at the same dose also prolonged the latency period in the tail-flick response test, which was reverted by naloxone. The results suggested that the extract possesses potential anti-inflammatory and analgesic properties.

Anti-inflammatory activity of linalool and linalyl acetate constituents of essential oils.

Linalool and linalyl acetate are the principal components of many essential oils known to possess several biological activities, attributable to these monoterpene compounds. In this work, we evaluated individually the anti-inflammatory properties of (-) linalool, that is, the natural occurring enantiomer, and its racemate form, present in various amounts in distilled or extracted essential oils. Because in the linalool-containing essential oils, linalyl acetate, is frequently present, we also examined the anti-inflammatory action of this monoterpene ester. Carrageenin-induced edema in rats was used as a model of inflammation. The experimental data indicate that both the pure enantiomer and its racemate induced, after systemic administration, a reduction of edema. Moreover, the pure enantiomer, at a dose of 25 mg/kg, elicited a delayed and more prolonged effect, while the racemate form induced a significant reduction of the edema only one hour after carrageenin administration. At higher doses, no differences were observed between the (-) enantiomer and the racemate; a further increase in the dose of both forms did not result in an increased effect at any time of observation. The effects of equi-molar doses of linalyl acetate on local edema were less relevant and more delayed than that of the corresponding alcohol. These finding suggest a typical pro-drug behavior of linalyl acetate. The results obtained indicate that linalool and the corresponding acetate play a major role in the anti-inflammatory activity displayed by the essential oils containing them, and provide further evidence suggesting that linalool and linalyl acetate-producing species are potentially anti-inflammatory agents.

Anti-inflammatory and Antioxidant Activity of Ageratum conyzoides

Ageratum conyzoides L., a plant widely used in African and South American folk medicine, contains many active principles, including pyrrolizidine alkaloids and polymethoxyflavones. We undertook the present study to evaluate the effect of the methanol extract and of the flavonoid fraction of the aerial part of the plant on carrageenan-induced edema in rat. We subjected the methanol extract to column chromatography to separate the flavonoids and assayed the radical scavenging activity of this fraction by the DPPH method. The two preparations produced significant inhibition on carrageenan-induced rat paw edema, until 2 h after carrageenan treatment. The flavonoids exhibited a strong inhibitory activity on the DPPH radical. The anti-inflammatory effect of A. conyzoides methanol extract depends on the flavonoid fraction, which could produce a protective action against free-radical mediated damage in cells and tissue. Therefore, it is possible to hypothesize that flavonoids influence inflammatory gene protein expression.

Synthesis and characterization of a diruthenium–ibuprofenato complex: Comparing its anti-inflammatory activity with that of a copper(II)–ibuprofenato complex

The ibuprofen complex of diruthenium(II,III) was prepared and characterized by electronic (UV-Vis) and vibrational (FTIR) spectroscopies and thermogravimetry. The copper(II)–ibuprofenato complex was prepared by a different route from that described in the literature. Both complexes were tested in vivo for anti-inflammatory activity. Oral administration of the two complexes inhibited development of carrageenin-induced edema in rats, this inhibition being similar to that observed for oral administration of the parent drug (free ibuprofen). However, gastric irritation was lower as compared to that of ibuprofen. Diruthenium–ibuprofenato exhibited a protective effect at light intensity ulceration while the copper–ibuprofenato complex was more effective in the protection of severe intensity ulceration.

Anti-Inflammatory Activities of Urtica pilulifera

The petroleum ether extract of Urtica pilulifera (Urticaceae) seeds showed anti-inflammatory activity in carrageenan-induced edema in rats.

Inhibitory effect of Shimotsu-to, a traditional Chinese herbal prescription, on acute inflammation in rats and guinea pigs

We examined the effect of topical application of Shimotsu-to, a traditional Chinese herbal prescription, on carrageenin-induced edema in rats and ultraviolet radiation-induced erythema in guinea pigs. Shimotsu-to (5% in water) markedly suppressed an acute edema of rat hindpaw induced by 1% carrageenin, and was more effective than any other single crude drug componcent of Shimotsu-to, Topical treatment with this prescription also inhibited ultraviolet erythema on the back skin of guinea pigs (a human sunbrun model). These results suggest the therapeutic effect on acute inflammation by topical application of Shimotsu-to.

Effect of nonapeptide fragments of uteroglobin and lipocortin I on oedema and mast cell degranulation.

The anti-inflammatory action of nonapeptide fragments of uteroglobin or lipocortin I known as antiflammins, was tested in the carrageenan or phospholipase A2 rat paw oedema model. The development of carrageenan-induced oedema in rats was significantly inhibited during the early and late phases of the oedema by the local administration of antiflammins 1 and 2. However, the peptides were not able to inhibit phospholipase A2-induced oedema. The time course of the anti-oedematous activity of nonapeptides after intradermal carrageenan injection may be attributed to their effect on mast cell degranulation and accumulation and activation of leukocytes. Naja naja phospholipase A2 exhibited strong histamine release-inducing activity, which may have contributed to the rat paw oedema induction. Surprisingly, antiflammins had a limited but significant inhibitory effect on histamine secretion.

Anti-inflammatory properties of IL-1 in carrageenan-induced paw oedema

To evaluate any inhibitory effect of a single dose of human recombinant interleukin-1 beta (hrIL-1 beta) on the severity of carrageenan-induced oedema in rats (a commonly used model of acute inflammation), we first injected 0.1 ml of carrageenan (0.2%, 0.5%, or 2%) to induce mild, moderate, or severe inflammation, respectively into the right rear footpad. Then we promptly injected the interleukin (0.02, 0.2, or 2 micrograms) subcutaneously into the flank. The initial rapid increase in volume of the injected paw (within 2 h of the subplantar injection) was independent of the dose of carrageenan, whereas the increase in volume by 6 to 10 h was dose-dependent. All doses of HrIL-1 beta inhibited the carrageenan-induced swelling at the 6th hour. In the moderate and severe carrageenan-induced oedemas, the higher dose of HrIL-1 beta induced a delayed inflammation peaking at 10 h instead at 6 h.

Pharmacological and pharmaceutical properties of freeze-dried formulations of egg albumin, indomethacin, olive oil, or fatty acids.

Formulations consisting of egg albumin, indomethacin (IND), and olive oil or fatty acids, were prepared by vigorous stirring using a high-speed homogenizer and subsequent freeze-drying. To confirm the anti-inflammatory properties and ulcerogenic effects of the formulations, we examined the action of the formulations on carrageenan-induced edema in rats as well as their ulcerogenic actions in the same species. Compared with IND alone, albumin-IND-olive oil (9:1:4.3), albumin-IND-linolenic acid (9:1:4.3), albumin-IND-linolic acid (9:1:4.3), albumin-IND-oleic acid (9:1:4.3), albumin-IND-stearic acid (9:1:4.3), and albumin-IND-tristearin (9:1:4.3) formulations all exhibited a more potent inhibitory effect on carrageenan-induced edema. In addition, the inhibitory effects on edema formation of an albumin-IND (9:1) complex was as strong as that of IND alone. These results suggested that the bioavailability of IND was increased by olive oil, fatty acid, and tristearin as absorbefacient agents. The increase in the bioavailability was evident from the fact that the mean plasma levels, maximum plasma levels (Cmax), and area under plasma concentration-time curve (AUC) values after oral administration of the albumin-IND-olive oil (9:1:4.3) formulation was significantly greater than that after administration of the drug alone. With respect to their ulcerogenic properties, the formulations were significantly less active than IND alone, suggesting that a reduction in the ulcerogenic activity of IND was by produced complexation with egg albumin.

Synthesis and Anti-Inflammatory Activity of 3-(Benzylideneamino)Coumarins in Rodents

A series of substituted 3-(benzylideneamino)coumarins was synthesized and evaluated for anti-inflammatory activity against carrageenan-induced edema in rats. Halogenated derivatives 4g and 4c, at oral doses of 100 mg/kg, showed 75 and 60% antiedematous activity, respectively (phenylbutazone antiedematous activity, 58%). The analgesic activity of 4g and 4c, based on inhibition of acetic acid-induced writhing in mice (67 and 62%, respectively, at oral doses of 100 mg/kg) was comparable with that of aspirin (58%). However, these derivatives were devoid of antipyretic activity and showed low activity against adjuvant-induced arthritis.

Anti-inflammatory Effect of Zingiber cassumunar ROXB. and Its Active Principles.

The present study was carried out to elucidate the anti-inflammatory effect of the methanol extract obtained from the rhizomes of Zingiber cassumunar Roxb. and its active principles. The methanol extract was partitioned between ether and water, and then the ether-soluble fraction was extracted with n-hexane. The n-hexane-soluble fraction was chromatographed and part of the fraction was rechromatographed by silica gel column. Three compounds were isolated from the n-hexane-soluble fraction and the chemical structures of these compounds were identified as (E)-1-(3,4-dimethoxyphenyl)but-1-ene, (E)-1-(3,4-dimethoxyphenyl)butadiene and zerumbone. The anti-inflammatory activity of these fractions was investigated on carrageenin-induced edema in rats, as well as on acetic acid-induced vascular permeability and writhing symptoms in mice. The methanol extract (p.o.) showed both anti-inflammatory activity and analgesic activity. These activities shifted successively to ether-soluble and n-hexane-soluble fractions and to (E)-1-(3,4-dimethoxyphenyl)but-1-ene. These results suggest that the anti-inflammatory action and analgesic action of Zingiber cassumunar is the result of the (E)-1-(3,4-dimethoxyphenyl)but-1-ene that it contains.

Antiinflammatory effect of Curcuma xanthorrhiza Roxb. and its active principles.

The rhizomes of Curcuma xanthorrhiza Roxb, are used in Indonesian folk medicine as cholagogues, aromatic stomachics, analgesics, a rheumatic remedy, etc. The present study was carried out to elucidate the antiinflammatory effect of the methanol extract obtained from these rhizomes and its active principles. The methanol extract was partitioned between ether and water, and then the ether-soluble fraction was extracted with n-hexane. The n-hexane-soluble fraction was chromatographed (fr. I-IV), fr. II was rechromatographed (fr. V-VII), and then fr. V was rechromatographed (fr. VIII-X) by silica gel column chromatography. The antiinflammatory activity of these fractions was investigated on carrageenin-induced edema in rats and acetic acid-induced vascular permeability as well as the writhing symptom in mice. The methanol extract (p.o.) showed both an antiinflammatory activity and an analgesic activity and these activities shifted successively to the ether-soluble fraction, the n-hexane-soluble fraction, fr. II, V and IX. The chemical structure of fr. IX was identified as germacrone. These results suggest that the antiinflammatory action of Curcuma xanthorrhiza is the result of the germacrone that it contains.

Pharmacological study of Cymbopogon citratus leaves

Cymbopogon citratus leaves are employed by the Cuban population as an antihypertensive and anti-inflammatory folk medicine. A 10% or 20% decoction of leaves was tested using arterial pressure in rats, urine production and carrageenan-induced edema in rats. The decoction showed some dose-related hypotensive effects given intravenously and some weak diuretic and anti-inflammatory effect when given orally.