Hind Paw Edema Test Research Articles

Inhibition of Carrageenan-Induced Edema by Tripleurospermum Disciforme Extract in Rats

In this research anti-inflammatory effect of Tripleurospermum disciforme extract was studied in rats. The effect of the extract against acute inflammation was studied by hind paw edema test. Intraperitoneal injection of different doses (15, 30, 45, 60, 90 and 120 mg kg(-1)) of Tripleurospermum disciforme which was followed by hind paw carageenan injection 1 h later were investigated. The resultant edema was quantified by measuring changes of diameter of hind foot. After 2, 3, 4 and 6 h we measured the anti-inflammatory effect of Tripleurospermum disciforme extract. Tripleurospermum disciforme extract with doses of 45, 60, 90 and 120 mg kg(-1) and indomethacin 5 mg kg(-1) showed significant effect. It is concluded that Tripleurospermum disciforme extract has anti-inflammatory effect against acute inflammation.

The Study of Analgesic Effects and Acute Toxicity of Tripleurospermum disciforme in Rats by Formalin Test

ABSTRACTPrevious studies have demonstrated the anti-inflammatory effect of Tripleurospermum disciforme extract in rats with a hind paw edema test. The present study was done to further characterize this anti-inflammatory effect using a formalin test in the intact rats, specifically studying the analgesic effect as well as its toxicity effect by determination of LD50 using graded oral doses of T. disciforme. The effects of graded doses of T. disciforme were investigated following intraperitoneal (IP) administration. Forty-eight rats were used in six groups of studies. The first group (control) received formalin 2.5%, the second group formalin 2.5% + saline, and the third group formalin 2.5% and morphine; three other groups received formalin 2.5% and 15 mg/kg, 30 mg/kg, and 60 mg/kg. After 5, 15, 30, 45, 60 min the pain responses were measured T. disciforme 60 mg/kg had a significant analgesic effect and this effect was equal to morphine 2 mg/kg in the chronic phase of the formalin test. To assess the utility of T. disciforme, the toxic effect of extract was studied by determination of LD50 using graded oral doses of 50, 500, and 5000 mg/kg of T. disciforme to fasted rats and LD50 was measured after 24, 48, and 72 hours. In conclusion, these studies show that T. disciforme is significantly nontoxic at doses required as analgesic drug and higher doses of T. disciforme could produce significant analgesic effects and confirm its previous significant anti-inflammatory effect.

Synthesis, anti-inflammatory and analgesic activity of some new 4(3H)-quinazolinone derivatives.

4(3H)-quinazolinone and pyrazole derivatives have been shown to have analgesic and anti-inflammatory properties. In this study, 14 new 3-methyl-4(3H)quinazolinone derivatives bearing 2-[1'-phenyl-3'-(substituted-phenyl)-2'-propenylidene]hydrazino or 2[5'-(substituted phenyl)-3'-phenyl-2'-pyrazolin-1'-yl] groups have been synthesized with the aim of obtaining new analgesic and anti-inflammatory leads. The structures were elucidated by means of UV, IR, 1H-NMR, 13C-NMR, mass spectroscopy, and elemental analysis data. The anti-inflammatory activities of the synthesized compounds were determined by carrageenan-induced hind paw edema test in mice. All the compounds showed statistically significant effects. For analgesic activity assessment, p-benzoquinone-induced writhing test was applied in mice. The results obtained were in accordance with the anti-inflammatory activity tests.

An evaluation of the activity related to inflammation of four plants used in Thailand to treat arthritis

The leaves of Acanthus ebracteatus, stembark of Oroxylum indicum and the stems of Cryptolepis buchanani and Derris scandens are used as traditional remedies in Thailand for arthritis. Aqueous and alcoholic extracts were tested using three different in vitro systems for effects relevant to anti-inflammatory activity. The aqueous extracts of O. indicum and D. scandens significantly reduced myeloperoxide release. Eicosanoid production was reduced only by the aqueous extracts of A. ebracteatus and D. scandens. D. scandens extract showed potent inhibitory activity against generation of leukotriene B 4 and also displayed antioxidant activity. In the rat hind paw edema test, D. scandens extract showed significant activity when given intraperitoneally but did not produce a significant reduction when given orally. The results therefore supported to some extent the traditional use of D. scandens for arthritic conditions and provided slight indication of activity which could explain the use of O. indicum and A. ebracteatus. No relevant activity was demonstrated in any of the tests for C. buchanani extracts.

Coupling reaction and properties of poly(ethylene glycol)-linked phospholipases A2.

Secretory phospholipases A2 (PLA2) from Naja naja naja (cobra snake) venom, from Bothrops neuwiedii (crotalid snake) venom (two isoforms) and from bee venom were modified with tresylated monomethoxy poly(ethylene glycol) (TMPEG). The kinetic and inflammatory properties of the adducts (PEG-PLA2) were measured. As found by gel permeation chromatography, 95-100% of P-1 PLA2 from B. neuwiedii and PLA2 from N. naja naja venom change their chromatographic mobility after TMPEG treatment. By contrast, only 50-60% of both P-3-PLA2 from B. neuwiedii and PLA2 from bee venom modify their elution profile from Superdex 75. All the modified proteins preserved the enzymatic activity toward phospholipid monolayers, but with a reduced specific activity and greater lag times than the unmodified controls. These results suggest that the PEG-PLA2 complexes would have an altered interaction with lipid membranes. The PEG-linked proteins preserve their edema-inducing activity evaluated by the rat hind-paw edema test except for N. naja naja PEG-PLA2 in which inflammatory activity was significatively decreased. Altogether, the results show a partial dissociation of catalytic and inflammatory activities of Group II and III secretory PLA2s after their modification with PEG.

Evidence of a role for galectin-1 in acute inflammation.

Galectin-1 (Gal-1), a member of a family of beta-galactoside-binding proteins, has been suggested to play key roles in immunological and inflammatory processes. The present study deals with the concept of an in vivo role for Gal-1 in acute inflammation by using the rat hind paw edema test. Local administration of Gal-1 (0.5, 2, 4 and 8 microg/ml) inhibited acute inflammation induced by bee venom phospholipase A(2) (PLA(2)) when it was injected 30 min before the enzyme or co-injected together with PLA(2). The anti-inflammatory effect was prevented by a specific antibody, but independent of its carbohydrate-binding properties. In contrast, Gal-1 failed to inhibit histamine-induced edema. Histopathological studies showed a clear reduction of the inflammatory process when Gal-1 was injected before PLA(2), evidenced by a diminished number of infiltrated polymorphonuclear neutrophils and scarce degranulated mast cells. The anti-inflammatory effect was also assessed in vitro, showing that Gal-1 treatment reduced prostaglandin E(2) secretion and arachidonic acid release from stimulated peritoneal macrophages. Results presented here provide the first evidence for a role of Gal-1 in acute inflammation and suggest that the anti-inflammatory effect involves the inhibition of both soluble and cellular mediators of the inflammatory response.

Novel antiinflammatory analgesics: 3-(2-/4-pyridylethyl)-benzoxazolinone and oxazolo[4,5-b]pyridin-2-one derivatives.

Twenty-two new 3-[2-(2-and/or 4-pyridyl)ethyl]benzoxazolinone and oxazolo[4,5-b]pyridin-2-one derivatives have been synthesized by reacting 2- and/or 4-vinylpyridine and appropriate benzoxazolinones and oxazolo[4,5-b]pyridine-2-one. Their chemical structures have been proven by IR. 1H-NMR, 13C-NMR, mass spectroscopy, and elemental analysis. The analgesic activities of these compounds were investigated by a modified Koster's Test. Test results revealed that, at 100 mg/kg dose level, most of the compounds showed significant analgesic activities when compared to aspirin. Therefore the compounds were screened for their antiinflammatory activities using the carrageenan hind paw edema test. Compounds 1, 7, 10, 11, 12, 13, 15, 18, 20, 21 were found more active than indomethacine. In gastric ulceration studies gastrointestinal bleeding was not observed at 100 mg/kg dose level in compounds 1 and 2.

Condensed heterocyclic compounds: synthesis and antiinflammatory activity of novel thiazolo[3,2-alpha] pyrimidines.

In this study, thirty six new 2-benzylidene-7-methyl-3-oxo-5- phenyl-2,3-dihydro-5H-thiazolo[3,2-alpha]pyrimidine-6-carboxylic acid methyl esters were synthesized and characterized by spectral, crystallographic, and elemental analysis. The antiinflammatory activity of the compounds was tested by the carrageenan hind paw edema test. It was found that compound 6a having a 2-meth-oxyphenyl group at position 5 and a benzylidene group at position 2 was the most potent compound in this series. All the compounds that were tested for ulcer activity gave positive results.

Condensed Heterocyclic Compounds: Synthesis and Antiinflammatory Activity of Novel Thiazolo[3,2-a]pyrimidines

In this study, thirty six new 2-benzylidene-7-methyl-3-oxo-5-phenyl-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid methyl esters were synthesized and characterized by spectral, crystallographic, and elemental analysis. The antiinflammatory activity of the compounds was tested by the carrageenan hind paw edema test. It was found that compound 6a having a 2-methoxyphenyl group at position 5 and a benzylidene group at position 2 was the most potent compound in this series. All the compounds that were tested for ulcer activity gave positive results.

Anti-inflammatory action of Pluchea sagittalis: involvement of an antioxidant mechanism.

Pluchea sagittalis, (Lam.) Cabr., a popular medicinal herb grown in South America, was studied for anti-inflammatory and antioxidant activities. The anti-edema action of P. sagittalis aqueous extract was assayed in different models of inflammation: 1) the mouse ear edema test induced by arachidonic acid and croton oil; 2) the rat hind-paw edema test produced by several inflammatory inductors: carrageenan, dextran, zymosan, platelet-activating factor (PAF) and arachidonic acid; 3) a subacute model based on the rat carrageenan air-pouch granuloma test. Blood leukocyte free radical production was measured by flow cytometry with 2',7'-dichlorofluorescin diacetate (DCFH-DA) in vivo, in rats with induced air-pouch granuloma, and in a model in vitro. stimulating leukocytes with hydrogen peroxide. The aqueous extract of P. sagittalis showed a marked anti-inflammatory effect in both ear edema tests, dextran and carrageenan hind-paw edemas and carrageenan air-pouch model. It also had a potent antioxidant activity in blood leukocytes, both in vivo and in vitro. Our results correlate the reduction of free radical production with the anti-inflammatory effect of this plant.

1-(3-Methyl-2-benzoxazolinone-6-yl)-2-(4-substituted piperazine-1-yl)ethanones and ethanols: analgesic and antiinflammatory activities

Eight new 1-(3-methyl-2-benzoxazolinone-6-yl)-2-(4-substituted piperazine-1-yl)ethanone and 1-(methyl-2-benzoxazolinone-6-yl)-2-(4-substituted piperazine-1-yl)ethanol derivatives were synthesized and their chemical structures elucidated by UV, IR, 1H-NMR and elemental analysis. The analgesic activity of these compounds was investigated by a modified Koster test and constant temperature hot-plate test. Antiinflammatory activity of the compounds was screened by using the carrageenan hind-paw edema test. All the compounds showed higher analgesic activity than aspirin. Carrageenan edema inhibition of the compounds was higher than indomethacin. None of the compounds induced gastric ulceration.

Anti-inflammatory effect of gangliosides in the rat hindpaw edema test

The influence of total brain gangliosides on acute inflammation was investigated using the rat hind paw edema test. Total gangliosides (10 μg/paw) inhibited the edema produced by the injection of bee venom phospholipase A 2 (5 μg/paw) when the lipids were co-injected or injected 15 min before the phospholipase A 2. Sulphatide (10 μg/paw) did not inhibit the edema but potentiated it. Gangliosides (40 μg/paw) inhibited the edema induced by carrageenin 1% when they were injected 1 h before the agent. However, gangliosides (up to 200 μg/paw) failed to inhibit the dextran-induced edema. The edema test was also used to investigate the effect of gangliosides on the production of mediators of inflammation by peritoneal adherent macrophages. Gangliosides inhibited the production of mediators of inflammation only when they were incubated with these cells before the stimulation with phospholipase A 2 or carrageenin. Gangliosides did not inhibit the production of mediators of inflammation when arachidonic acid was added to the cells. These results suggest that the anti-inflammatory effect observed with gangliosides is mediated by inhibition at or before endogenous phospholipase activity.

Synthesis and antiinflammatory activity of cis- and trans-6,6a,7,8,9,10,10a,11-octahydro-11-oxodibenzo[b,e]thiepinacetic and -oxepinacetic acids

A series of cis- and trans-6,6a,7,8,9,10,10a,11-octahydro-11- oxodibenzo[b,e]thiepinacetic acids (6-9) and -oxepinacetic acids (10-13) were prepared and their antiinflammatory activity was examined in the rat carrageenan hind paw edema test. The antiinflammatory activity of these compounds depended on their stereochemical features (C6a, C10a, and C2'). The 6a,10a-trans compounds exhibited considerable antiinflammatory activity, whereas the 6a,10a-cis compounds were inactive. Among the trans compounds, 6,6a,7,8,9,10,10a,11-octahydro-11-oxodibenzo[b,e]thiepin-3-p ropionic acid (9a) and its oxepin analogue (13a) showed an antiinflammatory activity superior to that of indomethacin. The phenethyl ester (25) of 9a showed potent antiinflammatory activity, and its safety index (UD50/ED50) was over 14 times higher than that of indomethacin. The phenethyl ester (25) is the most favorable compound with high antiinflammatory activity and little ulcerogenicity.

A Thiazole Compound with Potential Antithrombotic Activity

A thiazole derivative, 4,5-bis(p-methoxyphenyl)-2-(trifluoromethyl)-thiazole was found to be a potent inhibitor of collagen-induced platelet aggregation, in vitro, using platelets from at at least six species, including man. It was active in human platelet-rich plasma at a concentration of 1 ng/ml. While its antiplatelet activity was greater than that of flurbiprofen, its cyclooxygenase activity was equivalent to that of flurbiprofen. Also, compared to flurbiprofen, the thiazole had less anti-inflammatory activity in the hind-paw edema test. The thiazole derivative inhibited platelet aggregation following oral administrative inhibited platelet aggregation following oral administration in five laboratory species. In the guinea pig it was active at 0.5 mg/kg. The LD50 in mice was greater than 1000 mg/kg (i.p.). This compound, which was designed through a systematic drug development program, may have high potential as an antithrombotic agent.