Induced Rat Paw Edema Model Research Articles

Anti-inflammatory, antinociceptive and diuretic activities of Trema orientalis Linn

The pharmacological interest coupled with traditional uses (antidiarrhoeal, antiseptic, analgesic etc) prompted us to test for anti-inflammatory, antinociceptive and diuretic activitities of Trema (T.) orientalis Linn. The crude methanolic leaves extract of T. orientalis was investigated for its possible anti-inflammatory activities using carrageenin induced rat paw edema model and cotton pellet implantation method in mice. Then the extract analyzed for its antinociceptive activities by acetic acid induced writhing model in mice. The extract possessed significant anti-inflammatory activity in both models at the doses of 200 and 400 mg/kg body weight of mice. Moreover, the extract showed significantly reduced the number of acetic acid-induced abdominal constriction in mice of 200 and 400 mg/kg body weight. The extract also showed positive diuretic activity in albino mice.

In vitro and In vivo anti-inflammatory activity of leaves of Symplocos cochinchnensis (Lour) Moore ssp laurina

The anti-inflammatory activities of different extracts of leaves Symplocos cochinchinensis Lour ssp laurina (Symplococaceae) were investigated for i n vitro anti-inflammatory activity by human red blood cell membrane stabilization method. The methanol extract showed effective in vitro anti-inflammatory activity was screened for in vivo antiinflammatory activity by carrageenan-induced paw edema in rat model. The potency of the extracts was compared with standard diclofenac (50 mg/kg). The methanol extract showed significant membrane stabilizing action on human red blood cell membrane and reduction of edema in carrageenan induced rat paw edema model.

Design, Synthesis and Evaluation of Antiinflammatory, Analgesic and Ulcerogenicity studies of Novel S-Substituted phenacyl-1,3,4-oxadiazole-2-thiol and Schiff bases of Diclofenac acid as Nonulcerogenic Derivatives

Diclofenac sodium is being used for its anti-inflammatory actions since 28 years, but as all the NSAIDs are suffering from the deadlier GI toxicities, diclofenac sodium is also not an exception to these toxicities. The free –COOH group is thought to be responsible for the GI toxicity associated with all traditional NSAIDs. In the present research work, the main motto was to develop new chemical entities as potential anti-inflammatory agents with no GI toxicities. In this paper, the results of synthesis and pharmacological screening of a series of S-substituted phenacyl 1,3,4-oxadiazoles and Schiff bases derived from 2-[(2,6-dichloroanilino) phenyl] acetic acid (diclofenac acid) are described. The 1,3,4-oxadiazoles and diclofenac moieties are important because of their versatile biological actions. In the present studies, the oxadiazole system has been functionalized onto the diclofenac acid moiety and 18 compounds in this series were synthesized. The structures of new compounds are characterized by TLC, FTIR, 1H NMR and Mass spectral data. These compounds were tested in vivo for their anti-inflammatory activity. The compounds, which showed significant activity (comparable to the standard drug diclofenac sodium), were screened for their analgesic activity and to check their ability to induce ulcers by ulcerogenicity and histopathology studies. Eight new compounds, out of 18, were found to have significant anti-inflammatory activity in the carrageenan induced rat paw oedema model, with significant analgesic activity in the acetic acid induced writhing model with no ulcerogenicity. The compounds, which showed negligible ulcerogenic action, also showed promising results in histopathology studies, that is, they were found to be causing no mucosal injury.

Niosomal Gel for Site-Specific Sustained Delivery of Anti-Arthritic Drug: In Vitro-In Vivo Evaluation

Celecoxib, a selective COX-2 inhibitor is commonly used in the treatment of arthritis. Recently, cardiotoxic effects associated with conventional modes of delivery of celecoxib have made it pertinent to develop alternate dosage forms capable of selectively delivering the drug topically to affected joints. The aim of the present study was to prepare and characterize niosomal gel formulation for sustained and site-specific delivery of celecoxib. Celecoxib loaded niosomes were prepared and characterized in vitro, ex-vivo and in vivo. The results of organ localization (deep skin layer + muscle) study showed that niosomal gel provided 6.5 times higher drug deposition as compared to carbopol gel (195.2+/-8.7 and 30.0+/-1.5 microg, respectively). The muscle to plasma concentration ratio for niosomal gel formulation was six (2.16+/-0.12 microg/g vs. 0.34+/-0.01 microg/ml) and for carbopol gel it was one (0.36+/-0.01 microg/g vs. 0.43+/-0.02 microg/ml). Biological effectiveness of optimized formulation was evaluated using carrageenan induced rat paw edema model. The application of niosomal gel produced significant reduction of rat paw edema as compared to that after application of conventional gel indicating better skin permeation and deposition of celecoxib from niosomes. The results of the present study demonstrated niosomal gel formulation possess great potential for enhanced skin accumulation, prolonging drug release and improving the site specificity of celecoxib.

Inhibitory effects of 2,3,5,4′-tetrahydroxystilbene-2-O-β-d-glucoside on experimental inflammation and cyclooxygenase 2 activity

The inhibitory effects of 2,3,5,4′-tetrahydroxystilbene-2-O-β-d-glucoside (THSG), extracted from the roots of Polygonum multiflorum Thunb, on inflammatory activity in animal models and cyclooxygenase-2 (COX-2) activity in lipopolysaccharide (LPS)-induced mouse RAW264.7 macrophage cells were investigated. The carrageenin (CGN)-induced rat paw oedema model and dimethylbenzene-induced mouse ear oedema model were prepared; MTT assay, semi-quantitative RT-PCR, Western blot and ELISA were adopted. THSG 2.3, 4.6 and 9.2 mg kg− 1 by oral administration inhibited mouse ear oedema and the percentage of inhibition of THSG 9.2 mg kg− 1 is 87%. THSG 3.2, 6.4 and 12.8 mg kg− 1 by oral administration dose-dependently inhibited rat paw oedema and the percentage of inhibition of THSG 12.8 mg kg− 1 is 56% at 6 h. Indomethacin 13 and 9 mg kg− 1 showed 90% and 57% inhibition in the same animal models, respectively. LPS 1 μg ml− 1 significantly up-regulated prostaglandin E2 (PGE2) production (inducing COX-2 activity) by 35% (exogenous arachidonic acid, AA), which was dose-dependently decreased by THSG 1, 10, and 100 μmol L− 1 and the percentage of inhibition of THSG 10 μmol L− 1 was 40%. NS-398 10 μmol L− 1 decreased PGE2 production by 42%. THSG 1, 10, 100 μmol L− 1 was shown to markedly inhibit the LPS-induced COX-2 protein and mRNA expression in RAW264.7 cells (P < 0.05) but had no effect on COX-1 protein and mRNA (P>0.05). In summary, the data showed that THSG possessed an anti-inflammatory effect, which was perhaps related to the inhibition of COX-2 enzyme activity and expression in RAW264.7 macrophage cells.

2-Amino-5-thiazolyl motif: A novel scaffold for designing anti-inflammatory agents of diverse structures

Substituted thiazoles with different structural features were synthesized and screened for their anti-inflammatory activity in acute carrageenin induced rat paw edema model and chronic formalin induced rat paw edema model. The compounds 1– 5 showed 83, 30, 63, 69 and 73% protection, respectively, in acute carrageenin induced rat paw edema model. In 5-day chronic formalin induced rat paw edema model on the fifth day 1 and 5 gave 66 and 41% protection. Both studies were carried out at a dose of 100 mg/kg body weight. The activity was compared with that of Ibuprofen, Rofecoxib, and Dexamethasone both in acute and chronic anti-inflammatory models. Compound 1 without COX-1 and COX-2 inhibitory activity showed good activity profile almost mimicking the gold standard Dexamethasone in terms of efficacy. A 7-day study in rats at dose of 100 mg/kg showed that this compound does not have any ulcerogenic activity and toxicity. The activity of 5 shows that incorporating two pharmacophoric features in one molecule can be a good drug designing strategy. 2,4-Diaminothiazoles with an aliphatic oxime esters attached via a ketone bridge to the 5th position of thiazole was identified as a novel scaffold for designing anti-inflammatory agents.

Identification of 2-hydroxymethyl-4-[5-(4-methoxyphenyl)-3-trifluoromethyl-pyrazol-1-yl]- N-propionylbenzenesulfonamide sodium as a potential COX-2 inhibitor for oral and parenteral administration

Synthesis of prodrugs of orally active COX-2 inhibitor 3 involving sulfamoyl (SO 2NH 2) and hydroxymethyl (CH 2OH) groups, and their biological evaluation are described. Of these prodrugs, the N-propionyl sulfonamide sodium 3k was found to be much superior to the parent compound 3 and other marketed COX-2 inhibitors in carrageenan induced rat paw edema model of inflammation due to highly elevated drug levels in systemic circulation. This prodrug has a potential both for oral as well as parenteral administration due to impressive analgesic activity, antipyretic potency, and extraordinary water solubility.

Tetra substituted thiophenes as anti-inflammatory agents: Exploitation of analogue-based drug design

A series of 17 novel tetra substituted thiophenes was designed, synthesized, and screened for anti-inflammatory activity in carrageenin induced rat paw edema model, an acute in vivo model. The lead molecule selected was Tenidap, a dual COX/LOX inhibitor. Compounds I (43%), III (60%), IV (60%), and VIII (64%) showed moderate to good anti-inflammatory activity. The best candidate among the whole series was VIII, which gave 64% protection to the inflamed paw. The side chain of candidate VIII had resemblance to that of Romazarit, a DMARD, which was withdrawn due to its toxicity profile. A probable reason for the metabolic stability of the proposed side chain not having the possibility of generating peroxy type radicals or acrylic acid moieties, unlike Romazarit, is discussed. The biological activity exhibited by the three designed series was in the order of methyl amino series > ethyl amino series > carbethoxy amino series. The –(C O)–CH 2–COOR side chain at the fifth position as in candidate VIII, the methyl amino group at the second position, and the ester at the third position of the thiophene can be considered as a three-point pharmacophore for designing better anti-inflammatory agents. The present study is a classical example of the exploitation of an analogue based drug design, which culminated in the development of good anti-inflammatory agents that have the potential of becoming dual inhibitors.

Transdermal Delivery of An Analgesic Agent Using Elastic Liposomes: Preparation, Characterization and Performance Evaluation

The aim of the present study was to prepare and characterize novel vesicular carrier elastic liposomes, of most commonly used non-steroidal anti-inflammatory agent diclofenac for its sustained and targeted delivery. Elastic liposomes of diclofenac were prepared and characterized in vitro and in vivo. The effect of different formulation variables like type of surfactant, concentration of surfactant and dose of drug on transdermal flux, amount of drug deposited into the skin, muscle and plasma concentration was investigated. The biological activity of optimized formulation was evaluated using carrageenan induced rat paw edema model and results were compared with commercial hydrogel formulation. The elastic liposomal formulations achieved muscle drug concentration between 2.2+/-0.14 to 5.3+/-0.22 microg/g at 12 hr. The same dose of commercial hydrogel formulation produced drug levels between 0.41+/-0.07 to 1.1+/-0.09 microg/g in the muscle. Plasma concentration study showed regiospecificity of elastic liposomal formulation. The results of in vivo study revealed that incorporation of diclofenac in elastic liposomes increased its biological activity two fold as compared to commercial hydrogel formulation. The results of the present study demonstrated greater effectiveness of dermaly applied diclofenac elastic liposomal formulation in comparison to conventional delivery system. The optimized elastic liposomal formulation offers a promising means for the non-invasive treatment of local pain and inflammation by topical application.

Anti-inflammatory, antinociceptive and diuretic activities of Amoora cucullata Roxb.

The crude methanolic extract of the leaves of Amoora cucullata Roxb. was investigated for its possible anti-inflammatory activity using carrageenin induced rat paw edema model and cotton pellet implantation method in rat. The extract was also studied for its antinociceptive activity using acetic acid induced writhing model in mice. At the doses of 200 and 400 mg/kg body weight, the extract showed significant anti-inflammatory activity in both models. At the same doses, the extract also significantly reduced the number of acetic acid-induced abdominal constriction (writhing) in mice. The crude extract also showed significant diuretic activity in albino mice.

Design, synthesis, and SAR studies of some 5-aliphatic oximino esters of thiophene as potential anti-inflammatory leads: comparative biological activity profile of aliphatic oximes vs aromatic oximes

A series of novel tetra substituted thiophenes were synthesized, characterized, and evaluated for their anti-inflammatory activity in carrageenin induced rat paw edema model—an acute in vivo model. Compounds V1, V3, V11, V12, V17, and V18 showed good anti-inflammatory activity, indicating the importance of oxime moiety in modulating the activity. The structure–activity relationship studies explore “ the aliphatic oxime esters” attached via a ketone bridge to fifth position of the thiophene, and indicate that this feature may enhance the anti-inflammatory activity as compared to aromatic oximes. Since free radicals are implicated in various inflammatory disorders, the free radical scavenging activity of some of the synthesized candidates was assessed using 1,1-diphenyl-2-picryl hydrazyl assay. The oxime containing analogs exhibited weak to moderate activity as free radical scavengers in DPPH assay. A plausible reasoning for its free radical scavenging ability is discussed. All the compounds were also screened in nitro blue tetrazolium model, to assess them as superoxide anion radical scavengers. A direct correlation between anti-inflammatory activity and free radical scavenging activity was not seen. The results disclose a new class of anti-inflammatory agents designed and synthesized for the first time wherein the utility of aliphatic oxime esters in modulating the anti-inflammatory activity profile is apparent. This will give us potential anti-inflammatory leads.

Anti-inflammatory, Antioxidant and Analgesic Amides

The synthesis of some new aryl acetic acids and amides and a pharmacochemical study and quantitative structure-activity relationships (QSAR) on them are described. The compounds were screened for their biological activity using the carrageenin induced rat paw oedema model and a significant inhibition of oedema occurred (44.1–80.1%) at a concentration of 0.01 mmol/1 kg. The analgesic activity, based on the inhibition of acetic acid-induced writhing in rats was also found to be significant. The compounds were found to interact with the stable free radical 1,1-diphenyl-hydrazyl DPPH and with DMSO (for hydroxyl radicals). The compounds were screened for radical scavenging activity with the xanthine/xanthine oxidase system for O2-• and for inhibition of soybean lipoxygenase (LOX). The results are discussed in terms of the structural and physicochemical characteristics of the compounds.

224 Toxicity testing protocol optimization with CACO-2 cells: A case-study on heavy metals

A series of 5-methanesulphonamido benzimidazole derivatives were designed by combining the structural features of clinically useful anti-inflammatory drugs (nimesulide and rofecoxib) and antiulcer drugs (lansoprazole, omeprazole, etc.) based on physicochemical and 3D similarity studies. The compounds were evaluated for their anti-inflammatory activity in carrageenan induced rat paw edema model taking rofecoxib and indomethacin as standard drugs. In vitro antioxidant activity of the compounds was assessed by potassium ferricyanide reducing power (PFRAP) assay. The compounds 9, 10 and 11 showed anti-inflammatory activity comparable to the standard group and were also non-ulcerogenic at the test doses. Compounds 6–11 exhibited good antioxidant effect in the concentration range (1.0–50.0 µmol/ml. Preliminary theoretical ADME profiling of the compounds based on computation of selected physicochemical properties showed an excellent compliance with Lipinski’s rule.

Antiinflammatory activity of extracts of Biophytum sensitivum in carrageenin-induced rat paw oedema.

The antiinflammatory activity of aqueous and methanol extracts of aerial parts, an aqueous extract of roots as well as ultrafiltration fractions of a methanol extract of roots of Biophytum sensitivum were evaluated in the carrageenin induced rat paw oedema model. All the extracts except the methanol extract of aerial parts exhibited antiinflammatory activity, but inhibition of oedema was found to be maximum with aqueous extracts.

Pharmacodynamic and pharmacokinetic evaluation of lipid microspheres of indomethacin

Lipid microspheres (LM) of indomethacin were prepared using phosphatidyl choline and soya bean oil. LM of required size (<1 μm) were obtained by intermittent microscopic observation while homogenization. Anti-inflammatory activity of lipo-indomethacin was compared with free indomethacin by carrageenan induced rat paw edema model. It was found that at 30% edema inhibitory dose, lipo-indomethacin was about 1.5 times more potent than free indomethacin, indicating possible localization of LM at the inflammatory site. Biodistribution studies were performed in rats at the dose of 12 mg/kg. After 2 h of the treatment, concentration of the drug was 0.31 μg/g of inflammatory tissue with lipo-indomethacin, whereas, only 0.05 μg/g of the tissue was found with free indomethacin. Maximum difference in drug concentrations between the above two formulations was observed in lungs. LM were found not to cross the BBB as drug concentration in the brain after lipo-indomethacin treatment was below the detectable level. Thus, the pharmacokinetic data gave a quantitative evidence for high anti-inflammatory potential of lipo-indomethacin.

Antiinflammatory Activity of Fractions of Latex ofCalotropis procera in Carrageenan Induced Rat Paw Oedema

The crude dry latex of Calotropis procerapossesses a potent antiinflammatory activity. The antiinflammatory activity of petroleum ether, acetone, methanol and aqueous extracts of dry latex of Calotropis procera was tested in the carrageenan induced rat paw oedema model. All the fractions exhibited antiinflammatory activity but inhibition of oedema was found to be greatest with the acetone and aqueous extracts. © 1997 by John Wiley & Sons, Ltd.

Effect of &lt;i&gt;Nigella sativa&lt;/i&gt; Linn (Ranunculaceae) ground seed extract on carrageenan induced inflammation in rats

Nigella sativa Linn (Family: Ranunculaceae) Bengali name “kalo jera” is used as spice in Bengali foods. Native to Western Asia, Turkey, Iraq and Egypt, the black seed oil has been valued for its health benefits for centuries. This plant has been used in traditional medicine for the treatment of stomach aches, asthma, bronchitis, coughs, fevers, tumour and as a tonic. The dried and grounded seed was extracted with ethanol and the extract was evaluated for anti-inflammatory activity in carrageenan induced rat paw edema model. The extracts were administered orally at the doses of 250 and 500 mg/kg body weight, and statistically significant (p&lt;0.05) anti-inflammatory effects were observed in a dose dependant manner. The extract showed 28.75% and 43.79% inhibition of inflammation at the doses of 250 and 500 mg/kg body weight after first hour of the carrageenan administration which was comparable to that of standard drugs aspirin 40.52% and hydrocortisone 47.71% respectively. The result of this study supported the traditional medicinal uses of this seed.Ibrahim Med. Coll. J. 2011; 5(1): 22-24 Key word: Nigella sativa; inflammation; carrageenanDOI: http://dx.doi.org/10.3329/imcj.v5i1.9857