Subacute Models Of Inflammation Research Articles

Evaluation of Anti-Inflammatory Activity of the Methanol Extracts of Premna schimperi Engl (Lamiaceae) Leaves in Rats.

Even though it is a protective reaction, inflammation continues to be one of the most challenging medical disorders. The current conventional anti-inflammatory drugs have many undesirable health effects and are in need of newer drugs. The purpose of this study was to evaluate the anti-inflammatory effects of an aqueous methanol crude extract of Premna schimperi leaves. Premna schimperi leaf was extracted with 80% methanol and concentrated; the concentrated extract was used to evaluate the acute toxicity and anti-inflammatory effects. For the acute toxicity study, a single dose of Premna schimperi extract at a dose of 2000 mg/kg was administered and observed for 14 days. Acute, sub-acute, and chronic anti-inflammatory models were employed to evaluate the anti-inflammatory effect of the extract compared to the standard drug. Data were analyzed with SPSS V. 27, and the significance was established with a one-way ANOVA followed by a post hoc Tukey's test. Acute oral toxicity testing at a dose of 2000 mg/kg did not show any sign of toxicity. According to the phytochemical study, the plants contained flavonoids, terpenoids, tannins, cardiac glycosides, steroids, phenolics, and anthraquinones. The extract doses of 200 mg/kg, 400 mg/kg, and 800 mg/kg of extracts effectively (p<0.001) reduced paw edema in the acute and sub-acute models of inflammation. When compared to the negative control group, all tested doses in the chronic model significantly (p<0.05) decreased the production of exudates and the amount of granuloma tissue. Premna schimperi displayed significant anti-inflammatory activity. The tested doses inhibit the formation of edema, granulomas, and exudates.

Effect of Bezafibrate, a PPARα Activator, on Acute and Subacute Inflammation in Male Wistar Rats

Aim To investigate the anti-inflammatory effect of bezafibrate on acute and subacute inflammation in adult male Wistar rats. Methods The study was carried out in adult male Wistar rats and they were allocated into three groups, that is, control, aspirin and bezafibrate, after obtaining clearance from Institutional Animal Ethics Committee. Acute inflammation was studied using carrageenan-induced rat paw oedema, and the volume displacement due to paw oedema using the plethysmograph. Subacute inflammation was studied using foreign body induced granuloma models. Analysis was performed using one-way ANOVA followed by post hoc tests of Dunnett’s. The value p &lt; 0.05 was considered statistically significant. Results Bezafibrate showed a significant anti-inflammatory effect in acute as well as subacute models of inflammation when compared to control in the present study. Conclusions In patients receiving bezafibrate for hyperlipidemia, its anti-inflammatory potential may have an additional benefit in preventing complication of atherosclerosis.

Effect of ethanolic extract of Stachys pilifera Benth on subacute experimental models of inflammation and some underlying mechanisms.

Background and purpose:This study was designed to evaluate the anti-inflammatory activities of S. pilifera (HESP) in two sub-acute models of inflammation and clarified some possible mechanisms.Experimental approach:Colorimetric methods were used to determine total phenol and flavonoid contents. Carrageenan or formalin-induced rat paw edema (seven days) and multiple application TPA-induced ear edema in mice (9 days) were used. The concentration of IL-1 and TNF-α were measured in the inflamed paw, as well as MDA levels in the serum and liver. Histopathological studies and in vitro anti-inflammatory effects of the extract were also studied using heat-or hypotonicity-induced hemolysis in RBC humans.Findings/Results:Total phenol and flavonoid contents of HESP were 101.35 ± 2.96 mg GAE/g extract and 660.79 ± 10.06 mg RE g extract, respectively. Oral (100 and 200 mg/kg) and topical application (5 mg/ear) of HESP significantly inhibited formalin-induced paw edema and multiple TPA-induced ear edema. The extract also significantly decreased the serum and liver levels of MDA in the carrageenan and formalin tests. The elevated levels of TNF-α and IL-1β in the carrageenan-injected paw were not affected by HESP. The extract (50-800 μg/mL) inhibited heat-or hypotonicity-induced hemolysis. Histopathological examination of the inflamed tissues revealed that HESP inhibited congestion and leukocyte infiltration.Conclusion and implications:The findings confirmed the potent anti-inflammatory effects of S. pilifera in two sub-acute inflammation models and suggested that these properties were not related to IL-1 and TNF-α, but could be attributed to inhibition of lipid peroxidation, membrane stabilization, and inhibition of leukocyte penetration.

Assessment of the effect of calcium on the anti-inflammatory activity of etoricoxib in albino rats

Background: It would be worthwhile to investigate if it is possible to obtain an anti-inflammatory effect with a lower dose of etoricoxib after it has been combined with calcium, the effect of which is equivalent to higher dose of etoricoxib. Hence the aim was to study effect of calcium and calcium gluconate on the anti-inflammatory activity of etoricoxib.Methods: Animals were distributed in five groups each group containing six rats. Experiments were conducted between 9:00 to 16:00 hours. All animal procedures were performed in accordance with the recommendations for proper care and use of laboratory animal .The doses of drugs employed in the study were based upon the human dose after conversion to that of rat.Results: The results of present study indicate that calcium gluconate (50 mg/kg) combined with etoricoxib (5 mg/kg) possesses significant anti-inflammatory property both in acute and subacute models of inflammation which was comparable to that of etoricoxib (8 mg/kg).Conclusions: From the present study it is concluded that calcium gluconate (50 mg/kg) possesses an anti-inflammatory activity. Lower dose of etoricoxib (5 mg/kg) if combined with calcium gluconate (50 mg/kg) can produce significant anti-inflammatory effect. The advantages of such combined preparations are obviously a reduction in the dose of etoricoxib that could still produce significant anti-inflammatory action and a possible protection against COX -2 inhibitor induced prothrombotic events. It is worthwhile to evaluate such preparations through clinical trials.

Effect of fenofibrate on acute and subacute inflammation in male Wistar rats

Background: The objective of the study was to investigate the effect of fenofibrate on acute and subacute models of inflammation in adult male Wistar rats.Methods: After obtaining clearance from Institutional Animal Ethics Committee, six adult male Wistar rats were allocated to each of the three groups i.e. control, aspirin and fenofibrate. Acute inflammation was studied using carrageenan induced rat paw oedema and the volume displacement due to paw oedema was measured using the plethysmograph. Subacute inflammation was studied using foreign body insertion (cotton pellet and grass pith) models. Dry granuloma weight and histopathological examination of the granuloma were the outcome measures for measuring subacute inflammation. The percentage inhibition of inflammation with aspirin and fenofibrate was calculated in both acute and subacute models. The experiments were conducted according to the guidelines of the Committee for the Purpose of Control and Supervision on Experiments on Animals (CPCSEA). The mean volume displacement obtained with a plethysmograph, the mean dry weight of granuloma and the percentage inhibition with aspirin and fenofibrate were analyzed by one way analysis of variance (ANOVA) using Graph pad prism software.Results: Aspirin and fenofibrate significantly reduced both acute and subacute inflammation (p&lt;0.001). Dunnet’s test showed a significant difference in the study groups when compared to the control. The reduction of inflammation with fenofibrate was comparable to aspirin.Conclusions: Oral fenofibrate showed significant anti-inflammatory activity, which was comparable to aspirin, in both acute as well as sub-acute models of inflammation. This anti-inflammatory effect may benefit atherosclerosis in patients receiving fenofibrate for hyperlipidemia.

ASSESSMENT OF ANTI-INFLAMMATORY ACTIVITY OF ETHANOLIC EXTRACT OF ASAM KANDIS (GARCINIA XANTHOCHYMUS HOOK. F. EX T. ANDERSON) FRUIT

Objective: The objective of this study was to evaluate the anti-inflammatory activity in acute and subacute models of inflammation from ethanolic fruit extract of Asam kandis (Garcinia xanthochymus Hook. f. ex T. Anderson) in animal (rats) models.Methods: Pleliminary phytochemical screening was carried out by using standard procedures.. Assessment of acute and subacute models of inflammation was using carrageenan-induced paw edema method and cotton pellet granuloma method using three dosage treatments; 200 mg/kg BW, 400 mg/kg BW, and 800 mg/kg BW along with a negative control group (0.5% Na CMC) and positive control (Na diclofenac 2.25 mg/kg BW). The inhibition period was observed at 30, 60, 90, 120, 150, and 180 min time intervals.Result: The phytochemical screening showed that the ethanolic fruit extract from Asam kandis contain contains flavonoids, glycosides, steroids, and triterpenoids. The anti-inflammatory result showed that the strongest inhibition produced by ethanolic fruit extract of Asam kandis occurred on the dosage of 800 mg/kg BW compared to the other doses (200 and 400 mg/kg BW) throughout the observation period.Conclusion: This finding indicated that ethanolic fruit extract of Asam kandis (G. xanthochymus Hook. f. ex T. Anderson) might become an interesting candidate for treatment of inflammation.

Effect of anti-inflammatory activity of ranolazine in rat model of inflammation.

Background & objectives:Inflammatory processes are a recognized feature of atherosclerotic lesions. Ranolazine inhibits the inflammatory markers such as C-reactive protein, interleukins-1 and -6 and tumour necrosis factor-alpha. The present study was planned to evaluate the effect of anti-inflammatory activity of ranolazine in acute and sub-acute models of inflammation in rats and compare the same with that of control (gum acacia 1%) and aspirin (standard anti-inflammatory drug).Methods:Adult male Wistar rats (150-180 g) were used for the study. They were divided into three groups (n=6). One per cent gum acacia (control), aspirin (200 mg/kg body weight) and ranolazine (180 mg/kg body weight) were given orally. Acute inflammation was induced by injecting carrageenan in the left hind paw. Paw oedema volume and percentage inhibition were measured. Subacute inflammation was induced by implanting foreign bodies subcutaneously. Percentage inhibition of granuloma dry weight and haematoxylin and eosin stained sections of granulation tissue were studied.Results:In acute and subacute model study, ranolazine significantly (P<0.01) decreased the paw oedema volume and granuloma dry weight as compared to control and it was comparable to that of aspirin and histopathological sections showed a decrease in granulation tissue formation as compared to control.Interpretation & conclusions:Ranolazine demonstrated significant anti-inflammatory activity in acute and subacute models of inflammation and needs further evaluation for its use in reducing atherosclerosis.

Effect of Solanum nigrum Linn on Acute and Sub-Acute Models of Inflammation

Objective: The aim of the study was to see the effect of ethanolic extract of Solanum nigrum Linn on Acute and Sub-acute inflammation. Method: Wistar rats weighing 150-200gms were used, divided into four groups Group 1 was control group, two groups Group 2 and 3 treated with the plant extracts at 100 & 200 mg/kg b.w and Group 4 treated with indomethacin, 10 mg/kg b.w. Acute inflammation was induced by injecting 0.1 mL of 1% homogenized carrageenan suspension in normal saline to the right hind paw of the rats prior to which drug treatment was given and paw volume was measured using a digital plethysmometer. Sub-acute anti-inflammatory studies were carried out as described by winter and Porter and hematological parameters were estimated. The granuloma tissue formed during the proliferative process was isolated and wet and dry exudates formation was estimated in various treatment groups. The effect of extract and indomethacin on vital organs like liver, kidney, stomach was also studied by performing histological studies. Results: Study shows that the hydroalcoholic extract of whole plant of Solanum nigrum L. is effective only at higher dose effectively suppressing carrageenan induced inflammation suggesting the inhibition of release of prostaglandin, bradykinin, leukotrienes and polymorphonuclear cells. The histological studies further confirm the anti-inflammatory property of the extract while simultaneously maintaining normal cellular architecture of vital organs than as compared to indomethacin treated group. Conclusion: The ethanolic extract of whole plant of Solanum nigrum Linn shows promising anti-inflammatory activity on both acute and sub-acute stages of inflammation. Key words: Acute Inflammation, Sub-acute Inflammation, Anti-inflammatory activity, Solanum nigrum , Hematological parameters, Histological studies.

An experimental evaluation of anti-inflammatory activities of some combined NSAID preparations in albino rats

Background: Non-steroidal anti-inflammatory drugs are among the most commonly used drugs across the globe and they are also available over the counter for minor symptoms of pain and inflammation. Their toxicity profile limits their continued usage and search is continuing for the better effective and safer agent.Methods: Interaction of paracetamol with diclofenac, ibuprofen and mefenamic acid were studied on carrageenan induced rat paw edema and cotton pellet induced granuloma models. Potentiation of these NSAIDs by paracetamol was also studied on same models.Results: Addition of paracetamol did not increase anti-inflammatory activity of diclofenac, ibuprofen and mefenamic acid in both acute and subacute models of inflammation. Paracetamol found to potentiate the ibuprofen action in anti-inflammatory model where as in subacute inflammatory model diclofenac action was potentited.Conclusions: Our study does not support the rationality of various fixed dose combination of NSAIDs with paracetamol available in market. Either NSAIDs to be used individually or their dose need to be decreased in fixed dose combination.

Effect of dipeptidyl peptidase 4 inhibitors on acute and subacute models of inflammation in male Wistar rats: An experimental study.

Introduction:The prevalence of Type 2 diabetes mellitus (T2DM) has reached alarming proportions due to the rapidly increasing rates of this disease worldwide. Preclinical and clinical studies have revealed elevated levels of inflammatory markers in a vast number of illnesses such as T2DM, obesity, and atherothrombosis collectively called metabolic syndrome leading to adverse cardiovascular events. Dipeptidyl peptidase 4 (DPP-4) inhibitors which are the enhancers of glucagon-like peptide 1 (GLP -1), could have anti-inflammatory potential which could help in reducing cardiovascular complications of diabetes and benefit patients suffering from the metabolic syndrome.Objective:The objective of this study was to analyze the effect of DPP-4 inhibitors, namely vildagliptin and saxagliptin on acute and subacute models of inflammation.Materials and Methods:Male Wistar rats were randomly divided into control, standard, and two treatment groups (6 animals in each group, total 24 animals). The animals received the drugs orally. The effects of vildagliptin and saxagliptin on inflammation were tested in acute (carrageenan-induced paw edema method) and subacute (grass pith and cotton pellet implantation method) models of inflammation.Results:Vildagliptin and saxagliptin used in the present study showed a significant anti-inflammatory activity in acute and subacute models of inflammation.Conclusion:The present study suggests that vildagliptin and saxagliptin have significant anti-inflammatory potential. Based on the findings of the present study and the available literature, it can be concluded that the anti-inflammatory potential of DPP-4 inhibitors could help to reduce the cardiovascular complications of Type 2 diabetes and the related cluster of metabolic disorders collectively called the metabolic syndrome.

Variable anti-edema and anti-granuloma effects of liraglutide and teneligliptin on experimental Wistar albino rat inflammatory models

Background: Diabetes mellitus is not only a chronic metabolic disorder but also an inflammatory one. Antidiabetic drugs are required to address both these entities to reduce the micro- and macro-complications associated with diabetes. Some of the incretin-based drugs have been shown to have decreased inflammatory markers. The studies on inflammatory models are very less. Aims and Objectives: The aim of this study is to evaluate anti-inflammatory activities of liraglutide, a glucagon-like peptide-1 analog, and teneligliptin, a dipeptidyl peptidase-4 inhibitor in experimental acute and subacute models of inflammation and also to evaluate their interactions with ibuprofen, a standard non-steroidal anti-inflammatory drugs. Materials and Methods: Carrageenan-induced paw edema to assess edema in acute anti-inflammatory action and cotton pellet-induced granuloma method to assess granuloma dry weight of liraglutide and teneligliptin in rats. Results: Liraglutide did not show anti-edema and anti-granuloma activity but potentiated the anti-granuloma effect of ibuprofen. Teneligliptin showed only anti-granuloma effect and potentiated both anti-edema and anti-granuloma activities of ibuprofen. Conclusion: Liraglutide and teneligliptin individually have variable anti-inflammatory activities, and they also have variable ibuprofen potentiating action. They have potentiated the subacute anti-inflammatory of ibuprofen by their anti-granuloma effect.

Effect of trimetazidine on acute and sub-acute models of inflammation in male wistar rats

Background: Coronary artery disease (CAD) is the leading cause of morbidity and mortality. Pathogenesis involved in angina pectoris and acute coronary syndrome (ACS) is atherosclerosis. Inflammation drives all phases of atherosclerosis, including initiation, progression of CAD and its complications. Drugs that reduce inflammation may have added benefit in the treatment of cardiovascular disease. Studies have shown that trimetazidine inhibits the inflammatory markers like C- reactive protein, interleukins (IL-1, IL-6) and tumor necrosis factor alpha. Objective of the study was to investigate the effect of trimetazidine on acute and sub-acute models of inflammation in adult male Wistar rats.Methods: Adult male Wistar rats (150 to 180 mg) were randomly divided into three groups (n=6 each) viz. control (vehicle), aspirin (200 mg / kg body weight of rat) and trimetazidine (5.4 mg / kg body weight of rat). Anti-inflammatory effects of these drugs were studied in acute (carrageenan induced rat paw oedema) and sub-acute (cotton pellet induced granulation tissue and histopathological examination of granulation tissue surrounding grass piths) models of inflammation. Data was expressed as mean±SEM and analysed by one way ANOVA followed by Dunnet’s and Bonferroni test. p&lt;0.05 was considered as significant.Results: Trimetazidine group showed significant (p &lt;0.05) anti-inflammatory effect both in acute and sub-acute models of inflammation which was comparable to that of aspirin group.Conclusions: Results of the study indicate that trimetazidine can reduce the complications of atherosclerosis which involves inflammation as the major steps in its pathogenesis.

Effect of rifampicin, isoniazid on acute and subacute inflammation in male Wistar rats: an experimental study

Background: Tuberculosis (TB) is characterized by significant inflammation leading to complications like pulmonary fibrosis, constrictive pericarditis, etc. Drugs possessing anti-inflammatory activity can reduce the complications of infections occurring due to inflammation and fibrosis. To study the effect of rifampicin, isoniazid on acute and subacute models of inflammation in male Wistar rats. Methods: The in vivo anti-inflammatory activity of rifampicin, isoniazid was studied using acute (carrageenan paw edema) and sub-acute (cotton pellet granuloma and histopathologic examination of grass pith) models of inflammation. Results: Rifampicin and isoniazid used in the present study showed significant anti-inflammatory activity in acute as well as subacute models of inflammation. Conclusion: Rifampicin and isoniazid when administered to treat TB can reduce complications of TB by virtue of its anti-inflammatory activity.

Evaluation of dipyridamole on acute and subacute models of inflammation in male wistar rats: An experimental study

Background: Atherosclerosis and its complications remains the major cause of death and premature disability. Atherogenesis involves elements of inflammation, a process that now provides a unifying theme in the pathogenesis of the disease. Anti-platelet drugs are currently used in the treatment of atherosclerosis and its complications. Our study evaluated the influence of dipyridamole on acute and sub-acute models of inflammation in male Wistar rats. Methods: Male Wistar rats (150-200g) were divided into three groups i.e. control, Aspirin and dipyridamole (n=6 animals in each group). The effect of dipyridamole, administered orally, on inflammation was studied using acute (carrageenan induced rat paw edema) and sub-acute (cotton pellet granuloma and histopathological examination of grass piths) models. Experiment was conducted according to the Committee for the Purpose of Control and Supervision on Experiments on Animals (CPCSEA) guidelines. Analysis was done using one way ANOVA followed by Post Hoc Test of Dunnets. P<0.05 was considered as statistically significant. Results: Dipyridamole showed significant inhibition of rat paw edema in acute model (P<0.01) and granuloma dry weight, in sub acute model of inflammation when compared to control (P<0.01). Histopathological examination of grass pith revealed markedly reduced fibroblasts, granulation tissue, fibrous tissue and collagen in dipyridamole group when compared to control. Conclusion: Dipyridamole exhibited a significant anti inflammatory activity in acute and sub-acute models of inflammation.

Evaluation of clopidogrel on acute and sub-acute models of inflammation in male Wistar rats

Background: Atherosclerosis and its complications remain the major cause of death and premature disability. Atherogenesis involves elements of inflammation, a process that now provides a unifying theme in the pathogenesis of the disease. Anti-platelet drugs are currently used in the treatment of atherosclerosis and its complications. Our study evaluated the influence of clopidogrel on acute and sub-acute models of inflammation in male Wistar rats. Methods: Male Wistar rats (150-200 g) were divided into three groups, i.e. control, aspirin and clopidogrel (n=6 animals in each group). The effect of clopidogrel administered orally on inflammation was studied using acute (carrageenan-induced rat paw edema) and sub-acute (cotton pellet granuloma and histopathological examination of grass piths) models. Experiment was conducted according to the Committee for the Purpose of Control and Supervision on Experiments on Animals guidelines. Analysis was done using one-way ANOVA followed by post-hoc test of Dunnets. p&lt;0.05 was considered as statistically significant. Results: Clopidogrel showed significant inhibition of rat paw edema in acute model (p&lt;0.01) and granuloma dry weight, in sub-acute model of inflammation when compared to control (p&lt;0.01). Histopathological examination of grass pith revealed markedly reduced fibroblasts, granulation tissue, fibrous tissue and collagen in clopidogrel group when compared to control. Conclusion: Clopidogrel exhibited a significant anti-inflammatory activity in acute and sub-acute models of inflammation.

Evaluation of antiinflammatory activity of centratherum anthelminticum (L) kuntze seed

In the present study petroleum ether and alcoholic extracts of Centratherum anthelminticum (L) Kuntze seed (100 mg and 200 mg/kg p.o.) were evaluated for antiinflammatory activity in acute and subacute models of inflammation. It was found that both petroleum ether and alcoholic extracts showed significant reduction in paw oedema in carrageenan-induced model. In subchronic inflammatory phase both extracts provoked a significant reduction of transudation phase and too little extent proliferative phase when tested in cotton pellet-induced granuloma model. Both the extracts also reduced alkaline phosphatase activity in serum. The histopathology of granuloma tissue showed significant inhibition of lymphocytes, neutrophils, exudates, necrosis and giant cell when compared with control without ulcerogenic effect. The results suggest that petroleum ether and alcoholic extracts may exert antiinflammatory activity through prostaglandin inhibition, reduced myeloperoxidase and antitransudation.

Effect of some clinically used proteolytic enzymes on inflammation in rats

The study was designed to investigate the role of three proteolytic enzymes viz., chymotrypsin, trypsin and serratiopeptidase on hind paw edema and cotton pellet induced granuloma and their possible interactions with aspirin in albino rats. Animals were treated with proteolytic enzymes alone in three different doses or aspirin or in combination with subantiinflammatory dose of aspirin or saline, 30 min before injection of 0.1ml 1% carrageenan. Paw volume was measured before and 3 h after the injection of carrageenan. Chymotrypsin, (5, 18 and 36 mg/kg), trypsin (1.44, 2.88 and 5.76 mg/kg) and serratiopeptidase (0.45, 0.9 and 2.70 mg/kg) were showed dose dependent antiinflammatory activity in acute model of inflammation. Serratiopeptidase showed better antiinflammatory activity on carrageenan induced inflammation than other two proteolytic enzymes and aspirin. However, chymotrypsin and serratiopeptidase were found to be more effective than aspirin in subacute model of inflammation. Chymotrypsin, trypsin and serratiopeptidase possess antiinflammatory activity and exhibit synergistic effect with aspirin in both acute and subacute models of inflammation in rats.

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.

Anti-inflammatory activity of Justicia prostrata gamble in acute and sub-acute models of inflammation

In this study, the aqueous (AQJP) and alcoholic (ALJP) extracts of the whole plant of Justicia prostrata Gamble (Acanthaceae) were screened for their acute and subacute anti-inflammatory activities using carrageenan-induced acute inflammation and cotton-pellet-induced granuloma (subacute inflammation), respectively, in rats. In the carrageenan-induced rat paw oedema model, both extracts were found to exhibit maximum reduction in paw volume at the first hour in a dose-dependent manner. At the dose of 500 mg/kg p.o., both extracts AQJP and ALJP showed maximum inhibition (51.39% and 62.5%, respectively) in rat paw oedema volume at the first hour of carrageenan-induced acute inflammation. In the cotton pellet granuloma assay, AQJP and ALJP at the dose of 500 mg/kg p.o. suppressed the transudative, exudative and proliferative phases of chronic inflammation. These extracts were able to (i) reduce the lipid peroxide content of exudates and liver and (ii) normalize the increased activity of acid and alkaline phosphatases in serum and liver of cotton pellet granulomatous rats. Preliminary phytochemical screening revealed the presence of lignans, triterpenes and phenolic compounds in ALJP, whereas phenolic compounds and glycosides in AQJP. The anti-inflammatory properties of these extracts may possibly be due to the presence of phenolic compounds. The anti-inflammatory effects produced by the extracts at the dose of 500 mg/kg, p.o. was comparable with the reference drug diclofenac sodium (5 mg/kg p.o.).

Nonsteroidal antiinflammatory agents - Part 1: Antiinflammatory, analgesic and antipyretic activity of some new 1-(pyrimidin-2-yl)-3-pyrazolin-5-ones and 2-(pyrimidin-2-yl)-1,2,4,5,6,7-hexahydro-3 H-indazol-3-ones

In our reinvestigation of the cyclocondensation reaction of aminoguanidine bicarbonate 1 with 2-acetylbutyrolactone 2 and ethyl cyclohexanone-2-carboxylate 6, we have obtained the respective 1-amidino-3-pyrazolin-5-one derivative 3 and the 2-amidino-1,2,4,5,6,7-hexahydro-3 H-indazol-3-one 7. These intermediates were utilized for the synthesis of two novel series of 1-(pyrimidin-2-yl)-3-pyrazolin-5-ones and 2-(pyrimidin-2-yl)-1,2,4,5,6,7-hexahydro-3 H-indazol-3-ones. Selected analogs from both series (15 compounds) were evaluated for their antiinflammatory activity in an acute and subacute model of inflammation. The analgesic and antipyretic activity of the target compounds were also evaluated. A structure-activity relationship (SAR) comparative study indicated that some compounds from both series exhibited excellent antiinflammatory activity, together with good analgesic and antipyretic activity and were found to be more potent than the reference drugs at a dose of 50 mg/kg, po. In consideration of the efficacy of the compounds in these assays, the 5-phenyl derivative 18 from the 1-(pyrimidin-2-yl)pyrazolinone series, the 5-butyl and 5-phenyl derivatives 26, 27 from the 2-(pyrimidin-2-yl)indazolone series were further studied at graded doses for their acute toxicity (ALD 50) and ulcerogenic activity and were shown to have a large safety margin (ALD 50 > 4.0 g/kg, po) and devoid of ulcerogenic potentialities when administered orally at a dose of 300 mg/kg.