Pleural Exudate Volume Research Articles

Anti-Inflammatory Potential of Pteropodine in Rodents.

Pteropodine (PT) is a component of some plants with potentially useful pharmacological activities for humans. This compound has biomedical properties related to the modulation of the immune system, nervous system, and inflammatory processes. This study addresses the anti-inflammatory and antioxidant capacity of pteropodin in a murine model of arthritis and induced edema of the mouse ear. To evaluate the anti-inflammatory activity, we used the reversed passive Arthus reaction (RPAR), which includes the rat paw edema test, the rat pleurisy test, and a mouse ear edema model. The antioxidant effect of PT was evaluated by determining the myeloperoxidase enzyme activity. PT showed an anti-inflammatory effect in the different specific and non-specific tests. We found a 51, 66 and 70% inhibitory effect of 10, 20 and 40 mg/kg of PT, respectively, in the rat paw edema test. In the pleurisy assay, 40 mg/kg of PT induced a low neutrophil count (up to 36%) when compared to the negative control group, and 20 mg/kg of PT increased the content of lymphocytes by up to 28% and the pleural exudate volume decreased by 52% when compared to the negative control group, respectively. We also found an 81.4% inflammatory inhibition of the edema ear with 0.04 mg/ear of PT, and a significant myeloperoxidase enzyme inhibition by the three doses of PT tested. We conclude that PT exerted a potent anti-inflammatory effect in the acute inflammation model in rodents.

Comparative study of the antioxidant and anti-inflammatory effects of the natural coumarins 1,2-benzopyrone, umbelliferone and esculetin: in silico, in vitro and in vivo analyses.

The aim of this work was to compare the anti-inflammatory and antioxidant effects of three natural coumarins: 1,2-benzopyrone, umbelliferone and esculetin. The antioxidant capacity of coumarins was evaluated using both chemical and biological in vitro assays. Chemical assays included DPPH and ABTS∙+ radical scavenging as well as ferric ion reducing ability power (FRAP) assay. Inhibition of mitochondrial ROS generation and lipid peroxidation in brain homogenates were used as biological in vitro assays. The experimental method of carrageenan-induced pleurisy in rats was used for the in vivo investigation of the anti-inflammatory activity. In silico molecular docking analysis was undertaken to predict the affinity of COX-2 to the coumarins. Considering the antioxidant capacity, esculetin was the most efficient one as revealed by all employed assays. Particularly, the mitochondrial ROS generation was totally abolished by the compound at low concentrations (IC50 = 0.57μM). As for the anti-inflammatory effects, the COX-2 enzyme presented good affinities to the three coumarins, as revealed by the molecular docking analyses. However, considering the in vivo anti-inflammatory effects, 1,2-benzopyrone was the most efficient one in counteracting pleural inflammation and it potentiated the anti-inflammatory actions of dexamethasone. Umbelliferone and esculetin treatments failed to reduce the volume of pleural exudate. Overall, therefore, our results support the notion that this class of plant secondary metabolites displays promising effects in the prevention and/or treatment of inflammation and other diseases associated with oxidative stress, although the singularities regarding the type of the inflammatory process and pharmacokinetics must be taken into account.

Bee venom stimulation of a lung meridian acupoint reduces inflammation in carrageenan-induced pleurisy: an alternative therapeutic approach for respiratory inflammation.

Respiratory inflammation is a frequent and fatal pathologic state encountered in veterinary medicine. Although diluted bee venom (dBV) has potent anti-inflammatory effects, the clinical use of dBV is limited to several chronic inflammatory diseases. The present study was designed to propose an acupoint dBV treatment as a novel therapeutic strategy for respiratory inflammatory disease. Experimental pleurisy was induced by injection of carrageenan into the left pleural space in mouse. The dBV was injected into a specific lung meridian acupoint (LU-5) or into an arbitrary non-acupoint located near the midline of the back in mouse. The inflammatory responses were evaluated by analyzing inflammatory indicators in pleural exudate. The dBV injection into the LU-5 acupoint significantly suppressed the carrageenan-induced increase of pleural exudate volume, leukocyte accumulation, and myeloperoxidase activity. Moreover, dBV acupoint treatment effectively inhibited the production of interleukin 1 beta, but not tumor necrosis factor alpha in the pleural exudate. On the other hand, dBV treatment at non-acupoint did not inhibit the inflammatory responses in carrageenan-induced pleurisy. The present results demonstrate that dBV stimulation in the LU-5 lung meridian acupoint can produce significant anti-inflammatory effects on carrageenan-induced pleurisy suggesting that dBV acupuncture may be a promising alternative medicine therapy for respiratory inflammatory diseases.

A single administration of fish oil inhibits the acute inflammatory response in rats.

To investigate the antiinflammatory effects of a single administration of fish oil (FO) on the acute inflammatory response. The paw edema and pleurisy models were used to evaluate the effects of FO dissolved in olive oil (FOP) orally administered in a single dose in rats. Nitric oxide (NO) concentrations in the pleural exudate were performed according to the Griess method and the cytokine concentrations were determined by Luminex bead-based multiplex assay. FOP treatment (30 and 300mg/kg) significantly reduced paw edema. FOP treatment at 18.75, 37.5, 75.0, 150.0, and 300mg/kg decreased both the volume of pleural exudate and cellular migration into the pleural cavity and each of these doses presented the same effectiveness. Treatment with FOP (300mg/kg) reduced NO, TNF-α, IL-1β, and IL-6 concentrations in the pleural exudate. The present data provide evidence that FO has inhibitory effects on the acute inflammatory response when administered in a single dose in rats. This effect might be attributable to a direct inhibitory effect of FO on the production or release of inflammatory mediators that are involved in the pathological processes evaluated herein.

The (+)-enantiomer is responsible for the antiplatelet and anti-inflammatory activity of (±)-indobufen

The racemic compound indobufen and its (+)- and (-)-enantiomers have been compared for their effects on blood platelet function and rat carrageenan pleurisy. The antiplatelet properties were studied in-vitro in human platelets by measuring the inhibition of platelet aggregation and generation of serum thromboxane (Tx) B2. In-vivo, the antiplatelet and anti-inflammatory properties were studied in rats by measuring the inhibition of serum TxB2, the amount of 6-keto-PGF1 alpha in pleural exudate and pleural exudate volume. In all tests the (+)-enantiomer was slightly more potent than the racemate, while the (-)-enantiomer was far less potent. In the same rats, treatment with the lowest doses of the compounds giving 90% inhibition of serum thromboxane B2 generation was associated with occasional macroscopic lesions of the gastric mucosa.

Anti-Inflammatory and Antinociceptive Effects of Rosmarinus officinalis L. Essential Oil in Experimental Animal Models

Rosmarinus officinalis L. (Family Lamiaceae), popularly named rosemary, is a common household plant grown in many parts of the world, including Brazil. Rosemary leaves are used for food flavoring and have been used in folk medicine for many conditions; they have antispasmodic, analgesic, antirheumatic, carminative, cholagogue, diuretic, expectorant, and antiepileptic effects. The objective of this study was to evaluate the effects of rosemary essential oil (REO) on experimental models of nociception and inflammation in animals. The anti-inflammatory effect of REO was evaluated by inflammatory exudate volume and leukocyte migration in carrageenan-induced pleurisy and carrageenan-induced paw edema tests in rats. Antinociception was evaluated using the acetic acid-induced writhing and hot plate tests in mice. REO (500 mg/kg) significantly reduced the volume of pleural exudate and slightly decreased the number of cells that had migrated compared with the control animals. At doses of 250, 500, and 750 mg/kg, REO significantly inhibited carrageenan-induced edema 1-4 hours after injection of the phlogistic agent. In the hot plate test, REO administration (125, 250, and 500 mg/kg) showed unremarkable effects on response latency, whereas control injection of meperidine induced significant antinociceptive effects. REO at doses of 70, 125, and 250 mg/kg had a significant antinociceptive effect in the acetic acid-induced abdominal writhing test compared with control animals. These data suggest that REO possesses anti-inflammatory and peripheral antinociceptive activity.

Chlorpropamide treatment restores the reduced carrageenan-induced paw edema and pleural exudate volume in diabetic rats

Knowing that hyperglycemia is a hallmark of vascular dysfunction in diabetes and that neonatal streptozotocin-induced diabetic rats (n-STZ) present reduced inflammatory response, we decided to evaluate the effect of chlorpropamide-lowered blood glucose levels on carrageenan-induced rat paw edema and pleural exudate in n-STZ. Diabetes was induced by STZ injection (160 mg/kg, ip) in neonates (2-day-old) Wistar rats. n-STZ diabetic rats were treated with chlorpropamide (200mg/kg, 15d, by gavage) 8 weeks after STZ injection. Carrageenan-induced paw edema and pleural exudate volumes were assessed concomitantly with peripheral and exudate leukocyte count. We also evaluated the expression of inducible nitric oxide synthase (iNOS) in lungs of all experimental groups. Chlorpropamide treatment improved glucose tolerance, beta-cell function (assessed by HOMA-beta), corrected paw edema, and pleural exudate volume in n-STZ. Neither leukocyte count nor iNOS expression were affected by diabetes or by chlorpropamide treatment. Chlorpropamide treatment by restoring beta-cell function, reducing blood sugar levels, and improving glucose tolerance might be contributing to the correction of the reduced inflammatory response tested as paw edema and pleural exudate in n-STZ diabetic rats.

Interaction between cyclooxygenase (COX)-1- and COX-2-products modulates COX-2 expression in the late phase of acute inflammation

Prostanoid production depends on the activity of two cyclooxygenase (COX) isoforms. It is appreciated that COX-1 plays a role in physiological processes, whereas COX-2 acts in pathological conditions. However their roles, particularly roles of COX-1, have not yet been fully established in inflammation. Here, we examined the effects of COX inhibitors, having differential isoform selectivity, on the late phase of rat carrageenin-induced pleurisy to elucidate the role of COX-2 expressed in the draining lymph nodes and found substantial contribution of COX-1-product(s). Protein and mRNA of COX-2 were detectable with Western blotting analysis and reverse-transcription polymerase chain reaction (RT-PCR) analysis in parathymic lymph nodes, peaking at 48 h after induction of pleurisy. Microsomal prostaglandin E synthase (mPGES)-1 was detectable by immunohistochemical analysis in cells with dendritic processes, a morphological characteristic similar to that of COX-2 expressing cells. Although aspirin, indomethacin and a COX-1 inhibitor, ketorolac, significantly decreased the volume of pleural exudate, they did not affect the levels of COX-2 and mPGES-1 in the lymph node 24 h after induction of pleurisy. In contrast, COX-2 inhibitors, nimesulide and NS-398, had no effect on the exudate volume, but they increased the number of COX-2- and mPGES-1-expressing cells and extension of their dendritic processes with significant increase in the COX-2 level, which were antagonised by ketorolac. These results suggest that COX-2-expressing cells may negatively self-regulate their functions by producing PGE 2 via mPGES-1: migration into the draining lymph node and their differentiation. Moreover, COX-1- and COX-2-derived prostanoids may play differential or sometimes antagonistic roles in the late phase of acute inflammation.

Inhibitory effects of proanthocyanidins from Ribes nigrum leaves on carrageenin acute inflammatory reactions induced in rats

BackgroundThe anti-inflammatory effects of proanthocyanidins (PACs), isolated from blackcurrant (Ribes nigrum L.) leaves, were analysed using carrageenin-induced paw oedema and carrageenin-induced pleurisy in rats.ResultsPretreatment of the animals with PACs (10, 30, 60 and 100 mg/kg, i.p.) reduced paw oedema induced by carrageenin in a dose and time-dependent manner. PACs also inhibited dose-dependently carrageenin-induced pleurisy in rats. They reduced (A) lung injury, (B) pleural exudate formation, (C) polymorphonuclear cell infiltration, (D) pleural exudate levels of TNF-α, IL-1β and CINC-1 but did not affect IL-6 and IL-10 levels. They reduced (E) pleural exudate levels of nitrite/nitrate (NOx). In indomethacin treated rats, the volume of pleural exudate was low, its content in leukocytes and its contents in TNF-α, IL-1β, IL-6 and IL-10 but not in NOx were reduced. These data suggest that the anti-inflammatory properties of PACs are achieved through a different pattern from those of indomethacin.ConclusionThese results suggest that the main mechanism of the anti-inflammatory effect of PACs mainly lies in an interference with the migration of the leukocytes. Moreover, PACs inhibited in vivo nitric oxide release.

Effect of the selective COX-2 inhibitors, celecoxib and rofecoxib in rat acute models of inflammation.

This study evaluates the action of celecoxib and rofecoxib, two selective cyclooxygenase-2 (COX-2) inhibitors in two acute models of inflammation, carrageenan (Cg)-induced rat pleurisy, and paw oedema formation. Male Wistar rats (N = 4-10 per group) were used. A fixed volume of PBS or carrageenan was injected into the pleural cavity or into the paw. Furthermore, the myeloperoxidase (MPO) activity and the levels of nitrite/nitrate (NOx), interleukin-1beta (IL-1beta), tumor necrosis factor-a (TNF-a) and PGE2 were also assessed in the paw tissue or in pleural exudate. Dexamethasone (DEX, 0.5 mg kg(-1), s.c., -4 h) and indomethacin (INDO, 3 mg kg(-1), p.o., -1 h) suppressed Cg-induced pleural exudate accumulation by 84 and 77% and inflammatory cell influx by 66 and 47%, respectively. In contrast, celecoxib (CLX, 10 mg kg(-1), p.o., -1 h) or rofecoxib (RFX, 10 mg kg(-1) , p.o., -1 h) only reduced the Cg-induced pleural exudate volume by 44 and 40%, respectively, but had no significant effect over inflammatory cell influx. At the same doses used for pleurisy, DEX, INDO, CLX, RFX and SC-560 (a selective COX-1 inhibitor, 40 mg kg(-1), p.o., -1 h), inhibited the Cg-induced paw oedema by 49, 31, 21, 21 and 17%. DEX, INDO or SC-560 reduced the level of MPO by 71, 78 and 59%, while CLX or RFX produced a small, but significant increase (28 or 16%) in MPO activity. In the rat model of pleurisy, PGE2 levels in cell-free exudates were significantly attenuated by 91, 89, 57 and 65% in animals treated with DEX, INDO, CLX or RFX. In contrast, INDO reduced significantly the whole bloodTXB, synthesis (59%) while DEX and INDO reduced the pleural content of NOx significantly. Treatment of animals with CLX or RFX did not alter the content of pro-inflammatory cytokines IL-1beta or TNF-alpha in the pleural exudate, but CLX reduced IL-1beta levels in the rat paw tissue and RFX increased TNF-alpha in this tissue. Together these results provide consistent evidence indicating that the selective COX-2 inhibitors CLX and RFX, in contrast to DEX, INDO or SC-560, despite reducing greatly the Cg-induced pleural exudation, PGE2 content and paw oedema have only partial acute anti-inflammatory properties in two different rat acute models of inflammation.

Effect of a Novel Non-steroidal Anti-inflammatory Drug (M-5011) on Cytokine Levels in Rats With Monosodium Urate Crystal-Induced Pleurisy

We evaluated the effects of a new non-steroidal anti-inflammatory drug (NSAID), d-2-[4-(3-methyl-2-thienyl)phenyl]propionic acid (M-5011), and indomethacin on the production of arachidonate metabolites and pro-inflammatory cytokines in male Sprague-Dawly rats with monosodium urate crystal (MSU)-induced pleurisy. Levels of tumor necrosis factor (TNF), interleukin (IL)-1 and IL-6 in the pleural exudate were determined by biological assays, while prostaglandin E2 (PGE2), leukotriene B4 (LTB4) and cytokine-induced chemoattractant-1 (CINC-1) levels were quantified by enzyme immunoassays. Orally administered M-5011 (5 mg/kg) decreased the pleural exudate volume at 3 and 4 hr after MSU injection. Indomethacin (10 mg/kg) decreased the volume at 3–5 hr. These drugs reduced the number of leukocytes in the pleural cavity at 6 hr. Both NSAIDs also reduced the content of PGE2 in the exudate without affecting LTB4 levels. Increased productions of both IL-6 and CINC-1 in the exudate were reduced by pretreatment with M-5011 or indomethacin, and TNF levels in the exudate were increased by pretreatment of these drugs. Thus, M-5011 inhibits the production of both IL-6 and CINC-1 at lower doses than those of indomethacin, and the inhibitory effect of M-5011 on CINC-1, but not IL-6, may partly contribute to the inhibition of leukocyte infiltration in rats with MSU-induced pleurisy.

Increased migration of neutrophils to granulocyte-colony stimulating factor in rat carrageenin-induced pleurisy: roles of complement, bradykinin, and inducible cyclooxygenase-2.

Administration of human recombinant granulocyte colony-stimulating factor (G-CSF, 100 micrograms/kg/day, s.c) to rats for 4 days significantly increased circulating neutrophil counts (by 1130%), together with an increase in mononuclear leukocyte counts (by 119%). Infiltrated pleural neutrophil counts in G-CSF-treated rats (G-CSF-r) 5 h after the intrapleural injection of zymosan-activated serum were significantly higher (by 155%) than those in control rats (Vehicle-r). In carrageenin-induced pleurisy, counts of infiltrated pleural neutrophils in G-CSF-r 5 and 7 h after carrageenin were significantly higher (by 119% and 116%) than those in Vehicle-r. G-CSF treatment increased the volume of pleural exudate and the plasma exudation rate by 122% and 226%, compared to values in Vehicle-r 5 h after carrageenin. Cobra venom factor (75 micrograms/kg, i.v.) significantly reduced pleural neutrophil migration in G-CSF-r (by 53%) and Vehicle-r (by 49%). Bromelain (10 mg/kg, i.v.) and aspirin (100 mg/kg, p.o.) reduced pleural neutrophil migration and reduced exudate volume and plasma exudation. Intrapleural bradykinin-(1-5) and prostaglandin E2 levels were significantly higher in G-CSF-r than in Vehicle-r. The increased neutrophil migration in G-CSF-r may be attributed to enhanced activation of the complement system facilitated by increased plasma exudation due to bradykinin and prostaglandins.

Anti‐inflammatory activity of Lannea coromandelica bark extract in rats

AbstractOral administration of an ethanolic extract of Lannea coromandelica (ELC) demonstrated a dose related antiinflammatory activity (AIA) in carrageenan and dextran induced oedema and adjuvant induced arthritis in rats. ELC reduced the pleural exudate volume and inhibited leucocyte migration in carrageenan‐induced pleurisy in rats. It lacked analgesic, antipyretic or ulcerogenic effect and failed to exhibit any effect in cotton pellet granuloma. It did not prolong the gestation period, parturition time in pregnant rats or the onset time of diarrhoea in rats induced by castor oil. The ALD50 is greater than 2 g/kg p.o. in mice.

Role of type II phospholipase A2 in the inflammatory process of carrageenan-induced pleurisy in rats

In order to investigate the role of type II phospholipase A2 (PLA2) in the inflammatory process, the effect of a monoclonal antibody specific to type II PLA2 on carrageenan-induced pleurisy was studied in rats. Intravenous injection of the antibody (MB5.2), which inhibits the catalytic activity of type II PLA2, significantly reduced both the pleural exudate volume and the intrapleural leukoeyte count, while a control antibody did not have any appreciable effect. MB5.2 caused no change in the level of type II PLA2 in the pleural fluid. These results suggest that type II PLA2 generated at inflamed sites, at least in part, have a crucial role in the pathogenesis of acute inflammation.

Immunopharmacological properties of azepino [2, 1-b] quinazolin-12(6H)-one-7, 8, 9, 10-tetrahydro (RLX)

The effect of azepino [2,1-b]quinazolin-12(6H)-one-7, 8, 9, 10-tetrahydro (RLX) was studied on cell-mediated and humoral components of the immune system. In single (50, 100 and 200 mg/kg) and multiple (6.25, 12.50, 25 and 50 m/kg) oral dose schedules RLX significantly reduced the early (4 h) and delayed (24 and 48 h) hypersensitivity reactions to SRBC in mice. Daily oral administration of RLX (25, 50 and 100 mg/kg) produced a dose-related reduction in developing adjuvant arthritis in rats. In carrageenan-induced pleurisy in rats RLX (25, 50 and 100 mg/kg p.o.) caused a marked reduction in the volume of pleural exudate (25.26 – 59.64%) and infiltration of leucocytes (28.75 – 50.29%) into the pleural cavity. RLX produced marked inhibition of humoral antibody synthesis both in mice and rats and that of complement fixing antibody in mice. It was not cytotoxic and showed no appreciable effect on the responsiveness of splenocytes to mitogens. The observed effect of RLX on cell-mediated and humoral immune responses does not appear to be the result of general toxicity.

Endothelin-1 inhibits PAF-induced paw oedema and pleurisy in the mouse.

1. The current study analyses the effects of endothelin-1 (ET-1) on paw oedema and pleurisy induced by platelet activating factor (PAF) and other inflammatory agents in the mouse. 2. Combined subplantar injection of ET-1 (0.5 pmol/paw) did not modify oedema caused by histamine (1 to 100 mumol/paw), 5-hydroxytryptamine (1 to 100 mumol/paw) or bradykinin (1 to 100 nmol/paw) but markedly inhibited the response to PAF (0.95 to 3.8 nmol/paw). The selective action of ET-1 against PAF-induced (1.9 nmol/paw) oedema was dose-dependent, reaching a maximum at 0.5 pmol/paw and lasted up to 2 h. 3. ET-1 (0.5 pmol/paw) also inhibited paw oedema (3-4 h) caused by zymosan (500 micrograms/paw). In contrast, it did not modify either the early (1-4 h) or late (48-72 h) phases of the oedematogenic response to carrageenin (300 micrograms/paw), when given either together with or 24 h after the carrageenin. 4. Intrathoracic injection of PAF (1.9 nmol/cavity) induced pleurisy characterized by an increase in pleural exudate volume, and in accumulation of Evans Blue which was maximal at 30 min and lasted up to 4 h. When injected together with PAF, ET-1 (0.5 pmol/cavity) virtually abolished PAF-induced pleurisy. 5. It is concluded that ET-1 is a potent inhibitor of PAF-induced inflammation in the mouse. Its mechanism of anti-inflammatory action in this species, in contrast to what has been found in other species, does not appear to derive from its potent vasoconstrictor properties as ET-1, at the doses used, failed to affect oedematogenic responses to other inflammatory mediators.

Captopril Uncovers Kinin-Dependent Release of Arachidonic Acid Metabolites in Carrageenin-Induced Rat Pleurisy

As previously reported, pretreatment with Captopril significantly enhanced pleural exudation of rat carrageenin-induced pleurisy. However, in high molecular weight kininogen-deficient rats (B/N-Katholiek), the pleural exudate volume was significantly less than that of the normal strain (B/N-Kitasato), and Captopril pretreatment did not enhance exudation. In the present study, the following additional evidences were demonstrated: 1) Captopril did not increase 6-keto-PGF1α level in the deficient strain, but it was significantly increased in the normal strain after Captopril treatment; 2) simultaneous administration of soybean trypsin inhibitor with carrageenin markedly suppressed the exudate volume and levels of 6-keto-PGF1α, in the normal strain; and 3) indomethacin also suppressed pleural fluid accumulation and the production of arachidonate metabolites. These data suggest that carrageenin causes intrinsic kinin-release through the activation of plasma kallikrein and then in turn, the kinin stimulates the production of arachidonic acid metabolites. Thus these products and kinin may interact to induce more plasma exudation in carrageenin inflammation. The results also indicate that Captopril uncovers the effects of bradykinin on exudation and stimulation of arachidonate metabolite production; otherwise, the biological effect of kinin is too slight to produce a clear effect at the initial phase of the inflammation.

Captopril uncovers kinin-dependent release of arachidonic acid metabolites in carrageenin-induced rat pleurisy.

As previously reported, pretreatment with captopril significantly enhanced pleural exudation of rat carrageenin-induced pleurisy. However, in high molecular weight kininogen-deficient rats (B/N-Katholiek), the pleural exudate volume was significantly less than that of the normal strain (B/N-Kitasato), and captopril pretreatment did not enhance exudation. In the present study, the following additional evidences were demonstrated: 1) Captopril did not increase 6-keto-PGF1 alpha level in the deficient strain, but it was significantly increased in the normal strain after captopril treatment; 2) simultaneous administration of soybean trypsin inhibitor with carrageenin markedly suppressed the exudate volume and levels of 6-keto-PGF1 alpha in the normal strain; and 3) indomethacin also suppressed pleural fluid accumulation and the production of arachidonate metabolites. These data suggest that carrageenin causes intrinsic kinin-release through the activation of plasma kallikrein and then in turn, the kinin stimulates the production of arachidonic acid metabolites. Thus these products and kinin may interact to induce more plasma exudation in carrageenin inflammation. The results also indicate that captopril uncovers the effects of bradykinin on exudation and stimulation of arachidonate metabolite production; otherwise, the biological effect of kinin is too slight to produce a clear effect at the initial phase of the inflammation.

Effect of salai guggal ex-Boswellia serrata on cellular and humoral immune responses and leucocyte migration.

Effect of alcoholic extract of salai guggal (AESG) was studied on cellular and humoral immune responses in mice and leucocyte migration in rats. Oral administration of AESG strongly inhibited the antibody production and cellular responses to sheep red blood cells in mice. It inhibited the infiltration of polymorphonuclear leucocytes and reduced the volume of pleural exudate in carrageenan induced pleurisy in rats. It showed no cytotoxic effect.

Pharmacological properties of N-methoxy-3-(3,5-ditert-butyl-4-hydroxybenzylidene)-2-pyrrolidone (E-5110), a novel nonsteroidal antiinflammatory agent

The antiinflammatory activity of a novel pyrrolidone derivative E-5110 was investigated using anti-inflammatory, analgesic and antipyretic animal models in comparison to indomethacin (IND) and piroxicam (PIR). The acute antiinflammatory activity of E-5110 on carrageenin paw edema was similar to IND, and half of PIR. E-5110 inhibited the pleural exudate volume and leucocyte infiltration in a reversed passive Arthus reaction more potent than IND. The chronic inflammatory responses in the established adjuvant- and type II collagen-induced arthritis were suppressed by E-5110 similar to IND and PIR. The analgesic potency of E-5110 was similar to IND and PIR, but the antipyretic activity of E-5110 was more potent than that of IND, and slightly more potent than that of PIR. The ulcerogenic effect of E-5110 on rat gastric mucosa was less than that of the reference drugs.