The involvement of the HO-1 pathway in the anti-inflammatory action of a sulfated polysaccharide isolated from the red seaweed Gracilaria birdiae

Objectives

The aim of this study was to investigate the involvement of the hemoxigenase-1 (HO-1) pathway in the anti-inflammatory action of a sulfated polysaccharide from the red seaweed Gracilaria birdiae (SP-Gb).

Methods

SP-Gb (5, 10 and 20?mg/kg) was administered to Wistar rats in a peritonitis model using carrageenan or a paw edema model using carrageenan or dextran. To analyze the involvement of HO-1 in the anti-inflammatory activity of SP-Gb, the animals were pretreated subcutaneously with a specific HO-1 inhibitor (ZnPP IX). To evaluate the systemic effects, SP-Gb (10?mg/kg) was administered to mice intraperitoneally before waiting for 48?h or for 14?days.

Results

SP-Gb (10?mg/kg) caused an anti-inflammatory effect that was evidenced by a decrease in leukocytes in the peritoneal cavity. SP-Gb also reduced the paw edema induced by carrageenan and inhibited the paw edema induced by dextran in the first half-hour. After being inhibited by ZnPP IX, the anti-inflammatory effect of SP-Gb on carrageenan-induced rat paw edema was not observed. SP-Gb did not cause mortality or significant changes in the biochemical, hematological and histopathological parameters.

Conclusion

SP-Gb may be used as a tool for further investigations into the inflammatory processes associated with the hemoxigenase-1 pathway.     

Anti-inflammatory effects of insulin regular and flunixin meglumine on endotoxemia experimentally induced by Escherichia coli serotype O55:B5 in an ovine model

Background

Endotoxemia is a major cause of mortality in large animals and there are several therapeutic regimens for the treatment of endotoxemia. Recent studies have suggested the anti-inflammatory effects of insulin in endotoxemic human and laboratory animal models but to the best of our knowledge there is no report on the possible therapeutic effect of insulin in large animal endotoxemia.

Objective

This experiment was conducted to evaluate the anti-inflammatory effects of insulin regular compared with flunixin meglumine on the treatment of endotoxemia in sheep.

Methods

Lipopolysaccharide from Escherichia coli was administered intravenously to ewes. Anti-inflammatory effects of flunixin meglumine (at 2.2 mg/kg) and insulin regular (at 1.5 and 3 IU/kg) were evaluated by determination of serum concentrations of acute phase proteins, inflammatory cytokines and oxidative stress biomarkers.

Results

Insulin regular at 3 IU/kg controlled the acute phase response following endotoxemia induction. The anti-inflammatory potency of insulin regular at 3 IU/kg was significantly higher than at 1.5 IU/kg and of flunixin meglumine at 2.2 mg/kg (P < 0.05).

Conclusion

Insulin regular induces its anti-inflammatory effects in a dose-dependent manner. Intravenous use of insulin regular can be a potential new therapeutic regimen for endotoxemia in large animal medicine.     

Anti-inflammatory effect of quinoline alkaloid skimmianine isolated from Ruta graveolens L.

Objective

The present study evaluates the anti-inflammatory effect of the quinoline alkaloid skimmianine (SKM), isolated from Ruta graveolens L., against carrageenan-induced acute inflammation.

Methods

SKM at a dose of 5.0 mg/kg body weight was found to be the minimal concentration for maximal edema inhibition. Carrageenan suspension was administered into the sub-plantar tissue of the right hind paw 1 h after SKM and diclofenac (20 mg/kg) administration (i.p.). Paw edema was determined 3 h after carrageenan administration. The rats were then killed and mRNA expressions of TNF-α and IL-6, levels of PGE₂ and TBARS, activities of COX-2, 5-LOX, SOD, catalase, glutathione peroxidase (GPx) and myeloperoxidase (MPO) and the level of nitrite were measured.

Results

SKM treatment resulted in a decrease in the mRNA levels of TNF-α and IL-6, which are upstream events of the inflammatory cascade. The levels of PGE₂ and NO and the activities of COX-2 and 5-LOX were also significantly reduced after SKM treatment. Neutrophil infiltration, lipid peroxidation and associated oxidative stress in the paw tissue were reduced following SKM treatment.

Conclusion

These results support the anti-inflammatory properties of skimmianine and its multi-targeted mechanism of action, suggesting its potential therapeutic efficacy in various inflammatory diseases.     

The anti-inflammatory action of Bothrops jararaca snake antithrombin on acute inflammation induced by carrageenan in mice

Objective and design

Antithrombin is known as the most important natural coagulation inhibitor and has been shown to have anti-inflammatory properties. The present study aimed to investigate the effects of Bothrops jararaca antithrombin on acute inflammation induced by carrageenan in mice.

Methods

We evaluated the anti-inflammatory activity of antithrombin on models of paw edema formation, cell migration and leukocyte–endothelium interaction in mice (Swiss; n = 5). Acute inflammation was induced by the administration of carrageenan (15 mg kg^?1).

Results

Treatment with B. jararaca antithrombin (1 mg kg^?1) 1 h before or after carrageenan administration significantly inhibited paw edema formation, reduced cell influx to the peritoneal cavity due to reduction in the migration of polymorphonuclear cells, and attenuated leukocyte rolling in the microcirculation of the cremaster muscle.The effects of antithrombin on vascular and cellular events of inflammation were completely abolished by treatment with the cyclo-oxygenase inhibitor indomethacin (4 mg kg^?1), suggesting the involvement of prostacyclin in the mechanism of inflammation inhibition by B. jararaca antithrombin.

Conclusion

This work showed for the first time the anti-inflammatory properties of B. jararaca antithrombin on vascular and cellular events of inflammation. These findings suggest that antithrombin is effective in preventing paw edema formation, cell migration and leukocyte rolling induced by carrageenan in mice.     

Anti-inflammatory and anti-arthritic activities of 3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b]pyran-5,6-dione (β-lapachone)

Objective and design

The purpose of this study was to evaluate the anti-inflammatory and anti-arthritic activities of 3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b]pyran-5,6-dione (β-lapachone; β-lap) and to elucidate its probable mode of action.

Methods

Carrageenan-induced paw edema, cell migration evaluation and production of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-6 and nitric oxide were used for this study. Freund’s complete adjuvant (FCA)-induced arthritis was used as a model of chronic inflammation. β-Lap was tested in doses of 40 and 60 mg/kg, orally.

Results

In the paw edema test, the dose of 60 mg/kg gave a higher percentage inhibition of edema (49.3 %) than control. β-Lap inhibited neutrophil migration and reduced concentrations of TNF-α, IL-6 and NO in peritoneal exudates of animals with peritonitis. In the arthritis test, β-lap inhibited edema and NO production in the serum of treated animals.

Conclusion

Significant anti-inflammatory and anti-arthritic activities were observed in animals treated with β-lap. The effects of β-lap can be attributed in part to immunomodulation with reduction of pro-inflammatory cytokines and NO.     

Central and peripheral anti-inflammatory effects of maprotiline on carrageenan-induced paw edema in rats

Objective

To explore the site of action of maprotiline, as an atypical antidepressant, on carrageenan-induced paw edema.

Subjects

Male Wistar rats were used.

Methods

Firstly, the anti-inflammatory effect of systemic maprotiline (12.5, 25 and 50 mg kg^?1) was assessed using a paw edema model. Secondly, different doses of maprotiline were administrated intracerebroventricularly, intrathecally and locally before carrageenan challenge. Finally, we tried to reverse the anti-inflammatory effect of maprotiline by propranolol (10 mg kg^?1), prazosin (4 mg kg^?1), yohimbine (10 mg kg^?1), naloxone (4 mg kg^?1) and mifepristone (5 mg kg^?1).

Results

Systemic, intracerebroventricular and subplantar application of maprotiline significantly inhibited peripheral edema, but intrathecal maprotiline did not alter the degree of paw swelling. The applied antagonists failed to change the anti-inflammatory activity of maprotiline.

Conclusion

These results demonstrate that maprotiline has a potent anti-inflammatory effect and this effect is linked to the peripheral and supraspinal actions of the drug.     

Preclinical evaluation of the urokinase receptor-derived peptide UPARANT as an anti-inflammatory drug

Background

Inflammation plays a key role in the pathogenesis of several chronic diseases. The urokinase plasminogen activator receptor (uPAR) exerts a plethora of functions in both physiological and pathological processes, including inflammation.

Objective and design

In this study, we evaluated the anti-inflammatory effect of a novel peptide ligand of uPAR, UPARANT, in different animal models of inflammation.

Subjects and treatment

Rats and mice were divided in different groups (n = 5) for single or repeated administration of vehicle (9% DMSO in 0.9% NaCl), UPARANT (6, 12 and 24 mg/kg) or dexamethasone (2 mg/kg). Animals were subjected to carrageenan-induced paw oedema or zymosan-induced peritonitis.

Methods

UPARANT effects were tested on: (1) the carrageenan-induced paw oedema volume, (2) the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and the nitrite/nitrate (NOx) levels in the paw exudates, (3) cells recruitment into the peritoneal cavity after zymosan injection and (4) NOx levels in the peritoneal lavage.

Results

UPARANT (12 and 24 mg/kg) reduced inflammation in both experimental paradigms. Analysis of pro-inflammatory enzymes revealed that administration of UPARANT reduced iNOS, COX2 and NO over-production.

Conclusions

Our study provides a solid evidence that UPARANT reduces the severity of inflammation in diverse animal models, thus representing a novel anti-inflammatory drug with potential advantages with respect to the typical steroidal agents.

     

Flavones derived from nature attenuate the immediate and late-phase asthmatic responses to aerosolized-ovalbumin exposure in conscious guinea pigs

Objective

Asthma is an inflammatory disease of the lung that is characterized by airway hyperresponsiveness and the increase of inflammatory cell infiltration into the airways. Naturally occurring flavones have potent anti-inflammatory effects, but their effects on asthmatic responses are still relatively unknown.

Methods

We evaluated the inhibitory effects of flavone derivatives having the chromone moiety on the immediate-phase asthmatic response (IAR) and the late-phase asthmatic response (LAR) to aerosolized-ovalbumin (OA) exposure in conscious OA-sensitized guinea pigs.

Results

Luteolin and apigenin (30 mg/kg, p.o.) significantly (P < 0.05) decreased not only the specific airway resistance (sRaw) in IAR and LAR, but also the recruitment of leukocytes and the release of histamine and activities of phospholipase A₂ (PLA₂) and eosinophil peroxide (EPO) in bronchoalveolar lavage fluid (BALF), compared to control. However, their anti-asthmatic activities were less than those of cromolyn sodium and dexamethasone.

Conclusions

These results indicate that flavones containing more hydroxyl radicals have a greater anti-asthmatic effect. The potencies of flavone anti-asthmatic activities are, in order: luteolin ≥ apigenin > baicalein > chrysin > flavone.     

Effect of roxithromycin on mucosal damage,oxidative stress and pro-inflammatory markers in experimental model of colitis

Objective and design

Roxithromycin, a macrolide antibiotic, exhibits anti-inflammatory property. The present study was designed to evaluate its protective effect in a rat model of colitis.

Methods

The anti-inflammatory property of roxithromycin was first validated in rat paw edema model at 5 and 20 mg/kg doses where it produced 19 and 51% inhibition of paw swelling induced by carrageenan. The efficacy of roxithromycin was evaluated at these doses in a rat model where colitis was induced by intra-colonic instillation of acetic acid. Rats were divided into six groups viz. normal control, experimental control and drug-treated groups: roxithromycin 5 and 20 mg/kg, diclofenac 10 mg/kg and mesalazine 300 mg/kg. All drugs were given orally 1 h before induction of colitis. The macro and microscopic changes, mean ulcer score, mucus content and markers of oxidative stress and inflammation were evaluated in all the groups after 24 h.

Results

Pretreatment with roxithromycin markedly decreased hyperemia, ulceration, edema and restored histological architecture. The protection afforded by roxithromycin was substantiated by dose-dependent increase in mucus content, normalization of markers of oxidative stress (GSH and TBARS) and levels of TNF-α, PGE₂ and nitrite along with marked decrease in expression of NFκB (p65), IL-1β and COX-2. The protective effect of roxithromycin was found to be comparable to mesalazine while diclofenac was found ineffective.

Conclusion

Our study demonstrates that roxithromycin ameliorates experimental colitis by maintaining redox homeostasis, preserving mucosal integrity and downregulating NFκB-mediated pro-inflammatory signaling and suggests that it has a therapeutic potential in inflammatory conditions of the colon.

     

Attenuation of Carbon Tetrachloride-Induced Hepatic Injury with Curcumin-Loaded Solid Lipid Nanoparticles

Background and Objectives

Curcumin, an established pleiotropic agent, has potential for hepatoprotection owing to its powerful antioxidant, anti-inflammatory, and antifibrogenic properties. However, its poor bioavailability limits its use in therapeutics. In this study, we aimed to package curcumin into solid lipid nanoparticles (C-SLNs) to improve its bioavailability and compare the efficacy of C-SLNs with that of free curcumin and silymarin, a well-established hepatoprotectant in clinical use, against carbon tetrachloride (CCl₄)-induced hepatic injury in rats, post-induction. A self-recovery group to which no treatment was given was also employed for quantifying self-healing of hepatic tissue, if any.

Material and Methods

C-SLNs (particle size 147.6 nm), prepared using a microemulsification technique, were administered to rats post-treatment with CCl₄ (1 ml/kg body weight [BW] twice weekly for 2 weeks, followed by 1.5 ml/kg BW twice weekly for the subsequent 2 weeks). The extent of liver damage and repair in terms of histopathology and levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), oxidative stress markers (malondialdehyde, superoxide dismutase, and reduced glutathione) and a pro-inflammatory response marker, tumor necrosis factor (TNF)-α, were determined in both the CCl₄ group and the treatment groups.

Results

C-SLNs (12.5 mg/kg) significantly (p < 0.001–0.005) attenuated histopathological changes and oxidative stress, and also decreased induction of ALT, AST, and TNF-α in comparison with free curcumin (100 mg/kg), silymarin (25 mg/kg), and self-recovery groups.

Conclusion

Curcumin could be used as a therapeutic agent for hepatic disorders, provided it is loaded into a suitable delivery system.     

Blockade of proteinase-activated receptor 4 inhibits neutrophil recruitment in experimental inflammation in mice

Objective and design

The activation of proteinase-activated receptors (PARs) has been implicated in the development of important hallmarks of inflammation, including in vivo leukocyte recruitment; however, its role in the regulation of leukocyte migration in response to inflammatory stimuli has not been elucidated until now. Here, we examined the effects of the PAR4 antagonist YPGKF-NH 2 (tcY-NH₂) on neutrophil recruitment in experimentally induced inflammation.

Methods

BALB/c mice were intrapleurally injected with tcY-NH₂ (40 ng/kg) prior to intrapleural injection of carrageenan (Cg) or neutrophil chemoattractant CXCL8; the number of infiltrating neutrophils was evaluated after 4 h, and KC production was assessed at different times after Cg injection. Neutrophil adhesion and rolling cells were studied using a brain circulation preparation 4 h after the Cg or CXCL8 challenge in tcY-NH₂-treated mice.

Results

PAR4 blockade inhibited CXCL8- and Cg-induced neutrophil migration into the pleural cavity of BALB/c mice and reduced neutrophil rolling and adherence. Surprisingly, PAR4 blockade increased the level of KC in response to carrageenan.

Conclusion

These results demonstrated that PAR4 blockade impairs neutrophil migration in vivo, suggesting that PAR4 plays an important role in the regulation of inflammation, at least in part because of its ability to inhibit the actions of the neutrophil chemoattractant CXCL8.     

Colitis generates remote antinociception in rats: the role of the l-arginine/NO/cGMP/PKG/KATP pathway and involvement of cannabinoid and opioid systems

Objective and design

The aim of this study was to investigate the possible involvement of the NO/cGMP/PKG/K _ATP ⁺ pathway, cannabinoids and opioids in remote antinociception associated with 2,4,6-trinitrobenzene sulph onic acid (TNBS)-induced colitis.

Methods

TNBS-induced colitis was induced by intracolonic administration of 20 mg of TNBS in 50 % ethanol. After induction, carrageenan (500 μg/paw) or prostaglandin (PG) E₂ (100 ng/paw) was injected in the rat’s plantar surface and hypersensitivity was evaluated by the electronic von Frey test. Rats were pre-treated with l-Noarg one hour before carrageenan injection. l-Arginine was given 10 min before l-Noarg injections. ODQ, KT 5823, glibenclamide (Glib), naloxone and AM 251 or AM 630 were administered 30 min prior to carrageenan or PGE₂ treatments.

Results

Colitis induction by TNBS reduced PGE₂ or carrageenan-induced hypersensitivity. Antinociception produced by TNBS-induced colitis was reversed significantly (P < 0.05) by l-Noarg, ODQ, KT 5823, glibenclamide, naloxone, AM251 and AM630 treatments.

Conclusions

TNBS-induced colitis causes antinociception in the rat paw. This disorder appears to be mediated by activation of the NO/cGMP/PKG/K_ATP pathway, endocannabinoids and endogenous opioids. This information may contribute to a better understanding of peripheral neurological dysfunctions occurring in Crohn’s disease.     

Inhibiting mast cell degranulation by HO-1 affects dendritic cell maturation in vitro

Objective and design

Mast cell (MC) degranulation can break peripheral immune tolerance. However, its mechanism remains unclear. Our goal was to study the stabilization of MC membranes by heme oxygenase-1 (HO-1) in order to influence dendritic cell (DC) function.

Material

Mast cells and dendritic cells were prepared from 8-week-old to 10-week-old C57BL/6 mice; spleen mononuclear cells (SMCs) were prepared from 8-week-old to 10-week-old C57BL/6 and Balb/c mice.

Treatment

Mast cells were pretreated with PBS, DMSO, Hemin (50 μl/ml), and Znpp (50 μl/ml) for 8 h.

Method

Real-time PCR and western-blot tested the HO-1 of MC mRNA and protein. The co-stimulatory molecules of DCs (CD80, CD86, CD40) were measured by flow cytometry, and levels of TNF-α, IL-6, and IFN-γ were measured by ELISA. We set up a one-way mixed lymphocyte reaction (MLR) model to test the proliferation of SMCs after MC/DC interaction. *P < 0.05 (t test) was taken as the level of statistical significance.

Result

MCs pretreated with hemin induced HO-1 mRNA and protein expression, then interacted with DCs; expression of the co-stimulatory molecules was attenuated. The TNF-α, IL-6, and IFN-γ levels in the co-culture system were decreased. These DCs couldn’t stimulate the proliferation of SMCs.

Conclusion

Inhibiting MC degranulation by HO-1 restrained DC maturation and attenuated the proliferation of SMCs.     

Immunoglobulin Dosage and Switch from Intravenous to Subcutaneous Immunoglobulin Replacement Therapy in Patients with Primary Hypogammaglobulinemia: Decreasing Dosage Does Not Alter Serum IgG Levels

Objective

The impact of reducing immunoglobulin dosage while switching from intravenous to subcutaneous replacement therapy was evaluated.

Methods

Sixty-five patients with primary hypogammaglobulinemia on stable intravenous replacement therapy were included in a monocentric longitudinal trial. IgG trough levels were measured at baseline and during 1 year following the switch to the subcutaneous route.

Results

Mean IgG trough level after 12 months of subcutaneous therapy was increased by 5.4% (8.37–8.82 g/l, p?=?0.3), while immunoglobulin dosage had been reduced by 28.3% (151–108 mg/kg/week, p?<?0.0001). For the patients with the lowest serum IgG level upon intravenous infusions, serum IgG level rose by 37% (5.33–7.33 g/l, p?=?0.003), while mean immunoglobulin dosage was reduced by 36% (170–109 mg/kg/week, p?=?0.04).

Conclusion

The present study shows that sustained serum IgG levels can be achieved after switching towards subcutaneous replacement despite using reduced immunoglobulin doses.     

Diacerein decreases TNF-α and IL-1β levels in peritoneal fluid and prevents Baker’s yeast-induced fever in young rats

Objective

To investigate the effect of diacerein, an anti-inflammatory drug, on body temperature and protocols of fever induction in male Wistar rats.

Methods

The effect of diacerein (5.0 mg/kg, s.c.) on rectal temperature (T _R) changes induced by Baker’s yeast (0.135 g/kg, i.p.) and PGE₂ (10 ng/animal, i.t.) was evaluated. T _R changes were recorded over time. The leukocyte count and TNF-α and IL-1β content were evaluated in the peritoneal fluid by means of optical microscopy and enzyme immunoassay (ELISA kits), respectively.

Results

The administration of diacerein to febrile animals attenuated Baker’s yeast-induced fever but did not alter prostaglandin E₂-induced fever. Diacerein prevented the development of Baker’s yeast-induced fever and significantly attenuated the increase in peritoneal leukocytes and decreased IL-1β and TNF-α levels in peritoneal fluid.

Conclusions

These data suggest that diacerein partially protects against Baker’s yeast-induced fever and peritoneal leukocyte migration, and indicate that this effect appears to be due to inhibition of release of cytokines (such as TNF-α and IL-1β).     

Inflammatory Models

Objective and design

The sigma 1 (σ₁) receptor, which is widely distributed in the CNS in areas that are known to be important for pain control, may play a role in persistent pain characterized by the hypersensitivity of nociceptive transmission. Here, we investigated the effect of σ₁ blockade in an inflammatory pain model.

Treatment and methods

An intraplantar injection of carrageenan (2 %) was used to induce paw inflammation. The effects of the σ₁ antagonist (+)-MR200, given subcutaneously at a dose of 0.1, 0.25, 0.5,1, 1.5, and 2 mg/kg prior to injection of carrageenan, on inflammatory pain and inflammation were assessed. Mechanical allodynia with von Frey filaments, thermal hyperalgesia with the plantar test and edema evaluation with a plethysmometer were measured. Intergroup comparisons were assessed by one- or two-way analysis of variance when appropriate, followed by post-hoc tests (Dunnett’s test for one-way or Bonferroni for two-way ANOVA).

Results

(+)-MR200 dose-dependently prevented allodynia and hyperalgesia induced by carrageenan. Furthermore, it reduced paw edema with a significant inhibition percentage of 37.82 % at 3 h after carrageenan treatment.

Conclusions

The blockade of the σ₁ receptor with the selective antagonist (+)-MR200 may contribute to the suppression of the typical symptoms of inflammatory pain.     

Effect of salicin on gut inflammation and on selected groups of gut microbiota in dextran sodium sulfate induced mouse model of colitis

Objective and design

This study was undertaken to evaluate the anti-inflammatory effect of the pure compound salicin on dextran sulfate sodium (DSS)-induced colitis in a mouse model and to quantify the major gut bacteria during the treatment.

Material or subjects

Experimental colitis was induced in Swiss albino mice by dissolving 2 % DSS in their drinking water for 7 days. Five mice were used in each group.

Treatment

Salicin (100 and 200 mg per body weight) was administered daily through oral gavage for 7 days.

Methods

Disease activity index (DAI), colon length, myeloperoxidase (MPO) assay, pro-inflammatory cytokine expression, histological changes and absolute number of gut microbiota were measured after treatment. Student’s t test was applied for statistical analysis.

Results

Salicin significantly attenuated DSS-induced DAI scores, shortening of colon length and tissue MPO activity. Salicin administration also effectively and dose-dependently prevented pro-inflammatory cytokine expression in DSS-induced colitis mice. Histological examination indicated that salicin suppressed edema, mucosal damage and the loss of crypts induced by DSS. Oral administration of salicin in DSS-treated mice prevented loss of gut microbiota during the short period of treatment.

Conclusions

Salicin has an anti-inflammatory effect, and it may have therapeutic value in ameliorating inflammation during colitis.     

Dietary component p-coumaric acid suppresses monosodium urate crystal-induced inflammation in rats

Objective

This study was conducted to evaluate the effect of p-Coumaric acid, a common dietary phenol, on monosodium urate crystal-induced inflammation in rats—an experimental model for acute gouty arthritis.

Methods

Paw edema, levels/activities of lysosomal enzymes, lipid peroxidation, enzymic antioxidants and a histopathological examination of ankle joints were evaluated in control and monosodium urate crystal-induced inflamed rats. Further, an acetic acid-induced writhing test and tail immersion test were employed to screen for analgesic effects, yeast-induced pyrexia was used to test for antipyretic effects, and gastric ulceration was used to evaluate ulcerogenic effects.

Results

A significant increase in paw edema, lysosomal enzyme activity and lipid peroxidation levels was observed in monosodium urate crystal-induced rats, whereas activities of enzymic antioxidants were found to be decreased when compared to control rats. Nevertheless, treatment with p-Coumaric acid (100 mg/kg b.wt) significantly reverted the altered physical and biochemical parameters back to near normal levels, as evidenced by the histopathology of the ankle joints. In addition, p-Coumaric acid also exhibited potent analgesic and antipyretic effects devoid of any adverse impact on gastric mucosa.

Conclusion

The results of this study reveal the potential anti-inflammatory effect of p-Coumaric acid against monosodium urate crystal-induced inflammation in rats.     

Antinociceptive and anti-inflammatory activities of <Emphasis Type="Italic">Geranium bellum</Emphasis> and its isolated compounds

Background

Geranium bellum Rose, locally known as “Pata de león”, is a perennial plant distributed in the mountains of Hidalgo, Mexico. It is widely used in Mexican traditional medicine to treat fever, pain, and gastrointestinal disorders. To date, there are not published studies regarding the in vivo antinociceptive and anti-inflammatory potential of the acetone-aqueous extract from the aerial parts of G. bellum.

Methods

Antinociceptive effects of the acetone-aqueous G. bellum (AGB) extract and the isolated compounds were assessed using experimental pain models, including thermal nociception like hot plate test, and chemical nociception induced by intraperitoneal acetic acid or subplantar formalin injection in vivo. The anti-inflammatory properties of the extract were studied using systemic administration in carrageenan-induced paw edema.

Results

Intra-gastric administration of AGB (75, 150, and 300 mg/kg) showed a dose-dependent antinociceptive effect in intraperitoneal acetic acid (writhing), thermal nociception in CD1 mice, and subplantar formalin models, as well as anti-inflammatory effect in carrageenan- induced paw edema in Wistar rats. Geraniin and quercetin showed the highest antinociceptive activity in writhing test, whereas ellagic acid was the most active compound in the hot plate model.

Conclusion

These studies provide evidences that G. bellum shows antinociceptive and anti- inflammatory effects, and gives support to its use in treating pain in Mexican traditional medicine.