Carrageenan-induced Air Pouch Model Research Articles

Analgesic and anti-inflammatory investigation of 1,2,4- triazole derivatives in rats

Pain and inflammation are the major devastating health problems commonly treated with NSAIDs. NSAIDs are regularly employed to relieve pain and inflammation. However, the 1,2,4-triazole derivatives have been scientifically evaluated for their use in relieving pain and inflammation. The current research plan is to explore the analgesic and anti-inflammatory properties of 1,2,4-triazole derivatives. 1,2,4-triazoles was tested for their anti-inflammatory properties using carrageenan and formalin-induced paw oedema, acetic acid-induced writhing investigation, while its peripheral and central analgesic actions were assessed using the hot plate method and Carrageenan induced Air Pouch model respectively. The test compounds were administrated at dose of 55 mg/Kg. The standard Diclofenac drug was administrated at dose of 10 mg/Kg for Acetic acid induced writhing investigation, Anti-inflammatory activity and 10 mg/Kg dose of pentazocine was administrated for hot plate method. Rats given with distilled water (10 mL/kg) were designated as the negative controls. Oral administration of all treatments was used. Evaluation of the analgesic and anti-inflammatory investigation showed that the second compound (5-(4-nitrophenyl)-1-phenyl-1H-1,2,4-triazole-3-(2H)–one declines the number of abdominal cramps caused by 1�etic acid and increases the time of response in hot plate method and decreased the edema induced by carrageenan, formalin also decreased volume of exudates in air pouch model. The results of the research indicate that compound 5-(4-nitrophenyl)-1-phenyl-1H-1,2,4-triazole-3-(2H)-one has shown more effective analgesic and Anti-inflammatory properties than the other two compounds.

Anti-inflammatory and antinociceptive activities of Daniellia oliveri (Fabaceace) stem bark extract.

Daniellia oliveri (Rolfe) Hutch. & Dalziel (Fabaceae) is used for the treatment of inflammatory diseases and pains (chest pain, toothache and lumbago) and rheumatism. The study investigates the anti-inflammatory and antinociceptive properties of D. oliveri and possible mechanism of antiinflammatory action. Acute toxicity of the extract was evaluated in mice using the limit test. The anti-inflammatory activity was assessed in xylene-induced paw oedema and carrageenan-induced air-pouch models at doses of 50, 100 and 200mg/kg, p.o. Volume of exudate, total protein, leukocyte counts, myeloperoxidase (MPO) and concentration of cytokines (TNF-α and IL-6) were measured in the exudate of rats in the carrageenan-induced air-pouch model. Other parameters include lipid peroxidation (LPO), nitric oxide (NO) and antioxidant indices (SOD, CAT and GSH). Histopathology of the air pouch tissue was also carried out. The antinociceptive effect was assessed using acetic acid-induced writhing, tail flick and formalin tests. Locomotor activity was done in the open field test. The extract was analysed with HPLC-DAD-UV technique. The extract showed significant anti-inflammatory effect (73.68 and 75.79%, inhibition) in xylene-induced ear oedema test at the dose of 100 and 200mg/kg, respectively. In carrageenan air pouch model, the extract significantly reduced exudate volume, protein concentration, the migration of leukocytes and MPO production in the exudate. The concentrations of cytokines TNF-α (12.25±1.80pg/mL) and IL-6 (21.12pg/mL) in the exudate at the dose of 200mg/kg were reduced compared to carrageenan alone group (48.15±4.50pg/mL; 82.62pg/mL) respectively. The extract showed significant increase in the activities of CAT and SOD and GSH concentration. The histopathological assessment of the pouch lining revealed reduction of immuno-inflammatory cell influx. Nociception was significantly inhibited by the extract in acetic acid-induced writhing model and the second phase of formalin test indicating a peripheral mechanism of action. The open field test showed that D. oliveri did not alter locomotor activity. The acute toxicity study did not cause mortality or signs of toxicity at 2000mg/kg, p.o. We identified and quantified caffeic acid, p-coumaric acid, ferulic acid, rutin, apigenin-7-glucoside, quercetin and kaempferol in the extract. The results of our study showed that the stem bark extract of D. oliveri possesses anti-inflammatory and antinociceptive activities thereby supporting its traditional use in the treatment of some inflammatory and painful disorders.

Chemical characterization, anti-nociceptive and anti-inflammatory activities of Plukenetia conophora seed oil in experimental rodent models

Ethnopharmacological relevanceThe seed of the African walnut, Plukenetia conophora Mull.-Arg is well-known for its nutritional and medicinal values. The seed oil is widely used in massages to relieve pain, as nerve tonic and to enhance sexual performance. ObjectiveThe study aimed at investigating the chemical profile, antinociceptive and anti-inflammatory activities of P. conophora oil (PCO). MethodsSeed oil of P. conophora was characterized using Gas-Liquid Chromatographic method (GC-MS) and oral acute toxicity evaluated at 2000 mg/kg. Antinociceptive effects were evaluated in hot plate, acetic acid and formalin-induced paw licking tests. The anti-inflammatory effects were investigated in egg albumin and carrageenan-, formalin and complete Freund adjuvant (CFA)-induced paw oedema models. The levels of pro-inflammatory cytokines in the fluid exudates were also evaluated in carrageenan air pouch model. ResultsPCO exhibited high content of alpha linolenic acid (ALA). No toxicity was observed at 2000 mg/kg of PCO. PCO (50–200 mg/kg) demonstrated significant anti-nociceptive activity in pain models. PCO exhibited anti-inflammatory activity against oedema formation by phlogistic agents. The increased inflammatory oedema and oxidative stress in CFA-treated rats were also attenuated by PCO. The PCO (100 and 200 mg/kg) significantly reduced the levels of TNF-α (59.3% and 85.2%) and IL-6 (27.5% and 72.5%) in carrageenan-induced air pouch model. ConclusionThe results of this study suggest that ALA-rich seed oil of Plukenetia conophora demonstrated anti-nociceptive and anti-inflammatory activities via inhibition of pro-inflammatory cytokines and oxidative stress, lending supportive evidences for its use in painful inflammatory conditions.

Secondary Metabolite Profiling, Anti-Inflammatory and Hepatoprotective Activity of Neptunia triquetra (Vahl) Benth.

The present study aimed to analyze the phytoconstituents of Neptunia triquetra (Vahl) Benth. Anti-inflammatory and hepatoprotective activities of ethanol (EE), chloroform (CE) and dichloromethane (DCME) of stem extracts were evaluated using in vivo experimental models. The extracts were analyzed for phytoconstituents using GC-HRMS. Anti-inflammatory activity of CE, EE and DCME was accessed using carrageenan-induced paw oedema, cotton pellet-induced granuloma and the carrageenan-induced air-pouch model in Wistar albino rats. The hepatotoxicity-induced animal models were investigated for the biochemical markers in serum (AST, ALT, ALP, GGT, total lipids and total protein) and liver (total protein, total lipids, GSH and wet liver weight). In the in vivo study, animals were divided into different groups (six in each group) for accessing the anti-inflammatory and hepatoprotective activity, respectively. GC-HRMS analysis revealed the presence of 102 compounds, among which 24 were active secondary metabolites. In vivo anti-inflammatory activity of stem extracts was found in the order: indomethacin > chloroform extract (CE) > dichloromethane extract (DCME) > ethanolic extract (EE), and hepatoprotective activity of stem extracts in the order: CE > silymarin > EE > DCME. The results indicate that N. triquetra stem has a higher hepatoprotective effect than silymarin, however the anti-inflammatory response was in accordance with or lower than indomethacin.

Protective effect of the intravenous anesthetic propofol against a local inflammation in the mouse carrageenan-induced air pouch model

Aim: 2,6-Di-isopropylphenol (propofol) is an intravenous general anesthetic widely used in the operating room for general anesthesia and in the intensive care unit for sedation. The mouse air pouch model is versatile in studying the anti-inflammatory effect of a drug on a local inflammation, which is induced by a variety of substances. In this study, using the carrageenan-induced air pouch inflammation model, we tested whether propofol mitigates inflammation occurring locally in the mouse air pouch. Methods: Carrageenan-induced air pouch inflammation model. Results: Propofol inhibited the production of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in the pouch. Propofol also inhibited the production of neutrophil chemokines, KC and MIP-2, and decreased the number of both Ly-6G+/CD11b+ cells (assumed to be primarily neutrophils) and Ly-6G−/CD11b+ cells (assumed to be monocytes/macrophages), recruited into the pouch at 3 h after injection of carrageenan. Conclusion: Propofol has an anti-inflammatory property in the carrageenan-induced mouse air pouch local inflammation model, by inhibiting the production of pro-inflammatory cytokines (TNF-α and IL-6), as well as by inhibiting the production of chemokines (KC and MIP-2), which might be associated with the inhibition of intra-pouch recruitment of white blood cells.

Anti-nociceptive and anti-inflammatory activities of ethanol extract and fractions of Morus mesozygia Stapf (Moraceae) leaves and its underlying mechanisms in rodents

Ethnopharmacological relevanceMorus mesozygia Stapf (Moraceae), commonly known as African mulberry, is traditionally used for the treatment of inflammatory disorders such as rheumatism and dermatitis. AimThis work aimed to evaluate the anti-nociceptive and anti-inflammatory effects of its ethanol (EEMm) extract, and ethylacetate fraction (EAFMm). MethodsThe anti-nociceptive and anti-inflammatory effect of ethanol extracts of M. mesozygia (EEMm), and its ethylacetate (EAFMm) and residual aqueous fraction (RAFMm) was evaluated in hotplate, acetic acid and formalin tests and as well in membrane stabilizing assay and carrageenan-induced paw oedema models. Mechanism of anti-inflammation of EAFMm was investigated in the carrageenan-induced air-pouch model. ResultsIn the hot plate test of nociception, only the EAFMm showed significant (p < 0.05) anti-nociceptive activity. The extract and fractions significantly reduced number of writhing with EAFMm (400 mg/kg) showing highest inhibition (66.5%) in the acetic acid-induced writhing in mice. EEMm and EAFMm (400 mg/kg) significantly reduced the paw licking time in the early and late phases of the formalin test. The extract and fractions showed good membrane stabilizing activity comparable to indomethacin. EAFMm (100 and 400 mg/kg) showed the highest inhibition of paw oedema (53.4% and 58.1%) in the carrageenan-induced paw oedema model. The EAFMm (100 and 400 mg/kg) reduced exudate volume relative to carrageenan-control (2.64 ± 0.22, 2.08 ± 0.15 vs 3.83 ± 0.18 mL) and neutrophils (8.98 ± 1.36, 8.00 ± 0.22 vs 20.51 ± 1.14) in carrageenan-induced pouch. EAFMm significantly reduced exudate volume, pro-inflammatory cytokines and the expression of COX-2 and NFκB. ConclusionM. mesozygia leaves demonstrated anti-nociceptive and anti-inflammatory activities by suppressing oxidative stress, pro-inflammatory cytokines, cyclooxygenase-2, and nuclear factor kappa B.

Toxicity and Protective Effect of Phenolic-Enriched Ethylacetate Fraction of Ocimum gratissimum (Linn.) Leaf against Acute Inflammation and Oxidative Stress in Rats.

Preclinical Research Ocimum gratissimum L. leaves have attracted considerable attention from researchers because of their medicinal value that include anti-inflammatory, analgesic, antimicrobial, and antioxidant activities. In the present study, the toxicity and the protective effect of phenolic extract of O. gratissimum leaf (EAFOg) against acute inflammation and oxidative stress in rats was assessed. EAFOg, enriched in phenols had no cytotoxic effect against CHO-k1 cells, and no lethality against brine shrimp eggs or mice at a dose of 2000 mg/kg. EAFOg (50 and 100 mg/kg) reduced paw edema by 47% and 61%, compared to 29% with the COX-2 inhibitor, SC58125 (1 mg/kg) and 81% with indomethacin (5 mg/kg), respectively. In the rat carrageenan-induced air pouch model, EAFOg reduced exudate volume, leucocyte count, nitrite, TNF-α, and myeloperoxidase activity. EAFOg also protected against carrageenan-induced lipid peroxidation and glutathione depletion. These results provide evidence of the protective effects of EAFOg against acute inflammation and oxidative stress in rats. Drug Dev Res 78 : 135-145, 2017. © 2017 Wiley Periodicals, Inc.

Mangiferin from Pueraria tuberosa reduces inflammation via inactivation of NLRP3 inflammasome

Recent reports have demonstrated the role of phyto-constituents in modulating inflammatory responses. Mangiferin isolated from Mangifera indica is known to induce potent anti-oxidative, anti-diabetic and anti-inflammatory activity. However, the molecular mechanism of its anti-inflammatory activity is not properly understood. In this study we have isolated Mangiferin from the tubers of Pueraria tuberosa (PT-Mangiferin) and analysed the mechanism of its potent anti-inflammatory effects in LPS stimulated RAW 264.7 mouse macrophage cell line and in a carrageenan induced air pouch model. PT-Mangiferin was non-toxic to primary cells but showed significant toxicity and apoptotic effect on cancerous cells. It significantly reduced the production of pro-inflammatory mediators (COX-2, iNOS and TNF-α) in LPS stimulated RAW 264.7 cells. Further, it has also reduced the generation of ROS and inhibited LPS induced NF-kB translocation in these cells. Additionally, PT-Mangiferin significantly reduced inflammation in a mouse air pouch model by inhibiting the infiltration of monocytes and neutrophils and reducing the production of cytokines. These effects were mediated via inactivation of NLRP3 inflammasome complex and its downstream signalling molecules. Taken together these results suggest that PT-Mangiferin is potent anti-inflammatory compound that reduces inflammation and holds promise in development of herbal based anti-inflammatory therapeutics in future.

Evaluation of Anti-inflammatory and Anti-arthritic Activity of Ajmodadi Churna- A Polyherbal Formulation

Anti-inflammatory and anti- arthritic activity of aqueous extract of Ajmodadi Churna (AJM) were evaluated by three methods namely, Carrageenan paw edema, Carrageenan induced Air Pouch Model in Rats and Freunds’ complete adjuvant Arthritis. The Carrageenan paw edema was carried out to test the effect of the extract on acute phase of inflammation. Carrageenan induced Air Pouch Model was used for local inflammation and Freunds’ complete adjuvant Arthritis was used for evaluation of chronic inflammation. Results showed that AJM have significant anti-inflammatory activity and Anti-arthritic Activity in both the doses (200 mg/kg and 400 mg/kg) when compared to the Diclofenac but higher dose was found more effective.Key Words: Anti-inflammatory, Anti-arthritic Activity, Freunds’ complete adjuvant Arthritis, Ajmodadi churna.

Antipyretic, analgesic and anti-inflammatory effects of Kickxia ramosissima

Ethnopharmacological relevanceBranched cancerwort, Kickxia ramosissima (Wall.) Janchen (Scrophulariaceae) is traditionally used for the treatment of inflammatory disorders such as rheumatism, diabetes, jaundice and for activation of immune system. Local communities also used this plant for the treatment of spleen enlargement, as febrifuge and in dysmenorrhea. In this investigation antipyretic, analgesic and anti-inflammatory effects of K. ramosissima have been evaluated. MethodsDried powder of the whole plant of K. ramosissima was extracted with methanol (KRM) and partitioned with solvents to obtain the n-hexane (KRH), chloroform (KRC), ethyl acetate (KRE), n-butanol (KRB) and the residual aqueous (KRA) fraction. KRM and the derived fractions were analyzed for the phytochemical constituents, yeast induced pyrexia, analgesic and anti-inflammatory activities by using carrageenan and Freunds' complete adjuvant-induced paw edema model in rat. On account of appreciable effects of KRM in the aforesaid models, KRM was subjected to the carrageenan induced air pouch model in rat. The exudate of air pouch was analyzed for the count of neutrophils, monocytes, lymphocytes and WBCs and for the estimation of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nitric oxide (NO) and prostaglandin (PGE2). ResultsPhytochemical investigation of KRM indicated the existence of tannins, flavonoids, alkaloids, coumarins, cardiac glycosides, saponins, terpenoids and phlobatannins. Maximum concentration of total phenolic was determined in KRB followed by KRM while reverse was true for total flavonoids contents. KRM (200mg/kg) distinctly decreased the rectal temperature in yeast induced pyrexia comparable to standard, paracetamol. Pain sensation was effectively inhibited at 200mg/kg p.o. of KRM and KRB as manifested by a decrease (P<0.001) in count of writhing induced with acetic acid and increase of latency time in hot plate. Anti-inflammatory effects of KRM were evident and edema formation induced with carrageenan and Freunds' complete adjuvant-induced paw edema in rat was significantly (P<0.001) inhibited. Count of neutrophils, monocytes, lymphocytes, and WBCs along with inflammatory mediators; IL-6, NO, TNF-α and PGE2 was significantly (P<0.001) decreased in subcutaneous air pouch exudate with KRM. HPLC analysis of KRM indicated the presence of gallic acid, caffeic acid, rutin, catechin and myricetin. ConclusionThe results suggested the anti-inflammatory effects of KRM in inflammation related disorders, might be attributed by the presence of active phytoconstituents; flavonoids, saponins and terpenoids.

Modulatory effect of mycophenolate mofetil on carrageenan-induced inflammation in the mouse air pouch model

The treatment of some inflammatory diseases, such as rheumatoid arthritis, remains an important target for studies because some patients are refractory to conventional treatment. Mycophenolate mofetil (MMF), an immunosuppressive drug, has been shown to have a beneficial effect on the therapy of inflammatory and autoimmune diseases. In the present study, we aimed to analyse the anti-inflammatory effect of MMF administered by oral route in the mouse carrageenan-induced air pouch model. Results: MMF significantly inhibited the influx of leukocytes, exudate concentrations (P<0.01), activities of myeloperoxidase (MPO) and adenosine deaminase (ADA), levels of nitrite/nitrate (NOx) and inducible nitric oxide synthase (iNOS) mRNA expression, as well as the levels of mRNA expression and proteins of tumor necrosis factor-alpha (TNF-α), Interleukin-beta (IL-1β) and vascular endothelial growth factor-alpha (VEGF-α) (P<0.05). These results provide evidence that MMF has an important anti-inflammatory effect in reducing the influx of leukocytes and exudate concentrations. These inhibitory effects are correlated with the inhibition of specific pro-inflammatory enzymes (MPO, ADA and iNOS), and the levels of mRNA expression and proteins of TNF-α, IL-1β and VEGF-α.

Anti-inflammatory activity of Ajmodadi Churna extract against acute inflammation in rats

Background:Ayurvedic polyherbal formulations are widely prescribed for a wide range of inflammatory conditions, yet, despite widespread use, there has been no systematic documentation of their safety and efficacy.Objective:The present study was undertaken to evaluate the anti-inflammatory activity of aqueous extracts of Ajmodadi churna (AJM) in rats.Materials and Methods:Carrageenan-induced hind paw edema and air pouch inflammation models were used for the study.Results:The extracts showed significant antiinflammatory activity, reducing paw edema volume by 0.417 ± 0.097 and 0.379 ± 0.049, respectively. In the carrageenan-induced air pouch model, AJM reduced total leukocyte count by 73.09 ± 7.13 and 62.17 ± 10.53, granulocyte count by 69.48 ± 5.44 and 63.33 ± 4.13, and myeloperoxidase activity by 14.84 ± 0.91 and 18.44 ± 3.18, respectively, compared to controls.Discussion and Conclusion:AJM significantly reduced paw edema, during the second phase of edema development. In the carrageenan-induced air pouch model, AJM inhibited cellular infiltration into the air pouch fluid. We conclude that AJM is an effective candidate for prevention or treatment of acute inflammation

Evaluation of the Antiangiogenic, Anti-inflammatory, and Antinociceptive Activities of Morin

Morin displayed significant inhibition of chick chorioallantoic membrane (CAM) angiogenesis and was able to increase the endostatin level in human umbilical vein endothelial cells (HUVECs). Morin was shown to contain an in vivo anti-inflammatory activity using a carrageenan-induced air pouch model in mice. Antinociceptive activity of morin was also assessed using an acetic acid-induced writhing test in mice. Collectively, morin possesses antiangiogenic, in vivo anti-inflammatory, and antinociceptive activities.

Preclinical pharmacokinetic and pharmacodynamic evaluation of thiazolidinone PG15: an anti-inflammatory candidate

Novel 5-benzilidene thiazolidinones have been synthesized and exhibited anti-inflammatory activity. In this work one of the compounds of the thiazolidinone chemical series, (5Z,E)-3-[2-(4-chlorophenyl)-2-oxoethyl]-5-(1H-indol-3-ylmethylene)-thiazolidine-2,4-dione (PG15) was investigated aiming to determine the drug's anti-inflammatory potential in pre-clinical studies. Methods used included the in-vitro inhibition of cyclooxygenase-1 and -2, in-vivo evaluation of anti-inflammatory activity by air pouch and peritonitis models and the pharmacokinetic profile after intravenous (3 mg/kg) and oral (3 and 6 mg/kg) dosing to rats. A two-compartment model with a fast distribution and an elimination half-life of 5.9 +/- 3.8 h described the PG15 plasma profile after intravenous dosing. PG15 showed an erratic and rapid absorption following oral administration with peak concentrations between 0.5 and 1 h. PG15 0.1 microM inhibited more than 30% and 13% of purified cyclooxygenase-1 and -2 activity in vitro, respectively. A lack of dose dependency was observed for the anti-inflammatory effect in the dose range investigated (0.8-50 mg/kg), with a maximum of 67.2 +/- 4.6% inhibition of leucocyte migration in the carrageenan-induced air pouch model obtained with the 3 mg/kg dose, similar to that observed for indometacin 10 mg/kg. The erratic absorption of PG15 observed after oral dosing could explain the lack of anti-inflammatory dose dependency.

Preclinical pharmacokinetic and pharmacodynamic evaluation of thiazolidinone PG15: an anti-inflammatory candidate

Objectives Novel 5-benzilidene thiazolidinones have been synthesized and exhibited anti-inflammatory activity. In this work one of the compounds of the thiazolidinone chemical series, (5Z,E)-3-[2-(4-chlorophenyl)-2-oxoethyl]-5-(1H-indol-3- ylmethylene)-thiazolidine-2,4-dione (PG15) was investigated aiming to determine the drug's anti-inflammatory potential in pre-clinical studies. Methods Methods used included the in-vitro inhibition of cyclooxygenase-1 and -2, in-vivo evaluation of anti-inflammatory activity by air pouch and peritonitis models and the pharmacokinetic profile after intravenous (3 mg/kg) and oral (3 and 6 mg/kg) dosing to rats. Key findings A two-compartment model with a fast distribution and an elimination half-life of 5.9 ± 3.8 h described the PG15 plasma profile after intravenous dosing. PG15 showed an erratic and rapid absorption following oral administration with peak concentrations between 0.5 and 1 h. PG15 0.1 μM inhibited more than 30% and 13% of purified cyclooxygenase-1 and -2 activity in vitro, respectively. A lack of dose dependency was observed for the anti-inflammatory effect in the dose range investigated (0.8–50 mg/kg), with a maximum of 67.2 ± 4.6% inhibition of leucocyte migration in the carrageenan-induced air pouch model obtained with the 3 mg/kg dose, similar to that observed for indometacin 10 mg/kg. Conclusions The erratic absorption of PG15 observed after oral dosing could explain the lack of anti-inflammatory dose dependency.

Evaluation of anti-inflammatory activity of ethanolic extract of Borassus flabellifer L. male flowers (inflorescences) in experimental animals.

Borassus flabellifer L. (Arecaceae) had been widely used for its reported biological activities in indige-nous system of medicine. The present investigation was carried out to find the effect of ethanolic extract of male flowers (inflorescences) ofBorassus flabellifer for its anti-inflammatory activity in ro-dents. The anti-inflammatory activity was evaluated using acute inflammatory models like; carrageenan-induced paw oedema and chronic models like; cotton-pellet induced granuloma and carrageenan-induced air-pouch model in rats. The biochemical parameters like serum glutamate pyruvate trans-aminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), lipid per oxidation and alkaline phosphatase (ALP) were also estimated as supportive studies. Oral administration of the extract at the doses 150 and 300 mg/kg b.w. exhibited dose dependent and significant anti-inflammatory activity in acute (carrageenan- induced hind paw oedema, p < 0.0001) and chronic (cotton pellet granuloma and carrageenan-induced air-pouch models, p < 0.0001) of inflammation. The extract also showed signi-ficant (p < 0.0001) results for biochemical parameters. Hence, present investigation established some pharmacological evidences to support the folklore claim that B. flabellifer L. is used as anti-inflammatory agent. Key words: Borassus flabellifer L., inflorescences, male flowers, anti-inflammatory, ethanolic extract, SGOT, SGPT, lipid per oxidation, ALP.

A combination of aspirin and γ-tocopherol is superior to that of aspirin and α-tocopherol in anti-inflammatory action and attenuation of aspirin-induced adverse effects

Nonsteroidal anti-inflammatory drugs such as aspirin are used for pain relief and chemoprevention against cancer, but frequently cause gastric mucosal injury. We examined whether combinations of aspirin and α-tocopherol (αT) or aspirin and γ-tocopherol (γT), with αT and γT being the two major forms of vitamin E, are better anti-inflammatory agents than aspirin alone, and whether these combinations alleviate aspirin-associated side effects. In the carrageenan-induced air-pouch inflammation model in the rat, aspirin (150 mg/kg) or a combination of aspirin and γT (33 mg/kg) inhibited proinflammatory prostaglandin E 2 (PGE 2) by 70% ( P<.02) at the inflammation site 6 h after inflammation was initiated. However, at 18 h, only the combination decreased exudate volume (15%; P<.05) and showed modest inhibition of PGE 2 (40%; P<.07) and lactate dehydrogenase activity (30%; P=.07) in the fluid collected at the inflammation site. γT, but not αT, spared aspirin-induced reduction in food intake, partially reversed aspirin-depressed gastric PGE 2 and attenuated stomach lesions. Surprisingly, the combination of aspirin and αT (33 mg/kg) did not show more benefits than aspirin alone, but worsened gastric injury and food intake reduction. Our study demonstrated that a combination of aspirin and γT, but not a combination of aspirin and αT, has some advantage over aspirin alone in terms of anti-inflammatory effects and attenuation of aspirin-induced adverse effects. This combination may be useful in complementing aspirin in the treatment of chronic inflammatory conditions and cancer.

Anti-inflammatory activity of Taraxacum officinale

Taraxacum officinale has been widely used as a folkloric medicine for the treatment of diverse diseases. The dried plant was extracted with 70% ethanol to generate its ethanol extract (TEE). For some experiments, ethyl acetate (EA), n-butanol (BuOH) and aqueous (Aq) fractions were prepared in succession from TEE. TEE showed a scavenging activity in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, a diminishing effect on intracellular reactive oxygen species (ROS) level, and an anti-angiogenic activity in the chicken chorioallantoic (CAM) assay. In the carrageenan-induced air pouch model, TEE inhibited production of exudate, and significantly diminished nitric oxide (NO) and leukocyte levels in the exudate. It also possessed an inhibitory effect on acetic acid-induced vascular permeability and caused a dose-dependent inhibition on acetic acid-induced abdominal writhing in mice. Suppressive effects of TEE on the production of NO and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated macrophages were also assessed. Among the fractions, the n-butanol fraction (BuOH) was identified to be most effective in the CAM assay. Collectively, Taraxacum officinale contains anti-angiogenic, anti-inflammatory and anti-nociceptive activities through its inhibition of NO production and COX-2 expression and/or its antioxidative activity.

Anti-angiogenic, anti-inflammatory and anti-nociceptive activity of 4-hydroxybenzyl alcohol

4-Hydroxybenzyl alcohol (HBA), one of the well-known phenolic compounds in diverse plants, displayed a significant inhibition in the chick chorioallantoic membrane (CAM) angiogenesis assay. HBA was shown to contain an anti-inflammatory activity in carrageenan-induced air pouch model in rats and acetic acid-induced permeability model in mice. Anti-nociceptive activity of HBA was also assessed using the acetic acid-induced writhing test in mice. HBA was able to suppress production of nitric oxide (NO) and expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-activated RAW264.7 macrophages. In the macrophages, the level of reactive oxygen species (ROS) was diminished by HBA. Taken together, HBA possesses anti-angiogenic, anti-inflammatory and anti-nociceptive activity possibly via its down-regulating activity on NO production, which may be partly responsible for the pharmacological efficacy of several folkloric medicines.

Formation of 8-isoprostaglandin F 2α and prostaglandin E 2 in carrageenan-induced air pouch model in rats

To investigate a possible role of 8-isoprostaglandin F 2α in inflammation, 8-isoprostaglandin F 2α and prostaglandin E 2 levels were determined by enzyme immunoassay (EIA) in carrageenan-induced air pouch model in rats. In this model, 8-isoprostaglandin F 2α and prostaglandin E 2 levels were found to be increased significantly. To evaluate whether this increase was due to the development of inflammation or solely to cyclooxygenase-2 induction, a lipopolysaccharide-induced air pouch model, in which only cyclooxygenase-2 induction occurs without inflammation, was used. In this model, 8-isoprostaglandin F 2α was also found to be increased parallel to the increase in prostaglandin E 2 level. Cyclooxygenase-dependent formation of 8-isoprostaglandin F 2α was investigated in carrageenan-induced air pouch model by administrating nonselective cyclooxygenase inhibitor indomethacin, selective cyclooxygenase-1 inhibitor valeryl salicylate or selective cyclooxygenase-2 inhibitor SC-582368 (4-(5-(4-chlorophenyl)-3-3-trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonanmide) 1 h before carrageenan injection. All these inhibitors significantly inhibited the production of 8-isoprostaglandin F 2α and prostaglandin E 2. These findings show that 8-isoprostaglandin F 2α can be formed in carrageenan-induced air pouch model in rats. The formation of 8-isoprostaglandin F 2α in lipopolysaccharide-induced air pouch model and the inhibition of its production by various cyclooxygenase inhibitors provide evidence for cyclooxygenase-dependent formation of isoprostanes in this model.