Anti-inflammatory and anti-nociceptive activities of essential oil of Waltheria indica / Actividades antiinflamatorias y nociceptivas del aceite esencial de Waltheria indica

This paper reports for the first time volatile compounds, anti-nociceptive and anti-inflammatory activities of essential oils from the leaves of Waltheria indica L. (Stericullaceae) growing in Nigeria. The essential oil was hydro-distilled and characterized by gas chromatography-flame ionization detection (GC-FID) and gas chromatography coupled with mass spectrometry (GC-MS) analyses. The anti-inflammatory activity was evaluated on carrageenan induced rat paw edema while the anti-nociceptive test was based on hot plate model. The hydro-distillation afforded 0.41% (dry weight basis) of light green oil. Forty compounds representing 99.8% were identified in the oil. The main constituents of the oil were limonene (34.7%), sabinene (21.2%) and citronellal (9.7%). The anti-nociceptive property of the essential oils statically inhibited edema development (p<0.001) at a dose of 200 and 400 mg/kg independent of time of exposure. However, the 100 mg/kg Waltheria indica essential oils (WIEO) displayed a relatively low inhibition (p<0.01-p>0.5) which declines as exposure time increases. The anti-inflammatory activities shows a steady rate and non-dose dependent activity (p<0.001) up to the 3rd h of inflammation study. Conversely, a sharp reduction at the rate of p<0.5, 0.1 and 0.01 for the 100, 200 and 400 mg/kg WIEO doses respectively. Overall, the results presented sustain and establish the anti-nociceptive and anti-inflammatory properties and justifies the need for further evaluation and development of the essential oils from this plant.

Este artículo informa por primera vez de compuestos volátiles, actividades anti-nociceptivas y antiinflamatorias de aceites esenciales de las hojas de Waltheria indica L. (Stericullaceae) que crecen en Nigeria. El aceite esencial fue hidro-destilado y se caracterizó por cromatografía de gases-detección de ionización de llama (GC-FID) y cromatografía de gases junto con análisis de espectrometría de masas (GC-MS). La actividad antiinflamatoria se evaluó en el edema de pata de rata inducido por carragenano, mientras que la prueba antinociceptiva se basó en el modelo de placa caliente. La destilación hidráulica proporcionó 0,41% (en peso seco) de aceite verde claro. Cuarenta compuestos que representan el 99.8% fueron identificados en el aceite. Los principales componentes del aceite fueron el limoneno (34,7%), el sabineno (21,2%) y el citronelal (9,7%). La propiedad anti-nociceptiva de los aceites esenciales inhibió estáticamente el desarrollo del edema (p<0.001) a una dosis de 200 y 400 mg/kg independientemente del tiempo de exposición. Sin embargo, los aceites esenciales de Waltheria indica de 100 mg/kg (WIEO) mostraron una inhibición relativamente baja (p<0.01-p>0.5) que disminuye a medida que aumenta el tiempo de exposición. Las actividades antiinflamatorias muestran una tasa constante y una actividad no dependiente de la dosis (p<0.001) hasta la tercera hora del estudio de inflamación. Por el contrario, una fuerte reducción a una tasa de p<0.5, 0.1 y 0.01 para las dosis de 100, 200 y 400 mg/kg de WIEO respectivamente. En general, los resultados presentados sostienen y establecen las propiedades anti-nociceptivas y antiinflamatorias y justifican la necesidad de una mayor evaluación y desarrollo de los aceites esenciales de esta planta.

Liquid Chromatography-Mass Spectrometry-Based In Vitro Metabolic Profiling Reveals Altered Enzyme Expressions in Eicosanoid Metabolism

BACKGROUND: Eicosanoids are metabolites of arachidonic acid that are rapidly biosynthesized and degraded during inflammation, and their metabolic changes reveal altered enzyme expression following drug treatment. We developed an eicosanoid profiling method and evaluated their changes on drug treatment. METHODS: Simultaneous quantitative profiling of 32 eicosanoids in liver S9 fractions obtained from rabbits with carrageenan-induced inflammation was performed and validated by liquid chromatography-mass spectrometry coupled to anion-exchange solid-phase purification. RESULTS: The limit of quantification for the devised method ranged from 0.5 to 20.0 ng/mg protein, and calibration linearity was achieved (R 2>0.99). The precision (% CV) and accuracy (% bias) ranged from 4.7 to 10.3% and 88.4 to 110.9%, respectively, and overall recoveries ranged from 58.0 to 105.3%. Our method was then applied and showed that epitestosterone treatment reduced the levels of all eicosanoids that were generated by cyclooxygenases and lipoxygenases. CONCLUSIONS: Quantitative eicosanoid profiling combined with in vitro metabolic assays may be useful for evaluating metabolic changes affected by drugs during eicosanoid metabolism.

Efectos del policosanol en los modelos de pleuresía inducida por carragenina y granuloma por algodón / Effects of policosanol on carrageenan-induced pleurisy and cotton pellet granuloma models

Introducción: el policosanol, mezcla de alcoholes alifáticos primarios superiores purificada de la cera de caña, inhibe la actividad de la cicloxigenasa-1 (COX-1) in vitro, efecto que pudiera sustentar su acción antiagregante plaquetaria. Sin embargo, sus posibles efectos en modelos experimentales de inflamación no se habían investigado. Objetivo: determinar el efecto antinflamatorio in vivo del policosanol en un modelo de inflamación aguda (pleuresía por carragenina) y crónico (granuloma por algodón). Métodos: se distribuyeron las ratas Sprague Dawley en siete grupos para el modelo de inflamación aguda: un control negativo (vehículo) y seis a los que se les indujo la inflamación: un control positivo (vehículo), cuatro tratados con policosanol (50-800 mg/kg) y uno con aspirina (100 mg/kg). Se cuantificaron a las 5 h el volumen de exudado pleural, la concentración de proteínas y actividad de la enzima mieloperoxidasa. Se distribuyeron las ratas en seis grupos para el modelo crónico: un control (vehículo), cuatro tratados con policosanol (50-800 mg/kg) y uno con aspirina (100 mg/kg). Se extrajo el granuloma para determinar los pesos húmedo y seco seis días después de implantado el pellet. Resultados: dosis orales únicas de policosanol (200, 400 y 800 mg/kg) redujeron significativa y moderadamente el volumen, la actividad de la enzima mieloperoxidasa (¼ 12 por ciento) y la concentración de proteínas (¼ 20 por ciento) del exudado pleural, mientras la aspirina redujo estos indicadores en un 35,3, 19,9 y 19,1 por ciento, respectivamente. La administración oral de policosanol (400 y 800 mg/kg) durante 6 días disminuyó significativa y moderadamente el peso húmedo del granuloma (16,4 y 16,2 por ciento), y el peso seco (28,4 y 34,4 por ciento). La aspirina 100 mg/kg redujo estas variables en un 18,5 por ciento (peso húmedo) y 34,4 por ciento (peso seco). Ambos tratamientos produjeron mayores reducciones del peso seco que del peso húmedo del granuloma. Conclusiones: la administración oral de policosanol produjo un moderado efecto antinflamatorio in vivo en modelos de inflamación aguda y crónica(AU)

Introduction: policosanol, a mixture of higher aliphatic alcohols purified from sugarcane wax, inhibits cyclooxygenase-1 (COX-1) activity in vitro, an effect that could support its anti-platelet action. Its putative effects on experimental models of inflammation had not been yet investigated. Objective: to determine the in vivo effect of policosanol on acute (carrageenan-induced pleurisy) and chronic inflammation (cotton-pellet granuloma) in vivo models. Methods: in the acute model, rats were randomly distributed into seven groups: a negative vehicle control, and six with carrageenan-induced pleurisy: a positive control (vehicle), four treated with policosanol (50-800 mg/kg) and one with aspirin (100 mg/kg). Five hours later, volume of pleural exudate, protein concentration and myeloperoxidase activity were quantified. For the chronic model, rats were distributed into six groups: a control (vehicle), four treated with policosanol (50-800 mg/kg) and one group with aspirin (100 mg/kg). The cotton pellet was implanted and six days after treatment, it was extracted to determine the dry and the wet weights. Results: single oral doses of policosanol (200, 400 and 800 mg/kg) reduced significantly and moderately the volume (¼ 20 percent), the myeloperoxidase activity (¼ 12 percent) and the protein concentration (¼ 20 percent) in pleural exudates, whereas aspirin 100 mg/kg decreased significantly these indicators by 35.3, 19.9 and 19.1 percent, respectively. Oral administration of policosanol (400 and 800 mg/kg) for 6 days reduced significantly and moderately the wet (16.4 and 16.2 percent, respectively) and dry (28.4 and 34.4 percent, respectively) granuloma weights. Treatment with 100 mg/kg aspirin reduced these variables by 18.5 percent (wet weight) and 34.4 percent (dry weight), respectively. Both treatments reduced the dry more than the wet granuloma weight. Conclusion: oral administration of policosanol produced a moderate anti-inflammatory effect in vivo on models of acute and chronic inflammation(AU)

Chronic Anti-Inflammatory Activity of Ethanolic Extract of Leaves of Clerodendrum viscosum by Carrageenin Induced Paw Oedema in Wistar Albino Rats.

Aims: The aim of the study was to investigate chronic anti-inflammatory activity of ethanolic extract of the leaves of Clerodendrum viscosum (EELCV) by carrageenin induced paw oedema in Wistar albino rats. Study Design: Prospective. Place and Duration of Study: Dept of Pharmacology, Yenepoya Medical College, Yenepoya University, Derlakatte, Mangalore 575018, Karnataka, India. June 2010-August 2010. Methodology: Dried powdered leaves of Clerodendrum viscosum were subjected to Soxhlet extraction by using 90 % ethanol. Based on acute oral toxicity study according to Organization for Economic Cooperation and Development (OECD) guidelines no. 423, three doses of the test drug was selected (75, 150 & 300 mg/kg) for rats, and were subjected to screening for anti-inflammatory activity. Results: Oral administration of EELCV at doses of 150 mg/kg (P = .01) and 300mg/kg (P = .05) has shown significant anti-inflammatory activity by carrageenin induced paw oedema in Wistar albino rats compared to control. A significant inhibition of oedema formation was also observed at 4th hour. Conclusion: Administration of EELCV orally at the doses of 150 mg/kg (P = .01) and 300mg/kg (P = .05) showed significant anti-inflammatory activity by carrageenin induced paw oedema in Wistar Albino rats. The percentage inhibition of the oedema at 3rd hour was 63.75 % for the dose of 150 mg/kg and 46.30 % for the dose of 300 mg/kg. A significant inhibition was also observed at 4th hour.

Analgesic Mechanism of Electroacupuncture in an Arthritic Pain Model of Rats: A Neurotransmitter Study

PURPOSE: We investigated what kinds of neurotransmitters are related with electroacupuncture (EA) analgesia in an arthritic pain model of rats. MATERIALS AND METHODS: One hundred rats were assigned to six groups: control, EA, opioid, adrenergic, serotonin and dopamine group. A standardized model of inflammatory arthritis was produced by injecting 2% carrageenan into the knee joint cavity. EA was applied to an acupoint for 30 min in all groups except fo the control group. In the opioid, adrenergic, serotonin and dopamine groups, each receptor antagonist was injected intraperitoneally to their respective group before initiating EA. RESULTS: In the opioid receptor antagonist group, adrenergic receptor antagonist group, serotonin receptor antagonist group, dopamine receptor antagonist group and the control group weight-bearing force decreased significantly from 30 min to 180 min after EA in comparison with the EA group. CONCLUSION: The analgesic effects of EA are related to opioid, adrenergic, serotonin and dopamine receptors in an arthritic pain model of rats.

[Effects of green tea extract on experimentally induced toxicosis of carrageenan in male albino rats]

Green tea extract [GTE] is rich in polyphenolic compounds whose antioxidant activity is several fold higher than that of vitamins C and E. In the present study, the effect of GTE on the carrageenan toxicosis in male albino rats using intra-articular injection of 0.1 ml of carrageenan solution was investigated. Three groups of 10 rats each were used: Control, Carrageenan alone, and carrageenan plus GTE. After one week of treatment, the plasma levels of lipid -peroxides and nitric oxide as well as total thiol were measured. The histopathological examination of the liver, spleen and kidneys of the three groups were performed .Animals treated with carrageenan alone showed significant increase value in the levels of both lipid peroxides and nitric oxide in comparison to the control group. In rats that received GTE, the changes in plasma levels of lipid peroxides and nitric oxide were not statistically present from the control group, while the total thiol levels in the GTE group were significantly increased [p<0.05] in comparison with carrageenan only and control groups

Study of the inflammatory process induced by injection of carrageenan or formalin in the rat temporomandibular joint

O objetivo deste trabalho foi avaliar os efeitos da injecão de dois agentes flogísticos, ou seja, carragenina ou formalina, na ATM do rato, e a evolucão do quadro inflamatório provocado por essas substâncias. Foram utilizados 45 ratos, divididos em dois grupos experimentais e um grupo controle. Os animais foram sacrificados em lotes de três de cada grupo após três horas, 24 horas, três dias, sete dias e 15 dias da injecão. Histologicamente a reacão inflamatória em ambos os grupos experimentais iniciou-se com infiltrado inflamatório agudo, tornando-se misto e depois crônico. Sinais de hiperplasia da membrana sinovial foram observados aos três dias, intensos aos sete dias, estando presentes aos 15 dias somente no grupo da formalina. A injecão de solucão salina (grupo controle) não provocou reacão inflamatória. No presente trabalho foi concluído que uma injecão local única na região da ATM de carragenina ou de formalina foi suficiente para induzir reacão inflamatória na articulacão e nos tecidos moles periarticulares. As reacões inflamatórias resultantes da injecão desses agentes flogísticos foram semelhantes, mas o grupo da formalina mostrou infiltrado inflamatório mais persistente.

Synthesis, biological evaluation and kinetic studies of glyceride prodrugs of diclofenac.

The prodrugs (glyceride derivatives) 3a and 3b of diclofenac were prepared by reacting 1, 2, 3-trihydroxy propane-1,3-dipalmitate/stearate with the acid chloride of diclofenac as potential prodrugs to reduce the gastrointestinal toxicity associated with them. These prodrugs were evaluated for their ulcerogenicity, anti-inflammatory and analgesic activity. It was found that the prodrugs were significantly less irritating to the gastric mucosa as indicated by severity index of 0.86, 0.78 compared to 1.6 of diclofenac. The prodrugs 3a and 3b showed better anti-inflammatory and analgesic activity than the parent drugs. The hydrolysis of prodrugs 3a and 3b were studied at pH 3, 4, 5 and 7.4. The HPLC analysis showed that the prodrugs were resistant to hydrolysis at pH 3, 4 and 5 indicating that they did not hydrolyze in acidic environment, whereas at pH 7.4 the prodrugs readily released the parent drug in significant quantities. The plasma levels of diclofenac were also analyzed by HPLC in rats after single oral dose of the prodrugs. The results indicated that the parent drugs were readily released. The concentration of diclofenac during the study was found higher in animals treated with prodrugs 3a and 3b compared with animals treated with diclofenac. The concentration of diclofenac was found to be 38.59, 33.6 and 30.36 microg/ml in animals treated with prodrugs 3a, 3b and diclofenac respectively. In conclusion, all these studies indicated that the glyceride prodrugs of diclofenac might be considered as potential biolabile prodrugs of diclofenac.

Analgesic and anti-inflammatory effects of phosphodiesterase inhibitors.

The aim of the present study was to investigate the role of phosphodiesterase (PDE) enzyme inhibitors namely rolipram and theophylline in pain and inflammation in experimental animals. Rolipram, a selective PDE IV inhibitor and theophylline a nonspecific PDE inhibitor exerted dose dependent analgesic and anti-inflammatory effect against acetic acid-induced writhing in mice and carrageenan-induced paw edema in rats, respectively. Nimesulide (1, 2 mg/kg) produced significant anti-inflammatory effect. Further, nimesulide (0.5 mg/kg) potentiated analgesic effect of rolipram but it failed to modulate the anti-inflammatory effect of PDE inhibitors. Present study suggests that PDE enzymes might be playing a role in nociceptive and inflammatory responses in animals.

Mechanism of action of antiinflammatory effect of fixed oil of Ocimum basilicum Linn.

Fixed oil of O. basilicum was found to possess significant antiinflammatory activity against carrageenan and different other mediator-induced paw edema in rats. Significant inhibitory effect was also observed in castor oil-induced diarrhoea in rats. It also inhibited arachidonic acid- and leukotriene-induced paw edema. The results of antiinflammatory activity of O. basilicum support the dual inhibition of arachidonate metabolism as indicated by its activity in inflammation models that are insensitive to selective cyclooxygenase inhibitors. On the basis of these findings, it possible to conclude that O. basilicum may be a useful antiinflammatory agent which block both cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism.

Anti-Inflammatory activity od debaryomyces hansenii Cu, Zn-SOD

Background. Cu,Zn-superoxide-dismutase, Cu,Zn-SOD, can be obtained from different sources with different anti-inflammatory activities. In this study we compared the antiinflammatory capacity of the marine yeast Debaryomyces hanseii Cu,Zn-SOD (Dh-SOD) with that of bovine erythrocytes (Be-SOD) in preventive an a therapeutic fashion. Methods. Edema was induced by carrageenan injection into the rat hind paw and was evaluated using a mercury plethysmograph. Development of the inflammatory process was followed by volume displacement at time 0 (carrageenan injection), 1, 2, 3, 4, 5, 6, 9, 12, and 24 h thereafter. Three different SOD doses were used in preliminary experiments to prevent edema: 10, 100, and U/kg. Results. The results indicate that, at the lowest dose (10 U/kg), both SOD samples are effective in reducing inflammation in both the prostaglandin and amplification phases (-24.8 percent and -17.5 percent in the case of Be-SOD, and 11.8 percent and -18.7 percent in the case of Dh-SOD, respectively) (p<0.05). At 100 U/kg, Be-SOD also shows good anti-inflammatory activity in all edema phases (-27.1 percent in the serotonin phase; -19.4 percent in the prostaglandin phase; and -20 percent in the amplification phase) (p<0.05), but Dh-SOD was less effective (-10.9 percent, -9.1 percent, and -5.7 percent). At the highest dose tested (1000 U/kg), Dh-SOD was, again more effective than Be-SOD in all three edema phases (-33.1 percent and -1.5 percent; -17.9 percent and -2.6 percent; and -13.8 percent and 6.7 percent, respectively) (p >0.05). When evaluated as a therapeutic alternative, single doses of DH-SOD at 1,000 U/kg, and Be-SOD at 100 U/kg, both showed good anti-inflammatory activities (-31.7 percent and -23.5 percent, respectively) (p < 0.05). Conclusion. For therapy purposes alone, DH-SOD appears to be a better anti-inflammatory agent than Be-SOD in carrageenan-induced edema

Alteraçäo da resposta inflamatória e imunológica em animais portadores de tumor experimental / Alteration on inflammatory and immunological response in animal carriers of experimental tumor

Os autores estudaram em camundongos portadores de tumor de Walker as alteraçöes de resposta a agente inflamatório e as modificaçöes de reaçöes imunológicas, assim como o período no qual se tornam evidentes. Usaram como agente inflamatório a carragenina e como parâmetro imunológico o teste de hipersensibilidade ao BCG. As conclusöes foram que os animais portadores de tumor apresentam diminuiçäo na capacidade de resposta inflamatória inespecífica à carragenina e ao CBG, assim como no teste de hipersensibilidade tardia ao BCG

Anti-inflammatory derivatives of indan-1-acetic acids with low gastric irritancy.

In an attempt to minimize the gastric ulcerogenicity of 6-methoxyindan-1-acetic acid and 5,6-dimethoxyindan-1-acetic acid exhibiting high anti-inflammatory activity, we synthesized their esters, amides and nitrile derivatives. It was found that the anti-inflammatory activity of ethyl esters were almost equal to those of parent acids and phenylbutazone while other derivatives were less potent. Those ethyl esters were also found to be much less ulcerogenic than phenylbutazone.