The essential oil of Hyptis crenata Pohl ex Benth. presents an antiedematogenic effect in mice

Hyptis crenata, commonly known as "salva-do-Marajó", "hortelã-do-campo", and "hortelãzinha", is used in folk medicine in Northeast Brazil as tea or infusion to treat inflammatory diseases. Due to the pharmacological efficacy and the low toxicity of the essential oil of Hyptis crenata (EOHc), we decided to investigate the EOHc antiedematogenic effect in experimental models of inflammation. EOHc was administrated orally at doses of 10-300 mg/kg to male Swiss albino mice. Paw edema was induced by subcutaneous injection in the right hind paw of inflammatory stimuli (carrageenan, dextran, histamine, serotonin, and bradykinin) 60 min after administration of EOHc. EOHc significantly inhibited the induced edema. The inhibitory effect of EOHc on dextran-induced edema extended throughout the experimental time. For the 30, 100, and 300 mg/kg doses of EOHc, the inhibition was of 40.28±1.70, 51.18±2.69, and 59.24±2.13%, respectively. The EOHc inhibitory effect on carrageenan-induced edema started at 10 mg/kg at the second hour (h) and was maintained throughout the observation period. At 30, 100, and 300 mg/kg doses the inhibition started earlier, from 30 min. At the edema peak of 180 min, 56, 76, and 82% inhibition was observed for 30, 100, and 300 mg/kg doses, respectively. Additionally, the effect of EOHc on carrageenan-induced paw edema was influenced by the time of administration. The EOHc also inhibited myeloperoxidase activity. In conclusion, the EOHc showed a potent effect, both preventing and reversing the edema, consistent with its anti-inflammatory use in folk medicine.

Local and systemic effects caused by Crotalus durissus terrificus, Crotalus durissus collilineatus, and Crotalus durissus cascavella snake venoms in swiss mice

Abstract INTRODUCTION: Crotalus envenomations cause serious complications and can be fatal without appropriate treatment. Venom isoforms present and inter/intraspecific variations in the venom composition can result in different symptoms presented by bites by snakes from the same species but from different geographical regions. We comparatively evaluated the local and systemic effects caused by Crotalus durissus terrificus (Cdt), C.d. collilineatus (Cdcolli), and C.d. cascavella (Cdcasc) envenomation. METHODS: Venom chromatography was performed. Proteolytic, phospholipase, and LAAO activities were analyzed. Edema, myotoxicity, hepatotoxicity, nephrotoxicity, and coagulation alterations were evaluated. RESULTS: The venom SDS-PAGE analyses found the presence of convulxin, gyroxin, crotoxin, and crotamine in Cdt and Cdcolli venoms. Crotamine was not present in the Cdcasc venom. Cdt, Cdcollli, and Cdcasc venoms had no proteolytic activity. Only Cdcasc and Cdt venoms had phospholipase activity. LAAO activity was observed in Cdcolli and Cdcasc venoms. Cdcolli and Cdcasc venoms caused 36.7% and 13.3% edema increases, respectively. Cdt venom caused a 10% edema induction compared to those by other venoms. All venoms increased TOTAL-CK, MB-CK, and LDH levels (indicating muscle injury) and ALT, AST, GGT, and ALP levels (markers of liver damage) and were able to induce a neuromuscular blockade. Urea and creatinine levels were also altered in both plasma and urine, indicating kidney damage. Only Cdcolli and Cdcasc venoms increased TAPP and TAP. CONCLUSIONS: Together, these results allow us to draw a distinction between local and systemic effects caused by Crotalus subspecies, highlighting the clinical and biochemical effects produced by their respective venoms.

Polygala anatolica Boiss. et Heldr.: is a potential remedy for inflammation and pain? / Polygala anatolica Boiss. et Heldr.: ¿es un remedio potencial para la inflamación y el dolor?

Species of Polygala genus have been used for the treatment of inflamation and pain in Turkish traditional medicine. The aim of the present study is to assess the anti-inflammatory and analgesic activities of P. anatolica. n-Hexane, ethyl acetate and methanol extracts of the aerial parts and roots of P. anatolica were investigated for their anti-inflammatory and analgesic effects. The methanol extracts prepared from the aerial parts and roots of P. anatolica were found to be active in carrageenan- and PGE2-induced paw edema models and in Whittle method. Methanolic extract of the aerial part inhibited serotonin-induced hind paw edema, while the root extract did not exert inhibitory effect in the same model. In addition, Fr. B and C obtained from the methanol extract of P. anatolica aerial parts showed significant anti- inflammatory activity. Morover, the analgesic effect of the methanol extracts prepared from the roots and aerial parts and Fr.B and Fr.C were found to be statistically significant without inducing ulceration. The methanol extract obtained from the aerial parts of the plant and its saponoside and flavonoid fractions showed anti-inflammatory and analgesic activities in the trials.

Las especies del género Polygala se han utilizado para el tratamiento de la inflamación y el dolor en la medicina tradicional turca. El objetivo del presente estudio es evaluar las actividades antiinflamatorias y analgésicas de P. anatolica. Se investigaron los extractos de n-hexano, acetato de etilo y metanol de las partes aéreas y raíces de P. anatolica por sus efectos antiinflamatorios y analgésicos. Los extractos de metanol preparados a partir de las partes aéreas y raíces de P. anatolica se encontraron activos en modelos de edema de pata inducidos por carragenina y PGE2 por el método de Whittle. El extracto metanólico de la parte aérea inhibió el edema de la pata trasera inducido por serotonina, mientras que el extracto de raíz no ejerció un efecto inhibidor en el mismo modelo. En suma, la fracción B y C obtenidos a partir del extracto metanólico de partes aéreas de P. anatolica mostraron actividad antiinflamatoria significativa. Además, el efecto analgésico de los extractos de metanol preparados a partir de las raíces y las partes aéreas y la fracción B y C resultaron ser estadísticamente significativas sin inducir la ulceración. El extracto de metanol obtenido de las partes aéreas de la planta y sus fracciones de saponósidos y flavonoides mostraron actividades antiinflamatorias y analgésicas en los ensayos.

Antiedematogenic activity of the indole derivative N-salicyloyltryptamine in animal models

ABSTRACT The N-salicyloyltryptamine (NST) is an indole derivative compound analogue to the alkaloid N-benzoyltryptamine. In the present study, the antiedematogenic activity of NST was investigated in animal models. Firstly, the acute toxicity for NST was assessed according to the OECD Guideline no. 423. The potential NST-induced antiedematogenic activity was evaluated by carrageenan-induced paw edema in rats, as well as by dextran-, compound 48/80-, histamine-, serotonin-, capsaicine-, and prostaglandin E2-induced paw edema in mice. The effect of NST on compound 48/80-induced ex vivo mast cell degranulation on mice mesenteric bed was investigated. No death or alteration of behavioral parameters was observed after administration of NST (2000 mg/kg, i.p.) during the observation time of 14 days. The NST (100 and 200 mg/kg, i.p.) inhibited the carrageenan-induced edema from the 1st to the 5th hour (**p<0.01; ***p<0.001). The edematogenic activity induced by dextran, compound 48/80, histamine, serotonin, capsaicin, and prostaglandin E2 was inhibited by NST (100 mg/kg, i.p.) throughout the observation period (**p<0.01; ***p<0.001). The pretreatment with NST (50, 100 or 200 mg/kg, i.p) attenuates the compound 48/80-induced mast cell degranulation (**p<0.01; ***p<0.001). Thus, the inhibition of both mast cell degranulation and release of endogenous mediators are probably involved in the NST-induced antiedematogenic effect.

Severo edema inducido por la terapia dopaminérgica en la enfermedad de Parkinson. Caso clínico / Severe leg edema associated with the use of dopaminergic drugs in Parkinson's disease. Report of one case

The main adverse effects of dopaminergic drugs used in Parkinson's disease are hypotension, somnolence, hallucinations and impulse control disorder. Less common is leg edema. We report on a 68-year-old male receiving levodopa and pramipexole consulting for severe leg edema lasting two years, whose etiology was not ascertained with multiple lab tests. This edema subsided substantially when pramipexole was discontinued and the dose of levodopa was increased to treat motor symptoms.

Desarrollo de infección tuberculosa latente y efectos adversos de la isoniazida durante tratamiento con biológico por enfermedad de Crohn / Development of latent tuberculosis and adverse effects with isoniazid during biologist therapy´s in Crohn´s disease / Desenvolvimento de tuberculose latente durante e efeitos adversos da isoniazida o tratamento com biológicos para a doença de Crohn

Los fármacos anti factor de necrosis tumoral alfa (TNF-α) bloquean una de las citoquinas implicadas en la patogénesis de la Enfermedad Inflamatoria intestinal (EII). Su uso se relaciona con aumento de tuberculosis (TB), por lo que el despistaje previo es obligatorio. En la infección tuberculosa latente (ITBL) se utiliza isoniazida como quimioprofilaxis, fármaco que no se encuentra libre de reacciones adversas. Se presenta y discute el caso de una paciente con reacción adversa en piel secundaria al uso de isoniazida.

Anti-tumor necrosis factor alfa drugs are responsible for blocking one of the cytoquines implicated on inflammatory bowel disease pathogenesis. Its use has been linked to an increase in tuberculosis cases which is why screening before starting treatment is mandatory. Latent tuberculosis is treated with isoniazid as chemoprophylaxis although its use may provoke adverse effects. A case is presented of a patient with skin adverse reaction due to the use of isoniazid.

Os medicamentos anti factor de necrose tumoral alfa (TNF-α ) bloqueiam uma das citocinas envolvidas na patogénese da doença inflamatória intestinal (DII). A sua utilização está associada com um aumento da tuberculose (TB), de modo que a despistagem anterior dessa doença é necessária. Na TB latente, frequentemente se utiliza a isoniazida é usado como quimioprofilaxia, uma droga que não está livre de reações adversas. Apresentamos e discutimos o caso de uma paciente com reação adversa na pele secundária ao uso da isoniazida.

The superoxide anion donor, potassium superoxide, induces pain and inflammation in mice through production of reactive oxygen species and cyclooxygenase-2

It is currently accepted that superoxide anion (O2•−) is an important mediator in pain and inflammation. The role of superoxide anion in pain and inflammation has been mainly determined indirectly by modulating its production and inactivation. Direct evidence using potassium superoxide (KO2), a superoxide anion donor, demonstrated that it induced thermal hyperalgesia, as assessed by the Hargreaves method. However, it remains to be determined whether KO2 is capable of inducing other inflammatory and nociceptive responses attributed to superoxide anion. Therefore, in the present study, we investigated the nociceptive and inflammatory effects of KO2. The KO2-induced inflammatory responses evaluated in mice were: mechanical hyperalgesia (electronic version of von Frey filaments), thermal hyperalgesia (hot plate), edema (caliper rule), myeloperoxidase activity (colorimetric assay), overt pain-like behaviors (flinches, time spent licking and writhing score), leukocyte recruitment, oxidative stress, and cyclooxygenase-2 mRNA expression (quantitative PCR). Administration of KO2 induced mechanical hyperalgesia, thermal hyperalgesia, paw edema, leukocyte recruitment, the writhing response, paw flinching, and paw licking in a dose-dependent manner. KO2 also induced time-dependent cyclooxygenase-2 mRNA expression in the paw skin. The nociceptive, inflammatory, and oxidative stress components of KO2-induced responses were responsive to morphine (analgesic opioid), quercetin (antioxidant flavonoid), and/or celecoxib (anti-inflammatory cyclooxygenase-2 inhibitor) treatment. In conclusion, the well-established superoxide anion donor KO2 is a valuable tool for studying the mechanisms and pharmacological susceptibilities of superoxide anion-triggered nociceptive and inflammatory responses ranging from mechanical and thermal hyperalgesia to overt pain-like behaviors, edema, and leukocyte recruitment.

Resultados a 10 años en trasplantes renales con donantes vivos no relacionados: Experiencia de 22 años / Survival among renal allograft recipients from non related living donors

Background: There is a gap between the number of patients requiring a renal allograft and the number of potential deceased donors (DD). One alternative is using allografts from non-related living donors (NRLD). Aim: To compare survival and complications of renal allograft recipients from DD, related living donors (RLD) and NRLD. Material and Methods: Observational study of a cohort of renal allograft recipients. Of 253 transplants performed in a Chilean region between 1981 and 2003, 20 patients received and allograft from a NRLD. Graft and patient survival of these patients were compared with those of 93 patients receiving an allograft from a related living donor and 140 receiving it from a DD. Patients were followed for 10 years or until death or dialysis requirement. Results: No significant differences between groups in graft and patient survival, deaths with a functioning graft or return to dialysis were observed. Receptors of DD had more hospital admissions during the first years after receiving the graft, usually due to infections. Also a delayed graft function was more common among them. Glomerular filtration rate ten years after the graft was similar among the three groups. Conclusions: No differences in graft or patient survival was observed between patients receiving a renal allograft from NRLD, RLD or DD.

In vivo analgesic, antipyretic, and anti-inflammatory potential in Swiss albino mice and in vitro thrombolytic activity of hydroalcoholic extract from Litsea glutinosaleaves

BACKGROUND: The study was conducted to evaluate the in vitro thrombolytic activity, and in vivo analgesic, anti-inflammatory and antipyretic potentials of different hydrocarbon soluble extracts of Litsea glutinosaleaves for the first time widely used in the folkloric treatments in Bangladesh. This work aimed to create new insights on the fundamental mechanisms of the plant extracts involved in these activities. RESULTS: In thrombolytic activity assay, a significant clot disruption was observed at dose of 1 mg/mL for each of the extracts (volume 100 µL) when compared to the standard drug streptokinase. The n-hexane, ethyl acetate, chloroform, and crude methanolic extracts showed 32.23 ± 0.26, 37.67 ± 1.31, 43.13 ± 0.85, and 46.78 ± 0.9% clot lysis, respectively, whereas the positive control streptokinase showed 93.35 ± 0.35% disruption at the dose of 30,000 I.U. In hot plate method, the highest pain inhibitory activity was found at a dose of 500 mg/kg of crude extract (15.54 ± 0.37 sec) which differed significantly (P <0.01 and P <0.001) with that of the standard drug ketorolac (16.38 ± 0.27 sec). In acetic acid induced writhing test, the crude methanolic extract showed significant (P <0.01 and P <0.001) analgesic potential at doses 250 and 500 mg/kg body weight (45.98 and 56.32% inhibition, respectively), where ketorolac showed 64.36% inhibition. In anti-inflammatory activity test, the crude methanolic extract showed significant (P <0.001) potential at doses 250 and 500 mg/kg body weight (1.51 ± 0.04 and 1.47 ± 0.03 mm paw edema, respectively), where ketorolac showed 1.64 ± 0.05 mm edema after 3 h of carrageenan injection. In antipyretic activity assay, the crude extract showed notable reduction in body temperature (32.78 ± 0.46°C) at dose of 500 mg/kg-body weight, when the standard (at dose 150 mg/kg-body weight) exerted 33.32 ± 0.67°C temperature after 3 h of administration. CONCLUSIONS: Our results yield that the crude hydroalcoholic extract has better effects than the other in all trials. In the context, it can be said that the leaves of L. glutinosa possess remarkable pharmacological effects, and justify its traditional use as analgesic, antipyretic, anti-inflammatory, and thrombolytic agent.

Assessment of pharmacological activities of two medicinal plant of Bangladesh: Launaea sarmentosa and Aegialitis rotundifolia roxb in the management of pain, pyrexia and inflammation

BACKGROUND: The current study aims at evaluating the analgesic, anti-pyretic and anti-inflammatory properties of methanolic extract of the stem, bark and leaves of Launaea sarmentosa and Aegialitis rotundifolia roxb. RESULTS: The AELS and AEAR extract presented a significant (***p < 0.001) dose dependent increase in reaction time in writhing method and showed inhibition of 63.1% and 57.1% respectively at the doses of 400 mg/kg body weight while standard drug showed (P < 0.001) inhibition of 69.23%. In tail immersion method, AELS and AEAR showed maximum time of tail retention at 30 min in hot water i.e. 6.93 sec and 6.54 sec respectively at highest doses of 400 mg/kg body weight than lower dose while standard pentazocine showed reaction time of 7.62 sec. The AELS and AEAR extract also exhibited promising anti-inflammatory effect as demonstrated by statistically significant inhibition of paw volume by 32.48% and 26.75% respectively at the dose of 400 mg/kg body weight while the value at the dose of 200 mg/kg body weight were linear to higher dose at the 3rd hour of study. On the other hand, Standard indomethacin inhibited 40.13% of inflammation (***P < 0.001). In Cotton-pellet granuloma method, AELS and AEAR extract at the dose of 400 mg/kg body weight exhibited inhibition of inflammation of 34.7% and 29.1% respectively while standard drug showed (P < 0.001) inhibition of 63.22%. Intraperitoneal administration of AELS and AEAR showed dose dependent decrease in body temperature in brewer's yeast induced hyperthermia in rats at both doses. However, AELS significantly decreased body temperature (***p < 0.001) at 400 mg/kg compared to control. CONCLUSIONS: Present work propose that the methanolic extract of Launaea sarmentosa and Aegialitis rotundifolia roxb possesses dose dependent pharmacological action which supports its therapeutic use in folk medicine possibly mediated through the inhibition or blocking of release of prostaglandin and/or actions of vasoactive substances such as histamine, serotonin and kinins.

Amitriptyline, clomipramine, and maprotiline attenuate the inflammatory response by inhibiting neutrophil migration and mast cell degranulation

Objective: Despite the recognized anti-inflammatory potential of heterocyclic antidepressants, the mechanisms concerning their modulating effects are not completely known. Thus, we evaluated the anti-inflammatory effect of amitriptyline, clomipramine, and maprotiline and the possible modulating properties of these drugs on neutrophil migration and mast cell degranulation. Methods: The hind paw edema and air-pouch models of inflammation were used. Male Wistar rats were treated with saline, amitriptyline, clomipramine or maprotiline (10, 30, or 90 mg/kg, per os [p.o.]) 1 h before the injection of carrageenan (300 μg/0.1 mL/paw) or dextran (500 μg/0.1 mL/paw). Then, edema formation was measured hourly. Neutrophil migration to carrageenan (500 μg/pouch) and N-formyl-methionyl-leucyl-phenylalanine (fMLP) (10-6 M/mL/pouch) was also investigated in 6-day-old air-pouch cavities. Compound 48/80-induced mast cell degranulation was assessed in the mesenteric tissues of antidepressant-treated rats. Results: All tested antidepressants prevented both carrageenan- and dextran-induced edema. The anti-inflammatory effect of these drugs partially depends on the modulation of neutrophil migration, since they significantly counteracted the chemotactic response of both carrageenan and fMLP (p < 0.01). Furthermore, amitriptyline, clomipramine and maprotiline inhibited compound 48/80-induced mast cell degranulation (p < 0.001). Conclusions: These results suggest an important anti-inflammatory role of heterocyclic antidepressants, which is dependent on the modulation of neutrophil migration and mast cell stabilization. .

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.

Applications of the hexanic fraction of Agave sisalana Perrine ex Engelm (Asparagaceae): control of inflammation and pain screening

The present study evaluated the anti-inflammatory and analgesic properties of Agave sisalana Perrine in classic models of inflammation and pain. The hexanic fraction of A. sisalana (HFAS) was obtained by acid hydrolysis followed by hexanic reflux. Anti-inflammatory properties were examined in three acute mouse models (xylene ear oedema, hind paw oedema and pleurisy) and a chronic mouse model (granuloma cotton pellet). The antinociceptive potential was evaluated in chemical (acetic-acid) and thermal (tail-flick and hot-plate test) models of pain. When given orally, HFAS (5, 10, 25 and 50 mg/kg) reduced ear oedema (p < 0.0001; 52%, 71%, 62% and 42%, respectively). HFAS also reduced hind paw oedema at doses of 10 mg/kg and 25 mg/kg (p < 0.05; 42% and 58%, respectively) and pleurisy at doses of 10 mg/kg and 25 mg/kg (41% and 50%, respectively). In a chronic model, HFAS reduced inflammation by 46% and 58% at doses of 10 mg/kg and 25 mg/kg, respectively. Moreover, this fraction showed analgesic properties against the abdominal writhing in an acetic acid model (at doses of 5-25 mg/kg) with inhibitory rates of 24%, 54% and 48%. The HFAS also showed an increased latency time in the hot-plate (23% and 28%) and tail-flick tests (61% and 66%) for the 25 mg/kg and 50 mg/kg doses, respectively. These results suggest that HFAS has anti-inflammatory and analgesic properties.

Phytochemistry, anti-inflammatory and analgesic activities of the aqueous leaf extract of Lagenaria breviflora (Cucurbitaceae) in laboratory animals

The plant, and especially the fruit of Lagenaria breviflora is widely used in folklore medicine in West Africa as a herbal remedy for the treatment of human measles, digestive disorders, and as wound antiseptics (e.g. umbilical incision wound), while livestock farmers use it for Newcastle disease and coccidiosis treatment in various animal species, especially poultry. The purpose of this study was to contribute with new information on this plant leaves extract effect, as few studies have considered their effects. We collected fresh leaves of Lagenaria breviflora from the school farm of the University of Ibadan, Nigeria in May 2011. Dried leaves were ground and a 200g sample was used to prepare the extract. The grounded leaves material was allowed to shake in 1 000mL distilled water for 48h, in an orbital shaker at room temperature of 24°C. The obtained extract was filtered and concentrated to dryness under reduced pressure at 40ºC, and the thick solution was lyophilized, for a final extract yield of 12.6%. Standard phytochemical methods were used to test the presence of saponins, alkaloids, tannins, anthraquinones, cardiac glycosides, cyanogenetic glycosides and flavonoids. The anti-inflammatory activity of the aqueous leaf extract of the plant was assessed using carrageenan-induced paw edema and histamine-induced paw edema in rats. The analgesic effect was determined using the acetic acid writhing method as well as formalin test in mice. Our results showed that the extract at 100 and 200mg/ kg body weight significantly reduced the formation of the oedema induced by carrageenan and histamine. In the acetic acid-induced writhing model, the extract showed a good analgesic effect characterized by reduction in the number of writhes when compared to the control. The extract caused dose-dependent decrease of licking time and licking frequency in rats injected with 2.5% formalin, signifying its analgesic effect. These results were however less than those of indomethacin, the reference drug used in this study. Since the plant extract reduced significantly the formation of oedema induced by carrageenan and histamine, as well as reduced the number of writhes in acetic acid-induced writhing models and dose-dependent decrease of licking frequency in rats injected with 2.5% formalin, the results have validated the basis for the traditional use of Lagenaria breviflora against inflamed purulent wounds, swellings, and bruises seen in some infectious diseases such as New Castle disease.

La planta, y sobre todo el fruto de Lagenaria breviflora es ampliamente utilizada en medicina tradicional en África occidental como un remedio herbal para el tratamiento del sarampión humano, trastornos digestivos y como antiséptico de la herida umbilical (por ejemplo, herida de incisión), mientras que los ganaderos la utilizan para tratar la enfermedad de Newcastle y la coccidiosis en varias especies animales, especialmente aves de corral. El propósito de este estudio fue analizar el efecto del extracto de esta planta, ya que hay pocos estudios sobre la temática. Se recolectaron hojas frescas de Lagenaria breviflora en la finca demostrativa de enseñanza de la Universidad de Iba- dan, Nigeria, en mayo 2011. Las hojas secas se trituraron y una muestra de 200g fue utilizada para preparar el extracto. El material se mezcló en 1 000ml de agua destilada durante 48 horas, en un agitador orbital a temperatura ambiente de 24 C. El extracto obtenido se filtró y se concentró hasta sequedad a una presión baja y a 40 C, la solución espesa se liofilizó, para un rendimiento de extracto final de 12.6. Para probar la presencia de saponinas, alcaloides, taninos, antraquinonas, glucósidos cardíacos, glucósidos cianogénicos y flavonoides se utilizaron los métodos fitoquímicos estándares. La actividad anti-inflamatoria del extracto acuoso de hojas de la planta se evaluó mediante la inducción de un edema por carragenina e histamina en la pata de las ratas. El efecto analgésico se determinó utilizando el método de contorsiones inducidas por ácido acético y la prueba de formalina en ratones. Nuestros resultados mostraron que el extracto de 100 y 200mg/kg de peso corporal redujo significativamente la formación de edema inducido por la carragenina e histamina. En el modelo de contorsiones inducidas por ácido acético, el extracto mostró un buen efecto analgésico caracterizado por una reducción en el número de retortijones en comparación con el control. El extracto causó una disminución dependiente de la dosis en el tiempo y frecuencia de lameo en ratas inyectadas con 2.5% de formalina, demostrando su efecto analgésico. Estos resultados sin embargo fueron menores que los de la indometacina, fármaco de referencia utilizado en este estudio. El extracto de la planta redujo significativamente la formación de edema inducido por carragenina e histamina, así como la baja en el número de retortijones por ácido acético y una disminución de la dosis-dependiente de la frecuencia de lameo en ratas inyectadas con formalina al 2.5%, los resultados validan el uso tradicional de Lagenaria breviflora contra la inflamación de las heridas purulentas, inflamaciones y contusiones que se dan en algunas enfermedades infecciosas como la enfermedad de New Castle.

Pulsed ultrasound therapy accelerates the recovery of skeletal muscle damage induced by Bothrops jararacussu venom

We studied the effect of pulsed ultrasound therapy (UST) and antibothropic polyvalent antivenom (PAV) on the regeneration of mouse extensor digitorum longus muscle following damage by Bothrops jararacussu venom. Animals (Swiss male and female mice weighing 25.0 ± 5.0 g; 5 animals per group) received a perimuscular injection of venom (1 mg/kg) and treatment with UST was started 1 h later (1 min/day, 3 MHz, 0.3 W/cm², pulsed mode). Three and 28 days after injection, muscles were dissected and processed for light microscopy. The venom caused complete degeneration of muscle fibers. UST alone and combined with PAV (1.0 mL/kg) partially protected these fibers, whereas muscles receiving no treatment showed disorganized fascicules and fibers with reduced diameter. Treatment with UST and PAV decreased the effects of the venom on creatine kinase content and motor activity (approximately 75 and 48%, respectively). Sonication of the venom solution immediately before application decreased the in vivo and ex vivo myotoxic activities (approximately 60 and 50%, respectively). The present data show that UST counteracts some effects of B. jararacussu venom, causing structural and functional improvement of the regenerated muscle after venom injury.

Anti-venom potential of aqueous extract of stem bark of Mangifera indica L. against Daboia russellii (Russell’s viper) venom.

Several plant extracts rich in pharmacologically active compounds have shown to antagonize venom of several species. Mangifera indica has been used against snakebite by the traditional healers, However, there is paucity of scientific data in support. In this study, we evaluated the antivenom potential of aqueous extract of stem bark of M. indica against D. russellii venom-induced pharmacological effects such as life myotoxicity, edema, LD50 etc. The extract inhibited the phospholipase, protease, hyaluronidase, 5`nucleotidase, ATPase and alkaline phosphomonoesterase activities with varying IC50 values. It significantly inhibited both metalloproteases and serine proteases activities. Further, the extract significantly reduced the myotoxicity of the venom, as evident by the reduction of serum creatin kinase and lactate dehydrogenase activities. Though the extract completely inhibited in vitro PLA2 activity, it was unable to completely inhibit in situ hemolytic and in vivo edema-inducing activities, usually brought about by PLA2s. In lethality studies, co-injection of the venom preincubated with the extract showed higher protection than the independent injection of venom, followed by the extract in the mice. However, in both the cases the extract -a cocktail of inhibitors significantly increased the survival time, when compared to that of mice injected (i.p) with the venom alone. These results encourage further studies on the potential use of cocktail of inhibitors in improving the treatment of snake envenomation. Further, this study substantiates the use of M. indica as an antidote against snakebite by the traditional healers.

Anti-inflammatory, antinociceptive, and antipyretic effects of methanol extract of Cariniana rubra stem bark in animal models

Cariniana rubra Miers (Lecythidaceae), popularly known as "jequitibá-vermelho'', is a large Brazilian tree whose bark is used in infusion and decoction for the treatment of inflammatory conditions. This study aims to assess the anti-inflammatory, antinociceptive, and antipyretic effects of Cariniana rubra methanolic stem bark extract (EM Cr) using experimental animals. Anti-inflammatory activity of EM Cr was tested on carrageenan and dextran-induced rat paw edema, carrageenan-induced pleurisy in rats and acetic acid-increase vascular permeability in mice. Antinociceptive and antipyretic activities were evaluated using acetic acid-induced writhing, formalin and hot-plate tests in mice, as well as brewer's yeast-induced pyrexia in rats. The extract inhibitied carrageenan and dextran-induced edema, reduced exudate volume and leukocyte migration on the carrageenan-induced pleurisy and on the vascular permeability increase induced by acetic acid. The EM Cr inhibited nociception on the acetic acid-induced writhing and in the second phase of formalin test, and decreased rectal temperature. It was, however, inactive against thermal nociception.Phytochemical analysis with EM Cr showed the occurrence of saponins, triterpenes, sterols and phenolic compounds. Phytosterols (β-sitosterol, stigmasterol), pentacyclic triterpenes (α- and β-amyrin as a mixture), arjunolic acid, a phytosterol glycoside (sitosterol 3-O-β-D-glucopyranoside), and triterpenoid saponins (28-β-glucopyranosyl-23-O-acetyl arjunolic acid; 3-O-β-glucopyranosyl arjunolic acid and 28-O-[α-L-Rhamnopyranosyl-(1→2)-β-glucopyranosyl]-23- O-acetyl arjunolic acid) were the main identified compounds. It can be presumed that EM Cr caused their effects by inhibiting the liberation and/or action of different inflammatory mediators. These findings support the traditional use of Cariniana rubra preparations to treat inflammation.

Cariniana rubra Miers (Lecythidaceae), popularmente conhecido como "jequitibá-vermelho'', é uma árvore brasileira de grande porte, cuja casca é utilizada nas formas de infusão e decocção para o tratamento de condições inflamatórias. Os efeitos antiinflamatório, antinociceptivo e antipirético do extrato metanólico da casca do caule de Cariniana rubra (EM Cr) foram avaliados em animais experimentais. A atividade antiinflamatória do EM Cr foi testada nos modelos de edema depata induzido por carragenina e dextrana em ratos, pleurisia induzida por carragenina em ratos e permeabilidade vascular aumentada por ácido acético em ratos. As atividades antinociceptiva e antipirética foram avaliadas utilizando os modelos de nocicepções induzidos por ácido acético e formalina, placa quente em camundongos e de pirexia, pela injeção de levedura de cerveja em ratos. O extrato inibiu o edema induzido porcarragenina e dextrana, reduziu o volume de exsudato e a migração de leucócitos na pleurisia induzida por carragenina eo aumento da permeabilidade vascular induzida por ácidoacético. O EM Cr inibiu a nocicepção nas contorções induzidas por ácido acético e na segunda fase do teste de formalina e diminuiu a temperatura retal. No entanto, foi inefetivo no teste da placa quente. A análise química por via úmida deu resultados positivos para saponinas, triterpenos, esteroides e compostos fenólicos. Fitosteróis e triterpenóides pentacíclicos (β-sitosterol, estigmasterol, α and β-amirinas em mistura e ácido arjunólico) e as saponinas triterpenoidais: 3-O-β-D-glucopiranosideo de sitosterol; ácido arjunólico 28-β-glucopiranosila-23-O-acetila; ácido arjunólico 3-O-β-glucopiranosila e ácido arjunólico 28-O-[α-L-rhamnopiranosil-(1→2)-β-D-glucopiranosila]-23-O-acetila. Pode-se presumir que os efeitos do EM Cr foram causados pela inibição da liberação e/ou ação de diversos mediadores inflamatórios. Estes resultados validam o uso tradicional das preparações caseiras de Cariniana rubra para tratar a inflamação.

Anti-inflammatory and analgesic activities of red seaweed Dichotomaria obtusata / Atividades anti-inflamatória e analgésica da alga marinha vermelha Dichotomaria obtusata

The aim of the present work was to investigate the anti-inflammatory and analgesic effects of red seaweed Dichotomaria obtusata, using classic tests in mice (ear edema induced by TPA and writhing induced by acetic acid). The qualitative chemical composition of the aqueous extract (lactones, phenols, triterpenes, steroids and reduced carbohydrates) obtained from this alga was also determined. The results showed that Dichotomaria obtusata (12.5, 25 and 50 mg/kg, ip) inhibited mouse ear edema in a dose-dependent manner. In the writhing test, aqueous extract (12.5, 25, 50 and 100 mg/kg, ip and 100, 200, 400, 800 mg/kg, po) significantly reduced abdominal writhes. In conclusion, this study demonstrated the anti-inflammatory and antinociceptive activities of aqueous extract of D. Obtusata in experimental models. These results suggest that D. obtusata aqueous extract possesses therapeutic potential in the treatment of peripheral painful or/and inflammatory conditions.

O objetivo do presente trabalho é centrado nos efeitos antiinflamatórios e analgésicos da alga vermelha Dichotomaria obtusata por meio de clássicos testes em camundongos (edema de orelha induzido por TPA e contorção induzida por ácido acético). Também foi determinada a composição química qualitativa do extrato (lactonas, fenóis, triterpenos, esteróides e carboidratos reduzidos). Os resultados mostraram que de Dichotomaria obtusata (12,5, 25 e 50 mg/kg, ip) inibiu o edema de orelha do camundongo de forma dose-dependente. No teste de contorção, extrato aquoso (12,5, 25, 50 e 100 mg/kg, ip e 100, 200, 400, 800 mg/kg, po) reduziu o contorções abdominais de forma significativa. Em conclusão, o estudo demonstrou a atividades antiinflamatória e antinociceptiva do extrato aquoso em modelos experimentais. Estes resultados sugerem que o extrato aquoso D.obtusata possuem potencial terapêutico no tratamento de dor periférica e/ou de doenças inflamatórias.

Inhibition of carrageenan-induced expression of tissue and plasma prekallikreins mRNA by low level laser therapy in a rat paw edema model / Inibição da expressão de RNA mensageiro de pré-calicreínas tecidual e plasmática pela laserterapia em modelo de edema de pata induzido pela carragenina em ratos

BACKGROND: Low level laser therapy (LLLT) has been used clinically in order to treat inflammation, where tissue and plasma prekallikrein have crucial importance. Plasma prekallikrein (PPK) is synthesized by the hepatocytes and secreted into the bloodstream, where it participates in the surface-dependent activation of blood coagulation, fibrinolysis, kinin generation and inflammation. Tissue prekallikrein is associated with important disease states (including cancer, inflammation, and neurodegeneration) and has been utilized or proposed as clinically important biomarker or therapeutic target of interest. OBJECTIVE: To evaluate if LLLT modulates tissue and plasma prekallikreins mRNA expression in the carrageenan-induced rat paw edema. METHODS: Experimental groups were assigned as followed: A1 (Control-saline), A2 (Carrageenan-only), A3 (laser 660nm only) and A4 (Carrageenan + laser 660nm). Edema was measured by a plethysmometer. Subplantar tissue was collected for the quantification of prekallikreins mRNA by Real time-Polymerase Chain Reaction. RESULTS: A significantly decrease in the edema was observed after laser irradiation. Expression of prekallikreins increased after carrageenan injection. Tissue and plasma prekallikrein mRNA expression significantly decreased after LLLT's 660nm wavelength. CONCLUSION: These results suggest that expression of tissue and plasma prekallikreins is modulated by LLLT, which can be used in clinical practice due to its anti-inflammatory effects.

CONTEXTUALIZAÇÃO: A laserterapia de baixa potência tem sido usada para o tratamento de processos inflamatórios diversos em que a calicreína tecidual e a plasmática possuem participação ativa. A pré-calicreína plasmática (PPK) é sintetizada pelos hepatócitos e secretada na corrente sanguínea, onde participa da ativação da coagulação, fibrinólise, geração de cininas e inflamação. A pré-calicreína tecidual está associada com importantes doenças (incluindo câncer, inflamação e neurodegeneração) e tem sido utilizada ou sugerida clinicamente como importante biomarcador ou alvo terapêutico. OBJETIVO: Avaliar se a laserterapia altera a expressão gênica da pré-calicreína tecidual e da plasmática no modelo de inflamação aguda induzida pela carragenina. MÉTODOS: Quarenta ratos foram separados em quatro grupos experimentais: A1 (controle), A2 (carragenina, apenas), A3 (laser 660nm, apenas) e A4 (Carragenina + laser 660nm). O edema foi medido por um pletismômetro. Tecido subplantar foi coletado para a quantificação de RNA mensageiro (RNAm) de pré-calicreínas tecidual e plasmática por PCR em tempo real. RESULTADOS: Observou-se uma diminuição significativa no volume de edema após irradiação com laser 660nm. A expressão de RNAm de pré-calicreínas tecidual e plasmática aumentou após a inoculação de carragenina, entretanto a expressão gênica das pré-calicreínas diminuiu significantemente após laserterapia de baixa potência de 660nm. CONCLUSÃO: Os resultados sugerem que a expressão de RNAm das pré-calicreínas tecidual e plasmática é modulada pela laserterapia de baixa potência, podendo ser alvo terapêutico para tratamento de processos inflamatórios.

In vivo and in vitro anti-inflammatory and anti-nociceptive activities of lovastatin in rodents

Statins are among the most prescribed drugs in recent clinical practice. They are also known for their pleiotropic actions, which are independent of their lipid-lowering properties. The effect of lovastatin was investigated against carrageenan-induced paw edema in male Wistar rats (200-250 g) and on leukocyte migration, as measured by carrageenan-induced peritonitis in male Swiss mice (20-25 g), which are models of acute inflammation. Lovastatin (administered 1 h prior to carrageenan), at oral doses of 2, 5, and 10 mg/kg, markedly attenuated paw edema formation in rats at the 4th hour after carrageenan injection (25, 43, and 37 percent inhibition, respectively). Inhibitions of 20, 45 and 80 percent were observed in the leukocyte migration, as evaluated by carrageenan-induced peritonitis in mice with lovastatin doses of 0.5, 1 and 5 mg/kg, as compared to controls. Furthermore, lovastatin (administered 1 h before initiation) reduced the nociceptive effect of the formalin test in mice, at both phases, at doses of 2, 5, and 10 mg/kg: first phase (51, 65, and 70 percent, respectively) and second phase (73, 57, and 66 percent inhibition of licking time, respectively). The anti-nociceptive activity of lovastatin was inhibited by naloxone (3 mg/kg, sc). Lovastatin (0.01, 0.1, and 1 µg/mL) inhibited by 23, 79, and 86 percent, respectively, the release of myeloperoxidase from human neutrophils. Leukocyte (predominantly neutrophils) infiltration was almost completely reduced by lovastatin treatment, as observed in the model of acute paw edema with hematoxylin and eosin staining. In addition, lovastatin decreased the number of cells expressing tumor necrosis factor-α (TNF-α) and the inducible form of nitric oxide synthase (iNOS) activity. Therefore, the alterations in leukocyte activity and cytokine release could contribute to the anti-inflammatory activity of lovastatin.