Inyección Intraarticular Única de Ácido Hialurónico en la Artrosis de Rodilla: Estudio Multicéntrico Prospectivo Abierto (ART-ONE 75) mediante Comparación Post-Hoc con Placebo.

INTRODUCCIÓN: La viscosuplementación del líquido sinovial mediante la inyección intraarticular (IA) de ácido hialurónico (AH) es un tratamiento sintomático ampliamente utilizado en la artrosis de rodilla (AR). Además de los productos diseñados para realizar inyecciones múltiples (normalmente de 3 a 5 inyecciones, en intervalos de 1 semana), se presta especial atención a los productos de una única inyección, ya que ofrecen ventajas específicas, como son un menor número de visitas al médico y de intervenciones invasivas con sus riesgos asociados. Sin embargo, aún existen dudas sobre la eficacia de estas inyecciones únicas, en comparación con los regímenes de inyecciones múltiples. MÉTODOS: Se realizó un estudio multicéntrico, abierto, prospectivo, post-mercado (ART-ONE 75) con el producto de inyección única ARTHRUM 2,5% (3 ml, 75 mg AH), en 214 pacientes que sufrían de AR. Los pacientes fueron seguidos en D30, D60, D120 y D180 (días). El perfil promedio de los pacientes en el momento de la inclusión fue de 62,9 años, 56% mujeres, grados I-III de Kellgren-Lawrence (46% KL III), IMC de 27,2 kg/m2 y 4 años desde el diagnóstico de AR. Se realizó una comparación post-hoc con una inyección IA única de placebo (326 pacientes, agrupados de 3 estudios ECA), que proporcionaron un perfil de paciente similar. RESULTADOS: el criterio principal fue la variación desde el inicio de la puntuación de la escala WOMAC A (dolor, escala 0-100) en D60, que se redujo en 28,9 (17,4) para la población por intención de tratar (ITT, por sus siglas en inglés) (199 pacientes), 28,0 (17,8) para la población por protocolo (PP) en la inclusión (175 pacientes), y en 27,7 (16,8) para la población PP al finalizar (143 pacientes).Los criterios secundarios y accesorios incluyeron WOMAC A en otras ocasiones, WOMAC B (rigidez), WOMAC C (función), calidad de vida y discapacidad en cada momento de seguimiento. Todos los índices mejoraron significativamente y continuaron mejorando al final del estudio. La evaluación terapéutica en D180 mostró que más del 75% de los pacientes se encontraban satisfechos con la reducción del dolor, la mejora de la movilidad, y la reducción de analgésicos y AINE. El porcentaje de pacientes definidos como respondedores de OMERACT-OARSI fue superior al 86%, a partir de D60 y en adelante. La tolerancia general fue buena, sin que ocurriera ningún evento adverso grave. El resultado de la comparación post-hoc para la escala WOMAC A mostró un tamaño del efecto [IC 95%] desde TE = 0,33 [0,15; 0,51] en D60 a TE = 0,65 [0,45; 0,85] en D180 (p <0,001), frente a la inyección de placebo (solución salina), lo cual es un resultado clínicamente relevante a favor de ARTHRUM 2,5%. CONCLUSIÓN: El presente estudio confirma la eficacia clínica de una única inyección IA de 3 ml de solución de AH conteniendo 75 mg de AH nativo de alto PM (> 2 MDa).

[Anti-inflammatory effect of milk whey from different species after in vitro digestion]. / Efecto antiinflamatorio del suero de leche de diferentes especies tras una digestión in vitro.

Introduction: Introduction: there is a close relationship between obesity, gut health and immune system. A low-grade of inflammation, which could precede obesity, may have implications for the development of metabolic syndrome and insulin resistance. Objective: analyzing the anti-inflammatory capacity of several types of whey (cow, sheep, goat and a mixture of them). Methods: an in vitro model of intestinal inflammation employing a cell co-culture (Caco-2 and RAW 264.7) was performed after an in vitro digestion and fermentation (simulating mouth-to-colon conditions). Inflammatory markers such as IL-8 and TNF-α, as well as the transepithelial electrical resistance (TEER) of Caco-2 monolayer, were determined. Results: digested and fermented whey had a protective effect on cell permeability, being lower in the case of fermented goat whey and mixture. The anti-inflammatory activity of whey was greater the more digestion progressed. Fermented whey showed the greatest anti-inflammatory effect, inhibiting IL-8 and TNF-α secretion, probably due to its composition (protein degradation products such as peptides and amino acids, and SCFA). However, fermented goat whey did not show this degree of inhibition, perhaps due to its low SCFA concentration. Conclusion: milk whey, especially after being fermented in the colon, can be useful nutritional strategy to preserve the intestinal barrier and mitigate the low-grade of inflammation that characterizes metabolic disorders and obesity.

Introducción: Introducción: existe una estrecha relación entre obesidad, salud intestinal y sistema inmune. Un bajo grado de inflamación, que precedería a la obesidad, puede tener implicaciones en el desarrollo de síndrome metabólico y resistencia a la insulina. Objetivo: analizar el poder antiinflamatorio de varios tipos de lactosuero (vaca, oveja, cabra y mezcla de los anteriores). Metodología: se utilizó un modelo in vitro de inflamación intestinal, empleando un cocultivo celular (Caco-2 y RAW 264.7). Para ello, se realizó una digestión y fermentación in vitro (simulando las condiciones de boca a colon). Se estudiaron IL-8 y TNF-α como marcadores inflamatorios y la resistencia eléctrica transepitelial celular (RETE) de la monocapa celular Caco-2. Resultados: el suero digerido y fermentado tuvo un efecto protector sobre la permeabilidad celular que fue menor en el caso de lactosuero fermentado de cabra y mezcla. La actividad antiinflamatoria del suero fue mayor cuanto más progresaba la digestión. El lactosuero fermentado mostró el mayor efecto antiinflamatorio, inhibiendo la secreción de IL-8 y TNF-α, probablemente debido a su composición (productos de degradación proteica como péptidos y aminoácidos, y ácidos grasos de cadena corta [AGCC]). Sin embargo, el suero fermentado de cabra no mostró ese grado de inhibición, quizás debido a su baja concentración en AGCC. Conclusión: el lactosuero, sobre todo tras ser fermentado en colon, puede ser una estrategia nutricional útil para preservar la barrera intestinal y mitigar el bajo grado de inflamación que caracteriza a desordenes metabólicos y a la obesidad.

The effect of maternal treatment with diclofenac sodium and thymoquinone on testicular parameters in rat offspring.

INTRODUCTION AND OBJECTIVE: Diclofenac sodium (DS) can have toxic effects on various tissues and organs, as well as causing foetal and new-born malformations. Thymoquinone (TQ), the basic bioactive compound of black seed oil, is an antioxidant and antineoplastic substance. The aim of our study was to explore the effects of DS and TQ exposure during gestation on offspring rat testicular histology. MATERIALS AND METHODS: Mother pregnant rats were divided into five groups: control, saline, DS, TQ and DS plus TQ (DS+TQ) four animals for each group. They were then treated as follows between day of 5 and 15 of gestation: the control group received no treatment. The saline group received physiological saline (1mg/kg/d) via the intraperitoneal (IP) route; the DS group received an intramuscular (IM) injection of DS (6.1mg/kg/d); the TQ group received TQ (5mg/kg/d) dissolved in drinking water; and the DS+TQ group received DS (6.1mg/kg/d) and TQ (5mg/kg/d) dissolved in water. After birth, the male rats were fed for four weeks, and at the end of this period offspring were sacrificed. Stereological methods, physical disector and Cavalieri principle were used for particle counting and volume estimation respectively. RESULTS: The results revealed a significant decrease in the total number of Sertoli and Leydig cells in 4-week-old rats in the DS group (p<0.05), and TQ not have provide protection against this adverse effect of DS. CONCLUSIONS: In this study, DS at a dose of 6.1mg/kg, equivalent to a dose of 1mg/kg in humans, decreased the number of Sertoli and Leydig cells, and TQ did not have a protective effect against the adverse effect of DS during the gestation period. These results show that new dose depend studies on TQ and DS interaction are requested to see protective effect of TQ.

The Mexican consensus on the diagnosis, treatment, and prevention of NSAID-induced gastropathy and enteropathy. / Consenso mexicano sobre diagnóstico, prevención y tratamiento de la gastropatía y enteropatía por antiinflamatorios no esteroideos.

More than 30 million persons worldwide take nonsteroidal anti-inflammatory drugs (NSAIDs) on a daily basis, and annual consumption is increasing. In addition to their analgesic and anti-inflammatory properties, NSAIDs also produce well-known gastrointestinal adverse events. There is no consensus in Mexico on the diagnosis, treatment, and prevention of NSAID-induced gastropathy and enteropathy, and so the Asociación Mexicana de Gastroenterología brought together a group of experts to establish useful recommendations for the medical community. Thirty-three recommendations were formulated in the present consensus, highlighting the fact that the risk for NSAID-induced gastrointestinal toxicity varies according to the drug employed and its pharmacokinetics, which should be taken into account at the time of prescription. The risk factors for gastroduodenal complications due to NSAIDs are: a history of peptic ulcer, age above 65 years, high doses of NSAIDs, Helicobacter pylori infection, and the presence of severe comorbidities. The symptoms and gastroduodenal damage induced by NSAIDs vary, ranging from an asymptomatic course to the presentation of iron-deficiency anemia, bleeding, stricture, and perforation. Capsule endoscopy and enteroscopy are direct diagnostic methods in NSAID enteropathy. Regarding prevention, the minimum dose of an NSAID needed to achieve the desired effect, administered for the shortest period of time, is the recommendation. Finally, proton pump inhibitors are the gold standard for the prophylaxis and treatment of gastroduodenal effects, but they are not useful in enteropathy.

Melatonin ameliorates the drug induced nephrotoxicity: Molecular insights.

BACKGROUND: Drug-induced nephrotoxicity is a frequent adverse event that can lead to acute or chronic kidney disease and increase the healthcare expenditure. It has high morbidity and mortality incidence in 40-70% of renal injuries and accounts for 66% cases of renal failure in elderly population. OBJECTIVE: Amelioration of drug-induced nephrotoxicity has been long soughed to improve the effectiveness of therapeutic drugs. This study was conducted to review the melatonin potential to prevent the pathogenesis of nephrotoxicity induced by important nephrotoxic drugs. METHODS: We analyzed the relevant studies indexed in Pubmed, Medline, Scielo and Web of science to explain the molecular improvements following melatonin co-administration with special attention to oxidative stress, inflammation and apoptosis as key players of drug-induced nephrotoxicity. RESULTS: A robust consensus among researchers of these studies suggested that melatonin efficiently eradicate the chain reaction of free radical production and induced the endogenous antioxidant enzymes which attenuate the lipid peroxidation of cellular membranes and subcellular oxidative stress in drug-induced nephrotoxicity. This agreement was further supported by the melatonin role in disintegration of inflammatory process through inhibition of principle pro-inflammatory or apoptotic cytokines such as TNF-α and NF-κB. These studies highlighted that alleviation of drug-induced renal toxicity is a function of melatonin potential to down regulate the cellular inflammatory and oxidative injury process and to stimulate the cellular repair or defensive mechanisms. CONCLUSION: The comprehensive nephroprotection and safer profile suggests the melatonin to be a useful adjunct to improve the safety of nephrotoxic drugs.

Anti-inflammatory Therapies for Cardiovascular Disease: Signaling Pathways and Mechanisms.

Cardiovascular diseases (CVD) are the clinical manifestation of atherosclerosis, a chronic inflammatory disease promoted by several risk factors such as dyslipidemia, type 2 diabetes mellitus, hypertension, and smoking. Acute CVD events are the result of an unresolved inflammatory chronic state that promotes the rupture of unstable plaque lesions. Of note, the existing intensive therapies modify risk factors but do not prevent life-threatening recurrent ischemic events in high-risk patients, who have a residual inflammatory risk displayed by increased C-reactive protein (CRP) levels. Better understanding of the role of innate and adaptive immunity in plaque development and rupture has led to intensive investigation of anti-inflammatory strategies for CVD. Some of them are being tested in specific clinical trials and use lower doses of existing medications originally developed for other inflammatory diseases such as rheumatoid arthritis and psoriasis, which have high CVD risk. Other investigations are retrospective and meta-analyses of existing clinical trials that evaluate the incidence of CVD in these inflammatory diseases. Others are based on preclinical testing such as vaccines. In this article, we summarize the main anti-inflammatory strategies and associated molecular mechanisms that are being evaluated in preclinical or clinical CVD studies.

Croton stipulaceus Kunth, a native Mexican medicinal plant with antioxidant and anti-inflammatory activities / Croton stipulaceus Kunth, planta medicinal mexicana con actividad antioxidante y antiinflamatoria

Leaves of Croton stipulaceuswere extracted (EHex, ECHCl3and EEtOH extracts) to assesstheir antioxidant potential, anti-inflammatory activity in murine models and acute toxicity. EEtOH showed the highest effect in DPPH (37.80% inhibition), FRAP (1065.00 ± 55.30 µmolFe2+) and total polyphenols (231.24 ± 9.05 meq AG/gM). EHex was the most active, ~ 50% inhibition of TPA-induced ear edema; while EEtOH (dose of 2 mg/ear) showed the highest inhibition in the chronic model (97% inhibition), and inhibited MPO activity (48%). In carrageenan-induced edema, ECHCl3(dose 500 mg/kg) was the most active. None of the extracts showed acute toxicity (LD50) at 2 g/kg (p.o.). This work is the first report that supports the traditional use of C. stipulaceusas an anti-inflammatory.

De las hojas de Croton stipulaceusse obtuvieron diferentes extractos (EHex, ECHCl3y EEtOH) evaluando el potencial antioxidante y la actividad antiinflamatoria en modelos murinos y la toxicidad aguda. El EEtOH mostró mayor efecto en DPPH (37.80% inhibición), FRAP (1065.00 ± 55.30 µmolFe2+) y polifenolestotales (231.24 ± 9.05 meq AG/gM). El EHex fue el más activo, cercano al 50% de inhibición del edema auricular inducido con TPA; mientras que el EEtOH (dosis de 2 mg/oreja) mostró la mayor inhibición en el modelo crónico (97% inhibición), e inhibió la actividad de la MPO (48%). En el edema inducido con carragenina, el ECHCl3(dosis 500 mg/kg) fue el más activo. Ninguno de los extractos mostró una toxicidad aguda (DL50) mayor a 2 g/kg (p.o). Este trabajo es el primer reporte que sustenta el uso tradicional de C. stipulaceuscomo antiinflamatorio.

Anti-inflammatory and antioxidant properties of Bertholletia excelsa (H. B. K) bark extract / Propiedades antiinflamatorias y antioxidantes del extracto de corteza de Bertholletia excelsa (H. B. K)

Bertholletia excelsa is native to the Amazon Rainforest and is popularly known as the Brazil nut. It has socioeconomic importance due its nuts being a great export product. There are few studies in the literature regarding the biotechnological potential of its bark, although it is used in folk medicine. The aim of this study was to determine the chemical constituents, anti-inflammatory and antioxidant properties of B. excelsa bark extract (BEB). Twelve substances were identified by LC/MS/MS, and cytotoxicity tests were carried out, as well as analyses of nitric oxide production and elimination of free radicals. BEB caused cytoprotection against oxidative stress in macrophages, increased HMOX-1 expression, overcame the antioxidant effects of GPx-1 and reduced its expression and was able to inhibit leukocyte migration in use peritonitis. BEB efficiently attenuated oxidative stress due to its antioxidant and anti-inflammatory properties and, as such, can be used as a safe and effective source of a natural herbal medicine.

Bertholletia excelsa es originaria de la selva amazónica y se la conoce popularmente como nuez de Brasil. Tiene importancia socioeconómica debido a que sus frutos secos son un gran producto de exportación. Existen pocos estudios en la literatura sobre el potencial biotecnológico de su corteza, aunque se utiliza en medicina popular. El objetivo de este estudio fue determinar los componentes químicos, las propiedades antiinflamatorias y antioxidantes del extracto de corteza de B. excelsa (BEB). Se identificaron 12 sustancias mediante LC/MS/MS y se realizaron pruebas de citotoxicidad, así como análisis de producción de óxido nítrico y eliminación de radicales libres. BEB causó citoprotección contra el estrés oxidativo en macrófagos, aumentó la expresión de HMOX-1, superó los efectos antioxidantes de GPx-1 y redujo su expresión y fue capaz de inhibir la migración de leucocitos en la peritonitis de uso. BEB atenuó eficazmente el estrés oxidativo debido a sus propiedades antioxidantes y antiinflamatorias y, como tal, puede utilizarse como una fuente segura y eficaz de un medicamento a base de hierbas naturales.

Actividad antiinflamatoria in vitro de Plantago major L. y Piper aduncum L. sobre la fosfolipasa A2 del veneno de la serpiente Lachesis muta muta / In vitro anti-inflammatory activity of Plantago major L. and Piper aduncum L. on phospholipase A2 from the venom of snake Lachesis muta muta

Objetivo. Evaluar la actividad inhibitoria in vitro de los extractos de Plantago major «llantén» y Piper aduncum «matico» sobre Fosfolipasa A2 (PLA2) del veneno de la serpiente Lachesis muta muta. Materiales y métodos. Esta investigación fue de tipo explicativa con diseño experimental. Se recolectaron hojas de P. major y P. aduncum en la provincia de Huarochirí en Lima, Perú. Se prepararon extractos alcohólicos diluidos en agua destilada y se realizaron los ensayos fitoquímicos, la cuantificación de fenoles y flavonoides, la cromatografía de capa fina (CCF) en celulosa y la actividad enzimática con PLA2. Se analizó la capacidad de inhibir la PLA2 con los extractos en estudio y sus fracciones. Para el análisis estadístico se utilizó la prueba de Kruskal Wallis y comparaciones múltiples de Bonferroni. Resultados. Tanto en P. major como en P. aduncum se identificó cualitativamente la presencia de fenoles, flavonoides y taninos; además, P. aduncum presentó saponinas. La inhibición de la actividad de la PLA2 del veneno por el extracto total de P. major fue del 45,3%, y sus fracciones mostraron valores de inhibición: LLF-1 con 31,1%, LLF-2 con 66,3% y LLF-3 con 65,5%. En P. aduncum, los valores de inhibición para el extracto total fueron de 86,9%, y sus fracciones presentaron inhibiciones: MF-1 con 34,3%, MF-2 con 67,1% y MF-3 con 54,9%. El análisis estadístico demostró diferencias significativas en la inhibición de la PLA2 (p=0,009) por los extractos. Conclusión. Los ensayos realizados demostraron una asociación entre el efecto antiinflamatorio de los extractos y la inhibición de la PLA2.

Objective. To evaluate the in vitro inhibitory activity of Plantago major "llantén" and Piper aduncum "matico" extracts on phospholipase A2 (PLA2) from the venom of the snake Lachesis muta muta. Materials and methods. We carried out an explanatory study with experimental design. Leaves of P. major and P. aduncum were collected in the province of Huarochirí in Lima, Peru. Then, we prepared alcoholic extracts diluted in distilled water and conducted phytochemical assays, quantification of phenols and flavonoids, thin layer chromatography (TLC) on cellulose and enzymatic activity with PLA2. The ability to inhibit PLA2 with the extracts under study and their fractions was analyzed. The Kruskal Wallis test and Bonferroni multiple comparisons were used during statistical analysis. Results. Phenols, flavonoids and tannins were qualitatively identified in both P. major and P. aduncum; in addition, P. aduncum presented saponins. The inhibition of PLA2 activity of the venom by the total extract of P. major was 45.3%, and its fractions showed the following inhibition values: 31.1% for LLF-1, 66.3% for LLF-2 and 65.5% for LLF-3. The inhibition values for the total extract of P. aduncum were 86.9%, and its fractions showed the following inhibition rates: 34.3% for MF-1, 67.1% for MF-2 and 54.9% for MF-3. Statistical analysis showed significant differences in the inhibition of PLA2 (p=0.009) by the extracts. Conclusion. The tests demonstrated an association between the anti-inflammatory effect of the extracts and PLA2 inhibition.

The essential oil from Kelussia odoratissima Mozaff. fruits exerting potent analgesic and anti-inflammatory effects / El aceite esencial de frutos de Kelussia odoratissima Mozaff. ejerce potentes efectos analgésicos y antiinflamatorios

Kelussia odoratissima fruits are utilized in Persian traditional medicine as a painkiller and to prevent inflammation-based disorders. Considering the higher content of essential oil in the fruits, the oil's anti-inflammatory and analgesic activities were investigated via the paw edema triggered in mice and the writhing test and hot plate technique, respectively. It was observed that the 100, and 200 mg/Kg doses of the oil revealed an analgesic impact (p<0.001) considering the increment in the reaction time needed for the hot plate approach. Furthermore, 100 and 200 mg/Kg doses of the oil caused a reduction in the frequency of writhes in the mice (p<0.01 and p<0.001, respectively). Using all examined doses of theoil (25, 50, and 100 mg/Kg) caused inflammatory reduction (p<0.001). The findings indicated that the oil possess significant activities against acute inflammation. It had both peripheral and central pain-killing impacts. The main components 3-n-butylphthalide (28.3%) and germacrene D (17.3%) can be considered as the responsible compounds to manage the inflammation and pain.

Las frutas de Kelussia odoratissima se utilizan en la medicina tradicional persa como analgésico y para prevenir los trastornos basados en la inflamación. Teniendo en cuenta el mayor contenido de aceite esencial en las frutas, se investigaron las actividades antiinflamatorias y analgésicas del aceite a través del edema de la pata desencadenado en ratones y la prueba de contorsiones y la técnica del plato caliente, respectivamente. Se observó que las dosis de 100 y 200 mg / kg del aceite revelaron un impacto analgésico (p<0,001) considerando el incremento en el tiempo de reacción necesario para el enfoque de placa caliente. Además, dosis de 100 y 200 mg / kg del aceite provocaron una reducción en la frecuencia de retorcimientos en los ratones (p<0,01 y p<0,001, respectivamente). El uso de todas las dosis examinadas del aceite (25, 50 y 100 mg/kg) provocó una reducción inflamatoria (p<0,001). Los hallazgos indicaron que el aceite posee actividades significativas contra la inflamación aguda. Tiene impactos analgésicos tanto periféricos como centrales. Los principales componentes 3-n-butilftalida (28,3%) y germacreno D (17,3%) pueden considerarse como los compuestos responsables del manejo de la inflamación y el dolor.

Drimys (cataia, canelo, quiebra-muelas): uma revisão literária sobre sua fitoquímica, atividades biológicas, farmacológicas e toxicológicas / Drimys (cataia, canelo, quiebra-muelas): a literature review on its phytochemistry, biological, pharmacological and toxicological activities / Drimys (cataia, canelo, quiebra-muelas): una revisión bibliográfica sobre sus actividades fitoquímicas, biológicas, farmacológicas y toxicológicas

Drimys é um dos gêneros mais conhecidos da família botânica Winteraceae. As espécies que compõe este gênero têm sido amplamente utilizadas na medicina popular latino americana para o tratamento de malária, dores gástricas, dor de dente, anemia, entre outros. Além do mais, em algumas localidades, as folhas secas e as bagas dos frutos são utilizadas na culinária como condimento pois possuem sabor apimentado. O objetivo deste trabalho foi realizar uma revisão sistemática sobre a fitoquímica, atividades biológicas, farmacológicas e toxicologicas das espécies do gênero Drimys. Para isso, foram realizadas buscas em diferentes plataformas, no período de 1987 e 2022, utilizando-se a palavra "Drimys", indicativa do gênero botânico, acompanhado dos descritores: "Winteraceae", "pharmacology", "neoplasm", "inflammation", "insecticides", "clinical trial", "pain", "food", "ulcer", "malaria" e "toxicity". Incluiu-se trabalhos sobre o perfil fitoquímico, atividades biológicas e potencial farmacológico. Foram selecionados 77 artigos científicos sobre as espécies D. winteri, D. brasiliensis, D. angustifolia, D. granadensis e D. piperita com informações de estudos in vivo e in vitro que possibilitam o conhecimento medicinal, a conservação e o uso sustentável destas espécies.

Drimys is one of the best known genera of the botanical family Winteraceae. The species that make up this genus have been widely used in Latin American popular medicine for the treatment of malaria, gastric pain, toothache, anemia, among others. Moreover, in some places, the dried leaves and berries of the fruits are used in cooking as a condiment because they have a spicy flavor. The objective of this work was to perform a systematic review on the phytochemical, biological, pharmacological and toxicological activities of the species of the genus Drimys. For this, searches were made in different platforms, between 1987 and 2022, using the word "Drimys", indicative of the botanical genus, accompanied by the descriptors: "Winteraceae", "pharmacology", "neoplasm", "inflammation", "insecticides", "clinical trial", "pain", "food", "ulcer", "malaria" and "toxicity". Papers on phytochemical profile, biological activities, and pharmacological potential were included. A total of 77 scientific articles on the species D. winteri, D. brasiliensis, D. angustifolia, D. granadensis and D. piperita were selected, with information from in vivo and in vitro studies that enable medicinal knowledge, conservation and sustainable use of these species.

Drimys es uno de los géneros más conocidos de la familia botánica Winteraceae. Las especies que componen este género han sido ampliamente utilizadas en la medicina popular latinoamericana para el tratamiento de la malaria, dolor gástrico, dolor de muelas, anemia, entre otros. Además, en algunos lugares, las hojas secas y las bayas de los frutos se utilizan en la cocina como condimento porque tienen un sabor picante. El objetivo de este trabajo fue realizar una revisión sistemática sobre las actividades fitoquímicas, biológicas, farmacológicas y toxicológicas de las especies del género Drimys. Para ello, se realizaron búsquedas en diferentes plataformas, entre 1987 y 2022, utilizando la palabra "Drimys", indicativa del género botánico, acompañada de los descriptores: "Winteraceae", "farmacología", "neoplasia", "inflamación", "insecticidas", "ensayo clínico", "dolor", "alimentación", "úlcera", "malaria" y "toxicidad". Se incluyeron artículos sobre perfil fitoquímico, actividades biológicas y potencial farmacológico. Se seleccionaron 77 artículos científicos sobre las especies D. winteri, D. brasiliensis, D. angustifolia, D. granadensis y D. piperita, con información de estudios in vivo e in vitro que permiten el conocimiento medicinal, la conservación y el uso sostenible de estas especies.

Rubiadin exerts an acute and chronic anti-inflammatory effect in rodents / A Rubiadina exerce um efeito anti-inflamatório agudo e crônico em roedores

Rubiadin is identified as a bioactive anthraquinone that exists in some quinone rich plants. The current research was carried out to evaluate the potential anti-inflammatory impact of Rubiadin in acute and chronic inflammation test models in rodents. The anti-inflammatory activity of Rubiadin was examined in cotton pellet-induced granuloma and carrageenan-induced edema as chronic and acute inflammation models in rats. TNF-α level and histopathological changes were assessed using sampled foot tissue of rat in the acute model. Also, the IL-1β level was assessed in the chronic model. One-way ANOVA (post hoc Tukey’s) analysis was used for comparing the groups. Rubiadin (0.5 mg/kg, i.p.) induced a significant reduction in TNF α level and the paw edema compared to the control group in carrageenan test. Also, it was observed that the anti-inflammatory activity of Rubiadin (0.5 mg/kg, i.p.) is comparable to mefenamic acid (30 mg/kg, i.p.) as the standard drug. Rubiadin was effective in granuloma induced by cotton pellet concerning the granuloma and transudate formation amount. Rubiadin's anti-inflammatory effects were associated with a significant IL-1β decrease in this model. The results suggest that Rubiadin as a natural compound can possess significant peripheral anti-inflammatory impacts.

A rubiadina é identificada como uma antraquinona bioativa que existe em algumas plantas ricas em quinonas. A presente pesquisa foi realizada para avaliar o potencial impacto anti-inflamatório da rubiadina em modelos de teste de inflamação aguda e crônica em roedores. A atividade anti-inflamatória da rubiadina foi examinada em granuloma induzido por pellet de algodão e edema induzido por carragenina como modelos de inflamação crônica e aguda em ratos. O nível de TNF-α e as alterações histopatológicas foram avaliados usando amostra de tecido do pé de rato no modelo agudo. Além disso, o nível de IL-1β foi avaliado no modelo crônico. A análise ANOVA de uma via (post hoc de Tukey) foi usada para comparar os grupos. A rubiadina (0,5 mg / kg, i.p.) induziu uma redução significativa no nível de TNF α e no edema da pata em comparação com o grupo de controle no teste de carragenina. Além disso, foi observado que a atividade anti-inflamatória da rubiadina (0,5 mg / kg, i.p.) é comparável ao ácido mefenâmico (30 mg/kg, i.p.) como o fármaco padrão. A rubiadina foi eficaz no granuloma induzido por pellet de algodão no que diz respeito à quantidade de granuloma e formação de transudato. Os efeitos anti-inflamatórios da rubiadina foram associados a uma redução significativa de IL-1β nesse modelo. Os resultados sugerem que a rubiadina como um composto natural pode ter impactos anti-inflamatórios periféricos significativos.

Rubiadin exerts an acute and chronic anti-inflammatory effect in rodents

Abstract: Rubiadin is identified as a bioactive anthraquinone that exists in some quinone rich plants. The current research was carried out to evaluate the potential anti-inflammatory impact of Rubiadin in acute and chronic inflammation test models in rodents. The anti-inflammatory activity of Rubiadin was examined in cotton pellet-induced granuloma and carrageenan-induced edema as chronic and acute inflammation models in rats. TNF- level and histopathological changes were assessed using sampled foot tissue of rat in the acute model. Also, the IL-1 level was assessed in the chronic model. One-way ANOVA (post hoc Tukeys) analysis was used for comparing the groups. Rubiadin (0.5 mg/kg, i.p.) induced a significant reduction in TNF level and the paw edema compared to the control group in carrageenan test. Also, it was observed that the anti-inflammatory activity of Rubiadin (0.5 mg/kg, i.p.) is comparable to mefenamic acid (30 mg/kg, i.p.) as the standard drug. Rubiadin was effective in granuloma induced by cotton pellet concerning the granuloma and transudate formation amount. Rubiadins anti-inflammatory effects were associated with a significant IL-1 decrease in this model. The results suggest that Rubiadin as a natural compound can possess significant peripheral anti-inflammatory impacts.

Resumo A rubiadina é identificada como uma antraquinona bioativa que existe em algumas plantas ricas em quinonas. A presente pesquisa foi realizada para avaliar o potencial impacto anti-inflamatório da rubiadina em modelos de teste de inflamação aguda e crônica em roedores. A atividade anti-inflamatória da rubiadina foi examinada em granuloma induzido por pellet de algodão e edema induzido por carragenina como modelos de inflamação crônica e aguda em ratos. O nível de TNF- e as alterações histopatológicas foram avaliados usando amostra de tecido do pé de rato no modelo agudo. Além disso, o nível de IL-1 foi avaliado no modelo crônico. A análise ANOVA de uma via (post hoc de Tukey) foi usada para comparar os grupos. A rubiadina (0,5 mg / kg, i.p.) induziu uma redução significativa no nível de TNF e no edema da pata em comparação com o grupo de controle no teste de carragenina. Além disso, foi observado que a atividade anti-inflamatória da rubiadina (0,5 mg / kg, i.p.) é comparável ao ácido mefenâmico (30 mg/kg, i.p.) como o fármaco padrão. A rubiadina foi eficaz no granuloma induzido por pellet de algodão no que diz respeito à quantidade de granuloma e formação de transudato. Os efeitos anti-inflamatórios da rubiadina foram associados a uma redução significativa de IL-1 nesse modelo. Os resultados sugerem que a rubiadina como um composto natural pode ter impactos anti-inflamatórios periféricos significativos.

[Risk of fatal/non-fatal events in patients with previous coronary heart disease/acute myocardial infarction and treatment with non-steroidal anti-inflammatory drugs]. / Riesgo de eventos fatales/no fatales en pacientes con enfermedad coronaria/infarto agudo de miocardio previo y tratamiento con antiinflamatorios no esteroideos.

BACKGROUND: Primary Care is the fundamental axis of our health system and obliges us to be consistent with our prescriptions. The non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with increased cardiovascular risk and increased risk of all causes of death, as well as acute myocardial infarction (AMI) in patients with a previous myocardial infarction. Pain and cardiac patient management are 2 basic pillars in our daily activity, and we must know the limitations of NSAIDs in patients with established cardiovascular risk. OBJECTIVES: We present a review of the scientific literature with primary interest in the role of NSAIDs and cardiovascular risk. The objective is to determine the relationship between the consumption of different NSAIDs and the fatal and non-fatal events among patients with known coronary disease. METHOD: This is a review of the scientific literature with primary interest in the role of NSAIDs and cardiovascular risk. The literature review was conducted in PubMed search engines like Tripdatabase and with certain keywords. Of the 15 original papers found, 9 did not correspond completely to the central focus, so the approach was decided from 6 original articles from the past 5 years, which address the central focus of increased cardiovascular risk found (fatal and non-fatal events) in patients with prior cardiovascular disease or AMI being prescribed NSAIDs for any reason. The risk of fatal/non-fatal events in each of the studies is expressed by the odds ratio (OR)/hazard ratio (HR), defined as the probability of an event occurring. RESULTS: A moderate risk was observed for ibuprofen. It increases the risk of acute coronary syndrome after 5 years of cardiovascular event, especially in the 2nd year (OR 1.63; 95% CI 1.42-1.87). It also increases the risk of stroke (HR 1.23; 95% IC 1.10-1.38). Cyclo-oxygenase-2 inhibitors were the third risk group, after nabumetone and diclofenac. Celecoxib increases risk from the 14th day of treatment (HR 2.3; 95% CI 1.79-3.02), having an OR of 1.47 (95% CI 1.05-2.07) for new AMI. Rofecoxib shows a risk of fatal cardiovascular events, even at low doses, and after 7 days of treatment (HR 2.5; 95% CI 1.91-3.46), with an OR of 2.30 (95% CI 1.76-2.99) for new AMI. Naproxen had a lower risk of cardiovascular death and new cardiovascular events, but no significant results except for treatment longer than 90 days (HR 1.55; 95% CI 1.10-2.17), with increased gastrointestinal bleeding and associated comorbidity during the first year of treatment (HR 1.44; 95% CI 1.07-1.94). Ketorolac is seen as the drug of greatest risk for new AMI: Oral treatment (OR 3.91; 95% CI 2.02-7.58). The review highlights the cardio-protective factor of certain drugs, such as antiplatelet agents and statins in patients, with NSAIDs use. For example, in patients with greater comorbidity, differences were observed in the OR, with antiplatelet agents consumption giving an OR of 1.37 (95% CI 0.68-2.74), compared to the non-consumption, OR 1.79 (95% CI 1.16-2.78). CONCLUSIONS: The consumption of various NSAIDs and their relationship to increased risk of fatal and non-fatal acute coronary syndrome is classified by years. Consumption increases the risk regardless of the time elapsed in relation to those that did not take them, with the figures remaining virtually stable for five years. Diclofenac and cyclooxygenase-2 inhibitors (especially Rofecoxib) showed an increased risk, unlike naproxen, which had a lower risk. However, naproxen, and because of its greater capacity to generate gastrointestinal bleeding, increased for this reason, fatal events and comorbidity in these patients. Despite this, it still has the best cardiovascular safety profile.

Anti-inflamatórios não esteroides tópicos para o alívio da dor artritica, beneficios para idosos / Non-steroid anti-inflammatory topics for arthritic pain relief, benefits for elderly / Temas antiinflamatorios no esteroides para el alívio del dolor artritico, beneficios para personas mayores

Objetivo: Identificar e analisar os anti-inflamatórios não esteroides tópicos para o alívio da dor artrítica, benefícios para idosos. Métodos: Trata-se de uma revisão integrativa realizada nas bases de dados no mês de maio de 2020, mediante consulta às bases de dados MEDLINE/PubMed, CINAHL, EMBASE, Web of Science, SCOPUS e índice bibliométrico LILACS, acessados por meio do Portal Periódicos da Comissão de Aperfeiçoamento de Pessoal de Ensino Superior, utilizando os descritores: idoso (Aged/elderly), anti-inflamatório não esteroide (Anti-Inflammatory Agents, Non-Steroidal) artrite (Arthritides/Polyarthritis). No qual foram selecionados 13 artigos sem limitador para tempo e idioma. Resultados: Detectou se que as variáveis mais evidenciadas foram: inglês (100%); artigos indexados na MEDLINE/PubMed (69,2%); pais com mais publicações Inglaterra (46%). Destaca-se que 69,3% dos artigos foram ensaios clínicos randomizados controlados; anti-inflamatório tópico mais usado diclofenaco sódico (61,5% seguido do cetoprofeno (38,7%). Conclusão: Concluiu se o diclofenaco e o cetoprofeno apresentam eficácia e segurança no alívio da dor artrítica, e baixa toxicidade cutânea local. (AU)

Objective To identify and analyze topical non-steroidal anti-inflammatory drugs for the relief of arthritic pain, benefits for the elderly. Methods: This is an integrative review carried out on the databases in May 2020, by consulting the MEDLINE / PubMed, CINAHL, EMBASE, Web of Science, SCOPUS and LILACS bibliometric index databases, accessed through the Portal Journals of the Higher Education Personnel Improvement Commission, using the descriptors: elderly (Aged / elderly), non-steroidal anti-inflammatory (Anti-Inflammatory Agents, Non Steroidal) arthritis (Arthritides / Polyarthritis). In which 13 articles were selected without time and language limitations. Results: It was found that the most evident variables were: English (100%); articles indexed in MEDLINE / PubMed (69.2%); parents with the most publications in England (46%). It is noteworthy that 69.3% of the articles were randomized controlled clinical trials; most commonly used topical anti-inflammatory diclofenac sodium (61.5% followed by ketoprofen (38.7%). Conclusion: Diclofenac and ketoprofen were concluded to be effective and safe in relieving arthritic pain and low local skin toxicity. (AU)

Objetivo: Identificar y analizar medicamentos antiinflamatorios no esteroideos tópicos para el alivio del dolor artrítico, beneficios para los ancianos. Métodos: Esta es una revisión integradora realizada en las bases de datos en mayo de 2020, consultando las bases de datos del índice bibliométrico MEDLINE / PubMed, CINAHL, EMBASE, Web of Science, SCOPUS y LILACS, a las que se accede a través del Portal Revistas de la Comisión de Mejoramiento del Personal de Educación Superior, utilizando los descriptores: artritis de edad avanzada (Ancianos / ancianos), antiinflamatorios no esteroideos (agentes antiinflamatorios, no esteroideos) (artritis / poliartritis). En el que se seleccionaron 13 artículos sin limitaciones de tiempo e idioma. Resultados: se encontró que las variables más evidentes fueron: inglés (100%); artículos indexados en MEDLINE / PubMed (69,2%); padres con más publicaciones en Inglaterra (46%). Es de destacar que el 69,3% de los artículos fueron ensayos clínicos controlados aleatorios; diclofenaco sódico antiinflamatorio tópico más utilizado (61.5% seguido de ketoprofeno (38.7%). Conclusión: Se concluyó que el diclofenaco y el ketoprofeno son efectivos y seguros para aliviar el dolor artrítico y la baja toxicidad local de la piel. (AU)

Anti-inflammatory effects and acute oral toxicity of Copaifera spp. essential oil-loaded nanoemulsion / Efectos antiinflamatorios y toxicidad oral aguda de nanoemulsión cargada de aceite esencial de Copaifera spp

Copaifera spp. essential oil (EOC) was extracted by hydrodistillation of Copaifera oleoresin (COR). The EOC was characterized by GC/MS and a novel EOC-loaded nanoemulsion was developed to enhance the EOC solubility and to evaluate its utility as antinflammatory. EOC contain 14 volatile compounds (including ß-caryophyllene: 51.52%) having a required HLB of 11. The Surfactant: EOC: Water ratio of 13:15:75 (%, w:w:w) produced the optimal formulation (particle size: 94.47 nm). The EOC-loaded nanoemulsion presented a pseudoplastic/thixotropic behavior with excellent shelf stability for 6 months. The anti-inflammatory effect of the nanoemulsion was more potent than that of the EOC, and statistically equal to diclofenac (50 mg/kg). The EOC-loaded nanoemulsion showed no oral acute toxicity (in mice) at 2000 mg/kg; hence, it is considered a nontoxic product. The development of the EOC-loaded nanoemulsion added value to both the COR and the EOC by providinga suitable formulation that could be used as an anti-inflammatory product.

El aceite esencial (EOC) fue extraído por hidrodestilación de oleoresina de Copaifera spp. El EOC fue caracterizado químicamente por GC/MS. Se formuló una nanoemulsión con EOC para mejorar la solubilidad del EOC y evaluar su utilidad como antiinflamatorio. El EOC contiene 14 compuestos volátiles (incluido el ß-cariofileno: 51,52%) con un HLB requerido de 11. La relación Tensioactivo: EOC: Agua de 13:15:75 (%, p:p:p) produjo la formulación óptima (tamaño de partícula: 94,47 nm).. La nanoemulsión cargada con EOC presentó un comportamiento pseudoplástico/tixotrópico con una excelente estabilidad en almacenamiento durante 6 meses. El efecto antiinflamatorio de la nanoemulsión fue más potente que el del EOC y estadísticamente igual al diclofenaco (50 mg/kg). La nanoemulsión cargada con COE no mostró toxicidad aguda oral (en ratones) a 2000 mg/kg; por lo tanto, se considera un producto no tóxico. El desarrollo de la nanoemulsión cargada con EOC agregó valor tanto al COR como al EOC al proporcionar una formulación adecuada que podría usarse como un producto antiinflamatorio.

Phytochemical composition and biological screening of two Lophophytum species / Composición fitoquímica y cribado biológico de dos especies de Lophophytum

Lophophytum species are holoparasites that grow on tree roots. The objectives of the work were to explore the chemical composition of the tubers of two Lophophytum species and to analyze the antioxidant, anti-inflammatory and antilithiatic activity of their extracts using in vitro methods. The chemical composition was determined by histochemical, phytochemical and TLC tests. In addition, the profile of phenolic compounds was determined by HPLC-MS. The presence of secondary metabolites of recognized activity was demonstrated. The results of the HPLC-MS/MS allowed the tentative identification of catechin, luteolin and glycosides of eriodictyol, naringenin and luteolin in the extract of Lophophytum leandriand eriodictyol, naringenin, luteolin and their glycosylated derivatives in Lophophytum mirabile. The extracts showed promising antioxidant (DPPH, ABTS and ß-carotene-linoleic acid), anti-inflammatory (inhibition of 5-LOX) and anti-urolytic (by bioautographic TLC) activity. It is noteworthy that these are the first results of the phytochemical composition and biological activity of L. mirabile. However, in vivo studies are required to corroborate these activities.

Las especies de Lophophytumson holoparásitas que crecen en raíces de árboles. Los objetivos del trabajo fueron explorar la composición química del túber de dos especies de Lophophytum y analizar la actividad antioxidante, antiinflamatoria y antilitiásica de sus extractos usando métodos in vitro. La composición química se determinó mediante pruebas histoquímicas, fitoquímicas y por TLC. Además, se determinó el perfil de compuestos fenólicos por HPLC-MS/MS. Se demostró presencia de metabolitos secundarios de reconocida actividad. Los resultados del HPLC-MS/MS permitieron identificar tentativamente catequina, luteolina y glucósidos de eriodictiol, naringenina y luteolina en el extracto de Lophophytum leandriy eriodictiol, naringenina, luteolina y sus derivados glicosilados en Lophophytum mirabile. Los extractos mostraron prometedora actividad antioxidante (DPPH, ABTS y ß-caroteno-ácido linoleico), antiinflammatoria (inhibición de la 5-LOX) y antiurolitiásica (por TLC bioautográfica). Es de destacar que estos son los primeros resultados de composición fitoquímica y actividad biológica de L. mirabile. Sin embargo, se requieren estudios in vivo para corroborar dichas actividades.

In vitro inhibitory potential of avocado fruits, Persea americana (Lauraceae) against oxidation, inflammation and key enzymes linked to skin diseases / Inhibidor potencial in vitro de frutos de aguacate, Persea americana (Lauraceae) contra la oxidación, inflamación y enzimas clave vinculadas a enfermedades de la piel

Abstract Introduction: Avocado (Persea americana Mill.) is a member of Lauraceae with one-seeded berry fruit and cultivated in all tropical, subtropical regions in the world and in the Southern coast region of Turkey. Oxidative damage caused by UV can trigger inflammation, resulting in serious inflammatory skin diseases including eczema, seborrheic dermatitis, hyperpigmentation and ageing. Enzyme inhibitors involved in melanogenesis, such as tyrosinase, have been used recently for hyperpigmentation and skin diseases in cosmetic products. Objective: This study aimed to evaluate the antioxidant, anti-inflammatory, anti-tyrosinase activities and total polyphenolic contents of the different parts of P. americana fruit. Methods: The fruit was divided into exocarp, mesocarp, seed, and then methanol and n-hexane extracts were prepared. DPPH and ABTS free radical scavenging capacities and inhibitory potentials on lipid peroxidation were determined to investigate the antioxidant potentials of the extracts. Anti-inflammatory activities of the extracts were evaluated by measuring the stabilization level of the human red blood cell membrane. The tyrosinase inhibitory activities of the samples were determined using mushroom tyrosinase. Results: In general methanol extracts possessed remarkable higher DPPH free radical scavenging activities than n-hexane extracts. The highest activity was determined in methanol extracts of seed (4.17 ± 0.04 mg/mL) followed by exocarp (5.25 ± 0.05 mg/mL). Overall methanol extracts possessed higher ABTS free radical scavenging activities than n-hexane extracts. The greatest ABTS free radical scavenging activity was obtained in methanol extracts of seed (0.03 ± 0.01 mg/mL). In the anti-lipid peroxidation assay, the greatest activity was noticed in methanol extracts of seed (7.71 ± 0.36 µg/mL) followed by exocarp (12.12 ± 0.34 µg/mL), while all n-hexane extracts were inactive. Overall methanol extracts exhibited higher anti-inflammatory and antioxidant properties than n-hexane extracts. However, the maximum anti-tyrosinase activity was determined in n-hexane extracts of exocarp (0.40 ± 0.01 mg/mL) followed by seed (0.46 ± 0.01 mg/mL). Conclusions: These extracts are promising candidates for use as natural products-based antioxidant and anti-inflammatory properties in inflammation-related disease, and also anti-tyrosinase properties in dermatological applications.

Resumen Introducción: El aguacate (Persea americana Mill.) es un miembro de Lauraceae, es una baya de una semilla que se cultiva en todas las regiones tropicales y subtropicales del mundo y la región costera sur de Turquía. El daño oxidativo causado por los rayos ultravioleta puede desencadenar inflamación, lo que posteriormente da como resultado enfermedades inflamatorias graves de la piel como eccema, dermatitis seborreica, hiperpigmentación y envejecimiento. Los inhibidores de enzimas implicados en la melanogénesis, como la tirosinasa, se han utilizado recientemente para la hiperpigmentación y enfermedades de la piel en productos cosméticos. Objetivo: Evaluar las actividades antioxidantes, antiinflamatorias, antitirosinasas y los contenidos polifenólicos totales de las partes del fruto de P. americana. Métodos: El fruto se dividió en tres partes: exocarpio, mesocarpio y semilla, y se prepararon extractos de metanol y n-hexano. Se determinaron las capacidades de eliminación de radicales libres de DPPH y ABTS y los potenciales inhibidores sobre la peroxidación de lípidos para investigar los potenciales antioxidantes de los extractos. Las actividades antiinflamatorias de los extractos se evaluaron midiendo el nivel de estabilización de la membrana de los glóbulos rojos humanos. Las actividades inhibidoras de tirosinasa de las muestras se determinaron utilizando tirosinasa de hongos. Resultados: En general, los extractos de metanol poseían actividades de eliminación de radicales libres de DPPH notablemente más altas que los extractos de n-hexano. La actividad más alta se presentó en extractos metanólicos de semilla (4.17±0.04 mg/mL) seguido del exocarpio (5.25±0.05 mg/mL). En general, los extractos de metanol poseían una mayor actividad de eliminación de radicales libres ABTS que los extractos de n-hexano. La mayor actividad captadora de radicales libres de ABTS se obtuvo en extractos metanólicos de semilla (0.03±0.01 mg/mL). En el ensayo de anti-peroxidación lipídica, la mayor actividad se observó en los extractos metanólicos de semillas (7.71±0.36 µg/mL) seguidos del exocarpio (12.12±0.34 µg/mL), mientras que todos los extractos de n-hexano estaban inactivos. En general, los extractos de metanol exhibieron mayores propiedades anti-inflamatorias y antioxidantes que los extractos de n-hexano. Sin embargo, la actividad anti-tirosinasa máxima se determinó en extractos de exocarpio de n-hexano (0.40±0.01 mg/mL) seguido de semillas (0.46±0.01 mg/mL). Conclusiones: Estos extractos son candidatos prometedores como productos naturales debido a sus propiedades antioxidantes y antiinflamatorias para tratar enfermedades relacionadas con la inflamación, y también propiedades antitirosinasas en aplicaciones dermatológicas.

Development and Optimization of Proniosomal Gel Containing Etodolac: In-vitro, Ex-vivo and In-vivo Evaluation / Desarrollo y optimización del gel proniosomal que contiene etodolaco: evaluación in vitro, ex vivo e in vivo

Introducción: Etodolac se usa en el tratamiento del dolor agudo y la inflamación. Tiene baja solubilidad debido a la alta hidrofobia y se informa que tras la administración oral muestra alteraciones gástricas. Esto fomenta el desarrollo de formulación tópica en lugar de oral. Método: En este trabajo utilizamos el método de separación de fase de coacervación para el desarrollo del sistema vesicular cargado con etodolaco mediante el uso de tensioactivos no iónicos, colesterol y lecitina de soja. El diseño central compuesto (rotativo) se utilizó para optimizar las concentraciones de lecitina de soja, surfactante y colesterol. Las formulaciones preparadas se caracterizaron por análisis de tamaño de vesículas, potencial zeta, eficiencia de atrapamiento, permeación in vitro, permeación ex vivo y estudio antiinflamatorio. Resultados: Etodolac quedó atrapado con éxito en todas las formulaciones que tenían una eficiencia en el intervalo de 74,36% a 90,85%, siendo mayor a 4 ° C que a temperatura ambiente. Cuando se hidrata con agua, los niosomas se producen espontaneamente el rango de 54 a 141 (por mm cúbico). Los resultados del estudio de difusión in vitro revelaron que el etodolaco se liberó en un rango de 71,86 a 97,16% durante un período de 24 horas. El tamaño medio de vesícula de la formulación optimizada se encontró en 211,9 nm con un PDI de 0,5. Las respuestas observadas, es decir,% de eficacia de encapsulación y liberación de fármaco, fueron 74,12 y 95,08 respectivamente. El potencial zeta fue de -19,4 mV y reveló la estabilidad de la formulación, que fue confirmada adicionalmente por la ausencia de cambios en el contenido del fármaco y la liberación del fármaco después de los estudios de estabilidad. El% de inhibición en el volumen de la pata fue del 40,52% y del 43,61% para la prueba y el gel proniosómico comercializado. (AU)

Introduction: Etodolac is used in the treatment of acute pain and inflammation. It has low solubility because of high hydrophobicity and it is reported that upon oral administration shows gastric disturbances. This encourages the development of topical vesicular formulation. Method: In this work we used coacervation-phase separation method for the development of etodolac loaded ve-sicular system by using non-ionic surfactants, cholesterol and soya lecithin. Central composite design (rotatble) was used to optimize the concentrations of soy lecithin, surfactant and cholesterol. The prepared formulations were characterized by number of vesicles formed, vesicle size, zeta potential, entrapment efficiency, in-vitro permeation, ex-vivo permeation and anti-inflammatory study. Results: Etodolac was successfully entrapped in all formulations having efficiency in the range of 74.36% to 90.85%, which was more at 4 °C than room temperature. When hydrated with water; niosome in the range of 54 to 141 (per cubic mm) were spontaneously produced. The results of in-vitro diffusion study revealed that etodolac was released in the range of 71.86 to 97.16% over a period of 24 hrs. The average vesicle size of optimized formulation was found 211.9 nm with PDI of 0.5. The observed responses i.e. % encapsulation efficiency and drug release were 74.12 and 95.08 respectively. The zeta potential was -19.4mV revealed the stability of formulation which was further confirmed by no changes in drug content and drug release after stability studies. The % inhibition in paw volume was 40.52% and 43.61% for test and marketed proniosomal gel. (AU)

Antioxidant potential, anti-inflammatory activity, antidiabetic and cardioprotective effect of Microsechium helleri (Peyr. ) Cong / Potencial antioxidante, actividad anti-inflamatoria, efecto antidiabético y cardioprotector de Microsechium helleri (Peyr. ) Cong

Microsechium helleri (Cucurbitaceae) has been used in ethnopharmacological as a lotion to prevent hair loss, diuretic and cathartic, in the region of central Veracruz, Mexico is used as antidiabetic. The antioxidant properties of the hexanic (EHex), chloroformic (ECHCl3) and ethanolic (EEtOH) extracts, were evaluated by 2,2diphenyl-1-pychrylhydrazyl (DPPH) test, the Ferric Reducing/Antioxidant Power (FRAP) and the total phenolic content test. The anti-inflammatory effect was evaluated in the acute ear edema induced with phorbol 12-myristate 13-acetate (TPA) in mouse and the hypoglycemic and cardioprotective effects of the EEtOH were determined in rats. The EEtOH was the most active in the antioxidant potential DPPH test and the ECHCl3 was the best in the FRAP assay and the total polyphenols content. In the anti-inflammatory assay, the ECHCl3 showed the most activity. The EEtOH had the decreased the glucose levels and reduced myocardial damage. The results support the use of this plant in folk medicine in Mexico as antioxidant, anti-inflammatory, hypoglycemic and cardioprotective.

Microsechium helleri (Cucurbitaceae) se utiliza en etnofarmacología como una loción para prevenir la caída del cabello, como diurético y catártico, en la región del centro de Veracruz, México es usado como antidiabético. Las propiedades antioxidantes de los extractos hexánico (EHex), clorofórmico (ECHCl3) y etanólico (EEtOH), se evaluaron mediante la prueba de 2,2difenil-1-psililhidrazilo (DPPH), el poder reductor férrico/poder antioxidante (FRAP) y el contenido fenólico total. El efecto anti-inflamatorio se evaluó en el edema agudo de la oreja inducido con forbol 12-miristato 13-acetato (TPA) en ratones y se determinaron los efectos hipoglucémicos y cardioprotectores del EEtOH en ratas. El EEtOH fue el más activo en la prueba DPPH de potencial antioxidante y el ECHCl3 fue el mejor en el ensayo FRAP y el contenido total de polifenoles. En el ensayo antiinflamatorio, el ECHCl3 mostró la mayor actividad. El EEtOH disminuyó los niveles de glucosa y redujo el daño miocárdico. Los efectos hipoglucémicos y cardioprotector del extracto de EEtOH se determinaron en ratas, donde el extracto disminuyó los niveles de glucosa y redujo el daño miocárdico. Los resultados apoyan el uso de esta planta en la medicina popular en México como antioxidante, anti-inflamatorio, hipoglucemiante y cardioprotector.