Immunomodulatory effects of two silymarin isomers in a Balb/c mouse model of allergic asthma

INTRODUCTION AND OBJECTIVES: Allergic asthma is a complex chronic disease of the respiratory system presenting with cough, dyspnea, wheezing and airway obstruction. More than 300 million people of all age spectrums suffer from asthma worldwide. Immunological and inflammatory processes are main contributors to asthma. Cytokines produced by T helper 2 lymphocytes play main roles in asthma development and progression. Silymarin, a therapeutic agent with anti-oxidative properties, is a main component of Silybium marinum. We herein aimed to compare the anti-inflammatory and anti-allergic effects of two silymarin isomers, isosilybin A and silydianin, in the treatment of allergic asthma. MATERIALS AND METHODS: After isolating and purifying isosilybin A and silydianin, Balb/c mouse model of allergic asthma was produced using ovalbumin injection. Seventy mice were categorized into five (1 normal and 4 asthmatic) groups (n = 14 per group). Mice in three of four asthmatic groups were treated with either isosilybin A, silydianin or budesonide. The 4th asthmatic group was used as positive control, with the non-asthmatic group serving as negative control. Airway hyperresponsiveness (AHR) and levels of IL-4, IL-5 and IL-13 in the BAL fluid were determined. Gene expressions of IL-4, IL-5, IL-13 and MUC5ac, as well as IgE serum level were also measured. Cellular composition of BAL fluid and lungs histopathology were finally investigated. RESULTS: Isosilybin A and silydianin reduced eosinophilic infiltration of lungs, IL-4 and IL-5 levels in BAL fluid, IL-4 and IL-5 gene expressions, as well as AHR in Balb/c mouse model of asthma. However, no significant changes were observed in IL-13 level and mucus hyper-secretion. CONCLUSION: According to our study, isosilybin A and silydianin can control main symptoms of asthma by modulating immune responses

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Patología otoñal: micetismos, intoxicación por Amanita virosa / Autumn pathology: micetisms, intoxication by Amanita virosa

La silibinina se emplea por vía intravenosa para el tratamiento de intoxicaciones por Amanita phalloides y especies similares como A. virosa y A. verna. Acude a Urgencias una familia con sospecha de intoxicación por Amanita virosa. Tras evaluar el testimonio de los pacientes, la sintomatología que presentaban (síndrome faloidiano característico), las pruebas clínicas y tras hacer revisión de la bibliografía desde el Servicio de Farmacia, se decidió solicitar al SUMMA silibinina y llevar a cabo su administrarción durante 3 días, hasta que los síntomas revirtieron por completo y se pudo proceder al alta de los pacientes, que no sufrieron complicaciones gracias al tratamiento precoz y a la colaboración multidisciplinar

Silibinin is used intravenously for the treatment of poisonings by Amanita phalloides and similar species such as A. virosa and A. verna. A family with suspected Amanita virosa poisoning comes to the Emergency Room. After evaluating the testimony of the patients, the symptoms they presented (characteristic phalloid syndrome), the clinical tests and after reviewing the bibliography from the Pharmacy Service, silibinin was requested from SUMMA and administered for 3 days, until the symptoms completely reverted and the patients could be discharged from hospital, who did not suffer complications thanks to early treatment and multidisciplinary collaboration

Role of the PNPLA3 polymorphism rs738409 on silymarin + vitamin E response in subjects with non-alcoholic fatty liver disease

Background: non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in developed countries. Lifestyle changes are the pillar of the treatment, although a pharmacological approach is sometimes required in the case of a failure to respond/adhere to the diet. Objective: the aim of this study was to evaluate the effect of silymarin and the influence of the patatin-like phospholipase domain-containing protein 3 (PNPLA3) variant on the response to treatment in patients with NAFLD in a pilot study. Methods: a total of 54 patients with a NAFLD proven biopsy were enrolled in an open prospective study and were treated with Eurosil 85(R) (silymarin + vitamin E) for six months. Biochemical parameters and cardiovascular risk factors (diabetes mellitus, dyslipidemia, hypertriglyceridemia, arterial hypertension and HOMA-IR > 2.5) were recorded before and after six months of treatment. Non-invasive indexes (fatty liver index, lipid accumulation product and NAFLD-fibrosis score) were also calculated. The rs738409 PNPLA3 gene polymorphism status was also determined. Results: significant statistical changes from baseline values after six months of treatment were observed in transaminases levels but not in non-invasive index markers. Twenty patients (37.1%) were G allele carriers and had a higher percentage of lobular inflammation and ballooning on the basal liver biopsy. Patients with the G allele had a smaller decrease in transaminases levels after treatment with silymarin + vitamin E than non-G-allele carriers. Conclusions: treatment with silymarin + vitamin E produced a decrease in transaminases after six months of treatment without an accompanying weight loss. PNPLA3 G-allele carriers responded poorly to the treatment

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Silymarin prevents diabetes-induced hyperpermeability in human retinal endothelial cells / La silimarina previene la hiperpermeabilidad inducida por la diabetes en células endoteliales de retina humana

Introduction: Vascular endothelial growth factor (VEGF) plays an essential role in development of diabetic macular edema (DME). While there is evidence suggesting that silymarin, a flavonoid extracted from Silybum marianum, could be useful for prevention and treatment of diabetic nephropathy, no studies have been conducted in diabetic retinopathy (DR). The aim of this study was to assess the effect of silymarin on disruption of inner blood retinal barrier (BRB), the primary cause of DME. Materials and methods: Human retinal endothelial cells (HRECs) were cultured under standard (5.5mM D-glucose) and diabetogenic conditions (25mM D-glucose and 25mM D-glucose + recombinant vascular endothelial growth factor [rVEGF, 25mg/mL]). To assess cell viability, three concentrations of silymarin were tested (2, 4 and 10μg/mL). The effect of silymarin on HREC disruption was determined using a dextran (70kD) permeability asssay. Results: No differences were found in the viability of HRECs treated with 2 or 4μg/mL of silymarin as compared to untreated cells, but viability significantly decreased after using 10 μg/mL. The concentration of 4 μg/mL was therefore selected. Silymarin (4μg/mL) caused a significant decrease in VEGF-induced permeability in both media with 5.5nM (422±58 vs. 600±72 ng/mL/cm2; p<0.03) and 25nM of D-glucose (354 ± 28 vs. 567 ± 102 ng/mL/cm2; p<0.04). Discussion: Our results show that silymarin is effective for preventing hyperpermeability induced by diabetic conditions in HRECs. Further studies are needed to assess whether silymarin could be useful to treat DME (AU)

Introducción: El Vascular endothelial growth factor (VEGF) juega un papel esencial en el desarrollo del edema macular diabético (EMD). Existe evidencia que indica que el uso de la silimarina, extracto flavonoide del Silybum marianum, podría ser útil en la prevención y el tratamiento de la nefropatía diabética pero no se dispone de datos en retinopatía diabética (RD). El objetivo del estudio es evaluar el efecto de la silimarina sobre la disrupción de la barrera hematorretininana, que es la causa primaria del EMD. Material y métodos: Células endoteliales de retina humana (HRECs) se cultivaron en condiciones estándar (5.5mM de D-glucosa) y en condiciones suprafisiológicas de glucosa (25mM de D-glucosa y 25mM de D-glucosa + VEGF 25mg/dl). Para evaluar la viabilidad de las células se probaron 3 concentraciones de silimarina (2, 4 y 10μg/ml). El efecto de la silimarina sobre la disrupción de las HRECs se determinó mediante análisis de permeabilidad a dextrano (70kD). Resultados: No se observaron diferencias en la viabilidad de las HRECs tratadas con 2 o 4μg/ml de silimarina en comparación con las células no tratadas, pero se observó una reducción de la viabilidad con la concentración de 10μg/ml. Por consiguiente, se seleccionó la concentración de 4μg/ml de silimarina. La silimarina (4μg/ml) produjo un descenso significativo de la permeabilidad inducida por VEGF tanto en medio con 5.5mM de D-glucosa (422 ±58 vs. 600 ±72 ng/ml/cm2; p<0.03) como en medio con 25mM de D-glucosa (354±28 vs. 567±102 ng/ml/cm2; p<0.04). Discusión: Nuestros resultados demuestran que la silimarina es efectiva para prevenir la hiperpermeabilidad inducida por condiciones suprafisiológicas de glucosa en HRECs. Son necesarios más estudios para evaluar si la silimarina podría ser útil para el tratamiento del EMD (AU)

Chemoprevention of polyp recurrence with curcumin followed by silibinin in a case of multiple colorectal adenomas

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Ascorbic acid is superior to silymarin in the recovery of ethanol-induced inflammatory reactions in hepatocytes of guinea pigs

Both oxidative stress and inflammatory reactions play a major role in alcoholic liver fibrosis. We evaluated the efficacy of ascorbic acid (AA) and silymarin in the regression of alcohol-induced inflammation in hepatocytes of guinea pigs (Cavia porcellus). Animals were administered with ethanol at a daily dose of 4 g/kg body weight (b.wt) for 90 days. On the ninety-first day, ethanol administration was stopped and animals were divided into alcohol abstention group and silymarin- (25 mg/100 g b.wt) and AA- (25 mg/100 g b.wt) supplemented groups and maintained for 30 days. There was a significant increase in the activities of alanine aminotransferase, aspartate aminotransferase, and Gamma-glutamyl transpeptidase in the serum of the ethanol group. The intracellular reactive oxygen species (ROS) and expressions of cytochrome P4502E1 and nuclear factor KappaB1, tumor necrosis factor-Alpha, and transforming growth factor-Beta(1) in hepatocytes were significantly increased in ethanol group. The fibrotic markers Alpha -smooth muscle actin and Alpha(1)(I) collagen and activity of cytotoxicity marker caspase-3 were significantly increased and AA content was significantly reduced in hepatocytes of alcohol-treated guinea pigs. But the AA and silymarin supplementation significantly reduced these changes in comparison with alcohol abstention group. AA could induce greater reduction of inflammatory and fibrotic markers in hepatocytes than silymarin. This indicates that AA is superior to silymarin in inhibiting intracellular ROS generation and thereby reducing the ethanol-induced inflammation in hepatocytes

Interés terapéutico del fruto cardo mariano / Therapeutic interest of milk thistle fruit

La actividad antipatotóxica del fruto de cardo mariano y de la silimarina es conocida desde hace muchos años. Su efecto positivo sobre el hígado está basado en las acciones antioxidante, estabilizadora de membrana, favorecedora de la síntesis proteica, antivirásica, antiinflamatoria, inmunomoduladora y anticolestásica de la silimarina y su principal componente, la silibinina. Su eficacia clínica ha sido demostrada en distintos tipos de alteraciones hepáticas, principalmente en las producidas por alcohol y las causadas po virus. Diversos estudios han establecido el papel quimiopreventivo de la silimarina y de la silibinina en distintas áreas celulares cancerosas, así como su efecto estimulante sobre la secreción láctea, además de su actuación en otros ámbitos (protección ósea, neuroprotección, aterogénesis, etc.). a este conjunto de datos, que apuntan hacia posibles nuevas aplicaciones de los productos obtenidos a partir del cardo mariano, se une su amplio margen terapéutico y su baja toxicidad (AU)

Antihepatotoxic activity of milk thistle fruit and silymarin has been known for many years. The positive effect on the liver is based on the antioxidant, membrane stabilizing, protein synthesis increase, antiviral, anti-inflammatory, immunomodulatory and anticolestatic actions of sylimarin and its major constituten, silybinin. Its clinical efficacy has been shown in several types for liver disorders, namely those produced by alcohol and those caused by virus. Several studies have established the chemopreventive role of sylimarin and silybinin in different cancer cell lines and its stimulating effect on lactation, as well as their beneficial effects in other areas (bone protection, neuroprotection, atherogenesis,e tc.). All these data point to possible new applications of the products derived from milk thistle that, in addition, show a wide therapeutic range and low toxicity (AU)

Estabilización clínica en enfermedades neurodegenerativas: estudio clínico en fase II / Clinical stabilisation in neurodegenerative diseases: clinical study in phase II

Introducción. Los trastornos neurodegenerativos, como enfermedad de Parkinson (EP), enfermedad de Alzheimer (EA) y esclerosis múltiple (EM), son patologías progresivas cuyos tratamientos actuales no han demostrado eficacia para detener su progresión (estabilización clínica). Aunque tienen características clínicas muy distintas, comparten mecanismos fisiopatológicos de progresión. Desarrollamos un compuesto diseñado para obtener estabilización clínica, al controlar el daño celular por apoptosis aberrante, oxidación, depósito de metales y proteínas anormales y de vías enzimáticas fisiopatológicas, como la de las caspasas y el sistema MAPK. Pacientes y métodos. Incluimos 42 pacientes con EA, EP y EM. Les administramos el compuesto cada 12 horas y los citamos trimestralmente para evaluación clínica y revisión de exámenes de laboratorio generales. Resultados. Se realizó seguimiento de 3 a 24 meses (media: 8,85 ± 5,99 meses). No se registraron efectos clínicos adversos y sólo aisladas y leves alteraciones en los resultados de laboratorio, sin importancia clínica. Obtuvimos estabilización clínica en todos los pacientes (100%) con EM y mejoría en las puntuaciones de la Expanded Disability Status Scale en 4 pacientes (40%); estabilización clínica en 17 pacientes (100%) con EP y mejoría en puntuación de la Unified Parkinson’s Disease Rating Scale en 15 (88,2%); y estabilización clínica en los 12 pacientes (100%) con EA y aumento de la calificación del test minimental en 9 (75%). Conclusión. El compuesto es seguro y una opción terapéutica prometedora, al observarse una evidente tendencia hacia la estabilización clínica por medio de su utilización. Debe realizarse un estudio experimental para establecer el alcance terapéutico del compuesto, su posible efecto preventivo y valorar otras indicaciones (AU)

Introduction. Neurodegenerative disorders, such as Parkinson’s disease (PD), Alzheimer’s disease (AD) and multiple sclerosis (MS), are progressive pathological conditions in which current treatments have not proved to be effective at curbing their progress (clinical stabilisation). Although they have very different clinical characteristics, they share the same pathophysiological mechanisms of progression. We developed a compound designed to obtain clinical stabilisation which acts by controlling cell damage due to aberrant apoptosis, oxidation, abnormal deposits of metals and proteins, and pathophysiological enzymatic pathways, such as that of caspases and the MAPK system. Patients and methods. Forty-two patients with AD, PD and MS were included in the study. The compound was administered to them every 12 hours and they were given appointments every three months for a clinical evaluation and a review of general lab analyses. Results. Subjects were submitted to a follow-up of between 3 and 24 months (mean: 8.85 ± 5.99 months). No clinical side effects were recorded and there were only some slight alterations in the lab test results, although they were not clinically relevant. Clinical stabilisation was achieved in all the patients (100%) with MS and the scores on the Expanded Disability Status Scale improved in four patients (40%); clinical stabilisation in 17 patients (100%) with PD and improvements in the score on the Unified Parkinson’s Disease Rating Scale in 15 of them (88.2%); and clinical stabilisation in 12 patients (100%) with AD, and an increase in the score obtained on the minimental test in nine cases (75%). Conclusions. The compound is safe and a promising therapeutic option, since there is a clear tendency towards clinical stabilisation when it is being used. An experimental study needs to be conducted in order to determine the therapeutic scope of the compound and its possible preventive effects, as well as to evaluate other indications (AU)

Análisis fitofarmacológico de los frutos de Luffa acutangula para determinar su actividad antihepatotóxica / Phytopharmacological screening of Luffa acutangula fruits for its antihepatotoxic activity

Se examinó el extracto acuoso y etanólico (100 mg/kg) de Luffa acutangula Linn (frutos) para determinar la actividadantihepatotóxica en ratas druckrey mediante la hepatotoxicidad inducida por tetracloruro de carbono (CCl4)y paracetamol (PCM). Se demostró que el extracto posee un efecto hepatoprotector signifi cativo, ya que reduce losniveles séricos de transaminasas (SGPT y SGOT), fosfatasa alcalina (ALP) y bilirrubina. La signifi cativa actividadhepatoprotectora de Luffa acutangula es comparable a la de la silimarina, agente hepatoprotector estándar, lo quejustifi ca su uso en afecciones del hígado

The ethanolic and aqueous extract (100mg/kg) of Luffa acutangula Linn(fruits) was examined for antihepatotoxic activityin druckrey rats by inducing hepatotoxicity with Carbon tetrachloride(CCl4) and Paracetamol(PCM). The extracthas shown to posses signifi cant hepatoprotective effect by lowering the serum level of transaminases (SGPT & SGOT),Alkaline phosphatase (ALP) and bilirubin. The signifi cant hepatoprotective activity of Luffa acutangula is comparableto that standard hepatoprotective agent silymarin, which justify its use in liver affection

Sillybum marianum / Sillybum marianum

El cardo mariano ha sido utilizado en Europa desde el siglo IV aCpara el tratamiento de trastornos hepáticos, picaduras de animalese intoxicaciones. Actualmente, se sabe que la molécula activa es unflavonoide llamado silimarina, que se utiliza, además de para estas“indicaciones” clásicas, por su efecto citoprotector ante el envejecimientoy los mecanismos moleculares que provocan daño celularmediados por agentes relacionados con la respuesta inflamatoria.Existen estudios in vitro e in vivo con animales que apuntan a unacierta actividad citoprotectora ante moléculas oxidantes derivadasdel metabolismo. Además, también se ha demostrado que la silimarinaes capaz de modificar ciertos pasos previos a la formaciónde moléculas relacionadas con la respuesta inflamatoria.No existe evidencia que demuestre un efecto beneficioso sobre lostrastornos hepáticos (hepatitis, cirrosis, etc.).El consumo de cardo mariano provoca en algunos casos leves alteracionesgastrointestinales. No existen tampoco interaccionesmedicamentosas descritas

A plant called sillybum marianum has been used in Europe sincethe IV century BC for the treatment of hepatic disorders, animalbites and intoxications. At present, we know that the active moleculeis a flavonoid called silimarine used, besides this classical indications,for its cytoprotector effect on the ageing process and themolecular mechanisms that cause cell damaged mediated by inflammatoryresponse-related agentsThere is no evidence showing a beneficial effect on liver disorders(hepatitis, cirrhosis, etc.).The consumption of sillybum marianum causes in some cases mildgastrointestinal alterations. No drug interactions have been described

Intoxicación fatal por Lepiota brunneoincarnata / Fatal intoxication due to Lepiota brunneoincarnata

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