Evaluation of Gemcitabine and Epigallocatechin-3-Gallate Loaded Solid Lipid Nanoparticles on Benzopyrene Induced Lung Cancer Model Via Intranasal Route: Improved Pharmacokinetics and Safety Profile.

The objective of this study was to create a new treatment for lung cancer using solid lipid nanoparticles (SLNs) loaded with gemcitabine (GEM) and epigallocatechin-3-gallate (EGCG) that can be administered through the nose. We analyzed the formulation for its effectiveness in terms of micromeritics, drug release, and anti-cancer activity in the benzopyrene-induced Swiss albino mice lung cancer model. We also assessed the pharmacokinetics, biodistribution, biocompatibility, and hemocompatibility of GEM-EGCG SLNs. The GEM-EGCG SLNs had an average particle size of 93.54 ± 11.02 nm, a polydispersity index of 0.146 ± 0.05, and a zeta potential of -34.7 ± 0.4 mV. The entrapment efficiency of GEM and EGCG was 93.39 ± 4.2% and 89.49 ± 5.1%, respectively, with a sustained release profile for both drugs. GEM-EGCG SLNs had better pharmacokinetics than other treatments, and a high drug targeting index value of 17.605 for GEM and 2.118 for EGCG, indicating their effectiveness in targeting the lungs. Blank SLNs showed no pathological lesions in the liver, kidney, and nasal region validating the safety of SLNs. GEM-EGCG SLNs also showed fewer pathological lesions than other treatments and a lower hemolysis rate of 1.62 ± 0.10%. These results suggest that GEM-EGCG SLNs could effectively treat lung cancer.

Simultaneous determination of five constituents of areca nut extract in rat plasma using UPLC-MS/MS and its application in a pharmacokinetic study.

Areca nuts have been used as a traditional Chinese medicine (TCM) for thousands of years. Recent studies have shown that it exhibits good pharmacological activity and toxicity. In this study, the pharmacokinetics of five major components of areca nut extract in rats were investigated using a highly sensitive ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-MS/MS) method. Arecoline, arecaidine, guvacoline, guvacine, and catechin were separated and quantified accurately using gradient elution with mobile phases of (A) water containing 0.1 % formic acid-10 mM ammonium formate, and (B) methanol. The constituents were detected under a timing switch between the positive and negative ion modes using multiple reaction monitoring (MRM). Each calibration curve had a high R2 value of >0.99. The method accuracies ranged -7.09-11.05 % and precision values were less than 14.36 %. The recovery, matrix effect, selectivity, stability, and carry-over of the method were in accordance with the relevant requirements. It was successfully applied for the investigation of the pharmacokinetics of these five constituents after oral administration of areca nut extract. Pharmacokinetic results indirectly indicated a metabolic relationship between the four areca nut alkaloids in rats. For further clarification of its pharmacodynamic basis, this study provided a theoretical reference.

Enhanced in vitro bioavailability of resveratrol-loaded emulsion stabilized by ß-lactoglobulin-catechin with excellent antioxidant activity.

The study aimed to fabricate ß-Lactoglobulin-catechin (ß-La-Ca) conjugates as a natural designed antioxidant emulsifier to improve the physicochemical stability of resveratrol emulsion delivery system. Fourier transform infrared (FT-IR) and fluorescence spectroscopy analysis confirmed the formation of conjugates using free radical grafting. The antioxidant ability of emulsion was evaluated by DPPH scavenging activities and ORAC experiments. The emulsion stabilized by ß-La-Ca conjugates exhibited strong antioxidant activity with ORAC value of 2541.39 ± 29.58 µmol TE/g, which was significantly higher than that by ß-Lactoglobulin alone with 387.96 ± 23.45 µmol TE/g or their mixture with 948.23 ± 32.77 µmol TE/g. During the whole simulated gastrointestinal digestion, emulsion stabilized by ß-La-Ca conjugates exhibited excellent oxidative stability that the lipid was mainly digested in the small intestine. This behavior attributed to the greater stability of resveratrol to chemical transformation leading to a higher overall bioavailability in vivo. These results suggested that the ß-La-Ca conjugates could be used to fabricate the emulsion-based delivery system to improve the oxidative stability and bioavailability of chemically labile hydrophobic bioactive compounds.

Photodynamic effect of vascular-targeted polyphenol nanoparticles on Endothelial cells.

BACKGROUND: Port wine stains (PWS) are vascular malformations, and photodynamic therapy (PDT) is a promising treatment. Emerging drug delivery methods employ nanoparticles (NPs) to enhance drug permeability and retention in diseased blood vessels and improve drug bioavailability. (-) -epigallocatechin-3-gallate glycine (EGCG) has anti-angiogenetic effects and boosts photodynamic therapy. Chlorin e6 (Ce6) is capable of efficiently producing singlet oxygen, rendering it a very promising photosensitizer for utilization in nanomedicine. MATERIAL AND METHODS: EGCG-Ce6-NPs were synthesized and characterized using various techniques. The photodynamic effects of EGCG-Ce6-NPs on endothelial cells were evaluated. The compatibility and toxicity of the nanoparticle was tested using the CCK-8 assay. The intracellular uptake of the nanoparticle was observed using an inverted fluorescence microscope, and the intracellular fluorescence intensity was detected using flow cytometry. The ROS generation and apoptosis induced by EGCG-Ce6-NPs was observed using confocal laser scanning microscopy and flow cytometry respectively. RESULTS: EGCG-Ce6-NPs exhibited stability, spherical shape of uniform size while reducing the particle diameter, low polydisperse profile and retaining the ability to effectively generate singlet oxygen. These characteristics suggest promising potential for enhancing drug permeability and retention. Additionally, EGCG-Ce6-NPs demonstrated good compatibility with endothelial cells and enhanced intracellular uptake of Ce6. Furthermore, EGCG-Ce6-NPs increased activation efficiency, induced significant toxicity, more reactive oxygen species, and a higher rate of late apoptosis after laser irradiation. CONCLUSION: This in vitro study showed the potentials EGCG-Ce6-NPs for the destruction of endothelial cells in vasculature.

Enfermedad renal crónica y su relación con la ingesta de cúrcuma, catequinas, proantocianidinas y omega-3 / Chronic kidney disease and its relationship with intake of turmeric, catechins, proanthocyanidins and omega-3

La enfermedad renal crónica se caracteriza por disminución de la velocidad de filtración glomerular (VFG) < 60 ml/min/1,73m2 y/o la presencia de daño renal independiente de la causa durante un periodo superior a tres meses. El tratamiento de las etapas más avanzadas de la enfermedad renal crónica (ERC) es la diálisis, y su forma más frecuente la hemodiálisis. Este tratamiento tiene un coste elevado en nuestro país, correspondiendo a USD 900 mensuales por persona. La causa principal de ingreso a diálisis corresponde a la nefropatía diabética, con un 34% de todos los ingresos. Solo estos indicadores justifican los esfuerzos en investigación por mejorar el tratamiento de la ERC. Existe evidencia disponible acerca del rol fundamental de cúrcuma, prontocianidinas, catequinas y omega-3 sobre cómo estos compuestos se relacionan con una mejor respuesta al tratamiento de la enfermedad renal crónica por distintas causas (AU)

Chronic renal disease is characterized by decreased glomerular filtration rate (GFR) < 60 ml/min/ 1.73m2 and/or the presence of kidney damage independent of the cause for a period of 3 months or more. The treatment of more advanced stages of chronic kidney disease is dialysis, and most common form of hemodialysis. This treatment is costly in our country reaching USD 900 per person. The main cause of admission to dialysis, diabetic nephropathy remains with 34% of all revenue. This alone makes any improvement in the treatment of CKD is highly desirable. There is evidence available about the fundamental role of turmeric, proanthocyanidins, catechins and omega-3 on how these compounds are related to the response to treatment of chronic kidney disease for various reasons (AU)

Efecto del consumo de té verde o extractos de té verde en el peso y en la composición corporal; revisión sistemática y metaanálisis / Effect of green tea or green tea extract consumption on body weight and body composition; systematic review and meta-analysis

Introducción: La cafeína y las catequinas contenidas en el té verde podrían tener un efecto termogénico que favorece la pérdida de peso y de grasa corporal. El objetivo del presente estudio es evaluar la magnitud del efecto del té verde o de sus extractos (cafeína y catequinas) sobre el peso corporal y la composición corporal. Material y Métodos: Se realizó una revisión sistemática y metaanálisis para determinar la magnitud del efecto del té verde o de sus extractos sobre el peso corporal (kg), índice de masa corporal (IMC) (kg/m2), masa grasa (%), y perímetro de cintura (cm), o de cadera (cm). Se incluyeron estudios publicados entre los años 2000 y 2013, recuperados de PubMed/Medline con las siguientes características: ensayos controlados aleatorizados (ECA) de grupos paralelos (intervención y placebo), con asignación aleatoria, doble cegado, y un seguimiento mínimo de 12 semanas, en individuos sanos de cualquier género, de edades superiores a los18 años, con IMC de 25-40 kg/ m2. De cada estudio incluido se estableció su calidad y riesgo de sesgos, y se realizó el análisis estadístico, con el software RevMan Crochrane Collaboration 5.1.6, según el modelo de efectos aleatorios con un intervalo de confianza del 95% (IC 95%). Se estimó que el efecto era estadísticamente significativo en p < 0,05, y se evaluó la homogeneidad de los estudios mediante el índice I2. Resultados: La estrategia de búsqueda recuperó 154 estudios, de los cuales solamente 5 pudieron ser incluidos en el análisis cuantitativo. El análisis reveló una diferencia media (DM) estadísticamente no significativa de pérdida de peso, tanto en el análisis de subgrupos: individuos asiáticos -0,81 kg (95% IC: -2,76 a 1,13; P = 0,41; I2 = 0%; n = 210), individuos caucásicos -0,73 kg (95% IC: -3,22 a 1,75; P = 0,45; I2 = 0%; n = 91); como en su conjunto: -0,78 kg (95% IC: -2,31 a 0,75; P = 0,32; I2 = 0%; n = 301). Tampoco se observó una DM estadísticamente significativa de disminución del IMC, tanto en el análisis de subgrupos: individuos asiáticos -0,65 (95% IC: -1,85 a 0,54; P = 0,29; I2= 0%; n = 71), individuos caucásicos -0,21 (95% IC: -0,96 a 0,53; P = 0,58; I2 = 22%; n = 91); como en su conjunto: -0,31 kg (95% IC: -0,88 a 0,27; P = 0,30; I2 = 0%; n = 162), ni para el perímetro de cintura 0,08 cm (95% IC: -0,39 a 0,55; P = 0,73; I2 = 3%; n = 301) o cadera (95% IC: -1,14 a 0,93; P = 0,85; I2 = 0%; n = 210). En la evaluación del efecto sobre el porcentaje de masa grasa (%MG), no se halló una DM estadísticamente significativa para los subgrupos de población: individuos asiáticos -0,76 (95% IC: -1,59 a 0,08; P = 0,08; I2 = 0%; n = 169), individuos caucásicos -0,76 (95% IC: -2,22 a 0,70; P = 0,31; I2 = 36%; n = 93); pero sí una pequeña, aunque estadísticamente significativa, disminución en su conjunto -0,76 (95% IC: -1,44 a -0,09; P = 0,03; I2 = 0%; n = 260). Discusión: El efecto estadísticamente significativo del té verde sobre el %MG de toda la muestra no fue clínicamente relevante, hecho remarcado en los resultados de otros metaanálisis. Conclusión de los autores: La ingesta de té verde o de sus extractos no ejerce efectos estadísticamente significativos sobre el peso de adultos con sobrepeso u obesidad. Se observa un pequeño efecto sobre la disminución del porcentaje de masa grasa, pero no es clínicamente relevante (AU)

Introduction: Caffeine and catechins contained in green tea may have a thermogenic effect favoring weight and body fat loss. The aim of this study is to evaluate the magnitude of the effect of green tea or its extracts (caffeine and catechins) on body weight and body composition. Material and methods: A systematic review and metaanalysis was conducted to determine the magnitude of the effect of green tea or its extracts on body weight (kg), body mass index (BMI) (kg/m2), fat mass (%), and waist and hip circumference (cm). We included studies published between 2000 and 2013, retrieved from PubMed/Medline with the following characteristics: randomized controlled trials (RCTs) of parallel groups (intervention and placebo), randomized, double-blind, and a minimum 12-week follow-up, in healthy individuals of either gender, 18 years or older, with a BMI of 25-40 kg/m2. Quality and risk of bias was assessed for every included study, and the statistical analysis was performed with the Crochrane Collaboration RevMan 5.1.6 software, according to the random effects model with a confidence interval of 95% (95%). It was established that the effect was statistically significant at p < 0.05, and the homogeneity of the studies was assessed using the I2 index. Results: The search strategy retrieved 154 studies, of which only five could be included in the quantitative analysis. The analysis revealed a not statistically significant mean difference (MD) in weight loss in the analyzed sample and subgroups: Asian individuals -0.81 kg (95% CI: -2.76 to 1.13; P = 0.41; I2 = 0%, n = 210), Caucasians -0.73 kg (95% CI: -3.22 to 1.75; P = 0.45; I2 = 0%; n = 91), as well as in the sample as a whole: -0.78 kg (95% CI: -2.31 to 0.75; P = 0.32; I2 = 0%; n = 301). No statistically significant decrease was revealed in BMI in the analyzed sample and subgroups: Asian individuals -0.65 (95% CI: -1.85 to 0.54; P = 0.29; I2 = 0%; n = 71), -0.21 Caucasians (95% CI: -0.96 to 0.53; P = 0.58; I2 = 22%; n = 91), as well as in the sample as a whole: -0.31 kg (95% CI: -0.88 to 0.27; P = 0.30; I2 = 0%; n = 162), nor for the waist circumference 0.08 cm (95% CI: -0.39 to 0.55; P = 0.73; I2 = 3%; n = 301) or hip (95% CI: -1.14 to 0.93; P = 0.85; I2 = 0%; n = 210). In the evaluation of the effect on the percentage of fat mass (FM%), MD was found not statistically significant for population subgroups: Asian individuals -0.76 (95% CI: -1.59 to 0.08; P = 0.08; I2 = 0%; n = 169), Caucasians -0.76 (95% CI: -2.22 to 0.70; P = 0.31; I2 = 36%; n = 93), but a small, although statistically significant, decrease in the overall effect was found -0.76 (95% CI: -1.44 to -0.09; P = 0.03; I2 = 0%; n = 260). Discussion: The statistically significant effect of green tea on the FM% of the entire sample was not clinically relevant, a fact also highlighted in the results of other meta-analysis. Conclusion of the authors: Green tea or gree tea extracts intake or its extracts exerts no statistically significant effect on the weight of overweight or obese adults. There is a small effect on the decrease in the percentage of fat mass, but it is not clinically relevant (AU)

Evidencias clínicas de la fitoterapia en las infecciones genitales bajas / Clinical evidences of phytotherapy in lower genital tract infections

El interés por la fitoterapia en el tratamiento dela vulvovaginitis es reciente y se debe principalmente a las reacciones adversas, la toxicidad y las recidivas que se producen que se producen a menudo con los tratamientos farmacológicos habituales. Se realizó una búsqueda en bases bibliográficas médicas y páginas web de medicina alternativa, detectándose un total de 13 ensayos clínicos. Tres de ellos están escritos en chino, de los que sólo fue posible obtener el resumen. Se valoró su calidad metodológica, infiriéndose el nivel de evidencia. Se comentan los hallazgos fundamentales (AU)

The interest of Phytotherapy in the treatment of vulvovaginitis is recent and it is mainly due to the adverse reactions, toxicity and relapses that are often produced by standard drug therapies. A literature search using medical bibliography databases and alternative medicine websites detected a total of 13 clinical trials. Three of them were in Chinese, for which it was only possible to obtain the summary. Methodological quality was assessed, inferring the level of evidence. Key findings are discussed. We emphasize the usefulness of green tea catechins in the syntomatic treatment of genital warts (AU)