Phenolics as GABA-A receptor ligands:an updated review

Natural products can act as potential GABA modulators, avoiding the undesirable effects of traditional pharmacology used for the inhibition of the central nervous system such as benzodiazepines (BZD). Phenolics, especially flavonoids and phlorotannins, have been considered as modulators of the BZD-site of GABAA receptors (GABAARs), with sedative, anxiolytic or anticonvulsant effects. However, the wide chemical structural variability of flavonoids shows their potential action at more than one additional binding site on GABAARs, which may act either negatively, positively, by neutralizing GABAARs, or directly as allosteric agonists. Therefore, the aim of the present review is to compile and discuss an update of the role of phenolics, namely as pharmacological targets involving dysfunctions of the GABA system, analyzing both their different compounds and their mechanism as GABAergic modulators. We focus this review on articles written in English since the year 2010 until the present. Of course, although more research would be necessary to fully establish the type specificity of phenolics and their pharmacological activity, the evidence supports their potential as GABAAR modulators, thereby favoring their inclusion in the development of new therapeutic targets based on natural products. Specifically, the data compiled in this review allows for the directing of future research towards ortho-dihydroxy diterpene galdosol, the flavonoids isoliquiritigenin (chalcone), rhusflavone and agathisflavone (biflavonoids), as well as the phlorotannins, dieckol and triphlorethol A. Clinically, flavonoids are the most interesting phenolics due to their potential as anticonvulsant and anxiolytic drugs, and phlorotannins are also of interest as sedative agents

Beneficial effect of shikonin on experimental colitis induced by dextran sulfate sodium in Balb/C mice.

The naphthoquinone shikonin, a major component of the root of Lithospermum erythrorhizon, now is studied as an antiinflammatory agent in the treatment of ulcerative colitis (UC). Acute UC was induced in Balb/Cmice by oral administration of 5% dextran sodium sulfate (DSS). The disease activity index was evaluated, and a histologic study was carried out. Orally administered shikonin reduces induced UC in a dose-dependent manner, preventing the shortening of the colorectum and decreasing weight loss by 5% while improving the appearance of feces and preventing bloody stools. The disease activity index score was much lower in shikonin-treated mice than in the colitic group, as well as the myeloperoxidase activity. The expression of cyclooxygenase-2 was reduced by 75%, activation of NF-κB was reduced by 44%, and that of pSTAT-3 by 47%, as well as TNF-α, IL-1β, and IL-6 production. Similar results were obtained in primary macrophages culture. This is the first report of shikonin¿s ability to attenuate acute UC induced by DSS. Shikonin acts by blocking the activation of two major targets: NF-κB and STAT-3, and thus constitutes a promising potential therapeutic agent for the management of the inflammatory bowel disease

Report of the Scientific Committee of the Spanish Agency for Consumer Affairs, Food Safety and Nutrition (AECOSAN) on the risk of Tribulus te- rrestris in food supplements

Tribulus terrestris L. es una planta de la familia Zygophyllaceae cuyo uso en complementos alimenticios está autorizado en varios países de la Unión Europea y que contiene de manera natural varias sustancias activas, entre las que destacan saponósidos esteroídicos, alcaloides b-carbolínicos, favonoides y lignanamidas. La toxicidad de Tribulus terrestris en animales ha sido ampliamente documentada a lo largo de su historia como planta medicinal y se describen efectos negativos a nivel neuronal, muscular, hepático y renal. Algunos países consideran que utilizar partes de la planta de Tribulus terrestris en la elaboración de complementos alimenticios no es seguro, por lo que impiden su comercialización y lo comunican al sistema de alertas europeo RASFF (Rapid Alert System for Food and Feed). El Comité Científico ha realizado una evaluación del riesgo a fin de determinar si el consumo de frutos, partes aéreas de la planta y sus extractos de Tribulus terrestris en complementos alimenticios es seguro y ha concluido que no hay disponibles datos toxicológicos suficientes que permitan evaluar la seguridad del uso de partes de la planta de Tribulus terrestris en complementos alimenticios. En cualquier caso, se considera que las cantidades máximas diarias de Tribulus terrestris en complementos alimenticios no deberían superar las dosis de uso farmacológico y que en los complementos debería constar la parte de la planta empleada, y si se trata de un extracto u otra forma de preparación, así como el contenido en saponósidos.Tribulus terrestris L. is a plant from the Zygophyllaceae family whose use in food supplements is authorised in various European Union countries. In its natural form, it contains various active substances, the most notable of which are steroidal saponins, b-Carboline alkaloids, flavonoids and lignanamides. Tribulus terrestris’ toxicity to animals has been widely documented throughout its history as a medicinal plant and it has been reported to have negative neuronal, muscular, hepatic and renal effects. Some countries consider using parts of the Tribulus terrestris plant to produce food supplements to be unsafe so they do not allow such supplements to be sold. This is reported through the European Rapid Alert System for Food and Feed (RASFF). The Scientific Committee has conducted a risk assessment with the aim of determining whether consuming fruit, plant shoots and their extracts from Tribulus terrestris in food supplements is safe, concluding that there is insufficient toxicological data to assess how safe using parts of the Tribulus terrestris plant in food supplements is. In any case, the maximum daily quantity of Tribulus terrestris in food supplements should not exceed the dose used for pharmacological purposes and the part of the plant used, whether it was extracted or prepared in some other way and its saponin content should all be made clear on the supplement itself

Report of the Scientific Committee of the Spanish Agency for Consumer Affairs, Food Safety and Nutrition (AECOSAN) on the conditions of use of certain substances to be used in food supplements-4

Los complementos alimenticios son alimentos cuyo fin es complementar la dieta normal y que consisten en fuentes concentradas de nutrientes (vitaminas y minerales) o de otras sustancias que tienen un efecto nutricional o fisiológico, en forma simple o combinada. Los complementos se comercializan en forma dosificada, se entregan al consumidor final únicamente preenvasados. En ningún caso, deben sustituir al uso de medicamentos sin una supervisión médica adecuada. Sólo deben utilizarse para complementar la dieta y, de forma general, su uso no es necesario si se sigue una dieta variada y equilibrada, a la que no pueden reemplazar. En España los complementos alimenticios están regulados por el Real Decreto 1487/2009 que traspuso a la legislación española la Directiva 2002/46/CE relativa a la aproximación de las legislaciones de los estados miembros en materia de complementos alimenticios. Sin embargo, actualmente sólo está regulado el uso de vitaminas y minerales, por lo que se ha solicitado al Comité Científico que realice una valoración de la propuesta de autorización de la utilización de determinadas sustancias distintas de vitaminas y minerales en la fabricación de complementos alimenticios. Las sustancias propuestas por la Agencia Española de Consumo, Seguridad Alimentaria y Nutrición (AECOSAN) son: ácido L-aspártico, L-citrulina, glicina, L-prolina, L-serina, L-arginina-L-aspartato, L-lisina-L-aspartato, L-lisina-L-glutamato, N-acetil-L-cisteína, N-acetil-L-metionina, hidroximetilbu- tirato, ácido lipoico, Monascus purpureus, carbón activo y lactulosa. El Comité Científico ha valorado cada propuesta, analizando las características y fuentes de cada sustancia, así como la nutrición, metabolismo y seguridad y ha concluido, en cada caso, si la presentada por la AECOSAN era aceptable desde el punto de vista de su seguridad en su uso como complemento alimenticio. En ningún caso, la evaluación realizada supone un aval de la eficacia biológica de las sustancias y dosis valoradas. El Comité Científico indica que, en todo caso es necesario que las personas que estén sometidas a tratamientos con medicamentos consulten con su médico la oportunidad o conveniencia de consumir complementos alimenticios dada la posibilidad de que existan interferencias en algunos casos.Food supplements are foods, the purpose of which is to supplement the normal diet and which consist of concentrated nutrient sources (vitamins and minerals) or other substances with a nutritional or physiological effect, alone or in combination. The supplements are marketed in dosage form and are only supplied to the end consumer prepacked. In no event should they replace the use of medicines without suitable medical supervision. They should only be used to supplement the diet and, on the whole, their usage is not required if the individual has a varied and balanced diet, which cannot be replaced. In Spain, food supplements are regulated by Royal Decree 1487/2009, which transposed Directive 2002/46/EC on the approximation of the laws of the Member States relating to food supplements into Spanish law. However, only the use of vitamins and minerals is currently regulated. Therefore the Scientific Committee has been asked to make an assessment of the proposal to authorise certain substances other than vitamins and minerals in the manufacture of food supplements. The substances proposed by the Spanish Agency for Consumer Affairs, Food Safety and Nutrition (AECOSAN) are food supplements, L-aspartic acid, L-citrulline, glycine, L-proline, L-serine, L-arginine-L-aspar- tate, L-lysine L-aspartate, L-lysine-L-glutamate, N-acetyl-L-cysteine, N-acetyl-L-methionine, hidro- xymethylbutyrate, lipoic acid, Monascus purpureus, activated carbon and lactulose. The Scientific Committee has assessed each proposal, analysing the characteristics and sources of each substance, and the nutrition, metabolism and safety and has concluded, in each case, whether that submitted by the AECOSAN is acceptable from a safety viewpoint for use as a food supplement. In no event is the assessment intended as a guarantee of the biological efficiency of the substances and doses assessed. The Scientific Committee states that, in any case individuals undergoing medical treatment must seek medical advice as to the suitability of taking food supplements, given the possibility of interactions in certain cases

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Fitoterapia de la inflamación

lnflammation is an organic reactive defense mechanism against exogenous and endogenous stimuli. lnflammation has tumor (swelling), rubor (redness), dolor (pain) and calor (heat), as ancient greeks said. Plants like Chamomilla recutita are studied extensively for its antiinflammatory properties. Several phytochemical families, specially flavonoids, iridoids, polysacharides and phenols are identified as inductors of theses properties. Many tropical plants are newly introduced as antiinflammatory agents, like Sizygium aromaticum, Boswellia serrata, Schinus therebenthifolius. Others, like Harpagophytum, procumbens or Sabal serrulata, instead of its tropical origin, are best known and used in western countries

Exploring occurrence and molecular diversity of betaine lipids across taxonomy of marine microalgae

Betaine lipids (BL) from ten microalgae species of the kingdoms Plantae and Chromista were identified and quantified by HPLC/ESI-TOF-MS. Diacylgyceryl-N-trimethylhomoserine (DGTS) was detected in Trebouxiophyceae and Eustigmatophyceae species, whereas Tetraselmis suecica was described as the first green algae containing diacylglyceryl-hydroxymethyl-N,N,N-trimethyl-beta-alanine (DGTA). DGTA molecular species where also characterized in Cryptophyceae species as well as in the Bacillariophyceae diatom Phaeodactylum tricornutum. The Mediophyceae diatom Chaetoceros gracilis had no DGTA, but contained diacylglyceryl-carboxyhydroxymethylcholine (DGCC). A principal coordinate (PCO) analysis of microalgae species revealed the existence of three main clusters around each BL type. The first PCO axis (43.9% of total variation) grouped Chlorophyceae, Trebouxiophyceae and Eustigmatophyceae species and positively correlated with DGTS. The second PCO axis (27.8% of total variation) segregated DGTA from DGCC containing species. Cryptophyceae, Bacillariophyceae and Chlorodendrophyceae were the more closely associated species to DGTA. Mediophyceae and Dinophyceae species contained DGCC as the only BL. Molecular diversity varied from the simplest DGCC composition in Gyrodinium dorsum to the highest spectrum of ten different molecular species detected for DGTA (Rhodomonas baltica) and DGCC (C. gracilis). The fatty acid profile of DGTS was very dissimilar to that of the whole lipid cell content. DGTS from Nannochloropsis gaditana was highly unsaturated respecting to total lipids, whereas in Picochlorum atomus DGTS unsaturation was nearly one half to that of total lipids. Dissimilarity between DGTA and total lipid fatty acid profile was minimum among all BL and DGTA fatty acid unsaturation was the maximum observed in the study. New DGCC molecular species enriched in 20:5 were described in Mediophyceae diatoms. Multivariate microalgae ordination using BL as descriptors revealed a higher chemotaxonomic potential than that based on their respective BL fatty acid profile. Nevertheless, taxonomic resolution was improved when fatty acids from the whole cell lipid pool were used

Exploring occurrence and molecular diversity of betaine lipids across taxonomy of marine microalgae

Betaine lipids (BL) from ten microalgae species of the kingdoms Plantae and Chromista were identified and quantified by HPLC/ESI-TOF-MS. Diacylgyceryl-N-trimethylhomoserine (DGTS) was detected in Trebouxiophyceae and Eustigmatophyceae species, whereas Tetraselmis suecica was described as the first green algae containing diacylglyceryl-hydroxymethyl-N,N,N-trimethyl-beta-alanine (DGTA). DGTA molecular species where also characterized in Cryptophyceae species as well as in the Bacillariophyceae diatom Phaeodactylum tricornutum. The Mediophyceae diatom Chaetoceros gracilis had no DGTA, but contained diacylglyceryl-carboxyhydroxymethylcholine (DGCC). A principal coordinate (PCO) analysis of microalgae species revealed the existence of three main clusters around each BL type. The first PCO axis (43.9% of total variation) grouped Chlorophyceae, Trebouxiophyceae and Eustigmatophyceae species and positively correlated with DGTS. The second PCO axis (27.8% of total variation) segregated DGTA from DGCC containing species. Cryptophyceae, Bacillariophyceae and Chlorodendrophyceae were the more closely associated species to DGTA. Mediophyceae and Dinophyceae species contained DGCC as the only BL. Molecular diversity varied from the simplest DGCC composition in Gyrodinium dorsum to the highest spectrum of ten different molecular species detected for DGTA (Rhodomonas baltica) and DGCC (C. gracilis). The fatty acid profile of DGTS was very dissimilar to that of the whole lipid cell content. DGTS from Nannochloropsis gaditana was highly unsaturated respecting to total lipids, whereas in Picochlorum atomus DGTS unsaturation was nearly one half to that of total lipids. Dissimilarity between DGTA and total lipid fatty acid profile was minimum among all BL and DGTA fatty acid unsaturation was the maximum observed in the study. New DGCC molecular species enriched in 20:5 were described in Mediophyceae diatoms. Multivariate microalgae ordination using BL as descriptors revealed a higher chemotaxonomic potential than that based on their respective BL fatty acid profile. Nevertheless, taxonomic resolution was improved when fatty acids from the whole cell lipid pool were used

Modulation of Diabetes by Natural Products and Medicinal Plants via Incretins

Incretins are metabolic hormones released after a meal that increase insulin secretion from pancreatic β-cells. The two main incretins are the intestinal peptides glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. Both induce a decrease in glycemia, slow down the absorption of nutrients, and are inactivated by the enzyme dipeptidyl peptidase-4. Recently, incretin-based therapies have become a useful tool to treat diabetic patients, and different studies have focused on the identification of glucagon-like peptide-1 receptor agonists, including those of natural origin. This review focuses on the new findings of medicinal plants and natural products as possible active agents on the potentiation of incretin receptor signaling. Among these, soluble fiber from species of Plantago and guar gum show promising effects, iridoid derivatives are relevant activators of incretin receptors, and derivatives of cyanidin, especially diglycosylated ones, are an interesting source of dipeptidyl peptidase-4 inhibitors.Sin financiación2.687 JCR (2019) Q1, 7/28 Integrative & Complementary Medicine0.572 SJR (2019) Q1, 19/111 Complementary and Alternative MedicineNo data IDR 2019UE