Dual Role of Phenyl Amides from Hempseed on BACE 1, PPARγ, and PGC-1α in N2a-APP Cells.

In Alzheimer's disease (AD) the accumulation of amyloid ß (Aß) plaques in the brain leads to neuroinflammation, neuronal cell dysfunction, and progressive memory loss. Therefore, blocking the formation of Aß plaques has emerged as one of the most promising strategies to develop AD treatments. Hempseed is widely used as a food, and recently its compounds have shown beneficial effects on neuroinflammation. The objective of this study was to investigate whether a fraction rich in phenyl amide compounds, N-trans-caffeoyltyramine (CAFT) and N-trans-coumaroyltyramine (CUMT), can affect gene expression: ß-site amyloid-precursor-protein-cleaving enzyme 1 (BACE 1), peroxisome proliferator-activated receptor gamma (PPAR γ), and PPARγ-coactivator-1α (PGC-1α) in N2a-APP cells. The mRNA levels were measured using RT-qPCR. The ethyl acetate fraction and CAFT were found to reduce BACE1 gene expression and are promissory PPARγ and PGC-1α natural agonists. The results show that hempseed compounds can inhibit the expression of BACE 1, which is involved in the accumulation of Aß plaques and positively affect transcription factors involved in complex and diverse biological functions.

Interacciones potenciales entre productos fitoterápicos con laxantes antracénicos y otros fármacos. Detección en farmacias comunitarias de Sevilla / Potential interactions between phytotherapycs anthracenics laxatives products and other drugs. Detection in community pharmacies of Seville

Introducción: Los productos fitoterápicos más dispensados en España son los laxantes. Los laxantes antracénicos como el acíbar de aloe (Aloe spp.) o la corteza de cáscara sagrada (Rhamnus purshianus), entre otros, podrían estar implicados en interacciones farmacológicas debido al riesgo de hipopotasemia que produce su uso continuado. Objetivos: Realizar un análisis de la situación de dispensación de estos laxantes y detectar potenciales interacciones con otros fármacos en farmacias de la Provincia de Sevilla. Material/Métodos: Estudio descriptivo, observacional, realizado desde 14 farmacias comunitarias, mediante aplicación de un cuestionario acerca del uso de plantas medicinales. Se identificaron las interacciones potenciales descritas en las monografías EMA y ESCOP, y se analizaron los factores de riesgo para las mismas (edad avanzada, polimedicación y frecuencia de consumo). Resultados: La muestra fue constituida por 252 pacientes. El 24,6% (n = 62) consumían laxantes antracénicos, más del 50% de forma diaria. El porcentaje de asociación con otros fármacos fue del 70%. Se han identificado potenciales interacciones en el 40% (n = 26) de los pacientes, basadas en la asociación del laxante con fármacos diuréticos, con fármacos que podrían prolongar el intervalo QT, o con ambos a la vez. En todos ellos se detectó la existencia de uno o varios Factores de Riesgo para la Interacción (FRI). Conclusiones: Los resultados obtenidos reflejan la necesidad de formación actualizada por parte de los farmacéuticos comunitarios sobre los beneficios y riesgos de estos fitomedicamentos. Su dispensación protocolizada favorecería la identificación de posibles interacciones farmacológicas y su uso seguro y racional

Background: The most dispensed phytotherapeutic products in Spain are laxatives. An-thracenic laxatives such as aloe vera (Aloe spp.) or cascara sagrada (Rhamnus purshianus) could be involved in drug interactions due to the risk of hypokalemia caused by their continued use. Objectives: To carry out an analysis of the dispensing situation of these laxatives and detect potential interactions in pharmacies of the Province of Seville. Material / Methods: A descriptive, observational study made from 14 Pharmacy Offices, through the application of a questionnaire about the use of medicinal herbs. The potential interactions described in the EMA and ESCOP monographs were identified, and the risk factors for them (advanced age, polymedication and frequency of use) were analyzed. Results: The sample was constituted by 252 patients. 24.6% (n = 62) consumed anthracene laxatives, more than 50% daily. The percentage of association with other drugs was 70%. Potential interactions have been identified in 40% (n = 26) of the patients, based on the association of the laxative with diuretic drugs, with drugs that could prolong the QT interval, or with both at the same time. In all of them, the existence of one or several Risk Factors for Interaction (FRI) was detected. Conclusions: The results obtained show the need for updated training by community pharmacists on the benefits and risks of these phytoterapics products. Its protocolized dispensation would favor the identification of possible pharmacological interactions and their safe and rational use

Ginger rhizome enhances the anti-inflammatory and anti-nociceptive effects of paracetamol in an experimental mouse model of fibromyalgia.

BACKGROUND: The dried rhizome of ginger has been widely used for more than 2500 years in folk medicine for the treatment of various diseases that involve inflammation or are caused by oxidative stress. AIMS: This study was designed to compare the anti-nociceptive and anti-inflammatory effect of dried powdered ginger rhizome (GR) and paracetamol (APAP) on an experimental mouse model of fibromyalgia syndrome (FMS) induced by intermittent cold stress (ICS). METHODS: Forty-eight female C57BL/6 J mice were used for the experiments. The animals were allocated in six groups (n = 8). Each group received one of the following treatments for 8 weeks: healthy control, ICS group, ICS + APAP (40 mg/Kg/day), ICS + GR (0.5%); ICS + GR (1%), and ICS + GR (0.5%) + APAP (40 mg/Kg/day). After treatment, symptoms of FMS were induced by intermittent cold stress (ICS). RESULTS AND CONCLUSIONS: GR consumption improved mechanical and thermal allodynia and mechanical hyperalgesia and improved behavioural changes related to cognitive disturbances, anxiety, and depression. In addition, GR also significantly decreased the inflammatory response of proinflammatory mediators such as NO, PGE2, TXB2, and IL-1ß in LPS-stimulated macrophages. The effects of APAP were significantly enhanced by co-administration with GR. These findings provide evidence that the daily consumption of GR enhances the anti-nociceptive effect of APAP in mice, improves other cognitive disturbances associated with chronic pain, and reduces the inflammatory state generated in an experimental FMS model.

Mitraphylline inhibits lipopolysaccharide-mediated activation of primary human neutrophils.

BACKGROUND: Mitraphylline (MTP) is the major pentacyclic oxindolic alkaloid presented in Uncaria tomentosa. It has traditionally been used to treat disorders including arthritis, heart disease, cancer, and other inflammatory diseases. However, the specific role of MTP is still not clear, with more comprehensivestudies, our understanding of this ancient herbal medicine will continue growing. HYPOTHESIS/PURPOSE: Some studies provided its ability to inhibit proinflamatory cytokines, such as TNF-α, through NF-κB-dependent mechanism. TNF-α primes neutrophils and modulates phagocytic and oxidative burst activities in inflammatory processes. Since, neutrophils represent the most abundant pool of leukocytes in human blood and play a crucial role in inflammation, we aimed to determine the ability of MTP to modulate neutrophil activation and differentially regulate inflammatory-related cytokines. METHODS: To determine the mechanism of action of MTP, we investigated the effects on LPS-activated human primary neutrophils responses including activation surface markers by FACS and the expression of inflammatory cytokines, measured by real time PCR and ELISA. RESULTS: Treatment with MTP reduced the LPS-dependent activation effects. Activated neutrophils (CD16(+)CD62L(-)) diminished after MTP administration. Moreover, proinflamatory cytokines (TNF-α, IL-6 or IL-8) expression and secretion were concomitantly reduced, similar to basal control conditions. CONCLUSION: Taken together, our results demonstrate that MTP is able to elicit an anti-inflammatory response that modulates neutrophil activation contributing to the attenuation of inflammatory episodes. Further studies are need to characterize the mechanism by which MTP can affect this pathway that could provide a means to develop MTP as new candidate for inflammatory disease therapies.

Bioactive constituents from "triguero" asparagus improve the plasma lipid profile and liver antioxidant status in hypercholesterolemic rats.

We have previously shown that the Andalusian-cultivated Asparagus officinalis L. "triguero" variety produces hypocholesterolemic and hepatoprotective effects on rats. This asparagus is a rich source of phytochemicals although we hypothesized there would be some of them more involved in these functional properties. Thus, we aimed to study the effects of asparagus (500 mg/kg body weight (bw)/day) and their partially purified fractions in flavonoids (50 mg/kg bw/day), saponins (5 mg/kg bw/day) and dietary fiber (500 mg/kg bw/day) on oxidative status and on lipid profile in rats fed a cholesterol-rich diet. After 5 weeks treatment, plasma lipid values, hepatic enzyme activities and liver malondialdehyde (MDA) concentrations were measured. With the exception of the saponin fraction (SF), the administration of lyophilized asparagus (LA), fiber fraction (FF), and flavonoid fraction (FVF) to hypercholesterolemic rats produced a significant hypolipidemic effect compare to a high-cholesterol diet (HCD). In addition, the LA and FVF groups exhibited a significant increase in enzyme activity from multiple hepatic antioxidant systems including: superoxide dismutase, catalase, and gluthatione reductase/peroxidase as well as a decrease in MDA concentrations compared to HCD group. These results demonstrate that "triguero" asparagus possesses bioactive constituents, especially dietary fiber and flavonoids, that improve the plasma lipid profile and prevent hepatic oxidative damage under conditions of hypercholesterolemia.

The sterols isolated from Evening Primrose oil modulate the release of proinflammatory mediators.

Evening Primrose oil is a natural product extracted by cold-pressed from Oenothera biennis L. seeds. The unsaponifiable matter of this oil is an important source of interesting minor compounds, like long-chain fatty alcohols, sterols and tocopherols. In the present study, sterols were isolated from the unsaponifiable matter of Evening Primrose oil, and the composition was identified and quantified by GC and GC-MS. The major components of sterols fraction were ß-Sitosterol and campesterol. We investigated the ability of sterols from Evening Primrose oil to inhibit the release of different proinflammatory mediators in vitro by murine peritoneal macrophages stimulated with lipopolysaccharide. Sterols significantly and dose-dependently decreased nitric oxide production. Western blot analysis showed that nitric oxide reduction was a consequence of the inhibition of inducible nitric oxide synthetase expression. Sterols also reduced tumor necrosis factor-α, interleukine 1ß and tromboxane B2. However, sterols did not reduce prostaglandin E2. The reduction of eicosanoid release was related to the inhibition of cyclooxygenase-2 expression. These results showed that sterols may have a protective effect on some mediators involved in inflammatory damage development, suggesting its potential value as a putative functional component of Evening Primrose oil.