Evaluation of the toxicological effects of Neltuma alpataco (Prosopis alpataco) pod alkaloid extract.

The pods of Neltuma spp. have shown potential as a source of protein and energy in livestock. However, prolonged consumption of some of these species can lead to neurological symptoms in ruminants. This study aimed to determine the alkaloid content, as well as the in vitro and in vivo effects of an alkaloid-enriched extract (AEE) from N. alpataco pods. High performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS) identified juliprosine and juliprosopine as primary alkaloids, with juliprosine being most abundant. AEE from N. alpataco demonstrated dose-dependent cytotoxicity on glioma cells after 48 h, with a 50% cytotoxic concentration (CC50) of 24.69 µg/mL. However, the release of LDH was observed only at the highest tested concentration, indicating cellular damage. Further examination through phase-contrast microscopy and dual acridine orange/ethidium bromide fluorescence staining revealed morphological changes consistent with an apoptotic mechanism of cell death, ultimately leading to secondary necrosis. Finally, the LD50 after intraperitoneal injection in mice was determined to be 12.98 mg/kg. Taken together, these findings demonstrated for the first time the in vivo and in vitro toxicity of the AEE from N. alpataco pods.

Effect of online Kundalini Yoga mental health of university students during Covid-19 pandemic: A randomized controlled trial.

University students were at an increased risk for psychological distress during the COVID-19 pandemic. Using a randomized controlled trial, we examined the efficacy of an online Kundalini Yoga intervention on students' psychological functioning. Healthy university students (N = 106) were randomly assigned to a Kundalini Yoga group, an active control group, or a passive control group in a 1:1:1 ratio. The experimental group attended six Yoga sessions over 6 weeks and the active control group attended to six autogenic relaxation sessions over 6 weeks. All participants completed the study protocol, which involved answering questionnaires related to psychological distress, emotion regulation, self-compassion, self-concept, spiritual well-being, and subjective happiness at three different time points: baseline, at the end of the intervention, and at 1-month follow-up. Results showed that Yoga contributed to improving self-compassion, extrinsic affect improving, and personal and communal spiritual well-being, in comparison to the control groups.

Evaluation of a group intervention based on Mindfulness in patients with anxiety and depression cared for in mental health community center: a quasy-experimental study.

OBJECTIVE: To evaluate the effectiveness a group intervention based on Mindfulness in patients with anxiety and depression treated in a community mental health center. Secondarily, evaluate quality of life and adherence to the intervention. METHODS: Quasi-experimental study with evaluations pre-post intervention in people over 18 years of age treated at the Les Corts Adult Mental Health Center (AMHC), Barcelona, between March 2015 and December 2019. INCLUSION CRITERIA: (1) anxiety symptoms (Hamilton Anxiety Rating Scale >10 points); (2) sign informed consent. Variables collected: (1) anxiety; (2) depression (Beck Depression Inventory); (3) quality of life (EuroQoL) and (4) adherence to the intervention. The intervention (9 weekly sessions; 75min) was carried out by two nurses. Each group consisted of 10-15 patients. RESULTS: 128 patients were included, of which 103 were women with a mean age of 52.23 years (SD 12.78). Comparisons pre and post measures, its showed improvements in relation to anxiety, depressive symptoms and general quality of life (p<0.001) and in its dimensions of anxiety-depression (p=0.003). The mean number of sessions attended was 6.17 (SD 2.31), and they were statistically significant and positively correlated with an improvement in anxiety (p<0.001) and depressive symptoms (EQ-5D) (p=0.021). There were no differences between age groups. CONCLUSION: The group intervention based on Mindfulness improves anxiety and depressive symptoms, as well as the quality of life. This improvement in the symptomatology is associated to greater adherence to the intervention.

Ipomoea carnea alkaloid extract vs swainsonine: A comparative study on cytotoxic activity against glial cells.

The consumption of Ipomoea carnea produces a neurological syndrome in animals. The toxic principles of I. carnea are the alkaloids swainsonine (SW) and calystegines B1, B2, B3 and C1. In this study, we investigated the cytotoxicity of an alkaloid extract of Ipomoea carnea (AEE) and natural swainsonine (SW) isolated from Astragalus lentiginosus (25-1000 µM of SW) for 48 h in a glioma cell line. Although the natural SW did not induce any changes in cell viability, the AEE exhibited a dose dependent cytotoxic effect and release of lactate dehydrogenase (LDH) indicative of cytolysis. In order to evaluate the morphological changes involved, cells were examined using phase contrast and fluorescence microscopy with acridine orange-ethidium bromide staining. The AEE caused a cell death compatible with necrosis, whereas exposure to 1000 µM of SW resulted in cytoplasmic vacuolation. Immunocytochemical studies revealed that astrocytes treated with 150 µM of AEE from I. carnea or 1000 µM of SW exhibited morphological characteristics of cell activation. These findings suggest that swainsonine would not be the only component present in the AEE of I. carnea responsible for in vitro cytotoxicity. Calystegines might also play a role in acting synergistically and triggering cell death through necrosis.

The anti-snake activity of Nectandra angustifolia flavonoids on phospholipase A2: In vitro and in silico evaluation.

ETHNOPHARMACOLOGICAL RELEVANCE: Lauraceae family includes Nectandra angustifolia a species widely used in the folk medicine of South America against various maladies. It is commonly used to treat different types of processes like inflammation, pain, and snakebites. Snakes of the Bothrops genus are responsible for about 97% of the ophidic accidents in northeastern Argentina. AIM OF THE STUDY: To evaluate the anti-snake activity of the phytochemicals present in N. angustifolia extracts, identify the compounds, and evaluate their inhibitory effect on phospholipase A2 (PLA2) with in vitro and in silico assays. METHODS: Seasonal variations in the alexiteric potential of aqueous, ethanolic and hexanic extracts were evaluated by inhibition of coagulant, haemolytic, and cytotoxic effects of B. diporus venom. The chemical identity of an enriched fraction obtained by bio-guided fractioning was established by UPLC-MS/MS analysis. Molecular docking studies were carried out to investigate the binding mechanisms of the identified compounds to PLA2 enzyme from snake venom. RESULTS: All the extracts inhibited venom coagulant activity. However, spring ethanolic extract achieved 100% inhibition of haemolytic activity. Bio-guide fractioning led to an enriched fraction (F4) with the highest haemolytic inhibition. Five flavonoids were identified in this fraction; molecular docking and Molecular Dynamics (MD) simulations indicated the binding mechanisms of the identified compounds. The carbohydrates present in some of the compounds had a critical effect on the interaction with PLA2. CONCLUSION: This study shows, for the first time, which compounds are responsible for the anti-snake activity in Nectandra angustifolia based on in vitro and in silico assays. The results obtained in this work support the traditional use of this species as anti-snake in folk medicine.

Social mindfulness predicts concern for nature and immigrants across 36 nations.

People cooperate every day in ways that range from largescale contributions that mitigate climate change to simple actions such as leaving another individual with choice - known as social mindfulness. It is not yet clear whether and how these complex and more simple forms of cooperation relate. Prior work has found that countries with individuals who made more socially mindful choices were linked to a higher country environmental performance - a proxy for complex cooperation. Here we replicated this initial finding in 41 samples around the world, demonstrating the robustness of the association between social mindfulness and environmental performance, and substantially built on it to show this relationship extended to a wide range of complex cooperative indices, tied closely to many current societal issues. We found that greater social mindfulness expressed by an individual was related to living in countries with more social capital, more community participation and reduced prejudice towards immigrants. Our findings speak to the symbiotic relationship between simple and more complex forms of cooperation in societies.

Beneficial Effect of Melatonin Alone or in Combination with Glatiramer Acetate and Interferon ß-1b on Experimental Autoimmune Encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is a relevant animal model of multiple sclerosis (MS). Oxidative stress and chronic inflammation play a major role in the pathogenesis of MS and EAE. Melatonin, a neurohormone, has potent anti-inflammatory properties. The aim of our study was to assess the therapeutic properties of melatonin alone or in combination with interferon ß-1b (IFNß-1b) or glatiramer acetate (GA) on EAE. EAE was induced in male Sprague-Dawley rats with an intraperitoneal injection of a homogenate of spinal cord and pig brain. At day 10 post immunization, rats were euthanized, and their brains were immediately excised and processed to measure oxidative stress markers and membrane fluidity. In addition, proinflammatory cytokines were quantified in plasma. Melatonin alone or in combination with GA and IFNß-1b inhibited the disease process of EAE and the synthesis of proinflammatory cytokines, caused a significant decrement in oxidative stress markers, and preserved the membrane fluidity in the motor cortex, midbrain, and spinal cord. The cumulative index score was significantly reduced in EAE rats treated with melatonin alone or in combination with GA and IFNß-1b. In conclusion, our findings provide preclinical evidence for the use of melatonin as an adjuvant therapeutic treatment for MS.

Breastfeeding, feeding practices and stunting in indigenous Ecuadorians under 2 years of age.

BACKGROUND: The indigenous child population in Ecuador has a high prevalence of stunting. There is limited evidence of the association between breastfeeding, feeding practices, and stunting in indigenous children. This study aimed to analyze the prevalence of breastfeeding and complementary feeding practices and explore their association with stunting in Ecuadorian indigenous children under two years of age. METHODS: Cross-sectional study of secondary data analysis using the 2012 Ecuador National Health and Nutrition Study, in 625 children aged 0-23 months (48,069 expanded sample), representative for the indigenous population. Breastfeeding and complementary feeding indicators were analyzed by age groups. Timely initiation of breastfeeding (within one hour after birth), exclusive breastfeeding (infants under six months who received only breast milk for the previous day), and other indicators were measured. Chi-square test or Fisher's exact test and logistic regression for complex samples were used to explore association with demographic and socioeconomic factors and stunting. RESULTS: Twenty-six-point eight percent of the children were stunted. Stunting occurred mainly in children with rural residence, on poor households, and where there were four or more children. Most of the children had a timely initiation of breastfeeding (69.5% for 0-12 months and 75.5% for 13-23 months) and exclusive breastfeeding up to six months (78.2%). Among children between 6-12 months of age, 99.3% continued to be breastfed. In children from ages 6 to 12 months, 32.5% received food with adequate dietary diversity. Lower percentages of complementary feeding occurred in the poorest, adolescent mothers or those with less education. Children who did not receive the minimum frequency of meals for their age had higher odds of stunting (OR 3.28; 95% CI 1.3, 8.27). Children from age 19 to 23 months who consumed foods rich in iron showed lower probabilities of stunting (OR 0.04; 95% CI 0.00, 0.51). CONCLUSIONS: Breastfeeding practices reached a prevalence of 70% or more, without being associated with stunting. Complementary feeding practices showed differences by socioeconomic condition. Not reaching the minimum meal frequency between 6 and 12 months of age was associated with stunting. Plans and strategies are necessary to promote adequate feeding and breastfeeding practices in the indigenous population.

Prevalence of goiter and iodine deficiency in indigenous pregnant women from five nonmetropolitan areas of Colombia 2019 / [Prevalencia de bocio y yodo-deficiencia en embarazadas indígenas de cinco áreas no metropolitanas de Colombia 2019].

Objective: To assess the prevalence of goiter and iodine deficiency in indigenous pregnant women coming from five non-metropolitan areas in Colombia. Materials and methods: Descriptive cross-sectional cohort study that included pregnant women of any gestational age with no pregnancy-related conditions, seen in community health centers or in their homes. Patients with comorbidities at the time of pregnancy and those who were receiving iodine supplementation were excluded. Simple random sampling was used. The sociodemographic and obstetric characteristics, urinary iodine concentration and the presence of goiter were measured in accordance with the World Health Organization methodology. A descriptive analysis was performed. Results: Of 189 indigenous pregnant women who were candidates to enter the study, 2 declined participation, and 62 had exclusion criteria, and 125 were included in the final analysis. The mean urinary iodine concentration was 184.4 µg/L (min-max: 12.0-390.0). A total of 42 women (33.6%) had iodine deficiency (< 100 µg/L), and goiter (grade 1-2) was found in 43 (34.4%). No grade 3 or 4 goiter was identified. Conclusions: A high prevalence of goiter and iodine deficiency was found in indigenous pregnant women living in non-metropolitan areas. There is a need to assess maternal and perinatal effects and to implement nutritional interventions.

Objetivo: evaluar la prevalencia de yodo deficiencia y de bocio en mujeres indígenas gestantes de cinco áreas no metropolitanas en Colombia. Materiales y métodos: estudio de corte transversal descriptivo. Se incluyeron mujeres embarazadas de cualquier edad gestacional sin condiciones patológicas del embarazo, atendidas en los centros de salud comunitarios o en sus residencias. Se excluyeron aquellas con comorbilidades presentes al momento del embarazo y también a quienes recibían suplementos con yodo. Muestreo aleatorio simple. Se midieron las características sociodemográficas y obstétricas, la concentración de yodo en orina y la presencia de bocio de acuerdo a la metodología de la Organización Mundial de la Salud. Se realizó un análisis descriptivo. Resultados: 189 gestantes indígenas fueron candidatas a ingresar al estudio, de las cuales 2 no aceptaron participar y 62 tenían criterios de exclusión, finalmente se analizaron 125. La concentración urinaria de yodo tuvo una mediana de 184,4 µg/L (min-max: 12,0-390,0). Un total de 42 gestantes (33,6%) tenían yodo deficiencia (< 100 µg/L) y se evidenció bocio (grado 1-2) en 43 (34,4%). No se identificó bocio grados 3 o 4. Conclusiones: embarazadas indígenas residentes en áreas no metropolitanas evidenciaron alta prevalencia de bocio y yodo deficiencia. Se requiere evaluar los efectos materno-perinatales e implementar intervenciones nutricionales.

Prevalencia de bocio y yodo-deficiencia en embarazadas indígenas de cinco áreas no metropolitanas de Colombia 2019 / Prevalence of goiter and iodine deficiency in indigenous pregnant women from five non-metropolitan areas of Colombia 2019

RESUMEN Objetivo: evaluar la prevalencia de yodo deficiencia y de bocio en mujeres indígenas gestantes de cinco áreas no metropolitanas en Colombia. Materiales y métodos: estudio de corte transversal descriptivo. Se incluyeron mujeres embarazadas de cualquier edad gestacional sin condiciones patológicas del embarazo, atendidas en los centros de salud comunitarios o en sus residencias. Se excluyeron aquellas con comorbilidades presentes al momento del embarazo y también a quienes recibían suplementos con yodo. Muestreo aleatorio simple. Se midieron las características sociodemográficas y obstétricas, la concentración de yodo en orina y la presencia de bocio de acuerdo a la metodología de la Organización Mundial de la Salud. Se realizó un análisis descriptivo. Resultados: 189 gestantes indígenas fueron candidatas a ingresar al estudio, de las cuales 2 no aceptaron participar y 62 tenían criterios de exclusión, finalmente se analizaron 125. La concentración urinaria de yodo tuvo una mediana de 184,4 µg/L (min-max: 12,0-390,0). Un total de 42 gestantes (33,6%) tenían yodo deficiencia (< 100 µg/L) y se evidenció bocio (grado 1-2) en 43 (34,4%). No se identificó bocio grados 3 o 4. Conclusiones: embarazadas indígenas residentes en áreas no metropolitanas evidenciaron alta prevalencia de bocio y yodo deficiencia. Se requiere evaluar los efectos materno-perinatales e implementar intervenciones nutricionales.

ABSTRACT Objective: To assess the prevalence of goiter and iodine deficiency in indigenous pregnant women coming from five non-metropolitan areas in Colombia. Materials and methods: Descriptive cross-sectional cohort study that included pregnant women of any gestational age with no pregnancy-related conditions, seen in community health centers or in their homes. Patients with comorbidities at the time of pregnancy and those who were receiving iodine supplementation were excluded. Simple random sampling was used. The sociodemographic and obstetric characteristics, urinary iodine concentration and the presence of goiter were measured in accordance with the World Health Organization methodology. A descriptive analysis was performed. Results: Of 189 indigenous pregnant women who were candidates to enter the study, 2 declined participation, and 62 had exclusion criteria, and 125 were included in the final analysis. The mean urinary iodine concentration was 184.4 µg/L (min-max: 12.0-390.0). A total of 42 women (33.6%) had iodine deficiency (< 100 µg/L), and goiter (grade 1-2) was found in 43 (34.4%). No grade 3 or 4 goiter was identified. Conclusions: A high prevalence of goiter and iodine deficiency was found in indigenous pregnant women living in non-metropolitan areas. There is a need to assess maternal and perinatal effects and to implement nutritional interventions.

Anti-inflammatory activity of Nectandra angustifolia (Laurel Amarillo) ethanolic extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Nectandra angustifolia belongs to the Lauraceae family and it is widely known in phytomedicine by local inhabitants of South America against various maladies. It is popularly used for the treatment of different types of inflammatory processes, like rheumatism, arthritis and its associated pain. AIM OF THE STUDY: To characterize the phytochemicals in an ethanolic extract of Nectandra angustifolia and to evaluate the total antioxidant content and its anti-inflammatory effect with multiparametric analyses through in vitro assays and an in vivo model. METHODS: Leaves and stems of Nectandra angustifolia were air-dried and an ethanolic extract (NaE) was further obtained. Total phenolic, flavonoid and tannin content were determined and the antioxidant activity was addressed by DPPH and FRAP assays. NaE was first analyzed by HPLC and then two tests were carried out as screening assays for anti-inflammatory activities: red blood cell membrane stabilization and protein denaturation. The non-cytotoxic concentration of NaE was determined for in vitro biological assays using RAW 264.7 (murine macrophages) cell cultures through cell counting with Trypan-blue and XTT assay. Subsequently, the cell cycle of RAW 264.7 cells exposed for 24 h to NaE was analyzed. Additionally, the anti-inflammatory capacity of NaE was evaluated by RT-qPCR of pro-inflammatory cytokines. Furthermore, NF-κB translocation was observed by confocal microscopy at different times. Finally, formalin-induced mice paw inflammation was used as an in vivo model. RESULTS: The chromatographic profile of NaE showed peaks compatible with flavonoids content. NaE exhibited better membrane stabilization effect on HRBC and protection of BSA denaturation than the standard drug (diclofenac). NaE diminished mRNA levels of pro-inflammatory cytokines when added 1-h prior LPS stimulation. Moreover, NaE prevented the translocation of NF-κB to the nucleus and in formalin-induced mice paw inflammation, reduced the edema and the stimulus of inflammatory phase. CONCLUSION: This study shows for the first time, that Nectandra angustifolia ethanolic extract has a high content of flavonoids and that possess antioxidant and anti-inflammatory biological properties as demonstrated by multiparametric analyses from in vitro assays and an in vivo model of inflammation.

Cytotoxic activity induced by the alkaloid extract from Ipomoea carnea on primary murine mixed glial cultures.

The prolonged consumption of Ipomoea carnea produces neurologic symptoms in animals and a typical histological lesion, cytoplasmic vacuolization, especially in neurons. The toxic principles of I. carnea are the alkaloids swainsonine and calystegines B1, B2, B3 and C1. In this study, primary brain cultures from newborn mouse containing mixed glial cells were utilized. These cells were exposed to Ipomoea extracts containing between 0 and 250 µM swainsonine for 48 h. Morphological changes were investigated through Phase Contrast microscopy and Rosenfeld's staining. The extract induced cytoplasmic vacuolization in astrocytes and microglia in a dose dependent manner, being more evident when cultures were exposed to 250 µM of swainsonine. In addition, acridine orange staining evidenced an increase in the number of lysosomes in both microglia and astrocytes cells. Consistent with this, scanning electron microscopy also showed that both types of cells presented morphological characteristics of cell activation. Ultrastructurally, cells showed vacuoles filled with amorphous material and surrounded by a single membrane and also multilayer membranes. Taken together, these findings suggest that swainsonine along with calystegines, are probably responsible for the activation of glial cells due to a possible lysosomal dysfunction and therefore intracellular storage. Our results demonstrate that this in vitro glial cell model is a very good alternative to in vivo studies that require several weeks of animal intoxication to observe similar neurotoxic effects.

Notch signaling in mouse blastocyst development and hatching.

BACKGROUND: Mammalian early embryo development requires a well-orchestrated interplay of cell signaling pathways. Notch is a major regulatory pathway involved in cell-fate determination in embryonic and adult scenarios. However, the role of Notch in embryonic pre-implantation development is controversial. In particular, Notch role on blastocyst development and hatching remains elusive, and a complete picture of the transcription and expression patterns of Notch components during this time-period is not available. RESULTS: This study provided a comprehensive view on the dynamics of individual embryo gene transcription and protein expression patterns of Notch components (receptors Notch1-4; ligands Dll1 and Dll4, Jagged1-2; and effectors Hes1-2), and their relationship with transcription of gene markers of pluripotency and differentiation (Sox2, Oct4, Klf4, Cdx2) during mouse blastocyst development and hatching. Transcription of Notch1-2, Jagged1-2 and Hes1 was highly prevalent and dynamic along stages of development, whereas transcription of Notch3-4, Dll4 and Hes2 had a low prevalence among embryos. Transcription levels of Notch1, Notch2, Jagged2 and Hes1 correlated with each other and with those of pluripotency and differentiation genes. Gene transcription was associated to protein expression, except for Jagged2, where high transcription levels in all embryos were not translated into protein. Presence of Notch signaling activity was confirmed through nuclear NICD and Hes1 detection, and downregulation of Hes1 transcription following canonical signaling blockade with DAPT. In vitro embryo culture supplementation with Jagged1 had no effect on embryo developmental kinetics. In contrast, supplementation with Jagged2 abolished Jagged1 transcription, downregulated Cdx2 transcription and inhibited blastocyst hatching. Notch signaling blockade by DAPT downregulated transcription of Sox2, and retarded embryo hatching. CONCLUSION: Transcription of Notch genes showed a dynamic pattern along blastocyst development and hatching. Data confirmed Notch signaling activity, and lead to the suggestion that Notch canonical signaling may be operating through Notch1, Notch3, Jagged1 and Hes1. Embryo culture supplementation with Jagged1 and Jagged2 unveiled a possible regulatory effect between Jagged1, Cdx2 and blastocyst hatching. Overall, results indicate that a deregulation in Notch signaling, either by its over or under-activation, affects blastocyst development and hatching.

Effect of fish oil on oxidative stress markers in patients with probable Alzheimer´s disease

High intake of omega-3 fatty acids has been associated with synaptic plasticity, neurogenesis and memory in several experimental models. To assess the efficacy of fish oil supplementation on oxidative stress markers in patients diagnosed with probable Alzheimer´s disease (AD) we conducted a double blind, randomized, placebo controlled clinical trial. AD patients who met the inclusive criteria were given fish oil (containing 0.45 g eicosapentaenoic acid and 1 g docosahexaenoic acid) or placebo daily for 12 months. Oxidative stress markers [lipoperoxides, nitric oxide catabolites levels, oxidized/reduced glutathione ratio, and membrane fluidity] and fatty acid profile in erythrocytes were assessed at enrollment, and 6 and 12 months after the start of the testing period. At the end of the trial, in patients who received fish oil, we detected a decrease in the omega 6/omega 3 ratio in erythrocyte membrane phospholipids. This change was parallel with decreases in plasma levels of lipoperoxides and nitric oxide catabolites. Conversely, the ratio of reduced to oxidized glutathione was significantly increased. In addition, membrane fluidity was increased significantly in plasma membrane samples. In conclusion fish oil administration has a beneficial effect in decreasing the levels of oxidative stress markers and improving the membrane fluidity in plasma(AU)

El alto consumo de ácidos grasos omega-3 se asocia con la plasticidad sináptica, neurogénesis y memoria en varios modelos experimentales. Para evaluar la eficacia de la suplementación con aceite de pescado en los marcadores de estrés oxidativo en pacientes con diagnóstico de la enfermedad de Alzheimer (EA) probable realizamos un ensayo clínico doble ciego, aleatorizado, controlado con placebo. A los pacientes con la EA que cumplían los criterios de inclusión se les administró aceite de pescado (que contenía 0,45 g de ácido eicosapentaenoico y 1 g de ácido docosahexaenoico) o placebo diariamente durante 12 meses. Los marcadores de estrés oxidativo plasmático [niveles de lipoperóxidos y catabolitos del óxido nítrico, cociente de glutatión reducido a glutatiónoxidado) y fluidez de la membrana] y el perfil de ácidos grasos en los eritrocitos se evaluaron al inicio, 6 meses y alos 12 meses. Al final del ensayo, en pacientes que recibieron aceite de pescado detectamos una disminución en el cociente de ácidos grasos omega 6/omega 3 en los fosfolípidos de la membrana eritrocitaria. Este cambio ocurrió en paralelo a la disminución de los niveles plasmáticos de lipoperóxidos y catabolitos del óxido nítrico. Por el contrario, el cociente de glutatión reducido a glutatión oxidado se incrementó significativamente. Además, la fluidez de la membrana aumentó significativamente en las muestras analizadas. En conclusión, la administración de aceite de pescado tiene un efecto beneficioso al disminuir los niveles de marcadores de estrés oxidativo plasmático y mejorar la fluidez de la membrana plasmática(AU)

Inhibitory Effect of Cuphea aequipetala Extracts on Murine B16F10 Melanoma In Vitro and In Vivo.

Cuphea aequipetala (C. aequipetala) has been used in Mexican traditional medicine since prehispanic times to treat tumors. In this paper, we evaluated the antiproliferative and apoptotic effect of the methanolic and aqueous extracts of C. aequipetala on several cancer cell lines including the B16F10 cell line of murine melanoma and carried a murine model assay. In vitro assay analyzed the effect in the cellular cycle and several indicators of apoptosis, such as the caspase-3 activity, DNA fragmentation, phosphatidylserine exposure (Annexin-V), and induction of cell membrane permeabilization (propidium iodide) in the B16F10 cells. In vivo, groups of C57BL/6 female mice were subcutaneously injected with 5x105 B16F10 cells and treated with 25 mg/mL of C. aequipetala extracts via oral. Aqueous and methanolic extracts showed a cytotoxic effect in MCF-7, HepG2, and B16F10 cell lines. The methanolic extract showed more antiproliferative effect with less concentration, and for this reason, the in vitro experiments were only continued with it. This extract was able to induce accumulation of cells on G1 phase of the cell cycle; moreover, it was able to induce DNA fragmentation and increase the activity of caspase-3 in B16F10 cells. On the other hand, in the murine model of melanoma, the aqueous extract showed a greater reduction of tumor size in comparison with the methanolic extract, showing an 80% reduction versus one of around 31%, both compared with the untreated control, indicating a better antitumor effect of C. aequipetala aqueous extract via oral administration. In conclusion, the in vitro data showed that both C. aequipetala extracts were able to induce cytotoxicity through the apoptosis pathway in B16F10 cells, and in vivo, the oral administration of aqueous extract reduces the melanoma tumoral mass, suggesting an important antitumoral effect and the perspective to search for effector molecules involved in it.

Isorhamnetin glycoside isolated from Opuntia ficus-indica (L.) MilI induces apoptosis in human colon cancer cells through mitochondrial damage.

This work aimed to evaluate the mechanisms involved in the apoptosis induction of isorhamnetin-3-O-glucosyl-pentoside (IGP) in metastatic human colon cancer cells (HT-29). To achieve this, we assessed phosphatidylserine (PS) exposure, cell membrane disruption, chromatin condensation, cell cycle alterations, mitochondrial damage, ROS production, and caspase-dependence on cell death. Our results showed that IGP induced cell death on HT-29 cells through PS exposure (48%) and membrane permeabilization (30%) as well as nuclear condensation (54%) compared with control cells. Moreover, IGP treatment induced cell cycle arrest in G2/M phase. Bax/Bcl-2 ratio increased and the loss of mitochondrial membrane potential (63%) was observed in IGP-treated cells. Finally, as apoptosis is a caspase-dependent cell death mechanism, we used a pancaspase-inhibitor (Q-VD-OPh) to demonstrate that the cell death induced by IGP was caspase-dependent. Overall these results indicated that IGP induced apoptosis through caspase-dependent mitochondrial damage in HT-29 colon cancer cells.

Determination of Calystegines in Several Tomato Varieties Based on GC-Q-Orbitrap Analysis and Their Classification by ANOVA.

In this study, several calystegines (A3, A5, B1, B2, B3, B4, and C1) were determined in tomato. A simple extraction followed by a derivatization step with silylating agents was performed prior to their analysis by gas chromatography coupled to high resolution mass spectrometry (GC-HRMS-Q-Orbitrap), which allowed the monitoring of several ions at accurate mass. The validation of the method has provided suitable values of linearity, trueness (73.7-120.0%), and precision (≤20.0%, except for calystegines B3 and B4 at 0.5 mg/kg). The limit of quantitation was set at 0.5 mg/kg for all analytes. The validated method was successfully applied to the analysis of nine different tomato varieties, and calystegines A3, A5, B2, and C1 were found at concentrations ranging between 0.65 mg/kg (C1) and 12.47 mg/kg (B2). Tomato varieties were classified according to their calystegines content by applying an analysis of variance (ANOVA).

Leptin regulates neuropeptides associated with food intake and GnRH secretion.

The present review focused on the most important effects of leptin on the hypothalamus and on how leptin regulates neuropeptides associated with food intake and GnRH secretion. This review of the literature suggests that a reduction in leptin serum concentrations results from lower body energy reserves or poor energy availability, leading to hypothalamic secretion of neuropeptides such as NPY/AgRP and QRFP to stimulate food intake. Under these negative metabolic conditions, GnRH secretion is reduced, impairing reproductive functions. In contrast, when metabolic status is inversed by an increase in food availability, energy reserves or both, leptin serum concentrations increase to an action threshold reversing the pattern of secretion: i.e., reducing NPY/AgRP and QRFP and increasing POMC and Kisspeptin, and thereby reducing food intake and stimulating GnRH secretion to promote reproductive function.

Analytical methods, occurrence and trends of tropane alkaloids and calystegines: An update.

In the last years, the interest in secondary metabolites from plants has been growing, and even more if they have or would have medical applications, as it happens with tropane alkaloids and calystegines. Therefore, the number of analytical methods for the analysis of these compounds has been increasing. In this review, the extraction methods as well as the chromatographic separation and detection techniques based on mass spectrometry to determine tropane alkaloids and calystegines in plant raw material and food have been described. Finally, a summary of the natural occurrence of tropane alkaloids and calystegines in the studied matrices, as well as their accidental presence in food, is presented, highlighting current and future determination trends.

Simultaneous analysis of tropane alkaloids in teas and herbal teas by liquid chromatography coupled to high-resolution mass spectrometry (Orbitrap).

A new method has been developed for the simultaneous determination of 13 tropane alkaloids in tea and herbal teas using high-performance liquid chromatography coupled to an Exactive-Orbitrap analyzer. A mixture of methanol, water, and formic acid was used for the extraction of the target compounds followed by a solid-phase extraction step. The validated method provided recoveries from 75 to 128% with intra- and interday precision lower than or equal to 24% (except for apoatropine). Limits of quantification ranged from 5 to 20 µg/kg. Eleven tea and herbal tea samples and two contaminated samples with Datura stramonium seeds were analyzed. Tropane alkaloids were detected in six samples with concentrations from 5 (apoatropine) to 4340 µg/kg (sum of physoperuvine, pseudotropine, and tropine), whereas concentrations from 5 (apoatropine) to 1725 µg/kg (sum of physoperuvine, pseudotropine, and tropine) were found in the contaminated samples.