Mexican calea (Calea zacatechichi Schltdl.) interferes with cholinergic and dopaminergic pathways and causes neuroglial toxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: The use of "Mexican calea" (Calea zacatechichi Schltdl.) in ritualistic ceremonies, due to its dream-inducing effects, was until recently limited to indigenous communities in Mexico. However, the plant has recently gained popularity in Western societies being commonly used in recreational settings. Despite the traditional and recreational uses, mechanisms underlying its reported oneirogenic effects remain unknown, with no data available on its neurotoxic profile. AIM OF THE STUDY: The scarcity of toxicological data and the unknown role of major neurotransmitter systems in the dream-inducing properties of the plant prompted us to investigate which neurotransmitters might be affected upon its consumption, as well as the potential cytotoxic effects on neurons and microglial cells. Furthermore, we aimed to explore a relationship between the recorded effects and specific constituents. MATERIALS AND METHODS: Effects on cholinergic and monoaminergic pathways were investigated using enzymatic assays, with the latter also being conducted in neuronal SH-SY5Y cells along with the impact on glutamate-induced excitotoxicity. Investigation of the neurotoxic profile was approached in neuronal SH-SY5Y and microglial BV-2 cells, evaluating effects on metabolic performance and membrane integrity using MTT and LDH leakage assays, respectively. Potential interference with oxidative stress was monitored by assessing free radical's levels, as well as 5-lipoxygenase mediated lipid peroxidation. Phenolic constituents were identified through HPLC-DAD-ESI(Ion Trap)MSn analysis. RESULTS: Based on the significant inhibition upon acetylcholinesterase (p < 0.05) and tyrosinase (IC50 = 60.87 ± 7.3 µg/mL; p < 0.05), the aqueous extract obtained from the aerial parts of C. zacatechichi interferes with the cholinergic and dopaminergic systems, but has no impact against monoamine oxidase A. Additionally, a notable cytotoxic effect was observed in SH-SY5Y and BV-2 cells at concentrations as low as 125 and 500 µg/mL (p < 0.05), respectively, LDH leakage suggesting apoptosis may occur at these concentrations, with necroptosis observed at higher ones. Despite the neurocytotoxic profile, these effects appear to be independent of radical stress, as the C. zacatechichi extract scavenged nitric oxide and superoxide radicals at concentrations as low as 62.5 µg/mL, significantly inhibiting also 5-lipoxygenase (IC50 = 72.60 ± 7.3 µg/mL; p < 0.05). Qualitative and quantitative analysis using HPLC-DAD-ESI(Ion Trap)MSn enabled the identification of 28 constituents, with 24 of them being previously unreported in this species. These include a series of dicaffeoylquinic, caffeoylpentoside, and feruloylquinic acids, along with 8 flavonols not previously known to occur in the species, mainly 3-O-monoglycosylated derivatives of quercetin, kaempferol, and isorhamnetin. CONCLUSIONS: Our findings regarding the neuroglial toxicity elicited by C. zacatechichi emphasize the necessity for a thorough elucidation of the plant's toxicity profile. Additionally, evidence is provided that the aerial parts of the plant inhibit both acetylcholinesterase and tyrosinase, potentially linking its psychopharmacological effects to the cholinergic and dopaminergic systems, with an apparent contribution from specific phenolic constituents previously unknown to occur in the species. Collectively, our results lay the groundwork for a regulatory framework on the consumption of C. zacatechichi in recreational settings and contribute to elucidating previous contradictory findings regarding the mechanisms underlying the dream-inducing effects of the plant.

Risk of endometrial cancer after RRSO in BRCA 1/2 carriers: a multicentre cohort study.

OBJECTIVE: To know the risk of endometrial cancer (EC) in a population of women with BRCA 1/2 pathogenic or likely pathogenic variants after risk-reducing salpingo-oophorectomy (RRSO). METHODS: The study cohort included data from 857 women with BRCA mutations who underwent RRSO visited four hospitals in Catalonia, Spain, from January 1, 1999 to April 30, 2019. Standardized incidence ratio (SIR) of EC was calculated in these patients using data from a regional population-based cancer registry. RESULTS: After RRSO, eight cases of EC were identified. Four in BRCA 1 carriers and four in BRCA2 carriers. The expected number of cases of EC was 3.67 cases, with a SIR of 2.18 and a 95% CI (0.93-3.95). CONCLUSIONS: In our cohort, the risk of EC in BRCA1/2 carriers after RRSO is not greater than expected. Hysterectomy is not routinely recommended for these patients.

Dietary antioxidant intake is inversely associated with 2,3-dinor oxylipin metabolites, the major excreted oxylipins in overweight and obese subjects.

Cardiometabolic disease risk factors, including obesity, insulin resistance, high blood pressure, and dyslipidemia, are associated with elevated oxidative stress biomarkers like oxylipins. Increased adiposity by itself induces various isomers of this oxidized lipid family, while dietary polyphenols show benefits in its regulation. Previously, we showed that specific co-abundant microorganisms characterized the gut microbiota of Colombians and associated differentially with diet, lifestyle, obesity, and cardiometabolic health status, which led us to hypothesize that urinary oxylipins would reflect the intensity of oxidative metabolism linked to gut microbiota dysbiosis. Thus, we selected a convenience sample of 105 participants (age: 40.2 ± 11.9 years, 47.6% women), grouped according to microbiota, cardiometabolic health status, and body mass index (BMI); and evaluated 33 urinary oxylipins by HPLC-QqQ-MS/MS (e.g., isoprostanes, prostaglandins, and metabolites), paired with anthropometry and blood chemistry information and dietary antioxidants estimated from a 24-h food recall. In general, oxylipins did not show differences among individuals who differed in gut microbiota. While the unmetabolized oxylipin levels were not associated with BMI, the total content of oxylipin metabolites was highest in obese and cardiometabolically abnormal subjects (e.g., insulin resistant), mainly by prostaglandin-D (2,3-dinor-11ß-PGF2α) and 15-F2t-IsoPs (2,3-dinor-15-F2t-IsoP and 2,3-dinor-15-epi-15-F2t-IsoP) metabolites. The total polyphenol intake in this cohort was 1070 ± 627 mg/day. After adjusting for body weight, the polyphenol intake was significantly higher in lean than overweight and showed an inverse association with dinor-oxylipin levels in principal component analysis. These results suggest that the 2,3-dinor-oxylipins could be more specific biomarkers associated with BMI than their parent oxylipins and that are sensitive to be regulated by dietary antioxidants.

Comparative Study of Metabolomic Profile and Antioxidant Content of Adult and In Vitro Leaves of Aristotelia chilensis.

This work aimed to identify the bioactive compounds present in adult maqui (Aristotelia chilensis) leaves from different stages of development and seasons of the year and compare them with leaves obtained from maqui plants grown in vitro. The qualitative and quantitative analysis of maqui leaf extracts by HPLC-DAD-ESI-MSn showed the presence of different polyphenolic compounds classified into galloyl and caffeoyl quinic acids, ellagitannins and ellagic acid- and flavonoid-derivatives. In general, the total phenolic content of the in vitro samples was higher than that of ex vitro samples, whereas the total flavonoid content was higher in winter basal leaves. Additionally, the analysis by HPLC-MS showed that the extract from spring basal leaves was enriched in quercetin, catechin, kaempferol and 3-caffeoyl quinic acids, while in the in vitro leaves extract, quercetin was not present. As regards lipophilic compounds identified by GC/MS, the samples of in vitro leaves showed a high presence of α-tocopherol and ß-sitosterol. In contrast, the samples of adult leaves presented a hight level of linolenic and linoleic acids. These results suggest that maqui leaves could be an excellent source of antioxidants and lipophilic compounds for many industries, such as the nutraceutical and pharmaceutical industries.

Oxylipin regulation by phenolic compounds from coffee beverage: Positive outcomes from a randomized controlled trial in healthy adults and macrophage derived foam cells.

Oxylipins are considered biomarkers related to cardiovascular diseases (CVDs). They are generated in vivo via the oxygenation of polyunsaturated fatty acids as a result of oxidative stress and inflammation. Oxylipins are involved in vascular functions and are produced during foam cell formation in atherogenesis. Additionally, the consumption coffee is associated with the regulation on a particular oxylipin group, the F2t-isoprostanes (F2t-IsoPs). This function has been attributed to the chlorogenic acids (CGAs) from the coffee beverage. Considering the anti-inflammatory and antioxidant properties of CGAs, we evaluated the effects of two types of coffee that provided 787 mg CGAs/day (Coffee A) and 407 mg CGAs/day (Coffee B) by reducing 35 selected oxylipins in healthy subjects. Furthermore, we assessed the effect of CGAs on the cellular proatherogenic response in foam cells by using an oxidized LDL (oxLDL)-macrophage interaction model. After eight weeks of coffee consumption, the contents of 12 urine oxylipins were reduced. However, the effect of Coffee A showed a stronger decrease in IsoPs, dihomo-IsoPs, prostaglandins (PGs) and PG metabolites, probably due to its higher content of CGAs. Neither of the two coffees reduced the levels of oxLDL. Moreover, the in vitro oxylipin induction by oxLDL on foam cells was ameliorated by phenolic acids and CGAs, including the inhibition of IsoPs and PGs by caffeoylquinic and dicaffeoylquinic acids, respectively, while the phenolic acids maintained both antioxidant and anti-inflammatory activities. These findings suggest that coffee antioxidants are strong regulators of oxylipins related to CVDs. The clinical trial was registered on the International Clinical Trials Registry Platform, WHO primary registry (RPCEC00000168).

Phenolic, oxylipin and fatty acid profiles of the Chilean hazelnut (Gevuina avellana): Antioxidant activity and inhibition of pro-inflammatory and metabolic syndrome-associated enzymes.

Roasted cotyledons of the Chilean hazelnut (Gevuina avellana) are appreciated as snacks. The aim of our work was to assess the fatty acid, oxylipin and phenolic composition using gas chromatography (GC) coupled to mass spectrometry (MS), ultra- high performance liquid chromatography (UHPLC) coupled to MS and HPLC coupled to diode array detector (HPLC-DAD). Additionally, various antioxidant activities were assessed. The inhibition of α-glucosidase, α-amylase, lipase, cyclooxygenases-1 and -2 (COX-1/COX-2), and lipoxygenase was determined. The main fatty acids were oleic and 7-hexadecenoic acids. Eight phytoprostanes and three phytofurans were identified and quantified. Hydroxybenzoic and hydroxycinnamic acids were the main phenolic compounds. Oils showed antioxidant activity determined by EPR, and inhibition of COX-1/COX-2. The statistical analysis showed that the roasting does not affect the composition of the samples. The occurrence of oxylipins in this species is reported for the first time. Chilean hazelnuts can be considered a source of health promoting compounds.

Comparative study of different cocoa (Theobroma cacao L.) clones in terms of their phytoprostanes and phytofurans contents.

Cocoa has been widely discussed as a bioactive food rich in sensory stimulation and health benefits. However, no information has been provided concerning phytoprostanes (PhytoPs) and phytofurans (PhytoFs) in cocoa. These compounds are of interest because they play a role in the regulation of immune function. The present study included 31 cocoa clones. The PhytoPs and PhytoFs were quantified by UHPLC-QqQ-MS/MS. The total PhytoPs and PhytoFs contents ranged from 221.46 to 1589.83 ng g-1 and from 1.18 to 13.13 ng g-1, respectively. The profiles of the PhytoPs and PhytoFs identified in the cocoa beans showed significant differences among the clones analysed. The results indicate that dry fermented cocoa beans are rich in PhytoPs and PhytoFs, which may represent an additional benefit of the consumption of foods derived from cocoa.

Oxidized LDL triggers changes in oxidative stress and inflammatory biomarkers in human macrophages.

Oxidized low-density lipoprotein (oxLDL) is a well-recognized proatherogenic particle that functions in atherosclerosis. In this study, we established conditions to generate human oxLDL, characterized according to the grade of lipid and protein oxidation, particle size and oxylipin content. The induction effect of the cellular proatherogenic response was assessed in foam cells by using an oxLDL-macrophage interaction model. Uptake of oxLDL, reactive oxygen species production and expression of oxLDL receptors (CD36, SR-A and LOX-1) were significantly increased in THP-1 macrophages. Analyses of 35 oxylipins revealed that isoprostanes (IsoP) and prostaglandins (PGs) derived from the oxidation of arachidonic, dihomo gamma-linolenic and eicosapentaenoic acids were strongly and significantly induced in macrophages stimulated with oxLDL. Importantly, the main metabolites responsible for the THP1-macrophage response to oxLDL exposure were the oxidative stress markers 5-epi-5-F2t-IsoP, 15-E1t-IsoP, 8-F3t-IsoP and 15-keto-15-F2t-IsoP as well as inflammatory markers PGDM, 17-trans-PGF3α, and 11ß-PGF2α, all of which are reported here, for the first time, to function in the interaction of oxLDL with THP-1 macrophages. By contrast, a salvage pathway mediated by anti-inflammatory PGs (PGE1 and 17-trans-PGF3α) was also identified, suggesting a response to oxLDL-induced injury. In conclusion, when THP-1 macrophages were treated with oxLDL, a specific induction of biomarkers related to oxidative stress and inflammation was triggered. This work contributes to our understanding of initial atherogenic events mediated by oxLDL-macrophage interactions and helps to generate new approaches for their modulation.

Quantification of phytoprostanes - bioactive oxylipins - and phenolic compounds of Passiflora edulis Sims shell using UHPLC-QqQ-MS/MS and LC-IT-DAD-MS/MS.

The genus Passiflora, comprising about 500 species, is the largest in the Passion flower family. Passiflora edulis Sims f. edulis (gulupa) is one of the most important fruits cultivated in Colombia. In recent years and due to its organoleptic and bioactive properties, its exports have significantly increased. In this work, six new bioactive oxylipins -phytoprostanes - were detected in gulupa shell by a UHPLC-QqQ-MS/MS method: F1t-phytoprostanes and D1t-phytoprostanes were the predominant and minor classes, respectively. Moreover, the polyphenol profile of the shell was investigated and we were able to detect and quantify phenolic compounds that have not been described previously, like luteolin-8-C-(2-O-rhamnosyl)hexoside and quercetin-3-O-(6″-acetyl)glucosyl-2″-sinapic acid. Consequently, this study provides new insights into the importance of gulupa shell as a valuable option in the design of new beverages rich in antioxidant phytochemicals, as part of a well-balanced diet, and in the process and quality control of such products.

Manejo Holístico Rehabilitador del paciente con Enfermedad de Parkinson / Rehabilitative Holistic management of the patient with Parkinsons disease

Se realizó una revisión bibliográfica sobre el manejo del paciente en la enfermedad de Parkinson. Se describieron de forma breve los pilares del tratamiento de rehabilitación y las posibles técnicas de Medicina Tradicional y Natural que deben complementar el manejo integral de dichos pacientes, con toda la información se conformó una propuesta de manejo holístico rehabilitador de estos pacientes (AU)

A bibliographical review on the patient's management of the Parkinsons disease was performed. In a brief way the pillars of the rehabilitation treatment and possible techniques of Traditional and Natural Medicine that should complement the integral management of this patients were described, with all the information it was conformed a proposal of these patients' holistic rehabilitative management (AU)

Manejo holístico rehabilitador del paciente con enfermedad de Parkinson / Rehabilitative holistic management of the patient with Parkinson’s disease

Se realizó una revisión bibliográfica sobre el manejo del paciente en la enfermedad de Parkinson. Se describieron de forma breve los pilares del tratamiento de rehabilitación y las posibles técnicas de Medicina Tradicional y Natural que deben complementar el manejo integral de dichos pacientes, con toda la información se conformó una propuesta de manejo holístico rehabilitador de estos pacientes.

A bibliographical review on the patient's management of the Parkinson’s disease was performed. In a brief way the pillars of the rehabilitation treatment and possible techniques of Traditional and Natural Medicine that should complement the integral management of this patients were described, with all the information it was conformed a proposal of these patients' holistic rehabilitative management.

Eficacia de la reflexología podal en el tratamiento del dolor cervical / Efficacy of the podal reflexology in the treatment of the cervical pain

Se realizó un ensayo clínico fase II, secuencial, abierto, no controlado y unicéntrico en 47 pacientes con diagnóstico de dolor cervical en la consulta externa de ortopedia de la Clínica Provincial de Medicina Natural y Tradicional de Camagüey, desde enero hasta septiembre de 2002, con el objetivo de determinar la eficacia de la reflexología podal como tratamiento de elección. Se comprueba que la reflexología podal resultó eficaz en la mayoría de la muestra por la desaparición del dolor y síntomas acompañantes. Se determinó la modificación más significativa de estos síntomas, según sesiones de tratamiento ocurriendo en la tercera, sexta y novena sesión para el vértigo, dolor y contractura muscular respectivamente. No se reportaron reacciones adversas(AU)

Eficacia de la eeflexología podal en el tratamiento del dolor cerviall / Efficacy of the podal reflexology in the treatment of the cervical pain

Se realizó un ensayo clínico fase II, secuencial, abierto, no controlado y unicéntrico en 47 pacientes con diagnóstico de dolor cervical en la consulta externa de ortopedia de la Clínica Provincial de Medicina Natural y Tradicional de Camagüey, desde enero hasta septiembre de 2002, con el objetivo de determinar la eficacia de la reflexología podal como tratamiento de elección. Se comprueba que la reflexología podal resultó eficaz en la mayoría de la muestra por la desaparición del dolor y síntomas acompañantes. Se determinó la modificación más significativa de estos síntomas, según sesiones de tratamiento ocurriendo en la tercera, sexta y novena sesión para el vértigo, dolor y contractura muscular respectivamente. No se reportaron reacciones adversas.

A phase II clinical trial, sequential, open, not controlled and unicentric in 47 patients was carried out, with cervical pain diagnosis attended in the orthopaedics external consultation at the Provincial Clinic of Traditional and Natural Medicine of Camagüey, from January to September 2002, with the objective to determine the efficacy of the podal reflexology as election treatment. It is verified that podal reflexology turned out to be efficient in the majority of the sample by pain disappearance and the accompanying symptoms. The most significant modification of these symptoms was determined, according to sessions of treatment occurring in the third, sixth and ninth session for the vertigo, pain and muscular contraction respectively. No adverse reactions were reported.