Estudios etnofarmacológicos de Cecropia obtusifolia (Urticaceae) y su importancia en el tratamiento de la diabetes mellitus tipo 2 (DM-2): una mini-revisión

Background and Aims: Diabetes mellitus type 2 (DM-2) is one of the most recurrent chronic diseases worldwide, it is usually treated with synthetic medications, many of which have important repercussions on the patient's body. For this reason, ethnopharmacology has become more important in recent years, because a large number of plant resources origin are used in medicine and are shown as positive effect in the treatment of different diseases, including DM-2. Therefore, the aim of this review is to highlight how previous studies are adding to the understanding and knowledge of the biological effects reported in Cecropia obtusifolia, a tropical plant included in the Herbal Pharmacopoeia of the United Mexican States (FHEUM), which is commonly used to treat DM-2.Methods: A profound literature review was carried out on C. obtusifolia, focusing on diverse phytochemical, pharmacological, clinical and toxicological studies, as well as on some other relevant research findings.Key results: It is recognized that this species is able to decrease serum glucose, cholesterol and triglyceride levels due to its hypoglycemic and hypolipidemic properties, which has been demonstrated both in animal and human experimental models, attributing these effects to chlorogenic acid and isoorientin. These previous reports suggest that C. obtusifolia is a promising candidate for the development of a phytopharmaceutical which could be used in the treatment of DM-2.Conclusions: We provide an updated and complete overview of the phytochemistry, traditional uses, and pharmacological activities of C. obtusifolia. Regarding its pharmacological activities, we focus mainly on the hypoglycemic effect of this plant which supports its traditional use in DM-2 control. Moreover, the present knowledge was critically assessed to provide some evidence and justifications and propose future research prospects.Antecedentes y Objetivos: La diabetes mellitus tipo 2 (DM-2) es una de las enfermedades crónicas recurrentes más comunes, generalmente se trata con medicamentos sintéticos, muchos de los cuales tienen importantes repercusiones en el cuerpo del paciente. Por esta razón, la etnofarmacología se ha vuelto más importante en los últimos años, porque una gran cantidad de recursos de origen vegetal son utilizados en medicina y muestran un efecto positivo en el tratamiento de diferentes enfermedades, incluyendo DM-2. Por lo tanto, el objetivo de esta revisión es destacar cómo los estudios previos se suman a la comprensión y el conocimiento de los efectos biológicos informados en Cecropia obtusifolia, una planta tropical incluida en la Farmacopea Herbolaria de los Estados Unidos Mexicanos (FHEUM), comúnmente usada para tratar DM-2.Métodos: Se realizó una revisión profunda de la literatura sobre C. obtusifolia, centrándose en diversos estudios fitoquímicos, farmacológicos, clínicos y toxicológicos, así como en otros hallazgos relevantes de investigación.Resultados clave: Se reconoce que esta especie es capaz de disminuir los niveles séricos de glucosa, colesterol y triglicéridos, debido a sus propiedades hipoglucémicas e hipolipidémicas reductoras de lípidos, que se han demostrado tanto en modelos experimentales animales como en humanos, atribuyendo estos efectos al ácido clorogénico y la isoorienina. Estos informes previos sugieren que C. obtusifolia es un candidato prometedor para el desarrollo de un fitofarmacéutico que podría usarse en el tratamiento de DM-2.Conclusiones: Brindamos una visión general actualizada y completa de la fitoquímica, los usos tradicionales y las actividades farmacológicas de C. obtusifolia. En cuanto a sus actividades farmacológicas, nos centramos principalmente en el efecto hipoglucémico de esta planta que apoya su uso tradicional en el control de DM-2. Además, el conocimiento actual se evaluó críticamente para proporcionar algunas pruebas y justificaciones y proponer futuras perspectivas de investigación

Integrated Analysis of the Transcriptome and Metabolome of Cecropia obtusifolia: A Plant with High Chlorogenic Acid Content Traditionally Used to Treat Diabetes Mellitus

This investigation cultured Cecropia obtusifolia cells in suspension to evaluate the effect of nitrate deficiency on the growth and production of chlorogenic acid (CGA), a secondary metabolite with hypoglycemic and hypolipidemic activity that acts directly on type 2 diabetes mellitus. Using cell cultures in suspension, a kinetics time course was established with six time points and four total nitrate concentrations. The metabolites of interest were quantified by high-performance liquid chromatography (HPLC), and the metabolome was analyzed using directed and nondirected approaches. Finally, using RNA-seq methodology, the first transcript collection for C. obtusifolia was generated. HPLC analysis detected CGA at all sampling points, while metabolomic analysis confirmed the identity of CGA and of precursors involved in its biosynthesis. Transcriptome analysis identified differentially expressed genes and enzymes involved in the biosynthetic pathway of CGA. C. obtusifolia probably expresses a key enzyme with bifunctional activity, the hydroxycinnamoyl-CoA quinate hydroxycinnamoyl transferase and hydroxycinnamoyl-CoA shikimate/quinate hydroxycinnamoyl transferase (HQT/HCT), which recognizes shikimic acid or quinic acid as a substrate and incorporates either into one of the two routes responsible for CGA biosynthesis

Non-Targeted Metabolomic Analysis of <i>Arabidopsis thaliana</i> (L.) Heynh: Metabolic Adaptive Responses to Stress Caused by N Starvation

As sessile organisms, plants develop the ability to respond and survive in changing environments. Such adaptive responses maximize phenotypic and metabolic fitness, allowing plants to adjust their growth and development. In this study, we analyzed the metabolic plasticity of Arabidopsis thaliana in response to nitrate deprivation by untargeted metabolomic analysis and using wild-type (WT) genotypes and the loss-of-function nia1/nia2 double mutant. Secondary metabolites were identified using seedlings grown on a hydroponic system supplemented with optimal or limiting concentrations of N (4 or 0.2 mM, respectively) and harvested at 15 and 30 days of age. Then, spectral libraries generated from shoots and roots in both ionization modes (ESI +/−) were compared. Totals of 3407 and 4521 spectral signals (m/z_rt) were obtained in the ESI+ and ESI− modes, respectively. Of these, approximately 50 and 65% were identified as differentially synthetized/accumulated. This led to the presumptive identification of 735 KEGG codes (metabolites) belonging to 79 metabolic pathways. The metabolic responses in the shoots and roots of WT genotypes at 4 mM of N favor the synthesis/accumulation of metabolites strongly related to growth. In contrast, for the nia1/nia2 double mutant (similar as the WT genotype at 0.2 mM N), metabolites identified as differentially synthetized/accumulated help cope with stress, regulating oxidative stress and preventing programmed cell death, meaning that metabolic responses under N starvation compromise growth to prioritize a defensive response

Worldwide Disparities in Recovery of Cardiac Testing 1 Year Into COVID-19

BACKGROUND The extent to which health care systems have adapted to the COVID-19 pandemic to provide necessary cardiac diagnostic services is unknown.OBJECTIVES The aim of this study was to determine the impact of the pandemic on cardiac testing practices, volumes and types of diagnostic services, and perceived psychological stress to health care providers worldwide.METHODS The International Atomic Energy Agency conducted a worldwide survey assessing alterations from baseline in cardiovascular diagnostic care at the pandemic's onset and 1 year later. Multivariable regression was used to determine factors associated with procedure volume recovery.RESULTS Surveys were submitted from 669 centers in 107 countries. Worldwide reduction in cardiac procedure volumes of 64% from March 2019 to April 2020 recovered by April 2021 in high- and upper middle-income countries (recovery rates of 108% and 99%) but remained depressed in lower middle- and low-income countries (46% and 30% recovery). Although stress testing was used 12% less frequently in 2021 than in 2019, coronary computed tomographic angiography was used 14% more, a trend also seen for other advanced cardiac imaging modalities (positron emission tomography and magnetic resonance; 22%-25% increases). Pandemic-related psychological stress was estimated to have affected nearly 40% of staff, impacting patient care at 78% of sites. In multivariable regression, only lower-income status and physicians' psychological stress were significant in predicting recovery of cardiac testing.CONCLUSIONS Cardiac diagnostic testing has yet to recover to prepandemic levels in lower-income countries. Worldwide, the decrease in standard stress testing is offset by greater use of advanced cardiac imaging modalities. Pandemic-related psychological stress among providers is widespread and associated with poor recovery of cardiac testing. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation