Study of the Potential Value of Ilex affinis (Aquifoliaceae) as a Novel Source for the Food and Pharmaceutical Industries

Ilex paraguariensis St. Hilaire (Aquifoliaceae) is processed industrially to produce the commercial product “yerba mate” which is used as a tea-like beverage. It is one of the most commercialized plants of South America. It is exported to the US, Europe and Asia as vegetal drug or extracts used in complementary and alternative medicine and in formulations for functional foods due to its properties as a CNS stimulant, diuretic, weight reducing, antioxidant and antihypercholesterolemic, among others. Ilex affinis grows in the same habitat and is used as substitute or adulterant of I. paraguariensis. This species was never investigated before. The objective of this work was to assess the phytochemical composition and to determine the pharmacological activity, according with the major compounds present in it. The results showed small quantities of caffeine and theobromine, but a considerable amount of polyphenols, especially chlorogenic acid and isochlorogenic acid. I. affinis extracts presented scavenging activity on free radical DPPH in a concentration-dependent manner. Antiproliferative action on lymphoma cell line exerting both cytostatic and cytotoxic activities was also demonstrated.Fil: Cogoi, Laura Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Martino, Renzo Fabricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Giberti, Gustavo Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Anesini, Claudia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Filip, Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentin

Study of the bioactive compounds variation during yerba mate (Ilex paraguariensis) processing

Ilex paraguariensis St. Hil. (Aquifoliaceae) (yerba mate) is one of the most used plant species in South America due to its nutritional and medicinal properties. The industrial processing involves different stages (green leaves, zapecado, drying, forced or natural aging) which can modify the qualitative and quantitative composition and the pharmacological activities. In this work, the main compounds, caffeoyl derivatives (caffeic acid, mono- and dicaffeoylquinic acids), methylxanthines (caffeine and theobromine) and flavonoids (rutin, quercetin and kaempferol) were studied by HPLC in extracts obtained by decoction of samples of a large amount of I. paraguariensis during its industrial process stages. The comparative quantitative analysis of all the samples indicated that those obtained after the zapecado, drying and aging stages possess higher content of biologically active principles when compared with green leaves. No differences were found between the natural and forced aging processes. This is the first complete report on the quantitative variation of the bioactive compounds of I. paraguariensis during each step of the industrial processing. The results obtained in this work provide a guideline for the obtention of extracts enriched in biological principles for the pharmaceutical, food and cosmeceutical industry.Fil: Isolabella, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Cogoi, Laura Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: López, Paula Gladys. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Anesini, Claudia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Ferraro, Graciela Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Filip, Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentin

Anatomy, histochemistry, and comparative analysis of hydroxycinnamic derivatives in healthy leaves and galls induced by Baccharopelma spp. (Hemiptera: Psyllidae) in Baccharis spicata (Lam) Baill (Asteraceae)

Baccharis spicata is a plant native to the south of South America And is infected by psyllids of the Baccharopelma genus, which induce a fold gall in its leaves. This infection induces a series of anatomical and phytochemical variations compared to the healthy leaf: the content of total phenolic compounds and total hidroxycinnamic derivatives is lower, though the chlorogenic acid measured by HPLC remains the same and the 4,5 dichlorogenic acid content is near the half of the one observed in the one in the healthy leaf. Regarding to its anatomy, the gall has an homogeneous mesophyll and flavonoids in its outer epidermis compared to an isobilateral mesophyll and epidermal flavonoidic idioblasts observed in the leaf. The increase in the expression of waxes suggests it is a protective function against the desiccation by preventing water evaporation in the structure. The results here exposed suggest that the psyllid manipulates plant tissues, inducing hyperplasia and hypertrophy in the tissues, differentiating them from healthy structures and inducing changes in the biosynthesis of secondary polyphenolic metabolites that act like intermediary between the gall and the environment.Fil: Agudelo, Ignacio Jorge. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Cogoi, Laura Carolina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Filip, Rosana. Universidad de Buenos Aires; ArgentinaFil: Kuzmanich, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Wagner, Marcelo Luis. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Ricco, Rafael Alejandro. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

Intestinal/uterine antispasmodics, sedative effects of Fuchsia magellanica Lam. leaves’ and flowers’ extracts and their flavonolic components

Background: Fuchsia magellanica Lam. ( Onagraceae ) is a native plant of the Andean-Patagonian region, and it is also naturalized in Argentina and other parts of the world. Leaves are used for treating indigestion, stomachache, as sedative, for difficult delivery and as antiemmenagogue. However, up to now the pharmacological basis of such uses were not studied. Purpose: This work evaluates the gastrointestinal, uterine and sedative effects of leaves (L) and flowers (F) tinc- tures of F. magellanica from wild patagonian (T-Fm-P) and naturalized (T-Fm-BA) plants, as well as the mechanism of action and the flavonoids profile of both plants. Methods: Phytochemical studies were evaluated by using TLC and HPLC methodologies. The ex-vivo effects of T-Fm-BA and T-Fm-P were evaluated on contractile concentration-response curves (CRC) of carbachol (CCh) and calcium (Ca 2 + ) in rat isolated intestinal and uterine tissues. In vivo tests for intestinal transit, elevated cross plus-maze and open-field tests were performed in mice. Results: Wild and cultivated leaves and flowers ethanolic extracts induced antispasmodic effect, as a non- competitive inhibitor of the CCh-CRC in intestine, with IC 50 of 272.8 ± 64.3 μg/ml for T-L-Fm-P and 257.4 ± 36 μg/ml for T-L-Fm-BA. A similar effect was obtained in Ca 2 + -CRC with IC 50 of 152.9 ± 29.1 μg/ml and 138.4 ± 48.6 μg/ml respectively. Mice intestinal transit was reduced at oral doses of 73.5 mg/kg of T-L-Fm-P. In uterine tissues, both T-L-Fm reduced the contractions of CCh CRC´s as non-competitive antagonists, with IC 50 near those in intestine. The T-L-Fm-BA also inhibited the serotonin CRC´s and contribution of other relaxing mechanisms was investigated. Although extracts didn?t show anxiolytic effect in the elevated cross plus-maze test, they reduced the spontaneous activity of mice in the open-field at 32.7 mg/kg T-L-Fm-P and 41.7 mg/kg T-L-Fm-BA. Conclusions: Leaves and flowers ethanolic extracts from wild and cultivated plant F. magellanica showed intesti- nal and uterine antispasmodic effects, mainly by interfering with Ca 2 + influx. In mice, the ethanolic extracts reduced the intestinal transit and showed sedative effect. The effects agree with the presence of flavonoids, such as quercetin and kaempferol. This is the first study which gives experimental support for some of the traditional uses of F. magellanica .Fil: Bernal Ochoa, Ana María. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Farmacología; ArgentinaFil: Colareda, German Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Farmacología; ArgentinaFil: Matera, Soledad Inés. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Farmacología; ArgentinaFil: Ragone, María Inés. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Isolabella Capua, Santiago Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Filip, Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Consolini, Alicia Elvira. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Farmacología; Argentin

Uso potencial de extractos de Larrea divaricata con bajo contenido de NDGA como antioxidantes en comidas

Larrea divaricata Cav. is widely distributed in Argentina. Aqueous extract, of its leaves, has documented antitumoral and immunomodulatory activities. In this study, the antioxidant activity of aqueous extract and a component, nordihydroguaiaretic acid was determined and compared using different assays. Both the aqueous extract and nordihydroguaiaretic acid exhibited antioxidant activity. However, results show that it is very likely that compounds other than nordihydroguaiaretic acid could be involved in the antioxidant activity of the extract. Since nordihydroguaiaretic acid is nephrotoxic and hepatotoxic agent, it is important to direct efforts toward the potential use of low-nordihydroguaiaretic acid L. divaricata extracts as antioxidant in foods.Larrea divaricata Cav. está ampliamente distribuida en la Argentina. Se han documentado actividades antitumorales e inmunomoduladoras de los extractos acuosos de sus hojas. En este estudio, la actividad antioxidante del extracto acuoso y un componente, el ácido nordihidroguayarético, se determinaron y compararon mediante diferentes ensayos. Tanto el extracto acuoso como el ácido nordihidroguayarético mostraron actividad antioxidante. Sin embargo, los resultados muestran que es muy probable que otros compuestos diferentes al ácido nordihidroguayarético pudieran estar involucrados en la actividad antioxidante de los extractos. Dado que el ácido nordihidroguayarético es un agente nefrotóxico y hepatotóxico, es importante dirigir los esfuerzos hacia el uso potencial de extractos de L. divaricata con bajas cantidades de ácido nordihidroguayarético como antioxidantes en alimentos

Optimization and validation of the quantitative assay of flavonoids in Achyrocline satureioides and A. flaccida

Several populations of Achyrocline satureioides and Achyrocline flaccida from Argentina, two aromatic herbal species widely used in traditional medicine in South America and both known as marcela, were analyzed. The aims of this work were to evaluate the amounts of flavonoids that characterize these species in this country and provide a quantitative assay to be included in the monograph of marcela for future Argentine Pharmacopoeia editions. The extraction method and analysis by HPLC of the main flavonoids, quercetin and 3-O-methylquercetin, were optimized. The validation parameters of the method were determined. The analysis of the different parts of these plants was carried out thereafter. Inflorescences were the parts displaying the highest content of such flavonoids. It was found that A. flaccida had a slightly higher content of flavonoids than A. satureioides (1.2 ± 0.4 % of quercetin, 0.8 ± 0.3 % of 3-Omethylquercetin; 0.8 ± 0.2 % of quercetin and 0.7 ± 0.5 % of 3-O-methylquercetin, respectively).Colegio de Farmacéuticos de la Provincia de Buenos Aire

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016

Global, regional, and national under-5 mortality, adult mortality, age-specific mortality, and life expectancy, 1970–2016: a systematic analysis for the Global Burden of Disease Study 2016

BACKGROUND: Detailed assessments of mortality patterns, particularly age-specific mortality, represent a crucial input that enables health systems to target interventions to specific populations. Understanding how all-cause mortality has changed with respect to development status can identify exemplars for best practice. To accomplish this, the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) estimated age-specific and sex-specific all-cause mortality between 1970 and 2016 for 195 countries and territories and at the subnational level for the five countries with a population greater than 200 million in 2016. METHODS: We have evaluated how well civil registration systems captured deaths using a set of demographic methods called death distribution methods for adults and from consideration of survey and census data for children younger than 5 years. We generated an overall assessment of completeness of registration of deaths by dividing registered deaths in each location-year by our estimate of all-age deaths generated from our overall estimation process. For 163 locations, including subnational units in countries with a population greater than 200 million with complete vital registration (VR) systems, our estimates were largely driven by the observed data, with corrections for small fluctuations in numbers and estimation for recent years where there were lags in data reporting (lags were variable by location, generally between 1 year and 6 years). For other locations, we took advantage of different data sources available to measure under-5 mortality rates (U5MR) using complete birth histories, summary birth histories, and incomplete VR with adjustments; we measured adult mortality rate (the probability of death in individuals aged 15-60 years) using adjusted incomplete VR, sibling histories, and household death recall. We used the U5MR and adult mortality rate, together with crude death rate due to HIV in the GBD model life table system, to estimate age-specific and sex-specific death rates for each location-year. Using various international databases, we identified fatal discontinuities, which we defined as increases in the death rate of more than one death per million, resulting from conflict and terrorism, natural disasters, major transport or technological accidents, and a subset of epidemic infectious diseases; these were added to estimates in the relevant years. In 47 countries with an identified peak adult prevalence for HIV/AIDS of more than 0·5% and where VR systems were less than 65% complete, we informed our estimates of age-sex-specific mortality using the Estimation and Projection Package (EPP)-Spectrum model fitted to national HIV/AIDS prevalence surveys and antenatal clinic serosurveillance systems. We estimated stillbirths, early neonatal, late neonatal, and childhood mortality using both survey and VR data in spatiotemporal Gaussian process regression models. We estimated abridged life tables for all location-years using age-specific death rates. We grouped locations into development quintiles based on the Socio-demographic Index (SDI) and analysed mortality trends by quintile. Using spline regression, we estimated the expected mortality rate for each age-sex group as a function of SDI. We identified countries with higher life expectancy than expected by comparing observed life expectancy to anticipated life expectancy on the basis of development status alone. FINDINGS: Completeness in the registration of deaths increased from 28% in 1970 to a peak of 45% in 2013; completeness was lower after 2013 because of lags in reporting. Total deaths in children younger than 5 years decreased from 1970 to 2016, and slower decreases occurred at ages 5-24 years. By contrast, numbers of adult deaths increased in each 5-year age bracket above the age of 25 years. The distribution of annualised rates of change in age-specific mortality rate differed over the period 2000 to 2016 compared with earlier decades: increasing annualised rates of change were less frequent, although rising annualised rates of change still occurred in some locations, particularly for adolescent and younger adult age groups. Rates of stillbirths and under-5 mortality both decreased globally from 1970. Evidence for global convergence of death rates was mixed; although the absolute difference between age-standardised death rates narrowed between countries at the lowest and highest levels of SDI, the ratio of these death rates-a measure of relative inequality-increased slightly. There was a strong shift between 1970 and 2016 toward higher life expectancy, most noticeably at higher levels of SDI. Among countries with populations greater than 1 million in 2016, life expectancy at birth was highest for women in Japan, at 86·9 years (95% UI 86·7-87·2), and for men in Singapore, at 81·3 years (78·8-83·7) in 2016. Male life expectancy was generally lower than female life expectancy between 1970 and 2016, an