Gochnatia glutinosa (D.Don) D.Don ex Hook. & Arn.: A plant with medicinal value against inflammatory disorders and infections.

Gochnatia glutinosa is a shrub that grown in the Argentinean semiarid region (Monte region) used in the ancestral medicine as an antiseptic and anti-inflammatory agent. This study was aimed to examine the morpho-anatomical characteristics of G. glutinosa aerial parts, identify the chemical composition of traditionally used preparations to assess its pharmacobotanical characterization and evaluate its activity as antiseptic and anti-inflammatory to give scientific support to its traditional uses. G. glutinosa morpho-anatomical description was performed following standard histological techniques. Tincture and infusion of its aerial parts were prepared and were subjected to phytochemical analysis. Xanthine oxidase (XOD) and lipoxygenase (LOX) inhibition experiments, as well as ABTS•+, superoxide radical, and hydrogen peroxide scavenging activity, were carried out. The growth inhibition of methicillin-resistant Staphylococcus aureus (MRSA) strains was also determined. The morpho-anatomical traits of G. glutinosa leaves and stems were reported for the first time. The medicinal preparations exhibited a large amount of phenolic chemicals mainly flavonoids such as rhamnetin, arcapillin, rhamnacin, hesperetin, isorhamnetin, centaureidin, europetin 7-O-mehylmyricetin, cirsiliol, sakuranetin, genkwanin and eupatorine and also phenolic acids and diterpenoid derivatives. Both preparations had free radical scavenging activity and were able to reduce both XOD and LOX activity, indicating their anti-inflammatory properties. Besides, tincture was effective against all MRSA strains (MIC values ranging from 60 to 240 g DW/mL). The results obtained in this work scientifically support the medicinal popular use of G. glutinosa as an antiseptic and anti-inflammatory. The identification of bioactive compounds and their morpho-anatomical description contribute to the quality control of this medicinal plant from Argentine Calchaquí Valley.

Nicotiana tabacum Leaf Waste: Morphological Characterization and Chemical-Functional Analysis of Extracts Obtained from Powder Leaves by Using Green Solvents.

Tobacco cultivation and industrialization are characterized by the production of trillions of pre-harvest and post-harvest waste biomasses each year with the resulting negative effects on the environment. The leaves of blunt, pre-harvest waste, could be further used to obtain bioactive metabolites, i.e., polyphenols and alkaloids, for its potential cosmetic use. This study was conducted to obtain bio-compounds from pre-harvest tobacco leaf waste (var. Virginia) by applying conventional and green solvents (NaDES). Leaves and ground leaf waste were characterized based on their microscopic features. Conventional solvents, such as water, acetone, ethanol, and non-conventional solvents, such as Natural Deep Eutectic Solvents (NaDES), i.e., sucrose:lactic acid (LAS), frutose:glucose:sucrose (FGS), lactic acid:sucrose:water (SALA), choline chloride:urea (CU), and citric acid: propylene glycol (CAP) were used for bioactive extraction from tobacco waste powder. CU, FGS, and acetone/ethanol had similar behavior for the best extraction of alkaloids (6.37-11.23 mg ACE/g tobacco powder). LAS, FGS, SALA, and CU were more effective in phenolic compound extraction than conventional solvents (18.13-21.98 mg AGE/g tobacco powder). Because of this, LAS and SALA could be used to obtain phenolic-enriched extracts with lower alkaloid content rather than CU and FGS. Extracts of the powder obtained with conventional solvent or CU showed a high level of sugars (47 mg/g tobacco powder) The ABTS antioxidant capacity of tobacco leaf powder was higher in the extracts obtained with CU, FGS, and acetone (SC50 1.6-5 µg GAE/mL) while H2O2 scavenging activity was better in the extracts obtained with LAS, CAP and SALA (SC50 3.8-8.7 µg GAE/mL). Due to the biocompatibility of the NaDES with the components of tobacco leaf waste, the opportunity to apply these extracts directly in antioxidant formulations, such as cosmetics, phytotherapic, and other formulations of topic use seems promising. Furthermore, NaDES constituents, i.e., urea and organic acid can also have beneficial effects on the skin.

Exploring Next Generation Probiotics for Metabolic and Microbiota Dysbiosis Linked to Xenobiotic Exposure: Holistic Approach.

Variation of gut microbiota in metabolic diseases seems to be related to dysbiosis induced by exposure to multiple substances called Microbiota Disrupting Chemicals (MDCs), which are present as environmental and dietary contaminants. Some recent studies have focused on elucidating the alterations of gut microbiota taxa and their metabolites as a consequence of xenobiotic exposures to find possible key targets involved in the severity of the host disease triggered. Compilation of data supporting the triad of xenobiotic-microbiota-metabolic diseases would subsequently allow such health misbalances to be prevented or treated by identifying beneficial microbe taxa that could be Next Generation Probiotics (NGPs) with metabolic enzymes for MDC neutralisation and mitigation strategies. In this review, we aim to compile the available information and reports focused on variations of the main gut microbiota taxa in metabolic diseases associated with xenobiotic exposure and related microbial metabolite profiles impacting the host health status. We performed an extensive literature search using SCOPUS, Web of Science, and PubMed databases. The data retrieval and thorough analyses highlight the need for more combined metagenomic and metabolomic studies revealing signatures for xenobiotics and triggered metabolic diseases. Moreover, metabolome and microbiome compositional taxa analyses allow further exploration of how to target beneficial NGP candidates according to their alleged variability abundance and potential therapeutic significance. Furthermore, this holistic approach has identified limitations and the need of future directions to expand and integrate key knowledge to design appropriate clinical and interventional studies with NGPs. Apart from human health, the beneficial microbes and metabolites identified could also be proposed for various applications under One Health, such as probiotics for animals, plants and environmental bioremediation.

Flower beverages of native medicinal plants from Argentina (Acacia caven, Geoffroea decorticans and Larrea divaricata) as antioxidant and anti-inflammatory.

ETHNOPHARMACOLOGICAL RELEVANCE: Herbal beverages have been used as a natural part of the medicinal and food culture in northwestern Argentina. The flower beverages (infusion or decoction) of Acacia caven, Geoffroea decorticans and Larrea divaricata, three native species from arid and semiarid regions of Argentina are widely used as anti-inflammatory and anti-rheumatic by several local communities. AIM OF THE STUDY: The aim of this study was to analyze the phytochemical composition of some Argentine flower beverage and to validate its traditional use as an antioxidant and anti-inflammatory agent. MATERIALS AND METHODS: Phenolic profiles from all flower infusions and decoctions were analyzed by both spectrophotometric analysis and HPLC-DAD. ABTS•+; the scavenging activity of both hydrogen peroxide and hydroxyl radical was determined and finally, their ability to inhibit pro-inflammatory enzymes, such as xanthine oxidase (XOD), and lipoxygenase (LOX) was also assessed. RESULTS: The flower beverages of all assayed species showed a high level of phenolic compounds with similar chromatographic patterns in both infusions and decoctions of each plant species, the major components of which have been identified. The flower beverages, especially G. decorticans infusion and decoctions, displayed an important antioxidant activity (SC50 values between 18.14 and 47 µg/mL) through different mechanisms; all of them were able to inhibit the XOD enzyme activity and, consequently, the formation of uric acid and reactive oxygen species, the primary cause of arthritis-related diseases. The most active beverages as XOD inhibitor were G. decorticans flower infusion and decoctions (IC50 values of 20 and 35 µg/mL, respectively). Pro-inflammatory enzymes, such as LOX, were also inhibited by infusions and decoctions of G. decorticans, L. cuneifolia and A caven flowers, lessening inflammation mediators in all beverages. CONCLUSIONS: The present work validates the traditional medicinal use of flower beverages from Argentina as an anti-rheumatic and anti-inflammatory agent as it has been used for hundreds of years in several pathologies associated with oxidative stress.

Potential use of medicinal plants from Argentinean highland as agent anti-photoaging.

BACKGROUND: The overexposure to sun ultraviolet (UV) radiation produce photoaging by effect of free radicals on lipid, protein, and nucleic acid or by direct activation of responsible enzymes of cleavage of extracellular matrix components (EMC). AIMS: To develop new anti-photoaging agents, the anti-aging activity of four "jarillas" standardized extracts from Argentina (Zuccagnia punctata Cav.,Larrea divaricata Cav.,Larrea cuneifolia Cav., and Larrea nitida Cav.) were examined. METHODS: The effect on the activity and expression of enzymes related to photoaging (collagenase, hyaluronidase, elastase, tyrosinase) and the antioxidant capacity of four "jarillas" extracts were examined. RESULTS: The results suggest that "jarillas" extracts could protect EMC by inhibition of skin aging-related enzymes and suppression of the expression of metalloproteinases (MMP-1) in human skin fibroblasts from photoinduced damage. Modulation of MMP-1 expression induced by UV radiation in human skin cells could be associated, at least in part, with the ROS scavenging capacity of "jarilla" extracts. The extract of Z punctata was more active than Larrea species extracts in all the trials. The activity of Z punctata and Larrea extracts could be ascribed to chalcones and lignans, major constituents of "jarillas," respectively. CONCLUSIONS: The results obtained would indicate the potential of these adapted species to live in arid zones of Argentina, exposed to high ultraviolet radiation in production of cosmetic products and justify the promotion of their sustainable use and the development of crops.

Flourensia fiebrigii S.F. blake: A medicinal plant from the Argentinean highlands with potential use as anti-rheumatic and anti-inflammatory.

ETHNOPHARMACOLOGICAL RELEVANCE: Flourensia fiebrigii is a plant used in traditional medicine in the Argentine Calchaquí Valley as purgative, expectorant, anti-rheumatic and anti-inflammatory. AIM OF THE STUDY: The aim of this study was to analyze the macroscopic and microscopic characteristics of F. fiebrigii leaf and stem, the phytochemical composition of leaves ethanolic extracts and to validate its traditional use as anti-rheumatic and anti-inflammatory. MATERIALS AND METHODS: The macroscopic and microscopic description of F. fiebrigii leaf and stem was carried out. Two extracts (immersions and tinctures) from leaves were obtained. The phytochemical analysis and UHPLC-OT-MS metabolome fingerprinting of both extracts were performed. The anti-rheumatic and anti-inflammatory activities of both extracts were determined using enzymatic inhibition assays of xanthine-oxidase (XOD), secretory phospholipase A2 (sPLA2) and lipoxygenase (LOX). RESULTS: The macroscopic and micrographic characters of F. fiebrigii were described to allow the botanical characterization of the plant species. The leaves extracts showed a high level of phenolic compounds with similar chromatographic patterns. Forty-five compounds were identified based on UHPLC-OT-MS including several sesquiterpenes, chalcones, flavonoids, isoflavonoids, a lignan and phenylpropanoids phenolic acids that have been identified for the first time in this plant species. F. fiebrigii extracts were able to inhibit the XOD activity and, consequently, the formation of uric acid and reactive oxygen species, primary cause of diseases, such as gouty arthritis (IC50 values of 1.10-2.12 µg/mL). Pro-inflammatory enzymes like sPLA2 and LOX were also inhibited by F. fiebrigii extracts (IC50 values of 22.00-2.20 µg/mL) decreasing the production of inflammation mediators. CONCLUSIONS: The present work validates the traditional medicinal use of F. fiebrigii as anti-rheumatic and anti-inflammatory through the use of enzymatic assays. The presence of several chemical compounds with demonstrated anti-rheumatic and anti-inflammatory properties also supports the bioactivity of the F. fiebrigii.

Antifungal, anti-inflammatory and antioxidant activity of bi-herbal mixtures with medicinal plants from Argentinean highlands.

ETHNOPHARMACOLOGICAL RELEVANCE: Argentinean medicinal plants such as Larrea divaricata Cav., Larrea cuneifolia Cav., Larrea nitida Cav., Zuccagnia punctata Cav. and Tetraglochin andina Ciald. are used alone and in combination in traditional medicine by inhabitants from northwestern Argentina to solve mycosis, vaginal infections, gastrointestinal, respiratory, and inflammatory processes. AIM OF THE STUDY: To assess the effect of interactions between hydroalcoholic extracts of these five species of medicinal plants against yeast strains isolated from vaginal infections, select the most active mixtures and evaluate anti-inflammatory and antioxidant activities. MATERIAL AND METHODS: Synergy between the plant extracts was studied by using a broth microdilution assay by means of the checkerboard method against Saccharomyces cerevisiae, Candida albicans, and non albicans strains. The inhibitory effect on lipoxygenase and the antioxidant capacity in cell-free and cell systems were studied. The chemical profile was evaluated by qualitative and quantitative screening, whereas chemical markers were quantified by HPLC-DAD. RESULTS: A synergistic antifungal effect was observed in some binary combinations. Z. punctata/L. divaricata, Z. punctata/L. cuneifolia, and Z. punctata/L. nitida were the most active mixtures. Nordihydroguaiaretic acid and 2',4'-dihydroxychalcone, two antifungal compounds, present in these extracts, were identified and quantified by HPLC-DAD. Both single extracts and bi-herbal mixtures showed antioxidant activity (in cellular and in cell-free systems) and were active on pro-inflammatory enzymes (LOX). CONCLUSIONS: Our results indicated that the most active combinations of these species extracts could be useful in the treatment of vaginal infectious diseases caused by Saccharomyces cerevisiae and Candida spp. strains and in associated oxidative and inflammatory processes, supporting its traditional use. In addition, the results highlighted the phyto-therapeutic potential of total phytochemical compounds present in these medicinal plants.

Fitomedicamentos obtenidos de plantas medicinales argentinas como estrategia para la prevención y tratamiento de patógenos responsables de infecciones vaginales / Phytomedicines obtained from Argentine medicinal plants as a strategy for the prevention and treatment of pathogens responsible for vaginal infections

En los últimos años, la investigación de productos naturales ha atraído mucha atención en todo el mundo. Las plantas medicinales se han utilizado desde la antigüedad y constituyen una importante fuente de nuevos medicamentos. El objetivo de este trabajo de Tesis Doctoral fue avanzar en el diseño de productos fitoterapéuticos para la prevención y/o tratamiento de infecciones vaginales, utilizando extractos hidroalcohólicos de especies vegetales que crecen en el noroeste de Argentina, tales como Zuccagnia punctata, Larrea cuneifolia, Larrea divaricata, Larrea nitida y Tetraglochin andina. Estas especies se utilizan en la medicina tradicional para tratar infecciones fúngicas y procesos inflamatorios.Los perfiles fitoquímicos reflejaron la presencia de taninos, flavonoides, triterpenos y/o esteroides y derivados antracénicos en todas las especies vegetales. Se detectó la presencia de cumarinas en L. divaricata y de saponinas y glucósidos cardiotónicos en T. andina.Se realizaron estudios de HPLC-ESI-MS/MS y se identificaron 23 compuestos en extractos de Z. punctata (principalmente chalconas), 50 compuestos en T. andina (en su mayoría taninos hidrolizables) y 12 compuestos en las especies de Larrea (trihidroxi-6,7ʹ ciclolignano fue encontrado solo en L. divaricata y dihidroxi-metoxi-epoxilignano en L. cuneifolia y L. nitida).Se determinó la actividad antifúngica de los extractos hidroalcohólicos de las especies vegetales frente a hongos levaduriformes aislados de infecciones vaginales. De acuerdo a los resultados obtenidos, se podrían considerar a los fitoextractos de Z. punctata, L. divaricata y L. nitida como inhibidores fuertes del crecimiento de Candida spp., L. cuneifolia como inhibidor moderado y T. andina como inhibidor moderado o débil dependiendo de la cepa analizada. Se realizaron mezclas binarias entre las cinco especies vegetales utilizando el método del tablero de ajedrez. Algunas de las combinaciones mostraron efecto sinérgico, siendo las más activas las mezclas de Z. punctata/L. nitida (Zp/Ln); Z. punctata/L. divaricata (Zp/Ld) y Z. punctata/L. cuneifolia (Zp/Lc).En general, las infecciones vaginales están asociadas a situaciones de estrés oxidativo y procesos inflamatorios, por ello se analizó la actividad de estos productos naturales como antioxidantes y antiinflamatorios. Tanto los extractos como las mezclas más activas (Zp/Ln, Zp/Ld, Zp/Lc) presentan capacidad de depurar radicales libres y especies de oxígeno reactivas, capacidad de inhibir la hemólisis oxidativa de eritrocitos humanos22y de inhibir la actividad de enzimas que participan en el proceso inflamatorio (fosfolipasa, lipooxigenasa y ciclooxigenasa).Con el propósito de garantizar el uso terapéutico seguro de los extractos y mezclas binarias de los mismos, se evaluó el efecto genotóxico a través del test de Ames, demostrando que no presentan actividad mutagénica sobre ninguna de las dos cepas utilizadas (TA98 y TA100).Se desarrollaron formulaciones farmacéuticas (óvulos, tabletas y microcápsulas) tanto de los extractos individuales como de las combinaciones más activas. Los formulados mantuvieron las actividades biológicas ensayadas, comparando con los valores obtenidos con los extractos utilizados para su formulación. Además, los formulados no mostraron contaminación biológica con hongos ni bacterias.Estos resultados indicarían que los fitoextractos (individuales o combinados) y los formulados obtenidos a partir de ellos serían una buena alternativa para el tratamiento de las infecciones fúngicas y de los procesos oxidativos asociados.

Electrosprayed chitosan microcapsules as delivery vehicles for vaginal phytoformulations.

The design of novel delivery systems to treat vaginal fungal infections is a topic of high interest. Chitosan, being itself antimicrobial and having good mucoadhesive properties, is an excellent candidate as a delivery matrix for active compounds. In this work, chitosan microcapsules containing dry extracts of Argentinean medicinal plants with proved biological properties (Larrea divaricata, L. cuneifolia, L. nitida, Zuccagnia punctata and Tetraglochin andina) were developed through electrospraying and compared with conventionally used tablets containing the same extracts. Total phenolics, loading efficacy, physical properties, morphology and particle size, molecular organization, water sorption capacity, release of bioactive compounds and biological properties were assessed. The encapsulation process or the inclusion in tablets did not degrade the bioactive compounds of the extracts. The release of phenolic compounds from chitosan microcapsules was faster than from tablets. The fingerprint of released phenolic compounds from microcapsules and tablets was similar to that from the dry extracts and the antioxidant and antifungal capacity remained unchanged. The FT-IR analysis suggested interactions between the chitosan and the extracts, which explained why the microcapsules kept the integrity in slightly acidic media. Increased solubility of the extracts when incorporated in the microcapsules was seen in simulated vaginal fluid, potentially increasing the bioavailability of bioactive compounds in the vaginal environment. This work highlights the potential of the chitosan-based delivery systems for phytomedicines with antifungal and antioxidant activity to be used in vulvovaginal candidiasis.

Morphoanatomical and histochemical characterization of Larrea species from Northwestern of Argentina

Abstract Larrea divaricata Cav., L. cuneifolia Cav. and L. nitida Cav., Zygophyllaceae, are evergreen xerophytic shrubs occurring in Northwestern Argentina used in traditional medicine. The aim of this work was to characterize the morphology, anatomy and histochemistry of the vegetative organs of three Larrea species by light and scanning electron microscopy in order to provide supporting data for their correct identification and to determine the site of synthesis and accumulation of its main active compounds. The shape, number and percentage of coalescence of leaflets, presence or absence of mucrones and rachis and the shape of the stipules represented the main botanical differences between the studied Larrea species. Anatomically three species presented amphystomatic leaves, with thick resinous slightly striated cuticle with resinous deposits, polygonal epidermal cells with straight anticlinal walls, ciclocytic, brachy-paracytic and paracytic stomatal types, non-glandular trichomes and isolateral mesophyll. The position and abundance of the sclerenchyma at the mid vein and petiole transection allows the differentiation of the three species, been more abundant in L. cuneifolia. Secondary phloem and parenchyma cells presented abundant calcium oxalate druses and solitary rhomboidal crystals. Epidermal cells and cuticle layer of leaflets and stipules of the three species presented amber resin deposits and content which stained positively for polysaccharides, phenolic compounds, flavonoids and tannins, while mesophyll palisade cells showed small refracting droplets stained positively for lipophilic substances.

Tetraglochin andina Ciald.: A medicinal plant from the Argentinean highlands with potential use in vaginal candidiasis.

ETHNOPHARMACOLOGICAL RELEVANCE: The Argentinean medicinal plant Tetraglochin andina Ciald, formerly classified as T. cristatum (Britton) Rothm is used in traditional medicine by inhabitants from Argentinean northwestern highlands (Puna) to treat candidiasis and as anti-inflammatory. AIM OF THE STUDY: To assess the potential of the crude drug as an anti-Candida agent with anti-inflammatory properties. The bioactivity and phytochemical composition of a dry extract of the plant was investigated. MATERIAL AND METHODS: The pharmacognostic description of the crude drug is carried out for the first time, including macroscopic and microscopic examinations of the different organs, physicochemical and extractive values (petroleum ether-, ethanol- and water-soluble). The dry extract from T. andina was evaluated as antifungal against pathogenic Candida sp. and Saccharomyces cerevisiae isolated from vaginal infections and reference strains, by the macrodilution and microdilution assays. The normal vaginal microbiome in women is characterized by the dominance of lactic acid-producing bacteria, mainly Lactobacillus spp. The effect of T. andina extract on Lactobacillus strains was also assayed. The inhibitory effect on proinflammatory enzymes (cyclooxygenase, lipoxygenase and phospholipase A2) and antioxidant capacity was studied. The chemical profile was analyzed by HPLC-ESI-MS. RESULTS: The hydroalcoholic extract inhibited the growth of all yeasts with Minimal Inhibitory Concentration (MIC) values between 12.5 and 400 µg GAE/mL and the MIC values on Lactobacillus were higher than the MIC values against Candida isolates ( > 400 µg GAE/mL). These results indicate that the hydroalcoholic extract could be used without affecting the normal microbiota of vaginal fluid. The extract showed antioxidant activity and could modulate the inflammatory process by three pathways (sPLA2, COX-2, LOX). The plant extract contained high total phenolic levels (386.9±1.7 mg GAE/g dry extract) and flavonoid levels (260.4±2.7 mg GAE/g dry extract). Fifty phenolic compounds were identified by HPLC-ESI-MS. They were mainly hydrolysable and condensed tannins. The dry extract was chemically and biologically stable during one year at room temperature or 4 °C. CONCLUSIONS: The presence of anti-Candida and anti-inflammatory activities in Tetraglochin andina extracts give support to their traditional use for treating conditions associated with microorganism infections and inflammatory process in humans. This plant preparation could be used to design phytopharmaceutical preparations to inhibit yeast growth and moderate the inflammatory and oxidative process.

Zuccagnia punctata: A Review of its Traditional Uses; Phytochemistry, Pharmacology and Toxicology.

Zuccagnia punctata Cav. (Fabaceae, Caesalpiniaceae) is a plant with a long history of use in Argentine traditional medicines; it belongs to a monotypic genus, and is an endemic species of Argentina. This review provides a comprehensive overview of the traditional uses, phytochemistry, pharmacological activity and toxicology of Z. punctata. A wide range of traditional uses are cited in the literature such as antibacterial, antifungal, anti-inflammatory, and antitumor, among - others. Pharmacological studies to date have demonstrated significant activities that support the traditional uses of this plant. No human clinical trials had been - completed up to the time of this review and no toxic effect had been detected in animals. Compounds from different chemical groups have been isolated such las phenolic compounds and essential oils. Plant extracts and phytochemicals isolated exhibit a broad range of activities, anti-inflamnatory, antibacterial, antifungal, antigenotoxic, antioxidant, antiulcer, and nematicidal. The main bioactive phytochemicals in the aerial parts (leaf, stem and flower) were identified as 2', 4'-dihydroxy-3'-methoxychalcone and 2', 4'-dihydroxychalcone and were proposed as chemical markers. Consequently, standardized dry extracts of aerial parts of Z. puntacta could be used in herbal medicinal products. Also, they could be included in phytotherapeutic preparations such as capsules, creams, and gels, and for microencapsulation.