In Silico Research of New Therapeutics Rotenoids Derivatives against Leishmania amazonensis Infection.

Yearly, 1,500,000 cases of leishmaniasis are diagnosed, causing thousands of deaths. To advance in its therapy, we present an interdisciplinary protocol that unifies ethnobotanical knowledge of natural compounds and the latest bioinformatics advances to respond to an orphan disease such as leishmaniasis and specifically the one caused by Leishmania amazonensis. The use of ethnobotanical information serves as a basis for the development of new drugs, a field in which computer-aided drug design (CADD) has been a revolution. Taking this information from Amazonian communities, located in the area with a high prevalence of this disease, a protocol has been designed to verify new leads. Moreover, a method has been developed that allows the evaluation of lead molecules, and the improvement of their affinity and specificity against therapeutic targets. Through this approach, deguelin has been identified as a good lead to treat the infection due to its potential as an ornithine decarboxylase (ODC) inhibitor, a key enzyme in Leishmania development. Using an in silico-generated combinatorial library followed by docking approaches, we have found deguelin derivatives with better affinity and specificity against ODC than the original compound, suggesting that this approach could be adapted for developing new drugs against leishmaniasis.

Searching for Scientific Explanations for the Uses of Spanish Folk Medicine: A Review on the Case of Mullein (Verbascum, Scrophulariaceae).

Verbascum species (common mullein) have been widely used in Spanish folk medicine to treat pathologies related to the musculature, skeleton, and circulatory, digestive, and respiratory systems, as well as to treat infectious diseases and organ-sense illnesses. These applications support the potential anti-inflammatory action of Verbascum phytochemicals. Based on the aforementioned facts, and following a deep bibliographic review of the chemical composition of the 10 species of Verbascum catalogued by the Spanish Inventory of Traditional Knowledge related to Biodiversity, we look for scientific evidences to correlate the traditional medical uses with the chemical components of these plants. To support these findings, in silico simulations were performed to investigate molecular interactions between Verbascum phytochemicals and cellular components. Most of common mullein traditional uses could rely on the anti-inflammatory action of phytochemicals, such as quercetin, and it could explain the employment of these plants to treat a wide range of diseases mediated by inflammatory processes such as respiratory diseases, otitis, arthrosis, and rheumatism among others.

Piper aduncum essential oil: a promising insecticide, acaricide and antiparasitic. A review.

Several studies have assessed the potential of essential oils as substitutes for synthetic pesticides, in order to counter insect resistance to commercial pesticides. Piper aduncum L. is a very common shrub in the Amazon Rainforest and in other subtropical areas. The objective of this review was to analyse the existing information on P. aduncum essential oil as a raw material for new bioproducts for sustainable pest disease management. With this review, we collected and critically analysed 59 papers, representing all the studies that aimed to evaluate the essential oil properties of this species as an insecticide, acaricide and antiparasitic. The chemical composition differs depending on the origin, although phenylpropanoid dillapiole is the most cited component, followed by myristicin, 1,8-cineole and ß-ocimene. Between the acaricidal, antiparasitic and synergistic activities, the insecticidal effects are highly promising, with optimal results against the malaria vector Aedes aegypti, with an LC50 that ranges between 57 and 200µg/mL. Acaricidal activity has mainly been reported against Tetranychus urticae, showing an LC50 that ranges between 5.83 and 7.17µg/mL. Antiparasitic activity has predominately been found on Leishmania amazonensis, and antipromastigote activity has been found to be between 23.8 and 25.9µg/mL. Concerning the synergistic effect between dillapiole and synthetic insecticides, four studies on Spodoptera frugiperda found promising results with cypermethrin. In this review, we highlighted the potential of P. aduncum essential oil as a biopesticide, also focusing on the lack of information about applied research. We also provide suggestions for future investigations.

TITLE: L'huile essentielle de Piper aduncum: un insecticide, acaricide et antiparasitaire prometteur. Une synthèse. ABSTRACT: Plusieurs études ont abordé le potentiel des huiles essentielles comme substitut aux pesticides de synthèse, afin de lutter contre la résistance des insectes aux pesticides commerciaux. Piper aduncum L. est un arbuste très commun dans la forêt amazonienne et dans d'autres zones subtropicales. L'objectif de ce travail est d'analyser les informations existantes sur l'huile essentielle de P. aduncum comme matière première de nouveaux bioproduits pour une gestion durable des maladies nuisibles. Dans cette synthèse, nous avons collecté et analysé de manière critique 59 articles, représentant toutes les études qui visaient à prouver les propriétés des huiles essentielles de cette espèce en tant qu'insecticide, acaricide et antiparasitaire. La composition chimique diffère selon la provenance, bien que le phénylpropanoïde dillapiole soit le composant le plus cité, suivi de la myristicine, du 1,8-cinéole et du ß-ocimène. À côté des activités acaricide, antiparasitaire et de synergie avec les autres composants, les effets insecticides sont les plus prometteurs, avec des résultats optimaux contre le vecteur du paludisme Aedes aegypti, avec une CL50 comprise entre 57 et 200µg/mL. Une activité acaricide a été principalement rapportée contre Tetranychus urticae avec une CL50 comprise entre 5,83 et 7,17µg/mL. L'activité antiparasitaire a été montrée principalement sur Leishmania amazonensis et l'activité antipromastigote s'est avérée être comprise entre 23,8 et 25,9µg/mL. Concernant l'effet synergique entre le dillapiole et les insecticides synthétiques, quatre études sur Spodoptera frugiperda ont mis l'accent sur des résultats prometteurs avec la cyperméthrine. Avec cette étude, nous avons mis en évidence le potentiel de l'huile essentielle de P. aduncum en tant que biopesticide, en insistant sur le manque d'informations de la recherche appliquée et sur certaines propositions pour de futures recherches.

Three Alkaloids from an Apocynaceae Species, Aspidosperma spruceanum as Antileishmaniasis Agents by In Silico Demo-case Studies.

This paper is focused on demonstrating with a real case that Ethnobotany added to Bioinformatics is a promising tool for new drugs search. It encourages the in silico investigation of "challua kaspi", a medicinal kichwa Amazonian plant (Aspidosperma spruceanum) against a Neglected Tropical Disease, leishmaniasis. The illness affects over 150 million people especially in subtropical regions, there is no vaccination and conventional treatments are unsatisfactory. In attempts to find potent and safe inhibitors of its etiological agent, Leishmania, we recovered the published traditional knowledge on kichwa antimalarials and selected three A. spruceanum alkaloids, (aspidoalbine, aspidocarpine and tubotaiwine), to evaluate by molecular docking their activity upon five Leishmania targets: DHFR-TS, PTR1, PK, HGPRT and SQS enzymes. Our simulation results suggest that aspidoalbine interacts competitively with the five targets, with a greater affinity for the active site of PTR1 than some physiological ligands. Our virtual data also point to the demonstration of few side effects. The predicted binding free energy has a greater affinity to Leishmania proteins than to their homologous in humans (TS, DHR, PKLR, HGPRT and SQS), and there is no match with binding pockets of physiological importance. Keys for the in silico protocols applied are included in order to offer a standardized method replicable in other cases. Apocynaceae having ethnobotanical use can be virtually tested as molecular antileishmaniasis new drugs.

Food Identities, Biocultural Knowledge and Gender Differences in the Protected Area "Sierra Grande de Hornachos" (Extremadura, Spain).

A food tradition not only corresponds to the vital need to be nourished every day, but is part of the particularity of a territory as a consequence of its history, traditions, natural heritage, and capacity for ecological and social resilience. In the search for culinary identity, a valorization of a rural territory of high identity potential is carried out, such as in the environmental protection area "Sierra Grande de Hornachos" (Extremadura, Spain), and specifically the town of Hornachos. For this purpose, a series of workshops and interviews were held for men and women who had lived most of their lives in Hornachos and who were older than 70. Information on the food uses of wild and cultivated plants, as determined by the Cultural Significance Index (CSI) for 79 species, was extracted from the interpretation of the data collected. In addition, new uses were collected in Extremadura for 16 plants and in Spain for 3, with some of these data being of particular significance in the culinary culture of Hornachega. We conclude that the area "Sierra Grande de Hornachos" forms an environment of great culinary identity that must be preserved, not only for its heritage interests but also for its agroecological ones, which could be translated into measures of wealth creation and development.

Promising Potential of Lonchocarpus utilis against South American Myasis.

Traditional medicine is especially important in the treatment of neglected tropical diseases because it is the way the majority of populations of affected countries manage primary healthcare. We present a case study that can serve as an example that can be replicated by others in the same situation. It is about the validation of a local remedy for myasis in Amazonian Ecuador, which is contrasted by bibliographic chemical reviews and in silico activity tests. We look for scientific arguments to demonstrate the reason for using extracts of Lonchocarpus utilis against south American myasis (tupe). We provide a summary of the isoflavonoids, prenylated flavonoids, chalcones, and stilbenes that justify the action. We make modeling predictions on the affinity of eight chemical components and enzyme targets using Swiss Target Prediction software. We conclude that the effects of this extract can be reasonably attributed to an effect of the parasite that causes the disease, similar to the one produced by synthetic drugs used by conventional medicine (e.g., Ivermectine).

In Silico Molecular Studies of Antiophidic Properties of the Amazonian Tree Cordia nodosa Lam.

We carried out surveys on the use of Cordia nodosa Lam. in the jungles of Bobonaza (Ecuador). We documented this knowledge to prevent its loss under the Framework of the Convention on Biological Diversity and the Nagoya Protocol. We conducted bibliographic research and identified quercetrin as a significant bioactive molecule. We studied its in silico biological activity. The selected methodology was virtual docking experiments with the proteins responsible for the venomous action of snakes. The molecular structures of quercetrin and 21 selected toxins underwent corresponding tests with SwissDock and Chimera software. The results point to support its antiophidic use. They show reasonable geometries and a binding free energy of -7 to -10.03 kcal/mol. The most favorable values were obtained for the venom of the Asian snake Naja atra (5Z2G, -10.03 kcal/mol). Good results were also obtained from the venom of the Latin American Bothrops pirajai (3CYL, -9.71 kcal/mol) and that of Ecuadorian Bothrops asper snakes (5TFV, -9.47 kcal/mol) and Bothrops atrox (5TS5, -9.49 kcal/mol). In the 5Z2G and 5TS5 L-amino acid oxidases, quercetrin binds in a pocket adjacent to the FAD cofactor, while in the myotoxic homologues of PLA2, 3CYL and 5TFV, it joins in the hydrophobic channel formed when oligomerizing, in the first one similar to α-tocopherol. This study presents a case demonstration of the potential of bioinformatic tools in the validation process of ethnobotanical phytopharmaceuticals and how in silico methods are becoming increasingly useful for sustainable drug discovery.

Bioactive Phytochemicals from Mercurialis spp. Used in Traditional Spanish Medicine.

Plants from the genus Mercurialis have a long history of use as herbal remedies in traditional Spanish medicine. The growing interest in the conservation of knowledge related to biodiversity has encouraged us to review the bioactive phytochemicals from the four most widespread Mercurialis species in the Iberian Peninsula (M. annua L., M. ambigua L., M. perennis L., and M. tomentosa L.). First, the medicinal uses of these four species throughout Spain were compiled, and then a bibliographical search on their chemical composition was conducted in an attempt to justify their reported traditional uses. We found that most of the medicinal uses of Mercurialis spp. are supported by scientific evidence. This includes its antidiabetic and antihypertensive properties attributable to the flavonoid rutin and narcissin, respectively; its benefits in the treatment of skin dark spots, attributable to mequinol; and its anti-inflammatory activity, attributable to scopoletin, kaempferol, squalene, and cycloartenol. This review contributes to the validation of the medicinal uses of Mercurialis spp. in Spain and provides some new avenues for further investigations on the biological activity of this interesting medicinal plant.

Microstructural and Thermo-Physical Characterization of a Water Hyacinth Petiole for Thermal Insulation Particle Board Manufacture.

Water Hyacinth (Eichhornia crassipes) is a dangerous and invasive aquatic species, of which global concern has sharply risen due to its rapid growth. Despite ample research on its possible applications in the construction field, there are no clear references on the optimal use of the plant in finding the most efficient-use building material. In this paper, a microstructural and chemical characterization of the Water Hyacinth petiole was performed, in order to find the most efficient use as a construction material. Subsequently, two types of binder-less insulation panels were developed, with two types of particle size (pulp and staple). A physical, mechanical, and thermal characterization of the boards was performed. These results demonstrated that it is possible to manufacture self-supporting Water Hyacinth petiole panels without an artificial polymer matrix for thermal insulation. The boards showed good thermal conductivity values, ranging from 0.047⁻0.065 W/mK. In addition, clear differences were found in the properties of the boards, depending on the type of Water Hyacinth petiole particle size, due to the differences in the microstructure.

Providing added value to local uses of paparahua (Artocarpus altilis) in Amazonian Ecuador by phytochemical data review

Abstract Artocarpus altilis (Parkinson ex F.A.Zorn.) Fosberg, Moraceae, is a native tree of Southeast Asia introduced to South America at the beginning of the 19th century. It has been used by several indigenous communities. This paper aims to preserve the traditional knowledge at risk of loss and to validate some of the applications found. Current ancestral practices were documented, by interviews in a scarcely contacted Amazonic Kichwa community from the Bobonaza River (Ecuador). The findings were compared with bibliographic citations from other Amazonian cultures. A bioinformatics literature survey of articles that report experiments on the chemical constituents was executed. The major findings are that some uses given in this population may be considered surprising, but the molecular profile of this species justifies its local value. It has cycloartenol (terpenoid), artoindonesianin F (stilbenoid), and different groups of flavonoids (chalcones, prenylflavones, oxepinoflavones, pyrano-flavones, xanthones). This information can prove effective in a search for novel drugs, focused to merge potential innovative uses of the plant.

On the Possible Chemical Justification of the Ethnobotanical Use of Hyptis obtusiflora in Amazonian Ecuador.

In rural areas of Latin America, Hyptis infusions are very popular. Hyptis obtusiflora extends from Mexico throughout Central America to Bolivia and Peru. It has added value in Ecuador where it has been used by different ethnic groups. We aimed to learn about the traditional knowledge of ancient Kichwa cultures about this plant, and to contrast this knowledge with the published information organized in occidental databases. We proposed to use traditional knowledge as a source of innovation for social development. Our specific objectives were to catalogue the uses of H. obtusiflora in the community, to prospect on the bibliography on a possible chemical justification for its medicinal use, to propose new products for development, and to give arguments for biodiversity conservation. An ethnobotanical survey was made and a Prisma 2009 Flow Diagram was then followed for scientific validation. We rescued data that are novel contributions for the ethnobotany at the national level. The catalogued main activity of anti-inflammation can be related to the terpene composition and the inhibition of xanthine oxidase. This opens the possibility of researching the extract of this plant as an alternative to allopurinol or uricosuric drugs. This is a concrete example of an argument for biodiversity conservation.

Chiricaspi (Brunfelsia grandiflora, Solanaceae), a Pharmacologically Promising Plant.

This study's objective was to evaluate the rescued traditional knowledge about the chiricaspi (Brunfelsia grandiflora s.l.), obtained in an isolated Canelo-Kichwa Amazonian community in the Pastaza province (Ecuador). This approach demonstrates well the value of biodiversity conservation in an endangered ecoregion. The authors describe the ancestral practices that remain in force today. They validated them through bibliographic revisions in data megabases, which presented activity and chemical components. The authors also propose possible routes for the development of new bioproducts based on the plant. In silico research about new drug design based on traditional knowledge about this species can produce significant progress in specific areas of childbirth, anesthesiology, and neurology.