Alternativas para la atención oportuna de las intoxicaciones por consumo de hongos en México y Centroamérica / Alternatives for mushroom poisoning timely care in Mexico and Central America

Resumen Antecedentes: En países donde el consumo de hongos es frecuente ocurren cientos de casos de micetismos al año, por lo que representan un problema de salud pública. En México, los micetismos son clasificados como una intoxicación gastrointestinal de tipo no bacteriano, lo que impide su atención oportuna. Objetivo: Crear una plataforma de libre acceso que sintetice y estandarice la información de los casos de micetismos y ofrezca herramientas para su diagnóstico y tratamiento oportuno. Material y métodos: En localidades donde han ocurrido casos de micetismos se obtuvo información sobre los hongos involucrados, las intoxicaciones ocurridas, protocolos de atención y procesamiento de muestras. Resultados: Se generaron cédulas que sintetizan y describen las intoxicaciones por hongos con mayor probabilidad de ocurrencia en México. En ellas se describen las características biológicas de los hongos, síntomas que provocan y su tratamiento. Se presenta una propuesta de protocolo para la atención del paciente y para el procesamiento de muestras biológicas. Por último, se incluye un formulario para recopilar información sobre los casos de intoxicaciones. Conclusiones: La información sistematizada y analizada sobre los micetismos permite simplificar su diagnóstico, atención y tratamiento. Los protocolos para la atención clínica y el procesamiento de muestras son la base para generar estrategias que eviten decesos por micetismo.

Abstract Background: In countries where the consumption of mushrooms is common, hundreds of mushroom poisonings occur every year, which represents a public health problem. In Mexico, mushroom poisoning is classified as a non-bacterial gastrointestinal poisoning, which prevents timely care. Objective: To create a free-access platform that synthesizes and standardizes the information on mycetism cases and offers tools for diagnosis and timely treatment. Material and methods: In locations where cases of mycetism have occurred, information was obtained on the fungi involved, the poisonings that occurred, care protocols, and sample processing. Results: Infographics were generated that synthesize and describe the types of mycetism with the highest probability of occurrence in Mexico. Therein, the biological characteristics of fungi, the symptoms they cause and their treatment are described. A protocol proposal for patient care and for the processing of biological samples is presented. Finally, a form is included to collect information on cases of poisoning. Conclusions: Systematized and analyzed information on mycetism allows to simplify its diagnosis, attention and treatment. The protocols for clinical care and sample processing are the basis for generating strategies that prevent deaths due to mycetism.

Sobre el primer libro de plantas medicinales escrito en el Continente Americano: El Libellus Medicinalibus Indorum Herbis de México, 1552. Una revisión / On the first book of medicinal plants written in the American Continent: The Libellus Medicinalibus Indorum Herbis from Mexico, 1552. A review

Resumen: El "Libellus de Medicinalibus Indorum Herbis" (Librito de las Hierbas Medicinales de los Indios) fue elaborado por los sabios indígenas Martín De la Cruz y Juan Badiano, 31 años después de la caída del imperio azteca. El primero es su autor, el segundo tradujo el manuscrito del Náhuatl al latín. Contiene numerosas recetas para tratar enfermedades humanas y 185 dibujos a color de las plantas utilizadas. En 1939 se publicó por primera vez como "Un Herbario Azteca". Empero, también contiene enfermedades y prácticas médicas europeas del siglo XVI. Presentamos una revisión actualizada de este hermoso códice, su historia, concepción, creadores y botánica; además, la química y farmacología de cinco plantas ahí citadas. El Libellus es una ventana en el tiempo que permite la investigación científica del antiguo conocimiento etnofarmacológico en Mesoamérica y documentar su persistencia, desaparición o transformación. Sin embargo, esto requiere superar desafíos lingüísticos, pero también derivados de su contexto histórico, antropológico, cultural, botánico y médico.

Abstract: The "Libellus de Medicinalibus Indorum Herbis" (Little Book of Indian Medicinal Plants) was composed by the indigenous sages Martín De la Cruz and Juan Badiano, 31 years after the Aztec Empire fall. The former was the author, and the latter translated the manuscript from the Nahuatl language to Latin. It contains numerous recipes for treating human diseases and 185 colored drawings of the prescribed plants. In 1939 it was first published as "An Aztec Herbarium". However, it also contains XVI century European diseases and medical practices. We present an updated review of this beautiful codex, its history, conception, creators, and botany; as well as, the chemistry and pharmacology of five plants therein cited. The Libellus is a window in the time that allows the scientific research of ancient ethnopharmacological knowledge in Mesoamerica and document its persistence, disappearance, or transformation. However, this requires overcoming linguistic defies, but also derived from its historical, anthropological, cultural, botanical, and medical context.

Natural Compounds from Mexican Medicinal Plants as Potential Drug Leads for Anti-Tuberculosis Drugs

ABSTRACT In Mexican Traditional Medicine 187 plant species are used in the treatment of respiratory conditions that may be associated with tuberculosis. In this contribution, we review the ethnobotany, chemistry and pharmacology of 63 species whose extracts have been assayed for antimycobacterial activity in vitro. Among these, the most potent is Aristolochia brevipes (MIC= 12.5 µg/mL), followed by Aristolochia taliscana, Citrus sinensis, Chrysactinia mexicana, Persea americana, and Olea europaea (MIC<64 µg/mL). Other potent extracts (inhibition > 95%, 50 µg/mL) include: Amphipterygium adstringens, Larrea divaricata, and Phoradendron robinsoni. Several active compounds have been identified, the most potent are: Licarin A (isolated from A. taliscana), and 9-amino-9-methoxy-3,4-dihydro-2H-benzo[h]-chromen-2-one (transformation product of 9-methoxytariacuripyrone isolated from Aristolochia brevipes), both with MIC= 3.125 µg/mL, that is 8-fold less potent than the reference drug Rifampicin (MIC= 0.5 µg/mL). Any of the compounds or extracts here reviewed has been studied in clinical trials or with animal models; however, these should be accomplished since several are active against strains resistant to common drugs.

Volatile organic compounds from pachyrhizus ferrugineus and pachyrhizus erosus (Fabaceae) leaves / Compuestos orgánicos volátiles de las hojas de pachyrhizus ferrugineus y pachyrhizus erosus (Fabaceae)

In México, Pachyrhizus erosus (Fabaceae) commonly called "jícama", is widely known for its edible tubers. It is cultivated since the pre-Columbian period, and the powdered seeds have been used for the treatment of mange, lice, and fleas, due to their content of rotenone, a well-known insecticidal compound. On the other hand, P. ferrugineus, a wild species can only be found in the Tropical Forests, and has no commercial value. It is known that plants release volatile organic compounds (VOCs) showing qualitative and quantitative differences if are wild or cultivated. VOCs are also involved as repelling or attracting chemical signals to insect herbivores, and their natural enemies. Until now, the VOCs of the leaves of P. erosus and P. ferrugineus have not been investigated. In the present contribution the VOCs of both species were characterized by headspace solid-phase (HS-SPME) extraction and gas chromatography-mass spectrometry (GC-MS-TOF). In P. erosus 21 VOCs were found, being the most abundant: cyclohexanone (32.8 percent), 3-hexen-1-ol (Z) (32.7 percent), 3-hexenal (Z) (10.5 percent). The majoritarian compounds were C6 or C5 derivatives In P. ferrugineus, the most abundant VOCs were: 5-hexene-1-ol acetate (51.5 percent), undecanal (22.4 percent), 2-hepten-1-al (14.5 percent). The majoritarian compounds were C6, C7 or C11 derivatives.

En México, Pachyrhizus erosus (Fabaceae) es llamada comúnmente "jícama" y es conocida por sus tubérculos comestibles. Se ha cultivado desde el período pre-Colombino y las semillas se han utilizado para el tratamiento tópico de la sarna, piojos, pulgas; las semillas contienen rotenona, un compuesto insecticida. Por otra parte, P. ferrugineus solo está presente en estado silvestre en los bosques tropicales y carece de valor comercial. Se sabe que las plantas liberan compuestos orgánicos volátiles (COV) y muestran diferencias cualitativas y cuantitativas dependiendo, si son silvestres o cultivadas. Los COV también son señales químicas atrayentes o repelentes de los insectos herbívoros y a sus enemigos naturales. Hasta ahora, los COV en las hojas de P. erosus y P. ferrugineus no han sido investigados. En el presente trabajo, los COV se identificaron mediante la microextracción (HS-SPME) en fase sólida, e identificados por cromatografía de gases acoplada a espectrometría de masas (GC-MS-TOF). En P. erosus se encontraron 21 COV, siendo los más abundantes: ciclohexanona (32.8 por ciento), 3-hexen-1-ol (Z) (32.7 por ciento) y 3-hexenal (Z) (10.5 por ciento). Los compuestos mayoritarios son C6 y C5. En P. ferrugineus los más abundantes fueron: 5-hexen-1-ol acetato (51.5 por ciento), undecanal (22.4 por ciento) y 2-hepten-1-al (14.5 por ciento). Los compuestos mayoritarios son C6, C7 o C11.

Medicinal plants for the treatment of “nervios”, anxiety, and depression in Mexican Traditional Medicine

The term “nervios” is referred as a folk illness recognized by Mexican Traditional Medicine, and also widely reported across many countries in Latin America. “Nervios” are characterized by a “state of bodily and mental unrest”, which decreases the ability to achieve daily goals. The causes are varied; in fact, any situation that alters the emotional state or mood is interpreted as a possible triggering agent. Depression and anxiety are psychiatric disorders, which share symptoms, or can be included in the same group of disorders with “nervios”. The therapies are designed to reassure health, i.e. “calm the nerves”. For this propose, the oral administration of plants infusions is common. In this review we compile information regarding the plants used for the treatment of “nervios” in México, along with those for which reports of anxiolytic or/and antidepressive activity exist. We found 92 plant species used in folk medicine for the treatment of “nervios”, among these, sixteen have been studied experimentally. The most studied plant is Galphimia glauca Cav., Malpighiaceae, which current clinical studies have validated its efficacy in patients, and their active components, the triterpenes galphimine A, B, and C, identified. Interestingly only nine plants were found to be reported in folk medicine for the treatment of sadness or/and depression, but their antidepressant activity has not been investigated. However, among the plants used in folk medicine for treatment of “nervios”, several, as Litsea glaucescens Kunth, Lauraceae, have been proven to show antidepressant activity in experimental models, and some of their active compounds have been determined. These species could be a potential source of compounds with activity in the central nervous system.

El árbol tropical Calophyllum brasiliense: una revisión botánica, química y farmacológica / The tropical tree Calophyllum brasiliense: a botanical, chemical and pharmacological review

Antecedentes: Calophyllum brasiliense Cambess. Es un árbol de la familia Calophyllaceae, separada recientemente de Clusiaceae (Guttiferae). Se distribuye ampliamente en selvas tropicales lluviosas del continente americano, desde Brasil hasta México. Esta especie sintetiza diversos metabolitos secundarios en hojas, flores, frutos, corteza y raíz, tales como cumarinas, cromanonas, xantonas, terpenos, flavonoides y compuestos fenólicos, los cuales presentan múltiples propiedades biológicas. Objetivos: Ofrecer una visión general de las características botánicas, químicas y farmacológicas de C. brasiliense, así como evidencias químicas, anatómicas y genéticas que sugieren la existencia de quimiotipos (fenotipos químicos) en la especie. Métodos: Se revisó la información disponible en las bases de datos NCBI y SciFinder®, se seleccionaron investigaciones relevantes que permitieron conocer los compuestos químicos aislados y su actividad biológica. Resultados: Entre los compuestos sintetizados por C. brasiliense destacan calanólidos e inofilums, especialmente el (+)-calanólido A, como inhibidores potentes de la enzima transcriptasa reversa del virus de inmunodeficiencia humana tipo 1 (VIH-1) y baja toxicidad a linfocitos humanos. El (+)-calanólido A, una dipiranocumarina tetracíclica, podría ser el primer fármaco de origen natural aprobado por la FDA (EUA) en el tratamiento del VIH/SIDA. Otros compuestos, tales como cumarinas tipo mammea, cromanonas, xantonas y triterpenos, mostraron actividad contra protozoarios, células tumorales humanas, como bactericidas y antiespasmódicos. La actividad más importante de cumarinas tipo mammea es contra protozoarios como Leishmania y Trypanosoma. En relación a L. amazonensis, destacó (-)-mammea A/BB presentando buena actividad y selectividad contra amastigotes y promastigotes, y baja toxicidad en macrófagos humanos. La (-)-mammea A/BA, y las xantonas preniladas mostraron alta citotoxicidad sobre líneas celulares tumorales humanas y T. cruzi. Las evidencias químicas, anatómicas y genéticas indican que existen quimiotipos en C. brasiliense, sugiriendo un proceso de especiación en curso en el taxón. Las secuencias ribosomales (ITS) discriminaron al quimiotipo 1 (produce coumarinas tipo mammea) de los quimiotipos 2 y 3 (biosintetizan calanólidos e inofilums), siendo útiles como posibles códigos de barras. Conclusiones: El adecuado manejo de C. brasiliense mediante técnicas silvícolas y biotecnológicas, así como el conocimiento científico y tecnológico, podrían aportar soluciones a países en desarrollo, por ejemplo mediante producción de fitomedicamentos, a enfermedades como el VIH/ SIDA, Leshmaniasis y la Enfermedad de Chagas.

Rationale: Calophyllum brasiliense Cambess. Is a tree belonging to Calophyllaceae family, recently separated from Clusiaceae (= Guttiferae). This species is widely distributed in the Tropical Rain Forests of the American continent, from Brazil to Mexico. It synthesizes a wide variety of secondary metabolites isolated from leaves, flowers, fruits, bark and roots, such as coumarins, chromanones, xanthones, terpenes,flavonoids and phenolic compounds, which exhibit multiple biological properites. Objective: To provide a comprehensive view of the botanical, chemical and pharmacological characteristics of C. brasiliense, and to present chemical, anatomical and genetic evidences supporting the notion of chemotypes (chemical phenotypes) in this species. Methods: Information available in the databases NCBI and SciFinder® was reviewed, and relevant investigations were selected regarding to chemical compounds isolated and their biological activity. Results: Among compounds synthesized by C. brasiliense, calanolides and inophyllums stand out, specially (+)-calanolide A, since these can inhibit reverse transcriptase of human immunodeficiency virus type 1 (HIV-1). (+)-Calanolide A, a tetracyclic dipyranocoumarin, could be the first drug of natural origin approved by the FDA (US) in the treatment of HIV/AIDS. Other compounds, such as mammea type-coumarins, chromanones, xanthones, and triterpenes showed antitumor, antiparasitic, antibacterial and antispasmodic activity. Most important activity of mammea type-coumarins is against protozoa, such as Leishmania, and Trypanosoma. Regarding to L. amazonensis, (-)-mammea A/BB stands out, being highly potent and selective against amastigotes, and promastigotes, but poorly toxic to human macrophages. (-)-Mammea A/BA as well as prenylated xanthones showed high citotoxicity against human tumor cell lines and T. cruzi. The chemical, anatomical and genetical evidences supported the idea of chemotypes in C. brasiliense, suggesting a current process of speciation in this taxon. The ribosomal ITS sequences discriminate chemotype 1 (produces mammea type coumarins) from chemotypes 2 and 3(synthesize calanolides and inophyllums) being useful like possible barcodes. Conclusions: The proper management of Calophyllum brasiliense with forestry and biotechnological methods, as well as scientific and technological knowledge, could provide solutions to developing countries, for instance through the production of phytomedicines against HIV/AIDS, and illnesses caused by protozoa such as Leshmaniasis and Chaga's Disease.

Etnobotánica, micrografía analítica de hojas y tallos y fitoquimica de Cuphea aequipetala Cav. (Lythraceae): una contribución a la farmacopea herbolaria de los Estados Unidos Mexicanos (FHEUM) / Ethnobotany, analytical micrograph of leaves and stems and phytochemistry of Cuphea aequipetala Cav. (Lythraceae): a contribution to the herbal pharmacopoeia of the United Mexican States (FHEUM)

Cuphea aquipetala Cav. (Hierba del cancer) is used in Mexican traditional medicine. In the present work, its most frequent medicinal applications were determined through interviews, revision of herbarium specimens, and bibliography. The quoted applications were: to treat pounds and wounds. For these purposes, the drug (leaf and stem) is prepared and administered as infusion, or as poultice. In order to provide data for inclusion of this species in the Herbal Pharmacopoeia of the United Mexican States (FHEUM) we describe its leaf architecture and diagnostic anatomical characters of drug,. The anatomical study revealed that the three types of trichomes observed can aid to differentiate this species from other Cuphea species. Anatomical variation was observed mainly in the midrib of the leaf. Leaf architecture is first described for this species, and provides the basis for future comparisons. In addition, the acetone-water extract of the aerial parts previously reported as cytotoxic activity against DU-145 (human prostate carcinoma) and HCT-15 (human colon carcinoma), showed the presence of polyphenolic compounds of the type of hydrolysable and condensed tannins, mannitol was isolated and identified.

Cuphea aquipetala Cav., Lythraceae (Hierba del cáncer) es utilizada en la medicina tradicional mexicana. En el presente trabajo se determinó mediante entrevistas, consultas de herbario y revisión bibliográfica sus aplicaciones médicas más frecuentes, a saber: para tratar golpes y heridas, para lo cual la droga (hoja y tallo) es preparada en infusión, o administrada en emplastos. Con la finalidad de aportar datos que ayuden a la inclusión de esta especie en la Farmacopea Herbolaria de los Estados Unidos Mexicanos (FHEUM), se describen la arquitectura foliar y los caracteres anatómicos de la droga. El estudio anatómico reveló que los tres tipos de tricomas reconocidos en la especie estudiada apoyan a diferenciarla de otras especies de Cuphea sp. Se observó variación anatómica principalmente en la nervadura central de la hoja. La arquitectura foliar se describe por primera vez para la especie y sienta las bases para futuras comparaciones. Por otra parte, el extracto acetona-agua de las partes aéreas que previamente ha sido reportado con actividad citotóxica contra células DU-145 (carcinoma de próstata humano) y HCT-15 (carcinoma de colon humano) mostró la presencia de compuestos polifenólicos del tipo de los taninos hidrolizables, taninos condensados, y se aisló manitol.

Compuestos naturales de plantas de la familia clusiaceae: Inhibidores del virus de inmunodeficiencia humana tipo 1 / Natural compounds from plants of the clusiaceae family: Type 1 human immunodeficiency virus inhibitors / Compostos naturais de plantas da família clusiaceae: Inibidores do virus de imunodeficiência humana tipo 1

El SIDA es un problema de salud pública mundial, por lo que es necesario coordinar los esfuerzos para combatir esta enfermedad. En esta perspectiva, se revisan las investigaciones tendientes al descubrimiento y desarrollo de nuevos fármacos contra el virus de inmunodeficiencia humana (VIH) a partir de metabolitos secundarios de origen vegetal aislados de especies de la familia Clusiaceae. En particular, la revisión se enfoca en las cumarinas tetracíclicas inhibidoras de la transcriptasa reversa del VIH-1, como el (+)-calanólido A. También se presenta una semblanza sobre la biología del VIH y de los estudios llevados a cabo en México referentes a la búsqueda de compuestos antiVIH a partir de la flora local.

AIDS being a worldwide public health problem, it is necessary to coordinate efforts to fight the disease. Under this viewpoint, we review research aiming at the discovery and development of new drugs against the human immunodeficiency virus (HIV) from secondary metabolites of vegetal origin, isolated from species of the clusiaceae family. Particularly, the review centers on tetracyclic cumarines that inhibit the HIV-1 reverse transcriptase, such as the (+)-calanolide A. A summary of HIV biology and the studies carried out in Mexico concerning the search of anti-HIV compounds from the local flora is also presented.

A AIDS é um problema de saúde pública mundial, pelo qual é necessário coordenar os esforços para combater esta enfermidade. Nesta perspectiva, se revisam as investigações tendentes ao descubrimento e desenvolvimento de novos fármacos contra o virus da imunodeficiência humana (HIV) a partir de metabólitos secundários de origem vegetal isolados de espécies da família Clusiaceae. Em particular, a revisão é focada nas cumarinas tetracíclicas inibidoras da transcriptase reversa do HIV-1, como o (+)-calanolide A. Também é apresentado um esboço sobre a biologia do HIV e dos estudos levados a efeifo no México referentes à procura de compostos anti-HIV a partir da flora local.

Trypanocidal constituents in plants: 7. Mammea-type coumarins

Calophyllum brasiliense and Mammea americana (Clusiaceae) are two trees from the tropical rain forests of the American continent. A previous screening showed high trypanocidal activity in the extracts of these species. Several mammea-type coumarins, triterpenoids and biflavonoids were isolated from the leaves of C. brasiliense. Mammea A/AA was obtained from the fruit peels of M. americana. These compounds were tested in vitro against epimastigotes and trypomastigotes of Trypanosoma cruzi, the etiologic agent of Chagas disease. The most potent compounds were mammea A/BA, A/BB, A/AA, A/BD and B/BA, with MC100 values in the range of 15 to 90 g/ml. Coumarins with a cyclized ,-dimethylallyl substituent on C-6, such as mammea B/BA, cyclo F + B/BB cyclo F, and isomammeigin, showed MC100 values > 200 g/ml. Several active coumarins were also tested against normal human lymphocytes in vitro, which showed that mammea A/AA and A/BA were not toxic. Other compounds from C. brasiliense, such as the triterpenoids, friedelin, canophyllol, the biflavonoid amentoflavone, and protocatechuic and shikimic acids, were inactive against the epimastigotes. The isopropylidenedioxy derivative of shikimic acid was inactive, and its structure was confirmed by X-ray diffraction. Our results suggest that mammea-type coumarins could be a valuable source of trypanocidal compounds.