In silico molecular docking analysis of three molecules isolated from Litsea guatemalensis Mez on anti-inflammatory receptors.

BACKGROUND: The Litsea genus has four native species from Mesoamerica. Litsea guatemalensis Mez. is a native tree, traditionally used as a condiment and herbal medicine in the region. It has demonstrated antimicrobial, aromatic, anti-inflammatory and antioxidant activity. Bioactive fractionation attributed the anti-inflammatory and anti-hyperalgesic activities to pinocembrin, scopoletin, and 5,7,3´4´-tetrahydroxy-isoflavone. In silico analysis, these molecules were analyzed on receptors involved in the anti-inflammatory process to determine which pathways they interact. OBJECTIVE: To analyze and evaluate 5,7,3',4'-tetrahydroxyisoflavone, pinocembrin, and scopoletin using the in silico analysis against selected receptors involved in the inflammatory pathway. METHOD: Known receptors involved in the anti-inflammatory process found as protein-ligand complex in the Protein Data Bank (PDB) were used as references for each receptor and compared with the molecules of interest. The GOLD-ChemScore function, provided by the software, was used to rank the complexes and visually inspect the overlap between the reference ligand and the poses of the studied metabolites. RESULTS: 53 proteins were evaluated, each one in five conformations minimized by molecular dynamics. The scores obtained for dihydroorotate dehydrogenase were greater than 80 for the three molecules of interest, scores for cyclooxygenase 1 and glucocorticoid receptor were greater than 50, and identified residues with interaction in binding sites overlap with the reference ligands in these receptors. CONCLUSION: The three molecules involved in the anti-inflammatory process of L. guatemalensis show in silico high affinity to the enzyme dihydroorotate dehydrogenase, glucocorticoid receptors and cyclooxygenase-1.

Nephroprotective plant species used in traditional Mayan Medicine for renal-associated diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: The prevalence of kidney disease has increased rapidly in recent years and has emerged as one of the leading causes of mortality worldwide. Natural products have been suggested as valuable nephroprotective agents due to their multi-target and synergistic effects on modulating important proteins involved in kidney injury. There is a large number of plant species that have been used traditionally for kidney-related conditions in Mesoamerican medicine by different cultural groups that could provide a valuable source of nephroprotective therapeutic candidates and could lead to potential drug discovery. AIM OF REVIEW: This review aims to provide an overview of the currently known efficacy of plant species used traditionally in Mesoamerica by Mayan groups to treat kidney-related conditions and to analyze the phytochemical, pharmacological, molecular, toxicological, and clinical evidence to contribute to public health efforts and for directing future research. METHODS: Primary sources of plant use reports for traditional kidney-related disorders in Mesoamerica were searched systematically from library catalogs, theses, and scientific databases (PubMed, Google Scholar; and Science Direct), and were filtered according to usage frequency in Mayan groups and plant endemism. The database of traditional plants was further analyzed based on associations with published reports of the phytochemical, pharmacological, molecular, toxicological, and clinical evidence. RESULTS: The most reported kidney-related conditions used traditionally in Mayan medicine involve reducing renal damage (a cultural interpretation that considers an inflammatory or infectious condition), cleaning or purifying the blood and kidney, reducing kidney pain, and eliminating kidney stones. A total of 208 plants used for kidney-related problems by 10 Mayan groups were found, representing 143 native species, where only 42 have reported pharmacological activity against kidney damage, mainly approached by in vitro and in vivo models of chemical- or drug-induced nephrotoxicity, diabetes nephropathy, and renal injury produced by hypertension. Nephroprotective effects are mainly mediated by reducing oxidative stress, inflammatory response, fibrosis mechanisms, and apoptosis in the kidney. The most common nephroprotective compounds associated with traditional Mayan medicine were flavonoids, terpenoids, and phenolic acids. The most widely studied traditional plants in terms of pharmacological evidence, bioactive compounds, and mechanisms of action, are Annona muricata L., Carica papaya L., Ipomoea batatas (L.) Lam., Lantana camara L., Sechium edule (Jacq.) Sw., Tagetes erecta L., and Zea mays L. Most of the plant species with reported pharmacological activity against kidney damage were considered safe in toxicological studies. CONCLUSION: Available pharmacological reports suggest that several herbs used in traditional Mayan medicine for renal-associated diseases may have nephroprotective effects and consistent pharmacological evidence, nephroprotective compounds, and mechanisms of action in different models of kidney injury. However, more research is required to fully understand the potential of traditional Mayan medicine in drug discovery given the limited ethnobotanical studies and data available for most species with regards to identification on bioactive components, pharmacological mechanisms, and the scarce number of clinical studies.

Inhibition of enzymatic activities of Bothrops asper snake venom and docking analysis of compounds from plants used in Central America to treat snakebite envenoming.

ETHNOPHARMACOLOGICAL RELEVANCE: Snakebite envenoming is a public health problem of high impact in Central America. Bothrops asper, known as barba amarilla, terciopelo, and equis, is the snake species responsible for most snakebites in Central America. In this region, there is a long-standing tradition on the use of plants in the management of snakebites, especially in indigenous communities. Ethnomedical use of Eryngium foetidum L., Neurolaena lobata (L.) Cass. and Pimenta dioica (L.) Merr. to treat snakebite envenoming has been reported in Belice, Guatemala, Nicaragua, and Costa Rica. Extracts of the leaves of these plants have shown anti-venom activities in in vitro assays in previous studies. AIM OF THE STUDY: To assess the ability of organic fractions from these three plants to inhibit enzymatic activities associated with toxicity of the venom of B. asper, and to study, by docking analysis, the interaction of metalloproteinase and phospholipases A2 (PLA2) from B. asper venom with secondary metabolites previously described in these plants. MATERIALS AND METHODS: Organic fractions were obtained from these three plant species and their ability to neutralize proteolytic, PLA2 and in vitro coagulant activities of B. asper venom was assessed. A phytochemical analysis was carried out in these fractions. The interaction of secondary metabolites previously described in these plants with three toxins from B. asper venom (a metalloproteinase, a PLA2 and a PLA2 homologue) was investigated by docking analysis. RESULTS: The inhibitory activity of plants was mainly concentrated in their polar fractions. Acetonic fraction from P. dioica was the most active against PLA2 activity, while the acetonic fraction of E. foetidum completely inhibited the proteolytic activity of the venom. Coagulant activity was partially inhibited only by the acetone and ethyl acetate fractions of P. dioica. Phytochemical analysis of the most bioactive fractions identified flavonoids, saponins, essential oils, coumarins, alkaloids, tannins and sesquiterpene lactones. Docking analysis revealed high affinity interactions of several secondary metabolites of these plants with residues in the vicinity of the catalytic site of these enzymes and, in the case of PLA2 homologue myotoxin II, in the hydrophobic channel. CONCLUSIONS: Various fractions from these plants have inhibitory activity against enzymatic actions of B. asper venom which are directly associated with toxicological effects. Docking analysis showed structural evidence of the interaction of secondary metabolites with three toxins. These observations provide support to the potential of these plants to inhibit relevant toxic components of this snake venom.

Inhibición de las actividades proteolítica y fosfolipasa A2 del veneno de Bothrops asper por el extracto etanólico de Neurolaena lobata (L) Cass / Inhibition of proteolytic and phospholipase A2 activities of Bothrops asper venom by the ethanolic extract of Neurolaena lobata (L) Cass

Neurolaena lobata es utilizada tradicionalmente en Centroamérica para tratar la mordedura de serpiente, pero su efectividad para contrarrestar el envenenamiento producido por Bothrops asper ha sido poco estudiada. Se evaluó la capacidad del extracto etanólico de sus hojas para inhibir las actividades proteolítica, fosfolipasa A2 (PLA2; evaluada como hemólisis indirecta) y coagulante del veneno in vitro. El material vegetal fue colectado en Izabal, Guatemala, secado, se hicieron extracciones con etanol y se evaluó la presencia de actividades proteolítica, PLA2 y coagulante in-trínsecas en ensayos de concentración-actividad. Los efectos inhibitorios de la actividad proteolítica y PLA2 del veneno se evaluaron después de pre-incubar concentraciones variables del extracto con concentraciones fijas de veneno. La inhibición de la actividad coagulante del veneno no fue evaluada porque el extracto presentó actividad anticoagulante intrínseca dependiente de la concentración. El extracto inhibió completamente las actividades proteolítica (CE50 = 15.7 µg/µl) y PLA2 (CE50 = 32.5 µg/µl) del veneno. El análisis fitoquímico utilizando ensayos macro y semimicrométricos de cromatografía en capa fina, demostró la presencia de flavonoides, cumarinas, saponinas, taninos, sesquiterpenlactonas y aceites esenciales en el extracto. Su efecto sobre las proteínas del veneno se evaluó por electroforesis SDS-PAGE, mostrando cambios en el patrón electroforético atribuidos a la formación de complejos moleculares con los metabo-litos del extracto. Los resultados indican que el extracto podría inhibir los efectos tóxicos del veneno inducidos por las metaloproteinasas dependientes de zinc (SVMPs) y PLA2s, pero podría afectar las alteraciones en la coagulación, coadyuvando en la desfibrinogenación inducida por el veneno.

Neurolaena lobata has been used by traditional healers in Central America to treat snakebite, but its ability to neutralize Bothrops asper envenomations needs to be proved. This study evaluated the inhibitory potential of the ethanolic extract of the leaves of N. lobata against proteolytic, phospholipase A2 (PLA2) and coagulant activities of the venom in vitro. Leaves were collected in Izabal, Guatemala, dried, extracted with ethanol and concentration-response assays were conducted to detect intrinsic proteolytic, PLA2 (evaluated as indirect hemolysis) and coagulant activities. Assays for anti-proteolytic and anti-PLA2 activities were performed after pre-incubation of several amounts of extract with a fixed concentration of venom. Inhibition assay for the coagulant effect of the venom was not tested because pre-incubation of thrombin with the extract prolonged the clotting time of plasma in a concentration-dependent manner. Proteolytic (EC50 = 15.7 µg/µl) and PLA2 (EC50 = 32.5 µg/µl) activities of the venom resulted completely inhibited by the extract. Phytochemical profiles, determined by micrometric assays and semi microanalysis by thin layer chro-matography, showed the presence of flavonoids, coumarins, saponins, tannins, sesquiterpene lactones and essential oils in the extract. SDS-PAGE was used to assess the action of the extract on the venom proteins. Results showed changes in the electrophoretic profile, probably due to the formation of insoluble complexes with plant specialized metabolites. These findings demonstrated that the extract could be able to inhibit toxic effects triggered by zinc-dependent snake venom metalloproteinases (SVMPs) y PLA2s but might aggravate the alterations induced by the venom in coagulation.

Medicina tradicional y fitoterapia una alternativa para el mejoramiento de la salud en Guatemala / Traditional medicine and herbal medicine an alternative for the improvement of health in Guatemala

El empleo de las plantas medicinales con fines curativos es una práctica que se ha utilizado ancestralmente. Durantemucho tiempo los remedios naturales fueron el principal recurso disponible, esto hizo que se profundizaraen el conocimiento de las especies vegetales, surgiendo así como una disciplina la fitoterapia. En todo el mundo, la medicina tradicional, complementaria o no convencional ha constituido un pilar importante en la prestación deservicios de salud. Muchos países reconocen actualmente la necesidad de elaborar un enfoque coherente e integralde la atención de salud que facilite el acceso de la medicina tradicional de manera segura, respetuosa, asequible yefectiva, por lo que surge la estrategia de la Organización Mundial de Salud 2002-2005, que por su importancia fueactualizada para 2014-2023. En Guatemala existe una práctica tradicional de uso de plantas medicinales, además secuenta con un Programa Nacional de Medicina Tradicional y con el Vademécum Nacional de Plantas Medicinales,el cual contiene la información sobre plantas medicinales validadas y con suficiente evidencia científica. Derivadodel análisis de la situación del sistema de salud, se plantea como una de las estrategias para mejorar el acceso, lacalidad de la atención y la promoción de la salud, un abordaje intercultural, dándole un nuevo enfoque al sistemade salud de una forma integrada, incluyente y pluricultural, que promueva la calidad en el servicio y que respondaa las necesidades de la comunidad con los recursos que le brinda su ambiente.

Traditional use of herbal medicines refers to the long historical use of these medicines, for a long time naturalremedies were the main resource available, making the knowledge of plant species an emerging discipline,phytotherapy. Worldwide, traditional, complementary or unconventional medicine has constituted an importantpillar in the provision of health services, many countries recognize the need to develop a coherent and comprehensiveapproach in health care, facilitating access of traditional medicine in a safe, friendly, affordable, and effectiveway. From this reason arise the strategy of the World Health Organization 2002-2005, because of its importanceit was updated for 2014-2023. In Guatemala there is a traditional practical use of medicinal plants, also there isa National Program on Traditional Medicine and the National Vade mecum on Medicinal Plants, which containvalidated information about medicinal plants and with sufficient scientific evidence. Derived from the analysis ofthe national health system, medicinal plants are proposed as one of the strategies to improve access to health carequality, and health promotion of intercultural approach, giving a new proposal to health care systems as integrated,inclusive, accessible and multicultural that promotes quality in service and to answer the needs of the communitywith the resources provided by the environment.

Actividad hipotrigliceridémica de un extracto de rosa de Jamaica (Hibiscus sabdariffa L. ) al administrarse antes y durante las comidas / Hypotriglyceridemic activity of Hibiscus (Hibiscus sabdariffa L. ) extract administered before and after meals

La elevación de los lípidos sanguíneos se ha convertido en un riesgo común de enfermedades cardiovasculares, en especial en el caso del colesterol y triglicéridos, también a problemas pancreáticos, de la córnea, bazo e hígado. Hibiscus sabdariffa L., es una especie medicinal de la familia Malvaceae, su efecto sobre la reducción de los lípidos séricos se ha mencionado en varios estudios. El objetivo del presente estudio consistió en evaluar la actividad de un extracto acuoso de los cálices de H. sabdariffa, para reducir los lípidos séricos en dos grupos de individuos, con valores de triglicéridos mayores de 150 mg/dL, al recibir una dosis de 15 mg de antocianinas totales al día, dividida entres veces, por un periodo de dos meses para establecer su influencia, dependiendo del momento de su administración, un grupo recibiéndola antes de la comida y otro durante la misma. El extracto de H. sabdariffa mostró un efecto hipotrigliceridémico significativo (p = 0.034), al finalizar el tratamiento, únicamente al administrar el extracto antes de las comidas. Al mismo tiempo, no se observó alteración en los niveles de colesterol total, colesterol contenido en las lipoproteínas de baja densidad y colesterol contenido en las proteínas de alta densidad en ninguno de los dos grupos evaluados. Los resultados sugieren que los extractos acuosos de H. sabdariffa podrían ser utilizados para ejercer una acción en los triglicéridos plasmáticos, dependiente del consumo de alimentos, y del momento de administración.

Elevated blood lipids, cholesterol and triglycerides, has become a common health risk worldwide, not only for cardiovascular diseases, especially in the case of cholesterol and triglycerides, but also in pancreatic, corneal, spleen and liver problems. Hibiscus sabdariffa L., is a medicinal plant of the Malvaceae family, its effect on reducing serum lipids is mentioned in several studies. The purpose of this study was to evaluate the activity of an aqueous extract of H. sabdariffa at a dose of 15 mg of anthocyanins daily, divided in three times a day, either before or during meals, over a period of 2 months, to decrease plasma triglycerides in subjects with values above 150 mg/dL, in order to establish the influence of the time of administration in this effect. The extract showed a hypotriglyceridemic effect (p = 0.034) in the first and second month of treatment, only when administered before meals. At the same time, no significant changes were observed in levels of total cholesterol, cLDL, cHDL in any of the evaluated groups. These results suggest that the aqueous extracts of H. sabdariffa could be used to reduce action in plasma triglycerides levels only when administered prior to meals.

Ethnobotanical, pharmacognostical, pharmacological and phytochemical studies on Smilax domingensis in Guatemala

Smilax domingensis Willd., Smilacaceae, known as zarzaparrilla, is a climbing shrub from Tropical America. The rhizome is popularly used in medicine as anti-inflammatory, antiseptic, and tonic. Since 1983 studies are being conducted in Guatemala for validation of the ethnobotanical uses, particularly in vitro demonstration of antimicrobial activity, using wild material, with high variability and some taxonomic problems. This article reports the taxonomic determination, cultivation of drug material, evaluation of use by in vitro and in vivo pharmacological assays, and phytochemical characterization. Extracts from cultivated material was evaluated by antimicrobial, anti-inflammatory, analgesic and immunomodulatory models, confirming the antimicrobial and immunomodulatory activities. Phytochemistry was done in the crude drug and extracts. Quality control parameters are described (micrographic drawings and phytochemical characteristics). Evidence is presented that cultivated rhizome has antimicrobial and immunomodulatory activities, validating the popular use and helping the industrial development of phytopharmaceutical products.

Evaluation of Behavioral and Pharmacological Effects of Hydroalcoholic Extract of Valeriana prionophylla Standl. from Guatemala.

There are few studies on the pharmacological properties of Valeriana prionophylla Standl. (VP), known as "Valeriana del monte", and used in Mesoamerican folk medicine to treat sleep disorders. This study examines the pharmacological effects of the hydroalcoholic extract of the dry rhizome using the open field, rota rod, elevated plus-maze (EPM), forced swimming (FST), strychnine- and pentobarbital-induced sleeping time, PTZ-induced seizures, and the inhibitory avoidance tests. VP did not show any protective effect against PTZ-induced convulsions. In the EPM, exhibited an anxiolytic-like effect through the effective enhancement of the entries (38.5%) and time spent (44.7%) in the open arms, when compared with control group. Time spent and the numbers of entrances into the enclosed arms were decreased, similar to those effects observed with diazepam. In the FST, acute treatment with VP, produced a dose-dependent decrease in immobility time, similarly to imipramine. VP also produced a significant dose-dependent decrease in the latency of sleeping time, while producing an increase in total duration of sleep; influenced memory consolidation of the animals only at lower doses, unlike those that produced anti-depressant and anxiolytic effects. In summary, the results suggest that VP presents several psychopharmacological activities, including anxiolytic, antidepressant, and hypno-sedative effects.

Comparison of bioassays using the anostracan crustaceans Artemia salina and Thamnocephalus platyurus for plant extract toxicity screening / Comparação de bioensaios com os crustáceos Artemia salina e Thamnocephalus platyurus para abordagem de extratos de plantas com toxicidade

Three lethality bioassays, using the salt-water crustacean Artemia salina Leach, Artemiidae, (conventional 96 microwell plate test and the Artoxkit M microbiotest) and the freshwater crustacean Thamnocephalus platyurus Packard, Thamnocephalidae, (Thamnotoxkit F microbiotest), were compared using extracts of ten Guatemalan plant species. It was previously observed that five of them have anti-Artemia activity. These were: Solanum americanum Mill., Solanaceae, Gliricidia sepium (Jacq.) Kunth ex Walp., Fabaceae, Neurolaena lobata (L.) Cass., Asteraceae, Petiveria alliacea L., Phytolaccaceae, and Ocimum campechianum Mill., Lamiaceae. The five others: Curatella americana L., Dilleniaceae, Prunus barbata Koehne, Rosaceae, Quercus crispifolia Trel., Fagaceae, Rhizophora mangle L., Rhizophoraceae, and Smilax domingensis Willd., Smilacaceae, do not. All plants without anti-Artemia activity had no lethal effects in both assays with A. salina. For the plants with anti-Artemia activity the Artoxkit M was not sensitive to G. sepium and the conventional Artemia test was not sensitive to S. americanum, G. sepium and N. lobata. All the plant extracts, except for that of C. americana, had lethal effects on T. platyurus and the lethal median concentration (LC50) levels for this organism were in all cases substantially lower than those of the salt-water test species. This study revealed that T. platyurus is a promising test species worth further in depth investigation for toxicity screening of plant extracts with potential medicinal properties.

Três bioensaios de letalidade com o crustáceo de água salgada Artemia salina Leach, Artemiidae, (teste convencional em microplaca de 96 poós Artoxkit microbiotest M) e o crustáceo de água doce Thamnocephalus platyurus Packard, Thamnocephalidae (Thamnotoxkit microbiotest F), foram comparados utilizando extratos de dez espécies de plantas da Guatemala. Foi previamente observado que cinco delas possuem atividade anti-Artemia: Solanum americanum Mill., Solanaceae, Gliricidia sepium (Jacq.) Kunth ex Walp., Fabaceae, Neurolaena lobata (L.) Cass., Asteraceae, Petiveria alliacea L., Phytolaccaceae e Ocimum campechianum Mill., Lamiaceae. As outras cinco espécies, Curatella americana L., Dilleniaceae, Prunus barbata Koehne, Rosaceae, Quercus crispifolia Trel., Fagaceae, Rhizophora mangle L., Rhizophoraceae e Smilax domingensis Willd., Smilacaceae, não. Todas as plantas sem atividade anti-Artemia não tiveram nenhum efeito letal em ambos os ensaios com A. salina. Para as plantas com atividade anti-Artemia o M Artoxkit não foi sensível a G. sepium e teste convencional de Artemia não foi sensível a S. americanum, G. sepium e N. lobata. Todos os extratos vegetais, exceto o de C. americana, apresentaram um efeito letal sobre T. platyurus e a concentração letal média (CL50) para este organismo em todos os casos foram substancialmente inferiores aos da espécie de teste de água salgada. Este estudo revelou que T. platyurus é teste promissor para uma investigação aprofundada na seleção de extratos de plantas com potenciais propriedades medicinais.

Guatemalan plants extracts as virucides against HIV-1 infection.

Prevention methods to avoid transmission of pathogens, including HIV, are crucial in the control of infectious diseases, not only to block epidemic spread but to avoid long-term treatments leading to emergence of resistances and drug associated side effects. Together with vaccine development, the discovery of new virucidal agents represents a research priority in this setting. In the screening of new compounds with antiviral activity, three Guatemalan plant extracts from Justicia reptans, Neurolaena lobata and Pouteria viridis were evaluated with a classic antiviral assay and were found to inhibit HIV replication. This activity was corroborated by an original recombinant virus assay, leading us to perform a deeper study of the virucidal activity. Active fractions were non-toxic in vitro and also inhibited other enveloped viruses. Moreover, these fractions were able to inhibit the transfer of HIV from dendritic cells (DCs) to lymphocytes, that represents the main way of HIV spread in vivo.