RESUMO
Sensitizing activities exerted by 3,4-dihydro-7-hydroxycadalene (1), rac-3,7-dihydroxy-3(4H)-isocadalen-4-one (4) and (1R,4R)-4H-1,2,3,4-tetrahydro-1-hydroxycadalen-15-oic acid (9), the major cadinanes isolated from Heterotheca inuloides, towards multidrug-resistant MES-SA/MX2 and parental MES-SA epithelial human uterine sarcoma cell lines were evaluated. We also evaluated the in silico interactions (expressed as ΔGbinding in kcal/mol) of cadinanes 1, 4 and 9 in an in vitro assay, and also tested several structurally related natural compounds with the multidrug resistance protein (MDR1, P-glycoprotein), human multidrug resistance protein 1 (MRP1), and breast cancer resistance protein (BCRP) structures as pharmacological targets using AutoDock and AutoDock Vina. Compound 1 potentiated the cytotoxicity of doxorubicin and mitoxantrone drugs in resistant MES-SA/MX2 cells, compared to cells treated with each drug alone. Compound 1 could reverse the resistance to doxorubicin 12.44 fold at a concentration of 5⯵M. It also re-sensitized cells to mitoxantrone 3.94 fold. Hence, compound 1 may be considered as a potential chemosensitizing agent to overcome multidrug resistance in cancer. The docking analysis suggested that there are interactions between cadinanes from H. inuloides and MDR1, MRP1, and BCRP proteins mainly through π-π interactions and hydrogen bonds.
Assuntos
Transportadores de Cassetes de Ligação de ATP/química , Antineoplásicos Fitogênicos/farmacologia , Asteraceae/química , Produtos Biológicos/farmacologia , Sesquiterpenos Policíclicos/farmacologia , Transportadores de Cassetes de Ligação de ATP/genética , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Sesquiterpenos Policíclicos/química , Sesquiterpenos Policíclicos/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Heterotheca inuloides Cass. (Asteraceae) has been traditionally used to treat a wide range of diseases in Mexico in the treatment of rheumatism, topical skin inflammation, muscular pain colic, and other painful conditions associated with inflammatory processes, additionally has been used to treat dental diseases, and gastrointestinal disorders. This species has also been used for the treatment of cancer and diabetes. This review provides up-to-date information on the botanical characterization, traditional uses, chemical constituents, as well as the biolological activities of H. inuloides. MATERIAL AND METHODS: A literature search was conducted by analyzing the published scientific material. Information related to H. inuloides was collected from various primary information sources, including books, published articles in peer-reviewed journals, monographs, theses and government survey reports. The electronic search of bibliographic information was gathered from accepted scientific databases such as Scienfinder, ISI Web of Science, Scielo, LILACS, Redalyc, Pubmed, SCOPUS and Google Scholar. RESULTS: To date, more than 140 compounds have been identified from H. inuloides, including cadinane sesquiterpenes, flavonoids, phytosterols, triterpenes, benzoic acid derivatives, and other types of compounds. Many biological properties associated with H. inuloides. Many studies have shown that the extracts and some compounds isolated from this plant exhibit a broad spectrum of biological activities such as antioxidant, antitumor, anti-inflammatory, cytotoxic, and chelating activities, as well as insecticidal and phytotoxic activity. To date, reports on the toxicity of H. inuloides are limited. CONCLUSIONS: A comprehensive analysis of the literature obtained through the above-mentioned sources conï¬rmed that ethnomedical uses of H. inuloides have been recorded in Mexico to treat rheumatism, pain, and conditions associated with inflammatory processes. Pharmacological studies have demonstrated the activity of certain compounds associated with the traditional use of the plant such as the anti-inflammatory and cytotoxic activities of the species. The available literature showed that cadinene sesquiterpenes are the major bioactive components of H. inuloides with potential pharmacological activities. Further investigations are needed to fully understand the mode of action of the major active constituents.
Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Arnica/química , Medicina Tradicional , Compostos Fitoquímicos/uso terapêutico , Extratos Vegetais/uso terapêutico , Analgésicos/efeitos adversos , Analgésicos/isolamento & purificação , Animais , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/uso terapêutico , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/isolamento & purificação , Humanos , Compostos Fitoquímicos/efeitos adversos , Compostos Fitoquímicos/isolamento & purificação , Fitoterapia , Extratos Vegetais/efeitos adversos , Extratos Vegetais/isolamento & purificação , Plantas MedicinaisRESUMO
The people of San Rafael Coxcatlán use Cordia curassavica to treat gastrointestinal and respiratory disorders. The aim of this work was to investigate the temporal variation of chemical composition and antimicrobial activity of the essential oil of C. curassavica in two seasons of the year (dry and rainy). The essential oil of aerial parts was obtained by steam distillation, 12 and 17 compounds were identified for dry and rainy seasons respectively by GC-MS. The major component was for the dry season 1,7,7-trimethyl tricyclo (2.2.1.0(2,6)) heptane (20.3 percent), and for the rainy season was germacrene (24.41 percent). The antibacterial activity of essential oils varies temporarily because was active in nine strains in the dry season and four in the wet. The more sensitive strains were Stapahylococcus epidermidis and Vibrio cholera. The essential oil obtained in dry season presented a MIC of 0.75 and 0.125 mg/mL, and for the rainy season a MIC of 1.00 and 0.375 mg/mL respectively. Rhizoctonia solani was the more sensitive fungi strain (IC25 0.1300 mg/mL) in the rainy season. These results show that the chemical composition and biological properties of essential oil of the C. curassavica have temporal variation.
La población de San Rafael para tratar padecimientos gastrointestinales y respiratorios emplean Cordia curassavica. El objetivo del presente trabajo fue investigar la variación temporal de la composición química y la actividad antimicrobiana del aceite esencial de C. curassavica colectada en dos épocas del año (sequía y lluvias). El aceite esencial se obtuvo mediante la técnica de arrastre de vapor y los componentes se identificaron por CG-MS. En la época de secas se detectaron 12 compuestos y 17 en la de lluvias. El principal componente para la época de secas fue el 1,7,7 trimetil triciclo (2.2.1.0(2,6)) heptano (20.3 por ciento) y para la temporada de lluvias fue el germacrano (24.41 por ciento). La actividad antibacteriana del aceite esencial varía temporalmente porque fue activo sobre nueve cepas en la época seca y sobre cuatro cepas en la época lluviosa. Las cepas más sensibles para ambas estaciones fueron Stapahylococcus epidermidis y Vibrio cholerae. En la época de seca, el aceite esencial presentó la concentración mínima inhibitoria (CMI) de 0.75 y 0.125mg/mL, mientras que en la época de lluvias fueron de 1.00 y 0.375 mg/mL respectivamente. La cepa fúngica más sensible fue Rhizoctonia solani (IC25 0.130 mg/mL) en la época de lluvia. Estos resultados muestran que la composición química y las propiedades biológicas de los aceites esenciales de Cordia curassavica varian de acuerdo a la época del año.
Assuntos
Óleos Voláteis/farmacologia , Óleos Voláteis/química , Antibacterianos/farmacologia , Antibacterianos/química , Cordia/química , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Boraginaceae/química , Estação Seca , Cromatografia Gasosa-Espectrometria de Massas , Testes de Sensibilidade Microbiana , Estação Chuvosa , Estações do Ano , Sesquiterpenos/análise , Terpenos/análiseRESUMO
Argemone ochroleuca Sweet (Papaveraceae) is used to treat eye infection, respiratory and dermatological disorders in Tepotzotlán, State of México (México). The aim of this work was to investigate antimicrobial activity of hexane, ethyl acetate and methanol extracts from aerial parts of A. ochroleuca. The antimicrobial activity was evaluated against thirteen bacteria and nine fungal strains. Only methanol extract showed antimicrobial activity. S. aureus (MIC= 125 ug/mL) and C. neoformans (MIC= 500 ug/mL) were the most sensitive strains. The bioassay-guide purification of the methanolic extract resulted in the isolation and identification of the isoquinoline alkaloid berberine. The present study confirms the antimicrobial activity of methanolic extract of A. ochroleuca.
Infusiones de la parte aérea de Argemone ochroleuca Sweet (Papaveraceae) son utilizadas por los pobladores de Tepotzotlán, Estado de México, para el tratamiento de infecciones en los ojos, enfermedades respiratorias y dermatológicas. El objetivo de este trabajo fue investigar la actividad antimicrobiana de los extractos hexánicos, acetato de etilo y metanólico de la parte aérea de A. ochroleuca. La actividad antimicrobiana fue evaluada frente a trece cepas bacterianas y nueve cepas fúngicas. Solo el extracto metanólico presentó actividad antimicrobiana. S. aureus (MIC= 125 ug/mL) y C. neoformans (MIC= 500 ug/mL) fueron las cepas que presentaron mayor sensibilidad. La purificación biodirigida del extracto metanólico dio como resultado el aislamiento e identificación del alcaloide isoquinolínico berberina. El presente estudio confirma la actividad antimicrobiana del extracto metanólico de A. ochroleuca.
Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Argemone/química , Extratos Vegetais/farmacologia , Cryptococcus neoformans , Extratos Vegetais/química , México , Metanol/farmacologia , Staphylococcus aureus , Testes de ToxicidadeRESUMO
In traditional Mexican medicine Cordia curassavica (Jacq) Roemer & Schultes is used to treat gastrointestinal, respiratory and dermatological disorders in Zapotitlán de las Salinas, Puebla (México). The aim of this work was to investigate antimicrobial activity of the essential oil, obtained by using Clevenger distillation apparatus, and hexane, chloroform and methanol extracts from aerial parts of Cordia curassavica. Antimicrobial activity was evaluated against 13 bacteria and five fungal strains. The oil and extracts exhibited antimicrobial activity against Gram-positive and Gram-negative bacteria and five fungal strains. Sarcina lutea and Vibrio cholerae were the strains more sensitive to the essential oil effect (MIC=62 microg/mL) and Vibrio cholerae for the hexane extract (MIC=125 microg/mL). Rhyzoctonia solani was the strain more sensitive to the essential oil effect (IC(50)=180 microg/mL) and Trichophyton mentagrophytes for the hexane extract (IC(50)=230 microg/mL). The essential oil was examined by GC and GC-MS. A total 11 constituents representing 96.28% of the essential oil were identified: 4-methyl,4-ethenyl-3-(1-methyl ethenyl)-1-(1-methyl methanol)cyclohexane (37.34%), beta-eudesmol (19.21%), spathulenol (11.25%) and cadina 4(5), 10(14) diene (7.93%) were found to be the major components. The present study tends to confirm the use in the folk medicine of Cordia curassavica in gastrointestinal, respiratory and dermatological diseases.
Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Cordia , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Animais , Antibacterianos/química , Antibacterianos/toxicidade , Antifúngicos/química , Antifúngicos/toxicidade , Artemia/efeitos dos fármacos , Fracionamento Químico , Clorofórmio/química , Fungos/efeitos dos fármacos , Fungos/crescimento & desenvolvimento , Cromatografia Gasosa-Espectrometria de Massas , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/crescimento & desenvolvimento , Hexanos/química , Dose Letal Mediana , Metanol/química , México , Testes de Sensibilidade Microbiana , Óleos Voláteis/química , Óleos Voláteis/toxicidade , Componentes Aéreos da Planta , Extratos Vegetais/farmacologia , Óleos de Plantas/química , Óleos de Plantas/toxicidade , Solventes/químicaRESUMO
Se presentan los resultados de una evaluación de la distribución del conocimiento tradicional acerca del uso de plantas medicinales para el tratamiento de enfermedades gastrointestinales entre los habitantes de Zapotitlán de las Salinas, Puebla, México. La evaluación se realizó utilizando métodos etnobotánicos aplicados a 119 informantes representativos de la comunidad. Un total de 44 especies fueron registradas con uso en la curación de afecciones gastrointestinales. De ellas, las que tuvieron mayor importancia relativa por su frecuencia de mención en las entrevistas fueron Orégano (Lippia graveolens Kunth), Cinco Negritos Blanco (Lantana achyranthifolia Desf), Itamo Real (Turnera diffusa Willd), Salve Real (Lippia oaxacana Rob. & Greenm.), Zempoalxóchitl Chiquito (Gymno laena oaxacana (Greenm.) Rydb), Barredor (Cordia curassavica (Jacq) Roem. & Schul.), Cinco Negritos Rojo (Lan tana camara L) y Hierba del Pastor (Aca lypha hederacea Torrey). En cuanto al acceso del conocimiento, se observa un patrón de distribución al azar debido a que existe consenso entre los informantes, aun cuando también se observan variaciones en cuanto al acceso del conocimiento dado principalmente por el papel que cada informante desempeña en la sociedad