RESUMO
Dengue fever has emerged as a big threat to human health since the last decade owing to high morbidity with considerable mortalities. The proposed study aims at the in silico investigation of the inhibitory action against DENV4-NS1 of phytochemicals from two local medicinal plants of Pakistan. Non-Structural Protein 1 of Dengue Virus 4 (DENV4-NS1) is known to be involved in the replication and maturation of viron in the host cells. A total of 129 phytochemicals (50 from Tanacetum parthenium and 79 from Silybum marianum) were selected for this study. The tertiary structure of DENV4-NS1 was predicted based on homology modelling using Modeller 9.18 and the structural stability was evaluated using molecular dynamics simulations. Absorption, distribution, metabolism, excretion and toxicity (ADMET) along with the drug-likeness was also predicted for these phytochemicals using SwissADME and PreADMET servers. The results of ADMET and drug-likeness predictions exhibited that 54 phytochemicals i.e. 25 from Tanacetum parthenium and 29 from Silybum marianum showed effective druglikeness. These phytochemicals were docked against DENV4-NS1 using AutoDock Vina and 18 most suitable phytochemicals with binding affinities ≤ -6.0 kcal/mol were selected as potential inhibitors for DENV4-NS1. Proposed study also exploits the novel inhibitory action of Jaceidin, Centaureidin, Artecanin, Secotanaparthenolide, Artematin, Schizolaenone B, Isopomiferin, 6, 8-Diprenyleriodictyol, and Anthraxin against dengue virus. It is concluded that the screened 18 phytochemicals have strong inhibition potential against Dengue Virus 4.
Assuntos
Simulação por Computador , Proteínas/classificação , Dengue , Vírus da Dengue , Compostos Fitoquímicos/análise , Plantas Medicinais/metabolismo , Farmacocinética , Tanacetum parthenium/efeitos adversos , Simulação de Dinâmica MolecularRESUMO
Continuous use of glyphosate in citrus groves in the Gulf of Mexico region has selected for resistant Parthenium hysterophorus L. populations. In this study, the target-site and non-target-site resistance mechanisms were characterized in three putative glyphosate-resistant (GR) P. hysterophorus populations, collected in citrus groves from Acateno, Puebla (GR1 and GR2) and Martínez de la Torre, Veracruz (GR3), and compared with a susceptible population (GS). Based on plant mortality, the GR populations were 9.2-17.3 times more resistant to glyphosate than the GS population. The low shikimate accumulation in the GR population confirmed this resistance. Based on plant mortality and shikimate accumulation, the GR3 population showed intermediate resistance to glyphosate. The GR populations absorbed 15-28% less 14C-glyphosate than the GS population (78.7% absorbed from the applied) and retained 48.7-70.7% of 14C-glyphosate in the treated leaf, while the GS population translocated ~68% of absorbed herbicide to shoots and roots. The GR3 population showed the lowest translocation and absorption rates, but was found to be susceptible at the target site level. The 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene sequence of the GR1 and GR2 populations showed the Pro106-Ser mutation, conferring 19- and 25-times more resistance in comparison to the GS population, respectively. Reduced absorption and impaired translocation conferred glyphosate resistance on the GR3 population, and contributed partially to the resistance of the GR1 and GR2 populations. Additionally, the Pro-106-Ser mutation increased the glyphosate resistance of the last two P. hysterophorus populations.
Assuntos
Glicina/análogos & derivados , Herbicidas/farmacologia , Tanacetum parthenium/efeitos dos fármacos , Tanacetum parthenium/metabolismo , 3-Fosfoshikimato 1-Carboxiviniltransferase , Glicina/farmacologia , Resistência a Herbicidas , Mutação/genética , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Brotos de Planta/efeitos dos fármacos , Brotos de Planta/metabolismo , GlifosatoRESUMO
BACKGROUND: Herpes simplex type 1 (HSV-1) is widely distributed throughout the world's population. The virus spreads through direct contact with an infected individual. After primary infection, the virus remains in a latent state, and the recurrence of herpetic lesions is common. Standard treatment is performed with nucleoside analogues, but the selection of resistant strains have occurred, thus requiring the continual search for new antiviral agents. Plant extracts, fractions, and isolated compounds are a good source for studying possible antiviral compounds. HYPOTHESIS: Among plants with antiviral activity, the crude extract of aerial parts of Tanacetum parthenium (L.) Sch.Bip. (Asteraceae) have previously shown to inhibit HSV-1 infection in vitro. METHODS: The present study investigated the chemical composition of a crude hydroethanolic extract (CHE) of T. parthenium, and in vivo safety and therapeutic efficacy against HSV-1 infection. RESULTS: Liquid chromatography-mass spectrometry showed that the CHE was composed of phenolic acids (chlorogenic acids) and sesquiterpene lactones (parthenolide). Acute and subchronic toxicity and genotoxicity tests in vivo showed that oral CHE administration did not result in signs of toxicity, with no genotoxic potential. The CHE was also safe for topical administration, in which no irritation of the epidermis was observed in treated animals. Tests of topical and oral therapeutic efficacy showed that the CHE was effective against HSV-1 infection. Topical administration was the most effective, the results for which were comparable to acyclovir. CONCLUSION: These findings indicate that the CHE from aerial parts of Tanacetum parthenium has in vivo anti-HSV-1 activity and is safe for oral and topical application.
Assuntos
Antivirais/toxicidade , Antivirais/uso terapêutico , Herpes Simples/tratamento farmacológico , Herpesvirus Humano 1/efeitos dos fármacos , Extratos Vegetais/toxicidade , Tanacetum parthenium/química , Tanacetum parthenium/toxicidade , Animais , Antivirais/farmacologia , Camundongos , Modelos Animais , Extratos Vegetais/química , Espectrometria de Massas em TandemRESUMO
Multiple sclerosis is a chronic inflammatory and autoimmune disease of the central nervous system that affects more than 2.5 million people worldwide. Experimental autoimmune encephalomyelitis is a murine autoimmune disease used to study multiple sclerosis. Parthenolide, a natural sesquiterpene lactone found in Tanacetum parthenium L., is known for its strong anti-inflammatory activity. Herein, we have investigated the in vitro immunomodulatory effects of parthenolide on cytokine production and nitric oxide in cultured cells from myelin oligodendrocyte glycoprotein 35-55 amino acid peptide mice. Experimental autoimmune encephalomyelitis was induced in C57BL/6 mice with myelin oligodendrocyte glycoprotein 35-55 amino acid peptide, and parthenolide was isolated from T. parthenium. Splenocytes and peritoneal cells were obtained from experimental autoimmune encephalomyelitis-induced mice and incubated with parthenolide (1, 5, and 20 µM). After in vitro treatment with parthenolide, supernatants were collected, and nitric oxide and cytokines were measured. The results suggested that parthenolide may regulate the activity of Th17 and Th1 cells, mainly by decreasing IL-17, TNF-α, and interferon gamma production. This modulation may be related to the lower levels of IL-12p40 and IL-6 after treatment with parthenolide. It was shown, for the first time, that parthenolide presents in vitro immunomodulatory effects on inflammatory mediators produced by cells from experimental autoimmune encephalomyelitis-induced mice.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Encefalomielite Autoimune Experimental/tratamento farmacológico , Imunidade Celular/efeitos dos fármacos , Esclerose Múltipla/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Sesquiterpenos/uso terapêutico , Tanacetum parthenium/química , Animais , Citocinas/metabolismo , Encefalomielite Autoimune Experimental/imunologia , Fatores Imunológicos/uso terapêutico , Camundongos Endogâmicos C57BL , Esclerose Múltipla/imunologia , Sesquiterpenos/isolamento & purificação , Baço/citologia , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Linfócitos T Auxiliares-Indutores/imunologiaRESUMO
câncer colorretal constitui uma das principais causas de câncer no Brasil e no mundo. O microambiente inflamatório desempenha um importante papel na iniciação, promoção e progressão deste tipo de câncer. O TNF-α é um componente deste microambiente e conhecido por ativar via NF-κB. Neste contexto, o partenolídeo, uma lactona sesquiterpênica, com importante função anti-inflamatória por inibir a via NF-κB,apresenta-se como uma promissora molécula anticâncer por prevenir progressão no ciclo celular, migração, invasão e sobrevivência de células tumorais. No entanto, seus efeitos no câncer colorretal necessitam ser melhor definidos. O objetivo do presenteestudo foi analisar a ação do partenolídeo na reversão de características pró-tumoraisem células derivadas de câncer colorretal, Caco-2, HT-29 e HCT-116. Nossos resultados mostram que a atividade de NF-κB está diferencialmente ativa entre asdiferentes linhagens de células de câncer colorretal e que a resposta citotóxica ao tratamento com partenolídeo está relacionada com essa ativação. O partenolídeo foi capaz de prevenir a ativação da via NF-κB induzida por TNF-α através da redução da fosforilação do IκBα nas linhagens Caco-2 e HT-29, porém parece ter outro alvo inibitório nas células HCT-116, pois estas não apresentaram redução na translocação nuclear de NF-κB...
Colorectal cancer is one the main cancer types in Brazil and world. Inflammatorymicroenvironmet plays an important role in the initiation, promotion and progression of this cancer. TNF-a is an important constituent of this microenvironment, which is known as activator of NF-κB pathway. In this context, the parthenolide, a esquiterpene lactone that have anti-inflammatory function through NF-κB inhibition, presents promising anticancer properties for preventing cell cycle progression, migration,invasion and cell survival. However, the effects on colorectal cancer need to be best understood. This study aims to analyze the parthenolide action reversing pro-tumor characteristics of Caco-2, HT-29 and HCT-116 colorectal cancer cells. Our results shown the NF-κB pathway is differentially active among cell types of colorectal cancerand citotoxic response to parthenolide treatment has relationship with this level of activation. Parthenolide was able to prevent the TNF-α induced-activation NF-κB pathway through to decrease IκBα phosphorilation in Caco-2 and HT-29, but seem have another inhibitory target in HCT-116 cells, because it did not observed reduction of NF-κB nuclear in these cells...
Assuntos
Caderinas , Neoplasias Colorretais , Progressão da Doença , NF-kappa B , Tanacetum partheniumRESUMO
The discovery of new treatments for neglected diseases, including leishmaniasis, is a substantial challenge for scientific research. Plant extracts have shown potential in the selective treatment of tropical diseases. The present study evaluated the in vitro and in vivo antileishmania effects of a sesquiterpene lactone-rich dichloromethane fraction (DF) obtained from the aerial parts of Tanacetum parthenium (L.) Schultz-Bip. In vitro studies of the DF indicated an IC50 of 2.40±0.76 µg mL(-1) against the promastigote form and 1.76±0.25 µg mL(-1) against the axenic amastigote form of Leishmania amazonensis. In vivo intramuscular treatment with DF decreased the growth and size of footpad lesions in mice. The DF also significantly decreased the parasite population compared with animals that were treated with the reference drug. Plasma malondialdehyde levels were increased slightly by the DF, attributable to its parthenolide-rich composition that causes cellular apoptosis, compared with the control group, demonstrating treatment efficacy without toxicity or genotoxicity. Because the isolation and purification of plant compounds are costly and time-consuming and generate low yields, extract fractions, such as the DF studied herein, represent a promising alternative for the treatment of leishmaniasis.
Assuntos
Antiprotozoários/farmacologia , Leishmania mexicana/efeitos dos fármacos , Leishmaniose Tegumentar Difusa/tratamento farmacológico , Extratos Vegetais/farmacologia , Tanacetum parthenium/química , Animais , Antiprotozoários/uso terapêutico , Antiprotozoários/toxicidade , Linhagem Celular , Feminino , Humanos , Lactonas/farmacologia , Lactonas/uso terapêutico , Lactonas/toxicidade , Leishmaniose Tegumentar Difusa/parasitologia , Linfonodos/parasitologia , Macrófagos/efeitos dos fármacos , Masculino , Malondialdeído/sangue , Cloreto de Metileno/farmacologia , Cloreto de Metileno/uso terapêutico , Cloreto de Metileno/toxicidade , Camundongos , Camundongos Endogâmicos BALB C , Testes para Micronúcleos , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Extratos Vegetais/toxicidade , Sesquiterpenos/farmacologia , Sesquiterpenos/uso terapêutico , Sesquiterpenos/toxicidadeRESUMO
Los procesos inflamatorios no controlados producen daño celular donde los radicales libres están presentes y representan un peligro para la vida del paciente, en este contexto la búsqueda de moléculas de origen vegetal son incesantes por su aceptación cultural, una mejor compatibilidad con el cuerpo humano y menos efectos secundarios. El objetivo fue determinar la actividad antioxidante y antiinflamatoria del extracto hidroalcohólico de las flores de Tanacetum parthenium L. Sch. Bip. "santa maria", empleando la técnica in vitro del DPPH y el modelo in vivo de edema plantar inducida por carragenina en ratas Wistar. Se llevó a cabo en los laboratorios de la Escuela de Farmacia y Bioquímica de la Universidad Nacional de San Cristóbal de Huamanga, Ayacucho, Perú. La muestra fue recolectada en la ciudad de Huancayo, región Junin. Se ensayó concentraciones de 1, 2 y 3% en ungüentos base como vehículo semisólido usando el estándar de referencia diclofenaco gel 1%. El extracto hidroalcohólico contiene fenoles y taninos, flavonoides, faetonas y/o cumarinas, triterpenos y/o esteroides y aminoácidos. La concentración de extracto hidroalcohólico de las flores de Tanacetum parthenium L. Sch. Bip. "santa maria" con mayor actividad antiinflamatoria fue al 3%, con un porcentaje de desinflamación del84.6% {porcentaje de inflamación de 15.4%) y con un ABC de 6,214 mllt2. La concentración de extracto hidroalcohólico de las flores de Tanacetum parthenium L. Sch. Bip. "santa maria" con mayor actividad antioxidante fue a 100 ¡Jg/ml, con un porcentaje de 63,9%. Se concluye que el extracto hidroalcohólico de las flores de Tanacetum parthenium L. Sch. Bip. "santa maría" tiene poca actividad antioxidante in vitro pero buena actividad antiinflamatoria in vivo estadísticamente similar al diclofenaco por lo que constituyen una fuente potencial para el tratamiento antiinflamatorio tópico.
Assuntos
Animais , Ratos , Tanacetum parthenium , Anti-Inflamatórios , Antioxidantes , Peru , Técnicas In Vitro , Solução Hidroalcoólica , Modelos AnimaisRESUMO
BACKGROUND: The aim of the present study was to investigate the efficacy and tolerability of acupuncture (AC), Tanacetum (TAN) or combined treatment on quality of life in women with chronic migraine (CM). METHODS: A total of 69 women volunteers were randomly divided into 3 groups: AC, acupuncture administered in 20 sessions over 10 weeks (n=22); TAN, at 150 mg/day (n=23); and AC+TAN (n=23). The primary outcome was Short-Form 36 (SF-36) quality of life assessment score. Secondary outcomes included the Migraine Disability Assessment (MIDAS) and visual analogue scale (VAS) score experienced after randomisation. RESULTS: AC+TAN was statistically significantly more effective than AC or TAN alone in overall health-related quality of life (SF-36; p<0.05), on MIDAS score (-35.1 (10.6) AC vs -24.8 (11.7) TAN vs -42.5 (9.8) AC+TAN; p<0.05) and in reducing the mean score of pain on VAS (-5.6 (2.4) AC vs -3.7 (2.1) TAN vs -6.4 (3.1) AC+TAN; p<0.05). CONCLUSIONS: The present work shows an improvement of the quality of life and better analgesic effect of acupuncture combined with TAN treatment on migraine pain in women when compared with acupuncture or TAN alone.
Assuntos
Terapia por Acupuntura , Medicamentos de Ervas Chinesas/administração & dosagem , Transtornos de Enxaqueca/terapia , Qualidade de Vida , Tanacetum parthenium/química , Analgesia por Acupuntura , Adolescente , Adulto , Terapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Transtornos de Enxaqueca/tratamento farmacológico , Resultado do Tratamento , Adulto JovemRESUMO
Use of natural tannin in the screening of tannase producing microbes is really promising. The present work describes about the possibility and integrity of the newly formulated method over the previously reported methods. Tannin isolated from Terminalia belerica Roxb. (Bahera) was used to differentiate between tanninolytic and nontanninolytic microbes. The method is simple, sensitive and superior for the rapid screening and isolation of tannase-producing microbes.
Assuntos
Estruturas Vegetais/enzimologia , Fermentação , Tanacetum parthenium/enzimologia , Taninos Hidrolisáveis/análise , Taninos Hidrolisáveis/isolamento & purificação , Ativação Enzimática , Hidrólise , MétodosRESUMO
Leishmaniasis is one of the major infectious diseases affecting the poorest regions of the world. The present study evaluated the antileishmanial activity of a guaianolide purified from the hydroalcoholic extract of aerial parts of Tanacetum parthenium (L.) Schultz Bip. The isolated compound showed activity against the promastigote form of Leishmania amazonensis, with 50% inhibition (IC(50)) of cell growth at a concentration of 2.6 µg/ml. For the intracellular amastigote form, this guaianolide reduced by 10% the survival index of parasites in macrophages when it was used at 20.0 µg/ml. The selective index (SI) ratio (CC(50) for J774G8 cells/IC(50) for protozoans) was 385, showing that it is more selective against the parasite than mammalian cells. Morphological alterations of protozoans treated with IC(50) included changes in size, shape, and structure (more than one nucleus and flagellum) under both light and scanning electron microscopies.