RESUMO
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
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
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
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.
Assuntos
Antiprotozoários/farmacologia , Leishmania/efeitos dos fármacos , Sesquiterpenos de Guaiano/farmacologia , Tanacetum parthenium/química , Animais , Antiprotozoários/química , Antiprotozoários/toxicidade , Linhagem Celular , Humanos , Leishmania/classificação , Leishmania/crescimento & desenvolvimento , Leishmania/ultraestrutura , Macrófagos Peritoneais/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Varredura , Testes de Sensibilidade Parasitária , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Sesquiterpenos de Guaiano/química , Sesquiterpenos de Guaiano/toxicidadeRESUMO
This study reports the activity of crude extracts, fractions and parthenolide (pure compound) obtained from Tanacetum parthenium against two forms of the parasite Trypanosoma cruzi. Feverfew is a traditional herbal medicine that has been used for the treatment of migraine, fever and arthritis. Activity against epimastigote forms was observed for crude extracts, fractions and parthenolide, and a progressive increase in the antitrypanosomal effect was observed in the course of the purification process. The pure compound showed IC50/96h and IC90/96h of 0.5 microg/ml and 1.25 microg/ml, respectively. The cytotoxic effect of parthenolide in LLMCK2 cells was 3.2 microg/ml (CC50/96h) and the selectivity index was 6.4. No hemolysis was detected for the pure compound. The internalization index of T. cruzi in LLMCK2 cells was reduced almost 51% at the concentration of 2 microg/ml of parthenolide, and 96.6% at 4 microg/ml. Scanning and transmission electron microscopy permitted observation of morphological modifications and ultrastructural alterations.
Assuntos
Antiprotozoários/farmacologia , Extratos Vegetais/farmacologia , Sesquiterpenos/farmacologia , Tanacetum parthenium/química , Trypanosoma cruzi/efeitos dos fármacos , Animais , Antiprotozoários/isolamento & purificação , Antiprotozoários/toxicidade , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Concentração Inibidora 50 , Macaca mulatta , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Extratos Vegetais/toxicidade , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/toxicidade , Trypanosoma cruzi/crescimento & desenvolvimento , Trypanosoma cruzi/ultraestruturaRESUMO
LC-UV and LC-MS methods have been developed which permit the analysis of parthenolide in different Mexican/US feverfew samples and commercial products. The study was undertaken to confirm the presence of parthenolide in Mexican plant samples and its comparison with US feverfew samples. The best results were obtained with a Phenomenex Luna C18 (2) column using gradient mobile phase of water and acetonitrile:methanol (9 : 1). Elution was run at a flow rate of 1.0 mL per min and ultraviolet detection at 210 nm. The results obtained using LC-UV were comparable to those obtained using LC-MS. Parthenolide was detected in all the samples analyzed and is the major chemical constituent of feverfew. The samples collected in Oaxaca, Mexico (0.28%) and Puebla, Mexico (0.25%) showed the highest content of parthenolide. All Parthenium samples were also examined under light and fluorescent microscopy.
Assuntos
Anti-Inflamatórios não Esteroides/análise , Sesquiterpenos/análise , Tanacetum parthenium/química , Tanacetum/química , Calibragem , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , México , Microscopia de Fluorescência , Padrões de Referência , Espectrofotometria Ultravioleta , Tanacetum/anatomia & histologia , Tanacetum parthenium/anatomia & histologia , Estados UnidosRESUMO
The in vitro activity of parthenolide against Leishmania amazonensis was investigated. Parthenolide is a sesquiterpene lactone purified from the hydroalcoholic extract of aerial parts of Tanacetum parthenium. This isolated compound was identified through spectral analyses by UV, infrared, (1)H and (13)C nuclear magnetic resonance imaging, DEPT (distortionless enhancement by polarization transfer), COSY (correlated spectroscopy), HMQC (heteronuclear multiple-quantum coherence), and electron spray ionization-mass spectrometry. Parthenolide showed significant activity against the promastigote form of L. amazonensis, with 50% inhibition of cell growth at a concentration of 0.37 microg/ml. For the intracellular amastigote form, parthenolide reduced by 50% the survival index of parasites in macrophages when it was used at 0.81 microg/ml. The purified compound showed no cytotoxic effects against J774G8 macrophages in culture and did not cause lysis in sheep blood when it was used at higher concentrations that inhibited promastigote forms. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis with gelatin as the substrate showed that the enzymatic activity of the enzyme cysteine protease increased following treatment of the promastigotes with the isolated compound. This finding was correlated with marked morphological changes induced by parthenolide, such as the appearance of structures similar to large lysosomes and intense exocytic activity in the region of the flagellar pocket, as seen by electron microscopy. These results provide new perspectives on the development of novel drugs with leishmanicidal activities obtained from natural products.