RESUMO
Herpes simplex virus infections persist throughout the lifetime of the host and affect more than 80â% of the humans worldwide. The intensive use of available therapeutic drugs has led to undesirable effects, such as drug-resistant strains, prompting the search for new antiherpetic agents. Although diverse bioactivities have been identified in Schinus terebinthifolia, its antiviral activity has not attracted much attention. The present study evaluated the antiherpetic effects of a crude hydroethanolic extract from the stem bark of S. terebinthifolia against Herpes simplex virus type 1 in vitro and in vivo as well as its genotoxicity in bone marrow in mammals and established the chemical composition of the crude hydroethanolic extract based on liquid chromatography-diode array detector-mass spectrometry and MS/MS. The crude hydroethanolic extract inhibited all of the tested Herpes simplex virus type 1 strains in vitro and was effective in the attachment and penetration stages, and showed virucidal activity, which was confirmed by transmission electron microscopy. The micronucleus test showed that the crude hydroethanolic extract had no genotoxic effect at the concentrations tested. The crude hydroethanolic extract afforded protection against lesions that were caused by Herpes simplex virus type 1 in vivo. Liquid chromatography-diode array detector-mass spectrometry and MS/MS identified 25 substances, which are condensed tannins mainly produced by a B-type linkage and prodelphinidin and procyanidin units.
Assuntos
Anacardiaceae/química , Antivirais/farmacocinética , Herpes Simples/tratamento farmacológico , Herpesvirus Humano 1/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Antivirais/química , Antivirais/isolamento & purificação , Antivirais/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Cromatografia Líquida , Feminino , Herpes Simples/virologia , Herpesvirus Humano 1/ultraestrutura , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Transmissão , Casca de Planta/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Espectrometria de Massas em Tandem , Taninos/análise , Taninos/química , Células VeroRESUMO
Meliacine (MA), an antiviral principle isolated from leaves of Melia azedarach L., exhibits potent antiviral activity against herpes simplex virus type 1 (HSV-1) by inhibiting specific infected-cell polypeptides (ICPs) produced late in infection. Some of these are involved in DNA synthesis and in the assembly of nucleocapsids. The present report provides additional evidence to elucidate the mode of action of MA against HSV-1. Time-of-addition experiments confirmed that MA affects a late event in the multiplication cycle of HSV-1. We showed that MA diminished the synthesis of viral DNA and inhibited the spread of infectious viral particles when HSV-1 that expresses beta-galactosidase activity was used. In addition, the lack of a protein with an apparent MW of 55 KD was detected in MA-treated cell extracts. Ultrastructural analysis of infected cells showed that, in the case of MA treatment, a large number of unenveloped nucleocapsids accumulated in the cytoplasm and a minor proportion of mature virus was found in cytoplasmic vesicles.These findings suggest that MA exerts an antiviral action on both the synthesis of viral DNA and the maturation and egress of HSV-1 during the infection of Vero cells.
Assuntos
Antivirais/isolamento & purificação , Antivirais/farmacologia , Herpesvirus Humano 1/efeitos dos fármacos , Meliaceae/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Replicação Viral/efeitos dos fármacos , Animais , Antivirais/química , Transformação Celular Viral , Chlorocebus aethiops , DNA Viral/biossíntese , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/crescimento & desenvolvimento , Herpesvirus Humano 1/ultraestrutura , Folhas de Planta/química , Células Vero , Proteínas Virais/biossínteseRESUMO
INTRODUCTION: In spite of the human, social and economic impact of schizophrenia and to be considered a disease of organic origin by several evidences, there are relatively few studies about this disease using electron microscopic techniques. PATIENTS AND METHODS: For 23 years we made studies about the viral hypothesis of schizophrenia by means of this technique. We studied limbic structure samples from young adult s dead schizophrenic patients, from fetuses of schizophrenic mothers and from chicken embryos experimentally inoculated with cerebrospinal fluid from schizophrenic patients. In the last ten years we have performed studies of blood and cerebrospinal fluid samples from young schizophrenic patients. We have found some alterations with the same characteristic to those observed in the central nervous system, which are compatible with: a) the viral hypothesis and b) with herpes simplex hominis type I virus, when immuno electronmicroscopic techniques were made. RESULTS AND CONCLUSION: The results obtained in this work can constitute a new element favoring the possible viral etiology of this disease.