RESUMO
OBJECTIVES: ß-Escin, one of the constituents of Aesculus hippocastanum L. (Hippocastanaceae) seed extract (AH), inhibits NF-κB activation, which plays an important role in HSV-1 replication. The aim was to examine the antiherpetic activity of ß-escin and AH, as well as their effect on the activation of NF-κB and AP-1 and cytokine secretion in epithelial cells and macrophages. METHODS: Cell viability was evaluated using MTT assay, and antiviral and virucidal activity was determined by plaque assay. The effect on NF-κB and AP-1 signalling pathways activation was determined by a luciferase reporter assay, and cytokine production was measured by ELISA. KEY FINDINGS: ß-Escin and AH had virucidal and anti-HSV-1 activities, and the antiviral activity was discovered for other enveloped viruses (VSV and Dengue). Moreover, ß-escin and AH significantly reduced NF-κB and AP-1 activation and cytokine production in macrophages stimulated with HSV-1 and TLRs ligands. However, an enhanced activation of these pathways and an increase in the levels of pro-inflammatory cytokines in ß-escin and AH-treated HSV-1-infected epithelial cells were found. CONCLUSIONS: This study demonstrates virucidal and broad-spectrum antiviral activities for ß escin and AH. Besides, ß-escin and AH modulate cytokine production depending on the stimuli (viral or non-viral) and the cell type under study.
Assuntos
Aesculus , Antivirais/farmacologia , Células Epiteliais/efeitos dos fármacos , Escina/farmacologia , Fatores Imunológicos/farmacologia , Macrófagos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Vírus/efeitos dos fármacos , Células A549 , Aesculus/química , Animais , Antivirais/isolamento & purificação , Citocinas/metabolismo , Vírus da Dengue/efeitos dos fármacos , Vírus da Dengue/patogenicidade , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Células Epiteliais/virologia , Escina/isolamento & purificação , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 1/patogenicidade , Humanos , Fatores Imunológicos/isolamento & purificação , Mediadores da Inflamação/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/virologia , Camundongos , NF-kappa B/metabolismo , Extratos Vegetais/isolamento & purificação , Fator de Transcrição AP-1/metabolismo , Vesiculovirus/efeitos dos fármacos , Vesiculovirus/patogenicidade , Vírus/patogenicidadeRESUMO
In a previous work our group showed that some synthetic stigmastanes may play a role in immune-mediated inflammation. In this paper we report the syntheses of a series of new steroidal compounds derived from dehydroepiandrosterone and stigmasterol, and the evaluation of their in vitro inhibitory activity of the TNF-alpha production by macrophages. A preliminary qualitative structure-activity relationship was established.