RESUMEN
Zika virus (ZIKV) epidemic and its association with severe neurological syndromes have raised worldwide concern. Despite the great clinical relevance of this infection, no vaccine or specific treatment is available and the search for antiviral compounds against ZIKV is extremely necessary. Several natural compounds, such as silymarin, exhibit antioxidant, hepatoprotective, and antiviral properties; however, the antiviral potential of this compound remains partially investigated. Therefore, the objective of this study was to evaluate in vitro the antiviral activity of silymarin against ZIKV infection. Global antiviral activity, dose-dependent, plaque reduction, and time-of-drug-addition assays were used to determine the anti-ZIKV activity of silymarin. Additionally, to start characterizing the mechanisms of action we determined whether silymarin could have a virucidal effect and inhibit viral adsorption and penetration stages. Regarding its global antiviral activity, silymarin showed significant inhibition of ZIKV infection, protecting cells infected with EC50 equal to 34.17µg/mL, with a selectivity index greater than 17 and 4x greater than that of the positive control (ribavirin). Its greatest efficiency was achieved at 125µg/mL, whose cell viability did not differ from the control without infection and treatment. Furthermore, treatment with silymarin reduced viral load by up to two logs (> 90%) concerning viral control, when evaluating virucidal activity and the precocious times of infection. Thus, our results set to show the promising anti-ZIKV activity of silymarin, which does not seem to have a single inhibition mechanism, acting at different times of infection, and still has the advantage of silymarin be a phytotherapy already available on the market.
Asunto(s)
Antivirales/farmacología , Silimarina/farmacología , Virus Zika/efectos de los fármacos , Animales , Antioxidantes/farmacología , Relación Dosis-Respuesta a Droga , Humanos , Replicación ViralRESUMEN
Silymarin (Silybum marianum; SM), popularly known as milk thistle, is an extract that has been used for many centuries to treat liver diseases. In recent years, several studies have shown that SM is not only just another antioxidant but also a multifunctional compound that exhibits several beneficial properties for use in the treatment and prevention of different types of pathologies and disorders. This review aims at demonstrating the main protective activities of SM in diseases, such as cancer, diabetes, hepatitis, non-alcoholic fatty liver disease, alcoholic liver disease, hepatitis C virus, hepatitis B virus, metabolic syndrome, depression, cardiovascular diseases and thalassemia, in addition to its photoprotective activity in in vitro tests and preclinical studies. Its main functions include antioxidant and anti-inflammatory effects, and it acts as modulator of signaling pathways. It has been suggested that SM presents great multifunctional potential and is capable of achieving promising results in different types of research. However, caution is still needed regarding its indiscriminate use in humans as there are only a few clinical studies relating to the adequate dose and the actual efficacy of this extract in different types of diseases.