Núcleo de Pesquisas em Ciências Biológicas, NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil.
Departamento de Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil.
Antiviral Res. 2018 Oct;158:8-12. doi: 10.1016/j.antiviral.2018.07.023. Epub 2018 Aug 1.
Mayaro virus (MAYV) is a neglected arbovirus belonging to the family Togaviridae. Its infection leads to Mayaro fever, with clinical manifestations such as fever, myalgia, headache, rash, arthralgia, vomiting, and diarrhea. The most prominent complaint from infected person is the long-lasting arthritis/arthralgia. The treatment for Mayaro fever is mainly symptom-based and there are no vaccines or antiviral drugs currently available, thus, natural products with anti-MAYV activity may provide a potential alternative. Recent evidences suggest that oxidative stress plays an important role in MAYV infection and compounds capable of modulating oxidative stress could represent a novel therapeutic approach in modulating MAYV-associated oxidative cellular damage. Silymarin is a complex extracted of Silybum marianum, or milk thistle, and its major active compound is silybin, which has a remarkable biological effect. Its antioxidant and antiviral effects, including its antiviral activity against the Chikungunya virus (CHIKV), prompted us to think whether silymarin could also reduce the replication of the MAYV and restore the pro-oxidant/antioxidant balance in the context of MAYV infection, leading to reduced cellular oxidative stress. We assessed the antiviral activity and protective effect of silymarin against oxidative stress in MAYV-infected HepG2 cells. Cytopathic effect inhibition, viral replication, and plaque reduction assays were used to determine the anti-MAYV activity of silymarin. Additionally, we determined whether silymarin could reduce MAYV-induced oxidative cell damage. Briefly, silymarin exhibited potent antiviral activity against MAYV and reduced MAYV-induced ROS formation and levels of malondialdehyde (MDA) and carbonyl protein, which are biomarkers of oxidative stress. In conclusion, the ability of silymarin to inhibit MAYV replication and attenuate MAYV-induce oxidative stress warrants further investigation of this compound as a novel therapeutic approach to Mayaro fever disease.
玛雅罗病毒（MAYV）是一种被忽视的虫媒病毒，属于披膜病毒科。其感染可导致马雅罗热，临床表现为发热、肌痛、头痛、皮疹、关节痛、呕吐和腹泻。受感染者最突出的抱怨是持久的关节炎/关节痛。马雅罗热的治疗主要是对症治疗，目前尚无疫苗或抗病毒药物，因此，具有抗 MAYV 活性的天然产物可能提供一种潜在的替代方法。最近的证据表明，氧化应激在 MAYV 感染中起重要作用，能够调节氧化应激的化合物可能代表一种调节 MAYV 相关氧化细胞损伤的新治疗方法。水飞蓟素是水飞蓟素（Silybum marianum）或奶蓟的复杂提取物，其主要活性化合物是水飞蓟宾，具有显著的生物学作用。其抗氧化和抗病毒作用，包括其对基孔肯雅热病毒（CHIKV）的抗病毒活性，促使我们思考水飞蓟素是否也能降低 MAYV 的复制，并在 MAYV 感染的情况下恢复促氧化剂/抗氧化剂平衡，从而减少细胞氧化应激。我们评估了水飞蓟素对 MAYV 感染 HepG2 细胞的抗病毒活性和抗氧化应激保护作用。细胞病变抑制、病毒复制和蚀斑减少试验用于确定水飞蓟素的抗 MAYV 活性。此外，我们还确定了水飞蓟素是否能减少 MAYV 诱导的氧化细胞损伤。简而言之，水飞蓟素对 MAYV 表现出强大的抗病毒活性，并减少了 MAYV 诱导的 ROS 形成以及丙二醛（MDA）和羰基蛋白的水平，这些都是氧化应激的生物标志物。总之，水飞蓟素抑制 MAYV 复制和减轻 MAYV 诱导的氧化应激的能力需要进一步研究这种化合物作为治疗马雅罗热疾病的新方法。
