Flavolignans from silymarin as Nrf2 bioactivators and their therapeutic applications

Silymarin (SM) is a mixture of flavolignans extracted from the seeds of species derived from Silybum marianum, commonly known as milk thistle or St. Mary'sthistle. These species have been widely used in the treatment of liver disorders in traditional medicine since ancient times. Several properties had been attributed to the major SM flavolignans components, identified as silybin, isosilybin, silychristin, isosilychristin, and silydianin. Previous research reported antioxidant and protective activities, which are probably related to the activation of the nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2), known as a master regulator of the cytoprotector response. Nrf2 is a redox-sensitive nuclear transcription factor able to induce the downstream-associated genes. The disruption of Nrf2 signaling has been associated with different pathological conditions. Some identified phytochemicals from SM had shown to participate in the Nrf2 signaling pathway; in particular, they have been suggested as activators that disrupt interactions in the Keap1-Nrf2 system, but also as antioxidants or with additional actions regarding Nrf2 regulation. Thus, the study of these molecules makes them appear attractive as novel targets for the treatment or prevention of several diseases.