Flavolignans from Silymarin as Nrf2 Bioactivators and Their Therapeutic Applications

Abstract

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.

Effect of Silymarin Supplementation on Physical Performance, Muscle and Myocardium Histological Changes, Bodyweight, and Food Consumption in Rats Subjected to Regular Exercise Training

“…Dating from past years, a variety of studies have been carried out to probe the most observed properties such as antioxidant, liver protector, nephron and cardioprotective [ 8 , 9 , 10 ]. The mechanisms by which SM exerts any activity continue to be studied and some include the following: (1) free radical (FR) scavenging; (2) conducting the enzymatic and non-enzymatic antioxidant response through regulation of transcription factors such as nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2), the coordinator for the cytoprotective and antioxidant response [ 11 ], and nuclear factor-Kappa β(NF-Κβ), which is involved on the inflammatory process; (3) inhibiting FR production by blocking the producer enzymes; (4) inducing the gene expression of protector molecules, for example, heat shock proteins (HSP), thioredoxins (Txn), and sirtuins (Sirt), conferring protection against oxidative stress [ 12 ].…”

Silybin Alleviates Experimental Autoimmune Encephalomyelitis by Suppressing Dendritic Cell Activation and Th17 Cell Differentiation

“…Silybin is a flavonoid, a primary component of silymarin, extracted from the seed of species derived from S. marianum ( 19 ). S. marianum has been used in traditional medicine for many years.…”

Phytochemicals and Their Possible Mechanisms in Managing COVID-19 and Diabetes

“…Silymarin, an extract from the seeds of the milk thistle (Silybum marianum), of Mediterranean origin, contains a gamma of flavolignans such as silybin, isosilybin, silychristin, and silydianin [52]. Silymarin has been credited with having effects on liver disorders, in addition to anticancer, antihepatoprotector, antihyperlipidemic, antidiabetic, antiamnesic, anti-inflammatory, and antisclerotic activities, and it modulates T cells [53][54][55].…”