Abstract
Silymarin (SM), an extract from the Silybum marianum (milk thistle) plant containing various flavonolignans (with silybin being the major one), has received a tremendous amount of attention over the last decade as a herbal remedy for liver treatment. In many cases, the antioxidant properties of SM are considered to be responsible for its protective actions. Possible antioxidant mechanisms of SM are evaluated in this review. (1) Direct scavenging free radicals and chelating free Fe and Cu are mainly effective in the gut. (2) Preventing free radical formation by inhibiting specific ROS-producing enzymes, or improving an integrity of mitochondria in stress conditions, are of great importance. (3) Maintaining an optimal redox balance in the cell by activating a range of antioxidant enzymes and non-enzymatic antioxidants, mainly via Nrf2 activation is probably the main driving force of antioxidant (AO) action of SM. (4) Decreasing inflammatory responses by inhibiting NF-κB pathways is an emerging mechanism of SM protective effects in liver toxicity and various liver diseases. (5) Activating vitagenes, responsible for synthesis of protective molecules, including heat shock proteins (HSPs), thioredoxin and sirtuins and providing additional protection in stress conditions deserves more attention. (6) Affecting the microenvironment of the gut, including SM-bacteria interactions, awaits future investigations. (7) In animal nutrition and disease prevention strategy, SM alone, or in combination with other hepatho-active compounds (carnitine, betaine, vitamin B12, etc.), might have similar hepatoprotective effects as described in human nutrition.
Highlights
Silymarin (SM) is a C25 containing flavonoid mixture, extracted from the Silybum marianum plant
In the aforementioned studies the free radical scavenging and antioxidant properties of SM and silibinin are demonstrated by: (a) restoration of the endogenous AO enzymes (SOD, CAT, GSH-Px, GR and glutathione S-transferase (GST)) and non-enzymatic antioxidants in the liver and other tissues of stressed animals; (b) increased intracellular concentration of GSH in liver and other tissues; (c) decreased lipid and protein oxidation, detected as reduced MDA/thiobarbituric acid reactive substances (TBARS) and carbonyl content; (d) decreased DNA fragmentation/damage and apoptosis; (e) reduced secretion of ALT, aspartate transaminase (AST), alkaline phosphatase (ALP) from the liver into the plasma due to hepatic injuries caused by reactive oxygen species (ROS); (f) restored Nrf2 and HO-1 activities; (g) reduced NF-κB expression and concentration of pro-inflammatory cytokines, including tumor necrosis factor
Recent studies have confirmed that the protective anti-inflammatory effects of SM/silybin could be mediated by their inhibitory potential on the NF-κB, which is a key transcriptional factor for numerous genes involved in regulation of inflammation, immune system, cell differentiation, survival, apoptosis, etc
Summary
Silymarin (SM) is a C25 containing flavonoid mixture, extracted from the Silybum marianum (milk thistle) plant. Today’s standardized (according to its silibinin, often called silybin, content) SM extract contains approximately 65% to 80% flavonolignans (silybin A and silybin B, isosilybin A, isosilybin B, silychristin and silydianin), with small amounts of flavonoids, and approximately 20% to 35% of fatty acids and polyphenolic compounds possessing a range of metabolic regulatory effects [1]. That is why compounds containing milk thistle ingredients showing silybin content and silybin antioxidant, as well as other activities in various model systems, are used to explain the biological activity of SM. This review focuses on evaluating recent studies on SM (silibinin) antioxidant effects in various in vitro and in vivo model systems in the context of its contribution to the antioxidant systems regulation and participation in cell signaling
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