A well-researched and highly valued medicinal herb, Silybum marianum (milk thistle) has been the subject of over 12,000 published research papers. With a broad action on antioxidant defense, modulation of inflammation, and anti-cancer effects, it has been known mostly for its use in liver disease treatment and prevention; however, this herb is also neuro-, nephro- and cardio-protective.[1,2] Its beneficial effect across numerous systems is attributed to its main flavonoid ingredient, silymarin, which consists of the active component silybin (also called silibinin).
Silymarin achieves its strong antioxidant effect in the body through various mechanisms. Direct free radical scavenging and the inhibition of free radical producing enzymes are the most well-known mechanisms. In a recent study, diabetic patients given silymarin had improved levels of the important antioxidant indices, super oxide dismutase (SOD), glutathione peroxidase (GPX) and total antioxidant capacity (TAC). They also had reduced high-sensitivity C-reactive protein (hs-CRP) levels, showing reductions in systemic inflammation.
However, the direct antioxidant effect may not be the main actions of this herb. Emerging research shows silymarin modulates various transcription factors, such as nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and nuclear factor kappa B (NF-kB), and activates proteins responsible for protective molecules, such as heat shock proteins (HSPs).
Experimental evidence demonstrates that the main driving force behind the antioxidant effect of silymarin may be through its ability to activate Nrf2. This transcription factor is referred to as the master key to cellular health, detoxification and inflammation. Nrf2 is a significant factor in the body’s adaptive response to oxidative stress. Nrf2 goes beyond direct antioxidant effects by activating and regulating a wide variety of genes, which produce long lasting and highly efficient antioxidant proteins, detoxification enzymes, and other protective molecules.[2,4]
Other experimental research also shows silymarin mediates FXR signalling. This nuclear receptor is a key modulator of bile acid metabolism in the enterohepatic system. It acts through various feed forward and feedback loops. By activating FXR signalling, silymarin triggered negative crosstalk and the suppression of the inflammatory NF-kB. Along with the reduction in inflammation, researchers found silymarin ameliorated insulin resistance and hyperlipidaemia, suggesting an effect on FXR activation for metabolic disorders.
The emerging evidence behind the powerful actions of Silybum marianum and its active constituents changes the attitude that it simply acts as a free radical scavenger and traditional antioxidant, and may substantiate its effect on liver disorders, inflammatory disorders, cancer, neurological disorders, skin diseases and lipid disorders.[2,6]
- Polachi N, Bai G, Li T, et al. Modulatory effects of silibinin in various cell signaling pathways against liver disorders and cancer - a comprehensive review. Eur J Med Chem 2016;123:577-595. [Abstract]
- Surai PF. Silymarin as a natural antioxidant: An overview of the current evidence and perspectives. Antioxidants (Basel) 2015;4(1):204-247. [Full text]
- Ebrahimpour Koujan S, Gargari BP, Mobasseri M, et al. Effects of Silybum marianum (l.) gaertn. (silymarin) extract supplementation on antioxidant status and hs-CRP in patients with type 2 diabetes mellitus: A randomized, triple-blind, placebo-controlled clinical trial. Phytomedicine 2015;22(2):290-296. [Abstract]
- Houghton CA, Fassett RG, Coombes JS. Sulforaphane and other nutrigenomic Nrf2 activators: Can the clinician’s expectation be matched by the reality? Oxid Med Cell Longev 2016;2016:7857186. [Full text]
- Gu M, Zhao P, Huang J, et al. Silymarin ameliorates metabolic dysfunction associated with diet-induced obesity via activation of farnesyl x receptor. Front Pharmacol 2016;7:345. [Ful text]
- Neha, Jaggi AS, Singh N. Silymarin and its role in chronic diseases. Adv Exp Med Biol 2016;929:25-44. [Abstract]