Silymarin

What is Silymarin?

Silymarin refers to a group of flavonoid antioxidants that naturally occur in milk thistle seeds (used historically as an antidote for mushroom poisoning). The components of Silymarin are Silybin, Silibinin, Silydianin, and Silychristin. These compounds protect and treat the skin from oxidative stress caused by ultraviolet radiation. Silymarin also has powerful antioxidant properties that prolong cell life. Several studies prove its anti-free radical potency at about 10X that of vitamin E, preventing UVA and UVB exposure damage. It is also being studied for its ability to inhibit tyrosinase (a critical enzyme for melanin synthesis) and hyperpigmentation. In wound healing and anti-aging, silymarin can inhibit the production of inflammation-driving cytokines and oxidative enzymes. It can also increase collagen and glycosaminoglycans (GAGs) production, promoting a broad spectrum of cosmetic benefits. This makes the compound great in antioxidant serums or as a valuable ingredient in sunscreens. A considerable challenge is that it has a very dark colour, and it could stain the skin yellow if used in higher concentrations. 

What are the benefits of Silymarin?

• Antioxidant
• Anti-inflammatory
• Brightening
• Wound Healing
• Anti-photoaging

Silymarin is a highly powerful antioxidant that scavenges free radicals and modulates ROS free radical-associated pathways. It also plays a crucial role in repairing DNA damage caused by ultraviolet radiation. Among the several silymarin components, dehydrosilybin is the most potent, with the highest ability to scavenge DPPH radicals and having the most outstanding protection against UVA damage.3 In another study, silymarin is shown to reduce the number of UVB-induced H2O2-producing cells and inhibit the inducible nitric oxide synthase.4 The decrease of oxidative stress in the skin is vital for preventing apoptosis and signs of aging, such as the formation of wrinkles. As discussed earlier, wound healing and restoration of the barrier function are improved with oxidative stress markers inhibition.

The anti-inflammatory property of silymarin is important for protecting the skin against premature aging due to chronic stress. Examples of chronic stressors include UV exposure, injury, and environmental and intrinsic factors. Silymarin in skincare modulates the inflammatory response to accelerate wound healing, prevent cell death, and reduce the formation of scars and dark spots after sun exposure.1,5 This is why antioxidants are common ingredients found in sunscreens. Additionally, concentrations of as low as 5-15 µM 2,3-dehydrosilybin and quercetin can suppress the production of interleukin (IL)-6 and other pro-inflammatory cytokines.5

Topical silymarin is proven to increase the number of fibrocytes and the levels of glycosaminoglycans (GAG) and collagen in damaged skin. It reduces the number of lymphocytes and macrophages in the early and late stages of wound healing to control the inflammatory response. Silymarin improves the alignment of the healing tissue and enhances the maturity of the collagen fibers and fibroblasts.1 A 2% silymarin topical ointment improves wound healing, correlating with less redness, swelling, and exudates. The same treatment also decreases serum levels of the oxidative stress marker, malondialdehyde (MDA), and increases levels of estradiol, which is associated with wound healing by inducing the production of growth factors in various cell types.2 Overall, silymarin is involved in improving the morphology, structural integrity, barrier function, and biochemical and biomechanical properties of the skin through its antioxidation and anti-inflammatory action. 

Ultraviolet radiation is highly absorbed by our DNA, leading to structural and functional damage due to the formation of thymine dimers.6 Topical application of silibinin before or immediately after UV irradiation inhibits UV-induced thymine dimer positive cell generation in the epidermis.7 This research has also shown the inhibition of UV-induced terminal sunburn cell formation when silibinin is applied. Several experiments confirm the anti-carcinogenic and anti-inflammatory properties of silymarin following exposure to UV irradiation. The skin protective effects include the reduction of UVB-induced hydrogen peroxide and photoprotection against the sunburn response, DNA damage, and non-melanoma skin cancer.8,9 Silibinin decreases UVB-induced proliferation and apoptosis to prevent photocarcinogenesis.10 Based on these benefits it is not surprising to find silymarin in anti-aging skincare and sunscreens to improve their photoprotective effects. 

Usage Rate and Effective Concentration

You will most likely find silymarin at concentrations of 0.5-1% in daily skincare products such as anti-aging serums, moisturizers, and sunscreens. One thing to note is that Silymarin refers to a semi-standardized extract of Silybum marianum and it has to be around 70-80% flavonolignans to be called Silymarin. Even then, if you look at the INCI, it is referred to as Silybum marianum extract. Unfortunately, this standardization requirement isn’t strictly followed by everyone so there are diluted Milk Thistle extracts marketed as Silymarin. If using pure compounds, the INCI would show as Silybin, Silychristin, or Isosilybin.

Formulation Consideration

Silymarin is naturally yellow, so having too much of it in the formulation (or applying too much) could stain your skin. You should also keep in mind that if a product claims to contain a high concentration of silymarin, it should have a stronger yellow colour intensity.  

How does Silymarin work?

Antioxidant

The skin is constantly exposed to free radical-generating agents such as solar UV radiation and chemical and environmental pollutants. Topical silymarin can reduce the oxidative stress in our skin by inhibiting UVB-induced intracellular production of H2O2 and NO and the expression of iNOS. Silymarin is proven to inhibit the infiltration of CD11b+ cell types and the expression of ERK1/2 and p38 proteins of the MAPK pathway. This subsequently inhibits the activation of NF-κB/p65 by preventing degradation of the Iκ-Bα and activation of IKKα.4,6 In other words, the antioxidant activity of silymarin to protect our skin is supported by the modulation of the MAPK and NF-κB signaling pathways. In mice models, silymarin also inhibits radical-induced lipid peroxidation of the epidermis.

The antioxidant effects of silymarin are important for controlling the oxidative stress our skin is fighting against each day and providing an anti-carcinogenic effect to prevent further detrimental damage. This is seen with silibinin treatment to inhibit UVB-induced cell proliferation and apoptosis by upregulation of the p53/p21 pathway.10 

Anti-inflammatory

Silymarin has a pronounced immunomodulatory effect in the skin after injury or damage, which is known to release cytokines (such as IL-10) that permit the development of various skin tumors including melanoma and non-melanoma skin cancers. UVB-induced immunosuppression is reversed by silymarin by decreasing IL-10 production and draining the lymph nodes.4 It also reduces MHC+ CH11b+ cell types in UVB-irritated skin to prevent contact hypersensitivity suppression and inhibits oxidant-induced myeloperoxidase activity.6 Ultimately, this reduces the formation of reactive oxygen species in our cells.

Silymarin is shown to modulate the immune response by increasing antigen presentation and inhibiting T cell activation and proliferation, notably acting on the pathways of NF-κB activation/translocation and IL-2 production.12 Furthermore, it also inhibits the expression of cytokines IL-1α and TNF-α and lipoxygenase and cyclooxygenase activity to decrease the formation of prostaglandin metabolite.4,6 Pretreatment of bacterial lipopolysaccharide-induced cells with silymarin is shown to modulate the inflammatory response by attenuating COX-2 mRNA expression and diminishing the release of pro-inflammatory iL-6 and IL-8 via the NF-κB and AP-1 signaling pathways.5  

Protection against photoaging, photocarcinogenesis, melanin synthesis

The major mechanisms behind this are the modulation of ROS free radical-associated pathways and the repair of damaged DNA caused by UVB. Chronic oxidative stress, overexpression of protein tyrosine kinases (and receptors) and over-activation of the epidermal growth factor receptor (EGFR) signaling pathways are associated with various cutaneous tumors. Silymarin prevents induction of these processes by inhibiting ligand-induced activation of receptor tyrosine kinase EGFR and its intrinsic kinase activity. The resulting inhibitory effect on the EGFRShc-ERK1/2 pathway is also a major part of chemoprevention.6 Topical silibinin is found to inhibit acute UVB-induced activation of MAPKs, including ERK1/2, JNK1/2 and p38. This leads to a decrease in epidermal cell proliferation and may be related to the role of silibinin in preventing UVB-induced epidermal hyperplasia.8 The inhibitory effects of topical silymarin against photocarcinogenesis are also linked to the downregulation of UVB-induced immunosuppressive cytokines and augmentation of the immunostimulator IL-12.6,14

DNA repair is considered a primary biological response to extrinsic and intrinsic causes of DNA damage. The presence of insufficient repair mechanisms is linked to an increased rate of mutation and the chance of skin cancers. In animal studies, silibinin is shown to be a valuable agent for protecting the skin against photocarcinogenesis by decreasing UVB-caused thymine dimers and enhancing the rate of DNA repair via the excision repair mechanism in epidermal cells.8 It also activates apoptosis and p53, a key molecule in regulating DNA repair machinery and the cell cycle.

Silymarin has a role in preventing melanin synthesis by inhibiting L-DOPA oxidation of tyrosinase (a key enzyme in melanocytes) and decreasing tyrosinase expression.11,13

Wound healing

The antioxidant and anti-inflammatory activities of silymarin have a positive effect on burns and wound healing. An inhibitory effect on the synthesis of leukotrienes and prostaglandins is proven to accelerate wound healing. This is in addition to controlling the spread of cytokines and the infiltration of neutrophils. Using mice models, silymarin can increase the number of fibrocytes and decrease the number of lymphocytes in the early and secondary stages of wound healing.1,2 In human skin cell fibroblasts, pretreatment with silymarin before peroxide induction can protect them against H2O2-induced injury, and pretreatment before LPS induction can inhibit COX-2 mRNA expression.15 Topical silymarin decreases serum levels of the oxidative stress biomarker, malondialdehyde (MDA). It also increases levels of estradiol, which is associated with wound healing by inducing the production of growth factors in various cell types.2

Clinical trials 

The effect of silymarin on collagenase, elastase, and hyaluronidase activity was evaluated in an in vitro study. The results revealed that the compound effectively inhibited the activities of these isolated enzymes, promoting an anti-aging outcome by preventing sunlight-induced damage and photoaging.3 A separate in vivo study used pure silymarin (1 mg/cm2 skin area) topically applied to mouse skin 20-25 minutes before UVB exposure. The treatment prevented UV light-induced infiltration of inflammatory leukocytes, which is responsible for the induction of UV-induced suppression of contact hypersensitivity (CHS), oxidative stress, and numerous skin disorders including photoaging and photocarcinogenesis.4 

Does it penetrate the skin?

An in vivo study was done to determine the ability of silymarin to be absorbed by the skin. It showed that silibinin, the most abundant and biologically active of the three components, demonstrated significant absorption into the skin of a hairless ice.7 The study also concluded that the topical application of silymarin for up to 24 hours does not cause skin irritation. 

Abbreviations and Definitions  

References