Silymarin As an Anti-Inflammatory and Inhibitor of UV-Induced Skin Damage

It is a well-known fact of life that exposure to UV light, especially the UVA component, festers skin disorders like melanoma and non-melanoma skin cancers. Superficial remedies such as sunscreens are effective only to a limited extent. This realization has led to investigation of new methods to protect the skin from photo-damaging effects of solar UV radiation, or “photo-carcinogenesis” as it is called. Recent years have seen considerable interest in identifying naturally-occurring botanicals, such as silymarin, with anti-oxidant and anti-inflammatory properties, and which exhibit anti-carcinogenic and anti-mutagenic functionality.

It is in this light that the medicinal benefits of milk thistle have been a subject of intense research by scientists. Though its value as a medicine for a host of health conditions, including dermatological, has been known for over 2,000 years, it is only now that science has seriously begun looking at the role played by milk thistle and “Silymarin”, its active compound, in treating skin damage.

In an experiment conducted at Palacky University in Czechoslovakia (1), researchers studied the impact of two components of Silybum marianum (technical name for milk thistle) as both a preventative as well as treatment intervention for skin damage against UVA exposure. Their findings were positive, in that it was discovered that these two components – collectively known as “flavonolignans” – perform a host of functions, such as increasing the viability of keratinocytes in irradiated cells, inhibiting the production of ROS, stopping further depletion of ATP and GSH taking place at intracellular level, and halting the peroxidation of membrane lipids. Further, the activation of caspases-3 process that UVA exposure initiates gets halted and reversed when the two components of Silybum marianum are applied. The overall picture that emerges, therefore, is that Silybum marianum is a good candidate to be considered for inhibiting UV damage.

An interesting experiment conducted on mice at the University of Alabama in Birmingham has been reported in the March-April 2008 issue of Photochem Photobiology journal (2). Two observations from this research are of special relevance to us here. One, it is the CD11b+ cells, which are the major source of oxidative stress in UV-irradiated skin, were inhibited by Silymarin. The flavonoid also suppresses the infiltration of leukocytes that UV exposure had induced. The second important observation is that Silymarin not only halts UV damage, it also acts as a preventive measure. Another researcher has gone one step ahead with the identification of yet another reversal that this chemical performs to UV action: it reduces the volume of H2O2-producing and cytokine interleukin-10 producing cells, both of whose generation is activated by UV (6).

Nearly the same conclusion has been arrived at by researchers working in the Department of Pharmaceutical Sciences at the University of Colorado (3). Their research has shown a positive effect of Silibinin on the repair of UVB-induced DNA damage. Another experiment conducted at the Department of Dermatology of the University of Alabama has observed the inhibition affect that the flavonoid has on tumor promoters such as 12-O-tetradecanoylphorbol-13-acetate, mezerein, benzoyal peroxide and okadaic acid (4).

Topical application of Silibinin prior to, or immediately after, UV irradiation has been found to inhibit thymine dimer positive cell generation that UV induces in the epidermis (5). This research has also shown that terminal sunburn cell formation that is again induced by UV is inhibited too, when Silibinin is applied.

A strong case for Silymarin being a very effective agent in inhibiting and reversing carcinogen and tumor-promoter-induced cancers is made by two independent researches. In both the experiments (7), (8), it has been reported that Silibinin inhibits cancer-causing cells (ERK1/2 activation) and promotes benign cells (JNK1/2, p38), making it an effective cancer-intervention agent for cancer.

A paper published in the journal “Cancer Research” details yet another in-depth investigation carried out on the efficacy of Silymarin as a possible intervention agent against Stage I and Stage II tumors (9). The paper reports that the milk thistle extract has been found to be especially useful in Stage I tumor suppression, and inhibits edema, hyperplasia, proliferation index and oxidant state which take place due to UV irradiation. This same result has been arrived by an independent group of researchers, who used a different chemical to induce skin edema in mice (10).

From the above researches being conducted around the world, it may safely be concluded that Silymarin is proving to be very effective in inhibiting UV-induced skin damage, and the day may not be far when milk thistle becomes one of the major ingredients in sunscreen lotions.

References

Svobodová A, Zdarilová A, Walterová D, and Vostálová J. Flavonolignans from Silybum marianum moderate UVA-induced oxidative damage to HaCaT keratinocytes. J Dermatol Sci. 2007 Dec;48(3):213-24. Epub 2007 Aug 3.

Katiyar SK, Meleth S, and Sharma SD. Silymarin, a flavonoid from milk thistle (Silybum marianum L.) inhibits UV-induced oxidative stress through targeting infiltrating CD11b+ cells in mouse skin. Photochem Photobiol. 2008 Mar-Apr;84(2):266-71. Epub 2007 Nov 28.

Singh RP, and Agarwal R. Mechanisms and preclinical efficacy of silibinin in preventing skin cancer. Eur J Cancer. 2005 Sep;41(13):1969-79.

Katiyar SK. Silymarin and skin cancer prevention: anti-inflammatory, antioxidant and immunomodulatory effects. Int J Oncol. 2005 Jan;26(1):169-76.

Dhanalakshmi S, Mallikarjuna GU, Singh RP, and Agarwal R. Silibinin prevents ultraviolet radiation-caused skin damages in SKH-1 hairless mice via a decrease in thymine dimer positive cells and an up-regulation of p53-p21/Cip1 in epidermis. Carcinogenesis. 2004 Aug;25(8):1459-65. Epub 2004 Mar 19.

Katiyar SK. Treatment of Silymarin, a plant flavonoid, prevents ultraviolet light-induced immune suppression and oxidative stress in mouse skin. Int J Oncol. 2002 Dec;21(6):1213-22.

Singh RP, Tyagi AK, Zhao J, and Agarwal R. Silymarin inhibits growth and causes regression of established skin tumors in SENCAR mice via modulation of mitogen-activated protein kinases and induction of apoptosis. Carcinogenesis. 2002 Mar;23(3):499-510.

Jifu Zhao, Moushumi Lahiri-Chatterjee, Yogesh Sharma and Rajesh Agarwal. Inhibitory effect of a flavonoid antioxidant Silymarin on benzoyl peroxide-induced tumor promotion, oxidative stress and inflammatory responses in SENCAR mouse skin. Carcinogenesis, Vol. 21, No. 4, 811-816, April 2000.

Lahiri-Chatterjee M, Katiyar SK, Mohan RR, and Agarwal R. A flavonoid antioxidant, Silymarin, affords exceptionally high protection against tumor promotion in the SENCAR mouse skin tumorigenesis model. Cancer Res. 1999 Feb 1;59(3):622-32.

Zhao J, Sharma Y, and Agarwal R. Significant inhibition by the flavonoid antioxidant Silymarin against 12-O-tetradecanoylphorbol 13-acetate-caused modulation of antioxidant and inflammatory enzymes, and cyclo-oxygenase-2 and interleukin-1-alpha expression in SENCAR mouse epidermis: implications in the prevention of Stage I tumor production. Mol Carcinog. 1999 Dec;26(4):321-33.