Silymarin
Alan Datner¹
Dermatology Online Journal 6(1) assembly

Abstract

Silymarin, the active ingredient in Milk Thistle, exerts numerous effects of interest to Dermatologists. Although it has been primarily know as a herb for the liver, it exerts a number of important effects in the skin. It not only demonstrates anti-carcinogenic and anti-pruritic effects on the skin, but also holds great interest as a potential agent to reduce or ameliorate the liver toxicity caused by certain drugs employed by dermatologists.

Milk thistle is a spiny European plant which is now commonly found in North America that is a member of the Compositae or Asteracea family. Its use in diseases of the liver and bile has been well recorded over the past two thousand years.[1]

Figure 1	Figure 2
Figures 1 and 2. Silymarum marianum or Blessed Milk Thistle can be distinguished from other California thistles by its distinctive white-mottled leaves. (Photographs coutesy of The Nature Conservancy. Photographer John Randall).

It has the virtue of having almost no side effects, noting that seeds, leaves, and other plant have been eaten as foods. In rare cases, a mild laxative effect has been noted from the plant. The active ingredient, Silymarin, is extracted from the seeds using 95 percent ethanol. These components may be classified as bioflavinoids, or more specifically flavinolignans. Bioflavinoids are polyphenols which are well known to have anti-oxidant or free radical scavenging properties and are thought to be useful in protecting the plant from the free radicals induced by sunlight exposure. Silymarin is actually a collection of these flavinolignans including silybin, silydianin, silychristin, and apigenin. The extract also contains the fatty acids, myristic, palmitic, steararic and oleic acids. The flavinoids are also believed to act in mammalian tissues as free radical scavengers, as well as plasma membrane stabilizers, and thus confer protection to the cells during free radical stress generated by chemical reaction or radiation. There is also evidence to support the combination of silymarin with other anti-oxidants to ameliorate liver disorders such as hepatitis C.[2]

Figure 3	Figure 4
Figures 3 and 4. "The seed leaves are 1/2 to 3/4 inch wide and 3/4 to 1 inch long, rather thick, succulent and light green. The first leaves are very conspicuously white-netted along the veins and have short yellowish prickles. The plant is mainly confined to high fertility soils. (Photographs coutesy of The Nature Conservancy. Photographer John Randall).

Liver effects:

One of the most dramatic effects of silymarin in humans is in protection against hepatic damage and death due to ingestion of death cap mushroom and it's components phalloidin, and alpha amantin. It is also well studied for it's protective effects against alcohol damage to the liver in humans as well as animals. It also has been shown to protect the liver against other toxins including carbon tetrachloride, galactosamine[3], thioacetamide[4,5], fanthanides, frog virus 3[6] , ethionine, praseodium nitrate, and psychotrophic medications such as, phenothiazines and buterophenalins. An additional method of hepatic protection against the deathcap fungus toxins is prevention of their entrance into hepatic cells by competitive inhibition of cell surface receptors[7].

All of these hepatoprotective effects raise the tantalizing possibility that silymarin could confer some protective effects during the use of dermatologic medications which are potentially hepatotoxic, thereby decreasing overall risk. Studies don in human hepatocyte cultures domonstrate that silymarin protects these cells against glutathione depletion which is enhanced by the addition of ethanol and acetaminophen. Glutathione is an important constituent for conjugating out drugs which been metabolized for elimination by the P450 system; in this case presumably P450 2E1.[8] Observations in this study have profound implications for silymarin and glutathione as hepatoprotective agents during the use of methotrexate for psoriaisis.

What is most intriguing about Silymarin is the number of different mechanisms by which Silymarin has been found to protect and support the liver. In the livers of partially hepatectomised rats, silymarin was shown to enhance hepatocyte protein synthesis by it's effects on RNA polymerase.[9]. It did not have this effect on hepatoma's or other malignant cell lines. It's also been show to prevent lipid peroxidation in rat liver microfilms and hepatocyte cell membranes.[10,11] It has also been shown to protect against glutathione depletion and lipid peroxidation induced by acetamenophen in the rat liver. Furthermore, it was shown to protect against radiation-induced depression of hepatic DNA and RNA synthesis. It's antioxidant activities have been shown by its binding of free radicals in test tubes situations.[12] The steroid-like portion of the silybin molecule enhances liver regeneration by stimulating DNA transcription, and by enhancing RNA production via stimulation of DNA polymerase 1.[13]

Beneficial effects on the skin

Silymarin also has a number of beneficial effects directly on the skin. These include use against Rosacea and Pruritis, inhibition of ultraviolet B induced carcinogenic effects, inhibition of endogenous tumor promoters and possibly treatment of Porphyria[14] and Psoriasis.

Pruritus intrahepatiic cholestasis of pregnancy is ameliorated by silymarin.[15]

Rosacure is a silymarin derivitive which is used in the treatment of Rosacea and is available OTC in Canada, but not the U.S., at present. The product contains the additional antioxidant vitamin E and silymarin extract in an olioresin base, which is designed to reduce the redness associated with rosacea. The product has apparently been available in Italy for a few years before it was made available in Canada. The CamDerm Company which produces this product quotes the number of studies showing the effects of silymarin on the microcirculation of the face, which are not available in the peer review literature. www.Canderm.ca/rosacure/index.html

Silymarin has also been used for its antipruritic effect. Haines Ely has a patent on a topical preparation of silymarin for this purpose. Silymarin has also been shown to inhibit mast cell degranulation, which may, in part, account for it's antipruritic effect.

Silymarin has also been shown to have a number of anti tumor effects in vitro and in animal systems. One study showed that it exerted anti tumor effects in mouse skin, by inhibiting the endogenous tumor promoter TNF alpha.[16] Silymarin has also been shown to prevent the formation of pyrimidine dimers in ultraviolet B exposed mouse skin.[17,18] This is evidence of it's potential usefulness in preventing carcinogenesis. A further study by the same author showed that silymarin protects against tumor promotion in the chemical induced mouse skin tumor model.

Furthermore, silymarin was shown to have chemopreventative effects in a human epiderdermoid carcinoma cell line by inhibiting induction of epidermal growth factor receptor, mediated tyrosine phosphorilation. Silymarin, therefore, can interrupt the effects of tumor promotion by inhibiting EGFR, which is a common pathway for both forbo ester and ultraviolet B radiation induced tumor promotion.

References