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.

What Are the Symptoms of Skin Cancer?

When recognizing what are the symptoms of skin cancer, it is always advantageous to do so in the early stages than in the late stages. Early recognition can be a life-saver.

There are many symptoms associated with skin cancer. This is one of the most common, yet most dangerous types of cancers that an individual may experience. It has been established that each year in the United States there are over one million diagnoses that are directly related to skin cancer. If you were to combine all the individuals who are diagnosed with breast cancer, colon cancer, prostate cancer, and even lung cancer, and compare that number to the individuals that are diagnosed with skin cancer, you would find that the skin cancer patients out number the patients of the other types of conditions. For this reason, it is important that you learn to identify the symptoms associated with skin cancer.

Early Stages of Skin Cancer

In the early stages of skin cancer, there are many distinct symptoms that may make themselves known. You should pay special attention to the following:

o You should pay special attention to the moles that you have on the body. It is essential to make a note of any changes that may occur on this skin marks. This includes changes that affect the overall size, changes that relate to the color, as well as changes that have to do with the shape.

o There are guidelines that you can use to determine if there is a cause for concern when it comes to moles. It is the “ABCD” model. This stands for “asymmetry”, “borders”, “color”, and “diameter”. If you notice any changes relating to moles and other skin markings that are affected in such a way that any of the areas that are part of the “ABCD” model are affected, it is essential to seek medical care.

o You should always pay special attention to the height or the overall elevation of a mole. This is especially true if that same mark on the skin had been flat in previous incidents.

o There are changes that may possibly occur on the actual surface of a mole that could indicate the onset of skin cancer. If you notice that the mole has a crust like substance, has breakage, bleeds, or releases a clear substance, you should be concerned.

o Many individuals may begin to notice that the area in and around a skin mole starts to experience a burning sensation. Many may also notice tingling and may even be tempted to scratch due to itching. If you experience any of these symptoms, you may need to consider setting up an appointment with your doctor for an examination.

o It is important to pay special attention to moles and other markings of the skin when it comes to skin cancer, but it is also important to ensure that you consider the areas around the marks as well. Be sure to watch for redness and tenderness. You will also want to be careful when it comes to changes as far as coloring is concerned.

Late Stages of Skin Cancer

In the late stages of skin cancer, there are many symptoms that one should pay special attention to. This is true even if you have never been diagnosed with skin cancer. It could just be that the early symptoms were not quite noticeable. The following represents the symptoms that you may discover:

o Many may notice that they experience pain in the location of where a mole is located on the skin. This pain may or may not be accompanied by skin breakage, bleeding, and even the oozing of a clear substance.

o The lymph nodes located in the area of the neck, groin, and even in the armpit may become swollen.

o Many may discover that they develop a persistent cough that may or may not be accompanied with mild to severe weight loss.

o Headaches are often an indication of a serious underlying issue if any other symptoms of skin cancer are present. This is especially true if they are accompanied by seizures.

If you notice any of these symptoms, you should seek assistance from a medical professional immediately. Skin cancer symptoms that are evident prove that there is an underlying medical condition that may require professional care.

The Best Ways To Beat The Deadliest Skin Cancer

We’re about halfway through the summer, and I’ll bet you’ve heard no end of warnings about sun exposure. Stay out of the sun for long periods of time. Avoid the sun during its peak hours. Wear lots of sunscreen when you go out. The litany goes on and on. The dangers of irresponsible sun exposure are real… but they are also misunderstood

It is true that repeated sunburns contribute to skin cancer, but not to the kind of skin cancer that you think. Sunburns can lead to the most common forms of skin cancer-basal cell and squamous cell carcinomas. These are superficial cancers, meaning that they don’t easily spread within your body. They are also easily treated when you catch them early.

The kind of cancer you think of when someone says skin cancer is melanoma. This is much more serious. Melanoma can spread throughout your body and be very deadly. But the link between sun exposure and melanoma is tenuous.

There is evidence that sunburn does increase the risk of melanoma. But there is also evidence that sun exposure without sunburn will actually lower your risks.

For example, in one study researchers found that people whose jobs force them to get regular sun exposure are less likely to develop melanoma than those who get no sun exposure as part of their jobs. (1)

In another study researchers discovered that people with melanoma had a greater chance of survival if they spent more time in the sun. (2)

As you can see, the connection between sun exposure and melanoma is more complicated than the simple “Sun is bad,” mantra that you hear from most dermatologists.

The two best ways to protect yourself from melanoma are to understand what responsible sun exposure means and to know how to recognize melanoma in its early stages–early treatment is key to survival.

Know the Skin You’re In

First, here are the keys to healthy sun exposure:

Do get some sunscreen-free sun exposure each week to bolster your vitamin D levels.

Do protect your skin from burning by covering up, finding shade, or using a safe sunscreen with zinc oxide as the active ingredient.

Don’t stay out in the sun for prolonged periods without taking measures to protect your skin.

Do take 1 gram of vitamin C before bed if you burn–it will help your body prevent long-lasting damage to your skin.

Do have a therapeutic lotion on hand in case of sunburn–my favorite is just straight aloe vera jelly.

Next, here are the ABCs of recognize a melanoma in its early stages

A. Asymmetrical Appearance: Take notice of moles that aren’t symmetrical in shape. This is a warning that something might be amiss.

B. Border Irregularity: Moles that have a rough or uneven border may be cancerous or in danger or becoming cancerous.

C. Color Variation: A healthy mole is usually uniform in color. Cancerous moles often have color variations within the mole, ranging from white to red to black to brown.

D. Diameter: Be concerned about any mole larger than a pencil eraser.

E. Elevation Change: Most healthy moles will not undergo any changes whereas a cancerous mole may change from a flat mole to one that is raised or it may grow in size.

If you have two or more of these ABCs in a single mole, it’s time to make an appointment with your dermatologist. It could save your life.

In Good Health,

Jay Brachfeld, M.D.