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Milk Thistle

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Silybum marianum, also called as milk thistle, is an annual or biannual plant of the Asteraceae family. It is native of Southern Europe and Asia but now it is found throughout the world. The medicinal parts of the plant are the ripe seeds. This fairly typical thistle has red to purple flowers and shiny pale green leaves with white veins. It grows 40 to 100 cm tall. The leaves are oblong to lanceolate.
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Botanical Names
Silybum marianum
Indian Names
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Chemical Constituents
The principal extract of milk thistle is silymarin up to 4% to 6% in ripe fruit. The major component (60%) is silybin and it is also the most biologically active component. Other components include silichristin, a metabolic stimulant, and silydianin. Silymarin is found in highest concentrations in the fruit of the plant. Silymarin, is a complex mixture of four flavonolignan isomers, namely silybin, isosilybin, silydianin and silychristin with an empirical formula C25H22O10. Silymarin is the bioactive extract from Silybum marianum L. seeds and contains 65-85% flavonolignans like silychristin, isosilychristin, silydianin, silybin A and B, isosilybin A and B, Figure 1), and also 20- 35% fatty acids, flavanoids, and other polyphenolics. The natural compound, silybin, is a mixture of two diastereomers silybin A/B. sylimarin is a flavonolignane complex consisting of silibinin A and B/silybin/silymarin I, isosilibinin A B, silicristin/silymarin II, and silidianin (1).
Pesticide Limits
A limit for pesticide is one of the major issues in standardization of medicinal plants and products in view of the worldwide widespread use of pesticides in cultivated plants. The presence of pesticides in extracts increase the health risk by many folds. The pesticides can be extremely irritant on skin as well as in the internal organs, it is essential to monitor its concentration as a part of GMP. Various analytical methods for the quantitative determination of pesticides by gas chromatography coupled with mass-spectrophotometer are in use. Konark Research Foundation (KRF), a NABL certified lab is well equipped with the latest technology and instruments and monitors the pesticide limit as part of its GMP.
Chromatographic Profile
From the pharmacopoeial perspective, a better quality control of raw material can be achieved by specifying quantitative test procedure for the determination of the range or a minimum content of the active ingredient or marker substances. A chromatographic finger profile represents qualitative/ quantitative determination of various components present in a complex plant extract, irrespective whether or not their exact identity is known. Thin layer chromatographic technique is the simplest and least expensive method that provides plenty of information on the composition of raw herbs and its preparation. For quantitative analysis of active ingredients or marker substances with simultaneous separation and detection High Pressure liquid chromatography is the best technique. We use the latest model of HPLC for all its analysis.
Limits of Impurities
A test requirement for foreign organic matter would ensure the extent of contamination of extraneous matters such as filth and other parts of botanicals not covered by the definition of the herbal drug. Since sand and soil are predictable contaminants of botanicals, test requirements for ‘total ash’, water soluble ash’, ‘acid soluble ash, residue on ignition and sulphated ash would be expected to limit such contaminants. Test requirement for heavy metals in botanical raw material are probably more relevant for parts of plants growing under ground than for the aerial parts of the plant. The presence of high levels of minerals interacts with the final product there by affecting its keeping quality.
Microbial Limits
If the raw herbs are to be used directly without boiling in water prior to consumption, restrictive limits on microbial contaminants are required for pathogens such as Salmonella sp. Enterobacter and E. coli which are causative agent for various gastrointestinal diseases. A lower level of yeasts and molds and a limit on total aerobes are considered appropriate in plant material for topical use. The presence of aflatoxins detected by chemical means is generally independent of the number of viable molds that are detected using microbiological methods. Aflatoxins in microgram quantity are capable of giving serious hypersensitivity reactions which can be extremely harmful to human health.
Pharmacology
Milk thistle contains silymarin, as the most active component. Silymarin may potentially be beneficial in a number of diseases involving liver disease. Silymarin possess anti viral, anti bacterial, anti oxidant, anti cancer, and hepatoprotective properties (2) Silymarin is a useful drug for hepato protection in hepatobiliary diseases and in hepato toxicity due to drugs (3). Silymarin is used for the treatment of numerous liver disorders characterized by degenerative necrosis and functional impairment. The compound also protects hepatocytes from injury caused by radiation, iron overload and viral hepatitis. As an antioxidant, silymarin scavenges free radicals that can damage cells exposed to toxins. Silymarin has been said to be ten times more potent in antioxidant activity than vitamin E. Silymarin also increases the level of the important antioxidant enzyme superoxide dismutase in cell cultures. It stimulates protein synthesis in the liver, which results in an increase in the production of new liver cells to replace the damaged ones (4). Silymarin consists of a family of flavonoids (silybin, isosilybin, silychristin, silydianin and taxifoline) commonly found in the dried fruit of the milk thistle plant Silybum marianum. Although silymarin's role as an antioxidant and hepatoprotective agent is well known, its role as an anticancer agent has begun to emerge. Extensive research has shown that silymarin can suppress the proliferation of a variety of tumor cells e.g., prostate, breast, ovary, colon, lung, bladder etc. this is accomplished through cell cycle arrest at the G1/S-phase, induction of cyclin-dependent kinase inhibitors (such as p15, p21 and p27), down-regulation of anti-apoptotic gene products (e.g., Bcl-2 and Bcl-xL), inhibition of cell-survival kinases (AKT, PKC and MAPK) and inhibition of inflammatory transcription factors (e.g., NF-kappaB). Silymarin can also down-regulate gene products involved in the proliferation of tumor cells (cyclin D1, EGFR, COX-2, TGF-beta, IGF-IR), invasion (MMP-9), angiogenesis (VEGF) and metastasis (adhesion molecules). Numerous studies have indicated that silymarin is a chemo-preventive agent in vivo against a variety of carcinogens/tumor promoters, including UV light, 7, 12-dimethylbenz (a) anthracene (DMBA), phorbol 12-myristate 13-acetate (PMA) and others.
Health Benefits
Milk thistle is a very beneficial plant it can be used to cure hepatitis as well as jaundice. It is a very useful remedy for the liver when it is under trauma owing to infection, excessive alcoholism or owing to chemotherapy while treating cancer. When milk thistle is used by cancer patients undergoing chemotherapy, it is beneficial in restricting the damages done to the liver owing to radiation therapy as well as helps in facilitating recuperation from the side effects after the chemotherapy treatment is over. Laboratory studies have shown that silymarin has the ability to inhibit cancer cell division, shorten the life span of cancer cells, and reduce blood supply to tumors. Silymarin is also effective in the treatment of type 2 diabetes. Silymarin has the ability to reduce insulin resistance in patients with type 2 diabetes. Flavonoids found in milk thistle extract are powerful antioxidants which scavenge harmful free radicals unstable and reactive compounds that damages DNA and cellular structures. Antioxidants are needed by the body to prevent cancer, diabetes, liver disease, cardiovascular disease, and other diseases. Results of clinical trials have shown that silymarin significantly reduced the harmful side effects of chemotherapy for leukemia (6). Several adverse reactions of anti-tuberculosis drugs are reported. The best known toxic drug effect is hepatotoxicity. In such cases Sylimarin acts as an effective agent in liver protection and liver regeneration. The first line anti-tuberculosis drugs isoniazid (INH), rifampicin (RIF) and pyrazinamide (PZA) continues to be the effective drugs in the treatment of tuberculosis, however, the use of these drugs is associated with toxic reactions in tissues, particularly in the liver, leading to hepatitis. Silymarin, a standard plant extract with strong antioxidant activity obtained from S. marianum, is known to be an effective agent for liver protection and liver regeneration. Sylimarin increases glutathione in the liver by more than 35% in healthy subjects and by more than 50% in rats. Glutathione is responsible for detoxifying a wide range of hormones, drugs, and chemicals. High levels of glutathione in the liver increases its capacity for detoxification.
Application in Cosmetics
Milk thistle plant contains silibinin and silymarin, two compounds that are well known for their anti-oxidant and anti-inflammatory properties. Topical application of milk thistle reduces free radical oxidation that happens as a result of UVA exposure. By inhibiting the spread of free radicals, silymarin can prevent cellular damage, thereby supporting the structural integrity of the skin. Hence, signs of premature aging, such as wrinkles, fine lines, and loss of elasticity, are less prevalent. Silymarin can protect the skin from UV damage and related influences that eventually lead to skin cancer (8). The demulcent properties of milk thistle cause it to soften and moisturize the skin. It can moisturize dry or cracked skin .It is greatly valued for its ability to give a healthy glow and balance to the skin. Because of the healing effects of milk thistle it is effective in the treatment of chronic skin disorders like eczema and acne. It helps acne to subside, reduce redness and irritation (9). Signs of cutaneous aging like wrinkling and sagging are develop earlier in sun-exposed skin. This is known as photoaging. It is characterized by a decrease in the amount and degeneration of collagen, dermal elastosis, and glycosaminoglycan deposition. It is investigated that silybin treatment on keratinocytes, modulated the expression of keratinocyte differentiation associated markers like RA, and stimulated the expression of basement membrane component proteins such as laminin-5 and laminin-5 receptor, integrin β4, effectively as RA. Unlike retinoic acid, however, silybin does not stimulate IL-1α production. These results suggest that silybin may have a functional component that improves wrinkling without inducing skin irritation.
Research References
1. Pradhan S. C. and Girish C. Hepatoprotective herbal drug, silymarin from experimental pharmacology to clinical medicine Indian J Med Res 2006.124: 491-504 2. Hadaruga D. I. and Hadaruga N. G. Antioxidant Activity of Hepatoprotective Silymarin and Silybum marianum L. Extract Chem. Bull. "POLITEHNICA" Univ. (Timisoara) 2009 54(68: 2 3. Sude E., Fikriye U., and Fikret V. Silymarin protects liver against toxic effects of anti-tuberculosis drugs in experimental animals Nutrition & Metabolism 2008, 5:18 4. Madani H. Talebolhosseini M., Asgary S., and Naderi G. H. Hepatoprotective Activity of Silybum marianum and Cichotrium intybus Against Thioacetamide in Rat. Pakistan Journal of Nutrition 2008 7(1):172-176. 5. Agarwal R, Agarwal C, Ichikawa H, Singh RP, Aggarwal BB Anticancer potential of silymarin: from bench to bed side. Anticancer Res. 2006 26(6B):4457-98 6. Tahera H., Ramza A. K. ., Eslam M., and Mohammad R. S. A. Analysis of Silybum marium (L.) Gaert from Iran Pakistan Journal of Biological Sciences 2005 8(12): 1778-1782. 7. Katiyar S. K. Silymarin and skin cancer prevention: anti-inflammatory, antioxidant and immunomodulatory effects. Int J Oncol. 2005. 26(1):169-76. 8. 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. 48(3):213-24. 9. Katiyar S. K., Meleth S., and Sharma S. D. 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. 84(2):266-71. 10. Singh R. P., and Agarwal R. Mechanisms and preclinical efficacy of silibinin in preventing skin cancer. Eur J Cancer. 2005. 41(13):1969-79. 11. Seiji K., and Kohji Y. Silybin fromeSilybum Marianum Seeds Inhibits Confluent-Induced Keratinocytes Differentiation as Effectively as Retinoic Acid without Inducing Inflammatory Cytokine J. Clin. Biochem. Nutr 2009. (45):178–184.