Silybum marianum - Milk thistle

Family: Asteraceae (Aster family) [E-flora]

Description

Status: Exotic [E-flora]

Synonyms: Carduus marianus L., Mariana mariana (L.) Hill [E-flora]


Hazards


Edible Uses

"All parts of this wholesome and nutritious plant have been eaten, raw or cooked, like the other Thistles (see Cirsium)." [UWP] "Traditionally, the whole Silybum marianum plant was used as food - leaves; young shoots, flower heads and stem were baked or boiled." [Boh,2015] Aerial parts - food - in salad or cooked [Montesano et al.,2012] "Some thorny plants (Carduae, e.g. Silybum marianum) are eaten also in the near Basilicata region [15,26]" [Passalacqua et al.,2006] "Milk Thistle seeds are beneficial to our livers when eaten. A tablespoon of the seeds can be chewed thoroughly 3 times a day, the taste being mild and pleasant to me. The ground seeds can be used as is or seeds can first be lightly dry-roasted in a cast iron skillet and sprinkled on food after grinding as a healthful condiment. Probably less healing, but still beneficial, is simmering ground roasted seeds with roasted dandelion and chicory roots for 20 minutes for a delicious beverage. Adjust amounts used to your taste. The leaves of Milk Thistle plants can also be eaten with spiny edges removed, like those of Bull Thistle. They are a lovely mottled green and white." [WFF(Vol. VII, No.4)]

Other Uses

Medicinal Uses

"The fruits of S. marianum are one of the most important herbal liver medicines. The plant is the most studied medicinal plant in the treatment of liver disease. Fruits of S. marianum have been used for more than 2000 years to treat a range of liver and gallbladder disorders, including hepatitis, cirrhosis, and jaundice, and to protect the liver against poisoning from chemical and environmental toxins, including snake bites, insect stings and mushroom poisoning. Extracts of S. marianum fruits have been recognized for centuries as “liver tonics” and are well known to prevent or reverse hepatotoxicity of reactive drug metabolites or naturally occurring toxins [4]." [hlangothia2016]

"In the USA, the popularity of MT derives from its use as a part of the naturopathic medical tradition of the Native Americans as well as of the Eclectic movement, a group of practitioners that recommended MT for varicose veins, menstrual problems, and congestion of the spleen, kidney, and liver in the first half of 19th century. Actually, MT is among the top‐selling herbal dietary supplements in the USA with retail sales amounting to 2.6 million dollars in the mainstream multioutlet channel in 2015 (Andrew & Izzo, 2017)." [abenavoli2018]

"Blessed thistle has a long history of use in the West as a remedy for depression and liver problems[254]. Recent research has confirmed that it has a remarkable ability to protect the liver from damage resulting from alcoholic and other types of poisoning[254]." [PFAF]

"The whole plant is astringent, bitter, cholagogue, diaphoretic, diuretic, emetic, emmenagogue, hepatic, stimulant, stomachic and tonic[4, 21, 160, 165, 238]. It is used internally in the treatment of liver and gall bladder diseases, jaundice, cirrhosis, hepatitis and poisoning[238]. The plant is harvested when in flower and dried for later use[238]." [PFAF]


Pharmacology

"It is also useful as a mild laxative and febrifuge" [UWP]

"Some of its beneficial substances are considered only extractable in alcohol, so many herbalists prefer alcohol-based extracts made with high alcohol content, like 95% grain alcohol, which results in a strong yellow color. Milk Thistle remedies are often found in stores selling herb products, but you can make your own which is vastly cheaper. Grind seeds into coarse pieces, not fine powder, in a nut/seed mill or coffee grinder that hasn't been used for coffee, or possibly, a strong blender. Fill a glass jar one-third with the ground seeds and then fill to the top with 190 proof grain alcohol (95% alcohol), if available, or high proof vodka. Label with content and date and let sit for at least 6 weeks, shaking the jar every other day or so to dislodge the seeds settled on the bottom. After that, you can pour off a couple ounces of the yellow liquid and begin using. Let the rest continue to steep, as the extract will get stronger. Usually one to 2 droppersful (like from a one ounce eyedropper bottle), two equaling a quarter teaspoonful of tincture, are taken 3 times daily. A one-time toxic exposure might mean using Milk Thistle for a week or so, while long-term exposure or liver damage calls for months of herb use. People with stressed livers need to avoid alcohol, so it's best to drop all the day's dosages of alcohol extracts in a cup of just-boiled water and let this sit for 15 minutes so 80% of the alcohol will evaporate. Then shake the jar of liquid and swallow a third of the total each time. If I'd just been exposed, I'd take it every hour or so the first day." [WFF(Vol. VII, No.4)]

"Due to its highly hydrophobic and nonionizable chemical structure, silybin is poorly soluble in water resulting in a low bioavailability (Bijak, 2017). However, silybin bioavailability can be influenced by several factors including the content of the accompanying molecules such as flavonoids, phenol derivates, amino acids, and many other substances (Voinovich, Perissutti, Grassi, Passerini, & Bigotto, 2009). " [abenavoli2018]

"St Mary's thistle may improve digestion, particularily of fatty foods, and afford protection against the toxic effects of a number of drugs and environmental poisons. It is also used as supportive treatment in chronic liver diseases and high cholestrol states." [NHS Cohen]

"As Rob McCaleb Presidential Commission on Alternative Medicine, puts it "Since the effective dose of milk thistle seed is only 12-15 grams (-one "half ounce), its development as a food crop could contribute to better liver health in Mali and perhaps throughout West Africa." (HG37: p. 9.1996) [WFF(Vol. VIII, No. 1)]

"Commission E approves the use of standardised St. Mary's thistle extracts (70-80% silymarin content) as supportive treatment in chronic inflammatory liver disease and hapatic cirrhosis (Blumenthal et al 2000)." [NHS Cohen]

"Silybum marianum, is an antioxidant, hepatoprotective, hepatotrophorestorattve and gastroprotectant. 43,124,125,257,317,355 It is used in liver disease like hepatitis, fatty liver and cirrhosis. It is also used for liver protection and/or regeneration immediately after exposure to liver toxins although it is best used as a protectant before exposure. The constituent, silymarin, shows antifibrotic effects in early and advanced biliary fibrosis secondary to complete bile duct obliteration in rats. 317" [HMHE]

"Holmes described Silybum marianum as pungent, bitter, warm, dry, stimulating, decongesting, astringent, restoring, dissolving, and softening. In contrast, the liver is associated with cold energetics and the tendency to cause stagnancy due to Yang deficiency, indigestion, nausea, headache, jaundice, constipation, and chilliness. Such ailments are remedied by the warm, stimulating energetics of Silybum marianum which restore the integrity of the liver by promoting bile flow, bowel movement, reducing liver congestion, and stopping free radical formation.17" [Boh,2015]

Antidiabetic - Infusion of leaves. 2-3 glasses for a day. [Guarrera2005] " Flavonoids from MT (ie, silibinin, Legalon) seem to normalize immunoregulatory defects via restoration of the cellular thiol status. T-cell activation (CD69), along with a significant decrease in TNF-α release (P < .05), was observed in 30 patients with end-stage diabetic nephropathy.45" [tamayo2007]

Silymarin


Phytochemicals

"Phytochemical investigations of silymarin led to the isolation of seven major compounds.... The fIrst isolated compound from silymarin is taxifolin, the flavanonol precursor of flavonolignans. Silychristin a and b are flavonolignans.... We isolated two molecules .... To our knowledge, only one silychristin was described in literature .... The four other major compounds isolated from silymarin correspond to silybins a and band isosilybins a and b." [Rauter NPNM]

Fructus Silybi Mariae
"The major active constituents are flavonolignans (1.5–3.0%), collectively known as silymarin. The major components of the silymarin complex are the four isomers silybin and isosilybin (a 1 : 1 mixture of diastereoisomers), silychristin and silydianin. Other flavonolignans identified include 2,3-dehydrosilybin and 2,3-dehydrosilychristin. Taxifolin, a 2,3-dihydroflavonol, which may be regarded as the parent flavonol of the silymarin compounds, is another major marker for Fructus Silybi Mariae (3, 4, 6–8, 19, 20)."[WHO]

"Silymarin is a well established MT seeds standardized dry extract containing mainly flavonolignans (about 70%–80% w/w) as well as polymeric and oxidized polyphenolic compounds consisting of a mixture of flavonoids. Flavonolignans, which have been first discovered in the seeds of Silybum marianum, are a relatively small subclass of compounds, where the flavonoid part of the molecule is fused with a lignan. The main silymarin flavonolignas are silybin, isosilybin (A and B), silydianin, and silychristin (Kvasnicka, Bíba, Sevcík, Voldrich, & Krátká, 2003; Figure 2)." [abenavoli2018]

"...a very recent investigation by Hohmann group revealed the presence of up to 23 flavolignan components [10]. The fruit is also known to be rich in lipids with up to 25% weight/weight [11] which interfere with the extraction of silymarin and has to be removed from the fruits (defatting) prior to silymarin extraction using nonpolar organic solvents." " Silymarin is usually extracted from the defatted fruits in methanol in a yield of less than 2%.... Silymarin was found to be only located in the pericarp section of the fruit. Extraction of silymarin from the pericarp gave higher yields of more than 6% and did not require defatting." [hlangothia2016]


Research

"Silymarin, an extract from the seed, acts on the membranes of the liver cells preventing the entry of virus toxins and other toxic compounds and thus preventing damage to the cells[244]. It also dramatically improves liver regeneration in hepatitis, cirrhosis, mushroom poisoning and other diseases of the liver[222, 238, 254]. German research suggests that silybin (a flavonoid component of the seed) is clinically useful in the treatment of severe poisoning by Amanita mushrooms[222]. Seed extracts are produced commercially in Europe[222]. Regeneration of the liver is particularly important in the treatment of cancer since this disease is always characterized by a severely compromised and often partially destroyed liver[K]." [PFAF]

Clinical pharmacology

"Fructus Silybi Mariae consists of the dried ripe fruits, freed from the pappus, of Silybum marianum" [WHO]

"Most of the biochemical and pharmacological studies have been performed using a standardized silymarin preparation, or its major constituent, silybin."[WHO]

Alcohol-induced hepatitis
"The efficacy of a standardized silymarin preparation for the treatment of alcohol-induced cirrhosis was assessed in six placebo-controlled clinical trials (24–27, 31, 33, 99). The majority of these studies involved between 50 and 100 patients, with one study including 170 patients (26). Patients generally received an oral dose of 280–420mg (140mg two or three times daily) of a standardized silymarin preparation or placebo. One of the studies had a treatment period of up to 4 years, and used survival rates as their outcome parameter. The results of this study showed a significant decrease in the mortality of patients treated with silymarin as compared with placebo (P < 0.05) (26)."[WHO]

"Five double-blind clinical trials assessed the efficacy of silymarin in the treatment of various chronic liver diseases induced by alcohol (22, 23, 25, 29, 30). In four of these trials, treatment of patients with 420 mg of the silymarin preparation daily for 6 months decreased the serum levels of bilirubin, procollagen III peptide and liver enzymes, and increased serum glutathione peroxidase activity and lectin-induced lymphoblast transformation (23, 25, 29, 30). In the fifth study, which was also placebo-controlled, the efficacy of silymarin was assessed in 20 patients with various chronic liver diseases. After 13 months of treatment (420 mg daily), histopathological findings showed improvements in the treated group as compared with the group that received placebo (22)."[WHO]

"The safety and efficacy of silymarin were evaluated in over 3500 patients in two drug-monitoring studies. In one study, 2637 patients with various liver disorders were treated with a standardized silymarin preparation (560mg, given in four divided doses) daily for 8 weeks. Subjective symptoms decreased by 63%, clinical findings improved and elevated serum levels of liver enzymes were reduced in the treated group. Treatment was rated as very good, good or satisfactory by 88% of the physicians (21). Minor gastrointestinal side-effects were reported in 1% of patients (21, 28)."[WHO]

Acute and chronic viral hepatitis
"In another trial, the duration of inpatient care was shown to be shorter for patients treated with silymarin, compared to those who received supportive care (23.3 and 30.4 days, respectively). In patients with viral hepatitis B, treatment with silymarin led to a shorter interval to the development of immunity (30.4 days), compared to supportive therapy only (41.2 days) (104). A double-blind study in patients with acute viral hepatitis indicated that daily treatment with 420mg silymarin (three doses of 140 mg) decreased the complications associated with the infection (106)."[WHO]

"A 12-month study combining two double-blind, placebo-controlled trials assessed the efficacy of silymarin in the treatment of chronic hepatitis, with or without cirrhosis, in 36 patients. Patients were treated with 420mg of a standardized silymarin preparation or placebo daily for 3–12 months. Assessment of serum levels of bilirubin and liver enzymes did not reveal any significant differences in liver function between the treatment and placebo groups. However, histological improvements were noted in patients who received silymarin (107)."[WHO]

"Patients receiving silymarin had earlier improvement in subjective and clinical markers of biliary excretion. Despite a modest sample size and multiple etiologies for acute clinical hepatitis, our results suggest that standard recommended doses of silymarin are safe and may be potentially effective in improving symptoms of acute clinical hepatitis despite lack of a detectable effect on biomarkers of the underlying hepatocellular inflammatory process." [el-kamary2009]

"In chronic hepatitis C virus (HCV) (Table 3), 373.5 mg of MT was safe and well tolerated for up to 1 year.51 In a follow-up study, 420 mg daily did not prevent complications of HCV but improved general health and symptoms for up to 2 years.52 Higher doses of 600 and 1200 mg/d were tolerated but had no significant effect on serum HCV ribonucleic acid titers (P = .52) and serum alanine aminotransferase (ALT) and other liver chemistries (P = .28) and did not improve quality of life or psychological well-being.53 A small beneficial, but not significant, effect of MT was observed in patients with chronic hepatitis C on sustained biochemical response and virologic response. However, the clinical effect of interferon therapy was 10-fold greater than MT.54 In another study, MT had an effect on liver chemistries but no apparent effect on viral load, suggesting that S marianum may have a protective effect in the inflammatory response to HCV but no role as an antiviral agent.55" [tamayo2007]

Organic compound-induced hepatitis
"A controlled clinical study of patients with a 5–20-year history of occupational exposure to toluene and/or xylene vapours was performed to assess the efficacy of a standardized silymarin preparation on liver function. Thirty patients were treated orally with 140 mg of the preparation three times daily for 30 days, and the results were compared with those from 19 untreated matched controls. Both liver function and platelet counts markedly improved in the treated patients (the elevated serum levels of glutamic oxaloacetic transaminase and glutamic pyruvic transaminase were reduced, and the low platelet numbers increased) as compared with the controls (32)."[WHO]

Drug-induced hepatitis
"A double-blind, placebo-controlled study assessed the efficacy of silymarin in the prevention of hepatic damage induced by psychotropic drugs. Sixty patients receiving chronic therapy with psychotropic drugs (butyrophenones or phenothiazines) were treated orally with 800 mg silymarin or placebo daily for 90 days. Silymarin treatment improved liver function and reduced lipoperoxidative hepatic damage as determined by serum malondialdehyde levels (the endproduct of the oxidation of polyunsaturated fatty acids) (109). A small clinical study found improvements in biochemical parameters in 19 patients using psychotropic drugs after 6 months of treatment with silymarin (110)."[WHO]

Toxin-induced hepatitis
"Numerous case reports have indicated that silymarin and silybin are effective in the treatment of poisoning due to ingestion of the deathcap mushroom Amanita phalloides (34, 111–114). Amanita toxins inhibit the activity of RNA polymerase in hepatocytes, causing cell death after 12–24 hours. In a clinical trial without controls, 60 patients were treated intravenously with silybin (20 mg/kg body weight, daily for 1–2 days), 24–36 hours after ingestion of Amanita phalloides. The survival rate was 100% (34). Results of a multicentre study of 252 cases of poisoning due to ingestion of Amanita phalloides indicated that intravenous infusion of silybin (20 mg/kg body weight, daily for 1–2 days), in combination with the standard management techniques, dramatically reduced mortality, without producing side-effects (111–113)."[WHO]

"Assessment of the clinical trials of silymarin for the treatment of hepatitis induced by alcohol, drugs or toxins, and acute and chronic viral hepatitis should be interpreted with caution because of the small number of patients involved, the heterogeneity of diagnoses and outcome parameters, and the inconsistent reporting of alcohol intake by patients during the studies (115)."[WHO]

"The Amanita phalloides (the so‐called death cap) mushroom poisoning is associated with a severe morbidity and a high mortality rate due to progressive fulminant hepatic failure. The main toxic agents of Amanita phalloides are amatoxins, that is, DNA‐dependent RNA polymerases II inhibitors that dysregulate protein synthesis causing liver necrosis (Santi et al., 2012). The human lethal dose is approximately 0.1 mg/kg body weight. There are no worldwide accepted guidelines on the treatment of amatoxins‐induced liver failure. Clearly, due to the ethical reasons, there are no controlled clinical studies available. However, uncontrolled trials and several case reports describe successful treatment with an intravenous silybin administration, even in the severely poisoned patients (Mengs, Pohl, & Mitchell, 2012). Empiric experience suggests the administration of 5 mg/kg silybin every 4 hr for 3–4 days after mushroom ingestion in association with N‐acetylcysteine and multiple‐dose activated charcoal (Karvellas et al., 2016; Trakulsrichai et al., 2017)" [abenavoli2018]

"On New Year's Day in 2007, six family members ate tacos they made from wild mushrooms they had colIected in a park in Santa Cruz, California. They were all admitted to the hospital suffering from amatoxin poisoning, with symptoms of eating death cap. The doctor treating them discovered references to milk thistle and to the effectiveness of an intravenous preparation of silibinin, one of the flavonolignans in milk thistle extract (made from the fruits of milk thistle, Silybum marianum) in treating amatoxin poisoning. He had to get special approval to import this standardized preparation, Legalon-Sil, into the United States. He then used it along with penicillin, activated charcoal, and an antidote for Tylenol overdose. Five of the patients recovered, but unfortunately, the oldest victim, an 83-year-old woman, who (characteristically) seemed to be recovering, succumbed to kidney failure (Cavaliere 2007)." [CPPM]

"Administration of silybin within approximately 48 hours after poisoning produced by the mushroom Amanita phalloides (death cap) seems to be an effective measure to prevent severe liver damage.25 Combination of standard therapy along with silibinin produced a rapid resolution of clinical symptoms.26 A retrospective analysis of 205 cases of clinical poisoning during 1971 to 1980 found positive results for MT’s silybin extract in increasing survival rates for adults and children exposed to this potentially lethal mushroom.27" [tamayo2007]

Dosage forms
"Usually standardized extracts for phytomedicine; crude drug for decoction (4). Store in a well-closed container, protected from light and humidity (2)."[WHO]

Posology
"(Unless otherwise indicated) Daily dosage: 12–15 g crude drug (35); 200–400 mg silymarin, calculated as silybin, in standardized preparations (35)."[WHO]

Potential anti-cancer Effects

"In summary, we report spontaneous regression of advanced HCC in the case of a 66-year-old male patient. Even after a literature review, spontaneous regression of HCC are still unclear. It is possible that circulatory disturbance and immune mechanisms may be major pathways. Silymarin should be further investigated for its anticancer effect. In conclusion, it is likely that treatment of HCC in the future will include a multimodal therapeutic method." [Hsu et al.,2009] "Silymarin ... inhibits chemically induced carcinogenesis and shows direct anticarcinogenic activity against several human carcinoma cells" "New activities based on specific receptor interactions have recently been reported and there is growing interest in its anticancer and chemopreventive effects, as well as in its hypocholesterolaemic, cardioprotective, neuroactive, and neuroprotective activities [11]." [P. Corchete,2008]

Animal Test "The chosen toxic dose of phalloidin caused a death rate of 90% within 3 to 5 hr after injection. But the treatment with silybin 1 hr before intoxication resulted in complete prevention of lethality. Silybin as curative treatment, on the other hand, offered full protection only if given up to 15 min after phalloidin; after that time, it was not effective (Vogel and Trost, 1973)." [tuchweber1979]


Synonyms


Cultivation & Propagation

"Succeeds in any well-drained fertile garden soil[1, 200]. Prefers a calcareous soil[12] and a sunny position[200]. Hardy to about -15°c[200]. The blessed thistle is a very ornamental plant that was formerly cultivated as a vegetable crop[1, 61, 238]. Young plants are prone to damage from snails and slugs[200]. Plants will often self sow freely[K]." [PFAF]

" Seed - if sown in situ during March or April, the plant will usually flower in the summer and complete its life cycle in one growing season[K]. The seed can also be sown from May to August when the plant will normally wait until the following year to flower and thus behave as a biennial[K]. The best edible roots should be produced from a May/June sowing, whilst sowing the seed in the spring as well as the summer should ensure a supply of edible leaves all year round[K]." [PFAF]

"Biosynthesis and accumulation of active substances like silymarin in plant tissues highly interacts with the environmental conditions. Effects of moderate and severe drought stress (based on soil moisture depletion) on silymarin content and composition in milk thistle seeds were evaluated in a field study. Averaged across treatments, milk thistle seeds contained 19.3 g kg-1 silymarin. Drought stress enhanced silymarin accumulation in milk thistle seeds. Plants grown under moderate and severe drought stress treatments contained 4 and 17 % greater silymarin than those grown in well-watered condition, respectively. Greater content of sylimarin in stressed plants was attributed to more contents of silybin, isosilybin and silychristin, while silydianin content was lower under drought condition. According to the results obtained in this study, drought stress enhanced accumulation of silymarin in milk thistle seeds and improved its quality by increasing the share of silybin, which possess the greatest degree of biological activity among the silymarin components." [afshar et al.,2015]


SILYBUM MILK THISTLE

"Annual or biennial, taprooted. Leaf: basal and cauline, alternate, simple, spiny-dentate, often coarsely lobed, dark green with white blotches, ± glabrous, distal cauline reduced. Inflorescence: heads discoid, large; peduncles bracted; involucre ovoid to spheric; phyllaries graduated in 4–6 series, tips of outer and middle spreading, lanceolate to ovate, spiny-fringed and -tipped; receptacle flat, epaleate, white-bristly. Flower: many; corolla pink to purple, tube long, slender, throat abruptly wider, lobes linear; anther bases sharply short-sagittate, tips oblong; style tip long-cylindric distal to slightly swollen node, branches very short. Fruit: ovoid, slightly compressed, glabrous, attachment scar slightly angled; pappus of many flat, minutely barbed bristles, falling in a ring.
2 species: Mediterranean. (Greek: name for thistle-like plants) [Keil 2006 FNANM 19:164]" [Jepson]

"The genus contains two species: S. marianum (L.) Gaernt, with variegated leaves, and S. eburneum Coss. et Durieux, with totally green leaves [15]. However, the incompatibility barriers that are expected between two different plant species were not found by Hetz et al. [16], and the authors concluded that the genus Silybum has only one species: namely, S. marianum." [P. Corchete,2008]


Local Species;

  1. Silybum marianum - milk thistle [E-flora]

References

  1. abenavoli2018 - Abenavoli, Ludovico, et al. "Milk thistle (Silybum marianum): A concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases." Phytotherapy Research 32.11 (2018): 2202-2213.
  2. Adams et al.,2009 - Adams, Michael, et al. "Medicinal herbs for the treatment of rheumatic disorders—a survey of European herbals from the 16th and 17th century." Journal of ethnopharmacology 121.3 (2009): 343-359.
  3. afshar et al.,2015 - Afshar, Reza Keshavarz, et al. "Accumulation of silymarin in milk thistle seeds under drought stress." Planta 242.3 (2015): 539-543.
  4. Boh,2015 - Maureen Boh & Ian Breakspear, Silybum marianum – ancient medicine for modern times, Herbal Monograph - Australian Naturopathic Practitioners Association, February 2015
  5. el-kamary2009 - El-Kamary, Samer S., et al. "A randomized controlled trial to assess the safety and efficacy of silymarin on symptoms, signs and biomarkers of acute hepatitis." Phytomedicine 16.5 (2009): 391-400.
  6. E-flora - Silybum marianum, http://linnet.geog.ubc.ca/Atlas/Atlas.aspx?sciname=Silybum%20marianum, Accessed May 29, 2019
  7. Guarrera2005 - Guarrera, Paolo Maria. "Traditional phytotherapy in Central Italy (Marche, Abruzzo, and Latium)." Fitoterapia 76.1 (2005): 1-25.
  8. Hellerbrand et al.,2016 - Hellerbrand, Claus, et al. "The potential of silymarin for the treatment of hepatic disorders." Clinical Phytoscience 2.1 (2017): 7.
  9. hlangothia2016 - Saleh, Mahmoud. "Distribution of Silymarin in the Fruit of Silybum marianum L." Pharm Anal Acta 7.511 (2016): 2.
  10. Hsu et al.,2009 - Hsu, Chuan-Yuan, et al. "Spontaneous regression of advanced hepatocellular carcinoma: a case report." Cases journal 2.1 (2009): 6251.
  11. Lans et al.,2006 - Cheryl lans, Nancy Turner, Gerhard Brauer, Grant Lorenco and Karla Georges, Ethnoveterinary medicines used for horses in Trinidad and in British Columbia, Canada, Journal of Ethnobiology and Ethnomedicine 2006, 2:31
  12. Jepson - 2013. Silybum, in Jepson Flora Project (eds.) Jepson eFlora, http://ucjeps.berkeley.edu/cgi-bin/get_IJM.pl?tid=609, accessed on Jan 22 2015
  13. Montesano et al.,2012 - Vincenzo Montesano, Donatella Negro, Giulio Sarli, Antonino De Lisi, Gaetano Laghetti and Karl Hammer, Notes about the uses of plants by one of the last healers in the Basilicata Region (South Italy), Journal of Ethnobiology and Ethnomedicine 2012, 8:15
  14. P. Corchete,2008 - Ramawat KG, Mérillon JM (eds.), In: Bioactive Molecules and Medicinal Plants
  15. PFAF - Silybum marianum, https://pfaf.org/user/Plant.aspx?LatinName=Silybum+marianum, Accessed May 29, 2019
  16. tamayo2007 - Review of Clinical Trials Evaluating Safety and Efficacy of Milk Thistle (Silybum marianum [L.] Gaertn.), Carmen Tamayo and Suzanne Diamond, Integr Cancer Ther 2007 6: 146
  17. Tardio,2006 - Tardío, Javier, Manuel Pardo-de-Santayana, and Ramón Morales. "Ethnobotanical review of wild edible plants in Spain." Botanical Journal of the Linnean Society 152.1 (2006): 27-71.
  18. tuchweber1979 - Tuchweber, B., R. Sieck, and W. Trost. "Prevention by silybin of phalloidin-induced acute hepatoxicity." Toxicology and applied pharmacology 51.2 (1979): 265-275.
  19. WHO - WHO monographs on selected medicinal plants, Volume 2, WHO, 1999, P. 300- 316

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